Anesthesia Reference and Study

Guide:
For the SRNA and Practicing CRNA

Knowledge is Power!
This reference guide is a free resource for the SRNA and the Practicing CRNA. We believe that only through
knowledge and education can we achieve greatness. We share this for free because we believe in promoting
and helping our fellow CRNAs in every way possible. All we ask is that you consider our challenge that you
do the same and that you sign the pledge form below to make a yearly donation to the AANA foundation and
the AANA PAC.

IMPORTANT: PLEASE READ: You will notice in your reading of this review manual that there are
several areas that are repeated. For example the airway section has 3 different reviews, some of the
material is the same and some different. What this is attempting to do for the reader is explain the
concepts in different ways. We all learn differently and as we embrace a hybrid approach of the
flipped classroom model information needs to be explained differently. Please don’t panic and say
“They are repeating the material” YES WE ARE, we are doing it on purpose so each type of learner
can read the information in a different way. Thanks for understanding.

1st Edition; (2014)TWA Publication # PD9081027121602111. Mount Horeb, WI; TW Publishing

[Link]

1
In preparing this manual I am attempting to honor a promise made long ago to always give back to our
profession. I was honored to get accepted into school. I was even more honored to work with two great and
outstanding program chairs, Merri Moody and Thomas Healey. Both of whom in stilled in me a sense of
always wanting to give back to our profession. I was also blessed to work for my first chief Wilma Gillis and
she too offered me great guidance in my early years. Thank you to all those that helped shape this great
profession.

Dosage Selection: The authors have made every effort to ensure the accuracy of dosages cited herein.
However, this field of trauma resuscitation is changing as more research is being completed with the end of
the wars in Iraq and Afghanistan. It is the responsibility of every practitioner to consult appropriate information
and sources to ascertain correct dosages and current information for each situation. This is especially important
for any unfamiliar drugs, information or protocols and procedures. The authors cannot be held responsible for
this changing field of study.

Financial Disclosure: There is no financial incentive for this reference guide.

The contributors have received NO financial compensation for this reference guide.

It was all completed on a donation basis.

Clinical Information: The authors have made every effort possible to ensure all information is correct. If you
find an error in the information provided please send a professional email using the below listed criteria so a
correction can be made. Please include a main stream reference for this change. Please also send any
spelling, grammatical corrections or abbreviation corrections so the next edition can correct this information.
This book is a collection of reference material compiled over the last 6 years. It is a grouping of study
guides, class notes, professional mini-papers and several other sources of information and collection
methods. This is the first edition and we are committed to future editions. If you would like to write a section
or have information for a section please contact us through [Link] or send an email to
pstrube3000@[Link]. It is the duty of each and every practitioner to ensure correct information. We
have made our best effort to do that and ask to help be a passive editor if you find errors. You assume all
liability for your clinical practice. Be a purist, be the best at what you do each and every day.

We have made every effort to cite references and have included a reference list of texts used for this guide.
We would like to thank and acknowledge all the hard work every anesthesia practitioner has put into our
profession. IF we have missed a reference we apologize and if you let us know we will ensure it is included
in future editions.

2
 Contributing Authors:

Peter Strube CRNA MSNA APNP ARNP

Jacqueline Bertucci CRNA MSN

Jenea Nolan CRNA MSN

Michael Trenkle CRNA MSN

Julie Niedfeldt CRNA MSN

Sothida Berry CRNA MSN

Zarinah Ali Burford CRNA MSN

Kari Bently CRNA MSN

Kristen Burg CRNA MSN

Matt Burkart CRNA MSN

Casey Weiss CRNA MSN

Frank Lamphere CRNA MSN

Yelena Richman CRNA MSN

Lubavo Byrum RN SRNA

Kerrri Coons RN SRNA

Kristin Miller RN SRNA

3
Pledge Form:

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Reference Guide: Send either through [Link] through contact us tab or directly to
pstrube3000@[Link]

Please include the statement: In exchange for this FREE reference manual I pledge to support the AANA
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If you are a student, your pledge will begin the January after you have completed school and passed your
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Pledge form:

Your Pledge to support these organizations will help us continue the effort of research and education in the
AANA foundation and our life long goal of LIFE IN DISCOVERY. Your pledge to the AANA PAC will
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Email this form to either pstrube3000@[Link] or through [Link] under the

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4
ERROR Correction form OR additional Information FORM:

Please send email to [Link] or pstrube3000@[Link]

Subject line should be: ERROR Correction form OR additional Information

Page Number:

Information to correct:

(Please include full sentence before and after the section you are looking at)

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If you would information on a topic please include that information at a correctly cited reference.

If you would like to submit information on a topic not in this edition please send an email to
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Subject Line: Future edition to reference guide

Please send your topic. Once we receive it we will reply and set a time line to work with you. Please make
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There is NO financial compensation for this material. It is meant to be provide to our profession for FREE.
Thanks for understanding this principle. Your work will be donation to this publication. You will be ask to
sign an author form.

5
We believe that education is power, we also believe in a combination of the new education principle of the
flipped classroom as well as the traditional method. The answer to the best education is somewhere in the
middle of these two principles. What is important is a concept that Dr. Rosenthal talked about. This effect
tells us if we ask and demand the very best from ourselves and our students, they will perform to that very
level. If we expect little of them they will give us little. We need to challenge ourselves and our students to
perform to that very level.

Here is brief write up from the AANA journal about the flipped classroom principle:

“A Flipped Classroom: Now or Never?” AANA Journal; August 2014 Volume 82 number 4; ISSN 0094-
6354; Sharon J. Hawks, CRNA, MSN, DNP

Purpose: The purpose of this article was to provide a better understanding of the principle of the flipped
classroom. It strives to show us that the traditional paradigm of education is changing and that if we as a
profession and as educators are to bring our students to a new level of education we should consider making
these changes. The principles that are discussed focus on a new level of education standards and the idea that
new and innovative tools for educating our students need to be employed. This stems from the 2001 IOM
report and the article in medical education by Cooke et al titled: Educating Physicians: A Call for Reform of
Medical School and Residency.

Background: In 2001 the IOM report discussing the need for change in current medical education was
introduced. It demonstrated that we needed to change our thought pattern to produce better providers and a
better educated workforce. Although the article does not discuss the education principle of the Rosenthal
Effect, I believe it is addressed in concept. The idea of the flipped classroom is not new, but as we approach
a new style of learner and the ability of the current student to learn better and faster we must also use a new
style of education to meet these needs.

Methodology: This is not a study or double blinded random controlled study. It is an introduction to a new
concept. Like all new concepts, a paper must be written that introduces the concept. During this meta-
analysis we see reference to several studies done in different health care professions related the principle of
the flipped classroom. The studies cited are an excellent beginning and have positive results from other
professions. Many will argue that we need more studies to justify such a change in our own profession. If we
discard the other relevant material in other health care professions we may miss the educational revolution
that is occurring and find our profession lagging in many areas.

6
Results: During the cross profession review of the current information available we find great outcomes
related to the flipped classroom. Students come to class active and ready to learn. They are able to better
focus and participate in class. The research also found that students in the flipped classroom did better than
the traditional classroom. Hake et al found that the flipped classroom student significantly outperformed
traditional students. The studies also found that the students learned to work better collaboratively in this
environment. The use of case studies, scenarios, small group discussion and other interactive material
prepared them better for class. The information also showed that faculty could spend more time on problem
of misunderstood information during class. The studies also found that 70% of students found this style of
education to be more effective.

Conclusions: An interesting principle of this topic is a few key points to education. During the flipped
classroom we should not allow the online work to replace all lecture material or direct student interaction.
Online work should be used to augment and support the classroom experience. We must be strong enough as
educators to seek student review but not use a single student review to adjust our whole plan. Education is a
marketing product and if we bend to the unprofessional or personal opinion of a single student we will not
provide the best product for our students. We must also provide the evidence to the students that this change
is what is in the best interest for them. There are several pre-class preparation aspects for the student to
achieve to get the best from the class. The topics must be provided early and with plenty of time for the
student to be prepared for class. This pre-class material should not be limited to just lectures or power points.
There are multiple different media tools available to be used and utilized in the flipped classroom principle.

Comment: This is a very worthwhile article and concept. There must be a hybrid approach, we should not
lose the traditional methods, but rather bring what is best in those principles and meld them with the flipped
classroom approach. I would encourage us all to read it and understand the flipped classroom concept more.
We are at a crossroads in our profession of educating our students. Dr. Robert Rosenthal argued that if we
demand the very best from our students then they will perform at their very best. The negative can also be
said, if we expect little of them the will perform at that level. We do not need to be in a formal classroom
setting to use the flipped classroom model. The bulk of nurse anesthesia education is done in the one on one
role in the operating room. Our ability to mentor and foster the next generation of students hinges on
embracing new models of education. The interesting cross reference for this is the study of how our new
students learn different and better than we did, they are able to assimilate far greater amounts of information
and less amount of time. If we are going to keep up, we as nurse anesthesia need to set a new pace in
education. We must demand the very best from our students and they will give us the very best. We are
building a generation of students to promote our profession

Copyright statement: Under the fair use clause of copyright this material is for educational purposes only and
there is no financial gain. There is also no financial loss perceived or realized in any third party. Fair use
allows for limited or transformative information. Facts cannot be copyrighted, for example; a mathematical
formula is public domain. Of the four factors for fair use, we state there is no commercial use and this is only
for educational purposes, facts are not copyrighted, if any work is referenced it is only a small fraction of the
larger work from any one author and our reference list is extensive, there is no perceived or known economic
harm noted.

7
In honoring the flipped class principle we have compiled a list of vetted pharmacology web addresses that
can offer the student a different avenue to learn information: This is just the beginning of this concept.

Pharmacology Flipped Principle: Both Text and Web information:

Local Anesthetics:
Stoelting & Hillier, Chapter 7
[Link]

[Link] (math)

[Link] (math!!)

[Link]

[Link]
[Link]

[Link] (read entire web page related to Exparel)

[Link]

[Link] (watch slides 13-17 to help

understand pKa, potency, solubility)

[Link] (pKa and drugs)

[Link] (bupivacaine)

[Link] (Chloroprocaine, watch closely,

questions always come up as to why it does not follow all the rules of locals)

[Link] (Ropivicaine, but it is in with a

few other drugs, watch the entire video, this YouTube video is listed with ketamine and Vecuronium)

[Link] (lidocaine—this is a key drug to

know)

8
Lipid Rescue for Local Anesthetic Toxicity:
ASRA Checklist for Lipid Rescue

[Link]

[Link]

[Link]

[Link]

Histamine and histamine receptor antagonists:

Stoelting & Hillier, Chapter 21
Lieberman et al. article on anaphylaxis (2010)
[Link]

[Link]

[Link]

[Link]

[Link] (anaphylaxis)

Antacids, GI prokinetic:
Stoelting & Hillier, Chapter 26
[Link]

[Link]

[Link]

[Link] (Reglan, review this for both the

prokinetic material and PONV material)

9
Antiemetics:
Stoelting & Hillier, pp. 446-449
PONV Consensus article, Tong et al. (2003)
Ho & Chiu article on multimodal antiemetic therapy (2005)
ASA Practice Guidelines (2013)
[Link] (physiology of vomiting)

[Link]
documents/[Link]+&cd=1&hl=en&ct=clnk&gl=af

[Link]
ZDc1Z/EvidenceBased_Practice_for_Management_of_PONVPDNV_The_ASPAN_Guidelines_powerpoint_ppt_presentation

[Link]

[Link]

[Link]

[Link]

(Listen to Dr Harmans lecture on Nausea and medications, don’t get caught up in the chemotherapy or oncology part)

[Link] (Droperidol)

[Link] (Zofran)

[Link]/data/uploads/volume1/[Link]

Neuromuscular blocking drugs:

Stoelting & Hillier, Chapter 8
Train of Four Monitoring Self Learning Program
[Link]

[Link]

[Link]

[Link]

[Link] (train of four monitor)

[Link] (Atracurium)

[Link] (watch the entire video, has a

few other drugs listed but for this section listen for the Vecuronium section)

[Link] (Mivacurium)

[Link] (Nimbex)

[Link] (Pancuronium)

[Link] (Rocuronium)

[Link] (succinylcholine)

10
Anticholinesterase drugs, Cholinergic Agonists:
Stoelting & Hillier, Chapter 9
[Link] (neostigmine)

[Link] (Edrophonium)

[Link] (why do you need to give an antimuscarinics when

administering an anticholinesterase?)

Anticholinergics:
Stoelting & Hillier, Chapter 10
[Link]

[Link]

[Link] (atropine)

[Link] (Robinol)

Pain:
Young & Buvenandran article (2012)
Stoelting & Hillier, pp. 461-469 (corticosteroids)
[Link]

[Link]

[Link]

[Link]

[Link]

[Link]

[Link]

[Link]

[Link]

[Link]

[Link]

[Link]

[Link]

[Link] (chronic regional pain syndrome) ---This is the history and important concepts:

[Link] (Chronic regional pain syndrome and flows very nice)

11
Opioids:
Stoelting & Hillier, Chapter 3
[Link]

[Link]

[Link]

[Link] (ketamine)

[Link] (lots of video’s that need to be reviewed prior to class)

[Link]

[Link] (Alfenta)

[Link] (Dilaudid)

[Link] (Fentanyl)

[Link] (Remifentanil)

[Link] (sufentanil)

NSAIDS, COX-2 inhibitors, IV acetaminophen:

Stoelting & Hillier, Chapter, 11
Munir et al. article (2007)
[Link]

[Link]

[Link]

[Link]

[Link]

[Link]

[Link]

[Link]

[Link]

[Link] (non-opioid pain management)

12
Please enjoy the review guide. There is plenty of space on each page to make notes and add things. We
would like very much to hear from you about this review material and if we can make it better. Remember
we need to work together to ensure the best possible outcomes for the patient and for our profession. Enjoy
the guide, study hard and be good to each other.

This document is a living document and you can help update it and we can all learn together.

Please visit us at [Link]

Notice:
Anesthesia is an ever-changing science and art. As new research and clinical experience broadens our
knowledge, changes in treatment and drug therapy are required. We have made every effort and
believe our sources and information is reliable but final review is your responsibility. In the view of the
possibility of human error or changes in science, standards and information neither Trollway, the
authors nor other parties who have been involved in this work or publication of this work warrants,
you the clinician final and absolute authority in using information. We disclaim any and all
responsibility for errors or omissions or for the results obtained from the use of this information. You
and all readers are encouraged to confirm any and all information contained herein with others
sources. We, you should strive to read and learn as much as possible. For example, product
information sheet included with all devices should be read and understood. Each drug package insert
should be read and understood. This change and recommendations change as we learn and evolve in
practice. Please enjoy our joint life in discovery.

13
Table of Contents:

Introduction 1-----13

Anatomy of the Larynx and Airway Review 13----58

AANA Standards of Care 59-----62

PIN index, Scavenging, machine, vaporizers, CO2

Circuits, Oxygen, Carbon Dioxide 63-----80

Temperature 81-----84

Pulse Oximetry, Beer Lampert, Physics laws

Waveforms, ETCO-2, Lab, TEG, Bainbridge 85-----101

Pharmacology Review, Agents, Drugs 102----127

Antibiotics 128----159

Cox-1 and Cox-2, NSAID and Opioids 160----179

Hormonal Agents, antifungals, More antibiotics 180-----195

Diuretics 195-----197

NASH, Thalassemia, Porphyria, Treacher Collins

Cystic Fibrosis, Pierre Robin, Syndromes 198----216

Intraocular Pressure 217

GI Disorders, Carcinoid Tumor 218----220

Respiratory Study Guide 221----236

Pediatrics 237----280

Pulmonary Pathophysiology 280----307

Endocrine System 308----355

Renal Review 356----409

Neuro Review 410----465

Evoked Potentials 466----473

14
Cardiac Review (including valve issues)

Lab issues, murmurs, CHF 474---- 546

Illegal Drugs 547-----555

Immune System 556----561

Bleed and Clotting Cascade 562----565

Nerve Fiber Size, REGIONAL Anesthesia 565----628

Practice Questions

Oncology 629----634

OB including multiple complications 635----666

Anion Gap 667---- 673

Pimp Questions 674----690

Stats understanding and explanations

Thesis Planning ideas 691---- 711

Corneal Abrasions 712

Pimp Questions---Yes more… always good 713

Pain, anesthesia facts, questions, 714----725

Study Guide (highlights) 726---- 849

Basic pathophysiology 850----854

Cognitive Development 855----868

Basic Physiology Review 869----891

Mechanisms of Breathing 892----896

Infectious Lung Diseases 897----899
Kidney Review 899----905
Other Organ and System Review 906---917
Case Studies 918----935
References 936----949

15
Anatomy of the Larynx

The adult larynx is between the third and the sixth cervical vertebrae. It functions in the modulation of sound
and separates the trachea from the esophagus during swallowing. This protective mechanism, when
exaggerated, becomes laryngospasm. The larynx is composed of muscles, ligaments, and cartilages (thyroid,
cricoid, arytenoids, corniculates, and epiglottis). The vocal cords are formed by the thyroarytenoid ligaments
and are the narrowest portion of the adult airway. The anterior-posterior dimension of the vocal cords is
approximately 23 mm in males and 17 mm in females. The vocal cords are 6 to 9 mm in the transverse plane
but can expand to 12 mm. This calculates to a glottic aperture of 60 to 100 mm. An understanding of the
motor and sensory innervation of the laryngeal structures is important for performing anesthesia of the upper
airway. The muscles of the larynx are innervated by the recurrent laryngeal nerve with the exception of the
cricothyroid muscle, which is innervated by the external (motor) laryngeal nerve, a branch of the superior
laryngeal nerve.
Superior laryngeal nerve, internal division: Sensory – epiglottis, base of tongue, supraglottic mucosa,
thyroepiglottic joint, cricothyroid joint. Motor – none.
Superior laryngeal nerve, external division: Sensory - anterior subglottic mucosa. Motor - Cricothyroid
muscle.
Recurrent laryngeal nerve: Sensory - subglottic mucosa muscle spindles. Motor - thyroarytenoid muscle,
lateral cricoarytenoid muscle, interarytenoid muscle, posterior cricoarytenoid muscle.
The posterior cricoarytenoid muscles abduct the vocal cords, whereas the lateral cricoarytenoid muscles are
the principal adductors. Phonation involves complex simultaneous actions by several laryngeal muscles.
Damage to the motor nerves innervating the larynx leads to a spectrum of speech disorders. Unilateral
denervation of a cricothyroid muscle causes very subtle clinical findings. Bilateral palsy of the superior
laryngeal nerve may result in hoarseness or easy tiring of the voice, but airway control is not jeopardized.
Unilateral paralysis of a recurrent laryngeal nerve results in paralysis of the ipsilateral vocal cord, causing
deterioration in voice quality. Assuming intact superior laryngeal nerves, acute bilateral recurrent laryngeal
nerve palsy can result in stridor and respiratory distress because of the remaining unopposed tension of the
cricothyroid muscles. Airway problems are less frequent in chronic bilateral recurrent laryngeal nerve loss
because of the development of various compensatory mechanisms (e.g., atrophy of the laryngeal
musculature). Bilateral injury to the vagus nerve affects both the superior and the recurrent laryngeal nerves.
Thus, bilateral vagal denervation produces flaccid, mid positioned vocal cords similar to those seen after
administration of succinylcholine. Although phonation is severely impaired in these patients, airway control
is rarely a problem.

The blood supply of the larynx is derived from branches of the thyroid arteries. The cricothyroid artery arises
from the superior thyroid artery itself, the first branch given off from the external carotid artery, and crosses
the upper cricothyroid membrane, which extends from the cricoid cartilage to the thyroid cartilage. The
superior thyroid artery is found along the lateral edge of the cricothyroid membrane. When planning a
cricothyrotomy, the anatomy of the cricothyroid artery and the thyroid artery should be considered but rarely
should affect the practice. It is best to stay in the midline, midway between the cricoid and thyroid cartilages.

16
17
Pediatric Larynx:
Development of the respiratory system begins at approximately 3 weeks of gestational age with the
formation of the laryngotracheal tube from the ventral wall of the foregut. The normal laryngotracheal tube
grows faster than the esophagus, which forms from the caudal growth of the foregut. The laryngotracheal
tube then grows caudally into the splanchnic mesoderm on the ventral surface of the foregut, dividing into
the right and left lung buds. The epiglottis begins to forms from the hypobranchial eminence of the third and
fourth arches at approximately 30 to 32 days of gestation. The anlage of the arytenoid cartilages can be
identified on both sides of the laryngeal slit at this time and continues to grow during the fifth week of
development. The aryepiglottic folds develop from the lateral boundaries of the fourth arch along a line from
the hypobranchial eminence (epiglottis) to the arytenoid eminence of the sixth arch. Incomplete development
at this stage may produce variable degrees of persistent laryngeal cleft. A definite larynx may be seen by 41
days of gestation. The cricoid and thyroid cartilages begin to develop before the arytenoid cartilages and
begin chondrification at approximately 7 weeks of gestation. As the thyroid cartilages develop, the glottis
deepens and the true vocal cords are aligned within the thyroid laminae. Failure of the true vocal cords to
split at 10 weeks of gestation to form the primitive glottis results in congenital atresia of the larynx or, more
often, a complete or partial congenital laryngeal web. Although webs may be supraglottic or subglottic, most
occur at the level of the glottis. Congenital cysts of the supraglottic region are possibly remnants of the third
branchial pouch and lie superior to the derivatives of the fourth arch. By the 10th to 11th weeks of gestation,
the major structures of the larynx have developed and the cartilages are chondrifying.
An infant’s larynx is higher (more cephalad) in the neck, classically described at the level of C3-4, than is an
adult’s larynx which is at the level of C4-5. A study that used magnetic resonance imaging (MRI) and
computed tomography (CT) to localize airway structures confirmed that the larynx is higher (more cephalad)
in children than in adults and noted that the hyoid bone is at the C2-3 level in children from neonate to 2
years of age. Because the larynx is higher (more cephalad) in the neck of an infant, the distances between
the tongue, hyoid bone, epiglottis, and roof of the mouth are smaller than in an older child or adult. Thus, the
tongue easily obstructs the infant’s airway. The proximity of the tongue to the more superior larynx also
makes visualization of laryngeal structures more difficult because it produces a more acute angulation
between the plane of the tongue and the plane of the glottic opening. Therefore, the infant tongue is also
more likely to obstruct the view of the larynx. It is for this reason that a straight laryngoscope blade, which
more effectively lifts the tongue from the field of view during laryngoscopy, facilitates visualization of an
infant’s larynx. This anatomic relationship is further complicated in midfacial hypoplasia, the base of the
tongue is positioned more caudally (known as glossoptosis) and in closer proximity to the laryngeal inlet
than normal; the result is an even greater acute angulation between the plane of the tongue and the plane of
the laryngeal inlet (often 90 degrees). In this situation, conventional rigid laryngoscopy results in direct
visualization of the esophageal inlet rather than of the laryngeal inlet. In these children, special equipment or
special techniques may be required to intubate the trachea.
The large head and tongue, mobile epiglottis, and anterior position of the larynx characteristic of neonates
makes tracheal intubation easier with the neonate's head at a neutral or slightly flexed position than with the
head hyperextended. Because the infant's larynx is higher in the neck than in adults, the infant's tongue
obstructs the airway more easily. The cricoid cartilage (as opposed to the vocal cords in adults) is the
narrowest portion of the larynx in pediatric patients and necessitates the use of tracheal tubes that minimize
risks of trauma to the airway and subsequent development of subglottic edema.

18
Some pathophysiology:
Angioedema describes urticaria involving the mucous membranes, particularly those of the mouth, pharynx,
and larynx
Foreign body aspiration into the airways, with its resultant airway obstruction, can produce a wide range of
responses. For example, complete obstruction at the level of the larynx or trachea can result in death from
asphyxiation. At the opposite end of the spectrum, passage of a foreign body into distal airways may elicit
only mild symptoms that may go unnoticed.
Reflux into the pharynx, larynx, and tracheobronchial tree can result in chronic cough, bronchoconstriction,
pharyngitis, laryngitis, bronchitis, or pneumonia. Morning hoarseness may also be noted.
Cricoarytenoid arthritis is common in patients with generalized rheumatoid arthritis. With acute
cricoarytenoid arthritis, hoarseness, pain on swallowing, dyspnea, and stridor may accompany tenderness
over the larynx. Redness and swelling of the arytenoids can be seen on direct laryngoscopy. With chronic
cricoarytenoid arthritis, patients may be asymptomatic or manifest variable degrees of hoarseness, dyspnea,
and upper airway obstruction. Cricoarytenoid arthritis may make endotracheal intubation difficult.
Farber's lipogranulomatosis is an inherited disorder due to a deficiency of ceramidase that results in
accumulation of ceramide in tissues (pleura, pericardium, synovial lining of joints, liver, spleen, lymph
nodes). Progressive arthropathy, psychomotor retardation, and nutritional failure are present, and most
affected individuals die by 2 years of age as a result of airway and respiratory problems. Acute renal and
hepatic failure may reflect accumulation of ceramide in these organs. Difficult airway management is a
common problem because of granuloma formation in the pharynx or larynx. Tracheal intubation is best
avoided in patients with upper airway involvement because laryngeal edema or bleeding from laryngeal
granulomas is possible.
Pulmonary edema may occur in severe preeclampsia. Low colloid osmotic pressure due to urinary losses of
albumin and increased capillary permeability lead to interstitial accumulation of fluid in the lungs. Clinically,
decreases in PaO2 are suspicious for interstitial pulmonary edema. These parturients may be at increased risk
of the development of pulmonary edema in response to intravenous fluid administration. Edema of the upper
airway and larynx, which may accompany normal gestation, is exaggerated in preeclamptic patients. This
change may influence the size of the endotracheal tube selected for tracheal intubation.
Mandibular hypoplasia is a prominent feature of several syndromes that affect pediatric patients. The small
mandible leaves little room for the tongue and makes the larynx appear to be anterior. Therefore, upper
airway obstruction and difficult tracheal intubation are likely.
Laryngeal papillomatosis is the most common benign laryngeal neoplasm in children. The most likely
cause is a tissue response to human papillomavirus. The mechanism of human papillomavirus infection in
the larynx is unclear. In many cases, it is suspected, but unproven, that transmission of the virus to the child
from a mother with genital warts occurs during vaginal delivery.

19
Anesthesia Pharmacology and the Larynx – NM Blockade:
The onset and intensity of neuromuscular blockade vary among muscle groups. This may be due to
differences in blood flow, distance from the central circulation, or different fiber types. Furthermore, the
relative sensitivity of a muscle group may depend on the choice of muscle relaxant. In general, the
diaphragm, jaw, larynx, and facial muscles (orbicularis oculi) respond to and recover from muscle relaxation
sooner than the thumb. Although they are a fortuitous safety feature, persistent diaphragmatic contractions
can be disconcerting in the face of complete adductor pollicis paralysis. Glottic musculature is also quite
resistant to blockade, as is often confirmed during laryngoscopy. The ED95 for laryngeal muscles is nearly
two times that for the adductor pollicis muscle. Good intubating conditions are usually associated with visual
loss of the orbicularis oculi twitch response.

The Airway:

 Mallampatti Class: does NOT have a high positive predictive value of difficult intubation

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Physical Examination of the Airway

 Obvious findings that may indicate difficult airway

o Inability to open mouth
o Poor c-spine mobility
o Receding chin (micrognathia)
o Prominent incisors
o Short, muscular neck
o Morbid obesity
o Injuries to face, neck or chest
o Acute airway compromise: agitation, anxiety, changes in respiratory rate/pattern, tachycardia
 Patency of nares
 Mouth opening – at least 3 fingerbreadths
 Teeth
o Poor dentition may increase risk of dental damage and dislodgement during airway
manipulation.
o Loose teeth must be identified preop and protected with plastic dental guard
 Neck
o If thyromental distance is < 3-4 fingerbreadths or 6 cm, may be difficult to visualize vocal
cords
 C-spine mobility
o Should be able to touch chin to chest and extend neck as far posteriorly as possible
 Tracheostomy stoma
o Healed or patent tracheostomy stoma may indicate subglottic stenosis
o Airway Classification
 Mallampati: when base of tongue is too large, tongue overshadows larynx
o Assessment made when pt upright with head in neutral position, mouth open as wide as
possible, and tongue protruded maximally
 AIRWAY ASSESSMENT
o Mallampatti Score (standard of care, must do on everyone, not a good predictor of difficult
airway)
o Thyromental distance (TMD) <6cm potentially difficult at least 3 finger breadths
o Sternomental distance (SMD) <12.5 potentially difficult
o ROM of neck, flex, extend, side to side
o Inter-incisor gap (how wide can you open your mouth? At least 3 cm or finger breadths)
o Upper lip bite test
o Co-existing disease (trauma, severe RA, Downs syndrome)
o Physical Signs: short fat neck, receding chin (at least 3 finger breadths), dentation, voice
(document hoarse voice pre op)
o Review previous anesthesia records
o Loose teeth

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 Airway Anatomy
o Nasal passages: Septum, turbinates, adenoids
o Oral cavity: Dentition and tongue
o Pharynx: Tonsils, uvula, epiglottis
o Glottis: Vocal cords narrowest part of adult airway
 Larynx: At C4-C6 level
o Unpaired: thyroid, cricoid, epiglottis
o Paired: arytenoid, corniculate, cuneiform
o Cricoid: only complete cartilaginous ring in respiratory system
 Narrowest portion of airway in pediatric patient is Cricoid (Vocal Cord in adults)
o Two groups
 Muscles that open and close glottis
 Lateral cricoarytenoid,
 posterior cricoarytenoid,
 transverse arytenoid
 Muscles that control tension of the vocal ligaments
 Cricothyroid,
 vocalis,
 thyroarytenoid

 Diseases that affect the airway

– Arthritis may lead to markedly decreased neck mobility. In RA, c-spine instability is
common. Atlantoaxial subluxation can occur with protrusion of odontoid process into
foramen magnum.
– Infection of floor of mouth, salivary glands, tonsils, pharyngeal abscess may result in pain,
trismus, edema, limited mouth opening.
 Tumors
– May obstruct or cause extrinsic compression and tracheal deviation
 Morbid obesity
– Sleep apnea, hypertrophied tonsils/adenoids
 Trauma
– R/O c-spine injury, basilar skull fracture, intracranial injury
 Trisomy 21
– Macroglossia, Atlantoaxial instability
 Scleroderma
– Decreased mandibular motion, narrowed oral aperture
 Acromegaly
– Mandibular hypertrophy 2o excessive growth hormone. Large tongue, epiglottis.
 Congenital anomalies
– Craniofacial abnormalities, e.g., Pierre Robin, Treacher-Collins

22
  Old medical records
– Prior anesthesia records
– See if ease of ventilation and intubation were documented
– Check for number of laryngoscopy attempts, ability to mask ventilate, type of laryngoscope
blade used, use of stylet
 Symptoms related to airway compromise
– Hoarseness, stridor, wheezing, dysphagia, dyspnea, positional airway obstruction
Physical Examination of the Airway
 Obvious findings that may indicate difficult airway
– Inability to open mouth
– Poor c-spine mobility
– Receding chin (micrognathia)
– Prominent incisors
– Short, muscular neck
– Morbid obesity
– Injuries to face, neck or chest
– Acute airway compromise: agitation, anxiety, changes in respiratory rate/pattern, tachycardia
 Patency of nares
 Mouth opening – at least 3 fingerbreadths
 Teeth
– Poor dentition may increase risk of dental damage and dislodgement during airway
manipulation.
– Loose teeth must be identified preop and protected with plastic dental guard
 Neck
– If thyromental distance is < 3-4 fingerbreadths or 6 cm, may be difficult to visualize vocal
cords
 C-spine mobility
– Should be able to touch chin to chest and extend neck as far posteriorly as possible
 Tracheostomy stoma
– Healed or patent tracheostomy stoma may indicate subglottic stenosis
– Airway Classification
 Mallampati: when base of tongue is too large, tongue overshadows larynx
– Assessment made when pt upright with head in neutral position, mouth open as wide as
possible, and tongue protruded maximally
Recognition of Airway Obstruction
 Stridor
 High-pitched crowing sound
 Rocking motion of chest/abdomen
 No excursions in reservoir bag
 Maneuvers to Maintain Airway Patency
 Neck extension
 Jaw thrust
– Place fingers under angles of mandible and lift forward

23
Airway Devices
Oral airway
– Helps relieve obstruction from tongue, soft palate
– May not be tolerated if intact gag reflex
– Complications: vomiting, laryngospasm, dental trauma
Nasal airway
– Helpful in pts with minimal to moderate obstruction
Laryngeal Mask
– Adult and pediatric sizes
– Inserted into hypopharynx, passed downward behind larynx, sealing glottic opening and
enabling ventilation after cuff inflated
– Slight bulging in tissues overlying larynx indicates mask in position
– Allows positive pressure ventilation, can support airway when trachea can’t be visualized
– Rescue airway“Can’t intubate/can’t ventilate” scenario
– Does not protect against regurgitation/aspiration
– Requires anesthesia for placement
Endotracheal Intubation:
– Provide a patent airway
– Prevent aspiration of gastric contents
– Need for frequent suctioning
– Facilitate positive pressure ventilation
– Operative position other than supine
– Operative site near or involving the airway
– Macintosh
Inserted with slight sweeping motion from right side of mouth, scooping tongue to midline
Tip inserted in valecula, space between base of tongue and pharyngeal surface of epiglottis
Provides good view of oro- and hypopharynx
Allows more room for ETT passage
Most adults intubated with #3 or #4
– Miller blade
Also inserted through right side of mouth
Tongue displaced to midline
Passed so that tip of blade lies beneath laryngeal surface of epiglottis
Epiglottis lifted to expose vocal cord
Allows better exposure of glottic opening but smaller passage through oro- and hypopharynx
Most adults require a #2 or #3 blade
– Intubation Position
Head elevated ~10 cm
Pads under occiput
Jaw lifted forward
Can be accomplished by placing 2 folded blankets under head to achieve “sniffing position”
 Head extended, neck flexed
 Oral, pharyngeal, laryngeal axes aligned so path from lips to glottis straight
line

24
 Nasal Intubation Technique
– Nasal mucosa anesthetized and vasoconstricted with 4% cocaine solution or phenylephrine-
lidocaine mixture using cotton-tipped pledgets
– If both nares patent, R nares preferred since bevel of most tracheal tubes when introduced on
right, will face flat nasal septum, reducing damage to turbinates
– Inferior turbinates usually interfere with passage, limit size of NTT
Usually a 6-6.5 NTT used for women, 7-7.5 for men
– Passage under direct vision with laryngoscope and Magill forceps may be required
– Complications
Bleeding
Sinus infection
Awake Intubation - Indications
– Difficult intubation anticipated in pt at risk for aspiration
– Uncertainty about ability to ventilate or intubate following GA induction
– Need to assess neuro function after intubation, e.g., unstable c-spine
– Awake Intubation - Technique
– Topical anesthesia
Cetacaine spray/gargle or 4% lidocaine spray/gargle; viscous lidocaine; 4% lidocaine nebulized – all to ↓
upper airway sensation
– Nerve block
SLN: walk off of hyoid bone caudally until in thyrohyoid membrane. Confirm (-) aspiration, then inject
lidocaine 2% 2cc bilat
RLN: transtracheal block, through cricothyroid membrane in midline, after aspiration of air. 4%
lidocaine, 4cc. Pt coughs, aids proximal anesthetic spread. Risk of aspiration in pts with full stomachs.
– Sedation
Midazolam (Versed) 0.05 mg/kg IV
Diazepam (Valium) 2-10 mg IV or 0.25 mg/kg IV peds
Lorazepam (Ativan) 2 mg or 0.044 mg/kg
Flumazenil (reversal) 0.2 mg IV or 8-15 mg/kg IV
Ketamine (NMDA antagonist) 1-2 mg/kg
Dexmedetomidine (selective alpha 2 agonist; Precedex) –loading dose of 1 mcg/kg IV over 10
min, followed by a maintenance infusion of 0.2 to 0.7 mcg/kg/hr
– Opioids
Fentanyl (Sublimaze) 1-2 mcg/kg
Alfentanil (Alfenta) 100 mcg
Remifentanil (Ultiva) 0.025-0.0625 mcg/kg/min
– Antisialogogues
Atropine (0.1 mg/kg adult; 0.05 mg/kg peds)
Glycopyrrolate (Robinol) 0.01-0.05 mg/kg
– Local Anesthetics (inhibit Na channels)
Lidocaine (Xylocaine) 5 mg/kg or 7 mg/kg with epi, max 300 or 500 mg
Tetracaine 1.5 mg/kg or 2.5 mg/kg with epi, max 20 mg
Benzocaine – rapid onset often mixed with aerosol tetracaine (hurricaine) in dose of 30 mg,
max dose 100 mg

25
  Light wand
– Malleable lighted stylet
– ETT passed over it, blindly into trachea
– Dim ambient light when using
– Light dims when wand in esophagus, brighter when in trachea
Fiberoptic Intubation
 Visual field can be limited as FOB nears glottic opening
– Secretions, blood, lens fogging can obscure view
– Immersion of FOB tip in warm water or silicone helps prevent fogging
 Standard equipment
– Oral bite block, Ovassapian airway, topical anesthetics, suction, fiberoptic scope with light
source
Indications for Fiberoptic Intubation
 In both awake, anesthetized pts
– Evaluation and/or intubation of airways
 Can be used nasally or orally
 Should be used as first option in anticipated difficult airway rather than last resort
 Recommended
– C-spine pathology, head/neck tumors, morbid obesity, prior history of airway management
problems
Technique
 ETT styletted over FOB
 Oxygen tubing attached to suction port
 Control level grasped with right hand while scope is advanced or maneuvered with left hand
– Oral Ovassapian airway helpful for oral attempts
 Keep scope in midline when advancing to avoid pyriform fossa
 Tip of scope positioned anteriorly when in hypopharynx and advanced toward epiglottis
 As scope slides beneath epiglottis, vocal cords will be seen
 Scope advanced through vocal cords with tip in neutral position until tracheal rings seen
 If adequate topical anesthesia, pt will tolerate without cough
 Scope is stabilized, tube advanced over it into trachea
 If resistance, may need to turn ETT 180o counterclockwise to prevent contact with anterior comisure

26
Retrograde Approach
 Needle inserted cephalad into cricothyroid membrane
 Guide wire delivered through mouth
 Needle removed
 ETT passed over guide wire and advanced into trachea
 Two ends of guide wire carefully followed
Percutaneous needle circothyroidotomy
– 14G angiocath placed through cricothyroid membrane into trachea
– Oxygen can be administered by connecting breathing circuit to 3 mm ETT adapter inserted
directly into IV catheter or to a 7.5 mm ETT adapter inserted into a 3 cc syringe barrel
connected to the IV catheter
– Once in place, carefully secure to neck to avoid barotrauma, massive subcutaneous
emphysema
– Can give either oxygen at 10L or jet ventilate
Cricothroidotomy
– With neck extended, transverse incision made in cricothyroid membrane in midline
– Handle of scalpel used to separate tissues separating cartilages until trach tube or ETT
inserted
Rigid bronchoscopy
– To support airway obstructed by foreign body, traumatic disruption, stenosis, or mediastinal
mass
– Need wide range of scope sizes
– Topical or GA
Tracheostomy
– Under local anesthesia prior to GA induction
Rapid sequence induction
– Pts at high risk for aspiration, e.g., recently eaten, pregnant, bowel obstruction, morbid
obesity, symptomatic reflux
– Need functioning tonsil-tip suction, several different laryngoscope blades, several syletted
ETTs
– Preoxygenate, Sellick’s maneuver, no attempt to ventilate, maintain Sellick’s until successful
intubation confirmed (ETCO2, BBS=)
Eschmann catheter/Gum Elastic Bougie
– The gum elastic bougie (GEB) or Eschmann catheter is a flexible piece of plastic about 2 feet
long with a slight 45° angle on its end. This device is helpful when an anterior larynx is
encountered and there’s difficulty in visualizing and/or intubating the larynx. The GEB can be
placed through the vocal cords with the use of laryngoscopy and an ETT “railroaded” over it,
thus using it as a stylet. When the GEB is properly placed in the trachea, a characteristic
“clicking” sensation is felt as it advances over the anterior tracheal cartilaginous rings.

27
 Cook exchange catheter
– The Cook airway exchange catheter (CAEC) is a long, flexible, hollow tube designed to
facilitate the exchange of an in situ endotracheal tube.

Acute Epiglottitis Croup (laryngeal bronchitis)

Etiology – Influenza type B Common cold

High fever  fever

Difficulty swallowing slow onset
Supraglottic structures
Viral Bacterial
Inspiratory stridor Croupy “barking” cough
Drooling Rhinorrhea
Lethargy
Sitting forward to breathe
Tachypnea
Cyanotic
Acidotic / dehydrated

TX: ampicillin cool humidified O2, racemic epi

Vaccination for Haemophilus *(0.25-0.5 ml of 2.25% epi in 2.5 ml NS)

Influenza type B before 2 y/o

* Requires IMMEDIATE intubation

28
Laryngospasm:
-Caused by stimulation of the External branch of the SLN
-Hypocalcemia
-Stimulation during Phase II of anesthesia
- Respiratory secretions, vomitus, blood or foreign body in airway

Treatment:
-forceful jaw thrust
-continuous positive pressure ventilation
-Succinylcholine 1mg/kg mg and emergent intubation to secure airway (taking into consideration that
if the patient was previously paralyzed with a NDMB and reversed with a anticholinesterase the
block from Succs will be prolonged; anticholinesterase agents inhibit pseudo cholinesterase which
metabolizes the Succs, pt’s with a pseudo cholinesterase insufficiency will also have a prolonged
block. Pt’s with burns, liver disease, organophaopate poisoning, taking echotiopate, malnutrition and
pregnancy may have a decreased level of plasma cholinesterase.

29
 Airway Review
A second review to hear the information a little bit different: Make Notes!
Airway exam

 Interincisor gap (IIG)

o Adequate > 4.5 cm
o Borderline – 4 cm
o Limited < 3.5 cm

 Mallampati classification - PUSH

o Class I – P – Pillars/Tonsils fully visible
o Class II – U – Uvula partially visible
o Class III – S – Soft palate visible
o Class IV – H – Hard palate visible

 Dentition
o Edentulous – increased risk of mask ventilation
o Prominent upper incisors – increased risk of difficult intubation
o Overbite/underbite - increased risk of difficult intubation
o Loose, chipped, carious teeth - increased risk of difficult intubation
 Prognathism
o An inability to prognath – increases risk of difficult intubation
 Temporomandibular joint (TMJ) stability – utilized to assess space during laryngoscopy
 Neck
o Short/thick neck – increased risk of difficult intubation
o C-spine range of motion – used to assess ease of positioning
 Requires sniffing position – neck flexion w/ head extension for 3 axis alignment
 Thyromental distance (TMD): Patil’s test
o Short TMD restricts adequate alignment of the oral, pharyngeal and laryngeal axes
 Normal > 6.5 cm
 Limited < 6 cm
 Hypomental distance (HMD)
o Small receding chin prevents adequate alignment of the oral, pharyngeal, and laryngeal axes
 Normal > 4 cm
 Limited < 4 cm

30
Advanced airway devices

 Face mask
o Technique
 PPeak should be limited to 20 cm H2O to avoid insufflation of the stomach
o Advantages
 Noninvasive
 Disposable/multiple sizes
 Cost-efficient
 Transparent to evaluate ventilation
 FiO2 > 90% with adequate seal
 Reduced incidence sore throat
o Disadvantages
 Increased dead space
 Increased risk of aspiration
 Increased risk of eye injury
 Increased risk of facial nerve injury
 Increased c-spine movement
 OR pollution
o Predictors of difficult mask ventilation
 Age > 57
 Male gender
 Obesity
 Snoring/sleep apnea
 Short, thick neck
 Short TMD
 Large tongue
 Mallampati Class III or IV
 Edentulous
 Presence of a beard
 Limited jaw protrusion
 NGT in situ
 Facial burns or trauma
 Laryngeal mask airway (LMA)
o Technique
 Following placement assess for leak ≤ 20 cm H2O – may require inflation of cuff
 Use of soft bite block to prevent obstruction of Classic, Excel, Flexible, and Unique
LMA’s
o Advantages
 Preferred device for difficult airway management
 Relative ease of insertion
 Greater seal than face-mask
 Reduced risk facial nerve and eye trauma compared to facemask
 Reduced OR pollution compared to facemask
 Reduced risk of tooth and laryngeal trauma compared to ETT
 Reduced risk of bronchospasm compared to ETT
 No risk of accidental esophageal or Endobronchial intubation

31
 o Disadvantages
 More invasive than facemask
 Increased risk of airway trauma compared to facemask
 Requires deeper plane of anesthesia
 Requires some TMJ mobility
 Less secure than ETT
 Limits use of PPV compared to ETT
 Increased risk gas leak and OR pollution compared to ETT
 Increased risk of aspiration compared to ETT
o Contraindications
 Pharyngeal pathology/obstruction
 Full stomach/pregnancy/risk of aspiration
 Hiatal hernia
 Low pulmonary compliance requiring PIP > 30 cm H2O
 Endotracheal tubes (ETT)
o Advantages
 Provides seal to prevent aspiration
 Definitive airway
o Disadvantages
 Invasive technique
 Risk of esophageal intubation
 Risk of bronchial intubation
 Risk of laryngeal nerve injury
 Risk of laryngeal mucosal injury
o ETT size
 ETT size = [4 + age(years) / 4]
 ETT depth = 3 x tube size
 Nasal ETT depth = oral ETT depth + 5 cm
 Pediatric ETT depth = [age / 2] + 12 or [kg / 5] + 12
 Fiberoptic bronchoscope
o Advantages
 Allows visualization of the lower airway
 Useful in difficult airway
 Allows an ETT to be advanced over the FOB to secure the airway
o Disadvantages
 Invasive technique
 Requires light source and advanced skill
 Risk of esophageal intubation
 Risk of bronchial intubation
 Risk of laryngeal nerve injury
 Risk of laryngeal mucosal injury
 May be time-consuming in patients with a difficult airway

32
  Eschmann stylet/gum elastic bougie (GEB)
o Technique
 Semi-rigid stylet allow intubation during limited DL
 May be used if ETT advancement is difficult
o Advantages
 Allows intubation when a limited view is obtained during DL
 May be used during difficult intubation
o Disadvantages
 Risk of nerve damage
 Risk of tracheal mucosal damage
 Cook airway exchange catheter (CAEC)
o Technique
 Long, flexible stylet used to exchange a new ETT for an older one
 Contains a connector to allow ventilation during use
 The CAEC is advanced ~ 5 cm past the tip of the existing ETT
o Advantages
 Allows replacement of an existing ETT
 Allows ventilation during exchange
 Minimal training
o Disadvantages
 Risk of esophageal intubation
 Risk of laryngeal mucosal damage
 Risk of nerve damage
Awake fiberoptic intubation

 Advantages
o Maintains spontaneous ventilation with high success rate
 Disadvantages
o Requires patient cooperation and practitioner skill
o Failed attempt – consider alternative options (noninvasive vs invasive) or cancel the case
Pertinent medications

 Propofol (Diprivan)
o Dosage: 10 – 20 mg
o MOA: Sedative-hypnotic  via selective modulator of GABA (A) receptors (the principle
neuroinhibitory transmitter in the CNS). GABA (A) activation results in transmembrane Cl
channels increasing in conductance  results in hyperpolarization of the cell membrane and
functional inhibition of postsynaptic neurons  CL channel stays open longer which
hyperpolarizes the cell membranes.
o Indications: To induce loss of consciousness. Maintenance of GA in mechanically ventilated
patients. Break laryngospasm.
o Side effects: The respiratory effects of propofol are potentiated by other respiratory
depressants, including benzodiazepines. AVOID in pts allergic to soybeans (soybean oil is
biggest component) and egg yolk (egg lecithin)

33
  Succinylcholine (Anectine)
o Dosage: 20 mg
o MOA: Depolarizing NMB. Acts directly on nicotinic receptors found in skeletal muscle motor
end plate and mimics the action of ACh, thus depolarizing the postjunctional membrane. This
results in sustained opening of the receptor ion channels so that they cannot respond to
subsequent release of ACh. Stimulates muscarinic receptors at the SA node  mechanism of
bradycardia. Treatment  atropine
o Indications: Paralysis of patient for induction of anesthesia. Break laryngospasm
o Side effects: Anticholinesterase agents inhibit pseudocholinesterase and thus prolong a
succinylcholine block. Anticholinesterase agents prolong a succinylcholine block but
REVERSE a nondepolarizing block. Raises ICP and IOP. Contraindicated in MH, patients
taking echothiopate eye drops, neuromuscular degenerative diseases, CVA, spinal cord injury,
MS, burns. Hyperkalemia  degree of K+ release is unpredictable in a pt with burn injury.
K+ is elevated 0.5-1.0 meq/L after succinylcholine
Airway anatomy/nerves

 Airway anatomy

34
Airway nerves

Epiglottis

Laryngeal spasm/treatments

 Triggering factors
o Respiratory secretions
o Vomitus
o Blood
o Foreign body in the airway
o Pain in any part of the body
o Pelvic/abdominal visceral stimulation
 Airway obstruction during laryngospasm is the contraction of the lateral cricoarytenoids, the
thyroarytenoid, and the cricothyroid muscles
 Management
o Immediate removal of the offending stimulus
o Administration of oxygen with continuous positive airway pressure
o If other maneuvers are unsuccessful the use of small dose of short-acting muscle relaxants
 Negative-pressure pulmonary edema may result from any airway obstruction in a patient who
continues to have a voluntary respiratory effort
o Negative intrathoracic pressure is transmitted to the alveoli, which are unable to expand
owing to the more proximal obstruction
o Fluid is entrained from the pulmonary capillary bed.
o Negative-pressure pulmonary edema is treated as any other form of noncardiogenic edema

35
Pediatric situations/management

 Acromegaly – macroglossia, prognathism (possibly difficult intubation)

 Becker’s muscular dystrophy (BMD) - possibly difficult intubation/trismus
 Cleft lip/palate – difficult mask ventilation and intubation
 Complete tracheal rings – limited room for ETT
 Crouzon syndrome – premature fusion of cranial sutures and facial bones
 Down syndrome – macroglossia, flattened nasal bridge, atlanto-occipital instability
 Duchenne’s muscular dystrophy (DMD) – possibly difficult intubation/trismus
 Dwarfism – large tongue, c-spine instability (possible difficult intubation)
 Esophageal atresia (EA) – possibly difficult intubation
 Goldenhar syndrome – mandibular hypoplasia
 Klippel-Feil syndrome – cervical spine fusion restricts neck movement
 Pierre-Robin syndrome – macroglossia, cleft palate, micronathia
 Tracheal stenosis – limited room for ETT
 Tracheoesphageal fistula (TEF) – possibly difficult intubation
 Treacher-Collins syndrome – mandibular hypoplasia

36
 Airway Review
Think about things!

A proper Airway Exam includes:

1. Mallampati score
2. Any loose teeth or dentures
3. Mouth opening distance
4. Thyromental distance
5. Ability to prognath
6. Any history of neck/airway surgery
7. Range of motion of neck
8. History of difficult intubation
9. Length of neck
10. Circumference of neck
11. Presence of beard----can I use a tegaderm for a better seal?

Advanced Airway devices and indications:

1. Supraglottic airways – (Fast track LMA) The Laryngeal Mask Airway is a device that sits just
superior to the glottis. The LMA helps maintain a patent airway when the patient has redundant
tissue or OSA. The Fast track LMA was designed not only to be an effective airway device in and of
itself for short supine procedures, but also to facilitate blind intubation because the mask aperture is
aligned with the glottic vestibule. The ETT may be inserted blindly through the LMA and passed
through the vocal cords. Once the ETT is in place, the LMA may be removed while the ETT is held
in place. If the ETT does not pass through the LMA, the LMA may still be used to ventilate until
another viable option for intubation is found.
2. Fiberoptic: With the ETT on the distal end of the fiberoptic scope, the fiberoptic scope is placed into
the trachea and the ETT then slid into the trachea. This is helpful for difficult or anticipated difficult
airways, lower and upper airway obstruction, unstable or fixed C spine, dental risk or damage or
awake fiberoptic placement as described below.
3. Glidescope: The glidescope is much like a MAC blade with a camera on the end of it which provides
a picture on a larger screen. This provides a point of sight for the operator that is more distal on the
blade (more towards the base of the tongue) than what the operator might see with the normal DL.
This may ease placement for the anterior airway or unstable C spine. It also proves to be
advantageous when more than one operator needs to visualize tube placement (student/preceptor,
surgeon with NIM tube, etc).
4. Oral/Nasal RAE: The Oral and Nasal RAE tubes are ETT’s with curved tops to allow for space for
surgery. Rather than have the ETT and inspiratory and expiratory tubing sticking up or out, the RAE
tubes allow the tubing to pass off to the side and out of the surgical field. The Nasal RAE is placed
by first having the patient sniff Afrin (oxymetazolone) a few squirts in each side to vasoconstrict the
superficial vessels and open the airway and noticing which side is more open. Once the patient is
asleep, the chosen nare is dilated with nasal trumpets of increasing sizes until finally the Nasal RAE
is gently passed through the nares. Then, using a glidescope or chosen DL blade, the Nasal RAE is
passed through the vocal cords. A Magill forceps may be required to assist passage.

37
5. Bougie: A bougie stylet may be solid or hollow, semimalleable, and blindly manipulated into the
trachea. Then an ETT is placed over the Bougie and slid into the trachea. Once the bougie enters the
larynx and trachea, a distinctive clicking feeling occurs as the top passes over the cartilaginous
structures. The hollow bougies may even allow oxygen insufflation and release of CO2.
6. Awake Fiberoptic placement:
 Indications: difficult airway which may not be able to be secured under anesthetic state
 Advantages: maintain spontaneous ventilation, increased size and patency of pharynx, relative
forward placement of the base of the tongue, posterior placement of the larynx, patency of the
retropalatal space, maintenance of upper and lower esophageal sphincter tone reducing risk of
reflux, pt maintains ability to protect airway by closing glottis or expel aspirated material by
coughing, ability to perform active sensory motor testing immediately after tracheal intubation in
unstable C-spine patient.
 Cautions: possible cardiovascular stimulation in the face of cardiac ischemia or risk of ischemia,
bronchospasm, increased IOP or ICP, the patient who is unable to cooperate (mental retardation,
dementia, intoxication) or allergy to local anesthetics
 Medications: avoid polypharmacy (more than two drugs)
o small doses of benzodiazepines (alter GABA receptor to potentiate affinity for receptor)
may be used to alleviate anxiety, doses should not be large enough to cause airway
obstruction or apnea, interfere with ability to protect airway from regurgitated gastric
contents or cause the patient to be uncooperative
 Midazolam (Versed) 0.05 mg/kg IV
 Diazepam (Valium) 2-10 mg IV or 0.25 mg/kg IV peds
 Lorazepam (Ativan) 2 mg or 0.044 mg/kg, whichever is smaller
 Flumazenil (reversal) 0.2 mg IV or 8-15 mg/kg IV
o Opioids help with sedation and antitussive effects (thru mu, kappa and delta receptors in
the brain and spinal cord):
 Fentanyl (Sublimaze) 1-2 mcg/kg
 Alfentanil (Alfenta) 100 mcg
 Remifentanil (Ultiva) 0.025-0.0625 mcg/kg/min
 Naloxone (reversal) 1-4 mcg/kg
o Other sedatives
 Ketamine (NMDA antagonist) 1-2 mg/kg
 Droperidol (Butyrophenone – largely dopamine antagonist) 0.0625-1 mg IV
 Dexmedetomidine (selective alpha 2 agonist; Precedex) – given in loading dose of
1 mcg/kg IV over 10 min, followed by a maintenance infusion of 0.2 to 0.7
mcg/kg/hr
o Antisialogogues
 Atropine (0.1 mg/kg adult; 0.05 mg/kg peds)
 Glycopyrrolate (Robinol) 0.01-0.05 mg/kg
o Vasoconstrictor – oxymetazoline (Afrin)
o Local Anesthetics (inhibit Na channels)
 Lidocaine (Xylocaine) 5 mg/kg or 7 mg/kg with epi, max 300 or 500 mg
 Tetracaine 1.5 mg/kg or 2.5 mg/kg with epi, max 20 mg
 Benzocaine – rapid onset often mixed with aerosol tetracaine (hurricaine) in dose
of 30 mg, max dose 100 mg

38
  Anatomy:
 Nasal cavity/nasopharynx
 Innervated by greater and lesser palatine nerves (nasal turbinates and most
of septum) and anterior ethmoid nerve (innervating the nares and anterior
third of the nasal septum); originate from sphenopalatine ganglion which is
posterior to middle turbinate
o Local anesthetic soaked cotton applicator may be passed along
upper border of middle turbinate until posterior wall of
nasopharynx is reached and left for 5-10 minutes
 Oropharynx
 Innervated by branches of vagus, facial and glossopharyngeal nerves
o Glossopharyngeal – travels anteriorly along lateral surface of
pharynx
 3 sensory branches to posterior third of tongue, vallecula
and anterior surface of epiglottis (lingual branch), walls of
pharynx (pharyngeal branch) and tonsils (tonsillar branch)
o Internal branch of SLN provides sensory innervation to base of
tongue, epiglottis and aryepiglottic folds and arytenoids
 Vocal folds and trachea
 Innervated by sensory recurrent laryngeal nerve which can be anesthetized
with a transtracheal block (4 mL of 2 or 4% Lidocaine thru cricothyroid
membrane into trachea, patient cough will spread LA)

Laryngeal spasm and treatment:

o Triggers:
o Respiratory secretions, vomitus, blood or foreign body in airway, pain in any part of the body,
pelvic or abdominal visceral stimulation
o Treatment:
o Remove offending stimulus if known and apply continuous positive airway pressure with
oxygen
o If unsuccessful, may also use muscle relaxant (succinylcholine (anectine) 10 mg IV)
o If still unsuccessful, consider tracheostomy or cricothyrotomy
Epiglottitis and treatment (pediatric situations):
o Progesses quickly with symptoms of inspiratory stridor, retractions, tachypnea, drooling and
difficulty swallowing; many children also assume the tripod position
o Caused by influenza, streptococcus, staphylococcus, candida and other fungal pathogens, usually
affecting children ages 1-7
o The child should be emergently intubated if possible with a 0.5 smaller size ETT than would
normally be chosen for that child
o A MAC blade can be carefully advanced along the midline of the tongue to the base, into the
obliterated vallecula due to swelling of the lingual surface of the epiglottis
o A stylet within the ETT will be helpful in directing the tube past the swollen epiglottis
o If DL is unsuccessful, a rigid bronchoscope may be helpful or tracheostomy or cricothryotomy may
become necessary

39
o Once airway is secured, cultures should be sent and appropriate antibiotics started. The child should
remain intubated in the ICU for 24-48 hours until the swelling has resolved.
o Sedatives and narcotics (see types and doses above) may be used to keep the patient comfortable and
preferably maintaining spontaneous ventilation in case of self extubation, restraints may also be
necessary.

40
 All that is Airway- SRNA Study Guide for Boards

Airway Exam Review- At least 8 points, if not more

“Difficult intubation and inadequate ventilation/oxygenation account for the almost half closed damaging
events in trends of anesthesia related death and brain damage closed claim analysis”
Any single test on determining ease of DL/Mask/Intubation/LMA placement has a LOW
sensitivity/specificity, you need to use a multivariate index comparing/evaluating multiple factors when
determining difficult airway.
In the end predicting difficulty of mask/DL/intubation is an enigma- sometimes assessing can be misleading.
Some “good” airway assessments surprise you on DL/mask. The key here- BE PREPARED. Listen to your
instincts. Have your best tools upfront and used first when there is ANY QUESTION. Some studies suggest
video laryngoscopy may make assessment deficits irrelevant- interesting- although a tool is only as good as
the person using it
1. Look at any/all previous anesthetic/H +P records for previous DL, mask, intubations, LMA
placement, etc. You will find pearls in the records, be aware some details might be missing. That is
why it is important to properly document your airway management on record.
2. Ask the patient/family if any hx of difficult airway management, airway anomalies, congenital
disease, masses, laryngospasm/bronchospasm, airway dx, history.
3. There is a LARGE amount of pathologies associated with difficult airway management- many of
them simply require common sense- review records, diagnostics, proper questioning.
a. OSA- STOPGAP screening if they might have OSA but not diagnosed, yet. - Snore loudly?
Tired during daytime? Observed apnea during sleep? High blood Pressure? BMI>35? Age over
50? Neck circumference>15.75 inches? Male Gender?
b. Look at table 29-2, 29-3 p. 754 755 in BCS Clinical Anesthesia text.
4. Difficult Mask- M.O.A.D.S- Mask seal (beard/mustache) Obese (BMI>26), Age (>55), Dentures
(edentulous, if so use dentures for mask and take out for intubation), Snoring.
5. Difficult Laryngoscopy- L.E.M.O.N-
a. Look externally- abnormal faces? Micrognathia? Trauma? Patent nares?
b. Evaluate: mouth opening- Interincisor distance >3cm, preferably 6. TMD- >3 FB or 6cm.
Ability to prognath. No overbite. Long vs. short incisors. Dentition- loose teeth/missing teeth?
Crappy methhead teeth?
c. Mallampati class-
i. Grade 1- tonsillar Pillars, Uvula, Soft Palate, Hard Palate seen—PUSH
ii. Grade 2-As above- except uvula only partially seen, only partially see pillars
iii. Grade 3- Only soft palate visible- DIFFICULT INTUBATION POTENTIAL
iv. Grade 4- You can’t see anything- can’t even see the soft palate, even when they are
actually following direction and actually really opening their mouth wide- DIFFICULT
INTUBATION POTENTIAL

41
 d. Obstruction- macroglossia, Ludwig angina etc
e. Neck Mobility- Must be able to touch chin to chest and extend neck as far posteriorly as possible
w/o pain, numbness/tingling, etc. Short thick neck? Fat chunky neck? No neck?- if u see this,
with inability to prognath, and can’t see anything in the mouth in a fat OSA DM patient- just
make sure you have a video laryngoscope or FOB, and use it first, not second. Also- how is their
C-spine? Prior surgeries? Radiation to neck? Cervical radiculopathy? Things to look for- DM
and prayer sign, unstable fractures, Down Syndrome, RA, Ankylosing Spondylitis, Klippel-Feil
syndrome etc.
6. Difficult Supraglottic Airway- R.O.D.S.- Restricted mouth opening, Obstruction of upper airway,
Distortion/disruption of airway, Still lungs- reduced compliance
7. A difficult DL does not predict a difficult intubation, same with easy DL- could still be a difficult
intubation- conditions altering anatomy of larynx- pre-existing conditions- tracheal deviation, tumors,
bleeding disorders, neck abscesses, subglottic stenosis, croup, Ludwig angina etc. Also skill-
aligning tube- tool inexperience etc.

42
 Airway Anatomy
UPPER AIRWAY
THE PHARYNX- musculomembranous tube double role- passage of food and gases. Divided into regions-
NASOPHARYNX- posterior to nasal cavity. Communicates via posterior nasal apertures except for soft
palate which forms floor of the nasopharynx.
1. The roof/posterior walls- supported by sphenoid bone and basilar occipital bone.
2. The Nasopharynx contains- Pharyngeal tonsil- called adenoids- can interfere with breathing. Also
contains auditory tubes (Eustachian tubes) - connects nasopharynx to middle ear to equalize pressure
on both sides of tymp. Membrane.
3. Levator Veli Palatine- IS THE PRINCIPAL ELEVATING muscle of soft palate- Innervated by the
VAGUS Nerve. Say AHHH! - This is the vagus nerve in action here.
4. Nasopharynx contains septum, turbinates, and adenoids.
OROPHARYNX- Posterior to oral cavity- extends from soft palate to epiglottis.
Contains- Pharyngeal tongue, palatine tonsils, laryngopharynx, epiglottis

MUSCLES OF THE PHARYNX

Muscle Origin Insertion Actions Innervation

Superior side of tongue, median raphe of constricts walls pharyngeal
Constrictor M. mylohyoid line pharynx of pharynx branches of the
of the mandible posteriorly and during vagus nerve
and pterygo- the pharyngeal swallowing (CN X)
mandibular tubercle of
raphe basilar part of
occipital bone
Middle greater and lesser median raphe of
Constrictor M. horns of hyoid pharynx
bone and posteriorly
stylohyoid
ligament
Inferior cricoid cartilage
Constrictor M. and oblique line note: inferior
of thyroid constrictor
cartilage surrounds the
upper
esophagus
Salpingo- cartilaginous side of pharynx elevate the
Pharyngeus M. portion of blending palato- pharynx which
auditory tube pharyngeus shortens and
widens it
Palato- hard palate sides of during
pharyngeus M. pharynx, swallowing and

43
 Stylo- styloid process esophagus and speech glossopharynge
pharyngeus M. of temporal posterior border al nerve (CN
bone of thyroid IX)
cartilage - these
muscles blend at
their insertions

VASCULARIZATION OF THE PHARYNX

ARTERIES OF THE PHARYNX

Artery Origin Course Distribution
Ascending external carotid ascends on pharynx pharynx
Pharyngeal A. artery medial to the internal
carotid a.
Ascending Palatine facial artery passes over the upper soft palate and part
A. border of the superior of pharynx
constrictor
Tonsillar Br. pierces the superior major supply of
constrictor m. palatine tonsil
Inferior Thyroid A. thyrocervical trunk - see The Subclavian Pharyngeal brs.
a branch of the Artery and its supply part of
subclavian artery Branches pharynx

INNERVATION OF THE PHARYNX

NERVES OF THE PHARYNX

Nerve Origin Course Distribution
Glosso-pharyngeal motor to
(CN IX) N. see The Cranial Nerves stylopharyngeus m.
and sensory to
mucous membrane
Pharyngeal vagus nerve (CN X) contribute to the motor to superior
Branches of Vagus pharyngeal plexus and middle
N. on the pharynx which constrictors,
also includes palatopharyngeus,
sympathetic fibers salpingo-pharyngeus
from the mm.
sympathetic trunk,
branches from the
glossopharyngeal n.
(sensory) and
branches form the
external laryngeal n.
(motor)
44
 NERVES OF THE PHARYNX (CONT.)
Nerve Origin Course Distribution
External Laryngeal superior laryngeal descends deep to the inferior constrictor
N. nerve - branch of sternothyroid to (and cricothyroid of
vagus nerve reach the inferior the larynx)
constrictor and
cricothyroid
Maxillary N. (V2) trigeminal nerve see The Cranial sensory to mucous
(CN V) Nerves membranes of soft
palate

Lower Airway- LARYNX

1. Structure below vocal cords- larynx at C4-C6 level
2. 9 Cartilages-
a. Unpaired- cricoid, thyroid, epiglottis
b. Paired- arytenoid, corniculate, cuneiform
3. Cricoid is the ONLY COMPLETE cartilaginous ring in resp. system.
4. Cricoid is the narrowest portion of airway in peds. Where the vocal cords narrowest in adult.
5. Motor Innervation of Larynx- THE RLN- EXCEPT for the cricothyroid muscle- this is the external
branch of the SLN.

45
 6. Sensory innervation of the Larynx-
7. CN IX- Glossopharyngeal- Posterior one third of tongue sensation and taste. Also innervates
sensation to roof of pharynx, tonsils, and undersurface of soft palate.
8. Facial Nerve VII- sensory to ant. 2/3 of tongue, and sense of taste “You taste with your face”
9. The Cricopharyngeus is the primary muscular barrier to regurgitation.
10. Functions of Intrinsic Laryngeal Muscles-
Posterior Cricoarytenoids Abducts, or dilates cords PCA- Pulls Cords Apart
(PCA)
Lateral Cricoarytenoids Adducts, or closes cords
Transverse arytenoid Closes rima glottidis- vocal
fold closure
Oblique arytenoid Decreases volume of larynx-
narrows the inlet
Aryepiglottic Narrows inlet- controls
sphincters to vestibule
Cricothyroid Increases vocal cord tension Crikey, those cords are tight?
Thyroepiglottics Widens inlet- controls
sphincters to vestibule
Thyroarytenoids Reduces cord tension- relaxes
they cords

IF there is Hoarseness in voice quality-

Damage to external SLN- paralyzed cricothyroid muscle- weakness and huskiness
Damage to unilateral right RLN- hoarseness paralyzed cord on one side that is midway between ad and
abduction.
If Bilateral RLN injury- aponia and total paralysis of cords with each cord assuming midway between ab and
adduction- cords can flop together causing TOTAL OBSTRUCTION- emergency- intubation required.-
HOWEVER- pimp question- is this the same if acute vs. chronic bilateral RLN damage?? NO!! If chronic-
less frequent airway issues since there are compensatory mechanisms such as atrophy of the laryngeal
musculature.

46
Which RLN is more susceptible to injury? Why the left of course- due to long path under aortic arch and up
to larynx.

TRACHEA-
1. Fibromuscular tube 10-12 cm long- 20 mm in adults.
2. Supported by 20 U shaped cartilages
3. Bifurcates at T4
4. R Mainstem- 2.5cm long with 25 degree takeoff
5. L Mainstem- 5 cm long with 45 degree takeoff angle
LARYNGOSPASM- forceful involuntary spasm of laryngeal musculature
+++++++Caused by stimulation of the SLN nerve++++
The muscles involved in laryngospasm- Cricothyroids- since they adduct and tense the true vocal cords.
More specifically then- the external branch of the SLN is the nerve that causes laryngospasm. OTHER
SOURCES STATE that laryngospasm is from the afferent fibers of the internal branch of the SLN- KEY
HERE- IT is caused by stimulation of the SLN.
1. Inversely related to age- most common in pediatrics
2. Emergence- 48%, induction- 28%, maintenance 24%
3. Risk factors-Can happen during stage 2, pharyngeal secretions, passing TT through larynx during
extubation. Anxiety, GERD, URI or active asthma, chronic smokers, airway anomaly. Also surgery
related- T&As, LMS, thyroid surgery, hypoparathyroidism, esophageal procedures. Anesthesia
related- barbiturates, Ketamine---saliva production- spasm, LMA>ETT>facemask, mucous or blood
after extubation, pediatrics much higher risk esp. in hands of inexperienced providers.
4. – EXTUBATE patients either fully awake or deeply asleep.
5. Prevention---- Identify patients at risk. Nonirritant inhalational esp. in prone patients such as
asthmatics i.e. sevo vs. des. Deep anesthesia prior to intubation/DL. Extubate while lungs are
inflated by positive pressure- decreases adductor response of laryngeal muscle. 5% CO2 inhalation
for 5minutes prior to extubation- CO2 exhalation drive- the laryngospasm reflex. Acupuncture.

47
6. Prevention- Drugs- Premedicate with BZD- decreases UA reflex during induction. Anticholinergics-
decreases secretions. Lidocaine- spray to larynx at 4mg/kg.
7. Treatment-
a. Partial laryngospasm- identify and remove the stimulus. Apply jaw thrust maneuver. Insert oral
or nasal airway. Positive pressure ventilation with 1.0 FiO2.
b. Complete laryngospasm- CALL FOR HELP. Deepen anesthesia level
c. If this occurs without IV line- IO route is faster than peripheral or IM!!
d. Lidocaine- SLN block- 5ml of 2% lidocaine. Transtracheal injection of 1-2 ml 4% lidocaine.

e.
Advanced Airway Devices
1. LMA-Flexible- Wire reinforced LMA that has a flexible tube. Its tube is longer and narrower than an
LMA-Classic. It can be bent to any angle. This allows positioning it away from the surgical field
without occluding the lumen or losing the seal. It is designed for use with surgery on the head, neck
or upper torso whereas a normal LMA such as the classic would be in the way. The LMA-Flexible is
more difficult to insert- this is why a stylet, small tracheal tube or other device may be inserted into
the tube to stiffen it.
2. LMA-Fastrach- Designed to overcome limitations when trying to intubate through the LMA –Classic.
This device has a short stainless steel shaft with a 15mm connector. Metal handle is also securely
bonded to shaft to facilitate one-handed insertion. Available in sizes 3, 4, and 5. Insertion is with
head in neutral position. It should be deflated and lubricated prior to insertion. Mask tip is
positioned flat against hard palate, and inserted with rotational movement. DO NOT use handle to
force mouth open. Very useful device in an anticipated difficult airway. Cricoid pressure
DECREASES success of intubation through it. The TT recommended is a silicone wire reinforced
cuff tube.

48
3. Bullard Laryngoscope- Rigid metal blade specially shaped
to follow contour of oropharynx and rest beneath epiglottis. As seen, fiberoptic are used with a lens
to visualize fiber optically. There is also a working channel for suction, O2 insufflation,
administration of LAs or saline, or passage of an airway exchange or jet ventilation catheter. This
device can be used in awake or anesthetized pt. As shown a TT with stylet is loaded onto device, the
blade is inserted midline in oral cavity. Look through the eyepiece AFTER advancing blade and feels
it has seated in the pharynx. Upward movement along axis of handle is done to facilitate visualization
of larynx. This device has been proven useful in difficult intubation hx patients, and kids with
Treacher Collins or Pierre- Robin syndrome. The Bullard does provide quicker intubations than a
standard FOB.

4. Shikani optical stylet- This is a stainless steel malleable stylet.

Comes in preformed J-shape but is unique in that it is malleable and be bent at the tip. There is both
an adult and pediatric size. Use- antifogging agent on lens. Insert TT on it with its tip protruding
past TT tip. DL or jaw thrust should be used to lift epiglottis, then handle is held in right hand, and
stylet inserted midline just beyond epiglottis. The stylet is then advanced under direct vision through
vocal cords. When intratracheal position is reached, the TT should be advanced. Practice will be
required for proficiency in this item.

49
 5. Glidescope- Miniature digital camera on underside of a plastic blade. An LED
mounted beside the camera provides illumination. Image is transmitted via cable to monitor screen.
Advantages- displayed anatomy is magnified, larger viewing angle, good teaching tool, verifying
tube position especially w NIM tubes etc. While head is neutral insert midline, then look at camera.
The blade should be advanced anterior to epiglottis. Sometimes intubation fails- tips- insert TT
upside down and rotating it, insert or withdraw stylet, put hook in stylet so when withdrawing TT
angles up, relax blade elevation or insertion.
6. Flexible Fiberoptic Endoscope
‐ It is used to place and evaluate placement of tracheal, double-lumen, tracheostomy, and gastric
tubes and bronchial blockers; check tube patency; evaluate the airway; and locate and remove
secretions. It can also be hooked up to a video camera and a screen.
‐ Intubation- The choice of TT is important- it will be easier to intubate the trachea if the largest
scope that fits easily inside the TT is used. Warming a standard TT may facilitate passage.
‐ It can be inserted either orally or nasally in awake or anesthetized patients either breathing or not.
‐ Most authors recommend using this in the awake patient under light sedation and regional/topical
anesthesia.
‐ Because the optical elements are small minute amounts of secretions, blood or debris can hinder
visualization.
‐ First the FOB is inserted through ETT and then inserted through mouth or nose and advanced to
posterior pharynx.

Adverse airway events are a major source of anesthesia

morbidity and mortality. The American Society of
Anesthesiologists has developed guidelines for
management of patients in whom endotracheal intubation
may be difficult or impossible or in whom unexpected
difficulties arise during routine attempts at laryngoscopy.

Endotracheal intubation performed with the patient awake

but with the airway locally anesthetized remains one of the
safest methods of securing a “difficult” airway, because it
allows airway manipulation while the patient is conscious,
can cooperate with the procedure, is most able to maintain
an open airway, and is less likely to regurgitate or vomit
and aspirate gastric contents. Expertise with awake
intubation techniques may be lifesaving and is part of the
core knowledge of every safe CRNA.

50
Both oral and nasal routes can be used for nonsurgical,
awake intubation of the trachea. Understanding of airway
anatomy and innervation is an essential requirement for
safe and atraumatic awake endotracheal intubation.
Practice with awake intubation techniques in the
nonemergency setting is essential preparation for
management of the difficult airway in emergency
situations.

INDICATIONS

 History of difficult intubation4

 Suspected difficult airway based upon findings in
history or physical exam including but not limited
to the following:
o Trauma to the airway
o Deep neck infections
o Tumors of the larynx or pharynx
o History of radiation to the airway
o Severe ankylosing spondylitis
o Acromegaly
o Congenital airway abnormality; such as
Treacher-Collins or Pierre Robin syndromes
o Inability to access the cricothyroid
membrane in case emergency surgical
airway is required
o Morbid obesity and history of sleep apnea
with suspected difficult airway requiring
intubation
o Anatomy that otherwise predisposes the
patient to difficult intubation and difficult
mask ventilation while asleep
 High risk for aspiration of gastric contents
 Need for neurological exam immediately following
intubation
o Cervical spine instability due to trauma or
degenerative disease
o Vertebrobasilar artery insufficiency

51
CONTRAINDICATIONS

 Absolute contraindications
o Patient refusal
o Allergy to both ester and amide classes of
local anesthetics
 Relative contraindications, which may be
overlooked in the true emergency situation, because
the risk of the procedure is less than the risk of
hypoxemia or impending loss of the airway
o Infection at sites of local anesthetic
injection/application
o Raised intracranial pressure (ICP) that might
be exacerbated by coughing
o Penetrating eye trauma that might be
exacerbated by coughing

EQUIPMENT

 Flexible fiberoptic bronchoscope and light source

 Suction
 Oxygen source
 Cuffed endotracheal tubes (in several sizes)
 Warm solution, such as saline surgical irrigation, in
a 1-L bottle
 Lubricant, such as silicone gel or (less desirable)
Surgilube (Fougera, Melville, N.Y.)
 Antifog liquid drops for the fiberoptic camera lens
 Tongue depressor or laryngoscope blade
 Nasal trumpet with 7.0 endotracheal tube (ETT)
connector inserted in proximal end
 An antisialogogue, such as glycopyrrolate (0.2 to
0.4 mg for adult patients)
 Local anesthetic, such as lidocaine (viscous 2%,
4%, and 5% paste)
 Phenylephrine (10 mg/mL)
 Sedative hypnotics, such as benzodiazepines or low
dose propofol infusions, together with an opiate
delivered in small doses (fentanyl or Remifentanil),
with or without Droperidol (not to exceed 2.5 mg in
adult patients)

52
 Right-angle forceps
 Cotton soaked pledgets
 Atomizer or Cetacaine (Cetylite, Pennsauken, N.J.)
topical spray
 Williams or Berman intubating oral airway
 Appropriate vital signs monitor

 Administer an antisialogogue, such as

glycopyrrolate 0.003 mg/kg IV unless
contraindicated.
 Position the patient with the head up at a 30- to 45-
degree angle (prevents tongue and pharynx from
collapsing posteriorly and obstructing view) and
administer oxygen via nasal cannula.
 Begin sedation, titrating midazolam 0.01 to 0.03
mg/kg and fentanyl 0.04 to 2.0 mg/kg IV in small
doses to avoid apnea. Other sedative and narcotic
agents may be used.
 There are many techniques for performing awake
blocks, and one method- To avoid systemic effects
of local anesthetic toxicity, do not exceed 5 mg/kg
of lidocaine in adult patients.
o Combine 9.5 mL of viscous 2% lidocaine
with 0.5 mL of 10 mg/mL phenylephrine.
o Apply mixture in 3-mL aliquots in one
nostril to lubricate the inside of the nose,
vasoconstrict vessels in the mucosa, and
block relevant trigeminal nerve branches.
Wait 3 to 5 minutes and repeat. Apply 1 mL
of 5% lidocaine paste to both sides of tongue
depressor and have patient suck on this
“lidocaine lollipop,” gradually advancing the
tongue depressor posteriorly over tongue
and hard palate as tolerated.
o Use the remaining viscous lidocaine-
phenylephrine mixture to lubricate the distal
tip of a nasal trumpet. Attach a 7.0 ETT
connector with a corrugated, flexible
endotracheal adaptor into the proximal end
of the trumpet.
o Gently place the nasal trumpet into the
nostril that was blocked, being careful to
avoid trauma.

53
 o Attach the patient to the anesthetic circuit
via the modified nasal trumpet with fresh
gas flows of 10 L/min to improve
oxygenation, monitor ventilation, and
prevent obstruction. By closing the patient’s
mouth and contralateral nostril, it is possible
to deliver positive pressure ventilation;
however, the goal should be to maintain
spontaneous ventilation at all times.
o When patient is able to tolerate application
of the lidocaine lollipop to the back of the
tongue, use it to expose the palatine tonsil.
o Using Cetacaine spray or an atomizer
attached to 2% lidocaine in a 5-mL syringe,
spray local anesthetic (2.5 mL of 2%
lidocaine or three 1-second sprays) at each
tonsil upon inspiration to block the
glossopharyngeal nerve.
o Place two cotton pledgets soaked in 2%
lidocaine in right-angle forceps, ensuring
that the pledgets extend beyond metal tip,
and wind string around forceps so that
pledgets cannot be dislodged. Apply the
pledgets to the laryngeal mucosa overlying
the superior laryngeal nerve by angling the
forceps towards the pyriform fossae. Feel for
the pledgets externally by palpating the
inferolateral aspect of the mandible. Hold
pledgets over mucosa for 90 to 120 seconds
and then repeat on contralateral side.
 Place a size 10 Williams intubating oral airway in
mouth.
 Remove the ETT connector and place it within easy
reach.
 Apply lubricant, such as a small drop of silicone
gel, over the fiberoptic scope, spreading it up and
down the length of the scope, taking care to avoid
coating the lens.
 Apply Antifog drop to the lens of the scope.
 Thread the ETT over the fiberoptic scope and
loosely tape the two together with the bevel of the
endotracheal tube facing posteriorly during the
intubation.

54
  Insert the ETT (and fiberoptic scope) into the oral
airway and advance to the posterior pharynx.
 Obtain a view of the glottic opening, pinch off the
suction source, and squirt 2 mL of 2% lidocaine
through the injection port of the fiberoptic scope,
through the vocal cords and into the trachea to
anesthetize the recurrent laryngeal nerve. Injection
of local anesthetic into the trachea directly with a
needle risks trauma to the trachea, and should be
done only with caution.
 Advance the fiberoptic scope through the vocal
cords.
 Confirm that the fiberoptic scope is in the trachea
and not the esophagus by noting the presence of
tracheal rings.
 Slide the endotracheal tube into the trachea and off
of the fiberoptic scope.
o If ETT will not pass, the beveled tip is likely
inhibited by the right arytenoid cartilage.
Withdraw the ETT several cm and rotate it
90 degrees counterclockwise. Do not force
the tube against resistance.
o Should repeated attempts fail, because of
difficulty passing the endotracheal tube
through the vocal cords despite proper
visualization, consider changing to a Parker
endotracheal tube, which has a tapered bevel
located posteriorly?
 Confirm the correct depth of endotracheal tube by
measuring distance from the carina to tip of the
ETT, and reattach connector.

Pertinent Medications including those described above-

for awake FOB intubation.-

-Midazolam 0.01-0.03mg/kg MOA- Facilitates the action

of Gamma-aminobutyric acid (GABA) (The main
inhibitory NTM in body) by enhancing the affinity of
receptors for GABA- as a result of increasing the affinity
for this inhibitory neurotrans- there is enhanced opening of
the Cl gating channels resulting in increased CL
conductance- producing hyperpolarization of the
postsynaptic cell membrane making them more resistant to
excitation- causing 1. Anxiolysis, 2. Sedation, 3.

55
ANTEROGRADE amnesia, ETOH potentiation, 4.
Anticonvulsant and 5. Skeletal muscle relaxant effects.

Elim T1/2 1-4hours.

Side effects- Fatigue, drowsiness, hypoventilation,
hypercapnea. Impaired motor abilities, cognitive deficits,
decreased motor coordination. The old and liver failure
patients- very sensitive!!- decreased protein binding.

GABA- A-1 produces sedation

GABA A-2 produces anxiolysis.
GABA A-1 is the MOST ABUNDANT subtype.

Where are these receptors?- A-1 thalamus, cerebral and

cerebellar cortex
A-2- hippocampus and amygdala
-Is Versed initially water soluble, or lipid soluble? Why?
Water soluble- because IV pH is 3.5 Versed has a pH
dependent RING OPENING PHENOMENON- ring is open
at pH<4, which is water soluble. However, when it goes in
blood- physiologic pH brings it to >4, closing the ring-
making it very lipophilic.

-Lidocaine- max dose 4.5mg/kg, 7mg/kg with epi MOA

inhibits passage of Na ions through ion-selective sodium
channels in nerve membranes- subsequently slowing the
rate of depolarization so that a threshold potential is not
reached and an action potential is not propagated.

Side effects- just be careful about toxicity levels and know

how much you are giving. Most common cause of toxic
reactions are from intravascular injection.
 -CNS Effects
 1. Toxic reactions primarily involve the
CNS and secondarily the cardiovascular
system.
 2. Mild signs and symptoms:
 talkativeness
 sensory disturbances (tinnitus,
perioral tingling, slurred speech)
 drowsiness
56
  lightheadedness
 restlessness
 tremor

 Excitation related to selective blockade of inhibitory

cortical synapses which allows facilatory neurons to
function unopposed.
Progressing serum levels- seizures, lethargy, drop of BP,
HR, RR, and CV collapse. EKG changes, prolonged PR,
widened QRS.

Order of Block-
1. Sympathetic
2. Pain
3. Cold
4. Warmth
5. Touch
6. Deep Pressure
7. Motor

Glycopyrrolate 0.003mg/kg MOA- combines with

muscarinic cholinergic receptor-competitively
antagonizing- preventing AcH to these sites. M2 and M3
receptor-airway relaxation on airway smooth muscle. M3-
bronchial, salivary and bronchial secretion- mediates
against agonist induced bronchoconstriction, dries up
mucous membranes. M3- Cardiac- SA, AV and purkinje-
increase in HR.
- M1, M3, M5- G-protein activation- PL-C stimulation-
Ca2 mobilization.
M2, M4- G-protein activation- adenylyl cyclase activation-
inhibits voltage gated Ca2 channels
Glycopyrrolate acts at ALL AcH- Muscarinic receptor
subtypes.
Elimination 1/2T- 1.25hours. Onset 2-3minutes. DOA 6
hours.
Side Effects- Increase in HR- increase in O2 consumption.
Blurred vision, arrhythmias, palpitations, HTN,
Hypotension, excitement nervousness tremors- many more-

-Fentanyl- 0.01-0.08mcg/kg titrated in SMALL increments

MOA- Opioid/phenylpiperidine- Mu agonist. Ligands of
and actions mediated by the opioid receptors
Binding of the opioid peptides or opiates to these receptors
affects pain pathways via two
primary mechanisms:
closing presynaptic voltage gated Ca2+ channels, which
reduces neurotransmitter release
opening postsynaptic K+ channels, which hyperpolarizes
and inhibits the activity of those cells
57
Norepinephrine, glutamate, substance P, serotonin, and
acetylcholine are among the
Neurotransmitters whose release is reduced. In addition,
adenylyl cyclase activity is decreased,
And this appears to inhibit the inward Na+ current that
regulates spontaneous firing. Opioids act
both pre- and post-synaptically in the dorsal horn of the
spinal cord, where they thus inhibit
ascending transmission of nociceptive stimuli to the brain.
They also activate pain control circuits that descend from
the midbrain to the spinal cord, and the
actions at the spinal and supraspinal levels are synergistic.
In addition, they act at peripheral μ opioid
receptors that are localized on the terminals of sensory
neurons.

Effects of the opioid receptor agonists

Analgesia: an altered perception of and reaction to pain,
increased pain threshold, allaying of anxiety, euphoria, and
drowsiness or sedation. Spinal and supraspinal sites are
involved. Other sensory modalities are unaffected.
Respiratory depression: from decreased sensitivity of
the brain stem respiratory center to CO2 and from direct
depression of the respiratory center.
Cough suppression (antitussive action) results from
inhibition of the cough reflex, a direct effect on the cough
center of the medulla that is not linked to respiratory
depression.
Increased CSF pressure results from hypercapnia
(increased PCO2) and dilation of cerebral blood vessels.
Stimulation of chemoreceptor trigger zone of the
medulla produces nausea and vomiting in ambulatory
patients. Serotonin receptor (5-Ht3) antagonists can
alleviate this effect.
Miosis (pupillary constriction) results from disinhibition
of the Edinger-Westphal nucleus.
Hypothalamic and pituitary effects: Hypothermia is a
result of effects on the heat regulatory mechanism of the
hypothalamus. Other hypothalamic effects include
inhibition of gonadotropin releasing hormone (GnRH) and
corticotrophin releasing factor (CRF), with ensuing effects
on pituitary gonadotropin and ACTH release. Plasma
prolactin is increased due to decreased release of dopamine.
Mu agonists increase the release of vasopressin
(antidiuretic hormone, ADH), while agonists inhibit
ADH release and cause diuresis.
Effects on smooth muscle, most notably that of the
gastrointestinal tract, include increased muscle tone and
spasms, constriction of sphincters, decreased peristalsis,
58
decreased secretory activity, and a decreased defecation
reflex. Effects on the bile duct include constriction of
sphincter of Oddi and constriction and spasm of the smooth
muscle. Similarly, effects on the
urinary bladder include increased tone, rate, and amplitude
of contraction of the ureter, increased tone of the external
sphincter, increased bladder volume, and inhibition of the
urinary voiding reflex. Opioid analgesics also result in
constriction of bronchial smooth muscle secondary to
histamine release. In contrast, cutaneous blood vessels
dilate, in part due to histamine release, and pruritus is a
common side effect.
Cardiovascular effects vary. Most opioids produce
orthostatic (postural) hypotension.
Fentanyl DOA 1-2hours, Peak effect 30min, onset rapid 1-
5min.
Side effects- Dizziness
• Altered L. O. C.
• Hallucinations
• Euphoria
• Mental impairment
• Hypotension
• Seizures (rare)
• Lightheadedness
• Bradycardia,
Tachycardia
• N/V
• CNS Depression
• Respiratory Depression
• Muscles Rigid

Fentanyl Elim T1/2 LONGER than Morphine at 2-4hours.

This reflects a larger Vd than Morphine.

-Alfentanil 1-40mcg/kg MOA see Fentanyl. - FASTER

onset than Fentanyl with an effect-site equilibration time of
1.4minutes. This is because of the LOW pK of this opioid-
nearly 90% of drug exists in nonionized form at
physiologic pH. Elimination T/12 1.5-2hours. DOA 5-
10minutes. Onset immediate.
SEs- See fentanyl
-Remifentanyl 0.01-1mcg/kg/min MOA see fentanyl.
Similar effect site equilibration of Alfentanil- making its
onset almost immediate. Structurally unique- ester side
linkage chemically- so that it is metabolized by nonspecific
plasma and tissue esterases, giving it an extremely fast
offset. Elimination T/12 of 6 minutes, just about the same
as its context sensitive T/12 of 4 minutes. SEs- see
Fentanyl-

59
  -Dexmedetomidine 1mcg/kg bolus over 10min
followed by 0.2-0.7mcg/kg/hr. MOA- Highly
selective specific and potent A-2 agonist causing
neg. feedback which decreases NE release from
presynaptic terminal. Lowers MAC via
postsynaptic 2 mechanism

 Interacts with pre- & postsynaptic 2 adrenergic

receptors to ↓ central sympathetic tone
 Hypnotic effect due to hyperpolarization of cell
membranes and decreased firing in the Locus
Ceruleus (main adrenergic nucleus in brain)
function
 LC contains receptors for glutamate, GABA, ACh,
opioids, benzos Onset 5-8min. Peak 10-20min.
DOA 2-4 hours 1/2life 6minutes

Side Effects- Hypotension, BRADYCARDIA- esp. in

young patients, A-fib, Tachycardia, N/V, dry mouth,
vomiting, resp. depression, hypoxia, bradypnea,

Oxymetolazone 2-4gtts of 0.25% solution per nare. MOA-

selective alpha-1 agonist and partial alpha-2 agonist.
Selectively agonizes α1 and partially α2 adrenergic
receptors.[6] Since vascular beds widely express α1
receptors, the action of oxymetazoline results in
vasoconstriction. In addition, the local application of the
drug also results in vasoconstriction due to its action on
endothelial postsynaptic α2 receptors; systemic application
of α2 agonists, in contrast, causes vasodilation because of
centrally-mediated inhibition of sympathetic tone via
presynaptic α2 receptors.[7] Vasoconstriction of vessels
results in relief of nasal congestion in two ways: First, it
increases the diameter of the airway lumen; second, it
reduces fluid exudation from postcapillary venules.
Onset 5 minutes: Side effects when taken in large doses it
can cause hypotension because of a central clonidine like
effect. Rebound effect, rhinitis medicamentosa

60
 Pediatric Airway Stuff/Situations/Etc
Narrow nares. Preferential nose breathers in neonates. Large tongue. High glottis, slanting vocal cords,
narrow cricoid ring that is subglottic.
Infant larynx at C3-C4, where adult is C4-C5
Pediatric Airway Pathology-
Nasopharynx issues- Choanal atresia, stenosis, encephalocele, foreign body, nasal congestion, and teratoma.
Tongue issues- Hemangioma, Down syndrome, burn, laceration, Beckwith-Wiedemann syndrome,
hypothyroidism, mucopolysaccharidosis, cysts, etc.
Mandible/Maxilla issues- Hypoplasia- Pierre-Robin, Treacher-Collins, Goldenhar, Apert syndromes. Turner
syndrome, Cornelia de Lange, Smith-Lemli-Opitz, Hallermann-Streiff, Crouzan syndromes. Fractures,
trauma, RA, tumors.
Pharynx/Larynx issues- laryngomalacia, Freeman-Sheldon sx, laryngostenosis, laryngocele, laryngoweb,
hemangioma, trauma, epiglottitis, acute tonsillitis, abscesses and polyps, Arnold-Chiari malformations
Tracheal issues- vascular rings, tracheal stenosis, tracheomalacia, laryngotrecheobronchitis, mediastinal
tumors, neurofibroma, and lymphomas.
Cricoid cartilage is narrowest point of airway in kids.
-Epiglottitis- Caused by Hemophilus Influenza TYPE B.
1. Treatment- Ampicillin, vaccination before age 2
2. Age 2-7. High fever common. Difficulty swallowing obviously, rapid progression from sore throat to
complete airway obstruction. Inspiratory stridor, lethargy, tachypnea, neutrophilia, cyanotic, acidotic,
dehydrated, elevated CO2 and decreased pH.
3. These kids are sitting forward and upright, with chin up, mouth open, drooling.
4. Sedate in sitting position, NO muscle paralysis, airway exam before extubation. These patients require
IMMEDIATE INTUBATION- IN THE OR. Fluids, fluids, fluids. O2 plus Sevo. May develop pulm
edema, pericarditis, meningitis, septic arthritis. Have a small tube with a leak.
ALSO SEE COTE pp. 274-278

61
The following are the AANA standards of care in detail, what follows are my easy to remember way
for standards and definitions of standard, policy, guideline and suggestion.

Standards for Nurse Anesthesia Practice

These standards are intended to:
1. Assist the profession in evaluating the quality of care provided by its practitioners.
2. Provide a common base for practitioners to use in their development of a quality practice.
3. Assist the public in understanding what to expect from the practitioner.
4. Support and preserve the basic rights of the patient.
These standards apply to all anesthetizing locations and may be exceeded at any time at the discretion of the
CRNA. Although the standards are intended to promote high-quality patient care, they cannot assure specific
outcomes. The CRNA should consider the integration of new technologies into current anesthesia practice.
There may be exceptional patient-specific circumstances that require deviation from a standard. The CRNA
shall document any deviations from these standards (e.g., emergency cases for which informed consent
cannot be obtained, surgical interventions or procedures that invalidate application of a monitoring standard)
and state the reason for the deviation on the patient’s anesthesia record.

Standard I
Perform and document a thorough preanesthetic assessment and evaluation

Standard II
Obtain and document informed consent for the planned anesthetic intervention from the patient or legal
guardian, or verify that informed consent has been obtained and documented by a qualified professional.

Standard III
Formulate a patient-specific plan for anesthesia care.

Standard IV
Implement and adjust the anesthesia care plan based on the patient’s physiologic status. Continuously assess
the patient’s response to the anesthetic, surgical intervention, or procedure. Intervene as required to maintain
the patient in
Optimal physiologic condition.

62
Standard V
Monitor, evaluate, and document the patient’s physiologic condition as appropriate for the type of anesthesia
and specific patient needs. When any physiological monitoring device is used, variable pitch and threshold
alarms shall be turned on and audible. The CRNA should attend to the patient continuously until the
responsibility of care has been accepted by another anesthesia professional.
a. Oxygenation
Continuously monitor oxygenation by clinical observation and pulse oximetry. If indicated,
continually monitor oxygenation by arterial blood gas analysis.
b. Ventilation
Continuously monitor ventilation. Verify intubation of the trachea or placement of other artificial
airway devices by auscultation, chest excursion, and confirmation of expired carbon dioxide. Use
ventilatory pressure monitors as indicated. Continuously monitor end-tidal carbon dioxide during
controlled or assisted ventilation and any anesthesia or sedation technique requiring artificial airway
support. During moderate or deep sedation, continuously monitor for the presence of expired carbon
dioxide.
c. Cardiovascular
Continuously monitor cardiovascular status via electrocardiogram. Perform auscultation of heart
sounds as needed. Evaluate and document blood pressure and heart rate at least every five minutes.
d. Thermoregulation
When clinically significant changes in body temperature are intended, anticipated, or suspected,
monitor body temperature in order to facilitate the maintenance of normothermia.
e. Neuromuscular
When neuromuscular blocking agents are administered, monitor neuromuscular response to assess
depth of blockade and degree of recovery.
f. Positioning
Monitor and assess patient positioning and protective measures, except for those aspects that are
performed exclusively by one or more other providers. Interpretation Continuous clinical observation
and vigilance are the basis of safe anesthesia care. Consistent with the CRNA’s professional
judgment, additional means of monitoring the patient’s status may be used depending on the needs of
the patient, the anesthesia being administered, or the surgical technique or procedure being
performed.

Standard Vl
Document pertinent anesthesia-related information on the patient’s medical record in an accurate, complete,
legible, and timely manner.

63
Standard Vll
Evaluate the patient’s status and determine when it is safe to transfer the responsibility of care. Accurately
report the patient’s condition, including all essential information, and transfer the responsibility of care to
another qualified healthcare provider in a manner that assures continuity of care and patient safety.
Standard Vlll
Adhere to appropriate safety precautions as established within the practice setting to minimize the risks of
fire, explosion, electrical shock and equipment malfunction. Based on the patient, surgical intervention or
procedure, ensure that the equipment reasonably expected to be necessary for the administration of
anesthesia has been checked for proper functionality and document compliance.
When the patient is ventilated by an automatic mechanical ventilator, monitor the integrity of the breathing
system with a device capable of detecting a disconnection by emitting an audible alarm. When the breathing
system of an anesthesia machine is being used to deliver oxygen, the CRNA should monitor inspired oxygen
concentration continuously with an oxygen analyzer with a low concentration audible alarm turned on and in
use.
Standard IX
Verify that infection control policies and procedures for personnel and equipment exist within the practice
setting. Adhere to infection control policies and procedures as established within the practice setting to
minimize the risk of infection to the patient, the CRNA, and other healthcare providers.
Standard X
Participate in the ongoing review and evaluation of anesthesia care to assess quality and appropriateness.
Standard Xl
Respect and maintain the basic rights of patients.
Put simply:
1) Preop eval
2) Consent
3) Anesthetic plan
4) Implement the plan, tailor it per patient response.
5) Appropriately monitor the patient during the implementation of the plan.
6) Document the anesthetic
7) When appropriate, transfer care to responsible party
8) Fire and electricity safety
9) Follow infection control policy
10) Review your cases and see what worked and what you can do better
11) Respect, speaks for itself.
64
Standard: A set of agreed upon “rules” to define a level of acceptable service.

Policy: A statement of intent that is carried out as a procedure or protocol.

Guideline: Aimed to streamline a process, set a routine.

Suggestion: An idea or plan put forward for consideration.

65
 History of safety checks & pin index system

 Introduction of safety features by the American National Standards Institute (ANSI) Committee Z79
o Sponsored by American Society of Anesthesiologists, 1956-1983
o Since 1983, representatives from industry, government, and health care professionals have
met on Committee Z79 of the American Society for Testing and Materials
 They establish goals that may become accepted as national standards for the safety of
anesthesia equipment
 Ralph Tovell voiced the first call for standards during WWII, as U.S. Army Consultant in Anesthesia
o Found that it was problematic that there were four different dimensions for connectors, tubes,
masks, and breathing bags  supplies sent out to the field hospitals may not have matched
the anesthesia machines
o Tovell encouraged all manufactures to select uniform orifice of 22 mm for all adult and
pediatric face masks and to make tracheal tube connectors 15 mm in diameter
o Introduction of additional advances:
 Tracheal tubes designed of nontoxic plastic
 Touch identification of oxygen flow control, which reduced the risk that the wrong gas
would be selected before internal mechanical controls prevented the selection of a
hypoxic mixture
 Pin indexing reduced the hazard of attaching the wrong cylinder in the place of
oxygen
 Diameter indexing of connectors prevented similar errors in high-pressure tubing
o For many years errors committed in reassembling hospital oxygen supply lines led to a series
of tragedies before polarographic oxygen analyzers were added to the inspiratory limb of the
anesthesia circuit
Jacob, A. K., Kopp, S. L., Bacon, D. R, & Smith, H. M. (2009). The history of anesthesia. In P. G.

Barash, B. F. Cullen, R. K. Stoelting, M. K. Cahalan, & M. C. Stock (Eds.), Clinical anesthesia (6th
ed, pp. 12-13). Philadelphia, PA: Lippincott Williams & Wilkins.

66
 Scavenging Systems

Flows of volatile anesthetics (VA) are much higher than the patient actually retains. Excess VA is expired
and becomes waste that needs to be expelled somewhere other than in the building.

‐ NIOSH determined maximum concentrations of VA and N2O allowable in parts per million.
o Halogenated Agents 2 ppm
o Nitrous Oxide 2.5 ppm
o Combination of Halogenated Agent and N2O is 0.5 and 2.5 respectively
o However, dental facilities are allowed 50 ppm of N2O alone.
‐ Some side effects of exposure to these waste gases are:
o Nausea, dizziness, headache, fatigue, irritability, sterility, miscarriage, birth defects, cancer,
liver & kidney disease ([Link]

The scavenging system creates a safe way to bring waste gases from the patient to the outside atmosphere by
trapping the gas at the site of overflow from the circuit. Whatever is missed by the scavenging system, from
machine leaks or improper practice, is diluted in the HVAC system and exhausted into the atmosphere.

Components:

1. Gas collection assembly

a. May be a manifold or expandable bag
b. Captures gas at the emission site and sends them to the transfer tubing
2. Transfer tubing
a. The transfer tubing brings the gases to the interface
3. Interface – has a reservoir capacity which protects patient’s lungs from excess positive or negative
pressure
a. See diagrams of Active vs Passive systems at:
[Link]
b. If the system becomes occluded, the interface provides positive pressure relief. If the
scavenging system is active (using a vacuum force) rather than passive, the negative pressure
relief prevents active suction on the lung.
c. Open – only with an active system
i. Breathing provides intermittent waste gases, the reservoir serves as a feed to the
continuous suction of gas and prevent overflow
d. Closed – system is connected to atmosphere through valves, provides positive pressure relief
but releases gases into room if block occurs. When the active system is used, the negative
pressure relief uses entrained room air.
4. Gas Disposal Tubing – carries gases from the interface to the Gas Disposal

67
 5. Gas Discharge – expels gases safely into the atmosphere
a. Non-recirculating
b. Recirculating vent system
c. Central vacuum system
d. Single purpose waste gas exhaust
e. Passive duct system
f. Absorber

Morgan Jr., G. E., Mikhail, M. S., & Murray, M. J. (2006). Clincal Anesthesiology, fourth edition. Ney York:
McGraw-Hill Companies.

Riutort, K. T., Brockwell, R. C., Brull, S. J., & Andrews, J. J. (2009). The Anesthesia Workstation and
Delivery Systems. In P. G. Barash, B. F. Cullen, R. K. Stoelting, M. K. Cahalan, & M. C. Stock,
Clinical Anesthesia, sixth edition (pp. 681-684). Philadelphia: Lippincott Williams & Wilkins.

68
The most up to date full machine check protocol recommendations were published the Anesthesia Patient
Safety Foundation in 2008. The document can be accessed at the following website:
[Link]

The development of the current protocol seems as if it took a number of years to complete. In 2003 the ASA
recognized that the 1993 pre-use anesthesia apparatus checkout recommendations (AACR) were becoming
obsolete with respect to modern anesthesia machines. As such, a task force was established and met
beginning in 2004. The task force consisted of members representing the major anesthesia delivery system
manufacturers, the American Association of Nurse Anesthetists (AANA), The American Society of
Anesthesia Technicians and Technologists (ASATT), and the ASA. The task force ultimately developed a
list of 15 separate items to be checked. They published that list in 2008. The 15 items are as follows (with
rationale):

Verify auxiliary oxygen cylinder and self-inflating manual ventilation device are available &
functioning.
Rationale: Failure to be able to ventilate is a major cause of morbidity and mortality related to anesthesia
care. Because equipment failure with resulting inability to ventilate the patient can occur at any time, a self-
inflating manual ventilation device (e.g. AMBU bag) should be present at every anesthetizing location for
every case and should be checked for proper function. In addition, a source of oxygen separate from the
anesthesia machine and pipeline supply, specifically an oxygen cylinder with regulator and a means to open
the cylinder valve, should be immediately available and checked. After checking the cylinder pressure, it is
recommended that the main cylinder valve be closed to avoid inadvertent emptying of the cylinder through a
leaky or open regulator.

Verify patient suction is adequate to clear the airway.

Rationale: Safe anesthetic care requires the immediate availability of suction to clear the airway if needed.

Turn on anesthesia delivery system and confirm that AC power is available.

Rationale: Anesthesia delivery systems typically function with backup battery power if AC power fails.
Unless the presence of AC power is confirmed, the first obvious sign of power failure can be a complete
system shutdown when the batteries can no longer power the system. Many anesthesia delivery systems have
visual indicators of the power source showing the presence of both AC and battery power. These indicators
should be checked and connection of the power cord to a functional AC power source should be confirmed.
Desflurane vaporizers require electrical power and recommendations for checking power to these vaporizers
should also be followed.

Verify availability of required monitors and check alarms.

Rationale: Standards for patient monitoring during anesthesia are clearly defined. The ability to conform to
these standards should be confirmed for every anesthetic. The first step is to visually verify that the
appropriate monitoring supplies (BP cuffs, oximetry probes, etc.) are available. All monitors should be
turned on and proper completion of power-up self-tests confirmed. Given the importance of pulse oximetry
and capnography to patient safety, verifying proper function of these devices before anesthetizing the patient
is essential. Capnometer function can be verified by exhaling through the breathing circuit or gas sensor to
generate a capnogram, or verifying that the patient’s breathing efforts generate a capnogram before the
patient is anesthetized. Visual and audible alarm signals should be generated when this is discontinued.
Pulse oximeter function, including an audible alarm, can be verified by placing the sensor on a finger and
observing for a proper recording. The pulse oximeter alarm can be tested by introducing motion artifact or
removing the sensor. Audible alarms have also been reconfirmed as essential to patient safety by ASA,

69
AANA, APSF and JCAHO. Proper monitor functioning includes visual and audible alarm signals that
function as designed.

Verify that pressure is adequate on the spare oxygen cylinder mounted on the anesthesia machine.
Rationale: Anesthesia delivery systems rely on a supply of oxygen for various machine functions. At a
minimum, the oxygen supply is used to provide oxygen to the patient. Pneumatically-powered ventilators
also rely on a gas supply.

Oxygen cylinder(s) should be mounted on the anesthesia delivery system and determined to have an
acceptable minimum pressure. The acceptable pressure depends on the intended use, the design of the
anesthesia delivery system and the availability of piped oxygen. Typically, an oxygen cylinder will be used if
the central oxygen supply fails.

 If the cylinder is intended to be the primary source of oxygen (e.g. remote site anesthesia), then a
cylinder supply sufficient to last for the entire anesthetic is required.
 If a pneumatically-powered ventilator that uses oxygen as its driving gas will be used, a full “E”
oxygen cylinder may provide only 30 minutes of oxygen. In that case, the maximum duration of
oxygen supply can be obtained from an oxygen cylinder if it is used only to provide fresh gas to the
patient in conjunction with manual or spontaneous ventilation. Mechanical ventilators will consume
the oxygen supply if pneumatically powered ventilators that require oxygen to power the ventilator
are used.
 Electrically-powered ventilators do not consume oxygen so that the duration of a cylinder supply will
depend only on total fresh gas flow.

The oxygen cylinder valve should be closed after it has been verified that adequate pressure is present, unless
the cylinder is to be the primary source of oxygen (i.e. piped oxygen is not available). If the valve remains
open and the pipeline supply should fail, the oxygen cylinder can become depleted while the anesthesia
provider is unaware of the oxygen supply problem.

Other gas supply cylinders (e.g. Heliox, CO2, Air, and N2O) need to be checked only if that gas is required
to provide anesthetic care.

Verify that piped gas pressures are ≥ 50 psig.

Rationale: A minimum gas supply pressure is required for proper function of the anesthesia delivery system.
Gas supplied from a central source can fail for a variety of reasons. Therefore the pressure in the piped gas
supply should be checked at least once daily.

Verify that vaporizers are adequately filled and, if applicable, that the filler ports are tightly closed.
Rationale: If anesthetic vapor delivery is planned, an adequate supply is essential to reduce the risk of light
anesthesia or recall. This is especially true if an anesthetic agent monitor with a low agent alarm is not being
used. Partially open filler ports are a common cause of leaks that may not be detected if the vaporizer
control dial is not open when a leak test is performed. This leak source can be minimized by tightly closing
filler ports. Newer vaporizer designs have filling systems that automatically close the filler port when filling
is completed. High and low anesthetic agent alarms are useful to help prevent over- or under-dosage of
anesthetic vapor. Use of these alarms is encouraged and they should be set to the appropriate limits and
enabled.

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Verify that there are no leaks in the gas supply lines between the flow meters and the common gas
outlet.
Rationale: The gas supply in this part of the anesthesia delivery system passes through the anesthetic
vaporizer(s) on most anesthesia delivery systems. In order to perform a thorough leak test, each vaporizer
must be turned on individually to check for leaks at the vaporizer mount(s) or inside the vaporizer.
Furthermore, some machines have a check valve between the flow meters and the common gas outlet,
requiring a negative pressure test to adequately check for leaks. Automated checkout procedures typically
include a leak test but may not evaluate leaks at the vaporizer especially if the vaporizer is not turned on
during the leak test. When relying upon automated testing to evaluate the system for leaks, the automated
leak test would need to be repeated for each vaporizer in place. This test should also be completed whenever
a vaporizer is changed. The risk of a leak at the vaporizer depends upon the vaporizer design. Vaporizer
designs where the filler port closes automatically after filling can reduce the risk of leaks. (Technicians can
provide useful assistance with this aspect of the machine checkout since it can be time consuming).

Test scavenging system function.

Rationale: A properly functioning scavenging system prevents room contamination by anesthetic gases.
Proper function depends upon correct connections between the scavenging system and the anesthesia
delivery system. These connections should be checked daily by a provider or technician. Depending upon the
scavenging system design, proper function may also require that the vacuum level is adequate which should
also be confirmed daily. Some scavenging systems have mechanical positive and negative pressure relief
valves. Positive and negative pressure relief is important to protect the patient circuit from pressure
fluctuations related to the scavenging system. Proper checkout of the scavenging system should ensure that
positive and negative pressure relief is functioning properly. Due to the complexity of checking for effective
positive and negative pressure relief, and the variations in scavenging system design, a properly trained
technician can facilitate this aspect of the checkout process.

Calibrate, or verify calibration of, the oxygen monitor and check the low oxygen alarm.
Rationale: Continuous monitoring of the inspired oxygen concentration is the last line of defense against
delivering hypoxic gas concentrations to the patient. The oxygen monitor is essential for detecting disruption
of the oxygen supply. Most oxygen monitors require calibration once daily, although some are self-
calibrating. For self-calibrating oxygen monitors, they should be verified to read 21% when sampling room
air. When more than one oxygen monitor is present, the primary sensor which will be relied upon for
oxygen monitoring should be checked. The low oxygen concentration alarm should also be checked at this
time by setting the alarm above the measured oxygen concentration and confirming that an audible alarm
signal is generated.

Verify carbon dioxide absorbent is not exhausted.

Rationale: Proper function of a circle anesthesia system relies on the absorbent to remove carbon dioxide
from rebreathed gas. Exhausted absorbent as indicated by the characteristic color change should be replaced.
It is possible for absorbent material to lose the ability to absorb CO2 yet the characteristic color change may
be absent or difficult to see. Some newer absorbents do change color when desiccated. Capnography should
be utilized for every anesthetic and, when using a circle anesthesia system, rebreathing carbon dioxide as
indicated by an inspired CO2 concentration > 0 can also indicate exhausted absorbent.

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Breathing system pressure and leak testing.
Rationale: The breathing system pressure and leak test should be performed with the circuit configuration to
be used during anesthetic delivery. If any components of the circuit are changed after this test is completed,
the test should be performed again. Although the anesthesia provider should perform this test before each
use, anesthesia technicians who replace and assemble circuits can also perform this check and add
redundancy to this important checkout procedure. Proper testing will demonstrate that pressure can be
developed in the breathing system during both manual and mechanical ventilation and that pressure can be
relieved during manual ventilation by opening the APL valve. Automated testing is often implemented in
the newer anesthesia delivery systems to evaluate the system for leaks and also to determine the compliance
of the breathing system. The compliance value determined during this testing will be used to automatically
adjust the volume delivered by the ventilator to maintain a constant volume delivery to the patient. It is
important that the circuit configuration that is to be used be in place during the test.

Verify that gas flows properly through the breathing circuit during both inspiration and exhalation.
Rationale: Pressure and leak testing does not identify all obstructions in the breathing circuit or confirm
proper function of the inspiratory and expiratory unidirectional valves. A test lung or second reservoir bag
can be used to confirm that flow through the circuit is unimpeded. Complete testing includes both manual
and mechanical ventilation. The presence of the unidirectional valves can be assessed visually during the
PAC. Proper function of these valves cannot be visually assessed since subtle valve incompetence may not
be detected. Checkout procedures to identify valve incompetence which may not be visually obvious can be
implemented but are typically too complex for daily testing. A trained technician can perform regular valve
competence tests. Capnography should be used during every anesthetic and the presence of carbon dioxide
in the inspired gases can help to detect an incompetent valve.

Document completion of checkout procedures.

Rationale: Each individual responsible for checkout procedures should document completion of these
procedures. Documentation gives credit for completing the job and can be helpful if an adverse event should
occur. Some automated checkout systems maintain an audit trail of completed checkout procedures that are
dated and timed.

Confirm ventilator settings and evaluate readiness to deliver anesthesia care. (ANESTHESIA TIME
OUT)
Rationale: This step is intended to avoid errors due to production pressure or other sources of haste. The
goal is to confirm that appropriate checks have been completed and that essential equipment is indeed
available. The concept is analogous to the “time out” used to confirm patient identity and surgical site prior
to incision. Improper ventilator settings can be harmful especially if a small patient is following a much
larger patient or vice versa. Pressure limit settings (when available) should be used to prevent excessive
volume delivery from improper ventilator settings.

Subset of items in the daily checklist to be completed between cases:

 Verify patient suction is adequate to clear the airway.

 Verify availability of required monitors, including alarms.
 Verify that vaporizers are adequately filled and if applicable that the filler ports are tightly closed.
 Verify carbon dioxide absorbent is not exhausted.
 Breathing system pressure and leak testing.
 Verify that gas flows properly through the breathing circuit during both inspiration and exhalation.
 Document completion of checkout procedures.
 Confirm ventilator settings and evaluate readiness to deliver anesthesia care. (ANESTHESIA TIME OUT)

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Desflurane vaporizers
Desflurane vaporizers are different than other vaporizers because of the physical properties of desflurane.
The main issue with desflurane is that it has a high saturated vapor pressure at room temperature (700mmHg
at 20°C). It boils at just 22.8°C compared with sevoflurane at 58.5°C or isoflurane at 48.5°C. What this
means is that small changes in ambient temperature will cause marked changes in the performance of the
vaporizer and great difficulty in controlling the delivered concentration of desflurane. Traditional vaporizers
have temperature compensating mechanisms that are very good at minimizing changes in delivered agent
concentration (at least with more modern vaporizers).
There are actually at least two designs of vaporizer for delivering desflurane that overcome this problem. The
Tec6 vaporizer has a heated reservoir that heats desflurane to 39°C (which causes the pressure inside to
climb to about 1500mmHg – it also means that there is a warm up period before you can use the vaporizer).
The Tec6 vaporizer utilizes a transform to convert alternating current to direct current to power the unit.
When you turn the dial to deliver desflurane, a valve to the reservoir opens and allows pressurized vapor to
leave. The vapor then passes through a pressure regulator which drops the pressure of the vapor beyond that
point. If we then consider the fresh gas side of the vaporizer, the incoming fresh gas passes through a fixed
restrictor. A differential pressure transducer then compares the pressure upstream of this fixed restrictor (in
the fresh gas side of the vaporizer) with the pressure downstream of the pressure regulator. An electronic
feedback system then controls the pressure regulator so that the pressure on both sides of the pressure
transducer is the same. The control dial on the vaporizer then allows desflurane from the vapor circuit to join
the fresh gas side of the vaporizer in accordance with the calibration settings on the dial.
To help understand why the vaporizer is designed like this, consider what will happen if you increase the
fresh gas flow rate. Because of the fixed restrictor, the upstream fresh gas flow pressure will increase. This
will be sensed by the differential pressure transducer resulting in greater opening of the vapor pressure
regulating valve and a greater quantity of vapor being delivered to match the increase in fresh gas flow rate.
The Aladdin cassette vaporizer works in a different way. It has a vapor chamber with the fresh gas flow
being split into a vapor chamber path and a bypass path. Electronic circuitry takes into account the fresh gas
flow rate (and type, e.g. O2/air or O2/N2O) and temperature of the agent. This is used to control a flow valve
in the outflow side of the vapor chamber path to allow the correct amount of desflurane to be added to the
fresh gas. This is not much different to how the Aladdin vaporizers for sevoflurane or isoflurane work, the
main difference being how the electronics predict the performance of desflurane in the vaporizer. The
desflurane cassette also has a fan that switches on to direct heat from the anesthetic machine onto the vapor
chamber if it gets too cold (from vaporizing desflurane).
Reference: Dorsch & Dorsch - “Understanding Anesthesia Equipment, 5th Edition”.

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 CO2 Absorbent

 CO2 chemically combines with H2O to form carbonic acid, the absorbents contain hydroxide salts that
are capable of neutralizing the carbonic acid.
o Neutralization reactions that are exothermic
o End products; carbonates, hydroxides, H2O, heat
 Mesh size 4-8; the size is a compromise between absorptive capacity and resistance to air flow through
the canister
 Optimum Hydration; 14-22%
 The patients tidal volume should not exceed the airspace between the absorbent granules (which is about
50% of the absorbents capacity) to ensure complete absorption of the CO2
 Peak; indicated by a color change or increased levels of inspired CO2, no longer able to absorb CO2.
 Regeneration (Soda lime); Carbonates get converted back to hydroxides, this restores the color and
allows the soda lime to be reused for a short period.
 Exhaustion; when the absorbent peaks, is allowed to regenerate and peaks again. It is now exhausted and
will not be able to regenerate.
o Clinical signs of exhaustion;
 1st; increased EtCO2 =>increased respiratory rate, respiratory acidosis
 Color change
 Catecholamine release related to increased CO2
 Flushed, sweating, cardiac irregularities, increased BP and HR which later fall
 Increased bleeding at surgical site
 Channeling/Funneling; gas takes the path of least resistance, so when you replace the absorbent shake it
to more evenly distribute the absorbent. Channeling can lead to rebreathing of CO2.

Soda lime

 94% Ca(OH)2 + 5% NaOH + 1% KOH

o Forms; CaCO3 + NaOH (2KOH), H2O, heat
 Ingredients; Calcium hydroxide, sodium hydroxide, potassium hydroxide
 More common
 Can absorb up to 23L of CO2 per 100g of absorbent
 Color change to violet when exhausted; an increased in the FGF will reduce rebreathing of CO2 until
the canister can be changed
Baralyme

 80% Ca(OH)2 + 20% Ba(OH)2

o Forms; CaCO3 + BaOH, H2O, Heat
 Ingredients; Calcium hydroxide, Barium hydroxide, water

Amsorb

 Contains Calcium hydroxide and calcium chloride

 Possesses greater inertness then soda lime or baralyme resulting in less degradation of volatile
anesthetics (Sevo into compound A & Des into carbon monoxide)

Morgan Jr., G. E., Mikhail, M. S., & Murray, M. J. (2006). Clincal Anesthesiology, fourth edition. Ney York:
McGraw-Hill Companies.

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Delivery: Breathing circuits

Information well conveyed by UD Mercy anesthesia website:

Breathing circuit classification

The function of any breathing circuit is to deliver oxygen and anesthetic gases, and eliminate carbon
dioxide. Carbon dioxide may be eliminated by either washout with adequate fresh gas flow (FGF), or by
soda lime absorption.

Mode Reservoir Rebreathing Example

(breathing bag)

Open No No Open drop

Semi-open Yes No Nonrebreathing circuit, or

Circle at high FGF (> minute
ventilation [VE])

Semi-closed Yes Yes, partial Circle at low FGF

(< VE)

Closed Yes Yes, complete Circle (with pop-off valve

[APL] closed)

The Circle system can be either

1. closed (fresh gas inflow exactly equal to patient uptake, complete rebreathing after carbon dioxide
absorbed, and pop-off closed)
2. semi-closed (some rebreathing occurs, FGF and pop-off settings at intermediate values), or
3. semi-open (no rebreathing, high fresh gas flow [higher than minute ventilation])

Open systems have no valves, no tubing: for example open drop ether, or a nasal cannula. In either, the
patient has access to atmospheric gases.

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Non-rebreathing (Mapleson) breathing circuits

All non-rebreathing (NRB) circuits lack unidirectional valves and soda lime carbon dioxide absorption:
thus, the amount of rebreathing is highly dependent on fresh gas flow (FGF) in all. Work of breathing is
low in all (no unidirectional valves or soda lime granules to create resistance).

How do NRB’s work? During expiration, fresh gas flow (FGF) pushes exhaled gas down the expiratory
limb, where it collects in the reservoir (breathing) bag and opens the expiratory valve (pop-off or APL). The
next inspiration draws on the gas in the expiratory limb. The expiratory limb will have less carbon dioxide
(less rebreathing) if FGF inflow is high, tidal volume (VT) is low, and the duration of the expiratory pause is
long (a long expiratory pause is desirable as exhaled gas will be flushed more thoroughly). All NRB circuits
are convenient, lightweight, easily scavenged. One objection is that the circuit must be reconfigured between
cases, with the possibility of error.

Minimum FGF In practice, most anesthetists will provide a minimum 5 L/min for children on up to adults
to prevent rebreathing (or 2-3 x minute ventilation [VE], whichever is greater).

The Bain circuit is a "coaxial" Mapleson D- the same components, but the fresh gas flow tubing is directed
within the inspiratory limb, with fresh gas entering the circuit near the mask. Fresh gas flow requirements are
similar to other NRB circuits. The Bain has been shown to add more heat and humidity to inhaled gases than
other Mapleson circuits.

The Pethick Test for the Bain Circuit

A unique hazard of the use of the Bain circuit is occult disconnection or kinking of the inner, fresh gas
delivery hose. If this occurs, the entire corrugated limb becomes dead space. This results in respiratory
acidosis which is unresponsive to increased minute ventilation. To perform the Pethick test, use the
following steps:

1. Occlude the patient's end of the circuit (at the elbow).

2. Close the APL valve.
3. Fill the circuit, using the oxygen flush valve.
4. Release the occlusion at the elbow and flush. A Venturi effect flattens the reservoir bag if the inner
tube is patent.

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 5. Dorsch & Dorsch (Understanding Anesthesia Equipment 4th ed. Williams & Wilkins: Baltimore.
1999:950-1.) give a second test. If fresh gas flow is established, and the inner tube is occluded, the
flow meter bobbins should dip (due to back pressure) if the inner tube is patent.

Circle Breathing Circuit

The circle is the most popular breathing system in the US. It cleanses carbon dioxide from the patient’s
exhalations chemically, which allows rebreathing of all other exhaled gases (a unique breathing arrangement
in health care, but used extensively in other environments e.g. space, submarine).

Diagram of the Circle system. Click on the thumbnail, or on the underlined text, to see
the larger version (20 KB).

Circle components: fresh gas inflow source, inspiratory & expiratory unidirectional valves, inspiratory and
expiratory corrugated tubing, Y connector, overflow (called pop off, adjustable pressure-limiting valve, or
APL valve), reservoir bag, carbon dioxide absorbent canister and granules. Resistance of circle systems is
less than 3 cm H2O (less than the resistance imposed by the endotracheal tube). Dead space is increased (by
all respiratory apparatus). VD/VT= 0.33 normally, 0.46 if intubated and 0.65 if mask case. Mechanical dead
space ends at the point where inspired and expired gas streams diverge (the Y-connector).

Diagram of the King circuit (top) compared to the Bain. (Modified from Nakae Y et al.
Anesth Analg 1996; 83:488-492). Click on the thumbnail, or on the underlined text, to see the larger version
(28 KB).

A "Universal F" or "Mera F" circuit (KingTM circuit) is a coaxial circle system, with the inspiratory limb
contained within the expiratory. Like a Bain, it is less bulky, and may offer more heat and humidification of
the inspired gases. Like the Bain, occult disconnection or kinking of the inner limb causes a huge increase in
dead space and respiratory acidosis (Anesth Analg 2001; 93:973-4). This respiratory acidosis does not
respond to increased minute ventilation either- if exhaled gases are not forced through the absorbent
granules, no amount of ventilation will cleanse carbon dioxide from the patient's exhalations. The tests for
inner tube patency which can be used for a Bain circuit are not readily adaptable to the circle system
connected to a King circuit.

Circle system advantages and disadvantages

Circle advantages:

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  constant inspired concentrations
 conserve respiratory heat and humidity
 useful for all ages (may use down to 10 kg, about one year of age, or less with a pediatric disposable
circuit)
 useful for closed system or low-flow
 low resistance (less than tracheal tube, but more than a NRB circuit)

Circle disadvantages:

 increased dead space

 malfunctions of unidirectional valves

Semi closed system – partial rebreathing of gasses, where as in a closed system FGF = minute volume. What
we use every day in the U.S. for anesthesia most commonly is the semi closed system.

Pulse Oximetry
Pulse oximetry: The pulse oximeter is a wonderfully simple device. It is noninvasive, easy to apply, cheap to
use and overall pretty reliable. The theory behind which is works is dependent upon the absorption of red and
infrared light. The pulse oximeter probe can either shine light through an extremity or rely on the reflection
of light into a photo detector. Two species of hemoglobin predominantly exist in the human body,
oxyhemoglobin and deoxyhemoglobin. Oxyhemoglobin indicates hemoglobin molecules that are saturated
by 1 to 4 molecules of oxygen. Based on the percent of total of 4 sites for oxygen to bind to hemoglobin a
pulse oximeter reading of total Sp02 is projected. i.e. 2 molecules of oxygen bound to hemoglobin would
represent a pulse oximeter reading of ~50% (theoretically).

Now let’s consider that there are millions of hemoglobin molecules in the body and hundreds of
thousands of hemoglobin molecules on each red blood cell. The pulse oximeter looks at a relatively large
sample of blood vs. a single RBC or Hgb molecule. It then gives a percent reading of all of the blood area
sampled. If someone were to have a low hemoglobin level, it would be easier for less oxygen to occupy more
hemoglobin, thus manifesting into a higher pulse oximeter reading. If someone has a low Hgb level and
normal pulse oximetry readings one would anticipate to see smaller variations of pulse oximeter values as
more oxygen may be dissolved in the blood (until oxygen has been diffused out of the blood to equilibrate
with inspired oxygen Pa02 = PA02). Therefore one error in pulse oximetry involves anemia; manifests into
falsely elevated readings during hypoxic states.

Other conditions that may affect pulse oximetry include any substance or pigmentation that might
alter the ability to accurately distinguish the ratio of light absorbed by oxyhemoglobin and
deoxyhemoglobin. Oxyhemoglobin absorbs more infrared light and oxyhemoglobin will absorb more red
light. Indigio carmine, methylene blue, indocyanine blue, and nail polish may all decrease pulse oximetery
values below what is truly happening as the dark colors of blue and green may decrease the amount of red
and infrared light reflected to the photodiode. Carboxyhemoglobin is when carbon monoxide (CO) is bound
to hemoglobin. Unfortunately for us, CO binds to Hgb with 200x more affinity than oxygen. CO will reflect
the same infrared light as oxyhemoglobin, thus providing a falsely elevated Sp02. More sophisticated multi-
wavelength pulse oximeter can detect carboxyhemoglobin and distinguish it from oxyhemoglobin.
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Methemoglobin is a state that can be a congenital or iatrogenic manifestation. Drugs like nitroglycerine,
nipride, benzocaine and prilocaine can cause methemoglobinemia.
Sulfur containing drugs including sulfasalazine, metoclopramide, morphine, furosemide all may
cause a degree of sulfhemoglobin, a condition where sulfur molecules bind to oxygen binding sites on Hgb.
This condition may manifest into falsely low oxygen saturation readings.

Methemoglobinemia is a scenario where the central iron molecule is altered from a 2+ ionic charge to
a 3+ ionic charge. This change in the iron molecule causes irreversible biding of oxygen to hemoglobin.
Saturations from pulse oximetry may be erroneous as methemoglobinemia absorbs red and infrared light
equally. This will likely manifest as false high values below 85% Sp02, and false low values above 85%.
ABGs can be drawn to illustrate the discrepancy caused by methemoglobin.

Cyanosis and excessively low saturations of oxyhemoglobin can also cause false readings as part of
the mechanism by which pulse oximetry operates is by the pulsatile flow of blood. The pulse oximeter can
distinguish arterial vs. venocapillary blood by its ability to pulsate light several hundred times per second.
This random sampling of readings accounts for variations in the absorption of red and infrared light that
translates into a pulse waveform on the monitor. This pulse waveform is essential for certain surgeries. We
can even estimate systolic blood pressure by the return of this waveform. Pulse oximeters can be placed on
extremities/ operative or not, to verify circulatory flow to specific parts of the body. Central oximeters at the
end of a pulmonary artery line can measure the oxygen saturation of blood prior to entering the lungs to give
an idea of how well the body is consuming oxygen.
Pulse oximetry should be placed on the right extremity for mediastinoscopy cases as compression of the
innominate artery may occur. Dampened waveform would be indicative of such arterial compression.
A variation of pulse oximetery would include cerebral oximetery, which uses a similar non-invasive
means to assess oxygen saturation. However, at any given time there is more venous blood than arterial
blood in the brain. Cerebral oximetry gives more of a mixed indication of oxygen saturation and perfusion to
the brain. It is also useful for non-pulsatile blood for cases of cardio-pulmonary bypass.
Dorsch, J., Dorsch, S. 2008. Understanding anesthesia equipment. 5th ed. Lippincott Williams & Wilkins:
Philadelphia PA

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 The Circle Breathing Systems

Most Popular Breathing System in the United States

 Named “Circle” because its components are arranged in a circular manner.

 What are the components of this circuit?

Fresh gas inflow source, Inspiratory and expiratory unidirectional valves, inspiratory and expiratory
corrugated tubing, Y connector, APL valve, reservoir bag, CO2 absorber canister and granules.

 Is the Circle system closed, semi closed, semi open, or open?

Know that the most COMMONLY used system the circle goes by is SEMICLOSED. HOWEVER, the
Circle system can be Semi open, Semi closed, or Closed- ALL DEPENDING ON FGF!! The Circle system
adds the benefit of a CO2 absorber- so that lower gas flows can be used since CO2 will be neutralized
instead of rebreathed.

Semi open- No rebreathing, requires a high FGF (>5lpm)- Circle is semi open when you increase
flows during emergence, when your CO2 absorbent runs out, when you are inducting and want to get your
volatile onboard fast- there is no rebreathing of any gases!!

Semi closed- Some rebreathing of exhaled gases, but not CO2, as absorber neutralizes it- MOST
COMMON. FGF between 1-5lpm

Closed- When the inflow gas exactly matches what is being taken up, or consumed. There is
complete rebreathing of exhaled gases, and the APL valve remains closed. Not commonly employed by the
Circle- FGF can be as low as 150-250ml/min just to meet anesthetic/physiologic requirements. Closed is
when FGF is between 150ml-500ml/min. Advantages? Efficiency of gas usage, economy, maximum
humidification. Disadvantages? Higher chance of hypoxic mixture in circuit- Unknown concentration of O2
and volatile and vary markedly between gas at fresh gas inlet and gas in the inspiratory limb of breathing
tube. Also- inability to rapidly change delivered conc. of gas and O2.

 Circle Advantages: Conservation of gases, body heat, and moisture. Minimal OR pollution,
constant inspired concentrations.
 Circle Disadvantages: Higher risk of leaks, tubing disconnections, failure of unidirectional valves,
bulky and not moveable, and increased dead space.
 Why are there unidirectional valves? Prevents rebreathing of exhaled gases.
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  Where is the dead space in the Circle? Between the Y-Piece and the patient.
 Where does FGF enter in the Circle? Between the absorber and the inspiratory valve

Bibliography
Morgan, G., Mikhail, M. S., & Murray, M. J. (2006). Clinical Anesthesiology. New York: McGraw-Hill.

Nagelhout, J. J., & Plaus, K. L. (2010). Nurse Anesthesia. St. Louis: Saunders Elsevier.

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 Oxygen and Carbon dioxide

The dissociation curve:

The oxyhemoglobin dissociation curve mathematically equates the percentage saturation of
hemoglobin to the partial pressure of oxygen in the blood. The strange sigmoid shape of the curve relates to
peculiar properties of the hemoglobin molecule itself:
Hemoglobin and oxygen act a little like parents and children. When all are living at home (i.e.
hemoglobin is fully saturated) then the parents don’t want any to leave: but once one has flown the
nest (i.e. dissociated from hemoglobin) – parents find it progressively easier to let go. What this
means that the conformation of the hemoglobin molecule depends on the number of molecules
bound: as one molecule of oxygen becomes unbound, the affinity for the others falls [and vice-versa].
This is represented by the oxyhemoglobin dissociation curve.

The lack of linearity of the curve makes interpretation of the oxygen content of blood difficult. At higher
saturation levels, above 90%, the curve is flat, but below this level the PaO2 declines sharply, such that at
75% saturation the PaO2 is about 47mmHg (mixed venous blood), at 50% saturation the PaO2 is 26.6mmHg,
and at 25% saturation the PaO2 is a miserable 15mmHg

The position of this curve may shift rightwards (lower saturation for given PaO2) or leftwards (higher
saturation for a given PaO2). Certain circumstances make the blood more likely to dump oxygen into the
tissues, and others make it more likely to cling on to oxygen. Active muscle needs more oxygen, so heat,
exercise, acidosis, hypercarbia and increased 2,3-DPG all cause a shift in the curve rightwards – releasing
oxygen. Conversely, when activity is minimal – such as in cold weather or during rest, when the tissues are
cold, alkalotic, hypocarbic and low 2,3-DPG, then hemoglobin holds onto oxygen. The curve also shifts
leftwards in carbon monoxide poisoning.

The Haldane Effect:

Deoxygenated blood can carry increasing amounts of carbon dioxide, whereas oxygenated blood has a
reduced carbon dioxide capacity.

The Haldane Effect describes the effect of oxygen on CO2 transport. The Haldane Effect (along with the
Bohr Effect) facilitates the release of O2 at the tissues and the uptake of O2 at the lungs. This is represented
by a right shift of the oxyhemoglobin dissociation curve and a left shift of the oxyhemoglobin dissociation
curve respectively. The Haldane Effect results from the fact that deoxygenated hemoglobin has a higher
affinity (~3.5 x) for CO2 than does oxyhemoglobin. Deoxygenated hemoglobin has a higher affinity for CO2
because it is a better proton acceptor than oxygenated hemoglobin. Therefore, when hemoglobin is
deoxygenated (i.e. at tissues) there is a right shift of the carbonic acid-bicarbonate buffer equation to produce
H+ which in turn increases the amount of CO2 which can be carried by the blood back to the lungs to be
exhaled. Then, with oxygenation at the lungs CO2 dissociates more readily from hemoglobin.

CO2 + H2O ⇆ H2CO3 ⇆ H+ + H+CO3-

The following is the general equation of the Haldane Effect

H+ + HbO2 ←→ H+Hb + O2
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In the end, the Haldane effect allows for approximately 50% of the CO2 excreted by the lungs and is
physiologically much more important than its reciprocal counterpart, the Bohr Effect (the effect of carbon
dioxide on oxygen transport.)

The Bohr Effect:

The Bohr Effect is the shift of the oxyhemoglobin dissociation curve due to CO2 entering and leaving the
blood at the periphery and the lungs. As CO2 enters the blood at the periphery, the pH decreases and the
curve shifts to the right facilitating unloading of oxygen, whereas the reverse is true in the lungs. 2, 3-DPG
decreases the affinity of hemoglobin for oxygen. 2, 3-DPG in red cells is increased by anemia and high
altitude.

As a rough guide: blood unloads about 25% of delivered oxygen to the periphery,

97% of O2 is transported bound to hemoglobin, 3% is dissolved in plasma.

I thought this video was fantastic at bringing it all together – it’s worth the 13 minutes of your life. Copy and
paste the link below.

[Link]

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 Temperature and Anesthesia

Measurements

 C= 5/9 (F-32)
 F=9/5 (C+32)
 K = C + 273 (273K = 0 C)

o Routes of heat loss;

o Radiation; 60%
o Convection 15-30%
o Evaporation; 20% (8% by evaporation from resp. passages)
o Conduction; <5%

 After induction of anesthesia, the transfer of heat from the core to the periphery occurs via AV shunts
(vasodilation), and this process cannot be stopped once it starts!! Most of our anesthetics are
vasodilators
 Anesthetic gases are apt to stay in solution as opposed to vaporizing in the cold patient, so they will
take longer to wake up
 Core Temperature; intrathoracic and intracranial contents (vital organs). The lower esophagus and ear
are sites for core temperature.

Hypothermia
o <36 degrees Celsius
o Complications of hypothermia
o Cardiac arrhythmias and ischemia
o Increased PVR
o Left shift of the hemoglobin-oxygenation saturation curve
o Reversible coagulopathy d/t platelet dysfunction
o Postoperative protein catabolism and stress response
o Altered mental status
o Impaired renal function
o Decreased drug metabolism
o Poor wound healing
o Increased incidence of infection
o Pediatrics and hypothermia
o Thin skin, low fat content and a higher surface relative to weight allow greater heat loss to the
environment in neonates.
o Non-shivering thermogenesis; the major mechanism for heat production in neonates.
Metabolism of brown fat and shunting of hepatic oxidative phosphorylation to the
thermogenic proton leak pathway.

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Heat Loss in OR
‐ Inspiration of bone-dry anesthetic gases contributes to the risk of hypothermia
‐ All means of heat loss are directly proportional to the amount of exposed skin, and inversely
proportional to the amount of insulation which resists heat loss
‐ Under anesthesia, humans become poikilothermic, i.e., they begin to equilibrate with the temperature
of their surroundings, as cold blooded animals do.
‐ Anesthetics in general depress the thermoregulatory center, cause peripheral vasodilation (esp.
volatile anesthetics), and suppress shivering
‐ Effects of hypothermia become clinically relevant with core temp < 34 C

Shivering Prevention/Treatment
‐ Prevention best method!
‐ Vasodilators – Nirtoprusside during rewarming after CPB helps body heat equilibrate in periphery
‐ Radiant heating
‐ Meperidine (Demerol) – unique among narcotics, decreases shivering by direct hypothalamic effect.
25-50 mg IV will decrease shivering 50% (12.5 works)
‐ Muscle relaxants if ventilated and sedated
‐ Phenothiazines such as prochlorperazine (Compazine)

Clinical Implication: Choice of Sites for Temperature Measurement

Rectal
‐ Perforation (infants)
‐ Slow equilibration with core temperature in adults
Bladder
‐ Depends on degree of urine flow
‐ In low urine flow states, this approximates rectal temperatures
Esophagus (distal 1/3)
‐ Upper esophagus may reflect temperature of inspired gases; lower esophagus is most nearly core
temperature of all the sites which we measure in the OR, plus safe to measure.
Tympanic
‐ Close to core and brain temp
‐ Risks of perforation of tympanic membrane
‐ Artifact from cerumen
Nasal or nasopharyngeal
‐ Wide fluctuations unless intubated, in which case it reflects brain temperature (blood flow past the
cribiform plate).

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Skin
‐ Uses the liquid crystal method. These adhesive mylar strips use micrencapsulated liquid crystal color
changing inks to precisely (±0.5oF) and reliably indicate temperature. However this is shell
temperature.
‐ No risks in measurement.
‐ May be especially useful measured as a second site as it reflects the degree of shock and consequent
peripheral vasoconstriction.
‐ Remember—temperature strips do not correlate with core temperature.
Axillary
‐ Accuracy will vary with placement (how close to axillary artery), blood flow to arm, whether arm
adducted.
"Core"
‐ Tip of thermistor in the pulmonary artery directly reflects core temperature.

Deliberate hypothermia
‐ Induced in cardiac or some neurosurgeries to reduce metabolic and tissue demands for O2, hopefully
lessening tissue damage during times of relative or absolute tissue ischemia. At 30oC, time for safe
vascular occlusion is twice that at 37oC. The threshold for ventricular fibrillation is a core
temperature of 30oC (some sources say 28oC); lower temperatures may be seen with extracorporeal
circulation.

Pyrexia
‐ In fever, the central "thermostat" is reset at a higher level due to pyogens from bacteria (endotoxins) or
endogenous factors. If body temperature > 42oC: cerebral impairment and deranged sweating control.
If >45oC, usually fatal.

Burns
‐ Heating of skin or tissue to > 45oC (113oF) causes burns. Creation of a burn will be determined by the
balance between heat arrival from outside sources, and the rate that the circulation removes heat
energy from the tissue.
‐ Therefore, since they are vasoconstricted peripherally, patients in shock are more susceptible.
‐ The operating room temperature is raised into the 90°F range, since these patients have interrupted skin
and large surface exposure.
‐ The surgeon will always ask about temperature, and procedures are sometimes performed in stages if
the patient becomes too cold (Typically, these patients are coming to the OR for debridement and
skin grafting.).

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Preventing Hypothermia in the Operating Room:
Passive warming
‐ Room temperature at least 21-24oC, especially in pediatrics.
‐ Insulation
Active warming
‐ Infrared radiant warmers (overhead warming lamps)
‐ Circulating water mattresses
‐ Forced-air warming (#1! – Bair Hugger)
‐ IV fluid warmers
‐ Heated airway humidifiers
‐ Heat and moisture exchangers

Areas of Concern
‐ Patient's airway where normal mechanisms of humidification (i.e., nose) are bypassed by ETT or
tracheostomy.
‐ Low humidity in OR allows buildup of static charges; when combined with flammable agents (no
longer used) may increase risk of fire/explosions. Though we no longer use flammable agents, risk of
fire is ever-present because of presence of fuel and oxidizer.

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 Pulse Oximetry and the Beer Lambert Law

 Pulse oximetry is mandatory for use during general anesthesia to measure oxygenation. Since its
invention, respiratory related malpractice claims have decreased.
o Helpful to prevent retinopathy of prematurity, for use with lung disease, special surgical
procedures that require one lung ventilation, etc.
 Pulse oximeters continuously measure pulse rate and give an estimate of hemoglobin oxygen
saturation. They are easy to apply and non-invasive. The light emitting diodes are place on one side
while the light detector or photodiode is placed on the opposite side of any perfused tissue that can be
transilluminated.
 Let’s look at how SpO2 correlates best with the Oxyhemoglobin dissociation curve.
o On the steepest part of the curve, a strong correlation exists between SaO2 and PaO2. But, at
a PaO2 > 75, the SaO2 plateaus and loses its ability to reflect changes in PaO2. However, it
is reported that SpO2 is usually within 3% of SaO2
 Pulse oximetry is based on 3 things:
o The color of blood as a function of oxygen saturation.
o The change in color results from the optical properties of hemoglobin and its interaction with
oxygen.
o The ratio of oxygenated hemoglobin and deoxygenated hemoglobin can be determined by
spectrophotometry (utilizes the Beer Lambert Law)
 Oxygenated Hgb absorbs more infrared light while deoxygenated Hgb absorbs more
red light.
 Beer Lambert Law or spectrophotometry= at a constant light intensity and hemoglobin
concentration, the intensity of light transmitted through a tissue is a logarithmic function of the
oxygen saturation of hemoglobin. This requires two wavelengths of light to distinguish oxygenated
from deoxygenated hemoglobin. One diode emits red light (660 nm) and near infrared light (940
nm). The photo detector measures the ratio of infrared and red light to determine SaO2.
 Pulse oximetry uses plethysmography (pulsatile waveform produced by arteries but not veins or
other tissues like muscles, bones or skin)
 SpO2 is not equal to SaO2. SpO2 is calculated using this equation:
o SpO2= O2Hgb/(O2Hgb + reduced Hgb) x 100
 Problems where SpO2 can be misleading:
o MetHgb – produces a falsely low reading of SpO2at SaO2> 85% and a falsely high SpO2
when SaO2 is < 85%
o Carboxyhemoglobin (COHgb) – also may falsely elevate SpO2 levels
o Physiologic or technical limitations:
 Dyes (methylene blue, indocyanine green, indigo carmine)
 Nail polish or ambient light
 Motion artifact, background noise
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  Electro cautery – photo detector may sense radiofrequency emissions and there have
been reports of burns or pressure necrosis
 Newer technologies – able to interpret SpO2 despite motion, low perfusion or MetHgb/COHgb by
using up to 8 wavelengths of light


Sources:

Greenberg, S. B., Murphy, G. S., & Vender, J. S. (2009). Standard Monitoring Techniques. In P. G. Barash,
B. F. Cullen, R. K. Stoelting, M. K. Cahalan, & M. C. Stock, Clinical Anesthesia, Sixth edition (pp.
700-702). Philadelphia: Lippincott Williams & Wilkins.

Morgan, G. E., Mikhail, M. S., & Murray, M.

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 Arterial Waveforms

‐ Indwelling arterial cannulation allows for monitoring of arterial blood pressure continuously and for
access for arterial blood sampling.
‐ The waveform may show trending changes in- Volume Status, Contractility, and SVR.
‐ Best site of cannulation- Radial artery. The six sites in order of preference are – RUBAFD- at least
according to Memory master- radial, ulnar, brachial plexus, axillary, femoral, and then dorsalis pedis.

Below you see a picture of a normal waveform and variations-

The first line and upstroke up to A is the Anacrotic Limb.

The down stroke leading to the next bump- C- is the Dicrotic Notch.

The down stroke following the dicrotic notch= B- is termed the Dicrotic Limb.

What does this all mean? Anacrotic Limb- The area that correlates with the QRS Complex on ECG. - This
rate of rapid rise reflects the velocity of blood ejected from the left ventricle (contractility) through the aortic
valve.

Variations in the Anacrotic Limb- It is more vertical in patients with regurgitation, anemia, fever and
hyperthyroidism. The upstroke is slower, thus making it less vertical, suggesting either aortic stenosis or
ventricular failure. The peak of the upstroke is your SBP.

KNOW: The upstroke reflects contractility and SVR. The upstroke will be FASTER if contractility is
increased or SVR is decreased. Conversely, the upstroke will be SLOWER if contractility is decreased
or SVR increased.

Dicrotic Limb (B) - This is the area that correlates with the T wave on ECG. Decreased blood pressure and
blood flow to the periphery represent this portion of the waveform.

Dicrotic Notch C- This notch represents aortic valve closure with onset of diastole and coronary perfusion.
This occurs at the end of the T wave on ECG.

Here another fun picture- remember this one?

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So what if there is a flat or non-existent dicrotic notch? Can mean the patient is dehydrated. Low
notch may mean high pulse pressure such as low diastole in septic shock. A flattened notch may also
mean cardiopulmonary valve insufficiency.

Variations in BP- BP varies with the site of measurement due to a hydrostatic effect. This pic above
shows an example in differences when standing- it varies with vessel size and distance from heart.
This is why, while you do not have to zero transducer at phlebostatic access- for proper reading, the
transducer should be at the phlebostatic access for most accurate reading.
In a sitting position- the transducer should be at the level of the Circle of Willis (base of the ear).

Respiratory Cycle- On inspiration during spontaneous. Respiration, decreased intrathoracic pressure

enhances venous return which increases CO and BP. Mild reversal on expiration.
IPPV- Causes a reduction in BP secondary to increase mean intrathoracic pressure. Controlled vent.
Has a greater effect- during inspiration there is increased intrathoracic pressure, thus a decreased
venous return, decreased CO and BP. The reduction in art waveform amplitude with ventilator
inspiration is more pronounced in dehydration- So if you see SBP variations with inspiration
compared with expiration- will clue you in that patient is dry- This is where Stroke Volume
Variance (SVV) comes from. You will ESPECIALLY see this variation during Tension Pneumo, or
Cardiac Tamponade- also called Pulses Paradoxes.

SVV- or Arterial “swing”

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 Technical Issues - Since intra-arterial BP monitoring relies on a pressure transducer, which converts
the displacement of a silicon crystal into voltage changes, which are amplified and filtered, there can
be issues if something is off. Readings are optimized when pressure tubing connected to catheter is
stiff, the mass of fluid is small, the number of stopcocks is limited, and the connecting tubing is not
excessive.

Damping- Due to restriction of transmission of wave form between

artery and transducer – catheter against wall or kinked, air bubbles in system, clot in cannula, no fluid-
coupling. Underdamped waveforms OVERESTIMATE SBP by 15-30mmHG and amplifies artifact
(catheter whip or resonance).

Over damped waveforms UNDERESTIMATE SBP by 15-30mmHg, and OVERESTIMATES DBP.

Bibliography
Morgan, G., Mikhail, M. S., & Murray, M. J. (2006). Clinical Anesthesiology. New York: McGraw-Hill.

Nagelhout, J. J., & Plaus, K. L. (2010). Nurse Anesthesia. St. Louis: Saunders Elsevier.

Sauvage, T. R., & Schaus, S. S. (2012). Valley Anesthesia Sweat Book. Clive: Valley Anesthesia.

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 ETCO-2

Capnography refers to the comprehensive measurement and display of CO2 including end-tidal, inspired
and the capnogram (real-time CO2 waveform).

Capnograph is a device that measures CO2 and displays a waveform.

Capnometry refers to the measurement and display of CO2 in numeric form only.

Colorimetric CO2 detectors rely on a modified form of litmus paper, which changes color relative to the
Hydrogen ion concentration (pH) present

2 Kinds of Capnograph Analysis

 Mainstream CO2 sensor/Nondiverting/Flowthrough;

o Measures CO2 passing through an adapter by transmitting an infrared light through the gas
and determining the CO2 concentration.
o The major advantages of mainstream sensors are fast response time and elimination of water
traps.
 Side stream CO2 sensor/Diverting/Aspiration;
o Gas is continuously suctioned from the breathing circuit into a sample cell to determine the
CO2 concentration by comparing the infrared light absorption of the sample cell to a chamber
of free CO2.

Changes in expired or inspired CO2 can indicate changes in the patient status or equipment

• Metabolism
Factors which affect CO2 production; substrate metabolism, drug therapy and core temperature
Reliable when patient mechanically ventilated
unable to compensate and hyperventilate
• Circulation/CO2 transport
Positive correlation with cardiac output
Pulmonary perfusion; Reduced blood flow to the lungs will result in a decrease in EtCO2
• CPR
EtCO2 most accurate analysis of quality CPR
You will see a significant jump in EtCO2 with return of spontaneous circulation.
• Respiration
Rate frequency and depth of respiration
Assesses adequacy of spontaneous ventilation
Effects of bronchodilators
nitric oxide treatment
Factors which can affect ventilation include obstructive and restrictive diseases
• Breathing system
Inspired CO2 level greater than 0
Incompetent unidirectional valves are an inherent danger of a circle system

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Normal Values

 35-45mmHG
 A normal gradient between the arterial PaCO2 and the expired CO2 varies depending on the resource
but on average it is 5 in a healthy patient.
o Your arterial level of CO2 will be approximately 2-5 higher the EtCO2 reading

Waveform Analysis

 Phase I- begins with E, normally 0

o Inspiratory baseline
o Represents inspired gas
 Phase II- From B to C
o Rapid S shaped upswing
o Represents air transfer from dead space and alveolar gas that contains CO2
 Phase III- begins at C and continues to just before D
o Gas exhaled from alveoli
o Plateau is normally seen
o Without plateau, max value can be erroneous
 Alpha Angle or take off angle; Angle between phases II and III = Normally between 100-110
degrees
o Decreased with lung disease
o Increased with obstruction and PEEP
 Beta Angle= angle between the end of phase III and the descending limb of the capnogram
o Normally 90 degrees
o Increases with rebreathing and prolonged response time compared with respiratory cycle time
o Will decrease if the slope of Phase III is increased
 Phase IV represents inhalation, CO2 abruptly falls to zero

• Increase in EtCO2
Increased muscular activity (shivering)
Increased cardiac output (during resuscitation)
Tourniquet release
Insufflation of abdomen during laparoscopic surgery
Effective drug therapy for bronchospasm
Decreased minute ventilation, decreased respiratory rate or tidal volume
Malfunctioning exhalation valve
Increase in metabolic rate; as seen with a rapid rise in body temperature (malignant
hyperthermia)
94
 •
• Decrease in EtCO2
Decreased muscular activity (muscle relaxants)
Hypothermia
Decreased cardiac output
Pulmonary embolism
Bronchospasm
Increased minute ventilation; increased respiratory rate or tidal volume
Circuit leak or partial obstruction

•
• Curare cleft/notch
They appear when the action of the muscle relaxant begins to subside and spontaneous ventilation
returns.
Cleft occurs in later 1/3 of the waveform
Inadequate reversal
Depth of cleft represents degree of paralysis
Patient trying to breath against the ventilator

• Prolonged expiratory upstroke

If expiration is prolonged, inspiration may start before expiration and EtCO2 will decrease
Indicative of obstruction
• Bronchospasm
• COPD
• Kinked/obstructed tracheal tube

• Elevated Baseline
Normal shape, but does not return to zero
Exhausted absorbent, insufficient flows, faulty inspiratory valve
Rebreathing CO2

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 ETT in the esophagus


 Cardiogenic Oscillations
o Small regular tooth like humps at the end of expiratory phase
o Appear during the final phase of the alveolar plateau and during the descending limb. They
are caused by the heart beating against the lungs.
o Rhythmic and synchronized to heart rate
o May be observed in pediatric patients who are mechanically ventilated at low respiratory rates
with prolonged expiratory times
o Negative thoracic pressure
o Low respiratory rate
o Diminution in the vital capacity: heart size ratio, a low inspiratory: expiratory ratio, low tidal
volumes
o Add low PEEP, adjust ventilatory rate, flow, or tidal volume to improve pattern but cannot
always be fixed



o
 Biphasic expiratory plateau
o Differing compliance, resistance or VQ ratio between lungs
o Kyphoscoliosis
o Single lung transplantation


 Return to spontaneous ventilation


References

• Barash, P. G., Cullen, B. F., Stoelting, R. K., & Cahalan, M. (2009). Clinical anesthesia. (6th Ed.). Philadelphia, PA:
Lippincott Williams & Wilkins.

• Capnography Handbook; Critical Care. (2010). Retrieved from

[Link]

• Morgan Jr., G. E., Mikhail, M. S., & Murray, M. J. (2006). Clincal Anesthesiology, fourth edition. Ney York: McGraw-
Hill Companies.

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LaPlace's Law:

Relationship between wall tension (T), pressure (P) and the radius (r) of spheres and cylinders.
(If the blood pressure increases or the radius of the vessel increases, wall tension increases.) *Think "place of
aneurysm"
Laplace's Law in BP measurement: P = 2T/R
Laplace's Law in a distended failing heart: a distended failing heart has a larger radius than normal so it
produces less pressure, unless it can contract proportionately more forcefully
Anesthesia implications:
1. Ventilation and pressure
2. Aortic stenosis and preload
3. Collapsing pressure of alveoli and ability to keep open
4. Surface tension, Alveoli radius, Lung compliance
*The smaller the radius the greater the collapsing pressure
*The greater the radius the lesser the collapsing pressure

Poiseuille's Law:

Describes laminar flow using the formula: F = (πr4ΔP/8nl)

Q = πPr^4 / 8nL: Q=flow, pressure, radius, n=viscosity, Length
Describes the relationship of the amount of fluid flowing through tube
Viscosity is inversely proportional to the flow; Radius is directly proportional to flow
**Think long tube (Increasing the radius of the tube through which a fluid flows will have the most
dramatic effect on the rate of flow (because r is to the power of 4.))
**BEST: IV catheter short and wide diameter with blood diluted with saline
Anesthesia implications:
1. Gas through flow meters
2. Selection of ETT size
3. Selection of IV catheter size

Joule-Thompson Effect:

Describes the temperature change of a gas or liquid when it is forced through a valve or porous plug while
kept insulated so that no heat is exchanged with the environment. At room temperature, all gases except
hydrogen, helium and neon cool upon expansion.
Describes why allowing nitrous oxide to escape the gas cylinder at high flows can cause the tank to
accumulate frost on the cylinder outlet.
**"adiabatic expansion of a gas"-- pressure inside tank drops-->energy per area decreases as gas expands--
>decrease in energy results in lower temp

Boyle's Law

Pressure is inversely related to volume

P1V1=P2V2
Pick up a syringe, block the end of it with your finger and push the plunger. The further down the plunger
goes the harder it is to advance. This is because the pressure inside the syringe is increasing due to
compression of air. This is the basis of Boyle’s law which states: where temperature is constant the volume
of a gas is inversely proportional to pressure: V is proportional to 1/P or VP = constant.
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Anesthesia implications:
1. Squeezing bag to ventilate a patient
2. Diaphragm contracts and inspiration begins; diaphragm relaxes and exhalation beings
3. Hyperbaric O2 therapy
4. The bellows
Charles Law anesthesia implications
1. ETT cuff pressure
2. Regulation of anesthetic gas through metal strip

Charles Law

The volume of a gas at constant pressure is directly proportional to the temperature of the gas. Any change
in temperature will result in a change in the volume of the gas with the pressure being the same. That is if a
gas gets heated up, it will expand and when it gets cooled it diminishes in volume.
Temperature and volume are proportional.
Pick up a syringe, block the end of it with your finger and push the plunger. Imagine the same syringe, filled
with air, the plunger half way along and the end blocked. A heat source is applied. What happens? The gas
expands the plunger moves backwards, and the volume increases. This is Charles’ law which states that
volume is proportional to temperature, or V/T=constant.
Charles’s law states that for a constant pressure the volume of gas is directly proportional to its temperature.
The application for this gas law is when an LMA inflatable cuff expands when heated.

Anesthesia implications
1. ETT cuff pressure
2. Regulation of anesthetic gas through metal strip
V1T2 = V2T1

Ideal Gas Law

PV = nRT
pressure (volume) = moles of gas (universal gas constant) * Temperature
1. Combination of Gay-Lussac's, Boyle's Law, and Charles Law
3. Gas must be standard temperature pressure (STP) in Kelvin and mmHG
Anesthesia implications
1. The amount of inhalation agent delivered to a patient would increase or decrease depending on
temperature compensative valves
2. Emptying of an E-cylinder

*Reynolds’s Number: Determines whether or not a given flow will be

laminar or turbulent.
= vpd/ή.
(v= linear velocity of the fluid, p= density of the
fluid, d= diameter of the tube, ή= viscosity.)
**A Reynolds # > 2000 = turbulent flow.
**# <2000 =laminar flow.

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Third Gas Law

Pick up a syringe, block the end of it with your finger and push the plunger. Imagine the same scenario as
above, except that the plunger is prevented from moving backwards, what happens then? The pressure inside
the syringe increases. This is the third gas law, which states that pressure is proportional to temperature or
P/T is constant.

Bernoulli's Principle:

Flow of a gas or fluid through a tube increases if the diameter of the tube narrows. At the same time, there is
a drop in pressure (lateral pressure less time to push out with increased velocity) in the area of the
constriction.
**O2 Flow through anesthesia circuit 2L/min...Put ETT with half cross-sectional area of circuit on end-->
flow rate at end of ETT increases to 4L/min
(remember conservation of energy-- increase in kinetic energy, decrease in potential energy (pressure) to
maintain constant total energy)

Venturi Effect:

Entraining gas into a tube.

Decrease in pressure at the point of narrowing in a tube--> place an opening in the tube at that point, the
decreased pressure will act as a vacuum and draw in gas
through the opening.
**Jet ventilation flows at such a high velocity pulls in room air

Corneal reflex

The corneal reflex, also known as the blink reflex, is an involuntary blinking of the eyelids elicited by
stimulation of the cornea (such as by touching or by a foreign body), or bright light, though could result from
any peripheral stimulus. Stimulation should elicit both a direct and consensual response (response of the
opposite eye). The reflex consumes a rapid rate of 0.1 second. The evolutionary purpose of this reflex is to
protect the eyes from foreign bodies and bright lights (the latter known as the optical reflex. The reflex is
mediated by:

 The nasociliary branch of the ophthalmic branch (V1) of the 5th cranial nerve (trigeminal nerve)
sensing the stimulus on the cornea, lid, or conjunctiva (i.e. it is the afferent).
 The temporal and zygomatic branches of the 7th cranial nerve (Facial nerve) initiating the motor
response (i.e. it is the efferent).
 Mediated by center in the pons of brainstem.

H-reflex

The H-reflex (or Hoffmann's reflex) is a reflectory reaction of muscles after electrical stimulation of sensory
fibers in their innervating nerves (for example, those located behind the knee). The H-reflex test is performed
using an electric stimulator, which gives usually a square-wave current of short duration and small amplitude
(higher stimulations might involve alpha fibers, causing an F-wave, compromising the results), and an EMG
set, to record the muscle response. That response is usually a clear wave, called H-wave, 28-35 ms after the
stimulus, not to be confused with an F-wave. An M-wave, an early response, occurs 3-6 ms after the onset of
stimulation. The H and F-waves are later responses. As the stimulus increases, the amplitude of the F-wave
increases only slightly, and the H-wave decreases, and at supramaximal stimulus, the H-wave will disappear.
99
The M-wave does the opposite of the H-wave. As the stimulus increases the M-wave increases. There is a
point of minimal stimulus where the M-wave is absent and the H-wave is maximal.
H-reflex is analogous to the mechanically induced spinal stretch reflex (for example, knee jerk reflex). The
primary difference between the H-reflex and the spinal stretch reflex is that the H-reflex bypasses the muscle
spindle, and, therefore, is a valuable tool in assessing modulation of monosynaptic reflex activity in the
spinal cord. Although stretch reflex gives just qualitative information about muscle spindles and reflex arch
activity; if the purpose of the test to compare performances from different subjects, H-reflex should be used.
In that case, in fact, latencies (ms) and amplitudes (mV) of H-wave can be compared.

Hering-Breuer reflex

A reflex triggered to prevent over-inflation of the lung. Pulmonary stretch receptors present in the smooth
muscle of the airways respond to excessive stretching of the lung during large inspirations.
Once activated, they send action potentials through large myelinated fibers of the vagus nerve to the
inspiratory area in the medulla and pneumotaxic center of the pons. In response, the inspiratory area is
inhibited directly and the apneustic center is inhibited from activating the inspiratory area. This inhibits
inspiration, allowing expiration to occur.

Type and screen

(T&S) is performed on persons who may need a transfusion of blood products. In the first step, the patient's
blood is mixed with serum that contains antibodies against type A blood, then with serum that contains
antibodies against type B blood. A determination of the blood type is based on whether or not the blood clots
in the presence of these sera.

These tests are followed by the compatibility test (type and cross). This test insures that no antibodies are
detected in the recipient's serum that will react with the donor's red blood cells. To begin the cross-match, a
unit of blood from a donor with the same ABO and Rh type as the recipient is selected. Serum from the
patient is mixed with red blood cells from the donor. The cross-match can be performed either as a short (5–
10 min) incubation intended only to verify ABO compatibility or as a long (45 min) incubation with an
antihuman globulin test intended to verify compatibility for all other red cell antigens. If clumping occurs,
the blood is not compatible; if clumping does not occur, the blood is compatible. If an unexpected antibody
is found in either the patient or the donor, the blood bank does further testing to ensure that the blood is
compatible.

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In an emergency, when there is not enough time for blood typing and cross-matching, O red blood cells may
be given, preferably Rh-negative. O-type blood is called the universal donor because it has no ABO
antigens for a patient's antibodies to combine with. In contrast, AB blood type is called the universal
recipient because it has no ABO antibodies to combine with the antigens on transfused red blood cells. If
there is time for blood typing, red blood cells of the recipient type (type-specific cells) are given. In either
case, the cross-match is continued even though the transfusion has begun

Platelet Transfusion
• 1 unit ↑ platelets count 10,000 mm3
• adult dose: 1 unit/10 kg BW within 24 hrs
• indications (NIH)
▪ Thrombocytopenia with clinical coagulopathy
10, 000 in ITP
20, 000 in bone marrow suppression
40,000 during massive transfusion
▪ Platelet dysfunction even with platelets>100,000

Transfusion of FFP
1) Replacement of isolated factor deficiency
2) Reversal of coumadin
3) Antithrombin III deficiency
4) Treatment of immunodeficiency
5) Treatment of TTP
6) Massive blood transfusion

Prothrombin Time (PT)

• test of extrinsic pathway activity
• measures vitamin K - dependent factors activity (factors II, VII, IX, X)
• thromboplastin + Ca+2 to plasma = clotting time
• normal values: 12-14 seconds
• International Normalized Ratio (INR)
▪ standardizes PT reporting
• normal values: 0.8 -1.2 seconds
• monitors coumadin therapy
• most sensitive to alteration in F VII levels
• prolonged: 55 % ↓ of normal F VII activity
• antithrombotic activity: reduction of factor II and factor X activity (after several days)

Activated Partial Prothrombin Time (aPTT)

• test for intrinsic and common pathways
• dependent on activity of all coagulation factors, except VII and XIII
• normal values: 25 -35 seconds
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 • monitors heparin tx & screen for hemophilia
• prolonged: heparin, thrombin inhibitors, fibrin degradation products (FDP)
• citrated plasma + surface activators + phospholipid
• prolonged only if coagulation factors reduced to < 30 % of normal

Activated Clotting Time (ACT)

• monitors heparin anticoagulation in the OR (cardiac and vascular surgeries)
• normal values: 90 - 120 seconds

Thrombin Clotting Time (TCT)

• reflects abnormalities in fibrinogen → fibrin
• plasma + excessive amount of thrombin
• prolonged: heparin, thrombin inhibitors,
low fibrinogen, dysfibrinogenemia
• monitors hirudin, bivalirudin, LMWH tx
• INR & PT may be normal or ↑
• TCT prolonged with adequate therapeutic levels

Thromboelastography (TEG)
• continuous profiles during all phases of clot formation
• provides more accurate picture of in vivo coagulation process
• to evaluate:
• Hypo / hypercoagulable state
• Hemophilia
• Dilutional coagulopathy
• Rare coagulation disorders anticoagulation tx
• Coagulation problems with liver transplantation
Thromboelastogram (TEG)

Bleeding time
• monitors platelet function
• not specific indicator of platelet function
• not very reliable
• very operator - dependent
• variable from each institution
• other factors: degree of venostasis, depth and direction of incision
• no evidence as
• A predictor of risk of hemorrhage
• Useful indicator of efficacy of antiplatelet therapy
• insensitive to mild platelet defects

Platelet Function Analyzer (PFA) – 100

• relatively new global test of platelet adhesion and aggregation
102
 • advantages
• noninvasive, simple, easy to perform
• very sensitive in detecting platelet defects associated with vWD
• sensitive to dx of acquired platelet defects (ASA, NSAID, dietary factors: excessive
cocoa intake)
• monitors pro-hemostatic treatment
• DDAVP & platelet transfusions
Limitations
■ Inflexibility
■ Results should be interpreted in the context of either a simultaneously or recently drawn full blood
count
■ Platelet count < 80,000 or Hct < 30% will prolonged CT even if no platelet abnormal

[Link]
[Link]
[Link]
[Link]
[Link]

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Bainbridge

 The increase in HR secondary to an increase in central blood volume. The fluctuations in

intrathoracic pressure during inspiration and expiration can cause an increase/decrease in HR
 Inspiration accelerates the heart rate (preload increases)
 Expiration slows the heart rate (preload decreases)
 Can also be cause by IV fluid resuscitation and position changes that increase preload (lithotomy)
 Acts opposite to the carotid baroreceptor reflex
 Baroreceptors
o Located in the endocardium at the junction of the vena cava and the RA and the pulmonary
veins with the LA.
o Activate myelinated vagal afferent fibers that project to the nucleus tractus solitaries and
increase sympathetic activity to the SA node but not to the ventricles, thus increasing HR but
not contractility
o Increases HR by 10-15%
o Reflex helps to prevent accumulation of blood within the venous system and increase cardiac
output
o Distension of these receptors also increases renal excretion of free water by inhibition of
ADH secretion, leading to decreased circulating blood volume
o Atrial natriuretic peptide is increased which also promotes diuresis
 HR response depends on underlying rate prior to stimulation, faster heart rates are less likely to
increase
 Under anesthesia it is hard to decipher if increase in HR is from the Bainbridge reflex. Hypoxemia,
hypercapnia, PEEP, DL/intubation, surgical stimulation, aging, and OSA can cause increased activity
of SNS

Reverse Bainbridge

 A bradycardic response to a reduction in venous return (decreased preload). Same baroreceptors that
were described above.
 Spinal anesthesia causes a sympathectomy, this leads to dilation of arterioles and veins.
o Dilation of arterioles leads to decreased SVR
o Dilation of veins causes venous pooling and a decrease in venous return, stroke volume and
cardiac output.
o Cardio-accelerator fibers, T1-T4 can be blocked with spinal, typically causing a bradycardia.
If spinal is low, below T4, the patient theoretically should not become bradycardic. These pts
can become bradycardic d/t the reverse Bainbridge reflex.

104
 Pharmacology Review:

 Pharmacology- the study of substances that interact with living systems through chemical processes
 pharmacokinetics: time course of drug concentration in the body, Zero order (saturation) kinetics
 pharmacodynamics- mechanism of drug action including dose-response
 Ion trapping - a drug will accumulate on the side of the membrane that promotes ionization based on
the pKa value of the drug and difference of pH across the cell membrane.
 phase I reaction- chemical modification of parent compound which is more polar ‘HOR’
 phase II reaction- conjugation reaction where the metabolite is more polar and less lipid soluble
‘GAS’
 enterohepatic cycle – active drug or metabolite can be excreted in feces or reabsorbed (using
bacterial enzymes)
 first pass effect- orally administered drugs pass through liver before getting into systemic circulation
 Intrinsic clearance – intrinsic ability of the liver to eliminate a drug measured by the Michaelis-
Menen parameters. Important determinant of how aging influences hepatic drug metabolism.
 total body clearance- the volume of body fluid processed in a given time- constant and expressed as
volume per unit time
 first order kinetics- aka exponential kinetics; constant fractional change per unit time (ke)
 zero order kinetics- aka saturation kinetics; constant amount of change per unit time
 Biological half-life- for drugs eliminated by first-order kinetics. Time required for 50% of the drug to
be eliminated.
 Plateau principle- An IV drug will accumulate until it reaches a plasma concentration at which the
rate of elimination and administration are equal. The plasma drug concentration will remain constant
until there is a change in the dose.
 efficacy: maximum effect of a drug
 Potency: difference in doses of two drugs to achieve the same effect. Size of pill.
 full agonist- drug capable of generating a maximal response
 partial agonist- drug that will generate a response, but that response is less than the maximum
 Competitive antagonist- most antagonists are competitive. Agonist can overcome this. Shifts dose-
response curve to right
 Noncompetitive antagonist- binds another place on the receptor and may alter a receptor irreversibly
and decrease the maximal response. Shift dose-response curve to right.
 mechanism of action- effect of a drug is the result of their reversible association with a receptor
which initiates a chain of biochemical or physiological events
 Therapeutic index- measure of the safety of a drug. LD50/EC50
 Bioavailability: fraction of an administered drug that reaches the systemic circulation (f)
 Routes of administration
o Topical- dermal, intranasal, mucous membranes, eye
o Enteral-oral, sublingual, buccal, rectal
o Parenteral- IV, IM, SQ, transdermal, epidural
o Pulmonary- local effect and/or systemic effect
o Cavities- joints, peritoneum, bladder

105
  Drug transport mechanisms:
o Transporters are membrane proteins that control the influx of essential nutrients and ions and
the efflux of cellular waste, environmental toxins, and drugs.
o Passive diffusion- diffuses along concentration gradient based on solubility in membrane
o Facilitated diffusion- carrier-mediated transport. No ATP needed. Substance moves down its
electrochemical gradient
o active transport- needs energy to move drug against an electrochemical gradient by
cotransported compounds
o filtration- movement of H2O and solute through pores as a result of hydrostatic pressure
(GFR)
o Endocytosis- internalization of substances from extracellular environment through formation
of vesicles formed from the cell membrane
o ion pair transport – tow charged compounds interact to migrate through cell membrane

 Pharmaceutical/physical factors:
o Solubility
o Stability
o controlled release
 GI factors: emptying/motility, transit times; large surface area of small intestine (for passive
absorption)
Chemical properties

 MW (molecular weight), Kp (lipid solubility), pKa, pH

 GI mucosa impermeable to ionized form- uncharged species diffuse across lipid membranes
 Most drugs are weak electrolytes: ionization determined by pKa and local pH
 Henderson-Hasselbach equation: pH – pKa = log ([base]/[acid])
 Drugs accumulate where degree of ionization is greatest (ion trapping.) Absorption is facilitated at
sites where ionization is suppressed.
 Distribution
 Fluid compartments: vascular, interstitial, intracellular
 Rate of distribution dependent on MW, Kp, pKa, protein binding, blood flow
 Extent of distribution dependent on tissue binding (e.g. adipose, bone); barriers (blood-CSF-brain
barrier, placenta)
 Vd (volume of distribution) = dose / plasma concentration e.g. mg/(mg/L) = L
 Vd > total body water indicates tissue binding/ sequestration
 Plasma protein binding: Determined by law of mass action
o albumin (high capacity) –acidic drugs
o alpha1acid glycoprotein- basic drugs
o lipoproteins
o Consequences of drug binding to plasma proteins
 Reduces concentration of free drug
 slows distribution and elimination
 Potential site of drug interactions- depends on degree of protein binding, Vd of
displaced drug and elimination kinetics

106
Fluid Compartments

 Vascular 3-5 L
 Extracellular 10-20 L
 Total body water 35-50 L

 Vd = dose of drug/ drug in plasma. Theoretical volume in which the total amount of drug would need
to be uniformly distributed to produce the desired blood concentration.
 Cytochrome P450: mixed function oxidase; various isoforms, e.g. CYP3A4
 Primarily hepatic; Genetic variation
 Drug interactions: Induced or inhibited by drugs, competition between drugs
Drug accumulation following repeated doses:
1. Continuous IV infusion: plasma concentration increases until the rate of elimination and
administration are equal (steady state concentration, Css)
 Css = dosing rate/total body clearance e.g. Css = (mg/min)/(mL/min) = mg/ml
 Dosing rate for a desired concentration can be calculated if Cl is known = Cl x Css
 Time to reach steady state = 4 to 6 half-lives
2. Fixed rate multiple dose regimens: maintenance
 dose at constant interval (T)
 Drug accumulates if T < 4 half-lives
 Css is the mean during the dosing interval
 Effect of bioavailability (f)
 Css = (f x dose)/T x Cl)
3. Choice of dose:
 acceptable dose variation in circulation, based on therapeutic efficacy and toxicity
 patient convenience and compliance
4. Loading dose = Css x Vd
 When it is important to reach therapeutic concentration rapidly
Biotransformation

 Phase 1:
o minor modifications to generally produce more polar molecules, sometimes formation of
functional groups for subsequent conjugations
o Possible consequences: inactivation, activation (of prodrug), active or toxic metabolites
o Hydrolysis (ester and amide)
o Oxidations (e.g. cytochrome P450-linked, alcohol dehydrogenase, monoamine oxidase,
xanthine oxidase)
o Reductions (azo and nitro)
 Phase 2: conjugations, formation of more polar, pharmacologically-inactive molecules ‘GAS’
o Glucuronidation, sulfation, acetylation, amination, ribosylation, methylation
Other factors that influence drug metabolism: age, disease, gender, nutrition, hormonal status Excretion

 Clearance: volume of fluid from which drug is completely removed per unit time
 Total body clearance = sum of clearances of individual organ systems

107
Hepatic excretion: Biliary-fecal routes of elimination- hepatic excretion of conjugated metabolites in bile

 Enterohepatic cycling: excreted drug is converted into active drug by intestinal flora, reabsorbed
 Hepatic clearance: Cl = blood flow (Q) x extraction ratio (E) where E = (CA – CV)/CA
 CA = arterial concentration CV = venous concentration
Intrinsic clearance disregards limitations due to blood flow: when low, determines clearance (influenced by
protein binding); when high, blood flow determines clearance

 First pass effect: An orally administered drug with a high hepatic extraction ratio or a high rate of
hepatic metabolism relative to its rate of absorption will have reduced bioavailability.
Renal excretion:

 Glomerular filtration- unbound drug

 Tubular secretion- proximal tube actively transports many organic acids directly into the tubular
fluid; includes most penicillin’s, cephalosporin’s, many NSAIDs, thiazide and loop diuretics, and
conjugates; inhibited completely by probenecid
 Tubular reabsorption- passive movement along concentration gradient; influenced by Kp, MW,
degree of ionization (alkaline urine increases excretion of weak acids, acidic urine increases excretion
of weak bases
Renal clearance:

 Cl = (concentration in urine x urine volume/min)/concentration in plasma e.g. (mg/ml x

ml/min)/mg/ml = ml/min
o Cl = 0 Drug is filtered and completely reabsorbed
o Cl = 120 ml/min Drug is filtered and not reabsorbed
o Cl = 650 ml/min Drug is filtered and maximally secreted
Pharmacodynamics: Dose-effect relationships
o Occupation theory: drug + receptor D-R complex
o Effect of a drug is a function of its intrinsic activity and of the quantity of D-R complex (fractional
occupancy of R)
Quantity of D-R complex is determined by the amount of the drug and its affinity for R.
o graded dose-response
o Spare receptor concept: maximal effect may be produced at less than full occupancy of the receptor
-ASE: enzyme
-lukast: leukotriene receptor antagonists
-mab: monoclonal antibody
-platin: platinum derivative antineoplastic
-profen: anti-inflammatory/analgesic agents
-tinib: tyrosine kinase inhibitor
Vin-: vinca alkaloid
-zomib: proteozome inhibitor
108
 Calculations
Volume of Distribution
 Vd= dose/ C
o Vascular 3-5L
o Extracellular 10-20L
o Total body water 35-50L

Renal Clearance
 Cl=(U x V)/P
o U=concentration in urine
o V=urine volume/minute
o P=concentration in plasma
 CL= 0 ml/min then drug is filtered and completely reabsorbed
 CL= 120 ml/min then drug is filtered and not reabsorbed (renal GFR)
 CL= 650 ml/min then drug is filtered and maximally secreted (approximates renal blood flow)
Half life
 T1/2= 0.693/Ke
 For first order kinetics where Ke is fractional change per unit time
Steady state concentration
 Css= dosing rate/Cl
 Cl is the total body clearance

109
 Desflurane (Suprane)

 Fluorinated methyl ethyl ether

o substitutes fluorine for chlorine on alpha-ethyl component of isoflurane
o fluorination increases vapor pressure, enhances molecular stability, and decreases potency
 Most rapid achievement of PA; very low solubility
 High vapor pressure, ultra short DOA, moderate potency
 Solubility characteristics (blood: gas = 0.45) & potency (MAC = 6%) permit rapid achievement of
PA necessary for anesthesia & prompt awakening
o Lower blood: gas solubility & more precise control over delivery of anesthesia, more rapid
recovery from anesthesia

 Tec 6 Vaporizer
o The vapor pressure of desflurane is 669, which is 3-4 times that of the other inhaled
anesthetics. It has a boiling point of 22.8 degrees C.
o Electronically heated to 39 degrees C and pressurized to achieve controlled vaporization.
o Vaporizer may be filled during use
o The tec-6 works at absolute pressure, therefore ambient pressure makes no difference to its
performance
o DOES require a dial setting change at different altitudes

 Characteristic effects;
o Cardiovascular
 Dose-dependent decrease in mean arterial pressure, decreases SVR
 Cardiac output relatively unchanged
 Rapid increase in concentration can lead to transient increased HR, BP and
catecholamine release
 These effects can attenuated by Fentanyl, Esmolol, or Clonidine
o Respiratory
 Pungent airway irritant
 Poor choice for mask induction
 Can cause laryngospasm, breath holding, coughing, salivation
 Suppresses respiration
o Cerebral
 Minimal increase in cerebral blood flow
 Directly dilates cerebral vasculature =>increasing CBF and ICP However a
decrease in CMRO2 results in a vasoconstriction that blunts the rise in CBF
o Renal
 No nephrotoxic effects
o Hepatic
 No hepatotoxic effects
 0.02% metabolized (least metabolized of volatile anesthetics)

110
 o Cautions;
 Carboxyhemoglobin; broken down by absorbent into potentially significant amounts
of carbon monoxide which may be detected by arterial blood gas analysis or lower
than expected pulse ox, although still falsely high.
 Has been associated with emergence delirium in some pediatric patients
 Caution with asthma patients due to irritation
 Contraindicated with elevated ICP and patients with a history of malignant
hyperthermia

Sevoflurane (Ultane)

Molecular Weight 200 Preservative Water

Boiling Point 58.5 Stability in Soda No

(Celsius) Lime

Vapor Pressure 170 Blood: Gas 0.69

(mmHg) partition coefficient

Odor Ethereal MAC 1.8-2.2

Brain: Blood 1.7 Blood: Gas 0.69

Mechanism of Action:

As with ALL inhaled anesthetics= MOA is NOT FULLY UNDERSTOOD. Several successful hypotheses
based on research studies-

 The SPINAL CORD is where anesthetics act to inhibit purposeful responses to noxious stimulus.
 Inhalational depress the excitability of thalamic neurons, thus blocking thalamocortical
communication and potentially resulting in loss of consciousness.
 Volatiles inhibit excitatory transmission in the dentate gyrus of the hippocampus, and enhance
inhibitory transmission in the olfactory cortex and hippocampus. CONVERSELY, studies also show
depression of inhibition (stimulation) of transmission in hippocampus
 REMEMBER there is NO SINGLE SITE responsible- it is MULTIPLE SITES- spinal cord,
brainstem, hypothalamus, and cerebral cortex.
 On the molecular level, the SYNAPSE is the MOST RELEVANT site of anesthetic action- mediated
by voltage dependent ionic channels- Na, Ca2, and K. Also Ligand-gated Channels- GluR3/GluR6,
NMDA, GABAa, 5HT-3, nicotinic acetylcholine, glycine. ---- 5HT-3 potentiation would EXPLAIN
the SE of N/V of volatiles. Nicotinic acetylcholine inhibition would EXPLAIN why volatiles
prolong NDMRs.

111
  Current evidence STRONGLY indicates PROTEIN rather than the lipid as molecular target of
anesthetic action.
 Meyerton-Overton theory of course- The potency of anesthetics (Sevo) relate to their solubility in
olive oil. (Stoelting & Hillier, 2006).

Characteristics:

 Flourinated methyl isopropyl ether that exists as a clear, nonflammable liquid at room temperature
 Nonpungent, minimal odor
 LEAST AIRWAY IRRITATING of current inhalation agents.
 POTENT Bronchodilator.
 Half as potent a coronary vasodilator as Isoflurane
(Ebert & Schmid, 2009)
Decrement:

 Interestingly- Sevoflurane exhibits a degradation NOT shared with other volatiles. Hydrogen
fluoride is the degradation by-product (toxic) IF- there is a Lewis acid (ferric oxide) containing part
in the glass container, and if there isn’t a Lewis-acid inhibitor- WATER added as a preservative
(Baker, 2009).
Solubility:

 Low solubility in blood permits rapid onset and recovery

 Like Des, offers more precise control over induction, and more rapid recovery.
Metabolism:

 3-5% undergoes biodegration. Resulting metabolites include inorganic fluoride, and

hexafluoroisopropanol.
 DIFFERS from the other volatiles in that it DOES NOT metabolize into an acyl halide.
 The LEAST LIKELY to produce carbon monoxide on exposure to CO2 absorbents.
 The ONLY ONE to break down into Compound A (fluoromethyl-2, 2-difluoro-
1(trifluoromethyl) vinyl ether) - which is a dose-dependent nephrotoxin in RATS.
 The levels of Compound A in rats that cause nephrotoxicity is FAR GREATER than that seen
in humans- EVEN at FGFs at 1lpm.- suggesting that it isn’t a concern in humans however
undetermined fully.
System Effects:

 Cardiovascular:
o dose-dependent decrease in mean arterial pressure as a result of decrease in systemic vascular
resistance
o increase in heart rate
o Sevo has NO effect on AV or accessory pathways- good for ablative procedures.
 CNS
o Suppresses convulsants properties
o Does not evoke seizure activity on the EEG
o Will cause a dose-dependent decrease in amplitude and increase in latency of the cortical
component of somatosensory evoke potentials
o Produce dose-dependent increase in cerebral blood flow

112
Bibliography
Baker, M. T. (2009). Sevoflurane-Lewis Acid Stability. Anesthesia and Analgesia, 1725-1726.
Ebert, T. J., & Schmid, P. G. (2009). Inhaled Anesthetics. In P. G. Barash, B. F. Cullen, R. K. Stoelting, M.
K. Cahalan, & C. M. Stock, Clinical Anesthesia (pp. 413-443). Philadelphia: Lippincott Williams and
Wilkins.
Stoelting, R. K., & Hillier, S. C. (2006). Inhaled Anesthetics. In R. K. Stoelting, & S. C. Hillier,
Pharmacology and Physiology in Anesthetic Practice (pp. 42-86). Philadelphia: Lippincott Williams
and Wilkins.

Isoflurane

Molecular Weight 184 Preservative None

Boiling Point 48.5 Stability in Soda Yes

(Celsius) Lime

Vapor Pressure 240 Blood: Gas 1.46

(mmHg) partition coefficient

Odor Ethereal MAC 1.17

Mechanism of Action/Characteristics:

 Halogenated methyl ethyl ether that exists as a clear, nonflammable liquid at room temperature
 Pungent, ethereal odor
 Extreme physical stability
Decrement:

 The stability of isoflurane prevents the need to add preservatives such as thymol to the commercial
preparations
Solubility:

 Intermediate solubility in blood

 High potency permits rapid onset and recovery
Metabolism:

 0.2% of absorbed isoflurane undergoes oxidative metabolism by cytochrome P-450 enzymes

 Metabolism begins with oxidation of the carbon-halogen link of the alpha carbon atom, leading to an
unstable compound that decomposes to difluoromethanol and trifluoroacetic acid
 Trifluoroacetic acid is the principle organic fluoride metabolite of isoflurane
 Isoflurane is exhaled unchanged rather than repeatedly passing through the liver at low plasma
concentration, conducive to metabolism
113
System Effects:

 Cardiovascular:
o dose-dependent decrease in mean arterial pressure as a result of decrease in systemic vascular
resistance
o increase in heart rate
 CNS
o Suppresses convulsants properties
o Does not evoke seizure activity on the EEG
o Will cause a dose-dependent decrease in amplitude and increase in latency of the cortical
component of somatosensory evoke potentials
o Produce dose-dependent increase in cerebral blood flow

Stoelting, R. K., & Hillier, S. C. (2006). Pharmacology & physiology in anesthetic

Practice (4th Ed.). Philadelphia, PA: Lippincott Williams & Wilki

114
 Agents to Treat Hypotension

Sympathomimetic: drugs that evoke physiologic responses similar to those produced by endogenous
activity of the sympathetic nervous system. They cause vasoconstriction (cutaneous and renal circulation),
vasodilation (skeletal muscle), bronchodilation, cardiac stimulation (increased HR, myocardial contractility
and susceptibility to dysrhythmias), liberation of free fatty acids from adipocytes, hepatic glycogenolysis,
modulation of insulin, renin and pituitary hormone secretion, central nervous system stimulation.
Sympathomimetic exert their effects by activating adrenergic receptors (alpha and beta) or dopaminergic
receptors, which belong to the family of G protein-coupled receptors.
1.) Epinephrine
a. MOA- Direct acting endogenous sympathomimetic/catecholamine. Beta-1, Beta-2, Alpha-1,
and Alpha-2 Agonist. Epinephrine has a higher affinity for beta receptors than alpha
receptors, but, is the most potent activator of alpha-adrenergic receptors.
b. Pharmacokinetics- administered SQ, IV, IM or endotracheal. Poorly lipid soluble (doesn’t
cross BBB). Tachyphylaxis is not seen with repeated doses. Half-life is 2-3 minutes.
Termination of the effects of epinephrine occur principally due to reuptake.
c. Effects- increase HR, increase cardiac dysrhythmias, increase systolic blood pressure,
increased CO, and increased coronary blood flow, bronchodilation.
d. Use- addition to local anesthetic to decrease systemic absorption and prolong the duration of
action of the anesthetic, treatment of life-threatening allergic reactions, administration during
cardiopulmonary resuscitation as a single dose, continuous infusion to increase myocardial
contractility
e. Dosing-
i. Single dose- 2-8 mcg IV produces cardiac stimulation lasting 1-5 minutes.
ii. Infusion dose
1. 1-2 mcg/min IV- principally beta-2 stimulation
2. 4 mcg/min IV- Beta-1 stimulation
3. 10-20 mcg/min IV- alpha and beta receptor stimulation, with the effects of
alpha stimulation predominating in most vascular beds.
2.) Ephedrine
a. MOA- indirect and direct acting synthetic noncatecholamine that stimulates alpha- and beta
adrenergic receptors. Pharmacologic effects are due in part to endogenous release of
norepinephrine (indirect-acting).
b. Pharmacokinetics- Tachyphylaxis seen with ephedrine. Can be given IV or IM. Monoamine
oxidase inhibitors may potentiate the pressor effect of ephedrine, possibly resulting in a
hypertensive crisis.
c. Effects- CV effect resemble those of epinephrine, but its systemic blood pressure –elevating
response is less intense and lasts approximately 10x longer. IV administration results in
increases in heart rate, blood pressure, and cardiac output. Coronary blood flow and skeletal
muscle blood flow are increased. Renal and splanchnic blood flow are decreased. In the
presence of pre-existing beta-adrenergic blockade, the cardiovascular effects of ephedrine
may resemble alpha-adrenergic receptor stimulation.
d. Use- hypotension
e. Dose-
i. Adults- 5-25 mg IV, 25-50 mg SC or IM
ii. Children- 0.5 mg/kg SC or IM

115
3.) Neosynephrine (Phenylephrine)
a. MOA- synthetic non-catecholamine that stimulates principally alpha-1 adrenergic receptors
by a direct effect, with only a small part of the pharmacologic response being due to its ability
to evoke the release of norepinephrine (indirect-acting). There is a minimal effect on beta-
adrenergic receptors.
b. Pharmacokinetics- produces vasoconstriction that lasts longer than that of epinephrine and
ephedrine, lasting 20 minutes. No Tachyphylaxis
c. Effects- increased stroke output, decreased heart rate, increased systolic and diastolic BP,
constriction of pulmonary vessels/increased pulmonary arterial pressure (not for patients with
pulmonary hypertension)
d. Use- vasopressor, additive to regional anesthetic, antiarrhythmic, hemostatic, mydriatic.
e. Dose-
i. Hypotension
1. IV 40-100 mcg
a. Doses should not be repeated more often than every 10-15 minutes
ii. Prolongation of spinal anesthesia
1. 2-5 mg to anesthetic solution increases the duration of motor block by as much
as 50% without any increase in the incidence of complications.
4.) Vasopressin
a. MOA- Synthetic form of a hormone synthesized in the posterior pituitary gland.
b. Pharmacokinetics- must be administered parenterally. Effects within 1 minute, plasma half-
life is 4-20 min, so that continuous infusion is necessary for maintenance of effects
c. Use- DOC for refractory hypotension from ACEI and ARBs, reduce blood flow during an
operation. Antidiuretic (for diabetes insipidus)
d. Effects- increased peripheral resistance, NO increase in pulmonary vascular resistance.
e. Dose-
i. Intraoperative hypotension
1. 0.5-1 unit
ii. Septic shock
1. Infusion 0.01-0.04 units/min
iii. Cardiac arrest
1. 40 units IV/IO to replace first or second dose of epinephrine given every 3-5
minutes.
5.) Glucagon
a. MOA- produced in the alpha cells of the pancreas. Enhances the formation of cAMP.
Enhances automaticity in the nodal conduction system without increasing automaticity in the
ventricles. Stimulates catecholamine release.
b. Use- to increase myocardial contractility and HR in the setting of beta blocker toxicity.
c. Dose:
i. 1-5 mg IV slowly
ii. Infusion- 25-75 mcg/min
6.) Methylene blue
a. MOA- methylene blue is normally hemodynamically inert, however, for a variety of clinical
scenarios associated with an inflammatory response, it results in increases of systemic blood
pressure, systemic vascular resistance (SVR), and myocardial contractility->d/t prevention of
vasodilation d/t blockade of nitric oxide synthase.
b. Considerations- pregnancy category X (atresia of the ileum and jejunum, ileal occlusions, and
other adverse effects in the neonate. MB has been demonstrated to be a potent monoamine
oxidase inhibitor (MAO-I) and may cause potentially fatal serotonin toxicity when combined
with SSRIs.
116
 c. Use- delineation of certain body tissues during surgery, diagnostic procedures such as fistula
detection, treatment of methemoglobinemia, bacteriological stain, treatment of vasoplegic
syndrome.
d. Dose
i. Methemoglobinemia
1. 1-2 mg/kg IV slow. Repeat IV dose after 30-60 minutes if required.
ii. Hypotension
1. 1.5-2 mg/kg bolus followed by a continuous infusion of 0.5 mg/kg/hr

Alpha 1 blockers:
‐ Prazosin (minipress)
o Half-life 2-3 hours
o Dilates both arterioles and veins
o Used in the management of essential hypertension, Raynaud’s, pheochromocytoma
o Receptor selectivity produces less chance of reflex tachycardia
‐ Terazosin (Hytrin)
o Longer acting (half-life 12 hours)
o Used in management of HTN and BPH
‐ Tamulosin (Flomax)
o More selective for prostate vs blood vessel alpha 1
o Used for BPH and kidney stones
‐ Doxazosin (Cardura)
o Long acting (half-life 22 hours)
o Used for HTN and BPH
‐ Side effects- orthostatic hypotension, syncope, nasal congestion
Alpha 2 blockers:
‐ Yohimbine
o Used for impotence
o Crosses the BBB and is associated with tremor
Non-selective alpha blockers
‐ Phenoxybenzamine
o Prodrug; onset slow (45 min-1hr)
o Long half-life (24 hours)
o Dose 0.5-1 mg/kg PO
o Significant hypotension if the patient is hypovolemic or has preexisting hypertension.
o SE- tachycardia, N/V, somnolence, miosis and nasal stuffiness
‐ Phentolamine
o Onset 2 minutes, lasts 10-15 minutes
o IV for HTN emergency like intraoperative pheochromocytoma
o Dose- 30-70 mcg/kg IV, may start infusion 1-5 mg
o Decrease BP causes baroreceptor mediated increase SNS activity (tachycardia)

117
Alpha 2 agonist
‐ Clonidine and Dexmedetomidine
o Stimulate presynaptic alpha 2 receptors (brainstem and spinal cord). Inhibit Ca++ uptake
in neural terminal, prevents norepinephrine release from peripheral and central adrenergic
nerves->decreasing peripheral vascular resistance and heart rate.
o SE-
 Low BP
 Bradycardia
 Dry mouth
 Sedation
‐ Clonidine
o Up regulation of receptors with abrupt d/c of chronic clonidine therapy can cause HTN
crisis.
 Decreased norepinephrine release will cause up regulation of alpha 1 and beta 1
receptors, so if norepi release is no longer inhibited, one can see an exaggerated
increase in BP and HR
o 220:1 affinity for alpha 2 vs alpha 1 receptors
o Can be used as adjuvant in the management of acute ETOH withdrawal
o 75 mcg IV can be used to stop shivering, as clonidine inhibits central thermoregulatory
control
o Useful in patients with severe hypertension
o Decrease in sBP >dBP
o Augments the pressor response of ephedrine- may need lower doses of ephedrine to treat
hypotension
o Abrupt d/c produces rebound hypertension in 8-36 hours since last dose
o Transdermal clonidine is effective for 7 days
o Ineffective in the setting of pheochromocytoma (no effect on tumor diffusion of
catecholamines)
o Decreased risk of myocardial ischemia, infarction, and mortality following CABG
Dexmedetomindine
‐ Alpha 2:alpha 1- 1620:1
‐ Use- sedation in non-intubated and intubated patients
‐ Loading dose- 1 mcg/kg over 10 minutes
‐ Maintenance infusion- 0.3-0.7 mcg/kg/hr
Pheochromocytoma
‐ Preop preparation
o Phentolamine, prazosin 10-14 days before surgery
o Restoration of intravascular volume
o Beta blockade
o Goal- control HR, suppress arrhythmias, prevent BP lability
‐ Intraop
o Control BP with SNP, nicardipene
o Control tachydysrhythmias with propranolol, esmolol, or labetalol
o Anticipate hypotension with ligation of tumor’s venous blood supply
Initial Rx w/fluids and pressors.

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 DOPAMINE

Dopamineendogenous catecholamine that is the immediate precursor of norepinephrine.

 Regulates cardiac, vascular, and endocrine function

 Important neurotransmitter in CNS and peripheral nervous system
 Rapid metabolism necessitates a continuous infusion

Dopamine receptorsA/W the neural mechanism for “reward” that is A/W cocaine and alcohol abuse

 D1 receptorslocated postsynaptically, when activated cause

o vasodilation in renal, mesenteric, coronary and cerebral vessels
o inhibition of sodium/potassium adenosine triphosphate
o Activation is mediated by adenylate cyclase
 D2 receptorsprincipally presynaptic
o inhibit adenylate cyclase activity and release of norepinephrine
o N/V caused by dopamine is mostly mediated by D2

Dopamine infusion
o 0.5-3 mcg/kg/min“renal dose”, produces renal vasodilation
o given to pts at risk for developing acute renal failure (unproven)
o 3-10 mcg/kg/min stimulates β1 in the heart: increased CO, HR &risk of dysrhythmias
o >10 mcg/kg/min stimulates α1 receptors in peripheral vasculature leading to vasoconstriction

Other effects of dopamine

 Interferes with the ventilatory response to arterial hypoxemia leading to unexpected depression of
ventilation in pts who are being treated with dopamine to increase myocardial contractility.
 Continuous infusion in critically ill pts are a/w increases in intraocular pressuremay create risk in
pts with preexisting glaucoma
 Extravasation will cause profound vasoconstriction, treated with phentolamine injections at the site

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 ANTIHYPERTENSIVES

Labetalol/Normodyne

 Selective α1 & non-selective β1 & β2 adrenergic antagonist

 IV and PO forms β:α ratio in PO is 3:1 and IV is 7:1
 Metabolism by conjugation of glucuronic acid
 Elimination half time is 5-8 hours, prolonged in the presence of liver disease, unchanged by renal
dysfunction
 Lowers BP by decreasing SVR (α1 blockade) with reflex tachycardia from vasodilation attenuated by
beta blockade
 Cardiac output remains unchanged
 Max systemic BP lowering effect seen in 5-10 minutes

Esmolol/Brevibloc

 Selective β1 adrenergic receptor antagonist

 Only administered IV, rapid onset and short actingfull therapeutic effect within 5 minutes and
duration 10-30 minutes after administration
 Can cause pain on injection (pH=4.5-5.5)
 Hydrolysis of esmolol is caused by plasma esterase’s, independent of hepatic and renal function
 Elimination half time is about 9 minutes
 Doses of 1 mg/kg followed by 250 mcg/kg/min IV significantly decrease the plasma concentration of
propofol (mechanism of this is not explained by a pharmacokinetic interaction)

Metoprolol/Lopressor

 Selective β1 adrenergic receptor antagonist that prevents inotropic and chronotropic responses to
beta-adrenergic stimulation
 Selectivitiy to β1 can be overcome in large doses which will lead to metoprolol having non-selective
effects (blocking of β2 leading to bronchoconstriction)
 Readily absorbed from GI tract
 High first pass metabolismonly about 40% of drug reaches circulation
 Elimination half time is 3-4 hours

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 HYPERTENSTIVE CRISIS

 Typically BP > 180/120 mmHg

 Placement of arterial line for titration of anti-hypertensive drugs beneficial
 For a true crisis, decrease the BP by no more than 20-25% initially so that target organ hypoperfusion
is prevented
 Drug of choicesodium nitroprusside 0.5-10 mcg/kg/min
 Other drug optionsnicardipine, fenoldopam, esmolol, labetalol & clevidipine

HYPERTENSION IN THE OR

 Ensure adequate level of anesthetic

 Volatile anesthetics produce a dose dependent decrease in BP d/t decrease in SVR and/or myocardial
depression, attenuate sympathetic activity
 Narcotics to blunt sympathetic response to surgical stimulation/pain
 Esmolol IV push (20 mg bolus) or IV drip
 Metoprolol IV pushif pt is responsive to esmolol but unable to start a drip can give IV metoprolol
for longer acting selective β1 activity
 Labetalol IV push (2.5-20 mg initially then titrate to effect) max dose 300 mg total

Vasopressin (arginine vasopressin (AVP), antidiuretic hormone (ADH), or argipressin)

 A neurohypophysial hormone
 Functions:
o 1. retain water by ↑ water permeability of the kidney's collecting duct and distal convoluted
tubule by inducing translocation of aquaporin-CD water channels in the kidney nephron
collecting duct → ↑ concentration of the urine and ↓ urine volume
o 2. constrict blood vessels → ↑ peripheral vascular resistance → ↑ arterial blood pressure
 Derived from a preprohormone precursor that is synthesized in the hypothalamus and stored in
vesicles at the posterior pituitary to be released into the bloodstream.
 It has a very short half-life between 16-24 minutes.
Types of Vasopressin Receptors

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Vasopressin-1 Receptors
• Vasopressin interacts with vasopressin1-receptors (V1Rs), which are found in high density on
vascular smooth muscle.
• Another mechanism by which vasopressin exerts vascular control is through modulation of nitric
oxide (NO). Vasopressin may restore vascular tone in vasodilatory shock states by blunting the ↑ in
cGMP that is induced by NO and atrial natriuretic peptide (ANP), and by ↓ the synthesis of inducible
nitric oxide synthase (NOS). This inhibition occurs via the V1R.

Pitressin (vasopressin)
• Synthetic form of a hormone synthesized in the posterior pituitary gland.
• Drug of choice for refractory hypotension from ACE inhibitors and angiotensin II blockers (ARBs).
• Exogenous AVP must be administered parenterally, because the peptide is quickly hydrolyzed by
trypsin.
• Intravenous administration of exogenous AVP has effects within minutes.
• AVP rapidly distributes from plasma into the extracellular fluid volume.
• It is metabolized in the liver and kidneys, and a small proportion is eliminated with the urine.
• The plasma half-life is 4–20 min, so that continuous infusion is necessary for maintenance of effects.

122
Dosing of Vasopressin
• Intraoperative hypotension
 Dilute with 19 mL NS in a 20
cc syringe to create a
concentration of 1 unit/mL.
 Administer 0.5 – 1 unit to treat
hypotension in an adult.
• Septic Shock
 Exogenous vasopressin has
been used in patients with septic
shock in several studies. AVP
infusion (0.01–0.04 U/min) ↑
peripheral vascular resistance
and ↑ arterial blood pressure
within minutes of application.
No ↑ in pulmonary vascular
resistance or pulmonary artery
pressure was reported in patients treated with low-dose vasopressin (0.04 U/min), nor were
cardiac complications or changes in electrolyte, blood and urine osmolality, or metabolic
variables.

Vasopressin and Hemostasis

• To reduce ↓ blood loss during an operation, gynecologic surgeons often take the preventive step of
injecting a dilute solution of vasopressin into the uterus or cervix before they start the procedure.
• In randomized clinical trials, injection of vasopressin has been demonstrated to reduce ↓ blood loss in
several gynecologic surgical procedures, including myomectomy, hysterectomy, abortion, and
conization.
• The surgeon is advised to notify the anesthesia provider prior to injecting vasopressin.

Vasodilation Drugs = NO donors

• Nitric Oxide (NO)
• Nitroglycerin (NTG)
• Nipride (SNP)
• Hydralazine
• Diazoxide
• Isosorbide Dinitrate
• Minoxidil
• Trimethaphan (Arfonad)
• Adenosine

123
Vasodilators
• Arterial vasodilators ↓ blood pressure via ↓ SVR
• Venous vasodilators ↓ venous return, ↓ cardiac preload/output
• Nitroglycerin reduces preload (venodilation), whereas Sodium Nitroprusside (Nipride) ↓ peripheral
vasoconstriction effects (arterial dilatation)

Nitric oxide (NO)

• Generated in the vascular endothelium
• A role in the overall vasomotor tone of CV system
• Has platelet regulating (antithrombotic), immunomodulating and neurotransmitter (excitatory)
function
• As a gas, can be administered to produce pulmonary vascular relaxation in situations of pulmonary
HTN
• Half-time of < 5 seconds, producing localized action
• Bound and inactivated by adult hemoglobin
• Metabolically transformed into nitrate
• Released in response to ↓ oxygenation, and opposes the pulmonary HTN associated with arterial
hypoxemia
• Generated more by arteries than veins
• ↓ NO release in essential hypertension
• Inhaled NO modestly ↑ methemoglobin levels
• Rebound arterial hypoxemia and pulmonary HTN may accompany NO d/c >> must be weaned
slowly
• NO is oxidized to NO2 (Nitrogen Dioxide--a pulmonary toxin)

MOA
• NO can be released spontaneously or produced from L-arginine, with Nitric Oxide Synthases (NOS)
as catalyst enzyme in reaction
• Generation of intracellular Nitric Oxide (NO) produces vasodilation
• NO generation leads to stimulation of guanylate cyclase and ↑ c-GMP, producing smooth muscle
relaxation
• c-GMP leads to a decreased Ca++ ion concentration
• Phosphodiesterase 5 (or V) breakdown c-GMP to stop effects

Abnormal Production NO
• HTN
• Obesity
• HLD (particularly hypercholesterolemia and
hypertriglyceridemia)
• DM (Both type 1 and 2)
• Heart failure
• Smoking
• Age
• Atherosclerosis

Hydralazine
• Activates guanylate cyclase via generation of NO at the vascular wall to produce c-GMP (↑ c-
GMP)→ vasodilation
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 • Arteriolar dilation primarily
• ↓DBP decreased > SBP
• ↑SV and ↑CO increase
• ↑Heart rate increases reflecting a reflex baroreceptor-mediated ↑in SNS activity owing to ↓BP; Can
cause angina via this mechanism
• Lupus-like syndrome in 10-20% of patients on chronic hydralazine
• Slow onset--10-20 minutes wait for response before redose secondary to long onset time)
• Half-life ~4 hours (3-6 hrs).
• Metabolized by liver

Nitroglycerin (NTG)
• Principally venodilation
• Can be sublingual, Transdermal, or IV
• Generates NO in the presence of thio-containing compounds
• Not a good choice in Aortic Stenosis > venous pooling > syncope
• SVR relatively unchanged (venodilation vs arterial dilation)
• ↑ coronary flow to subendocardial layers > good
• Good for patients with HTN and CAD
• 0.3 mg sublingual for angina
• ↓ the area of cardiac muscle injury in MI by preferentially diverting flow to the ischemic area
• Side effects: Headache, facial flushing, tolerance (not with intermittent sublingual)
• Not to be used in patients taking drugs for ED (potentiating of hypotensive effects via inhibition of c-
GMP catabolism)
• Tolerance to vasodilation effects that is dose and duration dependent; treatment is to d/c drug for at
least 12 hours and restart
• Relaxes airway and biliary/GI tract smooth muscle (can relax sphincter of Oddi spasm)
• Cerebral vasodilator
• ↓ CO due to decreased venous return
• Baroreceptor mediated ↑HR tachycardia and ↑ contractility, especially if hypovolemic

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IV NTG dosing
• 4.7 mcg/kg/min dose per Stoelting to produce controlled hypotension
• 0.5-10 mcg/kg/min per Morgan + Mikhail
• Onset within 1 minute, duration ~5 minutes
• Clinically, I’ve most often seen run as gtt 10-100 mcg/min, OR even more so run on gtt tubing TTE
(titrated to effect)
• Another “trick” dilute down to 10 mcg/cc and give 1-2 cc boluses for quick/short lived stimulation
(DL, emergence, etc)
• Rapidly hydrolyzed by liver—nitrite is one end product which can convert hemoglobin to
methemoglobin and rarely cause methemoglobinemia. Treatment is methylene blue 1-2 mg/kg.

Sodium Nitroprusside (SNP)

• Direct acting, nonselective potent vasodilator, causing ↓BP
• SVR ↓ because of arterial dilation
• Venodilation produces ↓ venous return (↓ preload)
• Baroreceptor response to ↓ BP includes ↑ heart rate and ↑ contractility
• No direct inotropic or chronotropic effects on the heart
• ↓ systemic blood pressure may cause renin release, contributing to a spike in blood pressure once the
infusion is stopped
• May ↑ the area of an MI due to coronary steal
• ↓ DBP contributes to myocardial ischemia by ↓ coronary perfusion pressure and flow
• Immediate onset, requires continuous infusion
• Need an arterial line for safety
• NO is the active mediator and SNP is the prodrug
• SNP interacts with oxyhemoglobin to form methemoglobin, releasing cyanide and NO
• ↑CBF and ↑CBV--Not a good choice if ↑ICP of significant carotid disease
• ↓PaO2 via attenuation of HPV
• Must be mixed in 5% glucose in water and must be wrapped in a light-protecting cover (SNP
converts to aquapentacyanoferrate in the presence of light with release of hydrogen cyanide)
• Dose range is 0.3 - 10 mcg/kg/min, and the max rate should not be infused for > 10 min
• To lessen the likelihood of cyanide toxicity, use other drugs such as volatile agents, possibly beta-
blockers to help ↓BP

126
Metabolism of SNP
• After injection, SNP receives electron from iron of oxyhemoglobin to form methemoglobin +
unstable SNP which quickly decomposes to 5 cyanide ions (CN-)
• The 5 CN- ions can take one of 3 paths—
– 1) 1 CN- bind with methemoglobin to form cyanmethemoglobin
– 2) other 4 CN- via liver and kidney bind with thiosulfate (catalyzed by enzyme Rhodanase) to
form thiocyanate
– 3) CN- can also bind to tissue cytochrome oxidase
• Acute cyanide toxicity occurs when third path is taken (usually secondary to exhaustion of other 2
pathways) as it interferes with normal oxygen utilization!
• Cyanmethemoglobin remains in dynamic equilibrium with free cyanide and is nontoxic

SNP metabolism toxicity

• Cyanide Toxicity
• Methemoglobinemia
• High plasma concentrations of thiocyanate

Cyanide toxicity
• Seen with prolonged and/or high dose infusions
• Can occur with infusion rates > 2 mcg/kg/min
• Can occur when sulfur donors and methemoglobin are exhausted (accumulation of cyanide radicals)
• Free cyanide radicals bind to cytochrome oxidase and prevent oxidative phosphorylation (life-
sustaining process)
• ↑cyanide concentrations may precipitate tissue anoxia, anaerobic metabolism, and lactic acidosis

Cyanide toxicity—when to start suspecting it . . .

• Tachyphylaxis--resistance to the hypotensive effects of the drug at maximum infusion rates (10
mcg/kg/min)
• ↑ Mixed Venous PO2 is increased in cyanide toxicity, reflecting inability of tissues to utilize O2
• Metabolic acidosis
• CNS-mental status changes & seizures in awake patients
• Toxic blood level > 40 micromoles

Cyanide toxicity treatment

• Stop infusion
• 100% oxygen
• NaHCO3 to correct metabolic acidosis
• Sodium thiosulfate at 150 mg/kg IV over 15 minutes --sulfur donor to convert cyanide to thiocyanate
• If severe, sodium nitrate at 5mg/kg IV slowly--converts hemoglobin to methemoglobin, which
converts cyanide to cyanmethemoglobin
• Hydroxycobalamin (Vitamin B12) binds cyanide to form cyanocobalamin (expensive, reddish skin
discoloration)

127
Methemoglobinemia
• Unlikely even in patients with a congenital inability to convert methemoglobin to hemoglobin
• High ↑SNP doses would be required
• If pt receiving high doses and presents with impaired oxygenation despite adequate CO and arterial
oxygenation should have methemoglobinemia included in differential
• Measurement via co-oximetry may be helpful

Thiocyanate Toxicity
• Rare event
• Thiocyanate is 100-fold less toxic than cyanide
• Thiocyanate is cleared slowly by the kidneys, so CRF patients (not on dialysis) with prolonged
infusions may be at risk
• Is cleared by dialysis
• Nonspecific symptoms include tinnitus and N&V
• Hyper-reflexia, confusion, psychosis, miosis, seizure, coma

Calcium

Calcium Chloride (CaCl2) is 3 times as potent as Ca gluconate.

The Ca in Ca gluconate is less available due to binding of gluconate → not used in ACLS.
CaCl2 used in ACLS.
10% CaCl2 = 1.36 mEq Ca/ml
10% Ca Gluconate = 0.45mEq Ca/ml
1g CaCl2 = 272mg elemental Ca
1g Ca Gluconate = 93mg elemental Ca

Indications: ↓Ca, ↑K, ↑Mg, cardiac arrest

Action: Ca interacts with actin and myosin → enhances myocardial contraction.
Bolus dose: 250-1000mgIV.
Onset: < 1min
Peak Effect: <1 min
Duration: 10-20 min
Clearance: incorporated into muscle and bone, renal excretion.
Attention: ↑risk for ventricular arrhythmias, HTN. If extravasates irritating to veins and may cause necrosis.
Infusion through central line preferable.

128
↑Ca (Ca > 10.3 mg/dL):
 Due to: primary hyperparathyroidism, malignancy, Vit D and An intoxication,
immobilization, Thiazide drugs.
 Tx: correction of hypovolemia with NS, Biphosphonates, Calcitonin & Ca ↓ agents
(mithramycin, glucocorticoids)
↓Ca (Ca < 8.4 mg/dL):
 Due to: hypoparathyroidism, pseudoparathyroidism, hypomagnesemia, low vit D,
hyperphosphatemia, Ca chelating agents
 OR causes: hyperventilation, blood transfusion > 1.5ml/kg/min
 Symptoms: ↑nerve/muscle excitability, laryngospasm, ↓BP, dysrhythmias
 Tx: Ca gluconate (2g in 50-100ml saline) over 10-15 min → followed by Ca
Chloride/gluconate infusion (0.5-1.5 mg/kg/hr)

In pts with normal or ↑Ca →IV Ca bolus will produce transient ↑SVR.
In profoundly ↓ hypocalcemic pts →CaCl2 bolus will produce significant inotropic response (↑HR).

For ↓Ca secondary to citrated blood transfusion → 1.35 mEq Ca for each 100ml of citrated blood given.

129
Chloride
Normal level: 97 to 107 mEq/L.
It is an essential electrolyte located in all body fluids responsible for maintaining acid/base balance,
transmitting nerve impulses and regulating fluid in and out of cells.

Hyperchloremia Cl >107 mEq/L: associated with excess fluid loss such as vomiting and diarrhea. If the pt
is diabetic, hyperchloremia could lead to ↑blood sugar concentration. Hyperchloremia can be symptomatic
with signs of Kussmaul's breathing, weakness, and intense thirst. Elevations in chloride may be associated
with administration significant amounts of IV normal saline, diarrhea, kidney diseases and overactivity of the
parathyroid glands. Hyperchloremia is often comorbid with diabetes or hyponatremia. Certain drugs,
especially diuretics such as carbonic anhydrase inhibitors, hormonal treatments, and polypharmacy, may
contribute.
Treatment based on correcting the underlying cause.
If dehydrated: establishing and maintaining adequate hydration.
If caused or exacerbated by medications or treatments, these may be altered or discontinued, if deemed
prudent.
If there is underlying kidney disease (which is likely if there are other electrolyte disturbances), refer to a
nephrologist for further care.
If there is an underlying dysfunction of the endocrine or hormone system, refer to an endocrinologist for
further assessment.

Hypochloremia Cl<97: can be due to hypoventilation, chronic respiratory acidosis, metabolic alkalosis due
to vomiting. Treatment hypochloremia is to correct the underlying cause.

130
 ANTIBIOTICS: ANTIMICROBIAL DRUGS FOR TB, ATYPICAL MYCOBACTERIA
INFECTIONS AND LEPROSY

 DRUGS USED TO TREAT MYCOBACTERIAL INFECTIONS: OVERVIEW:

o Drugs used to treat Tuberculosis
 First-line drugs
 Isoniazid,
 Pyrazinamide,
 Rifampin,
 Ethambutol
 Streptomycin
 Second-line Drugs
 p- Aminosalicylic acid
o Drugs used to treat atypical Mycobacteria infections:
 Clarithromycin,
 Ethambutol,
 Rifabutin
o Drugs used to treat leprosy
 Dapsone,
 Clofazimine
 General considerations for the drug treatment of Mycobacteria infections:
o Intrinsically resistant to most antibiotics
 INTRINSICALLY RESISTANT TO MOST ABX* …
 KNOW THESE GENERAL CONSIDERATIONS. THEY HAVE AN
INTRACELLULAR LOCATION. THE TX OF MICROBACTERIAL
INFECTIONS IS DIFF THAN THE TX OF OTHER INFECTIONS B/C OF THE
RESISTANCE OF TB.
o notorious ability to develop resistance
o slow growth rate: can also be dormant
o intracellular location
o lipid-rich cell wall is impermeable to many drugs
o Chronic nature of M infections
o Treatment for periods of drug therapy longer than that of other infectious diseases.
 WHEN YOU HAVE THAT TX IS GOING TO BE FOR A LONGER PERIOD OF TIME
– WHAT BECOMES VERY IMP ARE THE S/E AND DRUG INTERACTIONS B/C
YOU’RE TREATING THE PT FOR MONTHS, YEARS, AND FOR LEPROSY FOR
SEVERAL YRS.

131
 TB

 TUBERCULOSIS: GENERAL
o GENERAL FACTS:
 In 2011, a total of 10,521 new TB cases were reported in the USA, an incidence of 3.4
cases per 100,000 population, which is 6.4% lower than the rate in 2010.
 Among persons with TB who had a known HIV test result, 7.9% were co-infected with
HIV.
 A total of 109 cases of multidrug-resistant TB were reported in 2010
 Drug-susceptibility test results for isoniazid and rifampin were reported for 97.5% and
97.1% of culture-confirmed TB cases in 2009 and 2010, respectively.
 THE NUMBER OF PEOPLE THAT ARE HAVING TB ARE COMING DOWN,
HOWEVER THE NUMBER OF PEOPLE THAT ARE MULTIDRUG
RESISTANCE IS GOING UP. NOT TOO GOOD. 97-98% OF PEOP W/PEOPLE
– BACTERIA ARE SUSCEPTIVE TO ISONIAZID AND RIFAMPIN.
o GENERAL TREATMENT:
 IMPORTANCE OF ADVERSE REACTIONS IN DRUG SELECTION
 ALL M TUBERCULOSIS INITIAL ISOLATES SHOULD BE TESTED FOR
SUSCEPTIBILITY TO DRUGS
 RESISTANT STRAINS OCCUR NATURALLY, ALTHOUGH AT A VERY LOW
FREQUENCY.
 USE OF COMBINED DRUG THERAPY WITH AT LEAST TWO DRUGS TO WHICH
ORGANISM IS SUSCEPTIBLE
 B/C YOU HAVE RESISTANCE THAT OCCURS NATURALLY – USE
THERAPY W/2 DRUGS TO WHICH ORGANISM IS SUSCEPTIBLE.
 TB therapy requires a multidrug regimen with agents active against the clinical isolate.
Susceptibility testing of initial isolates should always be obtained.
 The American Thoracic Society and the CDCP recommend that initial therapy be given
with four drugs; isoniazid, rifampin (or other rifamycin), pyrazinamide and ethambutol
(not recommended for children where visual acuity cannot be monitored) or streptomycin.
 CHILDREN – SUBSTITUE ETHAMBUTOL W/STREPTOMYCIN.
 After susceptibility of the clinical isolate has been determined, patients with drug-
susceptible isolates can be treated with isoniazid and rifampin.

 DRUG RESISTANT TUBERCULOSIS.

 Prevalence of drug resistant TB is increasing in the US
 Prevalence of INH resistant TB is ~ 10%
 US prevalence of INH-Rifampin resistant TB is ~3%
 Most TB patients can be treated entirely as outpatients.
 Hospitalization is required only for those seriously
 ill or requiring diagnostic evaluation
 TB treatment in HIV patients is extremely effective when begun promptly; use of
rifampin-based regimes gives clinical responses similar to that obtained in HIV-
free TB patients
o ***BEGAN PROMPTLY!!!
o
132
 First line drugs. based on their efficacy, activity and risk of adverse reactions:
o isoniazid (INH; generic)
o rifampin (rifadin)
o pyrazinamide (generic)
o ethambutol (myambutol)
o streptomycin (generic)
o THESE ARE ALL VERY DIFFERENT CHEMICAL STRUCTURES DOING VERY
DIFFERENT THINGS
 Second line drugs: used only when there are resistant organisms to first line drugs or exist other
overriding considerations:
o For information only:
 adverse reactions,
 effectiveness……limit their use
o Ethionamide,
o kanamycin,
o capreomycin,
o p-aminosalicylic acid,
o cycloserine,
o linezolid,
o fluoroquinolones
o The PRIMARY reason for the use of drug combinations in the treatment of TB is to delay the
emergency of resistance to INDIVIDUAL drugs***
o *DON’T NEED TO KNOW 2ND LINE DRUGS. THE ONLY INTEREST – WHICH THEY
EXIST.
o KNOW THAT PRIMARY REASON FOR THE USE OF DRUG COMBO.

133
 FIRST- LINE DRUGS:
o ISONIAZID (INH). HYDRAZIDE OF ISONICOTINIC ACID
 ANTIMICROBIAL ACTIVITY
 Acts only upon M, and is the most active drug available for the treatment of TB
caused by M susceptible strains;
 Less effective for the treatment of diseases caused by atypical M species.
 Small molecule, structurally similar to pyridoxine
 PHARMACOKINETICS:
 PRODRUG**
o After activation (by mycobacterial catalase-peroxidase KatG), has lethal
effect by forming a covalent complex with an acyl carrier protein (AcpM)
and a beta-ketoacyl carrier protein synthetase (KasA), blocking mycolic
acid synthesis killing the cell
o KNOW – THAT ISONIAZIDE HAS TO BE ACTIVATED AND AFTER
IT’S ACTIVATED IT FORMS ACTIVE SPECIES – KILLING THE
CELL.
 ABSORPTION:
o Well absorbed after oral administration, reaching peak plasma levels within
1-2 hrs.
 DISTRABUTION:
o Widespread distribution in body fluids and tissues, including:
 Brain, CSF, caseous TB lesions and phagocytic cells.
 ***WIDESPREAD DISTRIBUTION**** VERY IMP! GOES
ALL OVER THE PLACE.
o Active against intra- and extracellular organisms.
 ELIMINATION:
o N-Acetylated  N-acetylisoniazid by liver N-acetyltransferase
o N-acetylizoniazid + isonicotinic acid + little unchanged drug are eliminated
in the urine.
o Acetylisoniazid/isonizaid ratio is genetically determined by INH
acetylation rate
 INH average plasma conc. in rapid acetylators is ~1/3 to ½ of that
in slow acetylators,
 T½
o Rapid = 1 hr
o Slow = 3 hrs
 When using appropriate daily dosing this is of no
therapeutic consequence;
 Weekly NIH dosing (rapid acetylators) or malabsorption
may result in subtherapeutic levels ***

 HEPATOTOXICITY – PEO W/SLOW OR HIGH ACETYLATOR

– MUST ADJUST THE DOSE!

134
 RESISTANCE:
 to INH has been associated with various mutations:
o Over-expression of inhA gene encoding an NADH-dependent acyl carrier
protein reductase
o .Mutation or deletion of the katG gene
o Promoter mutations resulting in over-expression of ahpC, a putative
virulence gene involved in cell protection from oxidative stress.
o Mutations in kasA
 inhA overproducers express low level resistance to INH and cross
resistance to ethionamide.
 KatG mutants express high-level INH resistance and often are not
cross-resistant to ethionamide.
 REASON WHY TO USE MULTIPLE DRUGS: **
o INH resistant mutants occur in susceptible M populations with a frequency
of ~ 1 bacillus in a million.
o Since TB lesions often contain more than 100 million bacilli, addition of a
second independently acting drug, to which resistance also emerges at a
frequency of ~ 1 in a million, makes the odds that a bacillus proves
resistant to both drugs of ~ 1 in a billion.
 CLINICAL USES:
 DOC (Drug of Choice) when single agent used as chemoprophylaxis in individuals
at greatest risk for developing active disease after being infected:
o very young children,
o immunocompromised individuals testing positive within 2 years after
negative skin test
 Typical adult dose (300 mg/once/d) should be adjusted in serious infection (single
900 mg twice/w) in combination with a second agent (600 mg rifampin). Dose
modified in malabsorption or use of drug combinations
 Pyridoxine, 25-50 mg/d is recommended for those at risk of developing
neuropathy e.g., slow acetylators*

135
 
ADVERSE REACTIONS:
 Incidence and severity of untoward reactions related to dosage and duration of
treatment
 INH-induced clinical hepatitis, with histological evidence of necrosis and
hepatocellular damage, is the most common major toxic effect occurring in ~ 1%
of patients and can be fatal if not discontinued promptly.
o AGE – RARELY UNDER 20. RISK OF DEVELOPING THIS HEP LIKE
CONDITION GOES UP DRAMATICALLY W/AGE.
 Risk depends on age: rarely under 20 years; between 21-35 years (0.3%); 36-50
(1.2%), and 50 and above (2.3%)
 Greater risk in alcoholics and possibly during pregnancy and the post-partum
period.
 Peripheral neuropathy seen in 10-20% patients given dosages > 5 mg/kg/d.
Infrequent with standard 300 mg/d adult dose
 INH neuropathy due to a relative pyridoxine deficiency and is more likely to occur
in slow acetylators and patients with predisposing conditions such as malnutrition,
alcoholism, diabetes, AIDS, and uremia.
 INH promotes pyridoxine excretion and this toxicity is readily reversed by
administration of pyridoxine 10 mg/d CNS side effects include memory loss,
psychosis and seizures, allergic reactions………
o RIFAMPIN:
 ANTIMICROBIAL ACTIVITY and MOA
 Human RNA polymerase does not bind the drug nor is inhibited by it
 Effective against various bacteria, including bactericidal activity against
Mycobacteria. Binds to the beta subunit of bacterial DNA-dependent RNA
polymerase, inhibiting RNA synthesis.
 USES:
 Penetrates most tissues and fluids, including phagocytic cells; therapeutic CSF
levels reached only in the presence meningeal inflammation
o AGAIN, THIS TOO GOES ALL OVER THE PLACE.
 In combination with other drugs, rifampin 600 mg/d or twice/w 6 months, is
effective in some atypical M infections and leprosy
 Single drug, alternative to INH prophylactic treatment, in patients with latent TB
unable to take INH or when exposed to a case of active TB caused by INH-
resistant, rifampin- susceptible M strain

 RESISTANCE:
 Semisynthetic analog of the antibiotic rifamycin, present cross-resistance to other
rifamycin derived drugs e.g., Rifabutin, but not to other classes of antibiotics
 Resistance results from one of several point mutations in rpoB, the gene for the
beta subunit of RNA polymerase, resulting in reduced rifampin binding to RNA
polymerase.
 INH – FIRST LINE DRUG FOR TX OF MICROBACTERIAL TB. 80% OF
PEOPLE THAT HAVE THIS – BACTERIA IS SUSCEPTIBLE TO INH.
NUMBER OF POSSIBLE S/E. PARTICULARLY IN PEOP THAT ARE SLOW
ACEYLYTATORS.

136
 
Present of resistant mutants is seen in all microbial populations at ~ 1 in a million
bacillus, and rifampin 600 mg/d, must be administered with INH or other anti-TB
drugs to patients with active TB to prevent emergence of drug-resistant
mycobacteria
 PHARMOCOKINETICS:
 Well absorbed after oral administration, which decreases when taken with meals or
PAS acid. Excreted into bile, undergoes enterohepatic recirculation and eliminated
mostly in feces as a deacylated metabolite
 SE:
 Rifampin give the urine, feces, saliva, sweat, tears, and contact lenses a harmless
red orange color, producing patient’s anxiety.
 SE include light-chain proteinuria, and occasionally rash, nephritis, jaundice, and
hepatitis
 Intermittent administration, > 2w, causes a flu-like syndrome e.g., fever, myalgias,
thrombocytopenia
 DRUG INTERACTIONS
 Strongly induces most cytochrome P450 isoforms increasing the elimination rate,
thus lowering serum levels, of numerous drugs e.g., methadone, oral
anticoagulants, some anticonvulsants, etc
 IMP IN CERTAIN DRUGS WHERE THE DRUG MAY BECOME IN SHORT
SUPPLY – IF D/C FOR 2-3 WKS – BECAREFUL W/THIS.
o ETHAMBUTOL
 MOA
 Bacteriostatic agent. Inhibits mycobacterial arabinosyl tranferases enzymes,
encoded by the embCAB operon, which are involved in the polymerization
reaction of arabinoglycan, an essential component of the mycobacterial cell

 RESISTANCE:
 Resistance due to mutations resulting in over expression of emb gene products or
within the embB structural gene
 Rapid resistance emergency occurs if used alone. Given as single daily dose
combined with INH or rifampin. Effective against most M TB strains. Sensitivity
of other M variable
 PHARMACOKINETICS:
 Well absorbed from the GI, peak plasma levels reached within 2 hrs, excreted in
feces and urine. It accumulates in renal failure, reaches CSF only if meningeal
inflammation
 MENINGEAL INFLAMMATION – AN OPENIING THAT ALLOWS US TO
GET INTO THE CSF.
 SE:
 Most common serious side effect is dose-related retrobulbar neuritis resulting in
loss of visual acuity and red-green color blindness. It disappears after drug
discontinuation Hypersensitivity reaction to this drug is rare
 CONTRAINDICATIONS:
 Relatively contraindicated in children too young to permit assessment of visual
acuity and red-green color discrimination
 PEOPLE CANNOT DIFFERENTIATE BETWEEN RED AND GREEN.
 CHILDREN W/VISUAL ACUITY – MAY WANT TO USE ANOTHER DRUG.
137
o PYRAZINAMIDE:
 MOA:
 Prodrug
 Synthetic analog of nicotinamide. Converted to pyrazinoic acid, active form of the
drug, by mycobacterial pyrazinamidase, which is encoded by pncA. PZA target
and MA of action unknown
 RESISTANCE:
 Resistance may occur due to mutations in pncA, blocking drug conversion to its
active form, or by decreased drug uptake which develops rapidly
 PHARMACOKINETICS:
 Well absorbed from GI, widely distributed including inflamed meninges and
macrophages. Peak serum levels reached within 1-2 hrs and t1/2 ~ 10 hrs
 SE:
 Major adverse effects include hepatotoxicity (1-5% patients),****
 GI disturbances and hyperuricemia, which occurs in most patients; this is not a
reason to stop therapy unless patients suffers acute gout attack
 USE:
 Used together with INH and rifampin in short course regimes (e.g., 6 months) as a
“sterilizing” agent to prevent relapse. TB bacilli rapidly develops resistance to
pyrazinamide, however there is no cross-resistance between this drug and other
anti-TB agents
o STREPTOMYCIN
 MOA:
 Unknown MA against M TB.
 USES:
 Effective treatment of M tuberculosis, M avium complex and M kansaii; other M
species are resistant to this drug. Poor penetration into cells and is effective mainly
against extracellular tubercle bacilli.
 Used when injectable (IV or IM) therapy is recommended e.g., TB meningitis
(crosses the BBB achieving therapeutic levels with inflamed meninges) and
disseminated infection, or when TB is resistant to other drugs.
 Inhibits most tubercle bacilli, however all large populations contain some
streptomycin-resistant mutants (~ 1 in 100 million bacilli).
 RESISTANCE:
 Resistant due to a point mutation in either:
o the rpsL gene
 (encoding the S12 ribosomal protein gene)
o the rrs gene
 (encoding the 16S ribosomal rRNA, thus altering the ribosomal
binding site)
 Always given in a multidrug regime to prevent emergency of resistance. Treatment
continue for several months and dosage should be adjusted during the course of
therapy

 SE:
 Dose-related oto- and nephrotoxicity limits its use;
 Most common side effects:
o Vertigo and hearing loss, may become permanent.
 Risk increasing in the elderly and in patients with impaired renal function
138
 SECOND-LINE DRUGS
o SECOND LINE DRUGS – ONLY FOR OUR INFORATION. ** except for aminosalicylic acid
(PAS)
o GENERAL:
 These agents are considered only if:
 Resistance occurs to first-line drugs
 Failure of recommended conventional therapy
 Adverse effects limiting conventional therapy
 Ability to deal with these drugs toxicity
 The dosage, resistance emergency, and long-term toxicity of many of these drugs are not
yet well established
o Ethionamide:
 MOA:
 Inhibits mycolic acid synthesis.
 SE:
 GI irritation, neurophaties and liver toxicity
o Capreomycin:
 MOA:
 Protein synthesis inhibitor,
 USES:
 Given IM for the treatment of drug-resistant TB.
 SE:
 oto- and nephrotoxic
o Cycloserine:
 MOA
 Inhibits cell wall synthesis.
 SE:
 peripheral neuropathies and CNS depression and psychotic reactions
o Aminosalicylic acid (PAS) – NEED TO KNOW THIS ONE!!!
 MOA
 Folate synthesis antagonist.
 SE:
 GI irritation and hypersensitivity reactions
 USES:
 *PAS – STILL USED IN DEVELOPING COUNTRIES OR
UNDERDEVELOPED COUNTRIES FOR TX OF TB.
o PEOPLE FROM THERE COME HERE W/LATENT TB. BEFORE YOU
START TREATING PT – YOU ASK PT IF THEY HAD TB FLARE UP
IN COUNTRY OF ORIGIN. THEY MAY ANSWER YOU THAT THEY
USED THIS DRUG (PAS).

o SOME PEOPLE WERE GIVEN A TB TEST AND THEY RESPONDED.

THEN CHECKED HERE IN THE U.S. AND THEY COME OUT
POSITIVE. BUT THAT DOESN’T MEAN THAT THEY ARE
POSITIVE.
139
o OTHER DRUGS USED: (SLIDE #32/39 – NOT SURE ABOUT THIS SHIT)
 Kanamycin,
 Amikacin.
 Fluoroquinolones:
 ciprofloxacin,
 Levofloxacin and others.
 Linezolid.
 These drugs have some use, in combination with other agents, in multidrug resistance M
tuberculosis
 Rifamycin:
 TYPES:
o Rifabutin and
o Rifapentin.
 Similar MA than rifampin, remains the rifamycin of choice

140
 ATYPICAL MYCOBACTERIA DRUG TREATMENT

 GENERAL:
o Approximately 10% of Mycobacterial infections seen in the USA are not due to M tuberculosis or
M tuberculosis complex organisms, but to the so-called “atypical” mycobacteria:
 M kansaii,
 marinum,
 avium complex, etc
o These organisms, with specific lab characteristics and present in the environment, are not
communicable from person to person
o In general, these M species are less responsive than M tuberculosis to anti-TB drugs;
 however, they may respond to agents not active against M tuberculosis e.g., erythromycin
and sulfonamides
o Active infection should be treated with a multidrug regime to achieve optimal results in the
shortest period of time, while minimizing the development of resistance.
o Due to the many M strains identified as pathogenic consult the CDCP for latest research before
starting specific treatment
o Late stages of AIDS are commonly associated with disseminated M avium complex infection,
which includes the presence of M avium and M intracellular.
 Recommended treatment includes
 clarithromycin plus ethambutol and Rifabutin

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 LEPROSY
 GENERAL:
o Lepra, caused by Mycobacterium Lepra, is characterized by cutaneous lesions causing
disfiguration and peripheral nerve damage; affects ~ 250,000 individuals/year, particularly in
tropical and semitropical areas
o Very low incidence in the USA (~ 150 new cases);
 ~ 100 developed by individuals returning from foreign trips and the rest occurring mostly
in Louisiana and Texas residents as a result of contact with armadillos
 Recent evidence shows armadillos as host for the M Lepra; their low body temperature
makes them “ideal” incubators for the bacteria
 WHOA!
 TREATMENT (GENERAL)
o Specialized area of medicine.
o Assess host defenses to predict length of therapy and risk of adverse reaction to medications.
o Early diagnosis and prompt treatment is important to prevent deformity and incapacity, which
once produced are irreversibly.
o DRUGS:
 DAPSONE
 MOA:
o Dapsone (and other sulfone-like agents) are closely related to sulfonamides
and they competitively inhibit folate synthesis.
 PHARMACOKINETICS:
o Well absorbed from the GI, widely distributed in the body,
o t1/2 of 1-2d,
o Eliminated in the urine (use with dose adjustment in kidney failure).
o Significantly concentrated in the skin of patients with M Lepra skin
infection
 SE:
o Generally well tolerated;
o some hemolysis,
 Particularly in G-6-PD deficiency patients.
o Erythema nodosum leprosum responds to corticosteroids; FDA approved
thalidomide for the treatment of this conditions; may cause irreversible
neuropathy…
 RESISTANCE:
o For better results, and to avoid development of resistance, initial therapy
combines dapsone with rifampin and clofazimine

 CLOFAZIMINE
o Clofazimine, an alternative to dapsone,
 PHARMACOKINETICS:
o Has an erratic absorption rate
142
 o Stored in skin and reticuloendothelial tissues from where it is slowly
released;
 t1/2 ~2 months
 USES
o Used in sulfone-resistant leprosy or for sulfone intolerant patients.
 SE:
o Prominent SE
 skin discoloration from red brown to nearly black

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 ANTI – MICROBIALS

 CATAGORIES:
o II. Bacterial Protein Synthesis Inhibitors
o III. Folic Acid Metabolism Inhibitors
o IV. DNA Replication and Transcription Inhibitors
o V. Urinary Tract Antiseptics & Other Antibiotics

BACTERIAL PROTEIN SYNTHASIS INHIBITORS

 BACTERIAL PROTEIN SYNTHASIS INHIBITORS: OVERVIEW: (6 OF THEM)

o Streptogramins and Oxazolidinones:
 Quinupristin / Dalfopristin (Q/D)
 Linezolid
o Macrolides:
 Erythromycin,
 Clarithromycin,
 Azithromycin.
 Also Ketolides
 Telithromycin
o Lincosamides
 Clindamycin
o Aminoglycosides:
 Streptomycin,
 Gentamicin,
 Tobramycin,
 Kanamycin,
 Amikacin
o Tetracyclines:
 Tetracycline,
 Doxycycline,
 Minocycline
 Tigecycline
o Chloramphenicol

144
 STREPTOGRAMINS AND OXAZOLIDINONES
o TYPES:
 Quinupristin and Dalfopristin
 Formulated and used in combination, Q/D (Synercid).
 Linezolid (Zyvox) is an oxazoladinone derivative
o MOA:
 Inhibit bacterial protein synthesis.
 Bind to the 23S RNA of 50S ribosomal subunit of bacteria
 HOW THEY DO IT? BY BINDING TO 23S RNA OF 50 S --- MECHANISM OF
ACTION
 Quinupristin / Dalfopristin:
 Inhibits peptidyl transferase, thereby blocking the elongation of the peptide chain.
 2 COMPOUNDS THAT INHIBIT PROTEIN SYNETHSIS.
 Dalfopristin acts at the early phase of protein synthesis,
 Quinupristin acts at the late phase.
 Linezolid:
 Binds to the 23S RNA on the 50S subunit and inhibits the formation of ribosome
complex and initiation of protein synthesis.
o ANTIMICROBIAL ACTIVITY:
 Narrow-spectrum:
 active against gram-(+),
 some gram-(-) bacteria,
 anaerobes, and
 chlamydia
 Q/D: also active against
 Vancomycin-resistant Enterococcus (VRE) faecium,
 Methicillin-resistant Staphylococcus Aureus (MRSA),
 Penicillin-resistant Streptococcus Pneumoniae (PRSP), &
 S Pyogenes
 Bactericidal: when Linezolid & Q/D are combined.
 Bacteriostatic: Q/D ALONE IS USED.
 Linezolid
 represents a new class of antimicrobials, highly active against susceptible and
resistant gram-(+) bacteria, including:
o Vancomycin-Resistant Enterococcus (VRE)
o Methicillin-Resistant Staphylococcus Aureus (MRSA)
o Penicillin-Resistant Streptococcus Pneumoniae (PRSP), &
o Streptococcus Pyogenes.
 Primarily bacteriostatic agent except for streptococci, for which is bactericidal
 Not useful against gram-(-) species.

 THESE ARE USED VERY CAREFULLY B/C AT THIS MOMENT ACTIVATE SOME
BACTERIA THAT IS DIFFICULT TO TREAT W/OTHER ABX.
 DRUGS OF LAST RESORT – TODAY – MAY NOT BE IN A WK OR MONTH.

145
o CLINICAL USES:
 “The Drugs of Last Resort”:
 To reduce the development of drug-resistant bacteria and maintain the
effectiveness of these drugs, Q/D and Linezolid should be used only to treat severe
infections caused by VRE, MRSA, PRSP and Streptococcus Pyrogenes, or be
limited to those for which other drugs are ineffective or not tolerable.
 ONLY FOR SEVERE INFECTIONS!
 Partial list
 Septicemia
 Hospital-acquired pneumonia
 Bacterial endocarditis:
o Elders; acute ~ or sub-acute ~.
 Cellulitis
 PARTIAL LIST IS RATHER LIMITED USE OF THIS SUBSTANCE AS
POSSIBLE B/C DRUG OF LAST RESORT
o RESISTANCE:
 Little known resistance. Resistance to linezolid presented by some enterococcal strains.
 LITTLE RESISTANCE
o PHARMACOKINETICS:
 D/Q
 present poor oral absorption; mostly metabolized in the liver and
 eliminated in feces
 Linezolid:
 good oral absorption, also used IV, oxidized (metabolized by non-P450 enzymes),
 Excreted in urine and feces.
o SIDE EFFECTS:
 D/Q
 Causes pain and frequent thrombophlebitis at injection site; may
 Produce arthralgia and myalgia.
 A NUMBER OF SE WHEN YOU USE THIS – THIS DRUG SHOULD NOT BE
TAKEN LIGHTLY


Linezolid:
 GI distress: diarrhea, nausea, vomiting, thrombocytopenia (chronic use), inhibits
monoamine oxidase activity – MORE OF A CURIOUSITY – DON’T KNOW
THE MOA OF THIS.
o DRUG INTERACTIONS:
 Q/D
 increases the levels of warfarin, diazepam, non-nucleoside
 Reverse transcriptase inhibitors, and cyclosporine.
 Linezolid
 augments the action of SSRI (SERITONIN UPTAKE INHIBITORS), other
antidepressants, as well as increases action of pseudoephedrine &
phenylpropanolamine - SOME LEGAL, SOME NOT SO LEGAL
 CNS psychotic effects at higher doses.

146
 MACROLIDES
o TYPES:
 ERYTHROMYCIN
 CLARITHROMYCIN
 AZITHROMYCIN
 ALSO THE KETOLIDES
o MOA:
 Bind to the 50S ribosomal subunit and block the aminoacyl translocation and formation of
translation complex.
o CLINCAL USES:
 Bacteriostatic, but bactericidal at high doses;
 Limited coverage for gram-(+) and (-) bacteria, & anaerobes.
 Also: Chlamydia, Mycoplasma pneumoniae, Mycobacterium
 Hospital / community-acquired pneumonia.
 Mycobacterium avium complex (MAC) pneumonia
 MAC - VERY IMP – DRUG COMMON IN PTS W/AIDS OR HIV POSTIIVE.
 Legionnaire’s disease
 Alternative to penicillin’s (patients allergic to penicillin)
o PHARMACOKINETICS:
 Good oral absorption (except erythromycin-acid sensitive).
 Extensive distribution (except the brain)
 Erythromycin, clarithromycin: liver metabolized
 Azithromycin is eliminated unchanged via kidney & feces

o SE
 GI distress: particularly by erythromycin
 Cholestatic hepatitis with erythromycin estolate (causing failure of bile flow)
o DRUG INTERACTIONS:
 Erythromycin and clarithromycin increase serum levels of:
 Theophylline (bronchodilator)
 Warfarin (oral anticoagulant)
 Cyclosporine (immunosuppressive agent)
 Statins (cholesterol synthesis inhibitors)
 Astemizole (histamine H1 receptor inhibitor)
 Various anticonvulsants
o RESISTANCE:
 Methylation or mutation of binding site leads to Macrolide-Lincosamide-Streptogramin B
resistance
 Reduced access to cells
 Hydrolyzed by esterases
o KETOLIDES = SEMISYNTHETIC MACROLIDES
 TYPE: Telithromycin.
 ANTIMICROBIAL ACTIVITY:
 Effective against many traditional macrolide-resistant strains. Structural
modification makes them poor substrates for efflux pump-mediated resistance.
 WHY IMP? B/C WE HAVE A WHOLE BUNCH OF MACROLIDES. BUT
MACROLIDES HAVE RESISTANCE. PROBLEM W/ABSORPTION. NEWER
FAMILY OF MACROLIDES – NOW EFFECTIVE IN DIFFERENT STRANDS.

147
 
MOA:
 Bind to ribosomes of some bacterial species with higher affinity than macrolides
 PHARMACOKINETICS:
 Taken orally, good tissue and intracellular penetration
 CLINCAL USES:
 Use for respiratory tract infection, including community-acquired bacterial
pneumonia and S pharyngitis
 DRUG INTERACTIONS:
 Reversible inhibits CYP3A4 enzyme system,
 SE
 May slightly prolong QTc interval.
 Rare cases of hepatitis reported
 LINCOSAMIDES:
o CLINAMYCIN HCL
 MOA:
 Bind to the 23S RNA of 50S ribosomal subunit and inhibit the aminoacyl
translocation and formation of initiation complex (similar to
streptogramins/oxazolidenones and macrolides)
 ANTIMICROBIAL ACTIVITY:
 Narrow spectrum: active against some gram-(+), most anaerobes, and some
chlamydia, but not gram-(-) bacteria. Bacteriostatic.
 CLINCAL USES:
 Treatment of penicillin-resistant gram-(+) infections and in patients allergic to
penicillin’s.
 Streptococci, staphylococci, and pneumococci are inhibited by clindamycin
 Anaerobic infections. Polymicrobial peritoneal infections.
 Hospital-acquired pneumonia (combined with G3 or G4 cephalosporins).
o HOSPITAL ACQUIRED PNEUMONIA – IMP USE. A DISTURBING
NUMBER OF PEOPLE GOING TO HOSPITAL AND ACQUIRE AN
INFECTION FOR A DIFF REASON. SO THESE DRUGS THAT ARE
USED FOR HOSP ACQUIRED CONDITIONS ARE VERY IMP.
 RESISTANCE:
 Methylation or mutation of the binding site causes MLS-type B resistance.
 Reduced drug access to bacteria
 PHARMACOKINETICS:
 Good oral absorption.
 Extensive distribution (except into the brain). Metabolized in the liver, eliminated
in feces and by the kidneys
 SIDE NOTE:
o IN MANY CASES, THESE DRUGS HAVE EXTENSIVE
DISTRIBUTION BUT ARE NOT GOING TO THE BRAIN. IF WE
HAVE AN INF IN WHICH THE AGENT GOES TO THE BRAIN. WE
START LOOKING FOR DRUGS THAT WILL PENETRATE THE
BRAIN. PROBLEM W/HIV PTS – WHEN THE AGENT IS IN
CIRCULATION – NOT IN THE BRAIN – CAN TAKE CARE OF IT.
BUT IF INF GETS INTO THE BRAIN – DON’T HAVE ANTI-HIV
DRUGS THAT GO INTO THE BRAIN… REINFECTED BY DRUGS
COMING FROM THE BRAIN.
o BRAIN AND CSF INFECTION DRUGS ARE VERY IMP. DELICATE.
148
  SE

GI distress, Rash, Super infections, Hepatotoxicity, Neutropenia

Respiratory paralysis could be induced with use of muscle relaxants: baclofen,
diazepam, Atracurium
 AMINOGYCOSIDES:
o CHEMISTRY
 Aminoglycosides have two (or more) aminosugars linked to a hexose ring (or
aminocyclitol) via glycosidic links.
o MOA:
 Bind 16S RNA of the 30S ribosomal subunit and inhibit protein synthesis
o TYPES:
 Streptomycin:
 the 1st to be isolated, derived from Streptomyces griseus
 Neomycin
 Gentamicin
 Tobramycin
 Kanamycin,
 Amikacin
o ANTIMICROBIAL ACTIVITY:
 Narrow-spectrum, mostly Bactericidal
 Active against gram-(-) and limited gram-(+);
 Some are effective against Pseudomonas aeruginosa.
 Not effective against anaerobes
o CLINICAL USES:
 Infective bacterial endocarditis
 Septicemia
 Hospital-acquired pneumonia
 Chronic urinary tract infections
o RESISTANCE:
 Mutation at the ribosome binding site.
 Enzymatic Inactivation: by acetylation, adenylation or phosphorylation.
 Reduced permeability.
o PHARMACOKINETICS:
 Poor oral absorption.
 Variable distribution in body; do not enter the brain
 Reduced activity in low pH, hyperosmolarity, & anaerobiosis
 Unmetabolized and eliminated by the kidneys.

149
 o SIDE NOTE:
 CAN GET CONFUSED W/THIS – WHEN START LOOKING AT THIS – HOW DO
THEY WORK? ALL THESE FAMILIES WORK VERY SIMILAR MOA. VERY
SIMILAR POSSIBLE MECHANISM OF RESISTANCE. WORK IN SAME
INFECTIONS. MOST DON’T GET INTO THE BRAIN. VERY SIMILAR. WHY USE
ONE AND NOT THE OTHER?
LOOK AT GENERAL PHYSICAL OF PT, DRUG INTERACTION, AND DRUG
ALLERGIES (ALLERGIC TO PCN) – HAVE TO HAVE DRUGS THAT DON’T
HAVE SAME PROBLEM. WHEN YOU START LOOKING – CAREFUL – NOT
THAT COMPLICATED.
o ADVERSE REACTIONS: ****
 Ototoxicity
 Nephrotoxicity
 Neuromuscular blockade
o DRUG INTERACTIONS:
 Increased ototoxicity with loop diuretics, Vancomycin
 Increased nephrotoxicity with Vancomycin, cyclosporine, NSAIDs, radiographic contrast
(iodine-based) agents
 Respiratory depression with neuromuscular blockers
 In vitro mixing with penicillin’s reduces the activity of both
 TETRACYCLINES:
o TYPES:
 Tetracycline,
 Doxycycline,
 Minocycline
 Tigecycline (Glycycycline)
 Some isolated from certain species of Streptomyces. Others are semisynthetic.
 GENERAL FAMILY – 5TH. TETRACYCLINE – HAVE A WHOLE BUNCH OF
THEM.
o MOA:
 Bind 16S to the 30S ribosomal subunit and block the docking of tRNA on the ribosomes
(similar to aminoglycosides)
o ANTIMICROBIAL ACTIVITY:
 Broad-spectrum, Bacteriostatic
 Effective against many gram-(+) and -(-) bacteria, including,
 anaerobes,
 chlamydia,
 mycoplasmas,
 some protozoa

150
o USES:
 ***Use doxycycline unless otherwise noted:
 Chlamydial infections with gonorrhea,
 Mycoplasma pneumoniae
 Alternatives for (partial list):
 Hospital-acquired pneumonia
 Ulcers, Bronchitis, Syphilis, Cholera, Tularemia, Plague & anthrax.
 NOTE:
 CHOOSE AN ABX – WHICH ONE WILL I USE? LOOK AT ALL THE
THINGS HE TOLD US. ASK PT IF THEY’VE TAKEN THIS PARTICULAR
DRUG BEFORE. IF IT WORKS, MAYBE WE SHOULD USE IT AGAIN B/C
YOU CAN TOLERATE. BUT MAYBE THIS TIME THE BACTERIA IS
RESISTANT TO THAT. CONSIDER ALL THINGS FIRST.
 TIGECYCLINE
 CHEMISTRY
o Tetracycline derivative, the first glycylcycline
 MICROBIAL ACTIVITY:
o New IV broad spectrum antibiotic with activity against many drug-
resistant organisms.
 USES
o Approved for treatment of complicated skin/skin-structure infections and
intra-abdominal infections with resistant organisms (but not
Pseudomonas), particularly in patients who cannot tolerate other drugs
o Used judiciously minimize resistance development
o RESISTANCE:
 Enzymatic inactivation by phosphorylation, adenylation or acetylation.
 Reduced permeability into the cells
 Ribosome protecting proteins mutation
 Efflux pumping
o PHARMACOKINETICS:
 Variable oral absorption, reduced by food, dairy, aluminum hydroxide gels, cations, and
alkaline medium
 Extensive distribution in the body except the brain
 Metabolized in the liver
 Eliminated by the kidneys (doxy~ is eliminated in feces).

151
 o ADVERSE REACTIONS:

 Incorporates into teeth and bones (not given to children ≤8)-yellowish color ****
 Phototoxicity, GI distress, oto-, hepato-, and nephrotoxicity. super infections
o DRUG INTERACTIONS:
 Serum levels of doxycycline is reduced by some anticonvulsants and barbiturates.
 May cause increase digoxin toxicity
o CONTRAINDICATIONS:
 Pregnancy, renal or liver impairment or failure, children under 8 years of age***
 CHLORMPHENICOL
o MOA:
 Binds to the 50S ribosomal subunit A site (similar to macrolides and clindamycin),
preventing the docking of aminoacyl tRNA.
 Binds to mitochondrial ribosomes inhibiting the activity of peptidyl transferase, causing
side-effects
o ANTIMICROBIAL ACTIVITY:
 Broad-spectrum:
 Bacteriostatic: aerobic and anaerobic gram-(+) and - (-) bacteria. Bactericidal for
some gram-(-) bacteria, etc
o USES:
 Rarely used: potential toxicity, bacterial resistance, availability of effective alternatives;
may be considered e.g.,
 typhus and Rocky Mountain spotted fever
 Alternative to a B-lactam antibiotic in patients showing a major hypersensitivity reaction
to penicillin.
 Topical for eye infections-penetration of ocular tissues and aqueous humor
o SE:
 When prescribed make sure you understand the implications of chloramphenicol usage:
resistance, pharmacokinetics, adverse reactions and drug interaction
 ***HUGE CHANCE FOR TOXICITY!!**

152
 FOLIC ACID METABOLISM INHIBITORS

 GENERAL NOTES:
o 6 MAJOR FAMILIES, GROUPS – SIMILAR MOA – SIMILAR WAYS OF REISTANCE CAN
BE DEVELOPED. DIFFER IN THE TYPE OF INFECTIONS THAT YOU WILL USE THEM
FOR. ALSO DIFFER IN S/E AND IN HOW YOU USE IN PEOPLE THAT ARE
HYPERSENSITIVE TO PCN.

o NOW --- FOLIC ACID MET INHIBITORS. SULFONAMIDES – FIRST ABX TO BE USED
THEN WE FOUND ABX THAT WERE BETTER AND D/C’S USE OF SULFONAMIDES.
HOWEVER, IN LAST COUPLE OF YRS, THE USE OF SULFONAMIDE IN COMBO
W/TRIMETHOPRIM --- INFUSED TOGETHER.

 TYPES:
o Sulfonamides:
 Sulfadiazine
 Sulfamethoxazole
 Sulfasalazine
o Trimethoprim (not a sulfonamide):
 Formulated and given with sulfamethoxazole
 SULFONAMIDES:
o CHEMISTRY:
 The “Sulfa drugs” are structurally related to para-aminobenzoic acid (PABA)
o MOA:
 Competitively inhibit folic acid production by suppressing the activity of dehydropteroate
synthase
 Inhibition of tetrahydrofolate synthesis interrupts various metabolic reactions.
o ANTIMICROBIAL ACTIVITY:
 Broad-spectrum, Bacteriostatic Gram-(+) streptococci and pneumococci, Gram-(-)
meningococci and gonococci, Gram-(-) bacilli (E. coli and shigellae) and more
 Active against chlamydia and some protozoa. Stimulate Rickettsiae
 Largely replaced by less toxic, more effective agents. However,
Trimethroprim/sulfamethoxazole combo has increased their use for the prophylaxis
and treatment of specific microbial infections
o PHARMACOKINETICS:
 Good oral absorption, extensive distribution (body and brain), inactivated by acetylation
in the liver, eliminated by the kidneys, except sulfasalazine

o CLINICAL USES: A LOT

 Enterocolitis: sulfasalazine
 Burns: silver sulfadiazine
 Ocular infections
 Toxoplasmosis: sulfadiazine and pyrimethamine.
 Sulfamethoxazole can be formulated with phenazopyridine , an analgesic, to treat urinary
distress in UTIs
153
 o RESISTANCE:
 Overproduction of PABA (to compete with sulfonamides)
 MOST COMMON RESISTANCE TO SULFONAMIDES
 Reduced affinity of dehydropteroate synthase for the sulfa drugs.
 Natural resistance if organisms import folic acid.
o ADVERSE REACTIONS:
 Crystalluria, Hematopoeitic toxicities, Photosensitivity, Skin Rashes, Exfoliative
dermatitis, GI distress
 PHOTO SENSITIVITY – COMMON – USE THE DRUG, SUN OR LIGHT,
AND MAY PRODUCE RASHES (PRURITIS).
 Stevens-Johnson syndrome (skin and mucous membrane eruption)
 Kernicterus: damage to the brain of infants by jaundice (bilirubin), if given to mother. NO,
NO in pregnancy Newborn babies are often "polycythemic", meaning they have too many
red blood cells. When they break down the cells, one of the by-products is bilirubin,
which circulates in the blood, and causes jaundice.
 NOT DRUGS TO BE USED, BUT HAVE LITTLE USE THESE DAYS
W/TRIPMETHOPRIM
o DRUG INTERACTIONS:
 Increase serum levels of oral anticoagulants sulfonylureas, and hydantoin anticonvulsants.
Avoid use with methenamine (UTI) since it forms formaldehyde that condenses with
sulfonamides
 TRIMETHOPRIM/SULFAMETHAOXAZOLE
o CHEMISTRY
 Trimethoprim is used in combination with sulfamethoxazole
 Because the two drugs markedly potentiate each other.
o MOA:
 Trimethoprim inhibits dihydrofolate reductase, while sulfamethoxazole inhibits
dehydropteroate synthases, leading to an enhanced inhibition in THF synthesis.
 ***REMEMBER – THESE DRUGS INHIBIT OR DECREASE THE PRODUCTION
OF TETRACHILINE FOLIC ACID AND DISRUPT THE SYNTHASIS
o ANTIMICROBIAL ACTIVITY
 Broad spectrum, Synergism with a sulfonamide (bactericidal), but bacteriostatic if used
alone. Active against gram-(+), gram-(-), but not anaerobes
 Also active to chlamydia
o CLINICAL USES:
 Prevent recurrent UTI urinary tract infections, treat upper respiratory infections, bronchitis
 Mutations of dihydrofolate reductase.
 Natural resistance if organism imports folic acid
 Metabolic bypass
o PHARMACOKINETICS:
 Trimethoprim:
 Good oral absorption.
 Extensive distribution, including the brain.
 Inactivated by oxidation and conjugation.
 Excreted mostly by the kidney, some in feces
o AR
 Same as with other sulfonamides.
 Higher incidence of rash, neutropenia, and hematologic toxicities in AIDS patients
 No, NO in patients with liver impairment
154
 DNA REPLICATION ANF TRANSCRIPTION INHIBITORS:

 FLUOROQUINOLONES:
o CHEMISTRY:
 Fluoride derivatives of nalidixic acid
 ALL HAVE FLUORINATED R6 (-F)
o TYPES:
 VERY LARGE NUMBER OF THESE
 REMEMBER:
 CIPROFLOXACIN
 LEVOFLOXIACIN
o MOA:
 Block bacterial DNA synthesis (transcription & replication) by inhibiting α-subunit of
DNA gyrase (topoisomerase II) and topoisomerase IV (separating DNA strands).
 The two strands of double-helical DNA must be separated to permit DNA duplication
or transcription
o ANTIMICROBIAL ACTIVITY:
 BROAD-SPECTRUM. BACTERICIDAL EFFECTIVE AGAINST GRAM-(+) AND
(-), LIMITEDACTIVITY AGAINST ANAEROBES
 ONLY CIPROFLOXACIN AND LEVOFLUOXACIN ARE ACTIVE AGAINST
PSEUDOMONA AEUROGINOSA.
 Also effective against CHLAMYDIAE MYCOPLASMA
 SO THESE DRUGS ARE PRETTY EFFECTIVE AGAINST SOME RESISTANT
BACTERIA.
o CLINICAL USES:
 Genital (acute and chronic UTIs; Gonorrhea), GI, bone,
 Joint and complicated skin infections.
 Conjunctivitis: ciprofloxacin ophthalmic solution
 Anthrax: ciprofloxacin is FDA approved to treat and protect people who have been
exposed to anthrax spores
 CIPRO IN NEWS FOR A COUPLE OF YRS – APPROVED IN FDA TO TX
PEOPLE THAT WERE EXPOSED TO ANTHRAX SCARES, SPORINS.
 CIPRO CAME
 Different fluoroquinolones show specific pharmacological profile (antibacterial
effects)
 INTO THE NEWS THAT WAY – A LOT OF PEOPLE BOUGHT A BUNCH OF IT.


o RESISTANCE:
 Mutation at quinolone binding site
 Reduced access-reduced porin number
 Drug efflux
o AR:
 Generally well tolerated. May cause GI distress, headache, dizziness, insomnia, skin
rush; damage growing cartilage and cause arthralgia…….
 Precaution:
 They are not usually suggested for children younger than 18-yr-old (cartilage
damage) & contraindicated during pregnancy or patients allergic to other
quinolones.
155
  SIDE NOTE:
 A DRUG WELL TOLERATED – DOESN’T MEAN THAT THE DRUG
SHOULD BE USED W/O…JUST USE B/C IT’S WELL TOLERATED.
WELL TOLERATED IS STHG IN RELATION TO WHAT OTHER
SIMILAR DRUGS DO. TO DRUGS IN SAME TYPE OF FAMILY. OR
WELL TOLERATED DEPENDENT ON THE CONDITION PT IS. THERE
IS NO DRUG THAT IS NOT HARMFUL.
 PEOPLE SAY ASA IS WELL TOLERATED – IT MAYBE BUT IT CAN
CAUSE A NUMBER OF PROBLEMS IN A NUMBER OF PEOPLE –
BLEEDING, ETC.
 DIFF BTWN S/E, TOXIC EFFECTS, POISIONING, ADVERSE RXN, AND
OTHER RXN THAT YOU’D LIKE TO HAVE (WHEN YOU HAVE
ALLERGY AND TAKE ANTI-HISTAMINE) – TAKE OLDER ONES
THAT WILL CAUSE DROWSINESS. THAT S/E IS WHAT YOU’D LIKE
TO HAVE IF YOU STAY HOME. BUT IF YOU GO TO WORK, USE
NEWER THAT WON’T GO TO THE BRAIN. B/C YOU DON’T WANT
THE DROWSINESS.

o PHARMACOKINETICS:
 Generally good oral absorption and extensive body distribution (except the brain), but
enoxacin penetrates into the CNS.
 Mostly partially metabolized and eliminated via the kidneys (some exceptions).

o DRUG INTERACTIONS:
 Cause cardiac arrhythmias when used with some anti-arrhythmic agents
 Generally, there is an increased chance of seizures when used with NSAIDS
 Decreased absorption with sucralfate, cations, antacids, dairy and citric acid
 ***DAMAGED CARTIAGE – DON’T GIVE TO YOUNGER THAN 18.
 DO NO PENETRATE INTO BRAIN. CARDIAC ARRYTHMIAS.

156
 URINARY TRACT ANTISEPTICS AND OTHER ANTIBIOTICS:

 TYPES:
o Nitrofurantoin
 Acute (and chronic) urinary tract infection
o Methenamine
 UTIs prophylaxis but not as a primary agent for treatment
o Metronidazole:
 vaginitis and other bacterial infections
o Mupirocin:
 Used topically for staphylococci-caused impetigo. May cause local itching, rash
contact dermatitis……..
o Polymyxins:
 Because of toxicity use restricted to topical therapy of resistant gram-negative
infections
o DRUGS THAT YOU USE FOR UTI.
o VERY DIFF TO TX B/C YOU HAVE TO HAVE THE APPROPRIATE AMT OF DRUG
GOING TO THE URINE. NOT EASY TO GET PROPER DOSAGE TO GO TO URINE.
 NITROFURANTOIN:
o MOA:
 Bacteria reduce Nitrofurantoin more easily than mammalian cells and reduced drug
products damage bacterial DNA
o ANTIMICROBIAL ACTIVITY:
 Bacteriostatic, active against [Link] and enterococci, but not proteus, Pseudomonas
and Enterobacters.
 ***KNOW – ANTIMICROBIAL ACTIVITY. THE DRUG HAS TO BE REDUCED
AND THE REDUCED DRUG THAT DAMAGES BACTERIA DNA.
 DON’T NEED TO KNOW CHEM STRUCTURE.
o USES:
 Primarily to treat UTIs, also prophylaxis for recurrent UTIs.
 ADVISABLE TO TX INDIVIDUAL AND PARTNER(S) – TSK TSK!!! – B/C CAN GET
REINFECTED.
o PHARMACOKINETICS:
 good oral absorption; partially
 Eliminated by the kidneys.
o ADVERSE REACTIONS:
 GI distress, anorexia, hemolytic
 anemia, neuropathies, renal failure

o RESISTANCE
 Inability to reduce the drug nitrogen in
 The presence of oxygen. Susceptible bacteria rarely
 Become resistant.
 METHENAMINE:
157
 o MOA:
 Antiseptic converted to formaldehyde in water and low urinary pH; nearly all bacteria
are sensitive.
o CLINICAL USES:
 Prophylactic treatment for recurrent UTI, formulated with mandelate or hippurate to
increase effectiveness.
 IF PARTNERS DON’T WANT TO BE TREATED – AND YOU HAVE BEEN
TREATED – PARTNERS DON’T WANT TO BE TREATED – YOU CAN USE
THIS AS A PROPHYLAXIS.
o Pharmacokinetics
 Good oral absorption, concentrated in acidic compartments (e.g., in the urinary tract,
bladder, and gastric juices).
o Adverse Reactions:
 GI distress; frequency of micturition, albuminuria, hematuria and rashes
o Drug Interactions:
 Form insoluble compound with sulfa drugs
o Resistance:
 Proteus that raise pH in urine are resistant
o Contraindications:
 Hepatic disease since ammonia is produced

 METRONIDAZOLE:
o NOTE: Metronidazole is covered extensively in the protozoan lecture
o MA and Antimicrobial Activity:
 Anti-protozoal drug, with potent activity against anaerobes (e.g., trichomonas).
Inhibits DNA synthesis
o Clinical Uses:
 Vaginitis (trichomonas and bacterial vaginosis), amebiasis (intestinal, amebic
dysentery; hepatic, abscesses), & giardiasis (giardia, diarrhea).
 USED FOR A WHOLE BUNCH OF PARASITIC INFECTIONS.
158
159
 AMINOGLYCOSIDES; NARROW SPECTRUM

 According to a recent (2007) article in the Journal of the American Medical Association:
o Approx. 100,000 patients developed an invasive (not merely colonized on the skin, but has
attacked a normally sterile part of the body) infection from MRSA
o Prevalence of 32 cases per 100,000 people
o About 85% of invasive MRSA associated with health care treatment
o Responsible for ~20,000 deaths annually, exceedingly those attributed to HIV/AIDS,
Parkinson’s disease, emphysema or homicide
o Total infections associated with health care ~ 1.7 million, leading to ~ 100,000 deaths

 15 STEPS TO REDUCE RISK OF A HOSPITAL INFECTION:

o Hospital staff and visitors must clean their hands; “dirty hands on brand new gloves”
160
o Stethoscope must be clean
o If a “central line” catheter is needed, consider one which is antibiotic-impregnated or
antiseptic-coated
o If surgery is needed, choose a “low infection” rate surgeon
o Beginning 3 to 5 days before surgery, shower or bathe daily with chlorhexidine soap (get rid
of own skin bugs)
o Be tested for MRSA at least 1 week before admitted into the hospital
o Stop smoking well in advance of surgery
o On the day of the operation remind the doctor that an antibiotic may need before the first
incision
o Ask the doctor about keeping patient warm during surgery
o Do not shave the surgical site. Use clippers instead
o Wash hands frequently, avoid touching your hands to your mouth, do not set food or utensils
on bed sheets
o Monitor glucose continuously during and after surgery, especially cardiac surgery
o Avoid a urinary tract catheter if possible. Common cause of infection. If needed ask it to be
removed ASAP
o If you must use an IV, make sure it is inserted and removed under clean conditions, changed
every 3 to 4 days
o During Cesarean delivery, followed steps above

161
 PROTEIN SYNTHESIS INHIBITORS

AMINOGLYCOSIDES
STREPTOGRAMINS Streptomycin
Quinupristin/dalfopristin Amikacin
OXAZOLIDINONES Gentamicin
Linezolid Kanamycin
MACROLIDES Tobramycin
Erythromycin
Clarithromycin
Azithromycin
Ketolides/Telithromycin
LINCOSAMIDES
Clindamycin
57

Protein Synthesis Inhibitors (con’t)

TETRACYCLINES: DNA REPLICATION INHIBITORS:

Tetracycline Fluoroquinolones
Doxycycline Ciprofloxacin
Minocycline Levofloxacin

GLYCYCYCLINES URINARY TRACT ANTISEPTICS, ETC:

Tigecycline Metronidazole
Nitrofurantoin
CHLORAMPHENICOL Methenamine
Mupirocin
Polymyxins

FOLATE METABOLISM INHIBITORS:

SULFONAMIDES:
Sulfamethoxazole
Sulfasalazine
Sulfadiazine
Trimethoprim 58

162
 Cox-1 & Cox-2

Cyclooxygenase (COX) – is an enzyme that catalyzes the synthesis of prostaglandins from arachidonic acid

 Cyclooxygenase inhibitors bind to and prevent activation of the COX binding site, preventing
subsequent formation of prostaglandins and thromboxane
o Aspirin irreversibly acetylates platelets
o NSAIDs reversibly inhibit platelets
 Prostaglandins
mediate a large
number of bodily
processes:

o Inflammation pain secretion of a protective gastric layer

o Maintenance of renal perfusion
o Platelet aggregation

 Nonsteroidal anti-inflammatory drugs (NSAIDs) block the action of COX enzyme thus reducing the
production of prostaglandin mediators
o Result:
 Positive  analgesia, anti-inflammatory
 Negative  gastric ulceration, decreased renal perfusion, bleeding

163
 o Believed to reduce postoperative pain by suppressing COX-mediated production of
prostaglandin E2, which is thought to be the primary inflammatory prostaglandin that directly
activates and up-regulates the sensitivity of peripheral nociceptors to cause pain
o NSAID is an all-inclusive term denoting a varied group of drugs possessing analgesic, anti-
inflammatory, and antipyretic effects
 Non-specific inhibitors – ibuprofen, naproxen, aspirin, acetaminophen, ketorolac
 COX-2 selective inhibitors – celecoxib, rofecoxib, valdecoxib, parecoxib
Cyclooxygenase (COX) 1

 Found primarily in gastric mucosa, renal parenchyma, and platelets

 Possess analgesic, anti-inflammatory, and platelet inhibitory effects
 Is only slightly up-regulated in response to inflammatory hormones
 Essential in homeostatic processes:
o Platelet aggregation
o Gastrointestinal mucosal integrity
o Renal function
 Inhibition of COX-1 is responsible for many of the adverse side effects associated with conventional
NSAIDs
Cyclooxygenase (COX) 2

 Is expressed mainly in sites of injury  brain and kidneys

 They are highly lipophilic, neutral, nonacidic molecules with very limited solubility in aqueous media
 Metabolism by cytochrome P-450 enzyme to hydroxy, carboxylic acid, and glucuronide derivatives
with about 2% of the drug being excreted unchanged by the kidneys
 Mediates:
o Inflammation
o Fever
o Pain
o Carcinogenesis
 Common use in osteoarthritis, rheumatoid arthritis, acute gout, dysmenorrhea
 Transient up-regulation in the spinal cord in response to surgical inflammation may be important in
central sensitization
o Up-regulation 10- to 20-fold

 Represent a significant therapeutic advance with their improved side-effect profile compared with
conventional NSAIDs
o Lack effects on platelets at therapeutic doses and may be associated with decreased
gastrointestinal side effects in patients with arthritis, compared with nonspecific NSAIDs
 Incidence of gastrointestinal side effects (gastric and duodenal ulcers) is decreased by
approximately 50% in patients treated with selective COX-2 inhibitors
o A safer alternative to nonselective NSAIDs because they are well tolerated by patients with
asthma
o Reduce risk of developing Alzheimer’s disease
 Adverse effects:
o Commonly associated in those receiving these drugs chronically for the treatment of arthritis.

164
 o Risk of acute myocardial infarction and cerebrovascular accident may be increased in patients
treated chronically with selective COX-2 specific enzyme inhibitors
o May facilitate several oncogenic processes  tumor invasion, angiogenesis, metastasis
o Have no adverse effect on renal function in healthy individuals
 When renal toxicity does manifest, it is likely due to NSAID-induced inhibition of
prostaglandin synthesis, leading to renal medullary ischemia
 Factors favoring NSAID-induced nephrotoxicity include hypovolemia, preexisting
renal disease, congestive heart failure, sepsis, combination with other potentially
nephrotoxic drugs or radiographic contrast material, diabetes mellitus and cirrhosis
o Increases in plasma concentrations of liver transaminases may accompany treatment with
NSAIDs
 The analgesic effects may not be superior to that provided by historically older drugs

165
 NSAIDS & OPIOIDS
NSAIDS
NSAID is an all-inclusive term denoting a varied group of drugs possessing analgesic, anti-inflammatory,
and antipyretic effects.
Benefits:

 Decrease activation and sensitization of peripheral nociceptors,

 attenuate inflammatory response
 synergy with opioids
 long duration of action,
 no respiratory depression,
 less dosing variability
Disadvantages:

 inhibit platelet aggregation,

 gastric ulceration (interact with anticoagulants to cause hemorrhage; COX 2 increases Coumadin
levels),
 renal dysfunction, bronchoconstriction in susceptible asthmatics (blocks prostaglandin E2)
Two categories:
1. COX 2 inhibitors: celecoxib, rofecoxib, valdecoxib, parecoxib
2. Nonspecific COX inhibitors:
a. Carboxylic Acids:
i. Acetylated: aspirin (irreversibly acetylates COX enzyme leading to decreased
synthesis and release of prostaglandins)
1. Overdose – seizures, tinnitus, respiratory and metabolic acidosis – treat with
sodium bicarb
ii. Nonacetylated: sodium salicylate, salicylamide, diflunisal
b. Acetic Acids:
i. Indomethacin (most potent COX enzyme inhibitor known; used to prevent PDA
closure in infants), sulindac, tolmetin
c. Propionic acids: inhibit prostaglandin synthesis
i. Ibuprofen, naproxen, fenoprofen, ketoprofen
d. Enolic Acids: inhibit prostaglandin synthesis
i. Phenylbutazone, piroxicam
e. Pyrrolopyrrole
i. Ketorolac – potent analgesia, mild anti-inflammatory, potentiates antinociceptive
actions of opioids

166
 3. Acetaminophen (Tylenol) not actually an NSAID because it is not an anti-inflammatory agent
a. Dosing – 15 mg/kg to max 75 mg/kg/day for peds, < 4g/day for adults
b. Useful analgesic and antipyretic useful for patients in whom salicylates are not recommended
c. No gastric irritation, platelet problems
d. Extensive hepatic metabolism – hepatotoxicity and necrosis occurs with glutathione depletion
(acetylcysteine increases glutathione stores)
e. Mechanism of action is poorly understood, possibly COX 3 inhibition
f. Use caution in:
i. Careful with chronic alcoholism, liver dx, wasting chronic
ii. Avoid in G6-PD deficiency patients
Pharmacokinetics:

 NSAIDs are well absorbed from the GI tract with a low first-pass effect, highly albumin bound with
small Vd
 Most NSAIDs are weakly acidic, which is important for tissue distribution. Sequestration of drug in
inflamed joints is a desirable effect of this, for example.
 Selective COX2 inhibitors are different from NSAIDs in that they are all highly lipophilic, neutral
nonacidic molecules
OPIOIDS
Weak Bases:
Opioids pH
Morphine 7.9
Meperidine 8.5
Fentanyl 8.4
Sufentanil 8.0

Alkaloids of opium:

 Phenanthrene alkaloids - Highly ionized and water soluble at physiological pH

o Morphine, codeine, thebaine
 Benzylisoquinoline alkaloids – lack opioid activity
o Papaverine, noscapine
Semisynthetic Opioids

 Codeine (methylmorphine) – made by substituting a methyl group for the hydroxyl group on carbon 3
 Heroin (diacetylmorphine) – made by substituting acetyl groups on carbons 3 and 6 of morphine
Synthetic Opioids

 Morphine derivatives – Oxymorphone, hydromorphone, heroin

 Methadone derivatives
 Benzomorphan derivatives – pentazocine
 Phenylpiperidine derivatives – meperidine, fentanyl (similarities to amide LA’s in molecular weights
and pKs), Alfentanil, Naloxone, Naltrexone, Meperidine, Sufentanil, Remifentanil

167
Benefits of Opioid Anesthesia: Advantages
o minimal direct myocardial depression
o no myocardial sensitization
o no increased ICP
o no hepatorenal toxicity
o predictable post-op awakening
o antagonists available
o post-op analgesia
o facilitates post-op ventilation
o no environmental pollution
o safe in malignant hyperthermia
 Disadvantages
o As a sole agent, unpredictable amnesia and unconsciousness, requires background of volatile
agent, midazolam or N2O
o Does not suppress SNS response
o Addition of N2O causes CV depression
o Orthostatic hypotension
o increased venous vasodilatation (morphine)
o need for fluid replacement
o Vagal effects causing bradycardia (fentanyl, sufentanil)
o Histamine release (morphine)
o N/V from stimulation of CTZ
o Biliary tract constriction
o Muscle rigidity
o muscle relaxants may be needed
o Post-op respiratory depression
Opioid Mechanism of Action

 Act as agonists at stereospecific opioid receptors (classified as mu, delta and kappa) at presynaptic
and postsynaptic sites in the CNS (spinal cord and brainstem) and in peripheral tissues.
o Activate opioid receptors (which belong to the superfamily of guanine protein receptors)
located on primary afferent neurons which are normally activated by enkephalins (short
acting, poor analgesia), endorphins (long acting, potent analgesia) and dynorphins (all are
endogenous peptide opioid receptor ligands)
o Opioids are able to mimic these endogenous ligands by binding to their receptors and
activating pain modulating systems
o CNS - brain
 periaqueductal matter of brain stem
 amygdala, corpus striatum, hypothalamus
o Spinal cord - substantia gelatinosa
 dorsal horn of the spinal cord
 first site in the CNS for integration of sensory information
o Mu 1 - spinal (perception of pain is decreased) and supraspinal analgesia (“I feel the pain but I
don’t care), euphoria, bradycardia (Mu 1 = 1 heart to slow down), hypothermia, urinary
retention, miosis, pruritus
o Mu 2 - spinal analgesia, respiratory depression (Mu 2= 2 lungs for resp depression), physical
dependence, constipation
o Kappa - spinal and supraspinal analgesia, dysphoria, sedation, miosis

168
 o Delta - spinal and supraspinal analgesia, respiratory depression, physical dependence,
constipation (minimal), urinary retention
 Most currently used opioids highly selective for μ-opioid receptors
 Coupled to K+ conductance
 Inhibits neurotransmitter release
 Hyperpolarizes cell membranes
 All opioid receptors coupled to G proteins
 Regulate activity of adenylate cyclase, subsequent ion channel conduction
characteristics
 Major plasma proteins to which opioids bind:
o Albumin
o α1-acid glycoprotein
 Elimination:
o Biotransformation & excretion are principal elimination mechanisms
o Metabolized in liver - Conjugation, oxidative & reductive reactions
 Metabolites generally inactive EXCEPT: Normeperidine, morphine 6-glucuronide
o Hydrolyzed in plasma - Remifentanil
o Excretion via kidneys
Conversions between opioids:
10 mg Morphine = 100 mcg Fentanyl = 100 mg Demerol = 1 mg Dilaudid = 5 mg Methadone = 10 mcg
Sufentanil
Comparative Potency:
Sufentanil (3000) > Remifentanil (250) > Fentanyl (100) > Alfentanil (10) > Morphine (1) > Demerol (1/10)
Elimination (shortest to longest)
Remifentanil < Alfentanil < Morphine < Sufentanil < Meperidine < Fentanyl

Meperidine

 90% metabolized by liver forming demthylated normeperidine

 normeperidine elimination half-life of 15-40 hours
 CNS stimulation
 may cause confusion, hallucinations
 Protein binding: 64-82, pKa - 8.5
 Lipid solubility: Intermediate
 Side effects
o orthostatic hypotension (more profound that with MS)
o increased heart rate (atropine like effect)
o delirium and seizures (normeperidine)
o respiratory depression
o mydriasis instead of miosis
o dry mouth
 Stops shivering (kappa stimulation?)
169
  CV depression
o 20 X greater than morphine due to direct myocardial depression
o increased heart rate
o decreased cardiac output (exaggerated with N2O, valium)
 60% bound to plasma proteins
 Elderly manifest decreased protein binding and increased plasma concentrations
 Meperidine potentiates the CNS and circulatory depression of other opioids, sedative hypnotics,
volatile anesthetics, and TCAs
 Patients on MAOIs should NOT receive Meperidine, or the following may ensue: hyperpyrexia,
hypertension, hypotension, ventilatory depression, skeletal muscle rigidity, seizures, coma

Morphine

 Phenanthrene derivative
 Dose: 0.1-1.0 mg/kg IV used a lot in peds
 High dose: 1-5 mg/kg IV
 Protein binding: 26 - 36%
 Poor penetration of MS into CNS
o poor lipid solubility
o high degree of ionization
 Metabolism: 95% liver and kidneys
 Only small amount excreted unchanged - metabolites excreted renally
 renal failure results in increased plasma concentration; use with extreme caution
 Side effects – Euphoria, Miosis, No amnesia, Orthostatic hypotension (due to decreased SNS tone),
May see decreased systemic vascular resistance, decreased cardiac output, Bradycardia - increased
vagal activity, depressant effect on SA node, slow AV node conduction; Histamine release causes
hypotension, decreased MAP, decreased PVR, decreased Cerebral blood flow
 Respiratory effects:
o Increased CO2 threshold
o shifts CO2 response to the right
o direct depressant effect on brain stem ventilation centers
 reduces release of acetylcholine from neurons in the medullary ventilatory center in
response to hypercarbia
 physostigmine causes increased CNS acetylcholine
 antagonizes respiratory depression but not analgesia
o Peak onset of respiratory depression is slower than with fentanyl because of fentanyl’s greater
lipid solubility. Fentanyl gets into and out of the CNS more quickly.
o Depressant effects can last up to 5 hours
o Decreased respiratory rate and tidal volume
 Interferes with pontine & medullary ventilatory centers that regulate rhythm of
breathing
 may see some compensatory increase in TV
o sighing is minimized
o prolonged pauses between breaths
 delayed exhalation and periodic breathing
o increases chance of atelectasis
o cough reflex depressed
o Increased airway resistance
170
Fentanyl

 Phenylpiperidine derivative
 Rapid onset
 Short duration of action - .5 - 1 hour
 Good lipid solubility - passes blood/brain barrier quickly
 Metabolism
o metabolized by N-demethylation producing norfentanyl - excreted by the kidney
 longer elimination half-time than morphine - due to larger volume of distribution (Vd) because of
greater lipid solubility and passage into tissues
 prolonged effect in the elderly
 Dosing
o Low dose: 1 - 2 μg/kg IV for analgesia
o Adjuvant dose: 2 - 20 μg/kg IV as adjuvant to inhalational anesthesia
 used to blunt circulatory responses to intubation and changes in surgical stimulation
o High dose: 50 - 150 μg/kg IV used alone to produce surgical anesthesia
 Advantages
o lack of direct myocardial depressant effects
o absence of histamine release
o suppression of stress response to surgery
 Disadvantages
o fails to prevent SNS response to surgical stimulation
o possible patient awareness
o post-operative respiratory depression
o Cardiac depression seen with N2O, diazepam
o Hypotension rarely seen
o Hypertension with surgical stimulation
o Bradycardia due to vagal effect
o Decreased Cerebral blood flow and ICP unless increased PaCO2
 Respiratory effects
 Increased CO2 threshold and shift of CO2 to right
 Decreased rate and TV
 Depressed cough reflex
 Respiratory depression is dose related
 Truncal rigidity
o Decreased thoracic compliance with bronchial smooth muscle rigidity
o Decreased ventilation and venous return due to increased mechanical ventilation pressures
o may be central effect

171
Sufentanil

 Faster IV induction than fentanyl

 Very lipid soluble
o rapid penetration in blood/brain barrier
o cautious of cumulative drug effect
o rapid redistribution throughout body
 Bradycardia may cardiac output
 No change in cerebral blood flow
 Dose: .025 - 30 μg/kg
 Analgesic dose: 0.1 - 0.4 μg/kg IV
 Maintenance dose: 1μg/kg followed by 0.25-0.5 μg/kg/hr
 High dose: 10 - 30 μg/kg
Remifentanil

 Unique metabolism
o Hydrolysis by non-specific esterases
o Unaffected by age, gender, weight, hepatic or renal function
o Yet, the elderly are 2X as sensitive
 Metabolite is renally excreted
 Fast offset as it does not accumulate after long administration (5 - 10 minutes)
 Dose: 1 - 2 mcg/kg
 Allows reduction of induction agents
 May cause skeletal muscle rigidity
o dose and rate of administration dependent
o hypnotic agents or muscle relaxants decrease occurrence
o treatment includes:
 Reduction or discontinue infusion
 muscle relaxants
 Uses:
 MAC
 Neurosurgery
o minimal effect on ICP
o modest effects on MAP
 Post-operative considerations
o plan for analgesia must be in place prior to awakening
o local infiltration
o NSAIDs
o long acting narcotics given before emergence

172
Advantages of continuous opioid infusion: Hemodynamic stability

 Decreased side effects

 ↓ need for opioid reversal agents
 ↓ use for vasopressors
 Suppression of cortisol & vasopressin response to CPB
 ↓ total opioid dose
 ↓ total recovery time
Antagonists

 High affinity for the opioid receptors

 Displace the opioid agonist from the Mu receptor
 Antagonist binds to the Mu receptor
 does not activate the receptor
Intraspinal & epidural opioids

 Opioid receptors identified in substantia gelatinosa of spinal cord

 Epidural dose 5 - 10X more potent than intrathecal
 Morphine
o intrathecal (0.5 - 1.0 mg) - analgesia for an average of 20 hours
o epidural (2 - 8 mg) - intense and long acting analgesia
 Benefits of neuraxial opioids
o No sympathetic nervous system denervation
o No skeletal muscle weakness
o No loss of proprioception
o Patients can ambulate
o Decreased risk for orthostatic hypotension
o Pain unresponsive to systemic opioids may respond to same drugs given centrally
 Mechanism of action
o Injection (or diffusion into) CSF
 Delivers drug to spinal cord opiate receptors
o Analgesic activity
 Kappa receptors in substantia gelatinosa
 Lamina II of dorsal horn
o Combined with local anesthetics
 Synergy, ↓ dose requirement
 Side Effects:
o Early and delayed (8-12 hrs) respiratory depression
 cephalad spread in CSF to medullary centers in 4th ventricle
o Pruritus
o Urinary retention
o Nausea and vomiting
o Sedation
 Fentanyl has greater safety
o due to increased lipid solubility
 More rapid onset, shorter duration 2o rapid clearance
o less drug available for cephalad spread
 Poorly lipid soluble drugs have more side effects - Morphine, hydromorphone
173
 Anesthesia Cart Drug Information (Stoelting & Hiller Pharmacology & Physiology in Anesthesia
Practice)
Drug Dosage Onset/ Mechanism of Action/ Route of Indications Contraindications
Name Peak/ Classification Metabolism
Duration &
Elimination
entanyl Induction- 2- Almost Phenylpiperidine derivative synthetic Hepatic metabolism Analgesia for mod. To SEs- Bradycardia secondary to
20mcg/kg IV as immediate opioid- Highly lipophilic mu agonist that by N-demethylation severe pain. Also stimulation of vagal nuclei in
adjuvant to onset 1-5 distributes rapidly to the brain. Agonism production useful in medulla. Shifts CO2 to right,
inhalational minutes. Peak and binding to mu receptor closes norfentanyl. Excreted Subarachnoid. Useful increases CO2 threshold. Depressed
anesthesia. 5-15minutes. presynaptic Ca2 channels which inhibits by kidney. in GA, MAC, spinal. cough, respiratory depression,
1-2mcg/kg IV for Duration 0.5-1 neurotransmitter release, and opens Longer elimination ½ Used to blunt truncal rigidity. N/V, increases
analgesia hour. postsynaptic K channels- hyperpolarizes time than morphine circulatory response to biliary tone, ICP.
100x more potent and inhibits activity of those cells. This secondary to larger intubation and changes Caution in elderly, renal
than Morphine creates analgesia, altered perception and Vd from greater lipid in surgical stimulation impairment, hepatic impairment,
reaction to pain, increases pain threshold, solubility- prolonged ICP increased, pulm, CV
euphoria, drowsiness, sedation. effect in elderly. impairment. Also caution in CNS
depressant use, hypotension, biliary
disease, seizure disorder.
orphine (Post –op analgesia) 15-30 minutes Opioid agonist, poor cns penetration r/t Metabolism- analgesia kidney failure
2- 20 mg q 2-4 and peak in 45- poor lipid solubility, high degree of conjugation with Causes histamine release. may
hours 90 minutes ionization at physiologic ph, protein glucuronic acid in exacerbate asthma, hypotension
doa is 4 hours binding, and rapid conjugation with hepatic and may cause sphincter of Oddi spasm
glucorinic acid. extrahepatic sites,
especially the
kidneys.
elim ½ life- 2-4 hours
longer elimination
half-life of morphine
-3-glucuronide
idazolam (Anxiolysis dose 30-60 sec/3-5 Benzodiazepine with imidazole ring. (Met) Hepatic/SI (P- Premedication / CNS depression, COPD (depression
range) 0.05 mg/kg min/15-80 min Anxiolysis, sedation, anticonvulsant, 450) induction agent/potent of respiration)
IV skeletal muscle relaxation, and (Elim) Renal anticonvulsant
anterograde amnesia. Facilitate/enhance
the affinity of the receptors for GABA
etamine (Induction Dose 30-60 sec IV Phenylcycline derivative Rapid onset Intense analgesia Avoid in HTN, pulm HTN, and
Range) 1-2 mg/kg 2-4 min IM Non-Barbiturate induction agent Short DOA Acute hypovolemia ↑ ICP
IV or 4-8 mg/kg IM return to (Dissociative) High lipid solubility (has CV stimulant
consciousness Non-competitively binds to NMDA Large Vd effects to maintain BP)
10-20 min receptor (excitatory) High hepatic Good for burns,
return to full clearance debridement’s, and
orientation 60- Excreted by the skin grafting
90 min kidneys procedures
Bronchodilating effects
phedrine (As sympatho- Immediate Indirect Synthetic Noncatecholamine Depends on MAO for post-spinal and post- Caution in pts with HTN,
mimetic drug – (IV). More activates alpha and beta adrenergic metabolism, Small induction hypotension ischemic heart disease, depletion of
single dose) than 20 min receptors by the release of NT norepi amounts are slowly Tachyphylaxis occurs endogenous catecholamine stores,
5-10 mg IV (subcutaneous). from postganglionic sympathetic nerve metabolized in the with repeated doses avoid in cocaine using pts
increments 10 to 20 min endings liver.
(IM). 15 to 60 Slow inactivation and
min (oral). excretion of
ephedrine is
responsible for its
prolonged duration of
action.
Renally eliminated
and mostly as
unchanged drug. The
t ½ is approximately
3 to 6 h (dependent
on urinary pH).
ncef 1-2 grams IV- or Onset: Rapid MOA: First-generation semisynthetic metabolism: minimal Perioperative surgical Hypersensitivity to cephalosporin’s,
25mg/kg Peak: IV: 30 cephalosporin that by binding to 1 or hepatic infection prophylaxis penicillin’s.
min more penicillin-binding proteins arrests excretion: renal 80- Active against most
Duration- 6-12 bacterial cell wall synthesis and inhibits 100% gram - and gram +
hours bacterial replication. It inhibits cell wall cocci, with the
synthesis by inhibiting transpeptidase, exception of MRSA.

174
 thus blocking cross-link formation of
peptidoglycan.
Class: cephalosporin antibiotic
tropine (0.1 mg/mI (Adult) Onset: 1 min Binds reversibly with muscarinic Metabolism: 50% Treatment of reflex Be cautions to avoid Central
0.05 mg/mL Peak: 1- cholinergic receptors. Does not hydrolysed to tropine mediated bradycardia, Anticholinergic Syndrome.
(Pediatric) 4minutes discriminate among M1, M2, M3 and tropic acid sedation, Symptoms can range from
Duration: 30 - receptors. Highly competitive antagonist Excretion: About antisialogogue, Combo restlessness and hallucinations to
60 min of all muscarinic receptors. 60% is excreted with anticholinesterase somnolence and unconsciousness
unchanged in the drugs during A lipid soluble tertiary amine, so it
urine, most of the rest pharmacologic crosses the BBB.
appears in urine as antagonism of
hydrolysis and nondepolarizing
conjugation products neuromuscular
blockers. Also include
bronchodilation,
biliary and ureteral
smooth muscle
relaxation, prev of
motion-induced
nausea, and
antagonism of gastric
hydrogen ion secretion.
examethasone 4-8 mg (N&V Onset: 1 hr MOA: Dexamethasone is a potent Metabolism: Hepatic PONV. Corticosteroids may exacerbate
prevention dose) or Peak: 1 hr. synthetic member of the glucocorticoid excretion: Renal Chemotherarpy systemic fungal infections and,
0.1-0.25 mg/kg Duration: class of steroid drugs. It acts as an anti- induced PONV as therefore, should not be used in the
Antiemetic inflammatory and immunosuppressant. well. presence of such infections unless
effects often When taken orally, it is 26.6 times more they are needed to control drug
persist >24 hrs potent than the naturally occurring reactions due to amphotericin B.
hormone cortisol and 6.6 times more Contraindicated in use in poorly
potent than prednisone. MOA as managed diabetics, alterations in
antiemetic not fully understood. Studies hormone synthesis, excessive
suggest it exerts a central antiemetic hyperglycemia may result.
action through activation of Can cause “Crotch Fire” sensation.
glucocorticoid receptors in the bilateral
nucleus tractus solitarii in the medulla.
Hypothetically this would reduce immune
mediated inflammatory neurotransmitters
such as histamine, reducing this pathway
of activation on the CTZ at the area
postrema that would stimulate emesis.
Class:Glucocorticoid
lycopyrrolate (Reversal dose) Onset: 2 to 3 MOA: Competitively antagonize the Metabolism: Combination with Known hypersensitivity to
0.01-0.05 mg/kg minutes effects (parasympathetic) of acetylcholine Unknown anticholinesterase glycopyrrolate or any of its inactive
Peak: 3-4 at cholinergic postganglionic sites Elimination: 80% is drugs to prevent ingredients
minutes designated as muscarinic receptors eliminated unchanged parasympathetic Glycopyrrolate Injection may be
Duration: Class: Anticholinergic in the urine effects of contraindicated in patients with the
30 to 60 anticholinesterase following concurrent conditions:
minutes medications glaucoma; obstructive uropathy,
(bradycardia) obstructive disease of the GI tract,
paralytic ileus, intestinal atony,
unstable cardiovascular status in
acute hemorrhage; severe ulcerative
colitis; toxic megacolon,
myasthenia gravis.
henylephrine (As sympatho- Onset: Stimulates Alpha - 1 adrenergic receptors Metabolism : Hepatic Used to treat HOTN. Angle-closure glaucoma.
Mimetic drug – Immediate by direct effect. Also has an indirect effect / MAO Believed to be useful Pulmonary artery pressure is
single dose) 50 - Peak: 1- by evoking the release of norepinephrine. Elimination: Urinary in pts with coronary increased with Phenylephrine.
200 mcg IV for a 5minutes. artery disease and
single dose. Duration: 15- aortic stenosis because
Continuous dose is 20 min. the drug increases
20-50 mcg/min, or coronary perfusion
0.1- pressure without
0.75mcg/kg/min- or chronotropic side
as high as effects
20mcg/kg/min in In OB, phenylephrine
severe shock states is associated with a
Peds- 5mcg/kg. higher umbilical artery
pH than ephedrine (A
lower incidence of
fetal acidosis). Use this
with OB.
Drug Name Dosage Onset/ Peak/ Mechanism of Action/ Metabolism & Indications Contraindications
Duration Classification Elimination

175
iphenhydramine 25 – 50 mg IV Onset rapid First Generation H1 antagonist. Attach to Metabolism: HepaticAs a sedative, Produces sedation.
PONV- 12.5-25 mg Peak: 2 hrs the Histamine receptor and prevent Big first pass hepatic
antipruritic (stops
IV, or 0.1- Duration: 3-6 responses mediated by histamine. They do excretion. itching), and
0.3mg/kg hours NOT inhibit the release of histamine. As a antiemetic. Stimulates
first-generation they may activate ventilation via
muscarinic cholinergic, 5HT (serotonin) augmenting the
or Alpha-adrenergic receptors. interaction of the
hypoxic and
hypercarbia ventilatory
drives.
etoclopramide 10 - 20 mg IV Onset: Substituted benzamine. Chemical Metabolism: Hepatic Preop decrease of Crosses BBB and placenta. AVOID
(Gastric emptying Peak: 40 - 120 derivative of PABA and structurally (Big first pass gastric fluid volume, WITH PARKINSONS! Avoid with
before anesthesia) min related to procainamide. Complex MOA metabolism). production of an Bowel Obstruction. May inhibit
0.2mg/kg Duration: and involve 5-HT4 receptor agonism, Elimination: 70-85% antiemetic effect, effect of plasma cholinesterase so
vagal and central 5-HT3 antagonism, and renal, 2% fecal. treatment of may explain prolonged suxx and
possible sensitization of muscarinic gastroparesis, mivacurium.
receptors on smooth muscle, in addition symptomatic treatment
Dopamine (D2) antagonist. This acts as a of GERD.
cholinergic stimulation of the GI tract.
Acts as a GI prokinetic drug that increases
lower esophageal sphincter tone and
stimulates motility of lower GI.
aloxone 1- 4 mcg/kg IV Onset: 1-2 Nonselective antagonist of all 3 opioid Metabolism: Liver by Treat opioid-induced You reverse the depression of
(Opioid induced minutes receptors (Mu, Kappa, Delta). conjugation with depression of ventilation but also reverse the
analgesia) Peak: 5-15 min glucuronic acid. ventilation, treat analgesia. Finding a happy medium
Duration: 30- Extensive 1st pass opioid-induced of rev. of ventilation but still having
45 min metabolism. depression of a level of analgesia is the goal.
ventilation in neonate Give over 2 - 3 min. Fast injection
due to maternal admin can cause N/V.
of opioid, treatment of Crosses placenta. So, if in an
deliberate opioid OD, opioid-dependent mom, giving may
and detect suspected cause baby to go into withdrawal.
physical dependence.
umazenil 0.2 mg IV (8 -15 Onset: 2 min Benzodiazephine antagonist with a high Metabolism: Hepatic For patients who have Giving to patients who are on
mcg/kg IV). Further Peak- 6-10 min affinity for benzo receptors. A Elimination- urine, been given excessive antiepileptic drugs may be a bad
doses of0.1 mg IV Duration- 1 competitive antagonist. Prevents and 10% fecal benzodiazepines. idea since it may cause a precipitate
(Up to 1 mg IV) hour- reverses all the agonistic effects of withdrawal seizure.
may be used (Initial important- benzodiazepines.
dose & then generally less
subsequent dose) than that of
0.3 - 0.6 mg IV benzo given-
have been enough to with this
decrease the degree may/will need
of sedation while to give more
0.5 - 1.0 mg IV is than one dose.
sufficient enough to
completely abolish
the effects of
benzodiazepines.
eostigmine (Reversal dose) Onset: 5- 10 MOA: Bind covalently to Metabolism: Reversal of muscle DO NOT attempt reversal with zero
0.04-0.07 mg/kg minutes acetylcholinesterase to form an inactive Hydrolysis for relaxation twitches. Want at least 2-3 twitches,
Peak: complex, which then hydrolyzed to form acetylcholinesterase preferably 4 twitches.
Duration: 30- regenerated acetylcholinesterase and plasma esterase Hypersensitivity to
60minutes Class: Anticholinesterase Excretion: 50% anticholinesterases and bromides;
unchanged in the mechanical intestinal or urinary
urine obstruction; peritonitis
ydralazine (Hypertensive Onset: 10-20 - Phthalazine derivative that activates - Metabolism: - Reduction of DBP > - Causes sodium & water retention
Apresoline) crisis) min guanylate cyclase to produce vascular Acetylation with SBP - SE: vertigo, diaphoresis, nausea,
ial 2.5 - 10 mg IV Peak: 15- relaxation. hepatic metabolism - Reduces SVR tachycardia
oncentration: 0.5mg/kg 30min - Direct relaxant on vascular smooth - Excretion: Urine - SE: Reflex - Chronic use: systemic lupus
0 mg/ml Duration: 3-6 muscle. baroreceptor-mediated erythematosus-like syndrome in 10-
hrs - Dilation on arterioles > veins increase in HR, SV, 20% of patients
CO

pinephrine 10 mcg/kg Onset: 1-2 min A natural catecholamine that effects Metabolism: MOST POTENT Renal BF substantially decreased
(Standard dose) Peak: myocardial contractility, Heart rate, adrenergic synapse Alpha-adrenergic by epi.
Sm. doses (1-2 Duration: 5 - vascular and bronchial smooth muscle (MAO and COMT) receptor activator (10 There is relaxation of the GI
mcg/min IV) 10 min. tone, glandular secretions and metabolic Excretion: Urine times more active than smooth muscle as well as the
stimulate primarily processes such as glycogenolysis and Norepi). detrusor muscle of the bladder.
beta 2 receptors. lipolysis. Stimulates Alpha 1 and 2 Coronary arteries have Blood coagulation is accelerated by
At 4 mcg/min IV - receptors and Beta 1, 2, 3 receptors B2 receptors so Epi.
B1 receptors Stim primarily alpha 1 in skim, mucosa, stimulation with Epi
stimulated. and hepatorenal vasculature producing will cause vasodilation.

176
 At large doses (10 - intense vasoconstriction. In skeletal
20 mcg IV) both muscle vasculature it stim primarily Beta
alpha- and beta - 2 which causes vasodilation as well as
stimulated. dilation of airway smooth muscle.
smolol 10 mg IV initially O;1-2min Short acting selective B1 antagonist Hydrolysis in the -Prevent or treat BP & -
revibloc) then titrate to effect P;5min blood by plasma HR responses that
→ 0.5mg/kg D;10-20 min esterase; elimination occur in response to
independent of renal, noxious stimulation
hepatic function and -Treat intra-op cardiac
plasma cholinesterase ischemia, decrease HR;
-Elimination half Esmolol 1-1.5mg/kg
time 9min followed by infusion
50-300mcg/kg/min
Drug Name Dosage Onset/ Peak/ Mechanism of Action/ Metabolism & Indications Contraindications
Duration Classification Elimination
abetolol 5-10 mg IV initially O;1-2min -Selective Alpha 1 & Non-selective Beta -Metabolism by -HTN emergency
randate) then titrate to effect P;5-15min antagonisim (7B:1A) conjugation of (2mg/kg)
0.1-0.25mg/kg D; 2-4hrs -↓SVR (A1 blockade), reflex ↑HR d/t glucuronic acid, 5% -Rebound HTN post
(prolonged in vasodil. Blunted by the Beta blockade. of drug recovered d/c clonidine, Angina
liver disease) -No change in CO unchanged in urine pectoris, attenuate ↑HR
- and BP r/t abrupt
increases in surgical
stimulation
urosemide 0.1 - 1.0 mg/kg IV Onset: 15- 20 Inhibits reabsorption of sodium and Metabolism: Only give to pts with LASIX is contraindicated in
(Single Drug min chloride in the medullary portions of the Glomerular Filtration normal or increased patients with anuria and in patients
Therapy Dose) Peak: 1 hour. ascending limbs of the loop of henle. Also and renal tubular intravascular volume. with a history of hypersensitivity to
Duration: 4-6 produces renal production of secretion. Use for metabolism of furosemide.
hrs prostaglandins resulting in renal Excretion: ⅓ excreted edema fluid due to Avoid in pts with hypokalemia,
vasodilation and an increase in renal unchanged in bile renal, hepatic or hyponatremia, hypomagnesemia.
blood flow. cardiac dysfunction,
treatment of increased
ICP, inhibition of
cellular uptake of
Calcium for treatment
of hypercalcemia, and
differential diagnosis
of acute oliguria.
docaine KNOW MAX Fast inhibit passage of sodium ions through hepatic (various acute pain sensitivity to amides or
DOSE topical, Topical:30 - 60 ion-selective sodium channels in nerve pathways) management preservatives - methylparaben
infiltration, IVRA, mins membranes
PNB, Epidural - 300 Infiltration:60 -
mg or 500 with 240
epinephrine IVRA :30 - 60
Spinal - 100 mg PNB:60 - 180
Epidural:60 -
120
Spinal:30 - 60
lbuterol IH Metered dose Onset: 5-8 Selective Beta - 2 adrenergic agonist used Metabolism: Hepatic Treatment of acute Hypersensitivity to albuterol
inhaler with 100 minutes to treat acute bronchospasm due to Elimination: Renal bronchospasm.
mcg per puff (1-2 Peak: 30 - 60 asthma.
puffs via deep min
inhalations 1-5 min Duration: 4 hrs.
apart)
opofol 1.5 - 2.5 mg / Onset: 30 Sedative-hypnotic which works via Metabolism: Hepatic To induce loss of The respiratory effects of propofol
kg(Induction Dose seconds selective modulator of GABA (A) (resulting in water- consciousness. Maint are potentiated by other respiratory
Range) Peak: receptors (the principle neuroinhibitory soluble sulfates and of GA in mechanically depressants, including
100 - 300 Duration: T ½ - transmitter in the CNS). GABA (A) glucuronic acid ventilated patients. benzodiazepines.
mcg/kg/min IV for 30 to 60 min activation results in transmembrane Cl metabolites that are There has been no shown impaired
maint of anesthesia. channels increasing in conductance which excreted by the elim. Of propofol in pts with
results in hyperpolarization of the cell kidneys). cirrhosis of the liver.
membrane and functional inhibition of Elimination: Renal Elderly pts require a lower dose
postsynaptic neurons. SO the CL channel (25-50% decrease).
stays open longer which hyperpolarizes AVOID in pts allergic to soybeans
the cell membranes. (soybean oil is biggest component)
and egg yolk (egg lecithin)
hiopental (Induction Dose Onset: Sedative/hypnotic via interaction with Rapidly redistributed Induction of Higher concern. Available in those
Range) Peak: GABA (A) which increases chloride to inactive tissue sites anesthesia, treating with cirrhosis of the liver and
4 mg / kg Duration: membrane conductance and (Most rapid increased ICP uremia.
hyperpolarizing the cell. Thiopental slows redistribution is into —Barbiturates Use with caution in hypovolemia
the rate of GABA dissociation. Also skeletal muscles.) decrease ICP by patients due to increased HR with
stimulates glutamate receptors as well as Lipid solubility most decreasing cerebral decreased bp.
neuronal nicotinic acetylcholine receptors. important factor in blood volume 2ndary
distribution of to cerebral
thiopental vasoconstriction &
177
 Breakdown to small decreased cerebral
extent in kidney’s and blood flow; Thiopental
CNS classic induction drug
of choice for increased
ICP situations in
hemodynamically
stable patients
Ketamine (Induction Dose Onset: 30- Binds non-competitively with the Metabolism: —Ketamine Severe hallucinations as well as
Range) 60 seconds NMDA receptor (NMDA Antagonist). Hepatic produces a increase in HR and MAP.
1-2 mg / kg IV Duration: 60 Has weak GABA interactions. "different" kind of Emergence delirium common.
- 90 min. Rapid onset/relatively short duration of anesthesia than most Avoid in pts with systemic or
action. other anesthetics. It pulmonary HTN or increased
Has active metabolite which may is known as ICP (Potent cerebral
prolong duration of action. "dissociative vasodilator).
May be useful in asthma patients due to anesthesia" in which Nystagmus is associated with
bronchodilation. there is a marked admin of Ketamine.
sensory loss,
analgesia, amnesia
and paralysis of
movement without
actual loss of
consciousness. Its
cardiovascular and
respiratory effects
are also different
from most other
anesthetics; blood
pressure and heart
rate are usually
increased and
respiration is
unaffected (by
effective anesthetic
doses).
omidate (Induction Dose Onset: 30 - 60 Selective modulator of GABA (A) Metabolism: Hepatic Sedation/induction of Etomidate suppresses corticosteroid
Range) seconds receptors. (Look at propofol for further and plasma esterases general anesthesia. Is synthesis in the adrenal cortex by
0.2 - 0.4 mg/kg IV. Peak:1 min description of this). which cause the most cardiac stable reversibly inhibiting 11-beta-
Duration: 3-5 hydrolysis to a water- of all induction hydroxylase, an enzyme important
min (rapid soluble, sedative/hypnotics? in adrenal steroid production; it
redistribution. pharmacologically leads to primary adrenal
inactive compound suppression.
(carboxylic acid
ester). .
ecuronium (Induction Dose Onset: 3-5 min Nondepolarizing NMB. Metabolism: Hepatic For paralysis of Prolonged elim half time in pts with
Range & Duration: 20 - and biliary patient. renal failure.
Maintenance) 35 min. metabolism Liver Dz does not seem to have
Induction: Excretion: Mostly much of an effect on the use of vec.
biliary excretion
unchanged.
Drug Name Dosage Onset/ Peak/ Mechanism of Action/ Metabolism & Indications Contraindications
Duration Classification Elimination
satracurium Induction Dose onset: 2-4 non-depolarizing muscle relaxant metabolism: Hoffman advantages: - 5x more potent than rocuronium,
Range : 0.1 mg/kg minutes (absence of muscle fasciculation, reversal elimination (pH and maintenance of with a slower onset of action,
Maintenance dose: duration: 40-75 with anticholinesterase drugs) temperature cardiovascular stability longer duration, and slower
0.02 mg/kg minutes dependent) and non- and a lack of histamine spontaneous recovery.
specific ester release
hydrolysis useful in patients with
Elimination: urine renal failure
ocuronium Induction Dose: 0.6- onset: 1-2 non-depolarizing muscle relaxant Metabolism: largely Paralysis of patient. Those known to have
1.2 mg/kg minutes excreted unchanged hypersensitivity to Rocuronium.
Maintenance: 0.1 duration: 55-80 in the bile.
mg/kg minutes elimination: hepatic
RSI Dose: 0.6-1.2 and renal
mg/kg
uccinylcholine (Induction Dose Onset: <1 min Depolarizing NMB. —Acts directly on Metabolism: Plasma Paralysis of patient for Anticholinesterase agents inhibit
Range) & Duration 3-5 nicotinic receptors found in skeletal Cholinesterases. induction of pseudocholinesterase and thus
Maintenance& RSI min muscle motor end plate and mimics the anesthesia. prolong a succinylcholine block.
Dose) action of ACh, thus depolarizing the (Remember: anticholinesterase
1.5 - 2 mg / kg (2 postjunctional membrane. This results in agents prolong a succinylcholine
mg/kg for RSI) sustained opening of the receptor ion block but REVERSE a
channels so that they cannot respond to Nondepolarizing block)
subsequent release of ACh. —Raises ICP and IOP
— —

178
 Stimulates muscarinic receptors at the SA Contraindicated in MH, patients
node, and this is the mechanism of taking echothiopate eye drops,
bradycardia. Treatment is atropine. neuromuscular degenerative
— diseases, CVA, spinal cord injury
Phase 1 blockade. (Multiple sclerosis patients too),
burns,
hyperkalemia; degree of K+ release
is unpredictable in a pt with burn
injury
—K+ is elevated 0.5-1.0meq/L
after succinylcholine
etorolac 30 mg IV Q6 hrs for Onset: 10 min NSAID with potent analgesic effects but Metabolism: Post-operative Inhibits platelet thromboxane
age <65 Peak: 45 - 60 only moderate anti-inflammatory Glucuronic Acid analgesia. production and platelet aggregation.
15 mg IV Q6 hrs for min properties. Ketorolac blocks prostaglandin Conjugation By reversible inhibition of
age >65 Duration: 6 hrs synthesis by non-selectively inhibiting (Hepatic) prostaglandin synthetase.
or longer COX. Excretion: Renal May increase bleeding time.
May exacerbate bronchospasm in
asthma patients.
May also cause GI irritation (Peptic
Ulcers, GI Bleed).
AVOID in patient with renal
compromise.
ndansetron 4-8 mg IV Onset: 30 - 60 5-HT3 - Receptor antagonist. This blocks Metabolism: Liver Prevention of PONV Recent studies have shown QTc
min the vagus afferents associated with 5-HT3 Excretion: Renal prolongation. Think about in pts
Peak: 3-4 hrs. receptors in the GI. with cardiac issues.
Duration: up to
24 hrs
xytocin 10 – 30 units in liter Onset: It is a synthetic hormone named for the Metabolism: Liver Postpartum A second fetus.
itocin) of IV fluid Immediate natural posterior pituitary hormone. It Excretion: Renal. hemorrhage following
Duration: 20 stimulates uterine smooth muscle delivery of fetus and /
min after contractions indirectly and helps expedite or placenta.
infusion the normal contractions of spontaneous
stopped. labor. As in all significant uterine
contractions, there is a transient reduction
in uterine blood flow. Oxytocin also
stimulates the mammary glands to
increase lactation without increasing the
production of milk. The drug is
administered in the prehospital setting to
control postpartum bleeding.
upivacaine KNOW MAX BNP - Slow inhibit passage of sodium ions through Hepatic (various acute pain hypersensitivity to amides or
DOSE Epidural - Mod ion-selective sodium channels in nerve pathways) management preservatives - methylparaben
PNB or epidural - Spinal - Fast membranes
175 mg or 225 mg PNB - 240-960
with epi mins.
spinal 20 mg Epidural - 120
- 300
Spinal - 60 -
360
hloroprocaine KNOW MAX fast inhibit passage of sodium ions through cholinesterase acute pain hypersensitivity to esters or
DOSE PNB or 30 - 60 mins. ion-selective sodium channels in nerve management preservatives - paraaminobenzoic
epidural - 800 or membranes acid or methylparaben
1,000 mg with epi
spinal (off label) -
40 - 60 mg

Alkylating and Related Agents

*MOA: A nucleophile donates both bonding electrons to an electrophile forming a chemical
bond.

TOXICITY: GI mucosal, CNS and bone marrow suppression

179
DRUG SUB- DRUG USED TO TREAT COMMENT
CLASS
Nitrogen Mustards BROAD spectrum Bifunctional. Co-administer with Mesna to
conjugate acrolein in urine decreasing
nephrotoxicity.
Cyclophosphamide Malignant tissues Most widely used alkylating agent
Mechlorethamine Hodgkins Most reactive alkylating agent
Nitrosoureas Gliomas Produce inter and intrastrand DNA cross
linking. Highly lipophilic
Carmustine
Lomustine
Alkyl Sulfonates Busulfan CML Generally replaced by Imatininib mesylate
Triazenes Dacarbaine Methylating agent
Methylhydrazines Procarbazine Mehylates DNA, inhibits DNA, RNA and
protein synthesis and is monofunctional
Platinum Colorectal cancer Reacts with nucleophilic sites on DNA and
Complexes proteins and inhibits DNA replication and
transcription. Intra and interstrand crosslink
Cis-Platinum Produces breaks and miscoding causing
apoptosis
Carboplatin Not as toxic as Cis-platinum
Oxaliplatin Used in FOLFOX mechanism with 5-FU and
Leucovorin. Adverse effects: Peripheral
neuropathy.

180
 Anti-Metabolites
*Purine analogs/related inhibitors that inhibit purine synthesis and has potential lethal effects in
patients with mutation that blocks metabolism of 6-MP- Reduce dose if on Allopurinol

DRUG SUB- DRUG USES COMMENT

CLASS
6- Thiopurines 6-Mercaptopurine Maintenance of remission
ALL
6- Thioguanine Acute Granulocytic Combined with AraC and Daunorubicin
leukemia
Fludarabine Adenosine analog. Inhibits DNA/RNA
synthesis and induces apoptosis
Folic Acid Analogs Methotrexate Osteogenic sarcoma and
choriocarcinomas, RA
Folate Antagonist Leucovorin Prevent toxicity or Absorbed by normal cells
Rescue Agent reversal of Methotrexate.
Pyrimidine Analog 5-Flurouracil (5- #1 Colon cancer, Neg. Prodrug that impairs RNA processing and
FU) Estrogen receptor breast translation
CA
Cytarabine Non-functional, incorporated into
DNA/RNA
Gemcitabine Non-functional, incorporated into
DNA/RNA

181
 Plant Alkaloids

DRUG SUB-CLASS DRUG USES COMMENTS

Vinca alkaloids M-phase specific, blocks mitosis
Vinblastine Curative tx for met.
Testicular CA in combo
with Bleomycin &
Cisplatin
Vincristine Childhood ALL ADVERSE SE: Peripheral neuropathy
Taxanes Paclitaxel
Abraxane Pre-med with Decadron, Benadryl and H2
blocker. Albumin bound and carried to
leaky vessels- can use higher doses
Camptothecins Topotecan Previously tx’d met. S-phase specific, binds to and stabilizes
Ovarian and SCLC TOP I DNA complex
Epipodophyllotoxins Etoposide Complexes with TOP II preventing
resealing of breaks blocking DNA
replication

Antitumor Antibiotics (-mycin)

DRUG SUB CLASS DRUG USES COMMENTS

Actinomycin D Wilms tumor and Binds to DNA by intercalcating between
rhabdomyosarcoma GC base pairs
Anthacyclines Adriamycin Intercalcates with DNA and binds to the
backbone of DNA. Cardiotoxic due to
free radicals

182
 Hormonal Agents
*More specific interactions

SUB CLASS DRUG USES COMMENTS

Adrenocorticosteroids Prednisone Regulates transcription of proteins
involved in metabolism and
inflammatory response
Long Acting Leuprolide acetate Most common tx for
Gonadotropin meta gonadal steroid-
Releasing Hormone dependent prostate CA
Anti-estrogens Fulvestrant Meta breast CA in Selective estrogen receptor
post-menopausal downregulator. Increases receptor
women turnover
Selective Estrogen Tamoxifen Breast CA Anti-estrogen
Receptor Modulators
Raloxifene Prevention of post- Second generation SERM
menopausal
osteoporosis. Reduction
of breast CA in at risk
women
Aromatase inhibitors Exemestane Breast CA not
responsive to
Tamoxifen
Anastrozole Breast CA not Interrupts synthesis of estrogen
responsive to
Tamoxifen
Antiandrogens Flutamine Prostate CA Used with GnRH agonist

183
 Antifungal Agents
*”Polly Cyto Eats Allys’ moldy Azole”
Polyene Antibiotics
Amphotericin B: Used for life-threatening systemic fungal infections. Different routes of
administration depending on formulation used. MOA: Binds to ergosterol in fungal cell membrane
disrupting membrane integrity. SE: nephrotoxicity-use with caution in cardiac patients, pre-load with
NS. Pre-medicate with APAP, Benadryl, hydrocortisone and Meperidine to prevent infusion reaction
(caused by cytokine release)
Nystatin: Used topically for mucocutaneous infections
Cytosine Analog
Flucytosine: Used in combination with Amphotericin B for crytococcal meningitis (penetrates BBB)
or systemic candidiasis. MOA: 5-fluorouracil inhibits DNA and RNA synthesis. VD=total body
H2O. AE: Bone marrow toxicity/suppression.
Azoles- Decreases ergosterol synthesis by inhibition of fungal cytochrome P450 enzymes. SE: strong
inhibitor of CYP34A so will have increased serum concentrations of many other drugs. Used for
mucocutaneous infections.
Ketoconazole: No longer used commonly d/t SE, if used will be topical.
Itraconazole: broader spectrum use compared to Fluconazole. Contraindicated in patients with a
history of CHF/ventricular dysfunction. Topical or IV.
Clotrimazole aka Lotrimin: topical
Miconazole aka Monostat: topical
Posiconazole: Broad spectrum. Activity is twice that of itraconazole. SE: QT prolongation, Strong
CYP inhibitor
Voriconazole: Broad spectrum. Superior to Amphotericin for aspergillosis. SE: May cause visual
disturbances. Inhibits CYP enzymes.

184
Echinocandins- few drug interactions
Caspofungin: protype drug. MOA: inhibits synthesis of B-D glucan making cell wall more
permeable.
*Used to specifically to treat mucocutaneous infections (skin, nail, hair) others included above.
Griseofulvin: MOA: disrupts mitotic spindle blocking proliferation of cells. Take with a fatty meal.
SE: r/t induction of CYP450 isoforms. Also is keratophilic so it binds to keratin protecting skin and
nails from further infection
Terbinafine aka Lamisil: Allylamine drug and most EFFECTIVE antifungal (d/t high affinity for
fungal enzyme.) MOA: inhibits squaline epoxidase which interferes with ergosterol synthesis and
impairing cell membrane synthesis. Liver tests prior to TX.
Allylamines- effective against dermatophytes.
Naftifine: topical. MOA: inhibits squalene epoxide leading to high levels in cells= fungicidal.

185
 Antibiotics

Bacteria Cell Wall Synthesis Inhibitors: B-lactam Antibiotics- contains a thiazolidine ring and b-lactam
ring. MOA: inhibits synthesis of peptidoglycan by inhibiting transpeptidase. Effective for GPC and some
gram Neg and anaerobes.
Penicillin G: *only natural Abx. Is given IV. Narrow spectrum
Penicillin V: narrow spectrum
Oxacillin: narrow spectrum. Isoxazolyl PCN- anti-staph.
Dicloxacillin: Isoxazolyl PCN. Narrow spectrum
Ampicillin: broad spectrum. PO. Stronger than Amoxicillin.
Amoxicillin: broad spectrum. PO.
Ticarcillin: broad spectrum
B-lactam Antibiotics: “Cef”
Cephalosporins- more resistant to B-lactamases than PCNs. Broad spectrum. MOA: Inhibit cells
wall synthesis by inhibiting transpeptidase thus blocking cross-link formation of peptidoglycan. AE:
Disulfiram= toxic reaction when ETOH is ingested (face/neck is red and warm) Drug interactions:
Probenecid and Cephalosporins.

186
First Generation
Cefazolin
Cephalexin
Second Generation- “2 generations C Furry Fox”
Cefoxitin
Cefuroxime
Third Generation
Cefoperazone
Cefotaxime
Ceftriaxone
Cefixime
Fourth Generation- “4 Pimpirs”
Cefepime
Cefpirome
Carbapenems- Beta lactam Abx- MOA: inhibit cell wall synthesis by inhibiting transpeptidase, thus blocking
formation of peptidoglycan.
Imipenem/Cilastatin: broad spectrum. NOT effective in MRSA. Reserved for serious massive
infections. Cilastatin prevents degradation of Impipenem. 50% patients allergic to PCN will be
allergic to this drug. Resistance in some strains of Pseudomonas aeruginosa. Crosses BBB
Mezlocillin: broad spectrum
B-lactamase inhibitors- MOA: binds irreversibly to and inhibits bacterial B-lactamases. Has B-lactam ring
but lacks antimicrobial action- NOT ABX.
Clavulanate: Given PO with PCN to decrease resistance by preventing breakdown of Amoxicillin.
(Amoxicillin+Cluvulanate=Augmentin)
Sulbactam: Given IV due to poor oral absorption
Tazobactam

187
Monobactams
Aztreonam: SE: fever, rash, phlebitis
Other Cell Wall Synthesis Inhibitors
Vancomycin: Binds to D-alanine preventing transpeptidase from binding to it. ONLY used in serious
infections by gram pos. bacteria (i.e. MRSA). Usually given IV. SE: Nephro and ototoxicity. Red
man syndrome.
Bacitracin: No beta-lactam ring. Used topically due to severe nephrotoxicity.
Bacterial Protein Synthesis Inhibitors- binds to 23S RNA of 50S ribosomal subunit of bacteria
*”Tammy and Kristen Started Out Learning Math and PSI”
Streptogramins
Quinupristin/dalfopristin: DRUG OF LAST RESORT. Active against resistant microbes
(VRE, MRSA.) Inhibits peptidyl transferase blocking elongation of peptide chain. Poor oral
absorption. Dalfopristin acts at early phase of protein synthesis and Quinupristin acts at late
phase. Affects warfarin, diazepam…
Oxazolidinones
Linezolid: DRUG OF LAST RESORT. Active against resistant microbes. Inhibits formation
of ribosome complex and initiation of protein synthesis. Good oral absorption. NOT useful in
gram negative species. Affects SSRI’s.
Macrolides- binds to 50A ribosomal subunit. Bacteriostatic, but bactericidal at high doses.
Alternative to PCN’s. Also used to treat atypical mycobacterium avium.
Erythromycin: covers gram positive and negative as well as mycobacterium. Cholestatic
Hepatitis is possible, Increases levels of other drugs.
Clarithromycin
Azithromycin
Ketolides- semi-synthetic macrolides
Telithromycin: used in macrolide-resistance in respiratory infections. May prolong QTc or
cause Hepatitis

188
 Lincosamides
Clindamycin: inhibits aminoacyl translocation and formation of initiation complex. Extensive
distribution except to brain. Good for gram positive bacterial in PCN allergic patients.
Aminoglycosides- binds 16S RNA of the 30S ribosomal subunit and inhibits protein synthesis. Need to
check drug level peak and trough due to renal toxicity.
Streptomycin: gram negative and positive NOT active against anaerobes. GOOD against
pseudomonas. Can cause ototoxicity, nephrotoxicity, and NMB.
Amikacin
Gentamicin
Kanamycin- can be used topical or orally for bowel prep
Tobramycin
Tetracyclines
Tetracycline: blocks docking of tRNA on the ribosome. BROAD SPECTRUM against most
microbes.
Doxycycline: use unless otherwise indicated for chlamydial infections with gonorrhea,
mycoplasma pneumonia, malaria, acne
Minocycline
Glycycycline
Tigecycline: Tetracycline derivative. BROAD SPECTRUM. Incorporates into teeth and
bone- do not use in kids under 8yrs.
Chloramphenicol: binds to 50S ribosomal subunit A site and prevents docking of aminoacyl tRNA.
Rarely used d/t toxicity (Rocky Mountain spotted fever, topical for ocular issues)

189
Folate Metabolism Inhibitors-prevents cells from dividing
Sulfonamides- competitively inhibits folic acid production by inhibiting the activity of
dehydropteroate synthase. BROAD SPECTRUM.
Sulfamethoxazole: AE: Steven’s Johnson syndrome. DO NOT use in pregnancy. Given with
Trimethoprim because two drugs potentiate each other. Trimethoprim: NOT Abx, inhibits
dihydrofolate reductase. NO in liver pts.
Sulfasalazine: also a DMARD and used in IBD
Sulfadiazine

DNA Replication, Transcription and Metabolism Inhibitors

Fluoroquinolones
Ciprofloxacin: inhibits alpha subunit of DNA gyrase and top 4 by separating strands. Used for
Gram negative and positive (UTI’s) as well as pseudomonas. Causes cartilage damage in kids.
DO not give to pregnant women or those with quinolone allergy.
Levofloxacin

Urinary Tract Antiseptic

*Polly Must’ve Mixed Meth and Nitro and got a UTI
Metronidazole: anti-protozoal with potent activity against anaerobes. MOA: Inhibits DNA synthesis.
Disulfiram Rx.
Nitrofurantoin:
Methenamine: primary antiseptic drug. Converted to formaldehyde in water and low urinary pH.
Bacteria are sensitive, PROTEUS are resistant
Mupirocin:
Polymyxins:

190
 Antiviral Drugs
Treatment of Herpes, Varicella-Zoster and Megalovirus Infections
Acyclovir: used to treat DNA infections by competing with DNA prolimerase inhibiting DNA
replication. Usually used in immunocompromised patients.
Ganciclovir: Stops DNA virus. Intracellular concentration is 10X higher that Acyclovir and
eliminated slower. Can cause bone marrow suppression. DO NOT use during pregnancy. Used to
prevent CMV in transplant pts and to TX cytomegalic retinitis
Foscarnet: reversibly inhibits DNA and RNA and blocks transcription. Used in
HIV/immunocompromised pts resistant to Ganciclovir and Acyclovir
Trifluridine: inhibits DNA synthesis and may cause cornea inflammation
Idoxuridine
Treatment of Viral Respiratory Infections
Neuraminidase Inhibitors- causes decrease in release of virus from infected cells
Oseltamivir aka Tamiflu: works against Influenza A and B if taken within 36 hours of onset.
Zanamivir: give within 48 hours
Treatment of Viral Hepatic Infections
*”Hepatitis interferes with ribs”
Interferon alpha: anti-Hepatitis B and C. Not well tolerated, causes flu-like symptoms
Ribavirin: anti-Hepatitis C. Intracellularly phosphorylated to interfere with viral RNA and DNA
protein synthesis and viral replication. Can cause anemia and DO NOT use if pregnant.

191
Treatment of HIV infection
NRTIs (Nucleoside Reverse Transcriptase Inhibitors)
Zidovudine aka AZT: AZT-triphosphate is a competitive inhibitor of HIV reverse
transcriptase and terminates DNA synthesis. Protects fetus from being infected with HIV. Can
cause bone marrow suppression with macrocytosis. “I am a PAL I Care” drugs that increase
toxicity.
Didanosine: Used with AZT resistance. Take on an empty stomach
Stavudine: SE: Peripheral neuropathy
Lamivudine
Abacavir
Zalcitabine: used in combination with AZT or alone for AZT intolerance
Nucleotide Reverse Transcriptase Inhibitors (NtRTI)
Tenofovir: anti-retroviral used for Hepatitis B treatment. Same MOA as NRTIs. First drug to
prevent HIV spread (vaginal gel.) Can cause Fanconi syndrome in kidney. Drug reactions
possible with other antivirals.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Efavirenz: alters conformation of reverse transcriptase. LOTS of drug interactions. Do not
give to Hep B pts. Drug of choice due to once daily dosing.
Nevirapine:
Delavirdine
Protease inhibitors- interfere with proteolysis of the gag-pol precursor and lead to nonfunctional
virions.

192
 *”Nel IS A LiAR”
Atazanavir: SE: hyperbilirubinemia due to inhibition of glucuronyl transferase.
Lopinavir/Ritonavir: Ritonavir inhibits metabolism therefore boosting plasma levels of
Lopinavir.
Indinavir
Nelfinavir
Amprenavir
Saquinavir: Also used with Ritonavir for added effect. First PI approved. Inhibits the ability
to form mature viral proteins
HIV fusion/entry inhibitors
Enfuvirtide: blocks FUSION of HIV to CD4 lymphocyte membrane receptors blocking HIV
glycoprotein that is responsible for the fusion. SC injections. Not first line TX.
Maraviroc: Bind to CD4 lymphocyte surface receptor then blocks ENTRY of virus into cell.
Use Trophile test before treatment.
Antimycobacterial
*Primary reason for use of drug combinations is to delay emergency of resistance to individual drugs
Drugs to treat Tuberculosis- PRISE
Pyrazinamide: target and MOA unknown. SE: GI upset, hyperuricemia in most pts. Not indication to
stop TX.
Rifampin: binds to beta subunit of DNA-dependent RNA polymerase. Inhibits RNA synthesis. RED-
ORANGE excretions
Isoniazid: Prodrug- blocks mycolic acid synthesis. Has widespread distribution including brain. Can
induce hepatitis with necrosis as well as neuropathy.
Streptomycin: poor penetration into cells. Effective against extracellular organisms. Oto and
nephrotoxic- SE’s may become permanent
Ethambutol: inhibits mycobacterial ARABINOSYL transferase enzymes which inhibit arabinoglycan
production. DO NOT USE ALONE DUE TO RAPID RESISTANCE. CSF only if meningeal
inflammation.

193
 Second line treatment of TB
P-Aminosalicylic acid: older drug. Only used if organisms are resistant to first line drugs.
Drugs to treat atypical mycobacteria infections: more info under macrolides:
Erythromycin
Azithromycin
Ciprofloxacin
Dermatologic Agents
*GRIT is OK for acne
Topical Antibiotics for Infection
Bacitracin: inhibits cell wall synthesis. Used topically due to severe nephrotoxicity. GPC
Mupirocin: inhibits bacterial protein synthesis needed for RNA synthesis.
Neomycin: inhibits bacterial protein synthesis
Polymyxins: binds to phospholipids in bacterial cell membrane and alters permeability
For Acne
Erythromycin: topical. Used for GPC, GNC and mycobacterium.
Clindamycin: topical. Inhibits aminoacyl translocation and formation of initiation complex.
Good for PCN allergic patients
Amoxicillin: PO- broad spectrum
Tetracycline: PO- blocks docking of tRNA on ribosome.
Topical Glucocorticoids- penetrate cell membrane and binds to heat shock protein complex
Amcinonide:
Betamethasone
Hydrocortisone: decreases inflammation, causes vasoconstriction and decreases VitD in intestine,
increases bone reabsorption.

194
Immunosuppressant- calcineurin inhibitors used for eczema. MOA: inhibits production of IL, interferons and
inhibit release of pre-formed mediators from skin mast cells and basophils
Tacrolimus
Pimecrolimus
Keratolytics- surface acne
Benzoyl peroxide:
Salicylic acid:
Retinoids- effects on gene expression by activating 2 families of receptors. MOA: increases turnover of
follicular epithelial cells
Adapalene: derivative of naphthoic acid
Tazarotene: psoriasis.
Tretinoin: photo damaged skin, surface acne
Isotretinoin aka Accutane: severe cystic acne, teratogenicity is a major problem (iPLEDGE program.)
MOA: Inhibits sebum production and has some direct anti-inflammatory effect.
Drugs affecting the Peripheral Nervous System
Neurotransmitters
Acetylcholine: Used in ANS (decrease HR, CO, HR) and motor division of somatic nervous system
Dopamine: precursor to NE and then EPI
Epinepherine: hormone and NT. Increases HR, vasoconstrictor and bronchodilator. It is a
catecholamine, sympathomimetic produced only by adrenal glands from amino acids phenylalanine
and tyrosine
Norepinephrine: NT in CNS and SNS where it is release from noradrenergic neurons. Bind to
adrenergic receptors and decrease HR and increase BP

Sympathetic Modulators
Ephedrine: sympathomimetic. Release of NT from axonal terminal. Increases NE
Reserpine: reduces NT release by producing long term depletion of NE. Causes many SE d/t crossing
into BBB
Guanethidine: reduces NT release. Like reserpine but does not cross BBB and is less offensive
Tyramine: increases NE

195
 ADRENERGIC RECEPTORS

Agonist Antagonist
Alpha Non-Selective Oxymetazoline Phenoxybenzamine- non-competitive
Phentolamine- competitive
Alpha 1: constriction of Phenylephrine Doxazosin
sm. m Prazosin
Alpha 2: inhibits NT Clonidine
release. HTN
Beta Non-Selective Isoproterenol Propranolol
Pindolol
Labetalol- very potent, used in HTN crisis
Beta 1: cardio-selective Acebutolol-good for exercise test, little effect
affects renin release from on lipoproteins
kidney Atenolol
Metoprolol
Beta 2: pulmonary Albuterol
selective Metaproterenol
Vasodilation and Salmeterol
Bronchodilation. Terbutaline
Facilitates NT release
Beta 3: adipocytes
Alpha Agonists:
Alpha 1 selective: overall smooth muscle contraction increasing BP, sweat gland secretion, inhibits insulin
release and decreasing sympathetic outflow (pupil dilator.) Direct acting and may be used in shock.
Alpha 2 selective: centrally acting, used for HTN. Rebound HTN is common if drug is stopped suddenly.
Used in drug withdrawal and smoking cessation. Decreases serum cholesterol.

Alpha Antagonists:
Nonselective: decreases MAP, increases HR, CO, and improves urine flow. Can cause postural hypotension
and reflex tachycardia. Treats HTN and urinary obstruction. Can be competitive or noncompetitive.
Alpha 1 selective: blocks sympathetic tone without reflex tachycardia. Causes episodes of syncope with
initial treatment. Treats HTN
Beta Receptor Agonists:
Nonselective: increases CO and causes vasodilation and Bronchodilation. Increases insulin secretion.
Beta 2 Selective Agonists: used in asthma for Bronchodilation
Beta Receptor Antagonist:

196
Nonselective: anti-HTN and anti-arrhythmic. Reduces CO, inotropy, and renin secretion. Can lead to DM,
interacts with NSAIDs (decreases hypotensive effects) increases triglycerides, and decreases HDL. Controls
HR, exacerbates asthma, heart block, etc.
Beta 1 selective: does not cause bronchoconstriction. Used as anti-arrhythmic and anti-HTN.
Muscarinic Agonists:
Bethanechol:
Pilocarpine: used as mitotic agent in treatment of glaucoma. Sweat and salivary glands very sensitive
to this drug.
Muscarinic Antagonists: -trop= atropine derivative. Inhibits actions of Ach (low Ach) on autonomic
effectors innervated by postganglionic cholinergic nerves and on smooth muscle cells that lack
parasympathetic innervations. Uses: SB, anesthesia, AchE OD, asthma.
Atropine: low doses: cardiac slowing, increasing HR, inhibits sweating. High doses: decreased tone
and GI motility. Toxic doses: rapid and weak pulse, dilation of iris, ataxia, restlessness, coma.
Scopolamine: treats N/V, motion sickness
Ipratropium: used in bronchial asthma
Tiotropium

Ganglionic Blockers
Mecamylamine: blocks nicotinic receptor of postganglionic neuron
Neuromuscular Junction Blockers
Competitors- DOA: short too long, related to route of elimination (liver or kidney.) Onset 1-5
minutes. Histamine release or ganglionic block. Asthma is a contraindication- can cause
respiratory distress post-op. TX: Ach inhibitor
Isoquinolone derivatives
Tubocurarine: long acting, rapid motor weakness
Atracurium:
Mivacurium: lasts 10-15 minutes.
Steroid derivatives
Vecuronium: cardiac issues more likely but less histamine release. Countered by
Neostigmine.
197
Depolarizing- MOA: intense NMJ stimulation followed by depolarization blockade, prolonged channel
opening. Muscle refractory to all stimulation. Contraindicated in rhabdomyolysis and with atypical serum
ChE.
Succinylcholine: metabolized by AchE. Good for short procedures. Can result in HTN and
bradycardia. A/W MH.
Ach release inhibitor- Blocks release of Ach. Used for: focal dystonia’s and muscle spasticity.
Botulinum toxin
Acetylcholinesterase inhibitors
Donepezil: used for Alzheimer’s
Edrophonium: competitive and reversible
Organophosphates
Alternative substrates- -stigmine= cholinesterase inhibitor
Neostigmine: increases synaptic Ach levels by preventing Ach breakdown. Reversal of
NMB’s.

Physostigmine
Acetylcholinesterase reactivator
2-pralidoxime (2-PAM): reverses AchE inhibitors (decreases Ach) Used for atropine toxicity.
Skeletal Muscle Relaxants
Benzodiazepines: anti-anxiety meds that may produce sedation muscle relaxation. MOA: increases
frequency of interaction of GABA with GABA-A receptor.
Diazepam: long half- life 20-80
Midazolam:
Triazolam: short half- life 2-3 hours
Baclofen (GABA agonist): do not discontinue abruptly. Anti- spasmodic agent. Can be used
interthecally.
Dantrolene: binds to ryanodine receptor preventing calcium release from SER- thus preventing
muscle contraction.
Tizanidine: alpha 2 agonist.

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 Diuretics
Proximal Tubule (urine alkalinizing)
Acetazolamide: reversible inhibition of carbonic anhydrase which inhibits reabsorption of Na and
bicarb leading to dieresis. Can cause metabolic acidosis and renal stones. Used for CHF and urinary
alkalization (Acute Mountain sickness). Contraindicated in cirrhosis.
Loop
Furosemide: inhibits Na/K/2Cl pump in thick ascending limp of loop. Blocks NaCl reabsorption
leading to increased osmotic pressure and dieresis. High ceiling and may lead to metabolic alkalosis
(high urinary calcium) or hearing loss. Used for pulmonary edema and CHF. Not indicated in acute
renal failure.
Bumetanide:
Toresmide:
Ethacrynic Acid: ONLY loop diuretic that is NOT a sulfa drug. Most ototoxic.

Potassium-sparing
Spironolactone: MOA: competitively inhibitor of aldosterone, anti-androgenic effects
Eplerenone:
Amiloride: DO NOT use with NSAIDs due to increase in potassium
Triamterene: 10X less potent than Amiloride. Blocks Na channels in luminal sides. Used in combo
with HCTZ to avoid depletion plasma K
Thiazide
Hydrochlorothiazide: inhibits Na/Cl co-transporter in distal tubule creating an increase in Ca
reabsorption. AE: hyperGLUC (-glycemia, -Lipidemia, -uricemia, -calcemia) Contains sulfer. #1
choice: HTN
Metolazone: 10X more potent than HCTZ
Indpamide: not truly a thiazide, but acts like one. 20X more potent than HCTZ
Chlorthalidone: 1/10th potency of HCTZ

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Osmotic agent
Mannitol: has osmotic pull maximally in loop of Henle. May cause increase loss of electrolytes. High
ceiling. Needs to be IV. Uses: decreases ICP and promotes excretion.
Vasopressin (ADH) Antagonist
Tolvaptan: V2 receptor
Conivaptan: V1A and V2 receptor
Renin Inhibitor
Aliskiren: inhibits angiotensin (then inhibiting angiotensin II)

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 Non-Alcoholic Steatohepatitis (NASH) and
Anesthesia Considerations
Non-alcoholic Steatohepatitis, or NASH-
Most common cause of chronic liver cirrhosis- Estimated 24% American adults have it?
Risk factors- between fifth and sixth decades. Obesity, syndrome X, DM II, women.
Estimated 75% of DM 2 affected people have NASH.
Pathophysiology- Largely unknown. Initial steatosis, lobular inflammation and perisinusoidal fibrosis,
leading to cirrhosis. Two hit phenomenon between NASH and syndrome X- Initial insults such as obesity,
subclinical insulin resistance, hyperlipidemia, hypercholesterolemia causing fatty liver. The second hit is the
inflammatory factor, oxygen radicals, oxidative stress, lipid peroxidation and cytokine insults, mediating
fibrosis.
Most patients are asymptomatic initially. Slow, quiet disease progressing over years to decades. Initial
symptoms- fatigue, weight loss, weakness.
Detection- Hepatomegaly, Abnormal mildly elevated LFTs, up to 2 to 5 times elevated ALT, AST. Liver
biopsy showing fat, inflammation.
Treatment- NASH can stop and/or reverse with diet, exercise. It can be slowed/stopped as well in some
cases with the benefits of bariatric surgery. Many times it progresses over time to include the many
comorbid manifestations of associated with the insults of liver cirrhosis, leading to potential end-stage
parenchymal liver disease.
The key in preoperative evaluation is determining the extent of liver injury- trend LFTs, PT/INR, over
time- are they slowly elevating? Where are they? Are there comorbid diseases? How long ago was the
diagnosis, what are patients symptoms? Is there any associated renal disease (hepatorenal) - what is
BUN/Creat- trends? MELD score- Model for end-stage liver disease quantifies liver dysfunction utilizing
three parameters- serum bili, INR and serum creatinine. Child-Pugh scoring. Minor disease tolerates minor
to moderate procedures. However in moderate to advanced forms of NASH, especially in major operations
such as laparotomy often has postoperative hepatic dysfunction. DEFER elective procedures. Correct
varices, encephalopathy, and pancytopenia prior to surgery. Assess degree of comorbidities.
Moderate to advanced features and pathophysiology of liver cirrhosis- Perisinusoidal fibrosis increases
resistance to flow- backing flow up into portal, venous system- Portal Hypertension- hyper dynamic
circulation.

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 A. Cardiac- High CO. Low PVR. Low to norm. BP. Increased SV. Possible cardiomyopathy.
Review ECG, TTE, TEE, exercise capacity.
B. Portal, GI- Portal HTN- splenomegaly, ascites, GI Varices, hemorrhage. History of GI bleeding,
EGDs with banding, colonoscopies. Paracentesis, bacterial peritonitis.
C. Pulmonary- Ascites pushing on diaphragm- decrease in FRC, TLV, including. Work of breathing.
Interstitial edema, airway edema, V/Q mismatching, hypoxemia. Advanced- hepatopulm. Syndrome-
intrapulmonary vascular dilatations
D. Hematologic/Coag- Impairment of hemostasis decreasing production of clotting factors. Vit. K
dependent clotting factor deficiency secondary to impaired bile secretion from cholestasis. Bleeding
tendencies, low platelet, and fibrinogen. Elevated PT/INR.
E. Neuro- Hepatic encephalopathy
F. Renal/endocrine- Association of hepatorenal disease, hypo/hyperglycemia. Perioperative blood
glucose levels as warranted. Assess creat/kidney disease.
Anesthetic Considerations- Potential need to titrate lower doses of sedatives, especially benzos depending
on extent of liver dysfunction. CAREFUL giving benzos to patients with encephalopathy, or not at all.
Conversely- will need higher doses of catecholamine’s, or adding vasopressin if needed- because portal
HTN, cirrhosis- elevated glucagon-decreased response to catecholamine’s. REGIONAL PREFERRED- IF
NO COAGULAPATHY. These patients commonly have “full stomach” as they have ascites, hiatal hernia,
decreased motility, GERD--- RSI INDICATED.
PIMP Question - Advanced liver disease markedly reduces plasma cholinesterase- prolonged
succinylcholine effect.
In a patient with cirrhosis O2 of liver depends on hepatic artery blood flow- MAINTAIN IT. Isoflurane,
Des, Sevoflurane okay in liver cirrhosis. Fentanyl choice narcotic. MUSCLE RELAXANTS- Know there
is an increased volume of distribution, with lower plasma concentrations of water soluble drugs, and drugs
that depend on hepatic or renal excretion have prolonged clearance- GREATER LOADING DOSE,
SMALLER MAINENANCE DOSES. Vec, Panc, and Roc blockade are prolonged.
The PRIMARY GOAL in these patients preoperatively, especially intraop focuses on ENSURING the
adequacy of splanchnic, hepatic, and renal perfusion and oxygen delivery. T/S, T/C. Art line as indicated
for ABGs, labs? Central line if hemodynamically unstable, comorbid disease, associated cardiac pathophys,
or if large fluid shifts. Intraop coag monitoring. AVOID Halothane, enflurane. In advanced disease it would
seem prudent to avoid drugs that undergo extensive hepatic metabolism, however- these patients are not
undergoing elective procedures.

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 Thalassemia

Thalassemia, a blood disorders characterized by a deficiency of hemoglobin, the blood protein that transports
oxygen to the tissues.

Thalassemia is caused by genetically determined abnormalities in the synthesis of one or more of the
polypeptide chains of globin. It is more common in the Mediterranean, Middle Eastern, and Southeast Asian
regions.

It is one of the leading causes of microcytic anemia in children and adults

There are 3 different severities of the disease;

Thalassemia minor (heterozygous β-thalassemia)

o Usually only slight or no anemia
o Life expectancy is normal
o Occasional complications; slight enlargement of the spleen.
 Treatment; Usually none
o Morbidity associated with chronic hemolysis and ineffective erythropoiesis is rarely
encountered.

Thalassemia Intermediate
o Patients present with more severe but compensated anemia
o Prominent microcytosis (erythrocytes that are smaller than normal) and hypochromia (An
anemic condition in which the percentage of hemoglobin in red blood cells is abnormally low)
o May have hepatosplenomegaly, cardiomegaly, and skeletal changes secondary to marrow
expansion.

Thalassemia major (homozygous β-thalassemia, or Cooley anemia)

o Severe anemia
o Body deformities associated with massive marrow hyperplasia
 Frontal bossing, maxillary overgrowth, stunted growth, osteoporosis
o Hemolytic anemia may produce hepatosplenomegaly together with extreme dyspnea and
orthopnea, over time resulting in congestive heart failure and mental retardation.

 Treatment;
o Blood transfusions;
 Only temporary and leads to excessive iron in the tissues once the transfused red cells
break down. Transfusion therapy will improve many symptoms, but complications due
to iron overload such as cirrhosis, right-sided heart failure, and endocrinopathy
frequently require chelation therapy.
o Splenectomy;
 An enlarged spleen may further aggravate the anemia by pooling and trapping the
circulating red cells. Some patients demonstrate reduced transfusion requirements
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 after splenectomy. Due to the increased risk of sepsis post splenectomy in younger
patients it is recommended that the surgery be delayed until after the age of 5. For
well-transfused and well-chelated patients, splenectomy may not be indicated.
o Bone marrow transplantation;
 A therapeutic option for younger patients with HLA-identical siblings.

 In its most severe forms, patients exhibit three defects that markedly depress their oxygen-carrying
capacity:
o (1) Ineffective erythropoiesis
o (2) Hemolytic anemia
o (3) Hypochromia with microcytosis

Anesthetic Considerations

 Hypoxemia due to decreased oxygen carrying capacity of blood secondary to hemolytic anemia and
hypochromia.
 Consider the degree of thalassemia to determine the potential degree of organ damage.
 What is the degree of anemia is it compensated? Assess the need for a preoperative transfusion.
 T&C preoperatively
 Place arterial catheter to closely monitor oxygenation, obtain baseline ABG
 Hemoglobin is the major factor in oxygen delivery; therefore the decision to transfuse is based on the
carrying capacity of hemoglobin.

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 Porphyria

Defined as…

 A group of inborn errors of metabolism characterized by the overproduction of porphyrins and their
precursors (Tantawy, 2008, p. 312).
 Porphyrins are essential for many vital physiologic functions including oxygen transport and storage.
 The synthetic pathway involved in the production of porphyrins is determined by a sequence of
enzymes. A defect in any of these enzymes results in accumulation of the preceding intermediaries
and produces a form of porphyria.

Classification

 Porphyrias are classified by the site of the enzyme defect hepatic or erythropoietic, reflecting the
major sites of heme production in the liver and bone marrow (Tantawy, 2008, p. 312).
 Only acute forms of porphyria are relevant to the management of anesthesia.

Acute Porphyria

 Inherited, non-sex-linked autosomal dominant condition (Tantawy, 2008, p. 314).

 Attacks occur more frequently in women in the 3rd to 4th decades of life.
 Acute attacks are most commonly precipitated by events that decrease heme concentrations.

Diagnosis

 By direct assay of the intermediates themselves during an acute state to measure the elevated levels
of the heme intermediates (Rosenberg, Brandom & Sambuughin, 2009, p. 616).

Signs & Symptoms

 Acute attacks are characterized by severe abdominal pain, autonomic nervous system instability,
electrolyte disturbances, and neuropsychiatric manifestations ranging from mild to fulminating life-
threatening events (Rosenberg, Brandom & Sambuughin, 2009, p. 616; Tantawy, 2008, p. 315).
 Skeletal weakness may progress to quadriparesis and respiratory failure.
 Dehydration and electrolyte disturbances involving sodium, potassium, and magnesium may be
prominent in these patients

Triggering Drugs

 Drugs may trigger an acute attack of porphyria by inducing the activity of ALA synthetase or
interfering with the negative feedback control as the final common pathway (Rosenberg, Brandom &
Sambuughin, 2009, p. 616; Tantawy, 2008, p. 315).
 Allyl groups present on barbiturates and certain steroid structures have been incriminated in the
production of porphyria.
 Use of etomidate is questionable.

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  Analgesics: pentazocine, antipyrine, aminopyridine, lidocaine (Rosenberg, Brandom & Sambuughin,
2009, p. 616).
 Anticonvulsants: phenytoin, methsuximide.
 Antibiotics: sulfonamides, chloramphenicol
 Steriods: estrogens, progesterones
 Hypoglycemic sulfonylureas: tolbutamide, chlorpropamide
 Toxins: lead, ethanol
 Miscellaneous: ergot preparations, amphetamines, methyldopa
 Fasting, infection and estrogens, may also precipitate porphyria.

Management of Anesthesia

 Short acting drugs are presumed to be safe because their rapid elimination limits exposure time for
enzyme induction to occur (Tantawy, 2008, p. 317).
 Repeated or prolonged use of continuous intravenous infusion propofol may result in a response
 Benzodiazepines are commonly selected for preoperative anxiolytics.
 There is no absolute contraindication to the use of regional anesthesia in patients with porphyria.
 Induction: Dose of propofol or ketamine is considered safe for induction.
 Maintenance: Use of nitrous oxide, isoflurane, sevoflurane, desflurane, opioids and neuromuscular
blocking agents are considered safe.

Treatment of a Porphyria Crisis

 Removal of any known triggering factor (Tantawy, 2008, p. 318).

 Adequate hydration and carbohydrates.
 B-adrenergic blockers are administered to control tachycardia and systemic hypertension.
 In the case of a seizure a benzodiazepine may be administered, as anti-convulsants are unsafe.
 Hematin (3-4 mg/kg IV over 20 minutes) is the only specific form of therapy for acute porphyria
crisis. Presumed that hematin supplements the intracellular pool of heme and thus suppresses ALA
synthesis activity.

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 Treacher Collin Syndrome

AKA Mandibulofacial sysostosis or Fransechetti-Klein Syndrome

~A disorder of craniofacial development~

Think Airway!

 Caused by heterozygous mutation in the 'treacle' gene

 Autosomal dominant disorder, variable expression
 Most common of the mandibulofacial dysostoses

Features: (Lee, Luginbuehl, Bissonnette, & Mason, 2008, p. 613)

 Face
o Malar hypoplasia; underdeveloped mid-face (89%)
 Ears
o Ear tags
o Microtia; under development of the external ear (77%)
o Conductive hearing loss
 Eyes
o Atimongoloid (downward) slant of the palpebral fissures
o Colobomas or notching of lower eyelid (69%)
 Mouth
o Macrostomia; unusually wide mouth
o Cleft palate; 30%
 Can lead to feeding problems
o Palatopharyngeal incompetence
o Obstructive sleep apnea
 Heart
o Congenital heart defect; ventricular septal defect most common
Why might we see them…? (Katsanis & Jabs, 2004)

 Upper airway management

o Tracheostomy
 Correction of congenital heart defect

Palatoplasty
o Closure of soft palate as early as 3 months
o Hard palate is delayed until 18 months
 Correction of lower eyelids
o 3 years
 Lengthening of mandible
o 4-5 years
 Treatment of chronic otitis media or hearing loss
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 o Hearing aids should be fitted as soon as possible to aid in speech development
o External ear deformities are often corrected at age 5-7 years

Anesthetic Implications; ….AIRWAY, AIRWAY, AIRWAY

 Airway management (Agrawal, Asthana, Sharma, Sharma, & Meher, 2006)

o Difficult to mask ventilate
 macroglossia
 midface hypoplasia
o Difficulty to intubate
 small mandibular space
 ⇓ neck flexion/extension
 limited jaw opening
 retrognathia

o Awake intubation
 Is difficult due to child’s inability to cooperate
 Avoid use of paralytics
o Direct laryngoscopy
 Miller blade
 May be more effective in these cases because it equally distributes the tongue
on each side of the blade.
 Macintosh blade
 Difficult to use w/ macroglossia
 Glidscope
 May be the most effective
 LMA
 Cricothyroidotomy
 Tracheotomy

References
Agrawal, S., Asthana, V., Sharma, J., Sharma, U., & Meher, R. (2006). Alternative Intubation Techniques in
a Case of Treacher Collins Syndrome.
The Internet Journal of Anesthesiology, 11(1). Retrieved from
[Link]
1/[Link]
Katsanis, S., & Jabs, E. (2004). Treacher Collins Syndrome. Retrieved from
[Link]
Lee, C., Luginbuehl, I., Bissonnette, B., & Mason, L. J. (2008). Pediatric Diseases. In R. L. Hines, & K. E.
Marschall (Eds.), Stoelting’s Anesthesia and Co-Existing Disease (5th ed., p. 613). Philadelphia, PA:
Churchill Livingstone.

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 Cystic Fibrosis and Anesthetic Implications

Background- Cystic Fibrosis is the most common autosomal recessive disorder, shortening life, affecting
about 30,000 Americans (Kurup, 2008). It affects 1 in 3300 births in the white population, with a median
age of survival now at 31-40 years old (Karlet, 2000).

Pathophysiology- The cause is from a mutation in a single gene on chromosome 7 that encodes the cystic
fibrosis transmembrane conductance receptor. This causes a defective chloride ion transport in epithelial
cells in lungs, pancreas, liver, GI tract and reproductive organs.

 Diagnosis based on sweat chloride concentrations higher than 80mEQ/L.

 90% diagnosed within first 2 years of life.
 Chronic pansinusitus is almost universal (Kurup, 2008).

Manifestations/Complications- There is marked variability in manifestations.

 Some may be apparent at birth- such as meconium ileus.

 More common manifestations are during first year of life- exocrine pancreatic insufficiency,
steatorrhea, abdominal distention, failure to thrive.
 Respiratory tract involvement is A VERY common feature- with mucus plugging, inflammatory
infiltrates, recurrent pulmonary infections, chronic cough.
 Intestinal obstruction, hepatic involvement such as obstructive biliary tract disease can occur.
 COPD is present in ALL adult patients with cystic fibrosis.
 Nasal polyps and inflammation of nasal mucosa in 25% of patients.
 Infertility present in 95% of males.

Pulmonary changes are seen in nearly ALL patients with Cystic Fibrosis.

Advancing disease-

 Respiratory- Deterioration of gas exchange, V/Q mismatching, leading to CHRONIC HYPOXEMIA.

This leads to Pulm HTN- RV Failure in some patients. Over time recurrent infections, prolonged
obstruction, emphysematous blebs, bronchiectasis, purulent bronchitis. Risk of pneumothorax in
advanced disease is HIGH.
 Pancreatic involvement- Present in 85-90% of patients (Karlet, 2000). Insufficiency causes
deficiency of amylase, lipase, and protein and fat malabsorption, leading to malnutrition. Glucose
intolerance in 7-10% of patients (Karlet, 2000).
 Hepatobiliary- Fatty infiltration, obstructive cirrhosis, portal HTN are less frequent. Cholelithiasis
and impaired synthesis of Vit. K. dependent coag 2, 7, 9 and 10- increased risk for hemorrhage.
GERD incidence is HIGH.

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Pre-operative- It is the respiratory dysfunction that is most concerning to us.

 Need preoperative pulmonary function studies, commonly revealing an obstructive pattern- increased
FRC, decreased FEV1, decreased peak exp. Flow rate, and decreased VC.
 Chest x-ray.
 OPTIMIZE preop. Cardiopulm. Status. Intense preoperative chest PT and bronchial clearance
techniques, including ins. Spirometry, postural drainage, chest percussion, and pathogen specific
antibiotic therapy (Karlet, 2000). Need control of bronchial infections prior to surgery. Sputum C
and S.
 Need liver function tests, PT/INR, CMP, CBC, glucose preop. When indicated- ABGs, ECG, Echo
preop.
 CONTINUE all bronchodilators, corticosteroids periop. Potential stress dose of corticosteroid.
 Pre-op analgesics, sedatives, anxiolytics use SPARINGLY- may potentiate further ventilatory
depression, impaired ability to clear secretions.
 These patients have viscous mucous. DO NOT USE ANTISIALAGOGUES- i.e. anticholinergics.
 Use H-2 antagonist’s preop, possibly nonparticulate antacids.
 PRE-OXYGENATION ESPECIALLY IMPORTANT.

Intraoperative-

 Local and regional blocks are favored, rule out coagulopathy.

 RSI if significant GERD, otherwise standard IV or inhalational induction.
 Inhalational induction slowed due to small tidal volume, V/Q mismatching.
 Ketamine CONTRAINDICATED- increases bronchial secretions.
 Irritating properties of Desflurane make it a poor choice.
 Systemic hydration and humidification of inspired gases very important to decrease viscosity
of secretions. Frequent suctioning intraoperative.
 Early insertion of oropharyngeal airway, ESPECIALLY if nasal polyps present.
 Muscle relaxants with short DOA. Use minimum doses.
 DELAY EXTUBATION until adequacy of ventilation reaches preanesthetic levels.

Postoperative

 Aggressive respiratory therapy, O2 supplementation, clearance of secretions.

 Carefully administered opioids, NSAIDS very useful.
 Local wound infiltration with long acting LA.
 ICU may be the most appropriate setting for close monitoring.

Works Cited: CF

Karlet, M. C. (2000). An Update on cystic fibrosis and implications for anesthesia. AANA Journal, 141-148.
Kurup, V. (2008). Respiratory Diseases. In R. L. Hines, & K. E. Marschall, Stoelting's Anesthesia and Co-
Existing Disease (pp. 177-179). Philadelphia: Churchill Livingstone.

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 Pierre Robin Syndrome
Consists of…

 Micrognathia that is usually accompanied by glossoptosis (posterior displacement of the tongue) and
cleft palate (Lee, Luginbuehl, Bissonnette, & Mason, 2008, p. 612-613).
 Mandibular hypoplasia is a prominent feature.
 Respiratory distress that is seen in the first 24 to 48 hours of life (Engelhardt, Crawford, & Lerman,
2009, p. 709).

Mandibular hypoplasia

 The small mandible leaves little room for the tongue and makes the larynx appear to be anterior (Lee,
Luginbuehl, Bissonnette, & Mason, 2008, p. 612-613).
 May be responsible for displacement of the tongue into the pharynx, which prevents fusion of the
palate.
 May lead to feeding problems  failure to thrive.
 Incidence of difficult laryngoscopy ~ 50% (Engelhardt, Crawford, & Lerman, 2009, p. 709).
 Intubation difficulty decreased with age, with greatest difficulty in infants younger than 6 months old.

Associated with…

 Congenital heart disease (Lee, Luginbuehl, Bissonnette, & Mason, 2008, p. 612-613).

Anesthetic Implications

 Acute upper airway obstruction may occur in neonates or infants (Lee, Luginbuehl, Bissonnette, &
Mason, 2008, p. 612-613).
 Difficult tracheal intubation is likely.
 Induction of anesthesia via facemask is usually uncomplicated in infants with cleft lip and palate
(Engelhardt, Crawford, & Lerman, 2009, p. 709).
 Laryngoscopy should be performed with a straight blade, taking care to prevent the blade from
entering the cleft.
 In some centers, the tongue is sutured to either the mandible or lower lip to preclude airway
obstruction in infants with Pierre Robin sequence during the postnatal period.
 Bilateral infraorbital nerve blocks may be used to provide postoperative analgesia for cleft lip repairs
– will reduce the need for opioids and antiemetics and improve the ability to feed.
 During cleft palate repair, the pharyngeal space is reduced dramatically that increases the risk for
acute upper airway obstruction – related to upper airway narrowing, edema, and residual anesthetic
effects – the trachea is extubated after complete return of upper airway reflexes.
 URI’s are common – antibiotic treatment may reduce the incidence of postoperative respiratory
complications.
 A nasopharyngeal airway can be inserted before extubation to permit suctioning of the airway
without damaging the palatal repair and to provide a patent airway.

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  Postoperative observation is required for 48 hours, monitoring for signs of upper respiratory
obstruction.
 Emergent re-intubation postoperatively may be required in the event of blood, edema and/or
unfamiliar suture lines in the oropharynx.
 Postoperative pain may be managed with opioids in combination with acetaminophen.

References
Engelhardt, T., Crawford, M. W., & Lerman, J. (2009). Plastic and reconstructive
Surgery. In C. J. Cote, J. Lerman & I. D. Todres (Eds.), A practice of anesthesia for infants and
children (4th ed., pp. 709). Philadelphia, PA: Saunders Elsevier.
Lee, C., Luginbuehl, I., Bissonnette, B., & Mason, L. J. (2008). Pediatric diseases. In R.
L. Hines & K. E. Marschall (Eds.), Stoelting’s anesthesia and co-existing disease (5th ed., pp. 612-
613). Philadelphia, PA: Churchill Livingstone.

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 Prader- Willi Syndrome and Anesthetic Considerations

 Congenital disease- manifesting at birth- caused by a gene missing on part of chromosome 15.
 Autosomal recessive mode of inheritance. Usually no family history of this prior.
 Rare genetic disorder with hypothalamic pituitary abnormalities
 Estimated Prevalence- 1:15,000.
 2 stage disorder- Infantile hypotonic phase- followed by childhood obese phase.

 What are S/S of this disease?

1. Newborns are small and floppy.
2. INTENSE craving for food, will almost do anything to get it- potential for uncontrollable weight
gain, morbid obesity and everything that could potentially go with this- DM2, OSA, HTN, etc. etc.
3. MICROGNATHIA, high arched palate, strabismus, a straight ulnar border, and congenital dislocation
of the hip are often present.
4. Male infants may have undescended testicles
5. Almond-shaped eyes, short stature, slow mental development, RAPID WEIGHT GAIN.
6. Very small hands and feet in comparison to child’s body.
7. Mental Retardation is often SEVERE.
8. Hypotonia, weak cough, swallowing difficulties, and upper airway obstruction type of theme.
9. Seizures/ seizure disorders common in this population

 Concerns in this patient when they are adult?

1. Over time the complications secondary to this syndrome is often evident- DM2, OSA, Obesity,
Cor pulmonale, HTN, orthopedic issues, infections, pressure ulcers.
 What are anesthetic concerns?

1. Preop- consider state of nutrition and hydration. BMI, neck circumference. Dental issues.
Salivary composition- thick. Obesity later and its laundry list of comorbidities each with separate
anesthetic considerations- again OSA, HTN, cor pulmonale, HTN, DM2, infections, poor wound
healing etc.
2. Careful and thorough evaluation of patients past and current respiratory status including
polysomnography as preop workup to identify those with OSA.
3. Children with this syndrome frequently suffer from restrictive lung disease secondary to
hypotonia, obesity and kyphoscoliosis.
4. Typical surgeries- Ortho- scoliosis repair; squint correction; cleft lip and palatal repair; dental
treatment due to caries; orchidopexy (cryptorchism). Ambulatory (same day) procedures NOT
recommended.
5. These patients are hypotonic with altered carbohydrate and fat metabolism- many concerns here-
6. Weak skeletal muscles- Poor cough and increased pneumonia risk
7. Intraop blood glucose monitoring, may need exogenous glucose- these patients use glucose to
make fat instead of meeting basal energy requirements
8. Drug dosage considerations need to be adjusted based on patients decreased skeletal muscle and
increased fat content
9. Muscle relaxant requirements decreased secondary to hypotonia. - Judicious use during phase 1
stage especially. Some authors caution against their use entirely although others have
documented safe use in small increments.

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10. Hypotonia- theoretical risk of exaggerated hyperkalemic response, although several reports have
demonstrated safe use.
11. Often disturbances in thermoregulation- intraoperative hyperthermia and metabolic acidosis-
although no correlation with MH.
12. Increased incidence of aspiration pneumonitis- Consider - Preop famotidine, reglan, bicitra
13. Regional okay- landmarks for regional anesthesia may be obscured secondary to morbid obesity-
US is your friend.
14. Difficult IV access.
15. Aggressive and at times violent behavior- potential for ketamine/versed/glyco dart prior to OR/IV
access- although be VERY CAREFUL in any preop sedation
16. DIFFICULT AIRWAY!!! It would seem prudent to utilize/anticipate advanced airway options-
awake vs. asleep, having glidescope, FOB available- secondary to common micrognathia
17. Risk of aspiration, with OSA- awake extubations, not deep. Be mindful in usage of narcotics-
limit their use and consider NSAIDS, adjunct agents
18. Combined severe OSA and this syndrome highly suggests postoperative ICU vs. PACU. Well
documented common postoperative complications of hypoxia, aspiration pneumo, obstruction,
delayed emergence all point to consideration of postoperative ICU.

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 Bardet-Biedl Syndrome

Bardet Biedl Syndrome (BBS) is a rare autosomal recessive genetic disorder. Although there are varied
degrees of severity in phenotype, some commonly described pansystemic symptoms are:

 Polydactyl (extra digit), syndactyly (two digits fused together), brachydactyly (short digits)
 Cone-rod dystrophy with blindness usually occurring by adulthood, retinal abnormalities
 Truncal obesity
 Cognitive impairment – often speech disorder and developmental delay
 Diabetes mellitus or diabetes insipidus
 Complex female GU malformations or Male hypogonadotrophic hypogonadism
 Renal dysfunction and malformations
 Cardiovascular abnormalities (one study showed 11 out of 22 patients (50%) had hypertrophy of the
interventricular septum and dilated cardiomyopathy)
 Hepatic and dental involvement
The syndrome is much more common in the Middle East with an incidence of 1:13,500. In the rest of the
world, the incidence is 1:160,000 with a male-to-female ratio of approximately 1.3:1.
Anesthetic Considerations:
Renal Failure is a common cause of morbidity and mortality in these patients. Use renally metabolized and
excreted anesthetics sparingly.
Because of this reported cardiovascular abnormalities, it is prudent to consider a 12-lead ECG and
echocardiogram during the pre-anesthetic assessment.
This is a pansystemic genetic disorder meaning that any number of physical deformities may occur, even
including the airway. Be prepared to manage a difficult airway with these patients.

Bibliography
Chittoodan, S., & Crowe, S. (2010). Day Care General Anaesthesia for a child with Bardet-Biedl syndrome.
Case Reports in Medicine, published online [Link]
Iannello S, F. S. (1998). A case of familial Bardet-Biedl syndrome (obesity, slight mental retardation,
polydactyly, retinitis pigmentosum and renal failure) with insulin-resistant diabetes mellitus. Minerva
Endocrinology, 83-92.

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 Momo Syndrome

Macrocephaly, Obesity, Mental disability, Ocular abnormalities

 MOMO syndrome is an extremely rare genetic disorder which belongs to the overgrowth syndromes and
has been diagnosed in only six cases around the world, and occurs in 1 in 100 million births.
 The name is an acronym of the four primary aspects of the disorder:
o Macrosomia (excessive birth weight >90th percentile)
o Obesity
o Macrocephaly (excessive head size >90th percentile)
o Ocular abnormalities (generally retinal coloboma and nystagmus)
 It is unknown if it is a life-limiting condition. MOMO syndrome was first diagnosed in 1993 by
Professor Célia Priszkulnik Koiffmann, a Brazilian researcher in the Genetic and Clinical Studies of
neurodevelopmental disorders.

Signs and symptoms

Along with the four aspects of the disorder that give it its name, there are also other common
symptoms:
• A downward slant of the forehead
• Delayed bone maturation
• Mental retardation

Pathophysiology

 Because MOMO is such a rare disorder, very few studies have been conducted into its causes.
Current research suggests that it is linked to a new autosomal dominant mutation.

Confirmed cases
Archie Thompson was born in 2002 in Icklesham, England and weighed 8&nbsp; lb. 4 oz (3740 g). By 15
months his weight had increased to 4 stone (56&nbsp; lb.; 25&nbsp; kg) and by 24...

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 Cohen Syndrome
Cohen syndrome

 Background
o Rare genetic disorder associated with mutations present at COH1 gene within chromosome 8
 The function of the protein produced from the gene is unknown, however, researchers
suggest it may be involved in sorting and transporting proteins inside the cell
 Inherited in an autosomal recessive pattern
o Often undiagnosed for many years
o Globally fewer than 1000 cases have been reported
 Clinical symptoms
o Symptoms can go unnoticed during the first few months of life until parents notice the child is
not meeting developmental benchmarks
o May experience failure to thrive in infancy, seizure, high myopia and/or retinal dystrophy,
strabismus, nystagmus, deafness microcephaly, micrognathia, short philtrum, high vaulted
palate, developmental delay, late emerging speech/poor articulation/total apraxia, joint laxity,
narrow hands and feet/small stature, friendly disposition, neutropenia, characteristic facial
features
 Neutropenia may lead to dental issue and mouth sores
 Characteristic facial features include thick hair and eyebrows, long eyelashes,
unusually shaped eyes (down slanting and wave-shaped), a bulbous nasal tip, a smooth
or shortened area between the nose and the upper lip and prominent upper central teeth
 The combination of the last two facial features results in an open-mouth
appearance
 Early diagnosis
o Allows for early medical and therapeutic interventions
 Therapy – O.T., P.T., speech
 Other names for Cohen syndrome
o Hypotonia, obesity, prominent incisors
o Norio syndrome
o Obesity-hypotonia syndrome
o Pepper syndrome
o Prominent incisors-obesity-hypotonia syndrome

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 Prune Belly Syndrome
What is it?

 A congenital abnormality characterized by poor development of the lower central abdominal

musculature and the presence of urinary tract anomalies including gross ureteral dilatation, hypotonic
bladder, prostatic hypoplasia, and bilateral undescended testes.
 The full syndrome appears only in males, and an incomplete syndrome may include up to 3%
females.
o (Schwartz, 2008, p. 463)

Pathophysiology…. Unclear

 In utero the child's abdomen often swells with fluid (in the presence of oligohydramnios) that is
resorbed by birth, leaving the characteristic wrinkled redundant abdominal wall.
 It has been suggested that a urethral obstruction in utero leads to dilatation of the urethra
(megaurethra is a common finding) combined with bladder distention and ascites, which causes
distention of the abdomen in utero. This ultimately leads to vesicoureteral reflux and ureteral
dilatation in 80% of children.
 occurs predominantly in males (97% of cases) with an incidence of 1 : 40,000 births
o (Lonnqvist & Lerman, 2009)

Manifestations;

 Abnormalities ranges from stillborn to a full-term neonate with involvement of the abdomen, lungs,
cryptorchidism, and urologic anomalies.
 Orthopedic in 50% (congenital hip dislocation and scoliosis)
 Gastrointestinal in 30% (malrotation and volvulus)
 Congenital heart disease in 10% (tetralogy of Fallot and ventricular septal defect)
 Trisomy 18 (alternately known as Edward's syndrome)
 Trisomy 21
o (Lonnqvist & Lerman, 2009)

4 most common characteristics

1. Wrinkled/swollen belly
2. Undescended testes
3. Urinary tract abnormalities
4. Weak abdominal muscles that limit expiration and cough

218
Implications;

 Weak rectus abdominis muscles;

o Abdominal over distention in utero results in weak rectus abdominis muscles that limit
expiration and the ability to cough.
o This can result in chronic aspiration, pneumonia, and death.
 Aggressive intervention to correct the weak rectus muscles by plication and muscle
transfer can be done and may improve respiratory function.
 Controlling the type of feeds, preventing gastrointestinal reflux disease, and using
antibiotics to treat pneumonia permit the child to grow.
 Constipation
o A frequent problem secondary to an inability to increase intra-abdominal pressure during
defecation.
 Stool softeners; prevent constipation and the possibility of abdominal distention
 It is best to avoid placement of a percutaneous endoscopic gastroscopy tube because
abdominal wall surgery will be much more difficult.
 Trisomy 18
o The second most common autosomal trisomy
 occurs in 1 in 7,000 live births
 Associated with prune belly syndrome
 Approximately 80% of these infants are female.
 Characterized by
 Severe neurologic developmental problems (including microcephaly),
micro/retrognathia, microstomia, auricular abnormalities, and others.
 High rate of potentially lethal complications in the first years of life, 95% die
in utero with only 5% to 10% surviving 1 year after birth and 1% reaching 10
years.
 Cardiac anomalies (90% of affected children will have ventricular septal
defect, valvular heart defects, atrial septal defect, hypoplastic left heart
syndrome, tetralogy of Fallot, and others), renal anomalies, failure to thrive,
and apnea. Other findings include pulmonary hypoplasia and gastrointestinal
anomalies (including prune belly syndrome, omphalocele, ileal atresias, and
esophageal atresia).
 (Lonnqvist & Lerman, 2009)

Anesthetic implications

 Urologic surgery often required to correct vesicoureteral reflux and orchidopexy.

o Urethral obstruction may be due to the angulation of the urethra within the prostate.
 General anesthesia with tracheal intubation is required for most surgeries in these children.
 Controlled ventilation is recommended because of the variability in the strength of the abdominal
musculature.
 Suction the lungs while intubated to assess the extent of pulmonary infection.

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 Intraocular Pressure

Prevention of increased intraocular pressures (IOP):

 IOP normal: 10 to 21.7 mmHg (≥ 22 mmHg abnormal)

o Varies 1 to 2 mmHg with cardiac contraction
 During anesthesia, a rise in IOP can produce permanent visual loss
 Three main factors that influence IOP:
o External pressure on the eye by the contraction of the orbicularis oculi muscle, tone of
extraocular muscles and venous congestion
o Scleral rigidity
o Changes in intraocular contents that are semisolid or fluid
 Factors associated with elevated IOP:
o Trendelenburg position
o Cervical collar/tight neckties
o Straining/vomiting/coughing (raise IOP to 40 mmHg)
o Laryngoscopy/tracheal intubation
o Succinylcholine – attributed to tonic contraction of extraocular muscles, choroidal vascular
dilation, and relaxation of orbital smooth muscle
 On average, will rise 8 mmHg produced within 1 to 4 minutes.
 Return to baseline within 7 minutes
o Ketamine, but remains controversial as it has minimal to no effect
o Hypoventilation/asphyxia/elevated carbon dioxide
 Factors associated with a reduction in IOP:
o Dose-related decrease in IOP with inhalation anesthetics
o NMB’s – d-tubocuranine, pancuronium (relax extraocular muscles)
o CNS depressants – barbiturates, neuroleptics, opioids, tranquilizers, hypnotics (etomidate,
propofol)
o Ganglionic blockers – tetraethylammonium, pentamethonium
o Trimethaphan
o Hypertonic solutions intravenously administered – dextran, urea, mannitol, sorbitol
o Acetazolamide – inactivates carbonic anhydras and interferes with the sodium pump
o Hyperventilation
o Hypothermia

McGoldrick, K. E., & Gayer, S. I. (2009). Surgery for ophthalmologic surgery. In P. G.

Barash, B. F. Cullen, R. K. Stoelting, M. K. Cahalan, & M. C. Stock (Eds.), Clinical anesthesia (6th
ed, pp. 1324-1327). Philadelphia, PA: Lippincott Williams & Wilkins.

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 GI DISORDERS

ESOPHAGEAL DISEASES

 Achalasia
o Neuromuscular disorder of the esophagus
o Dysfunction of both the esophageal muscle and LES
o Etiology thought to be destruction of the nerves to the LES followed by degeneration of the
function of the esophageal body
o Results in hypertension of the LES and failure of the LES to relax when swallowing, reduced
peristalsis, and esophageal dilation
o s/s include dysphagia, weight loss, and regurgitation
o Long term disease is a/w increased risk or esophageal cancer
o Aspiration is common with resultant pneumonia, lung abscess and/or bronchiectasis
o All treatments are palliative, they can relieve the obstruction cause by the LES but cannot
correct the decreased motility of the esophagus.
o Medications include nitrates, nitroglycerin, and calcium channel blockers
 Esophagectomy
o Curative or palliative option for malignant esophageal lesions
o Morbidity/mortality is high, 10-15%
o Patients may be malnourished before esophagectomy and for several months after
 GERD
o Reflux of gastric contents in the esophagus a/w symptoms
o Natural antireflux mechanisms include the LES, crural diaphragm, and the anatomic location
of the gastroesophageal junction below the diaphragmatic hiatus
o Primary defect in GERD is a decrease in the resting tone of the LES- average in normal pts is
29 mmHg and in GERD pts it is only 13 mmHg
o Increased risk of aspiration, mucosal complicationsesophagitis or esophageal strictures, or
extra esophageal/respiratory complicationslaryngitis, bronchitis, bronchospasm, recurrent
pneumonia, and progressive pulmonary fibrosis
o Prophylaxis/treatment
 Anticholinergic drugs decrease LES tone, therefore increase the likelihood of silent
regurgitation and possibility of pulmonary aspiration
 Succs increases LES and intragastric pressure, but the barrier pressure (LES-
intragastric pressure) is the same
 Cimetidine and ranitidine decrease gastric acid secretion and increase gastric pH
 Cimetidine effect begins in 1-1.5 hours and lasts for 3 hours
 Ranitidine is 4-6x more potent than cimetidine
 Famotidine has similar effects to ranitidine but longer duration of action

 PPI’s given orally the night before and morning of surgery, although recent evidence
indicates that PPI’s inhibit the anti-platelet effects of clopidogrel and possibly aspirin
 Sodium citrate increases gastric pH, it should be given with a gastrokinetic agent such
as metoclopramide. Its use should be limited to those who are diabetic, severely
clinically obese, or pregnant
o Cricoid pressure compresses the lumen of the pharynx between the cricoid cartilage and the
cervical vertebrae
o ETT is essential for protecting the airway from aspiration in anesthetized pts with GERD
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  Hiatal Hernia
o Herniation of part of the stomach into the thoracic cavity through the esophageal hiatus in the
diaphragm
o Most pts are asymptomatic
o Hernia may result from weakening of the anchors of the gastroesophageal junction to the
diaphragm
 Mallory Weis syndrome
o Mucosal tear, usually caused by vomiting, retching, or vigorous coughing
o Tear typically involves the gastric mucosa near the squamocolumnar mucosal junction

INFLAMMATORY BOWEL DISEASE

 Ulcerative colitis
o Mucosal disease involving the rectum and extending proximally it involve all or part of the
colon
o Symptoms may include anorexia, N/V, fever weight loss, increased platelet count and
erythrocyte sedimentation rate and a decrease in Hot
o Severely ill pts may have low serum albumin and leukocytosis
o Can be a/w massive hemorrhage
 Crohn’s disease
o Extensive inflammatory disease that can be a/w a loss of digestive and absorptive surfaces,
which results in malabsorption and steatorrhea
o Bleeding is not as common as with UC
 Treatment for UC and Crohn’s
o Sulfasalazine
o Prednisonepts may need stress dose of steroids for surgery depending on the dose they take
daily
o Azathioprine and 6-mercaptopuringe
o Methotrexate
o Cyclosporine

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 CARCINOID TUMOR

 Can occur in any GI tissue, most often the jejunoileum or the colon/rectum
 Tumors that secrete GI peptides and/or vasoactive substances
 Carcinoid syndrome
o Occurs in approx. 20% of pts with carcinoid tumors
o Result of large amounts of serotonin and vasoactive substances reaching the systemic
circulation
 Anesthetic management
o Invasive arterial BP monitoring d/t rapid changes in hemodynamics
o Administration of octreotide preoperatively and before manipulation of the tumor will
attenuate most adverse hemodynamic responses
o General anesthetic with drugs tailored to patients needs
o Increased levels of serotonin have been a/w delayed awakening
o Ondansetron is a good choice d/t serotonin antagonism
o Epidural analgesia in pts who have been adequately treated with octreotide

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 Respiratory Study Guide
Disease Management

Upper respiratory tract infection

 Infectious (viral or bacterial) nasopharyngitis – 95% of URI’s – common viruses: rhinovirus,

coronavirus, influenza virus, parainfluenza virus and respiratory syncytial virus
 Non-infectious: allergic or vasomotor in origin
 S&S: sneezing, runny nose, infection, fever, purulent nasal discharge, productive cough, malaise,
tachypnea, wheezing
 Anesthetic Management:
o Pre-op: Evidence shows increased incidence of post-op complications with copious
secretions, ET intubation, prematurity, parental smoking, nasal congestion or reactive airway
disease (may take 6 weeks to abate after URI), particularly in those undergoing airway
surgery. Increased risk with active infection (fever, purulent rhinitis, productive cough,
rhonchi). Discuss risks benefits with surgeon and patient if elective surgery.
o General Anesthesia can decrease tracheal mucociliary flow and pulmonary bactericidal
activity.
o Positive pressure ventilation may spread infection from upper to lower resp tract.
o Immune response altered d/t General Anesthesia - ↓ B lymphocyte #s, T lymphocyte
responsiveness and antibody production.
o Intra-op: should include adequate hydration, reduce secretions, limit manipulation of
potentially sensitive airway (LMA rather than ETT to ↓ bronchospasm risk)
o Post-op: Adverse events include – bronchospasm, laryngospasm, airway obstruction, post
intubation croup, desaturation and atelectasis. Hypoxemia is common and usually easily
treated with supplemental oxygen.
Asthma: characterized by chronic airway inflammation, reversible expiratory airflow obstruction as response
to stimulus, bronchial hyper reactivity. (300 million people, F > M)

o S&S: episodic with acute exacerbations, attacks last minutes to hours with complete recovery.
o Wheezing, productive or non-productive cough, dyspnea, chest discomfort, tightness that
leads to air hunger and eosinophilia
o Status asthmaticus – life threatening bronchospasm that persists despite treatment.
 Inquire – previous intubation or admit to ICU d/t asthma? > 2 admits in last year? Co-
existing disease? Any of these elevate risk.
 Treatment:
 β2 agonist (inhaled or nebulized) admin q 15-20 min for several doses w/o
significant hemodynamic effects (poss adrenergic overstimulation)
 Corticosteroids – early as onset takes a few hours
o Cortisol 2 mg/kg IV followed by 0.5 mg/kg/hr. infusion
o Methyl prednisone 60-125 mg IV q 6 hrs.
 Oxygen to maintain SaO2 > 90%
 Mag Sulfate and Leukotriene inhibit may also help

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  Ventilation:
 FEV1 or Peak Exp flow rate < 25% of normal leads to ↑CO2 & resp fail
 CO2 > 50 despite treatment a sign of resp fatigue= intubation & vent
 High peak airway pressures may be required to deliver acceptable Vt
 High gas flows allow shorter insp and longer exhalation
 Require prolonged exhalation to prevent auto PEEP
 If swelling too great and airways plugged with mucus, consider GETA with
VA to produce bronchodilation
o Asthma Pathogenesis:
o Genetic and Environmental factors (viruses, occupational exposure, allergens) contribute to
initiation and continuance.
o Stimuli provoking asthma:
 Allergens (greatest risk with Atopy: genetic predisposition toward the development of
immediate hypersensitivity reactions against common environmental antigens)
 Rhinitis urticarial, eczema often present, IgE increased, + wheal and flare skin
rxn to intradermal injection of antigens
 ASA, BB, some NSAIDs, sulfating agents (stimulation of muscarinic receptors can
facilitate mediator release from mast cells providing a positive feedback loop for
sustained inflammation and bronchoconstriction
 Infections – resp viruses
 Exercise – usually follow exertion rather than during
 Emotional stress – endorphins and vagal mediation
o Diagnosis:
o Spirometry: FEV1 and MMEF (maximum mid-expiratory flow) directly measure severity of
expiratory airflow obstruction
 Asthmatic: FEV1 < 35% of normal, MMEF 20% or less of normal
 During attacks, FRC may increase substantially
 Flow-Volume loop: show characteristic downward scooping of exp limb of loop. If
inhaled or exhaled portion of loop is flat, distinguishes wheezing caused by airway
obstruction (foreign body, tracheal stenosis, mediastinal tumor) from asthma
o Aterial Blood Gas Analysis: Hypocarbia and resp alkalosis are most common with asthma
(tachypnea).
 As exp airflow obstruction increases, VQ mismatch results in ↓ PaO2 on RA,
 PaCO2 likely ↑ when FEV1 < 25%, skeletal muscle fatigue contributes to hypercarbia
o X-ray and ECG:
 X-ray – demonstrate hyperinflation of lung vs pneumonia, CHF
 ECG – acute R heart failure or ventricular irritability during asthmatic attack
o Differential Diagnosis: Viral tracheobonchitis, sarcoidosis, RA with bronchiolitis and
extrinsic compression (thoracic aneurysm, mediastinal neoplasm) or intrinsic compression
(epiglottitis, croup) of upper airway.
History of recent trauma, surgery intubation may be present, mimic’s asthma (upper
airway obstruction)
CHF or pulmonary edema (embolus) wheezing may be characterized as cardiac
asthma

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o Treatment:
o Prevent and Control bronchial inflammation – altho bronchodilators may mask inflammation
by relieving symptoms and allow continued exposure to allergens
o Controlling Agents: modify the airway environment so acute airway narrowing is less
frequent
 Inhaled and systemic corticosteroids, theophylline and anti-leukotriene
o Relieving Agents: for acute bronchospasm
 B agonists (albuterol) and anticholinergics (ipratropium, atropine, glycopyrrolate) may
be used together
o PFT’s useful for monitoring response to treatment (FEV1 > 50% - usually no symptoms)

o Management of Anesthesia:
 Bronchospasm occurs in 0.2-4% of all GETA with asthmatics
 Pathophys mechanisms: ↓ cough reflex, impaired mucociliary fxn, ↓palatopharyngeal
muscle tone, ↓ diaphragmatic fxn, ↑ fluid on airway wall, direct mech airway
stimulation, PSNS activation, release of pain NT (Substance P and neurokinins)
o Pre-op:
 Evaluate severity: age of onset, triggers, hospitalizations, allergies, cough, sputum
characteristics, current meds, anesthetic history
 Auscultation for wheezes or crepitations
 Blood eosinophil counts often parallel the degree of airway inflammation
 PFT’s before & after bronchodilators
 Chest physiotherapy, Abx, bronchodilator tx may improve reversible components of
disease
 Pre-op course of oral corticosteroids may be helpful
o Intra-op
 D/t irritable airway with mech stimulation, regional anesthesia attractive
 Propofol > Thiopental for airway reflex suppression
 Ketamine produces smooth muscle relaxation but ↑ secretions
 VA and opioids suppress cough reflex and allow deep anesthesia
 LMA less stimulating than ETT
 Provide humidification and warming of gases, liberal fluids IV to thin airway
secretions
 Extubate deep while airway reflexes suppressed, or admin IV lidocaine/inhaled
bronchodilators if necessary to extubate light
o Intraoperative Bronchospasm
 Consider differential diagnosis of wheezing before treating with B2 agonist
 Mechanical obstruction (Kinking, secretions, overinflated ET cuff), Inadequate
depth of anesthesia (active exp effort, ↓ FRC)
 Endobronchial intubation, pulmonary aspiration, pulmonary edema, pulmonary
embolus, pneumothorax, acute asthmatic attack.
 If bronchospasm persists despite deeper anesthesia and B2 agonist, use corticosteroids.

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Chronic Obstructive Pulmonary Disease: common condition mainly r/t smoking, respiratory infection,
occupational exposure to dust, genetic factors (α1 antitrypsin)

 1. Pathologic deterioration in recoil of lung parenchyma,

 2. Pathologic changes that decrease the rigidity of the bronchiolar wall and predispose them to
collapse during exhalation,
 3. Increase in gas velocity in narrowed bronchiole which lowers the pressure inside the bronchili and
further favors airway collapse.
 4. Active bronchospasm and obstruction resulting from increased pulmonary secretions and
 5. Destruction of lungparenchyma, enlargement of air sacs and development of emphysema.
o Signs & Symptoms: chronic productive cough with progressive exercise limitations and expiratory
airflow obstruction, tachypnea, decreased breath sounds, expiratory wheezes.
o Bronchitis = chronic productive cough, wheezing mimics asthma and with reversible
bronchospasm is termed asthmatic bronchitis
o Emphysema = dyspnea with ADL’s (FEV1 < 40%)
o Diagnosis:
o PFT: ↓FEV1/FVC, ↓ FEF (25-75%), ↑ RV, ↑FRC &TLC = greater work of breathing at
higher lung volumes
o Chest X-ray: Hyperlucency (arterial vascular deficiency in lung periphery) hyperinflation
(flattening of diaphragm, loss of dome shape), bullae (bubbles) = emphysema, Bronchitis
rarely diagnosed from x-ray
o COPD Classification based on post bronchodilator therapy FEV1 measurements
 0=at risk; 1=mild COPD; 2=Moderate COPD; 3=Severe COPD; 4=Very severe COPD
o Treatment: designed to relieve symptoms and slow Dz progression
o Smoking cessation and O2 supplementation
 Smoking cessation diminishes bronchitis symptoms and eliminates further loss of lung
function
 O2 therapy recommended for PaO2 < 55, Hct > 55%, cor pulmonale present to
achieve paO2 of 60-80, relief of arterial hypoxemia is more effective than any known
drug therapy in decreasing pulmonary vascular resistance and pulmonary HTN and
preventing erythrocytosis
o Drug Therapy
 Bronchodilators – alleviate symptoms, little change to PFT (B2 agonists)
 Anticholinergics, corticosteroids, Abx, vaccinations, diuretics, physical training
o Lung volume reduction surgery – removal of over distended poorly functioning lung tissue
 Median sternotomy or VATS (video assisted thoracoscopic surgery with DLT
 1. ↑ elastic recoil = ↑ expiratory airflow
 2. ↓ in hyperinflation = improved diaphragmatic and chest wall mechanics
 3. ↓ inhomogeneity of regional ventilation and perfusion = ↑ alveolar gas exchange
and effectiveness of ventilation

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o Management of Anesthesia
o Preoperatively – Hx reveals accurate assessment of postop complications
 Poor exercise tolerance, smoking, chronic productive cough, wheezing,
unexplained dyspnea with diminished breath sounds, wheezing, prolonged
expiratory phase
 Risk Factors for Post-op Complications
 Patient related – age > 60, ASA 2 or greater, CHF, COPD, smoking
 Procedure related = emergency surgery, Abdominal or thoracic, head and neck,
neuro, vascular/aortic aneurysm surgeries, prolonged duration of anesthesia,
General anesthesia
 Test predictors – albumin of < 3.5 g/dL
 Smoking Cessation (60 pk yr hx = 2x risk of pulmonary complication and 3x risk of
pneumonia)
 Short term effects = carbon monoxide diminishes within 12 hours of cessation
(PaO2 50% saturated moves from 22.9 to 26.4 on oxy-hgb curve) and
carboxyhgb ↓ from 6.5 to 1%
 Long term effects – slow improvements in cilliary and small airway fxn,
decreased sputum production, normal immune response returns in about 6
weeks
 Nutritional Status – low serum albumin level (<3.5 mg/dL) is powerful predictor of
postop pulmonary complications – prolonged postop air leaks in patients after lung
surgery
o Intraoperative
 Regional Anesthesia via peripheral nerve blockade with no need for sedative or
anxiolytic drugs carry a lower risk of pulmonary complication
 Spinal vs General controversial about decrease in risk
 General Anesthesia (6-8 ml/kg, 6-10 breaths per min)
 Volatile agents (Sevo & Des) rapidly eliminated
 Sevo- bronchodilation in asthmatic
 N20 may increase bullae to rupture causing pneumothorax
 TIVA with propofol and Remi nice option, both short acting
 Opioids prolong ventilator depression
 Air trapping may be detected during mechanical ventilation
o 1. Capnography still up sloping at time of next breath
o 2. Expiratory flow has not reached baseline before next breath
o 3. Direct measurement of the resulting PEEP
o 4. Patient may be disconnected from vent briefly to observe if BP ↑
significantly when PEEP is eliminated
o Postoperative
 Lung Expansion Maneuvers (deep breathing exercises, incentive Spirometry, chest
physiotherapy, positive pressure breathing techniques)
 Mechanical Ventilation
 If PaCO2 ↑ for prolonged period, do not correct quickly to cause metabolic
alkalosis that may cause cardiac dysrhythmias, CNS irritability or seizures
 Chest Physiotherapy
 Exercises taught pre-operatively, postural drainage, vibration therapy to
dislodge mucus plugs from peripheral airways

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Respiratory Failure:

 Acute Respiratory Failure – PaO2 < 60 with absence of R to L intracardiac shunt, PaCO2 > 50
mmHg with absence of respiratory compensation for metabolic alkalosis
o Abrupt ↑ in PaCO2 results in ↓ pH
o ↓ in FRC and lung compliance, ↑ PVR and pulmonary HTN are likely to develop if RF
persists

ARDS: Pathogenesis: inflammatory injury to the lung (pneumonia, gastric aspiration, pulmonary contusion,
fat emboli, near drowning, inhalational injury; sepsis, trauma with shock, multiple blood transfusions, CPB,
drug overdose, acute pancreatitis)
 Influx of protein rich edema fluid into alveoli as a result of ↑ alveolar capillary
membrane permeability
 Usually resolves completely OR it may lead to fibrosing alveolitis with persistent
arterial hypoxemia and decreased pulmonary compliance
o S & S: arterial hypoxemia that is resistant to supplemental oxygen, pulmonary HTN, PA
vasoconstriction leading to right heart failure, sepsis, death
o Diagnosis: diffuse infiltrates on chest x-ray from pulmonary edema, PaO2/FiO2 ration of <
200 mmHg or in less severe cases, < 300 mmHg

o Treatment: 1. Correct hypoxemia, 2. Remove excess CO2, 3. Secure patent upper airway
 O2 supplement, tracheal intubation, mechanical ventilation, PEEP, optimize
intravascular fluid volume, diuretic therapy, inotropic support, removal of secretions,
control infection, nutritional support, inhaled β agonists

Pulmonary Thromboembolism:

o Diagnosis: difficult due to extensive differential diagnosis (MI, pericarditis, CHF, COPD,
pneumonia, pneumothorax, pleuritis, anxiety/hyperventilation, thoracic aorta dissection)
 Acute dyspnea, tachypnea, pleuritic chest pain, rales, non-productive cough,
tachycardia, hemoptysis, fever
o Treatment:
 Anticoagulation, thrombolytic therapy, IVC filter and surgical embolectomy
o Anesthetic Management:
 Support vital organ fxn, minimize anesthetic induced myocardial depression, monitor
arterial pressures and CVP
 Use phosphodiesterase inhibitor (amrinone/milrinone) to increase myocardial
contractility and dilate the PA

Fat Embolism:
Occurs 12-72 hrs after long bone fracture, with acute pancreatitis, CPB, parenteral infusion of lipids,
liposuction
o Hypoxemia, mental confusion, petechiae

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Drugs Used Affecting Respiration and Ventilation:
Β2 Agonists: stimulate β2 receptors in the tracheobronchial tree to cause bronchodilation; may also cause
tachycardia, tremors (d/t chronic β2 stimulation in skeletal muscles), dysrhythmias, hypokalemia; may also
reduce infections as they decrease the adhesion of bacteria to airway epithelial cells
Albuterol: bronchial and uterine smooth muscle relaxation, presence of ETT ↓ drug delivery by 50-
70%, may need 10 puffs rather than 2-4 for same effect, may cause acute hypokalemia, hyperglycemia,
hypomagnesaemia
Corticosteroids: decrease airway inflammation, reduce airway hyper-reactivity
Cortisol: (2 mg/kg IV followed by 0.5 mg/kg/hr infusion)
Methylprednisolone: (60-125 mg IV q 6 hrs)

Opioids: suppress the cough reflex and aid in achieving deep anesthesia; prolonged effects can lead to
postop resp depression or large doses may lead to chest muscle rigidity
Receptors: CNS - periaqueductal matter of brain stem (amygdala, corpus striatum, hypothalamus) &
Spinal cord (substantia gelatinosa) – dorsal horn, 1st site in CNS for sensory info integration
Fentanyl family –much less, if any, histamine release than other opioids
↑CO2 threshold and shift CO2 curve to right, ↓RR & VT (dose related), ↓ cough reflex
Remifentanyl: (0.5-1 mg/kg/min) – ultra-short activity, does not accumulate, hydrolysis by non-
specific plasma esterase’s, ↓ requirements with use of midazolam
Volatile Anesthetics: produce a depth of anesthesia that depresses hyperreactive airway reflexes sufficiently
to permit tracheal intubation without precipitating bronchospasm, ALL decrease respiratory responsiveness
to hypoxia, hypercarbia and decrease min ventilation by ↓ VT and ↑ RR, potentiate neuromuscular blockade
to varying degrees, cerebral vasodilators (↑CBF & ↑ ICP), ↑ latency & ↓ amplitude of SSEP monitoring
Sevoflurane – (MAC 2.2%) less pungent, less likely to cause coughing which may lead to
bronchospasm, preservative is H2O, 3-5% metabolized by hepatic microsomes, depresses baroreceptor
activity more than other VA, produces Compound A (nephrotoxic)
Dose depend ↓ MAP, ↑ HR, ↓ SVR & CO, ↓ airway resistance
Ketamine (1-2 mg/kg) can produce smooth muscle relaxation (bronchodilation) and contribute to decreased
airway resistance, especially in patients who are actively wheezing
Noncompetitive NMDA receptor blocker (hippocampal formation and pre-fontal cortex), interacts
with opioid, monoaminergic & muscarinic receptors and voltage sensitive Na & Ca ++ channels to produce
intense analgesia and sub-anesthetic concentrations, produces amnesia, analgesia, sensory loss, paralysis
without actual LOC.

230
 High hepatic clearance, peaks 1 min IV, 5 min IM, high distribution to tissues
No significant ventilator depression, upper airway reflexes remain intact, MOA of bronchodilation
unclear (may be inhibition of catecholamine reuptake)
Anticholinergics: decrease vagal tone by blocking muscarinic receptors in airway smooth muscle (therefore
blocking PSNS effects: salivation, lacrimation, urination, defecation, erection, bradycardia, bronchial
constriction, pupillary constriction), sedative, antisialogogue and mydriatic effects

Atropine: (<0.1 mg/kg or 0.5-1 mg q 3-5 min for bradycardia) more potent bronchodilator than
Glyco, more tachycardia, crosses BBB
Glycopyrrolate: (0.1-0.2 mg) most potent antisialogogue, does not cross BBB

RESPIRATORY CHANGES BETWEEN PEDIATRICS, ADULTS AND GERIATRICS

PEDIATRICS
Atelectasis is more likely to occur in the infant, ↓number of alveoli and ↓ FRC, but the FRC/TLC ratio is
equal to adults
Chest wall is very compliant, creating a problem. If neonates try to overcome atelectasis by deep breathing -
the chest wall retracts inward preventing ↑ airway pressure or tidal volume
MV, RR, and alveolar ventilation are all ↑ in neonates compared to adults. MV/FRC is ↑. This along with
greater distribution of CO to vessel rich groups explains the increased speed of induction in neonates and
adults.
By the Law of Laplace, as the radius of the alveolus decreases, surface tension increases. Surfactant
decreases surface tension which allows small neonatal alveoli to remain open.
Narrowest part of the infant airway is the cricoid, compared to the glottic opening in adults. Small changes
in airway diameter result in large changes in resistance to flow - why you want a leak with your ETT or the
patient is at risk for subglottic edema
Large occiput = natural sniffing position
ADULTS
% VT in normal breathing adult that is dead space = 33%, under General Anesthesia = 40-60%
Dead space increases with increased age, positive pressure ventilation (d/t circuit), PE and lung Dz
Estimating PaO2 from FiO2 – multiply % FiO2 by 5 (50% x 5 = 250 mmHg) and to estimate PAO2 from
FiO2 – multiply %FiO2 by 6 (50% x 6 = 300 mmHg)
If SaO2 90%, PaO2 ~ 60 mm Hg

231
CaO2 – CvO2 = 5 ml O2/100 ml blood (normal gradient between O2 carrying of arterial vs venous blood),
1.34 ml O2 carried by each gm. saturated Hgb, Dissolved O2 = 0.003 x PaO2 (100 x 0.003 = 0.3 ml)
Maximum Total O2 = Hgb-bound O2 + dissolved O2 or 1.34 ml O2/g Hgb (g Hgb) + PaO2 (0.003)

Oxy-Hgb Dissociation Curve:

Left shift: evidenced by↓ P50 caused by ↓temp, ↑pH, ↓PaCO2, ↓2, 3-DPG, fetal hgb, carboxyhgb, and
methemoglobin
Right shift: evidenced by ↑P50 caused by ↑temp, ↓pH, ↑PaCO2, ↑2, 3-DPG, sickle cell disease
Shift in oxyhemoglobin dissociation curve caused by CO2 entering or leaving blood is Bohr Effect
Haldane Effect - Describes how changes in PaO2 alter PaCO2 (↑PaO2 in pulmonary capillaries causes CO2
blood dissociation curve to shift right), Facilitates unloading of CO2 by blood
Oxygen delivery to tissues based on CO, hgb concentration, abnormal hgb
Oxygen consumption ↑ by MH, thyroid storm, fever, shivering
Decreased mixed venous O2 due to: Decreased CO, anemia, increased O2 consumption
Best assessment of adequacy of CO: Mixed venous oxygen tension (saturation)
↓ MvO2 2̊ ↑demand reflects inadequate tissue perfusion
In absence of hypoxia or severe anemia, MvO2 (or saturation) is best measurement for adequacy of CO
Methemoglobinemia - Can be caused by nitrate poisoning (NTG overdose) or toxic reaction to prilocaine
Treatments: O2 therapy, Methylene blue: 1-2 mg/kg over 5 minutes IV, Ascorbic acid
GERIATRICS
Closing capacity and closing volume increase; closing volume > FRC after about age 45
Residual volume and FRC are increased
VC, TLC, and PaO2 progressively decrease in small increments after age 20
Structural changes Functional Changes
↑ central airway size ↓ resp center sensitivity
↓ small airway diameter ↓ effectiveness coughing, swallowing
↓ elastic tissue, reorientation of elastic fibers ↑ lung compliance; ↓ chest wall compliance
↑ amount of collagen ↓ functional alveolar surface area
↓ respiratory muscle strength ↓ ERV & VC; ↑ RV & FRC. No TLC
↑ chest wall stiffness ↑ RV/ TLC & FRC/TLC ratios
↓ chest wall height; ↑ A-P diam ↑ closing volume & capacity
↑ A-a gradient & ↓ PaO2

232
Age-related ↓ arterial oxygenation
Change in physical properties of lungs 2̊ V/Q mismatch
Elderly pts need supplemental oxygen perioperatively
↑likelihood of transient apnea when given opioids or benzos
↑threshold stimulus for vocal cord closure leads to ↑aspiration risk

Bernoulli – The Bernoulli principle states that as the speed of a fluid increases, the pressure exerted by the
fluid decreases. This phenomenon is called the Bernoulli Effect (the Bernoulli Effect provides the lift for
airplanes).
Bernoulli's principle states that in fluid flow, an increase in velocity occurs simultaneously with decrease in
pressure. This principle is a simplification of Bernoulli's equation which states that the sum of all forms of
energy in a fluid flowing along an enclosed path (a streamline) is the same at any two points in that path. It is
named after the Dutch/Swiss mathematician/scientist Daniel Bernoulli. In a fluid flow with no viscosity, and
therefore one in which a pressure difference is the only accelerating force, it is equivalent to Newton's laws
of motion. It is important to note that the only cause of the change in fluid velocity is the difference in
pressures either side of it. It is very common for the Bernoulli Effect to be quoted as if it states that a change
in velocity causes a change in pressure. The Bernoulli principle does not make this statement.
Venturi effect: This is a consequence of the Bernoulli principle. It states that the pressure drop induced by
the increase in velocity of a fluid passing through a narrow orifice can be used to entrain air or a nebulizer
solution. The Venturi mask is an application of the Bernoulli principle. It is named after Giovanni Battista
Venturi, (1746–1822), an Italian physicist. In a Venturi mask type system, 100% oxygen flows into the
wider area beyond a narrow orifice. Because of the narrowing the oxygen speeds up and the pressure drop at
that point is below atmospheric pressure and room air is drawn to this low pressure point, hence diluting the
100% oxygen to a calibrated value set by the nozzle. The nozzle has a varying aperture open to room air that
sets the entrainment ratio and hence the inspired concentration given to the patient. Another useful
application is the Venturi meter. A Venturi meter is a device that can allow determination of a velocity
(flow) in a narrowed region and then can be graphically displayed. Additionally, Venturi tubes are the basis
for Venturi injectors which may be used in providing suction or for producing diluted gas mixtures.
Surface Tension: Substances that have greater intermolecular attractions have greater surface tensions.
Molecules in the liquid state are attracted to all neighboring molecules by intermolecular forces. For
molecules deep within the sample, these forces operate in all directions, and, therefore, cancel each other out.
The forces bind the molecules into a compact state of matter, but there is no net force on any of the interior
molecules. This is not the case for the molecules near the surface, however. A molecule near the surface
experiences attractive forces to all of the surrounding surface molecules and with the molecules below.
However, there are no balancing attractions from above. This collection of unbalanced forces creates a
“skin” on the surface of a liquid. The attractive strength of this skin is called the surface tension. Surface
tension is responsible for many common experiences with water. For example, bugs can walk on water
because the force due to the bug’s weight is less than the surface tension of water. Water has a high surface
tension, and is, therefore, a very cohesive liquid. That means water molecules have a strong attraction for
other water molecules. Surface tension and cohesion causes water to readily form spherical drops when
falling through air and to coalesce into puddles on a surface. This high cohesion of water is also at least
partly responsible for the tendency of the lungs in premature infants to collapse.

233
Ideal Gas: The ideal gas law states the product of volume (V) and pressure (P) is equal to the product of a
constant (R, the universal gas constant), the amount of gas (n) and the Kelvin temperature. The ideal gas law
applies exactly only to ideal gases (which don’t exist). However, real gases approach ideal gas behavior as
pressure decreases and temperature increases. The ideal gas law is most useful when the problem describes
only a single state (temperature, pressure, and/or volume). The empirical gas laws are useful for changing the
state of a gas (P, n, V, and/or T change).
PV = nRT; where P = pressure; V = volume; n = Mass or number of gas molecules;
R = gas constant (8.317J / mole K); T= absolute temperature
Law of Mass Action – Basically states that the rate of a chemical reaction is directly proportional to the
molecular concentrations of the reacting substances. More formally, The Law of Mass Action states that the
rate of any chemical reaction is proportional to the product of the masses of the reacting substances, with
each mass raised to a power equal to the coefficient that occurs in the chemical equation. This law was
formulated over the period 1864–79 by the Norwegian scientists Cato M. Guldberg and Peter Waage. This
law was useful for obtaining the correct equilibrium equation for a reaction, but the rate expressions it
provides are now known to apply only to elementary reactions. The law of mass action is universal,
applicable under any circumstance. However, for reactions that are complete, the result may not be very
useful. Mathematically the mass action law can be expressed by using a general chemical reaction equation
in which reactants A and B react to give product C and D
{a A + b B --> c C + d D; where a, b, c, d are the coefficients for a balanced chemical equation}.

The mass action law states that if the system is at equilibrium at a given temperature, then the following ratio
is a constant.

[C]c [D]d
------------- = Keq
a b
[A] [B]

The square brackets "[ ]" around the chemical species represent their concentrations. This is the ideal law of
chemical equilibrium or law of mass action. The units for K depend upon the units used for concentrations.
Source: [Link]

How the mass action law is applicable in anesthesia: The Law of Mass Action is applicable to pharmacology,
since it is assumed that a drug interacts with a single receptor in a reversible manner:

Where, L is the ligand concentration, R is the unoccupied receptor concentration and LR is the concentration
of ligand-receptor complex; and the k's are proportionality constants: k1 is the association rate constant and
k2 is the dissociation rate constant, at equilibrium:

234
Which is the equation for a simple hyperbolic function. This equation can be rearranged to yield a scatchard
plot:

While application of the Law of Mass Action to ligand-receptor interactions is conceptually useful, it is
important to remember that it depends upon several assumptions. First, the formation of the [LR] complex
must be completely reversible. Second, the ligand and receptor must exist in only 2 states, bound or
unbound. Finally, ligand binds to each receptor with equal affinity and binding does not alter subsequent
affinity.

Source: [Link]

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 Asthma

 Disease characterized by chronic airway inflammation, reverse el expiratory airflow obstruction in

response to various stimuli and bronchial hyperreactivity
 General anesthesia can contribute to increased airway resistance d/t depression of the cough reflex,
impairment of mucociliary function, reduction of palatopharyngeal muscle tone, depression of
diaphragmatic function, and increase the amount of fluid on the airway wall.
 Direct mechanical airway stimulation by endotracheal intubation, PSNS activation, and/or release of
substance P and other neurokinins may also cause increased airway resistance
 Pre-op
o Assess severity of disease, current medical management, and if any changes need to be made
to optimize the patient prior to surgery
o Physical assessmentuse of accessory muscles for breathing, auscultation, eosinophil counts
often parallel the degree of airway inflammation
o PFT’s before and after bronchodilator therapy may be indicated in pts scheduled for major
surgery
 FEV1 is decreased in asthma (obstructive disorder)
o Baseline ABG’s if there is a question of adequate ventilation or oxygenation
o Continue anti-inflammatory and bronchodilator therapy until the time of induction
 Intra-op
o Very important to suppress airway reflexes with induction as stimulation can cause
bronchoconstriction, use of IV lidocaine 1-1.5 mg/kg 1-3 min before DL, use of sevo when
mask ventilating prior to DL
o Consider the increase in the viscosity of airway secretions when giving anticholinergic drugs
o LMA is less likely to cause bronchoconstriction than an ETT
o Maintaining adequate hydration to help prevent less viscous airway secretions
o Choose drugs with little or no histamine release
o Deep extubation when possibleremoving ETT when anesthetic level is still sufficient
enough to suppress the airway reflexes

o Bronchospasm
 Often caused by other factors than asthma
 Rule out obstruction of circuit, ETT, and airway before administering bronchodilator
therapy
 Corticosteroid administration if bronchospasm is not responsive to β2 agonist
 Volatile gases, sevo better than des or iso, to break severe bronchospasm
 Post-opcontinue pre-op drug regimen and PO/IV fluids
 Emergency surgery in asthmatic ptdilemma of RSI possibly triggering bronchospasm along with
insufficient time to give bronchodilator therapy. Regional anesthesia preferred if possible depending
on surgical site and medication history.

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 COPD

 Common condition, mainly related to smoking

 Characterized by progressive development of airflow limitation that is not fully reversible
 Causes
o Pathologic deterioration in elasticity or recoil within the lung parenchyma
o Pathologic changes that decrease the rigidity of the bronchiolar wall and thus predisposing
them to collapse after exhalation
o Increase in gas velocity in narrowed bronchiole, which lowers the pressure inside the
bronchiole and further adds to airway collapse
o Active bronchospasm and obstruction resulting from increased pulmonary secretions
o Destruction of lung parenchyma, enlargement of air sacs and development of emphysema
 Risk factors
o Cigarette smoking
o Respiratory infection
o Occupational exposure to dustespecially coal mining, gold mining, and the textile industry
o Genetic factors α1 antitrypsin deficiency
 PFT’s
o Results will show a decrease in the FEV1/FVC ratio and an even greater decrease in the
forced expiratory flow between 25-75% of vital capacity may also see and increased residual
volume and normal to increased FRC and total lung capacity.

Stages of COPD and Spirometry Classifications

Stage I: Mild COPD Mild airflow limitation (FEV1/FVC < 70%; FEV1 >80% predicted)

 Sometimes, but not always, chronic cough and sputum production. At this stage, the individual may
not be aware that his or her lung function is abnormal.

Stage II: Moderate COPD Worsening airflow limitation (FEV1/FVC < 70%; 50% < FEV1 < 80%
predicted)

 Shortness of breath typically developing during exertion. This is the stage at which patients typically
seek medical attention because of chronic respiratory symptoms or an exacerbation of their disease.

Stage III: Severe COPD Further worsening of airflow limitation (FEV1/FVC <70%; 30% < FEV1 < 50%
predicted)

 Greater shortness of breath, reduced exercise capacity, and repeated exacerbations, which have an
impact on patients’ quality of life.
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 Stage IV: Very Severe COPD Severe airflow limitation (FEV1/FVC < 70%; FEV1 <30% predicted) or
FEV1 < 50% predicted
Plus chronic respiratory failure (i.e.aO2 < 60 mmHg and/or PCO2 > 50 mmHg).

 Patients may have very severe COPD even if the FEV1 is > 30% predicted, whenever this
complication is present. At this stage, quality of life is very appreciably impaired and exacerbations
may be life threatening.

Pre-op

 Review PFT’s
 Encourage smoking cessation
 Optimize nutritional status

Intra-op

 Regional anesthesia when possible

 General anesthesia
o Sevo and des preferred d/t their rapid elimination also help with bronchodilation
o Des may cause irritation of bronchi and increased airway resistance
o Emergence can be significantly prolonged d/t airway obstruction as air trapping also traps
inhalational agents
o TIVA with propofol or Remifentanil
o Nitrous can be used in combo with volatile, there is potential for passage of nitrous into
pulmonary bullae, which could lead to enlargement and rupture causing a pneumothorax.
Nitrous will also limit the amount of O2 that can be inspired.
o Inhaled anesthetics may attenuate regional HPV and produce more shunting
o Long acting opioids can be associated with prolonged ventilator depression
o Tidal volumes of 6-8 mL/kg with slow inspiratory flow rates minimize the likelihood of
turbulent airflow and help maintain optimal ventilation/perfusion.
o Slower resp rates, 6-10 allow more time for exhalation
o Air trapping
 Seen on capnography as up-sloping
 Expiratory flow may not reach zero before initiation of the next breath
 Direct measurement of resulting PEEP can be monitored on newer ventilators
 Disconnect pt from ventilator briefly and observe if BP increases slightly as PEEP
would be eliminated
Post-op

 Lung expansion maneuversdeep breathing exercise, IS, chest PT, and positive pressure breathing
techniques
 Continued mechanical ventilation during immediate post-op period may be necessary in severe
COPD pt who has had major abdominal or intrathoracic surgery
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 Bronchiectasis

 Chronic suppurative disease of the airway, if severe, may cause airflow obstruction similar to that
seen in COPD
 Causes chronic productive cough with purulent sputum and accounts for a number of cases of
massive hemoptysis
 Characterized by localized, irreversible dilation of a bronchus caused by destructive inflammatory
processed involving the bronchial wall
 Highly susceptible to recurrent or persistent bacterial infection d/t impaired mucociliary activity and
pooling of mucus in dilated airways
 Once bacterial super infection is present, it is nearly impossible to eradicate

Anesthetic management

 Optimize patient prior to surgery

 Use of DLT to isolate infected area and prevent infection in non-infected areas of the lungs
 Avoid instrumentation of the nares d/t the high incidence of chronic sinusitis in these patients

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Pediatric Anesthesia Overview
Not little adults

Potential pitfalls
 Respiratory complications were 50% of pediatric malpractice claims in 70s & 80s
 Practice advances, e.g., SpO2 & ETCO2, may be reflected in liability trends
 Claims from 1990 to 2000 reviewed in detail
 Logistic regression evaluated factors associated w/death/brain damage vs claims for less
severe injuries

Closed claims analysis: pediatrics

 1973-2000: ↓ claims for death/brain damage & respiratory events, particularly for inadequate
ventilation/oxygenation
 Claims for death (41%) & brain damage (21%) were dominant injuries in 1990s
 50% of claims in 1990-2000 involved patients ≤ 3 yrs
 20% were ASA III-V
 C-V events (26%) & respiratory events (23%) were most common damaging events
 Death/brain damage continued to be dominant injuries in pediatric anesthesia malpractice claims in
1990s
 C-V events joined respiratory events as major source of liability

Preoperative evaluation
 On every patient:
 Review PMH, PSH, family history
 Chart review
 Physical exam
 When appropriate
 Preop therapy to optimize health status before anesthesia
 Consider emotional state of child and family
 Determine if preoperative/pre-procedure sedation needed

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Preoperative preparation
 Anesthesia/surgical/ nursing teams need to use appropriate & creative techniques to prepare child and
family
 Videotapes, booklets, hospital tours, web sites
 Logistical difficulties due to number of outpatient surgeries/same day admissions
 Not optimal to meet pt in OR
 Provider needs to understand proposed procedure
 Plan monitoring, selection of drugs/techniques
 Anticipate surgical needs for pt positioning, muscle relaxation
 Pt’s needs for fluids/blood/analgesics
 Complex cases
 Surgical & anesthesia teams need to formulate preop plan & explain to parents & child
 If consult needed, explain your concerns w/consultant to focus their attention on specific issue
 Fasting
 Guidelines for infants reflect avoidance of dehydration, hypoglycemia
 Children may still eat or drink despite need for NPO
 Risk for aspiration
 Obese, previous esophageal surgery, difficult intubation, hiatal hernia
 Psychological support, preop sedation
 Never neglect psychological support, even if pt/family seem calm
 Premed may not be used if child critically ill or very cooperative
 Once any medication given, child must be monitored
 Review postop care
 ICU?
 Effects of continuous caudal or epidural blocks
 Single-shot caudal or regional nerve block

Informed consent
 Risks & benefits of anesthetic procedure must be presented in clear terms
 Reinforce that key parameters, e.g., temperature, heart rate & breath sounds, SpO2, ETCO2,
will be monitored continuously
 Invasive monitors placed after induction
 Explain in unhurried manner
 Answer questions
 Interpreter for non-English speaking families/pts
 Reassure parent/child that anesthesia provider will be with patient continuously
 Child’s developmental status & level of understanding determine how to discuss anesthesia, surgery,
postop care
 Children need assurance that they won’t awaken during procedure & that they will wake up at
conclusion
 Possibility of postop pain & relief provided need to be clearly presented

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OR & monitoring
 Re-examine chart before inducing anesthesia
 Check ID bracelet, especially if anesthetizing team different than preop evaluation team
 Equipment for induction & maintenance of anesthesia/suction/monitors must be functioning &
reliable
 Equipment must be checked by anesthesia team caring for child
 Degree of monitoring adjusted to child’s underlying condition & planned surgery
 Always need standard monitors
 EKG, temp, FiO2, SpO2,, ETCO2, BP
 Observe pt’s color, chest movements, listen to heart/breath sounds, palpate arterial pulse, skin
temp
 IV unless very brief, noninvasive procedure
 Invasive monitors
 May be needed for major surgery if extensive blood loss or fluid shifts anticipated or pt
medically unstable
 Foley catheter
 Monitoring u.o. important in long operations, procedures w/potential for significant blood
loss, variations in BP/fluid balance anticipated, induced hypotension
 Do not let monitors distance you from patient
 Relying totally on mechanical monitors to detect clinical abnormalities is dangerous
 Focus must always be on child & surgical field
 Monitors may fail
 If provider focuses on monitor rather than attending directly to pt, patient may suffer
 Reason precordial stethoscope is so useful
 Strong heart tones in face of failed monitors provides assurance that child is likely not
in severe trouble

Induction & maintenance of anesthesia

 Infants have more rapid uptake of inhalation agents than adults
 Gradual changes in inspired concentration of agent
 Responses to oral & IV medications different than adults
 Dilute and titrate drugs carefully to given endpoint, e.g., μg/kg
 In stable child, may induce w/precordial stethoscope & SpO2
 Remaining monitors applied after induction
 Avoids prolonged preparation phase when child may become upset
 If child critically ill, will need at least standard monitors on before induction
Clinical monitors
 Sight
 Constant observation of chest excursion
 Depth/symmetry
 Color of nail beds, oral mucosa, capillary refill
 Vital info about V/Q
 Observation of surgical field, muscle relaxation, depth of anesthesia, problems related to
surgery
 Surgical retraction or field may cause venous obstruction or difficulty ventilating
242
Key Points in Pediatrics
Physiologic & Anatomic Differences: Adults vs Peds
 CV
 To compensate for ↑ O2 consumption (6 ml/kg/min v 3 ml/kg/min) & fetal hgb that binds
more tightly (P50 of 19 vs 27), infant CO is 30-60% > adult
• LV thin, poorly compliant
• ↓ contractile mass & ↓ extent & velocity of shortening
• CO is rate dependent
 Oxygen content of blood
• Neonatal hgb = 17
• Drops to 11 at 3-6 mo
• Physiologic anemia occurs at 1.5-3 mo as HbF replaced by HbA
Infant CV system
 1-5 to 3 mo
 Minimal acceptable hgb ~ 10
 Pts w/ L to R shunt prone to CHF at this time
 From birth to 2 wks, hgb ≤ 13.5 considered below normal
 If hct  65, permanent brain damage due to hyperviscosity can result
 May require exchange transfusion

Age-dependent parameters
Blood vol SBP HR RR

Neonates 0-30 d 85 ml/kg 65 130-160 40

Infants 1-12 80 ml/kg 75-95 120 30-35

mo

Children 1-12 yr 75 ml/kg 75-95 80-100 20-25

Respiratory: adult v child

 Atelectasis more likely in infant
 ↓ # of alveoli & ↓ FRC
 FRC/TLC ratio equal to adults
 Chest wall very compliant
 If neonates try to overcome atelectasis by deep breathing, chest wall retracts inward,
preventing increased airway pressure or tidal volume
• Neonate has difficult time responding to atelectasis
 Minute ventilation, resp rate, alveolar ventilation all increased in children compared to adults
 FRC/MV decreased, and MV/FRC increased
• This, along with greater distribution of CO to vessel rich groups, explains increased
speed of induction in infants & children
 By Law of LaPlace (P = T w/R), as radius of alveolus ↓, surface tension ↑
• Surfactant ↓ surface tension, which keeps neonatal alveoli open
243
Summary of respiratory differences: neonate’s v adults
 ↑Increased
 Chest wall compliance is increased
• Predisposes to atelectasis
 Alveolar ventilation & respiratory rate are increased
 ↓Decreased
 FRC
 Vital capacity
 # of alveoli
 Neonate has narrower, more anterior glottis
 Perpendicular to trachea & more cephalad (C3-C4 v C5-C6) than in adults

Neonate & adult respiratory parameters

Neonate Adult

VO2 (ml/min) 6 3

VT (ml/kg) 5-7 5-7

RR 35-45 12-20

MV (liters) ~1 ~6.5

VD/VT 0.3 0.3

FRC (ml/kg) 25 40

VC (ml/kg) 35 50-70

PaO2 60-90 75-100

Hypoxemia in infants
 Develops more rapidly than in adults
 Higher MV/FRC ratio
• ↑ metabolism drives ↑ VE, combined w/↓ FRC
• Propensity for hypoxemia is increased
 Infant is relatively closer to desaturation than adult 2o ↑VO2 & ↑ ratio of oxygen consumption to FRC

Characteristics of infant upper airway

 Pediatric airway is funnel-shaped
 Narrowest portion: cricoid
• Small changes in airway diameter result in large changes in resistance to flow
• If there is no lead around an ETT, pt is at increased risk to develop subglottic
edema

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  Adult is cylindrical
 Narrowest portion: glottic opening
 Infants have relatively larger tongue, tonsils, adenoids and epiglottis than adults
 Large occiput creates more natural sniffing position

Temperature regulation
 Neonates, infants & children have difficulty maintaining normothermia
 Lose heat more easily & have more difficulty generating heat
 ↑ BSA:weight
 Cannot shiver to create/maintain body heat
 Rely on nonshivering thermogenesis
 Cold stressed newborn has ↑ VO2 → norepinephrine (NE) release
 Brown fat located around scapular, clavicle, kidneys & adrenals
 NE activates lipase in brown fat to break down fat into triglycerides
• Triglycerides degraded into glycerol and nonesterified fatty acids → CO2, H2O & heat

Neonatal renal function

 Decreased GFR
 1st 3 mo: GFR increases 3X
 Adult values at 1 yr
 Decreased urine concentrating ability 2o immature renal tubular function
 Limited ability to concentrate urine
• 800 mOsm/L infant v 1400 mOsm/L adult
• Takes ~6 mo for infant to concentrate as effectively as adults
 Decreased ability to handle large solute loads
 Renal maturation improves after 1 mo
 At this point, infants can handle fluid & Na+ better
 Takes ~1 yr for GFR to mature completely
 Glucose-containing IV solutions often administered to neonates because of high metabolic rates and
low glycogen stores at this age

Fluid-electrolytes
 Infants have higher % total body weight as water than adults (80% v 60%)
 Neonates have higher blood volume per kg than adults
 Glucose-containing solutions may be needed intraop in neonates due to high metabolic rate and low
glycogen scores
 Neonates susceptible to over-hydration
 Can develop cerebral edema & seizures
 Fluid status must be monitored carefully

↓BS Hypoglycemia
 Three classes of hypoglycemia
 Preterm: < 25 mg/dL
 Term: < 35 mg/dL
 3 days: < 45 mg/dL

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  Signs and symptoms of hypoglycemia:
 Irritability, seizures, apnea, bradycardia
 Apnea following general anesthesia can be r/t hypoglycemia (also hypothermia, hypoxia, residual
anesthetic agents)
Hypocalcemia
 Fetal Ca++ stores achieved during 3rd trimester
 Preterm neonate more likely to develop hypocalcemia
 Hypocalcemia = Ca++ ≤ 3.5 mEq/L
 Associated w/rapid infusion of blood
Pharmacologic differences
 Kinetics altered due to ECF volume, rates of metabolism & GFR
 40% TBW infants; 20% TBW adults
 Remember that induction is faster in infants 2o MV/FRC ratio
 Dynamics different because:
 Infants are more sensitive to nondepolarizing muscle relaxants
 T1/2β prolonged 2o ↓GFR
 Halothane (? Other agents) MAC 40% higher
 Less sensitive to succinylcholine even though low pseudocholinesterase levels
• Neonates do not develop phase II block
 More sensitive to opioid-related respiratory depression 2o prolonged t1/2β

Preoperative concerns
 History
 Congenital anomalies
 Allergies
 Prematurity
 Recent URI
 Can delay surgery because of increased risk of airway hyperreactivity
 Physical exam
 V.S., auscultate heart, lungs, palpate abdomen
 Labs
 H/H, coags
 Hypoglycemia?
 Hypocalcemia?

Induction
 Thiopental 3-5 mg/kg IV
 Propofol 2.5-3 mg/kg IV
 Succinylcholine 1-2 mg/kg IV
 Ketamine 4-6 mg/kg IM
 Isoflurane and desflurane have very pungent odors
 Sevoflurane or halothane preferable for inhalation induction
 Place IV unless very short case (BMT)

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Monitoring
 Standard monitors
 Precordial stethoscope especially important
 Arterial line for major surgery w/large expected volume shifts or blood loss
 Urine output  0.5 ml/kg/hr
Maintenance of anesthesia
 Maintain PaO2 50-80 mmHg
 Mix air or N2O w/O2
 Hypoglycemia
 In neonate: glucose of 20-30
 Rx: 1-3 ml/kg of 20% glucose x 5 min
 Hypocalcemia
 If Ca++ < 4.5 → seizures, tetany, laryngospasm, hypotension, CHF
 Rx: Ca++ gluconate, 100 mg/kg
 Blood loss
 Weigh sponges
 Check suction canisters
 Estimate blood on drapes
 Strongly consider giving blood if hct < 30% or EBL 10-15% calculated blood volume
Breathing circuits
 Pediatric circle system advantages
 Conserves heat & humidity
 Less volatile agent consumed
 Protection against pollution
 Pediatric circle system disadvantages
 Higher resistance
 More dead space
 Nonrebreathing circuit advantages
 Low resistance
 Little dead space
 Rapid control of anesthetic concentration
 Low weight
 Ease of assembly
 Disadvantages of nonrebreathing circuits
 Heat & humidity loss
 Less economy in use of volatile agents
 More OR pollution
 Higher fresh gas flow requirement

Mapleson circuits
 Which are best for spontaneous ventilation?
 A>D>C>B
• “all do continuous breathing”
 Which are best for controlled ventilation?
 D>B>C>A
• “dead babies can’t assist”
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Mapleson vs semi closed circle system

248
Pediatric Growth & Development
Normal & abnormal growth
 Prenatal growth
 1st 8 weeks (embryonic growth): organogenesis
 Fetal growth: Development of organ system function
 Rapid growth in 2nd trimester
 Duration of gestation & infant weight closely related. Deviations due to:
 Inadequate maternal nutrition
 Significant maternal disease
 Maternal toxins
 Fetal infections
 Genetic abnormalities
 Congenital malformations

Gestational age & weight

Normal & abnormal growth
 Prematurity
 Infants weighing < 2500 gm at birth
 Preterm infant = one born before 37 weeks
gestation
 Term infant
 Born after 37 weeks, before 42 weeks gestation
 Post term infant
 Born after 42 weeks gestation

Birth weight
 Low birth weight infant
 < 2500 gm regardless of pregnancy duration
 Very low birth weight infant
 < 1500 gm
 Extremely low birth weight infant
 < 1000 gm
 Micropremies
 < 750 gm
 Small for gestational age (SGA)
 Weight < 10th percentile at any gestational age on fetal growth curve
 Affected by intrapartum factors led to intrauterine malnutrition
 Prone to hypoglycemia, hypocalcemia, polycythemia, poor temp regulation, potential mental
& physical handicaps

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  Large for gestational age (LGA)
 Weight > 90th percentile at any gestational age
 Often born to diabetic mothers
 Increased weight due to organomegaly and excessive subcutaneous fat 2o ↑fetal insulin due to
maternal hyperglycemia
 Manifestations: hypoglycemia, polycythemia, birth trauma, hyaline membrane disease,
congenital malformations

Gestation age assessment

 Crown-rump fetal length during 1st trimester ultrasound exam
 Calculating gestational age from 1st day of mother’s last menstrual period
 Dubowitz scoring system
 Combines neurologic and physical criteria of infant to provide accurate assessment of
gestational age

Weight & length

 Weight is more sensitive index of well-being, illness, or poor nutrition than length or head
circumference
 Change in weight reflects changes in muscle mass, adipose tissue, skeleton, body water
 Length
 Best indicator of skeletal growth
 Term infants
 May lose 5-10% of body wt during 1st 24-72 hrs from loss of body water
 Daily increase of 30 g expected for 1st 3 mo
 At 10-12 mo, weight gain is 70 gm/week
 Birth weight doubled at 6 mo, tripled at 1 year
 Preterm infants
 May lose up to 15% of body weight during 1st 7-10 days of life
 Higher % of total body water per unit weight than term infants
 Regaining birth weight varies r/t gestational age & medical problems
 Weight gain slower in preterm infants
 Use corrected gestational age instead of chronological age during 1st 2 years of life
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 Relationship of age to weight
Age and total body water

Common causes of failure to thrive

 Genetic
 Parental size, chromosomal disorder
 Nutritional
 Inadequate, inappropriate intake
 Malabsorption, diarrhea
 Cystic fibrosis
 Celiac disease
 CHO intolerance, milk protein allergy
 Malformations
 Cardiac or urinary tract
 Infections
 Pulmonary, renal, hepatic, enteral, congenital infections
 Metabolic/endocrine
 Hypothyroidism, renal tubual acidosis
 Preterm & SGA infants
 Malignancy
 Bronchopulmonary dysplasia

Teeth
 Deciduous dentition starts at ~ 6 mo
 Should be complete by 28 mo
 Permanent teeth: 6 yr
 Loose teeth should be sought in any child between 5-10 yr
 Or when severe dental caries 2o poor hygiene/infection
 Be careful when placing oral airway or intubating if loose teeth
 Abnormal dental development:
 Hereditary disturbances, Down syndrome, CP, nutritional defects

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Body composition
 Water content inversely related to maturity
 Total body water decreases at expense of extracellular compartment
 Adult levels attained at ~ 1 yr
 Implications for drug dosage and distribution

Development of airways & lungs

 Differentiation of anatomic structures for gas exchange occurs late in gestation
 Limit of viability ~ 24th week
 Lungs develop a gas exchanging surface & surfactant production begins
 Laws of lung development
 Airways: bronchial tree, including terminal bronchioles, formed by 16th week of gestation
 Alveoli: Develop after birth, increasing #s until 8 yr
 Pulmonary vessels: Arteries & veins that accompany bronchial tree formed by 16th week

Embryology of lungs
 Glandular stage (7-16 weeks)
 Formation of intrasegmental airways & associated vessels
 Differentiation of cartilage in trachea/bronchi at 10 weeks
 Canclicular stage (16-24 weeks)
 Growth of liquid-filled airways
 1st vestigaes of acinus
 Viable gas exchange surface forms
 Terminal saccule or alveolar stage (24 weeks to term)
 Further intra-acinar branching of airway epitherlium
 Surface area for gas exchange increases exponentially

Fetal circulation
 Circulation of blood through fetal pulmonary circuit limited by:
 Vessel diameter, vessel number, and vasoconstriction
 Increase in pulmonary blood flow following birth results from rapid arterial dilation and closure of
extrapulmonary shunt pathways
 Growth of pulmonary vascular bed disturbed by diaphragmatic hernia,
 1 few minutes of life, ‘normal’ asphyxia exists 2o impaired placental blood flow during labor
st

 PaO2 & pH are low, PaCO2 high immediately after birth

 Change rapidly in 1st hour
 Extrapulmonary shunting through fetal channels & intrapulmonary shunting persist so
that newborns have physiologic R to L shunt 3X > adults

Chest wall & respiratory muscles

 Tendency to respiratory muscle fatigue
 Due to metabolic properties of diaphragm
 Low content of Type I (slow twitch, high oxidative capacity) muscle fibers
 Before 37 weeks gestational age, fatigue-resistant fibers make up < 10% of total
 High proportion of Type I fibers compatible w/fatigue resistance
 Type I fibers are 50% of fibers in adult’s diaphragm but only 25% in term infant
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Elastic lung properties
 Changes in static pressure-volume relationship of lungs during growth caused by increases in volume
& changes in elastic properties of lung tissue
 Volume is main factor that determines lung compliance, which increases throughout
childhood
 Elastic recoil pressure (recoil pressure of lung at specified reference volume) increases throughout
childhood

Static lung volumes

 Total lung capacity
 Adults have markedly greater TLC than infants
 TLC is effort-dependent parameter
 Functional residual capacity
 Similar per kg across ages
 Unknown at what age FRC is determined by passive rather than dynamic factors
 Apneic infant has smaller store of intrapulmonary O2 to draw from than similar adult.
This is why hypoxemia develops rapidly if airway lost in anesthetized infant

 Case Study
 Desaturation, closing volumes and respiratory mechanics

 Closing capacity
 As exhalation finishes, small airways in dependent lung regions close
 Leads to air trapping in affected areas
 Closely related to age, declines throughout childhood and increases throughout adult years
 Airway dynamics
 Airway resistance higher in preterm than full-term infants
 Specific airways conductance (reciprocal of resistance) is higher in preterm infants

Airway dynamics
 Distribution of resistance
 Distribution of airways resistances changes markedly ~ 5 yr
 Young children w/inflammation of small airways (bronchiolitis) suffer severe impairment of
respiratory function
 Older children & adults w/similar pathology have milder illness
 Inspiratory & expiratory flow limitation
 Tracheal compliance in newborns 2X > adults
 Gas exchange
 Venous admixture in infants > adults
 Shunt fraction = 10-20% of CO (compared with 2-5% in adults)
 This is due to intrapulmonary anatomic shunting vs mismatch of ventilation/perfusion.

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Regulation of breathing
 In neonates & adults, PaO2, PaCO2, pH control ventilation
 PaO2 acts through peripheral chemoreceptors in carotid & aortic bodies
 PaCO2 & pH act on central chemoreceptors in medulla
 **Hypoxia depresses hypercapnic ventilatory response in term & preterm infants**
 High FiO2 depresses newborn respiration: sustained hypoxia promotes a return to baseline ventilation
at first then results in ventilatory depression
 Low FiO2 stimulate respiration
 Other factors that affect infant breathing:
 Hct, glucose, temp
 Periodic breathing often seen in newborns
 Prematurity important risk factor that increases chance of life-threatening apnea in infants undergoing
general anesthesia
 Risk of postanesthetic respiratory depression is inversely related to gestational age
 Infants may be at risk up to 60 weeks post conception
 Greatest risk is in infants ≤ 55 weeks post conception
 Infants considered at risk should be monitored in setting where resuscitative equipment and personnel
trained in neonatal resuscitation are readily available

Normal respiratory parameters

 Stimulus that drives pulmonary ventilation is metabolic demand
 Resting oxygen consumption in infants is 2X > adults
 Doubled alveolar ventilation on per kg basis
 Infants increase alveolar ventilation by increasing respiratory rate rather than increasing tidal volume
 Range of normal ABG values is stable from late infancy through adult life
 Average PaO2 increases throughout childhood
 Pattern related to lung closing capacity which is high in infancy, declines through
childhood to late adolescence, rises throughout adulthood

Cardiovascular system
 Autonomic control of heart in utero mediated by PNS
 After birth, SNS predominates
 Mean heart rate in newborns is 120
 Increases to 160 at 1 mo
 Gradually decreases to 75 at adolescence
 Mean systolic pressure
 Infants/neonates: 65 mm Hg
 6 weeks: 95 mm Hg
 Cardiac output
 Increases linearly w/increasing birth weight
 Resting CO 2-3X > adult values
 Reflects higher metabolic rate, increased VO2, loss of body heat 2o larger surface area
in relation to body mass
 *** Heart Rate dependent**

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Renal system
 Kidneys active in utero
 Produce Lg volume urine, help maintain amniotic fluid volume
 GFR 15-30% of adult value at birth
 Increases to normal by 1 yr
 Low GFR affects ability excrete Na+ and H2O loads & drugs
 Diminished renal tubular threshold for HCO3- → physiological acidemia of infancy
 Infant kidneys can concentrate urine to max of 200-800 mOsm/L
 Elevated BUN is abnormal. May be due to:
 Renal failure, excessive dietary protein intake, GI bleed, e.g., necrotizing enterocolitis

Hepatic system
 Liver is site for protein synthesis
 Active process in fetal/neonatal life
 Alpha-fetoprotein: 6-13 wks
 Albumin: 3-4 mo gestation
 Clotting factors
 Capacity to enzymatically break down proteins is depressed at birth
 Physiologic jaundice
 Hyperbilirubinemia important problem in neonates
 Nonhemolytic physiologic hyperbilirubinemia r/t
 Excessive bilirubin production from RBC breakdown & ↑ enterohepatic bilirubin
circulation of bilirubin w/deficient hepatic conjugation due to depressed glucuronyl
transferase
Causes of neonatal jaundice
 Excess bilirubin production
 Impaired bilirubin uptake
 Impaired bilirubin conjugation
 Defective bilirubin excretion
 Increased enterohepatic bilirubin circulation

Pathologic causes of neonatal jaundice

 Antibody-induced hemolysis (Rh & ABO)
 Hereditary RBC disorders
 Glucose-6-phosphate dehydrogenase deficiency → hemolysis 2o drugs/infection
 Infections
 Neonatal hepatitis, sepsis, severe UTIs
 Hemorrhage into the body, e.g., cerebral
 Biliary atresia
 Metabolic, e.g., hypothyroidism, galactosemia

G-I tract disorders

 Esophageal atresia & tracheoesophageal fistula
 When respiratory tract fails to separate completely from foregut
 May be seen as laryngeal cleft

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  Intestinal atresia & stenosis
 Common causes of obstruction in newborn
 Often associated w/Down syndrome
 Duplication & diverticulum
 May be blind pouches or may communicate w/intestinal lumen
 Hirschsprung disease
 Failure of development of Meissner & Auerbach plexus
 Omphalocele (failure of the closure of the rectus muscles at 8 weeks gestation)
 Gastroschisis (Intestine protrudes from abdominal wall 2o failure of rectus muscles to close)

Gastroesophageal reflux
 ~40% of newborns 1st few days of life regurgitate their food
 Lower esophageal pressures low
 Take 3-6 weeks to reach adult levels
 Symptoms
 Persistent vomiting, failure to thrive, hematemesis, anemia

Hematopoiesis & coagulation

 Newborn blood volume 82 ml/kg
 Preterm blood volume 90-105 m/kg due to increased plasma volume
 After 3rd month, hgb stabilizes at 11-12 gm/dL
 At birth, vitamin K-dependent factors, e.g., II, VII, IX, X, are 20-60% of adult values
 Prolonged PT
 All newborns should receive prophylactic vitamin K

Neurologic development
Relationship of fine motor/adaptive milestones to age

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 Relationship of language milestones to age
Relationship of personal-social milestones of age

Causes of mental handicaps

 Infections, e.g., meningitis, encephalitis
 Head injury
 Hypoxemia
 Near drowning, CO poisoning
 Metabolic
 Severe hypoglycemia, hypernatremia, hypothyroidism, phenylketonuria, chronic malnutrition
 Lead poisoning, addictive drugs
 Degenerative CNS diseases
 Cerebral tumor, vascular accident
 Congenital malformation
 Prematurity

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Preoperative Evaluation of Pediatric Patients

Review these special problems in pediatric anesthesia & preop evaluation

 Fasting, full stomach  Post-anesthesia apnea in former preterm
 Anemia infants
 Upper respiratory infection  Bronchopulmonary dysplasia
 Fever  Diabetic children
 Sickle cell disease  Seizure disorders
 Mentally handicapped children  Hyperalimentation
 Retinopathy of prematurity  Asthma & reactive airway disease

Psychological preparation
 Open house, brochure
 Ample lead time
 Children unable to articulate fears
 Reassure child that:
 Anesthesia is a deep sleep, not like usual nightly sleep
 They will feel no pain from surgery
 They will definitely awaken when surgery is over

Patient & parent preparation

 Provider should have calm, friendly face
 Offer warm introduction
 Touch child reassuringly
 Be honest
 Discuss anesthetic risk in clear terms
 Describe to parents exactly what measures will be taken to monitor the safety of their child

History of present illness

 Careful neonatal and gestational history
 Scoring systems for physical characteristics & neurologic examination provide estimates for
gestational age
 Plot gestational age against birth weight → defines several categories of neonates, e.g.:
 2000 g baby w/characteristics of 29 wk gestation: large for gestational age
 2000 g baby w/characteristics of 35 wk gestation: appropriate for gestational age
 2000 g baby w/characteristics of 40 wk gestation: small for gestational age
 Maternal medical & pharmacological history important

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Maternal history & common neonatal problems
Maternal hx Commonly Expected Neonatal Problems

Rh-ABO incompatibility Hemolytic anemia, hyperbilirubinemia,

kernicterus

Toxemia SGA & assoc probs; NMB prolonged 2o Mg++

HTN SGA & assoc problems

Drug addiction SGA & withdrawal

Infection Sepsis, thrombocytopenia, viral infection

Hemorrhage Anemia, shock

Diabetes Hypoglycemia, birth trauma, LGA, SGA

Polyhydramnios Tracheoesophageal fistula, anencephaly,

anomalies

Oligohydramnios Renal, pulmonary hypoplasia

C-P disproportion Birth trauma, hyperbilirubinemia, fractures

Alcoholism Hypoglycemia, congen malformations, FAS,

SGA

History of present illness

 Relevant involved organ systems
 Medications
 Previous surgical/hospital experiences
 Past history of other medical problems unrelated to present illness
 H/O prematurity or apnea alter postop course
 Family history of anesthesia-related complications
 Fever or death in periop period
 Prolonged neuromuscular blockade
 Time of last PO intake  H/O croup, allergic rxns
 Last urination  Bleeding tendencies
 Most recent episodes of vomiting, diarrhea  Anemia
 Hypovolemia  Seizures
 ↓ gastric motility begins w/illness or injury
 Review of other body systems, especially:
 Recent URI
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Past medical history
 Previous hospitalizations
 Immunizations
 Childhood illnesses
 Medication history
 Chemo?
 Infectious diseases?
 Prematurity & apneic or bradycardic spells significant
 Croup: could mean post-intubation croup
 Intubation as neonate assoc w/subglottic stenosis

Family history
 Determine whether following are included in FH:
 Prolonged paralysis assoc w/anesthesia
 Unexpected deaths
 SIDS, MH
 Genetic defects
 Familial medical conditions, e.g., muscular dystrophy, CF, sickle cell disease,
bleeding tendencies
 Allergic reactions
 Drug addiction
 Drug withdrawal, HIV carrier

Review of systems: anesthetic implications

System Questions to Ask Anesthetic Implications

Respiratory Cough, asthma, recent cold, Irritable airway, bronchospasm, medication hx,
croup atelectasis; subglottic stenosis; postop
Apnea, bradycardia apnea/bradycardia

C-V Murmur, cyanosis Septal defect (air bubbles in IV)

H/O squatting R to L shunt, Tetralogy of Fallot
HTN coarctation, renal dz
rheumatic fever valvular dz
exercise intolerance CHF, cyanosis

Neuro Seizures Meds, metabolic derangements

Head trauma Intracranial HTN
Swallowing difficulty Aspiration, reflux, hiatal hernia
Neuromuscular dz Sensitivity to NMB, MH

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 System Questions to Ask Anesthetic Implications

G-I, liver Vomiting, diarrhea Lytes imbalance, dehydration, full stomach

Malabsorption Anemia
Black stools Anemia, hypovolemia
Reflux Treat like full stomach
Jaundice Drug metabolism/hypoglycemia

G-U Frequency UTI, diabetes, hypercalcemia

Time last voided State of hydration

Endocrine Abnormal development Endocrinopathy, hypothyroid, DM

Hypoglycemia, steroid rx Hypoglycemia, adrenal insufficiency

Heme Anemia Need for transfusion

Bruising, bleeding Coagulopathy, thrombocytopenia
Sickle cell dz Hydration, possible transfusion

Physical exam
 Observe how child interacts w/others
 Determine anxiety level of child/parents
 Careful, nonthreatening approach
 Observe skin and faces for:
 Pallor, cyanosis, sweating, jaundice, apprehension, apin
 Obvious URI?
 Respiratory difficulty?
 Nasal flaring, grunting respirations, stridor, retraction, wheezing
 Abdominal distension?

Laboratory data
 Tests obtained r/t history, illness, surgical procedure
 Hgb in these pts:
 Surgery w/risk for bleeding
 Risk factors for hemoglobinopathy
 Former preterm infants
 Infants < 6 mo
 Room air SpO2 helpful
 Major reconstructive surgery, consider bleeding profile
 Platelets, PT, PTT

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Fasting
 Clear liquids rapidly reabsorbed from stomach w/half-life of 15 min
 No difference in gastric vol or pH in children who had clear liq 2-3 hr preop
 Continuing clears for up to 2 hrs preop avoids hypovolemia and hypoglycemia
 No breast milk 4 hrs preop
 No solids preop on day of surgery
 Incidence of aspiration in elective cases w/out known risk factors:
 4:10K adults, 10:10K children

Full stomach
 Children can never be trusted to fast
 If full stomach suspected, need IV rapid seq induction
 2 suctions, 2 laryngoscope handles/blades, leak-free anesthesia circuit, styletted
tubes of appropriate size
 Atropine 0.02 mg/kg, preoxygenate,cricoid pressure, propofol 3 mg/kg (ketamine
1-2 mg/kg if volume status questionable), succinylcholine 1-2 mg/kg
 Cricoid pressure released when tracheal intubation confirmed w/ETCO2 &
BBS
 Gastric volume less 4 hrs after admission to hospital
 Neonates may be intubated awake if needed, e.g., pyloric stenosis repair

 Case Study
 NPO and the “bargaining parent” - how to get to the bottom line

Anemia
 Elective surgery on anemic pt controversial
 Most prefer hct > 25%
 Lower value expected between 2-4 mo, CRF
 Significant anticipated blood loss:
 Determine cause of anemia
 Postpone surgery until hct normalized
 Children should not receive blood transfusions to bring hct to 30% preop due to risk of
blood-borne diseases
Upper respiratory infection
 Differentiate allergic rhinitis from URI
 Mild URI, not acute onset
 Probably safe to anesthetize for minor procedure
 If ETT inserted, propensity for bronchospasm, laryngospasm, desaturation events
 Postpone surgery on pts w/active infection, e.g.,
 Fever, recent onset purulent nasal drainage, wet cough
 Could be prodrome of more serious infectious illness, e.g., chickenpox,
measles
 Must have drugs necessary to treat bronchospasm, laryngospasm, hypoxemia

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Physical exam
 Congenital anomalies?
 Unusual features may represent a specific syndrome
 When a child has one congenital malformation, likelihood of another is
increased
 Devices attached to child provide clues to underlying conditions & ongoing therapy
 Warm the stethoscope & hands
 Begin with heart & lungs

Physical exam points of interest

 Fever
 Missing or loose teeth
 (possible dislodgement during intubation)
 Micrognathia
 (difficult intubation)
 Nasal speech or mouth breathing
 Lg tonsils/adenoids; difficult induction; potential bleeding with ETT or NGT,
sleep apnea, pulmonary HTN
 Heart murmurs
 Avoid air bubbles in IV lines
 Ensure murmur etiology clear from echo
 Abdominal distension
 Full stomach, impeded respiration
 Neurologic status
 ↑ ICP; loss of gag reflex; control of airway, breathing
 Edema
 CHF, nephrotic syndrome
Fever
 If fever of 0.5-1oC & otherwise asymptomatic, no contraindication to general anesthesia
 Fever w/recent onset rhinitis, pharyngitis, otitis media, dehydration
 Consider postponing case
 If necessary to anesthetize child w/fever, best to reduce fever since ↑ VO2 2o fever
occurs
 Acetaminophen absorption rapid po; up to 60 min rectally

Sickle cell disease

 Sickle cell disease, Hbg SS
 Sickle cell trait, Hgb Ss
 Family hx & sickle cell prep if pt not previously tested
 If sickle cell prep (+), then hgb electrophoresis needed to determine dz severity
 Hydration & oxygenation crucial in all pts w/sickle cell disease or trait
 Replace 1.5X maintenance rate

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  Children w/hgb SC especially at risk since they have normal hgb level but very
vulnerable to sickle cell crisis
 If undergoing abdominal surgery, preop transfusion recommended
 Preop hematology consultation recommended

Mentally handicapped children

 Difficult to explain procedures
 Pt may be scared from previous experiences
 Patience, understanding, preparation important
 Often have extensive histories & may be transported from chronic care settings
 May be ward of state & require special consent for surgery
 Continue meds
 Consider for sedation:
 Midazolam 0.5 mg/kg po
 Methohexital 25 mg/kg rectally
 Ketamine 3-4 mg/kg, Robinul 0.01 mg/kg & Versed 0.1 mg/kg IM, especially if
frightened/combative

Retinopathy of prematurity
 Occurs most frequently in sick low birth weight infants w/prolonged O2 exposure
 Assoc w/variety of factors
 Infants at greatest risk for ROP most likely to need surgery
 Retina matures at 42-44 wks gestation
 ? Delay elective surgery until 44 wks gestation
 Titrate FiO2 to maintain SpO2 93-95%
 Retinal vessels immature when birth weight < 1000 gm. O2 → neovascular buds that
bleed, scar & eventually detach retina.

Post-anesthesia apnea in former preterm infants

 Admit & monitor all former preterm infants of < 60 weeks of post-conceptual age
 Infants who have apnea in PAR or are anemic more likely to have postop apnea episodes
 Preop theophylline should be continued
 Therapeutic level = 10-15 μg/ml
 Caffeine 10 mg/kg may ↓ postop apnea
 Cannot give caffeine and discharge former premie home & assume they will be
OK

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Etiology of postop apnea

Postop apnea in former preterm infants: use of regional anesthesia

 May ↓ incidence of postop apnea
 Those at high risk still need postop monitoring
 Ensure child has no episodes of apnea for 12-24 hrs before discharge
 Infant < 44 wks post conceptual, although full-term, should be observed if any postop
respiratory abnormality

Bronchopulmonary dysplasia

 Chronic lung dz assoc w/prolonged mechanical ventilation (barotrauma) & O2 toxicity in

premie w/hyaline membrane dz
 Chronic hypoxemia, hypercarbia
 Abnormal response to hypoxemia
 Abnormal functional airway growth
 Tracheomalacia, bronchomalacia
 Increased incidence of reactive airway disease
 Predisposition to atelectasis and pneumonia
 Increased PVR
 May have cor pulmonale & CHF
 Frequently on diuretics
 Abnormally shaped chest

 May take several days to optimize for surgery

 May have developmental delays 2o intraventricular bleeds, seizures, hypoxic insults
 Pulmonary function abnormalities:
 ↓ FRC, ↓ FEV1, airway obstruction, ↓ diffusion capacity, abnormal response to
hyperoxia, ↓ exercise tolerance

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  Electrolyte abnormalities 2o diuretics
 Cardiomyopathy 2o neonatal steroid therapy
 May need O2 for transport to OR
 Chronic air trapping
 N2O bad idea
 Allow adequate expiratory time
 Avoid excessive positive pressure ventilation
 Use of LMA may ↓ incidence of coughing & related desaturation, wheezing, hoarseness
 SIDS increased in BPD pts
 May need postop apnea monitoring
 Regional for procedures like inguinal hernia repair

Diabetics
 Normal diet & insulin regimen maintained up to day before surgery
 Schedule as 1st case of day
 Baseline accu check; repeat intraop PRN & postop
 Preop IV w/D5 @ maintenance rate if possible
 Give ½ usual insulin dose after IV established
 Follow endocrinologist recommendations which usually include an insulin infusion and
separate glucose infusion
 Emergency surgery, e.g., appendectomy
 Hydrate & correct hyperglycemia & ketoacidosis preop
 Monitor glucose, K+, hourly during DKA treatment
 Sliding scale insulin vs loading dose/infusion

Seizure disorder
 Know antiseizure meds, schedule, possible interactions w/anesthetic agents
 Surgery stress may alter seizure threshold → ↑ seizure activity
 Continue anticonvulsants w/sips of H2O until time of surgery
 Monitor for adequate blood levels
 May need to replace IV/IM

Hyperalimentation
 Know composition & rate of administration
 Most solutions hypertonic, have high glucose content
 Administered centrally
 Avoid contaminating the line
 Do not suddenly stop hyperal solution
 Would leave pt hyperinsulinemic → profound hypoglycemia, masked by
anesthesia
 Use infusion device to ensure constant rate
 Rapid infusion → hypertonic nonketotic coma

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  ↓ rate 1/3-1/2 intraop to avoid hyperglycemia from reduced metabolic rate during
anesthesia
 Periop monitoring of glucose, K+, Na+, Ca++, acid-base status important

Asthma & reactive airway disease

 Pt for elective surgery should not be wheezing
 H/O prior ER visits or hospitalizations?
 Current/recent medications
 If on theophylline, level should be 10-20 μg/ml - rarely used in modern practice
 H/O resp events, bronchodilator use, steroids?
 3 day steroid prep beneficial in moderate and severe asthmatics
 Preop albuterol
 Use LMA if possible
 May have ↑ incidence of bronchospasm w/ETT
 Emergency surgery in bronchospastic pt:
 Give oxygen
 Hydrate
 Consider subcutaneous epinephrine
 Aminophylline infusion
 β2 agonist
 Steroids
 Antibiotics
 ABGs: PaCO2 > 45 → incipient resp failure

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Perioperative Behavioral Stress Response

Overview
 Anxiety in children undergoing anesthesia
 Feels of tension, apprehension, nervousness
 Related to separation from parents, loss of control, uncertainty about
anesthesia, surgery and outcome
 May not be explicitly expressed
 Anxiety-related behaviors may give child sense of control
 Up to 60% of children undergoing output surgery may develop negative postop
behavioral changes w/in 2 wks postop
 Sleep/eating disturbances, separation anxiety, apathy, withdrawal, new
onset enuresis

Preop anxiety
 Associated w/increased serum cortisol, epinephrine, growth hormone, ACTH & natural
killer cell cytotoxicity
 Significant correlations between HR, BP & behavioral ratings of anxiety

Developmental issues
 3 areas of development are most influential in determining child’s response to separation
experience:
 Social interaction, attachment, reactivity to novelty
 Social interaction
 1st weeks of life, infant can differentiate people but will accept care from other
than parents
 3 mo: different responses to familiar/unfamiliar people
 5-6 mo: separation anxiety begins
 cognitive ability of object permanence
 Separation anxiety r/t infant attachment to parents
 Develops as function of emotional experiences
 Manifests in how infants look at parents, respond to separation
 Sense of security/trust important in development of autonomy/independence
 Infants who are more securely attached to parents deal more adaptively w/stress
of brief separation
 Temperament
 Response to separation in infancy and preschool yrs reflects child’s relationships
w/parents & child’s temperament
 Emotional responses characteristic of individual infants & young children
 Genetic basis
 Later personality traits reflect interaction between temperament traits from early
childhood & environmental influences

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Temperament
 Emotionality
 Ease w/which infant becomes aroused or anxious
 Activity
 Customary level of energy and intensity of behavior
 Sociability
 Tendency to approach or avoid others
 Temperament is a behavioral descriptor that characterizes enduring cluster of traits
reflecting reactivity and anxiety regulation in face of novelty

Overview of perioperative anxiety

Demographic & personality factors related to preop anxiety

 Age
 Parental anxiety
 Temperament
 Previous experience
 Social adaptability
 Coping style
 Lack of premedication

Preoperative anxiety: interventions

 Preoperative preparation programs
 Parental presence during anesthesia induction
 The preoperative interview

Pharmacological interventions
 Wide variation in US preop sedation practices
 Avoids tachycardia in pt w/cyanotic lesion
 Preop sedation least often prescribed for pts < 3 yr & > 65 yr
 Most common preop sedation:
 Midazolam
 Ketamine
 Inverse relationship between parental presence and preop sedation use

Behavioral stress & pediatric surgery

 ~3M children undergo anesthesia/surgery each year in US
 Up to 60% develop behavioral stress prior to OR
 Current trend: ↓ behavioral/pharmacological preop interventions
 Need studies to determine if ↓ preop anxiety can change postop outcomes

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Peds Fluid & Blood Component Therapy

Circulating blood volume

 Newborns: ~82 ml/kg
 Low birth weight, premature, critically ill pts, blood volume may be 100 ml/kg

Homeostatic mechanisms
 Maturational features make it difficult for preterm or young infant to handle fluctuations
in fluid & solute loads
 Na+ conservation & regulation of ECF impaired relative to older child/adult
 Limited GFR makes excretion of fluid challenge difficult
 Excessive urinary Na+ leads to increased maintenance reqmts
 Hyponatremia common
 Diminished concentrating ability increases free water loss during excretion of solute load
 High surface area to volume ratios produces increased water vapor loss
 Fluid requirements are high and dehydration is common

Estimated blood volume

Relationship between weight and hourly/daily

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Normal water losses for infants & children

Intraoperative fluid management

 22 g IV may be sufficient in infant
 Larger lines:
 Antecubital or saphenous
 Central access:
 Femoral, subclavian, internal jugular
 Interosseous
 Initial resuscitation of critically ill or injured children
 To prevent volume overload, amt of fluid available to child at any one time should not be
> calculated hourly requirement
 Volumetric chamber, e.g., buretrol & microdrip
 When rapid infusion of resuscitation solutions, e.g., albumin, or blood products
anticipated, include in-line stopcock
 Additional fluids can be drawn up into 60 ml syringes and warmed separately
 When sudden blood loss, stored syringes can be inserted into stopcock and known
volume rapidly infused
 If long surgery, fluids must be warmed
Choice & composition of IV fluids
 Isotonic fluids preferred intraoperatively
 Most ongoing volume losses isotonic
 Blood, interstitial fluids
 Large volumes of hypotonic solutions may rapidly ↓ serum osmolality →
electrolyte imbalances & undesirable fluid shifts
 Plasma volume expansion difficult to achieve even with isotonic fluids
 Increased ADH → free water retention > Na+ if inadequate amts of Na+ provided
 Assuming normal plasma osmolality (275-290 mOsm/l):
 Normal saline slightly hypertonic to plasma
 LR is isotonic & slightly hyponatremic
 Dextrose-containing solutions:

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  Added osmolality ↓ as sugar metabolized
 D5W ~ free water
 When necessary, glucose-containing solutions should be run as piggybacks
 Debilitated infants, cardiac surgery
Fasting guidelines (fasting hours)

Deficit replacement
 Hourly maintenance fluid rate
 4 ml/kg/hr for 1st 10 kg = 40 ml/hr
 + 2 ml/kg/hr for 2nd 10 kg (11-20 kg) = 20 ml/hr
 + 1 ml/kg/hr for each kg > 20 kg thereafter
 Fluid requirements for 30 kg child:
 40 + 20 + 10 = 70 ml/kg/hr
 Estimated deficit calculated as above hourly requirement x number of hours NPO
 Deficits usually replaced by 50% in 1st hour, remainder over next 2 hrs

 Case Study
 Do you really know how to use 4-2-1?

Assessment of intravascular volume

 Age-related norms for HR & HP (tables 2-9 & 2-10)
 Is HR persistently high or does it vary w/surgical stimulation?
 Is pulse pressure narrow, or is BP low for age?
 Does it vary w/positive pressure breaths?
 Are the extremities warm?
 Is capillary refill brisk?
 What is urine output?
 When hypovolemia suspected, see response to 10-20 ml/kg of isotonic crystalloid or
colloid

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Ongoing losses & third spacing
 Surgical fluid loss from vascular space due to:
 Whole blood loss
 Capillary leak & surgical trauma → extravasation of isotonic, protein-containing
fluid into nonfunctional compartments (3rd spacing)
 ↓ sympathetic tone 2o anesthesia → vasodilation → hypovolemia
 Small circulating volume leaves little room for error:
 5 kg infant = 80 ml/kg x 5 kg = 400 ml
 Blood loss replaced 1 ml: 1 ml w/albumin or blood
 3 ml for 1 ml blood loss LR
 Isotonic crystalloid also used to replace 3rd space losses
 Degree of tissue trauma & fluid replacement
 Mild trauma: 3-4 ml/kg/hr
 More extensive: 5-7 ml/kg/hr
 Large abdominal procedures: 10 ml/kg/hr
Postop physiology and hyponatremia
 Postop pts retain Na+ & H2O
 Ongoing postop fluid/lyte losses may be large
 Unless isotonic, Na+-containing fluids provided, postop pts at risk for hyponatremia
 Etiology of hyponatremia:
 Extra renal loss of lyte-containing fluid
 IV replacement w/hypotonic solutions
 Rx:
 Don’t give hypotonic fluids w/out a specific reason
 Replace ongoing losses in timely fashion
 Measure lytes in pts w/s + s of hyponatremia
Pathophysiologic states & their management
 Review:
 Fluid overload & edema
 Dehydration states
 Hypernatremia & hyponatremia
 Hyperkalemia & hypokalemia
 SIADH
 DI
Blood replacement
 Maximum allowable blood loss:
 EBV x (pt’s hct – minimum acceptable hct)
pt’s hct
 10 kg child w/700 ml blood volume & 285 ml MABL, replacement strategies are:
 570-855 ml of isotonic crystalloid (2-3 ml per ml blood loss)
 285 ml 5% albumin
 If blood loss > MABL, or hct ↓ 20-25%, especially if more blood loss expected, give
PRBCs or whole blood

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  If 1 unit blood started, reasonable to give pt addition 5-10% rather than risk exposure to
2nd unit postop
Packed RBC replacement
 If 10 kg child’s hct is 23% & further blood loss expected, here is calculation to increase
hct to 35%:
 (Desired hct – present hct) x EBV (70 ml/kg x 10 kg)
Hct of PRBCs
 = (35-23) x (70 x 10) 60
 = 140 ml PRBCs
Blood products & adjuvants
 FFP
 1 unit represents 7-10% of coag factors for 70 kg pt
 After 6 hrs, amt of V & VIII ↓
 Should be ABO compatible w/recipient red cells
 Platelets
 For pts whose platelet count or function has fallen 2o disease or therapy
 When rapid ↓ platelets 2o hemorrhage & dilutional thrombocytopenia
 4-5 units of platelets provide clotting factors ~ 1 U FFP
 If pt thrombocytopenic preop, give platelets just before surgery
Worry about other than BLOOD products when 1 blood volume loss
First order platelets then FFPv (takes a lot longer to need to replace this because it can work at
lower levels)
 Factor concentrates
 Most commonly given: Factor VIII
 Desmopressin
 Synthetic analogue of vasopressin
 Can ↑ factor VIII:C & factor VIII:vWF
 Massive blood transfusion
 Replacing entire blood volume 1 or more times
 In peds, think in terms of % of blood volume lost rather than units of blood lost
Coagulopathy
 In massive blood transfusion, r/t dilution of clotting factors or platelets
 Contributory variables include:
 Volume of blood lost, type of blood component transfused, DIC
 Hypothermia
 Factor deficiency
 Massive replacement w/PRBCs results in dilution of factors V & VIII &
fibrinogen
 Review table 10-13, minimal FFP recommendations r/t blood products given and
EBL
 Case Study
 Common sense approach to massive bleeding

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Hyperkalemia
 When whole blood given rapidly
 Whole blood may have K+ of 26 mEq/L
 Hyperkalemia is r/t shelf age of blood
 If whole blood used in neonate, check K+ level before giving
Hypocalcemia
 Can occur w/massive transfusion of whole blood 2o binding of ionized Ca++ w/sodium
citrate
 Unlikely to have hypocalcemia following large volumes of citrated PRBCs
 Infusion rates of citrated WB that produce hypocalcemia & hyperkalemia are similar
 Observe EKG for widened QRS, prolonged QT, peaking or flattening of T wave
 Rx: Ca++
Whole blood has lots of citrate, needs to be with NS
Acid-base status
 Massive transfusion indications
 Severe trauma w/shock
 Severe metabolic acidosis may result 2o low CO & ↓ oxygen delivery
 To maintain intravascular volume during major surgery
 With massive blood loss, metabolic acidosis may not occur if severe hypovolemia
avoided
 Give NaHCO3- based on ABGs
Hypothermia
 Significant problem w/major blood loss & replacement
 Causes ↑ VO2, L shift of oxygen-hgb dissociation curve, potential for refractory VT
 Profound effects on platelets & coagulation cascade
 All banked blood products except platelets & FFP have temp of ~5oC
 Must be warmed prior to infusion
 >42oC causes RBC hemolysis
 Need warming measures
 High capacity fluid warmer, hot air warming blankets, radiant warmers, etc.
Oxygen-hemoglobin dissociation
 Oxygen binding to hemoglobin dependent on temp, acid-base status & 2,3-DPG
 Citrate metabolized to HCO3- & causes metabolic alkalosis
 IF NaHCO3 given, significant effect on dissociation of oxygen & hgb can occur
 Citrated WB & FFP have greatest effect on oxygen-hgb dissociation curve
 Large volume of citrate in each
Oxygen-hemoglobin dissociation
 Oxygen binding to hemoglobin affected by 2,3-DPG
 Low 2,3-DPG results in less oxygen delivery to tissues 2o increased affinity of
oxygen for hgb
 Citrated WB and PRBCs rapidly lose 2,3-DPG
 Frozen blood maintains it at normal levels
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Methods to reduce patient exposure to blood products
 Erythropoietin
 Pre-donation
 Directed donation
 Autotransfusion
 Controlled hypotension

Premedication & induction of anesthesia in pediatrics

General principles of premedication

 Objectives
 Allay anxiety
 Block autonomic (vagal) reflexes
 Reduce airway secretions
 Produce amnesia
 Provide prophylaxis against aspiration
 Facilitate induction of anesthesia
 Provide analgesia if necessary
 Factors to consider
 Child’s age, weight, drug history, allergic status
 Underlying medical/surgical conditions

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  Parent & child expectations
 Child’s emotional maturity, personality, anxiety level, cooperation, physiologic &
psychological status
 Infants < 6-10 mo generally tolerate short separations from parents
 Age 6 mo – 6 yr: more difficult separation
 Preschool children become very anxious in threatening situation like hospital
 Predictors of problematic separation behavior:
 No preop family tour
 Previous surgery
 Dependent or withdrawn affect
 Age 2-7:
 Midazolam po premed → fewer postop behavior changes
 Age > 6
 Curious, trusting of adults
 May accept mask induction of anesthesia
 Older children
 Fear of mutilation, being ‘put to sleep’
 Adolescents
 Labile moods, want to be in control
 Important to assess attitude/behavior of child
 Ideal pediatric premedication:
 Allays or minimizes anxiety
 Produces predictable effects in all pts
 Minimal undesirable side effects
 No or minimal adverse C-V or respiratory effects
 Rapid onset & recovery
 Easy to administer
 Painless when administered
 Route of administration
 Avoid needles
 Routes used include oral, nasal, rectal, buccal, IV, IM
 Small po dose may be sufficient for relatively calm child
 IM ketamine may be best for rambunctious, uncooperative, combative, anxious child
 Better than forcing po med, rectal route, or forcefully holding anesthesia mask on
face

Routes for premedication: nasal

 Review the anatomy of nasal mucosa-cribiform plate interface
 Nasal mucosa is only location in body w/direct connection between CNS & atmosphere
 Drugs administered to nasal mucosa rapidly traverse through cribiform plate into
CNS by 3 routes:
 Directly by olfactory neurons

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  Through supporting cells & surrounding capillary bed
 Directly into CSF

Doses of common premedicants

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Benzodiazepines
 Widely used to premedicate children
 Given to calm pts, allay anxiety, diminish recall
 Midazolam
 T1/2β = 2 hrs
 Rapid uptake, elimination
 Peak plasma concentrations:
 Intranasal – 10 min
 Rectal – 16 min
 Oral – 53 min

Barbiturates
 Advantages
 Sedation, minimal respiratory, C-V depression, anticonvulsants, minimal PONV
 Disadvantages
 Hyperalgesia
 Thiopental 30 mg/kg PR produces sleep in 15 min
 T1/2β = 9 ± 1.6 hrs
 Methohexital 20-30 mg/kg PR – sleep in 15 min
 T1/2β = 3.9 ± 2.1 hrs

Opioids
 Useful when preoperative pain present
 ↓ MAC requirements
 Smooth awakening 2o ↓ pain
 Disadvantages:
 Nausea, vomiting, respiratory depression
 Fentanyl can be given PO
 Avoid swallowing
 Fentanyl oralet: sedation w/in 10 min after 10-15 µg/kg
 Sufentanil
 Potency 10X > fentanyl
 T1/2β adults = 2.7 hrs
 T1/2β infants = 12.3 hrs
 T1/2β children = 3.5 hrs
 Nasal dose 1.5-3 μg/kg
 Usually calm/cooperative, separate easily from parents
 ↓ MAC reqmts

Ketamine
 T1/2β infants < 3 mo = 185 min
 T1/2β infants > 3 mo = 65 min
 Amount needed to prevent movement 4X > in infants < 6 mo vs 6 yr children

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Anticholinergics
 Block cholinergic drug effects
 Prevent bradycardia from laryngoscopy & intubation
 Reduce secretions
 Sedation, amnesia (scopolamine)
 Atropine, scopolamine dose = 0.01-0.02 mg/kg
 Glycopyrrolate dose = 0.01 mg/kg
 Young children more prone to bradycardia
 Parasympathetic tone > sympathetic tone
 Infants & small children who develop bradycardia should be treated promptly
 If ↓ HR → ↓ CO
 Need anticholinergic when succinylcholine used

Nonopioid analgesics
 Acetaminophen
 Most common nonopioid analgesic for postop pain in peds pts
 Can be given po preop or rectally after induction
 Peak blood levels of rectal Tylenol: 60-180 min
 Based on kinetics, recommended dose is 40 mg/kg initially followed by 20 mg/kg
q 6 hr

Antiemetics
 Ondansetron
 5 HT3 antagonist
 Decreases PONV when given prophylactically
 Usual dose is 0.1 mg/kg
 Droperidol
 50 μg/kg
 When combined w/metoclopramide or other antiemetic, superior to either drug
alone
 Dexamethasone
 Prolonged antiemetic effect
 0.15 mg/kg after induction before incision decreases PONV significantly

Doses of antacids, H2 antagonists & G-I motility drugs

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Induction of anesthesia
 Need thorough evaluation and preparation of children and families
 Can be stressful for all involved
 Always be prepared for the unexpected

Mask inhalation induction

 Most commonly used in children
 Easily accepted by infants 8-10 mo
 Toddlers may require premedication
 Cooperative older children will tolerate mask
 If given choice between mask and IV, children usually prefer mask
 High flow N2O:O2 w/sevoflurane
 2nd gas effect

Induction with scented masks

 Scents can provide distraction from smell of anesthetic agent
 Don’t want too strong scent
 Flavored lip balm may work

Distraction techniques
 Susceptibility to suggestion
 Suggest that pt ‘blow up balloon’ (rebreathing bag)
 Can be done with child in anesthetist’s or parent’s lap
 Allowing child some freedom in position is better than forcing them to lie supine
 See suggestions re: hypnotic induction techniques

Single-breath induction
 Need cooperative pt
 Coach to take vital capacity breath
 Prime circuit with agent
 Induction time similar to IV thiopental (30-45 sec)

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IV induction
 Older children who request IV induction
 Patients with existing IV catheter
 Those who need rapid sequence induction
 Ultra-short acting barbiturates
 Thiopental: t1/2β 15 hrs in newborns vs 7 hrs in their mothers
 Children require more thiopental/kg than adults
 Neonates, debilitated pts, premedicated pts, need less drug
 Ultra-short acting barbiturates
 Methohexital recovery more rapid than thiopental
 Higher doses cause skeletal muscle hyperactivity
 Pain at injection site more common after methohexital
 Associated w/hiccoughs
 Propofol
 Induction dose in children higher than adults
 Pain on injection
 Ketamine
 Useful in hypovolemic states or when SVR needs to be maintained
 Forms of congenital heart disease where balance between pulmonary and
systemic blood flow must be maintained
 Ketamine is a myocardial depressant
 Can result in hypotension in pts maximally responding with endogenous
catecholamines

IM induction
 May be necessary when child decompensates during planned inhalation induction
 Infants/small children
 Methohexital 10 mg/kg of 5% solution
 Question: how do you create a 5% solution of methohexital from a vial
containing 500 mg of powdered methohexital?
 Older children

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  Ketamine 6-10 mg/kg to induce anesthesia; 2-3 mg/kg for sedation
 Add glycopyrrolate 0.01 mg/kg & midazolam 0.15 mg/kg
 Mix in same syringe

Rectal induction
 Sedation produced ranges from drowsiness to general anesthesia
 Ideally suited for extremely frightened child who rejects needle or mask induction but
does not object to rectal thermometers
 Disadvantages
 Failure to induce small number of pts 2o poor bioavailability; defecation
 Delayed recovery 2o variable absorption of rectal drugs

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 Pulmonary Pathophysiology

Lung Mechanics

 Respiration center  medulla and pons

o Dorsal respiratory center – responsible for inspiration
 Most important
 In nucleus solitarius where vagal and glossopharyngeal nerve fibers
terminate and carry signals from peripheral chemoreceptors, baroreceptors
and lung receptors
 Responds to changes in CSF pH
o Ventral respiratory center – responsible for both expiration and inspiration
o Pneumotaxic center – control breathing rate and pattern
 Stimulation of breathing on chemosensitive area in the brainstem
o Carbon dioxide (indirectly)
o Hydrogen ions (directly)
 Laplace equation
P = 2T/R P = pressure within the bubble
T = surface tension of the liquid
R = radius of the bubble
o As radius decreases  pressure increases
o Surfactant reduces surface tension  decreasing pressure as the airways decrease
in size
 Functional residual capacity – volume in the lungs at the end of passive expiration
o Normal FRC – 1.7 to 3.5 L
o Increased by:
 Body size (increased height)
 Increasing age
 Conditions – asthma, COPD
o Decreased by:
 Sex (women < men)
 Posture (standing > sitting > prone > lateral > supine)
 Muscle tone (diaphragm)
 Conditions – interstitial lung disease, kyphoscoliosis
 Increased abdominal pressure – obesity, pregnancy
 General anesthesia
 Reduced by ~ 400 ml in an adult
 Reduced by ~ 800 ml in supine position

 Closing capacity – point during expiration when the small airways begin to close
o Is ~ ½ FRC when standing and ~ ¾ FRC when supine in young healthy individual

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 o Increases with:
 Age
 Intraabdominal pressure
 Decreased pulmonary blood flow
 Pulmonary parenchymal disease
 Compliance – measure of change in volume of the lung when pressure is applied

 Laminar vs turbulent flow - Hagen-Poiseuille relationship

R = (8 x L x µ) / (π x r^4) R = resistance
L = length
µ = viscosity
r = radius
o Laminar flow – low flow
o Turbulent flow – higher flow rates with obstructed airways
 Dead space
o Physiologic dead space = anatomic + alveolar dead space
o Anatomic dead space – volume of lung that does not exchange gas
 ~ 2 ml/kg in spontaneously breathing individual
o Alveolar dead space – volume of gas that reaches the alveoli but does not take
part in gas exchange (lack of alveoli perfusion)

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 West zones of perfusion and ventilation

o Change from upright to supine position increases pulmonary blood volume by

25% to 30%
 A-a gradient
o Systematic evaluation of hypoxemia in assessing the efficiency of gas exchange at
the alveolar-capillary membrane
o Causes of hypoxemia:
 Normal A-a gradient
 Low inspired oxygen concentration (FiO2)
 Hypoventilation
 Elevated A-a gradient
 Shunt – sepsis, liver failure, arteriovenous malformations,
pulmonary emboli, right-to-left cardiac shunt
 Ventilation-perfusion (V/Q) mismatch – atelectasis, lateral
decubitus position, bronchial intubation, bronchospasm,
pneumonia, mucus plug, pulmonary contusion, adult respiratory
distress syndrome
 Diffusion abnormality

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 Hypercarbia
o Causes
 Hypoventilation
 Increased CO2 production
 Iatrogenic
o Symptoms
 Direct vasodilator of systemic circulation
 Direct vasoconstrictor in pulmonary circulation
 Direct cardiac depressant
 Increased cerebral blood flow
 Increased catecholamines – increased heart rate, myocardial contractility,
blood pressure, respiratory rate, decreased systemic vascular resistance
 Hypoxic pulmonary vasoconstriction (HPV) – local response of pulmonary arterial
smooth muscle that decreases blood flow in the presence of low alveolar oxygen pressure
o Helps to maintain normal V/Q matching by diverting blood from under ventilated
areas
o Inhibited by:
 Volatile anesthetics
 Vasodilators
o Not effected by intravenous anesthesia
 Arterial/venous oxygen content (CaO2 and CvO2)
Oxygen content = 1.34 x [Hgb] x SaO2 + (PaO2 x 0.003)
1.34 = O2 content per gram hemoglobin
SaO2 = hemoglobin saturation
Hgb = hemoglobin concentration
PaO2 = arterial oxygen concentration

 Oxygen consumption
o Increased
 Hyperthermia
 Hypothermia with shivering
 Hyperthyroidism
 Pregnancy
 Sepsis
 Burns
 Pain
 Pheochromocytoma

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 o Decreased
 Hypothermia without shivering
 Hypothyroidism
 Neuromuscular blockade
 General anesthesia
 CO2 transport
o Dissolved ~ 7%
o Bicarbonate ions (HCO3) ~ 70%
o Combined with Hgb ~ 23%
Age Related Pulmonary Changes

 Pediatrics
o Infant’s tongue is relatively large in proportion to the rest of the oral cavity 
obstruction of the airway
o Larynx
 Pediatric – more cephalad at C3-4 level
 Adult – C4-5 level
o Epiglottis – in an infant is narrower, omega shaped, and angled away from the
axis of the trachea
 Provides more difficulty to lift with the tip of a laryngoscope blade
o Vocal folds – have a caudad attachment anteriorly than posteriorly in comparison
to an adult, where they are perpendicular to the trachea
o Chest wall – floppy
 Compliance of the chest wall declines throughout childhood and
adolescence
o Lung compliance determined by volume  increases throughout childhood
o Elastic recoil pressure increases throughout childhood
o Total lung capacity (TLC) reduced
o Functional residual capacity (FRC) is similar to adults on a per-kilogram basis at
all ages
o Closing capacity declines throughout childhood and adolescence and increases
throughout adult life
o Airway resistance declines with growth
 Aging
o Dilation of alveoli, enlargement of airspaces, decrease in exchange surface area,
enlargement of airspaces, decrease in exchange surface area, loss of supporting
tissue
o Decreased lung recoil (elastance)  increased FRC
o Diminished chest wall compliance  increased work of breathing
o Respiratory muscle strength decreases
o Expiratory flow rates decrease
o Respiratory centers in the nervous system demonstrate decreased sensitivity to
hypoxemia and hypercapnia  blunted ventilatory response with heart failure,
airway obstruction, pneumonia

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Pharmacology

 Albuterol – selective beta-2 adrenergic agonist

o Treatment of – acute bronchospasm
o Dose
 100 µg per puff (limit 16-20 puffs daily)
 Nebulization – 2.5 to 5 mg albuterol
o Duration of action – 4 hours
o Side effects – tachycardia, hypokalemia
o Anesthetic considerations:
 Inhaled albuterol blunts airway responses to tracheal intubation in
asthmatic patients
 Effects additive with volatile anesthetics on bronchomotor tone
 Epinephrine – protype drug, naturally occurring catecholamine
o Released from adrenal medulla, regulates – myocardial contractility, heart rate,
vascular/bronchial smooth muscle tone, glandular secretion, metabolic processes
(glycogenolysis, lipolysis)
o Most potent activator of alpha-adrenergic receptors
o Activates beta1 and beta2 receptors
o Relaxation of bronchial smooth muscle via activation of beta2 receptors
o Side effects – cardiac stimulation, increased systolic blood pressure, heart rate,
cardiac output. Stimulation of alpha1 receptors produces vasoconstriction in the
skin, mucosa and hepatorenal vasculature
 Furosemide (Lasix) – loop diuretic
o Dose: 0.1 to 1.0 mg/kg iv
o Clinical use – mobilization of edema fluid due to renal, hepatic, or cardiac
dysfunction, treatment of increased intracranial pressure, inhibition of cellular
uptake of calcium for treatment of hypercalcemia
o Management of acute pulmonary edema
o Side effects – abnormalities of fluid and electrolyte balance
 Loss of potassium and chloride
 Develop acute tolerance
 Nitrous oxide – low-molecular-weight, odorless to sweet-smelling nonflammable gas of
low potency and poor blood solubility (0.46)
o Most commonly administered in combination with opioids and volatile
anesthetics to produce general anesthesia
o Poor blood solubility permits rapid achievement of alveolar and brain partial
pressure of the drug
o Causes minimal skeletal muscle relaxation
o Side effects – speculated to increase PONV, potential toxic effect on organ
function and ability to inactivate vitamin B12

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  Protamine – antagonist of heparin’s anticoagulation effect
o Dose – 1 mg for every 100 units heparin predicted to still be circulating
o In the absence of heparin, protamine interacts with platelets and proteins,
including fibrinogen.
o Side effects:
 Hypotension – iv injection associated with histamine release, causing
facial flushing, tachycardia, and hypotension
 Pulmonary hypertension – protamine neutralization of heparin can result
in secretion of thromboxane and 5-hydroxy tryptamine (serotonin)
manifesting as pulmonary vasoconstriction, pulmonary hypertension, and
bronchoconstriction
 Allergic reaction – described most in patients receiving protamine-
containing insulin preparations and allergy to fish

References
Ault, M. L., & Stock, M. C. (2009). Respiratory function. In P. G. Barash, B. F. Cullen, R. K.
Stoelting, M. K. Cahalan, & M. C. Stock (Eds.), Clinical anesthesia (6th Ed, pp. 233-
255). Philadelphia, PA: Lippincott Williams & Wilkins.
Coleman, M. D. (2011). Respiratory and pulmonary physiology. In J. Duke, Anesthesia secrets
(4th
Ed, pp. 17-23). Philadelphia, PA: Mosby Elsevier.
Insoft, R. M., & Todres, I. D. (2009). Growth and development. In C. J. Cote, J. Lerman & I. D.
Todres (Eds.), a practice of anesthesia for infants and children (4th ed., pp. 13-16).
Philadelphia, PA: Saunders Elsevier.
Stoelting, R. K., & Hillier, S. C. (2006). Pharmacology & physiology in anesthetic practice (4th
ed., pp.
43-44, 297-298, 308, 488-489, 509-510). Philadelphia, PA: Lippincott Williams &
Wilkins.

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 PULMONARY REVIEW

o Airway Anatomy
o Nasal passages: Septum, turbinates, adenoids
o Oral cavity: Dentition and tongue
o Pharynx: Tonsils, uvula, epiglottis
o Glottis: Vocal cords narrowest part of adult airway
o Rima glottis; opening between the VC, aka true glottis
o Larynx: At C4-C6 level
o Unpaired: thyroid, cricoid, epiglottis
o Paired: arytenoid, corniculate, cuneiform
o Cricoid: only complete cartilaginous ring in respiratory system
 Narrowest portion of airway in pediatric patient is Cricoid (Vocal Cord
in adults)
o Order from top to bottom
 Epiglottis, thyroid, cuneiform, corniculate, arytenoids, cricoid
o Two groups
 Muscles that open and close glottis
 Lateral cricoarytenoidadduct (close) VC
o External branch of SLN
o Affected when SLN damaged prevents VC from
coming together (adducting)
 Posterior cricoarytenoidAbduct (open) VC
o External branch of SLN
o “P” pulls cords apart
 transverse arytenoidcloses rima glottis
 Muscles that control tension of the vocal ligaments
 Cricothyroid lengthens (tightens) VC, increases pitch
 vocalis,
 thyroarytenoid relaxes VC
 Cricopharyngeus Muscle; barrier to regurgitation
 Areyepiglottic Muscle; closes the laryngeal inlet

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Nerve innervations;
o Superior Laryngeal Nerve
o Internal branch;
 Sensory; epiglottis, airway mucosa above VC and the VC themselves
 Major sensory N of larynx
o External branch;
 Motor; Cricothyroid muscles (open and close glottis)
o Recurrent Laryngeal Nerve
 Motor; All other intrinsic muscle of the larynx
 Sensory; Trachea below VC
 Major motor N of the larynx
 Left RLN more susceptible to injury because of long path
down under aortic arch and up to larynx
o Glossopharyngeal Nerve (CN IX)
o Sensory & taste; posterior 1/3 tongue
o Motor; posterior 1/3 tongue, stylopharyngeus
o Hypoglossal Nerve (CN XII)
o Motor; tongue
o Trigeminal N; Lingual branch (V3)
o Sensory anterior 2/3 tongue
o Facial N (CN VII) chorda tympani;
o Taste anterior 2/3 tongue

Muscles of Inspiration; diaphragm, External intercostal

Muscles of Expiration; Abdominal recti, internal intercostal
Type I pneumocytes;

 cover 80% of alveoli, very flat and thin provide surface for gas exchange, metabolically
limited and highly susceptible to injury
Type II pneumocytes;

 more numerous, can divide and form type I cells, make surfactant, O2 toxic resistant
Surfactant;

 decrease surface tension so pulmonary compliance is increased and the WOB is reduced
 permits alveolar stability by keeping small alveoli from collapsing into larger alveoli
 helps keep alveoli dry
o Surface tension decreases as an alveoli becomes smaller (less surface area)
o Laplace P=2T/R (P; pressure, T; tension, R; radius)
o By decreasing the T you decrease the P, by decreasing the R you increase the P

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Goblet cells;

 secrete mucus
Bronchial Circulation

 Arises from the left heart and sustains the metabolic needs of the tracheobronical tree
down to the level of the pulmonary bronchioles
Pulmonary circulation

 Received the total output of the right heart via the pulmonary arteries to the lungs for gas
exchange
 ~5L/min, 70-100mL at any one time
V/Q

 Alveolar ventilation; 4L/min

 Pulmonary capillary perfusion 5L/min
 4/5 = 0.8 normal V/Q
o >1 indicates dead spacing
o <0.8 indicates a relative shunt
Lymphatics

 Total flow is normally as much as 20mL/h

 Travel up along the airways forming the tracheobronchial chain of lymph nodes
 Left lung; drains into the thoracic duct
 Right lung; drains into the right lymphatic duct

Compliance;

 A measure of distensibility of the lungs expressed in ml/cm H2O

 The change in volume in response to a change in pressure
 Components
o Lungs (lung water, fibrosis, alveolar surface tension)
o Chest wall
o Abdominal muscle tension
o Breathing system
 Changes
o Low compliance: stiff chest wall or lungs, increased abdominal pressure
o High compliance: muscle relaxants, COPD
o In anesthetized patients, changes in compliance reflect mainly alterations
in lung compliance or abdominal pressure

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 Dynamic compliance= tidal volume/ (peak pressure – PEEP)
Static compliance= tidal volume/ (plateau pressure – PEEP)
Normal 35-100ml/cmH2O (adults); more than 15ml/cm H2O in children

Resistance

 The change in pressure along a tube divided by flow

 A measure of the ease with which a fluid, gas, or liquid flows through a tube
 A measure of the tendency of a hollow organ to recoil toward its original dimensions
upon removal of a distending or compressing force. It is the reciprocal of compliance

Closing Capacity

 The point during respiration that the small airways begin to close in dependent parts of
the lung
 Normally well below FRC
 CC Steadily rises with age (age 44 FRC = CC in supine pt, age 66 CC > FRC in the
upright position)
 Unaffected by posture

Character of Flows

 Laminar and Turbulent (Poiseuille law)

o Laminar
 Low Reynolds # <2000
 Smooth tubes, low velocities, high viscosity, low density
 Distal to small bronchioles
o Turbulent
 Trachea to terminal bronchioles
o 4 things that change Laminar into Turbulent flow
 high gas flows, sharp angles within the tube, branching in the tube,
decrease in the tubes diameter

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Respiratory centers

 Primary respiratory centers

o Dorsal respiratory group (DRG)
 Found in medulla
 Basic rhythm of respiration, “inspiratory pacemaker”
 Sends action potentials via phrenic N to external IC nerves to the
diaphragm and external IC muscles
o Ventral respiratory group (VRG)
 Influences both inspiration and expiration
 Involved when high levels of respiration are required
 Secondary respiratory centers
o Pneumotaxic center (PnC) and Apneustic center (ApC)
 PnC located high in pons, shuts off inspiration (aka PRG pontine
respiratory group);
 ApC; located lower in pons, promotes deep and prolonged inspiration
 PnC &ApC work together to help control the rate and depth of inspiration

Peripheral Chemoreceptors
o Carotid Bodies –
o afferents in glossopharyngeal, efferent in vagus;
o located at the bifurcation of the common carotid;
o sensitive to PaO2 (<60), PaCO2, & pH (all 3 because “c” is the 3rd letter in
the alphabet)
o Most responsive to PaO2 when it falls below 60
o Aortic Bodies –
o afferents and efferent in vagus;
o located between the ascending aorta and pulmonary artery;
o sensitive to PaCO2 and PaO2, but NOT pH;
o less sensitive than carotid bodies
o * regarding aortic and carotid chemoreceptors… If the PaO2 <60mmHg, they respond
by causing hyperventilation and increasing CO thru SNS stimulation. This response
to hypoxia is reduced by anesthetic drugs and extends into postop period.

Central Chemoreceptors
 Respond to hydrogen ions, lie in the anterolateral surface of the medulla
 H+ concentration in the CSF increases as PaCO2 increases and decreases as
PaCO2 decreases.
 Normally CO2 drives ventilation
Sensory pathways

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 o Hering-Breur reflex –
o SARS(slow adapt stretch receptor); Not activated during normal tidal
volumes; (>1.5L TV in adult)
o activated during exercise with increased tidal volumes;
o ventilation stimulated by these receptors with increased lung compliance in
chronic diseases;
o stim terminates inspiration affecting respiratory frequency
o very strong in the neonate
o Vagus N carries afferent (sensory) information

o Rapidly Adapting Stretch Receptors (irritant receptors) –

o mechanical and chemical irritation increase secretions (cough, sneeze,
bronchoconstriction)
o located in epithelium of carinal regions

o J-Receptor Reflexes –
o respond to increased interstitial volume;
o mediate hyperapnea associated with increase in left atrial pressure as in
vascular congestion & pulmonary edema;
o mediate apnea of PE when arterial end of capillary is blocked

Lung Volumes and Capacities

o Functional reserve capacity (FRC) = "the amount of gas left in the lungs after normal
(unforced) exhalation".
 FRC = ERV + RV, where
o ERV = expiratory reserve volume which is the "maximum volume of gas that can be
forcefully exhaled after a normal exhalation"
o RV = residual volume-"the amount of gas left in the lungs after a maximum exhalation"
o Minute ventilation
 Respiratory rate x Tidal volume= Min. Vent.
 Adult range 5-10 L/minute;
 neonatal range = 200-300 ml/kg/min
o Factors that increase FRC include:
 Emphysema, aging, asthma, peribronchial asthma, COPD
o Factors the decrease FRC include:
 Age, obesity or pregnancy ( IAP), supine posture, sedation, ANESTHESIA

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o Normal Pulmonary Function
 Respiratory Rate 10-16 breaths/min
 Minute Ventilation 5-8 L/min
 Mv = RR x TV
 Alveolar Ventilation/min 3-5 L/min
 AV = RR x TV – Vd (dead space ~2mL/kg)
 Maximum Voluntary Ventilation 90-125 L/min (Male); 74-95 L/min (Female)
o
 Tidal Volume Vt ~500 mL
 Each normal breath
 Inspiratory Reserve Volume (IRV) ~3000 mL
 Max additional vol. that can be inspired above Vt
 Expiratory Reserve Volume (ERV) ~1100 mL
 Max. vol. that can be expired below Vt
 Total Lung Capacity (TLC) ~5800 mL
 RV+ERV+VT+IRV
 Functional Residual Capacity (FRC) ~2300 mL
 RV+ERV
 Inspiratory Capacity (IC) M-3600 F-
2400
 Vital Capacity (VC) ~60-70 mL/kg

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 How do we use the FEV1/FCV ratio to discriminate between obstructive and
restrictive lung disease?

 Step 1- look at the FCV (forced vial capacity) to see if its within normal limits
 Step 2- look at the forced expiratory volume in one second (FEV1) and determine
if it is within normal limits
 Step 3- if both FVC and FEV1 are normal, then you do not have to go any further-
the patient has normal PFTs
 Step 4- if FVC and/or FEV1 are low, then the presence of disease is highly likely
 Step 5- if step 4 indicates that there is disease then you need to go to the %
predicted for the FEV/FCV1.
i. If the % predicted for the FEV/FCV1 is 88%-90% or higher, then the
patient has a restricted lung disease.
ii. If the % is 69% or lower, then the patient has an obstructed lung disease
2. Anatomic Dead Space
 Volume of air in conducting airways not involved in gas exchange
 ~2 mL/kg
3. Alveolar Dead Space
 Air that enters non/poorly perfused alveoli
4. Anatomic + Alveolar = Physiologic dead space
 SV = 20-40% (avg 33%)
 CV = 40-60%
5. Things that increased dead space
 Age
 Positive pressure ventilation
 PE
 Lung disease

V/Q

 Alveolar ventilation; 4L/min

 Pulmonary capillary perfusion 5L/min
 4/5 = 0.8 normal V/Q
Shunts

 R  L; hypoxic, a portion of blood from the right side of the heart is shunted past the
lungs to the Left side of the heart and delivered to the body without being oxygenated
 Intrapulmonary shunt; blood passes from the PA to the pulmonary vein through
capillaries of unventilated or poorly ventilated alveoli

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Hypoxic pulmonary Vasoconstriction

 In response to alveolar hypoxia, pulmonary vessels constrict so that there is less blood
flow to the unoxygenated alveoli
 Homeostatic protective mechanism to divert blood away from hypoxic (atelectasis)
regions of lungs (local increases in PVR) optimizing oxygenation
 Significance of AHPAV
o Decrease shunt/decrease shunt severity
o Decrease perfusion to under ventilated or poorly ventilated alveoli
 Inhibition of HPV during 1-lung ventilation could make hypoxemia worse
 Vasodilators inhibit HPV: nitroprusside, NTG, hydralazine, B agonists, CCB
 Inhalation agents don’t seem to interfere with HPV < 1 MAC
 Other HPV inhibitors: very high or very low PAP, hypocapnia (it causes vasodilation),
high or very low mixed venous PO2, pulmonary infection, NO

Lung Zones

 Zone 1; PA > Pa > PV

o Top of lung Nondependent part, no gas exchange, NO blood flow
o Not normally present, it is a pathologic zone that develops with pulmonary
hypotension
 Zone 2; Pa > PA > PV
o Intermittent blood flow
o The waterfall zone
 Zone 3; Pa > PV > PA
o Dependent part of lung
o Continuous blood flow
o Gas exchange
o This is where the tip of the Swan should be, the LV pressure is reflected back
through zone 3 to the site of where the swan is wedged
 Zone 4; Pa > Pisf > PV > PA
o Proportional to the Pa pressure – pulmonary interstitial fluid
o Not normally present, a pathological zone present when there is pulmonary edema

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A-a gradient
• PAO2 = FiO2(PB-47) – 1.2(PaCO2)
• A-a gradient provides an assessment of alveolar capillary gas exchange.
• The larger the gradient, the more serious the respiratory compromise.
• Large A-a gradient indicates a R L shunt
• PaO2 = (FiO2 x (760-47)) – (PaCO2/0.8)
• A-a gradient = PA02-PaO2
• Normal A-a gradient = (Age+10)/4
o Normal A-a gradient when breathing RA 5-15mmHg
• Abnormal: V/Q mismatch, r-l shunt

The Oxyhemoglobin dissociation curve

o The position of this curve may shift rightwards (lower saturation for given PaO2) or
leftwards (higher saturation for a given PaO2).
o RIGHT SHIFT Unload O2 easier (decreased affinity)
 Certain circumstances make the blood more likely to dump oxygen into the
tissues,
 Active muscle needs more oxygen, so heat, exercise, acidosis,
hypercarbia and increased 2,3-DPG, low levels of carbamino
compounds all cause a shift in the curve rightwards – releasing oxygen
 R: right shift
 I: increase in
 G: 2,3 DPG
 H: [H+] Acidosis
 T: temperature
 S: sickle cell disease
o LEFT SHIFT  Hold on to O2 (increased affinity)
 Certain circumstances make the blood more likely to cling on to oxygen
 when activity is minimal – such as in cold weather or during rest,
when the tissues are cold, alkalotic, hypocarbic and low 2,3-DPG, high
levels of carbamino compounds then hemoglobin holds onto oxygen.
 The curve also shifts leftwards in carbon monoxide poisoning,
methemoglobinemia & fetal hemoglobin.

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 o P50
 The partial pressure of oxygen in the blood at which the hemoglobin is 50%
saturated, typically about 26.6 mmHg for a healthy person
 Decreased P50 Left Shift Increased Affinity
 Increased P50  Right Shift Decreased Affinity
o Left shift, a SaO2 reading of 95% (usually considered normal) denotes a PaO2 of 76,
which is hypoxic.
o Right shift, a SaO2 of 75% (usually considered severely hypoxic) denotes a PaO2 of
88. This patient is not nearly as hypoxic as the SaO2 would lead us to believe.
o Rough estimate
 PO2 SpO2
 40 70%
 50 80%
 60 90%

Estimate a pts PaO2 based onFIO2 assuming patient is without lung disease.

 Multiply inspired FIO2 by 5 to estimate the PaO2 (arterial)

 Multiply inspired FIO2 by 6 to estimate the PAO2 (alveolar)
i. Pt on 40% FIO2, PaO2=200mmHg, PAO2=240mmHg
ii. PAO2-PaO2 gradient in healthy adult with FiO2of .4
1. (40*6)-(40*5)=40mmHg
Oxygen consumption (VO2)

 VO2= 250mL/min
 This is 3-4mL/O2/kg/min
 250mL/min ÷ 70kg patient = 3.57 mL/min
o VO2 with
 Metabolic rate; Temp, shivering, thyroid, burns, sepsis, pregnancy
o VO2 with
 Metabolic rate; Temp, thyroid, general anesthesia

O2 Content = (Hgb x 1.36 x SaO2) + (0.0031 x PaO2)

 1.36 the amt. of O2 bound to hemoglobin at 1 atmosphere

 0.0031 the amt. of O2 dissolved in plasma

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Pressure volume loops

Pressure-Volume (compliance) loop

 Volume on vertical axis, pressure on horizontal

 Direction of the loop:
o clockwise with spontaneous
o counter clockwise with controlled ventilation
 VT= highest point on loop
o Read off vertical axis
 Expiration starts at highest point on the loop, and moves down to zero pressure
 PEEP is seen when the lowest point on the loop is non zero on the horizontal axis
 Area inside the loop corresponds to work of breathing
 Slope of the loop shows compliance
o A loop that is more horizontal than the baseline loop indicates a high pressure
required to deliver a relatively low volume

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Factors causing decreased compliance in clued stiffer lungs or chest wall for whatever reason:

 Inadequate muscle relaxation

 Air embolism
 Diseases such as tumor that invade large areas of the lung or decrease is distensibility
 Narcotics
 Bronchial intubation
 Bronchoconstriction
 Pneumothorax
 Position in lateral, lithoty, prone, or Trendelenburg
 External pressure on chest wall or abdomen
 Abdominal retraction or packing
 Abdominal enlargement
 Curvature of the spine
 Obesity
 Carbon dioxide insufflations of abdomen for laparoscopy

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Increased compliance= a loop that is more vertical than the baseline loop, a low pressure
required to deliver a high volume
Factors increasing compliance include PEEP and resolution of the factors that are decreasing
compliance
Increased resistance can also be seen in the pressure-volume loop

 Higher pressures with the same or diminished tidal volume are characteristic
 Seen in a clockwise shift loop with a large internal area
 Pressure falls rapidly at end-inspiration

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Flow-volume Loops

 Volume on the horizontal axis, flow on the vertical

 Zero point for volumes in on the right
o Corresponds to functional residual capacity
 Inspiratory flow is plotted below the horizontal axis
o Moves leftwards as volume increases
o Drops to zero flow at end-inspiration
 Corresponds to VT on the horizontal axis
 Expiratory flow is shown above the horizontal axis
o Shape is determined by passive lung deflation
 Determined by the elastic properties of the lung and chest wall and by the
total resistance of the trachea-bronchial tree, tracheal tube, and breathing
circuit
o Normal shape is a flow rate that increases rapidly in early expiration, quickly
reaches a peak, the slows and gradually returns to zero
 The shape of the expiratory portion of the flow-volume loop changes with alterations in
resistance

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 Increased resistance causes
o decreased peak expiratory flow rate,
o decreased flow throughout exhalation, and
o possibly a decrease in tidal volume
 progressive changes in expiratory, and even inspiratory flows, are seen as
bronchoconstriction increases in severity
Increased resistance may be caused by:
-tracheal tube obstruction (kinked, dislodged, secretions
-bronchoconstriction
-collapse of airways from loss of elastic recoil
-obstruction in a large airway (tumor, blood, secretions, foreign body
-tracheal tube too small or
-upper airway obstruction (if not intubated)

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Open Loops
o a loop should return to (or close to ) its starting point
o An open loop has a gap indicating that exhaled volume is less than inhaled.
o Caused by
o Incorrect calibration
o Exhalation incomplete before next inhalation (COPD, increased resistance to
expiration caused by apparatus, lung retraction, flap-valve obstruction in large
airway) or
o Leak distal to sensor (parietal disconnect, cuff leak, partial extubation, tension
pneumothorax
 A tension pneumothorax should also show decreased compliance

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Geriatric pulmonary changes:

 Loss of lung elastic recoil due to increase in fibrous connective tissue in lung parenchyma
 in post op ventilatory failure
 Age related arterial oxygenation. Change in physical properties of lungs (V/Q
mismatch)
 Likelihood of transient apnea when given opioids or benzos
 Threshold stimulus for vocal cord closure = aspiration risk
 Normal Physiological changes;
o Decreased
 Pulmonary elasticity
 arterial oxygen tension (by an average of 0.35mmHg per year) PaO2
 Muscle strength
 Cough effectiveness
 Breathing capacity
 small airway diameter
 Resp. center sensitivity
 chest wall compliance
 functional alveolar surface area
o Increased
 residual volume
 closing capacity
 chest wall rigidity
 A-P diameter (barrel chest)
 central airway size
 Lung compliance
 FRC
 Aa gradient
o V/Q mismatching
o Blunted response to hypercapnia and hypoxia

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Pediatric Pulmonology

 Alveolar maturation is not complete until late childhood ~8 years of age

 WOB and respiratory muscle easily fatigue
 Cartilaginous rib cage makes their chest wall very compliant
 High rate of O2 consumption
 Hypoxia and hypercapnia depress respiration
 Infants have a proportionately larger head and tongue, narrow nasal passages, anterior
and cephalad larynx, a long epiglottis, short trachea
 Obligate nasal breathers until 5 months of age
 Cricoid cartilage is the narrowest part of the pediatric airway, at level C4
 Infants have a higher alveolar ventilation and lower FRC then older children, this leads to
a rapid rise in alveolar anesthetic concentration and speeds inhalation induction.
 Tracheal compliance can lead to tracheal collapse

Drugs….

Albuterol (Proventil)

 Selective B2 agonist
 Treatment of acute bronchospasm
 HHN 2.5-5.0mg
 MDI about 100mcg per puff, dose 2 puffs QID (increase to 6-8 puffs if given through
ETT)
 Onset; 3-5min, Duration of action is about 4 hours
 Side Effects; tremor, tachycardia, hypokalemia

Ipratropium Bromide (Atrovent)

 Muscarinic antagonist in the smooth muscle of the bronchi causing bronchodilaton

 Anticholinergic drug used to treat COPD and acute asthma
 Can be combined with Albuterol (Combivent a MDI, or Duoneb via HHN)
 MDI 17mcg per puff, dose 2 puffs QID
 HHN 0.5mg
 Minimal systemic absorption, no increase in HR or intraocular pressure

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Budesonide (Pulmicort)

 Inhaled corticosteroid
 Used to prevent asthma attacks by decreasing irritation and swelling in the airways
 NOT used to treat an acute asthma attack
 90-180mcg via MDI

Lasix (Furosemide)

 Loop diuretic; inhibits loop of henle and proximal and distal convoluted tubule sodium
and chloride reabsorption
 Can cause hypokalemia and hyponatremia
 Cross sensitivity with sulfonamides
 Treatment of pulmonary edema
 Dose 2-100mg q 6-12 hours IV
o If the patient take Lasix on a regular basis know their typical daily dose, the IV
dose is about half of the PO dose

Theophylline (Aerolate)

 Competitive non-selective PDE inhibitor, increases intracellular cAMP

 Treatment of chronic asthma, COPD, bronchospasm
 Actions;
o relaxing bronchial smooth muscle
o increasing heart muscle contractility and efficiency; as a positive inotropic
o increasing heart rate: positive chronotropic
o increasing blood pressure
o increasing renal blood flow
o some anti-inflammatory effects
o Central nervous system stimulatory effect mainly on the medullary respiratory
center.
 Multiple drug interactions, given PO or IV
 Narrow therapeutic index; normal plasma level is 10-20mcg/mL, >20mcg/mL prone to
cardiac dysrhythmias

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 Endocrine System
Anatomy/Physiology

 Pituitary gland – connection between the nervous system and endocrine system via
hypothalamic pituitary axis (HPA)
o Located in sella turcica of the sphenoid bone
o Anterior pituitary
o Posterior pituitary

 Thyroid gland
o Stores oxidized iodine
o Secretes thyroxine (T4), triiodothyronine (T3), and calcitonin
 Calcitonin regulates Ca++ and iodine
 Calcitonin is an antagonist of PTH  Ca++ levels
 T3 is formed from deiodination of T4
 Autoregulation via hypothalamus
 Parathyroid gland – 4 to 5 on posterior aspect thyroid
o Regulator of Ca++ (factor IV) homeostasis
o Ca++ with enhancement of bone reabsorption, limit renal excretion, enhance
GI absorption (with vit D metabolism)

 Pancreas – contains å, ß, ∂ cells

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Pancreas:
The pancreas is a dual-function gland. While most glands are either exocrine or endocrine, the
pancreas has both exocrine and endocrine functions. Exocrine glands secrete substances outside
the body or into the gut, while endocrine glands secrete substances into the blood. Consequently,
the physiology of the pancreas can be considered in the context of the substances that the
pancreas releases into the gut (it does not excrete substances outside the body) or into the blood.

Products from the exocrine portion of the pancreas are called enzymes and include trypsin,
chymotrypsin, pancreatic amylase, and pancreatic lipase. Major products of the endocrine
pancreas are called hormones and include insulin, glucagon, and somatostatin.
 One of the greatest concerns with the pancreas and anesthesia is whether or not the
patient has diabetes mellitus. Want to know blood sugar day of surgery and A1C. How
long have they had the diagnosis? Do they have symptoms of neuropathy? Would they
know if they had chest pain? What about gastroparesis? Will you treat this patient as a
full stomach?

o Å cells – secrete glucagon  blood glucose

o ß cells – secrete insulin  blood glucose
 Insulin is an anabolic hormone
 Secretion of ~50 units/day or ~2 units/hr
 entry of glucose and K+ into adipose and muscle cells
 glycogen, protein and fatty acid synthesis
 glycogenolysis, gluconeogenesis, ketogenesis, lipolysis and protein
catabolism
o ∂ cells – secrete somatostatin  release of GH and digestive hormones
 Adrenal gland – regulates stress response via corticosteroids and catecholamines
o Adrenal cortex
 Glomerulosa 
aldosterone/mineralocorticoids
 Aldosterone  Na+/ H2O
reabsorption and K+/H+
excretion
 Fasciculata  cortisol/glucocorticoids
 Cortisol  ~20 mg
secreted/day
 Glucocorticoids
o lipolysis,
glycogenolysis,
gluconeogenesis
o peripheral glucose utilization hyperglycemia

 Reticularis  estrogen/testosterone

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 o Adrenal medulla – release catecholamines from chromaffin cells in response to
stress, hypotension, hypothermia, hypoglycemia, hyperglycemia, hypercapnia,
hypoxemia, pain, fear
 Epinephrine  ~80%
 Norepinephrine  ~15%
 Dopamine  ~5%
Pathophysiology

 Diabetes mellitus (DM) – impaired carbohydrate metabolism as a result of absolute or

relative deficiency of insulin or insulin responsiveness, leading to hyperglycemia and
glycosuria
o Dx: fasting blood glucose ≥ 126 mg/dL or fasting plasma glucose > 140 mg/dL;
glucose tolerance test 200 mg/dL
o Complications:
 Diabetic ketoacidosis (DKA)  associated with type I
 insulin ketone bodies metabolic acidosis DKA
 Primary cause infection
 Sx: tachypnea, nausea/vomiting, abdominal pain, changes in
sensorium
 Tx: correct hyperglycemia, dehydration, hypokalemia
o Insulin 0.1 unit/kg/hr
 Add D5W when glucose = 250 mg/dL
o 1 to 2 L 0.9% NS for 1 hour  250 to 500 ml/hr
 Avoid LR  converts to HCO-3
 Hyperglycemic hyperosmolar nonketotic syndrome (HHNKS) 
associated with type II
 Hyperglycemic diuresis  dehydration/hyperosmolarity without
ketone formation
 Sx: severe dehydration with lactic acidosis, renal failure, altered
mentation, seizure
 Tx: fluid resuscitation 0.9% NS, small dose insulin, K+
supplementation
 Hypoglycemia  result of excessive insulin with blood glucose < 50
mg/dL
 Sx: diaphoresis, elevated heart rate, nervousness r/t catecholamine
discharge
 Tx: D50  for each ml D50 should raise glucose 2 mg/dL

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 o Long term complications  hypertension, coronary artery disease, congestive
heart failure, myocardial infarction, diastolic dysfunction, peripheral vascular
disease, cerebral vascular disease, peripheral and autonomic neuropathies, renal
failure, optic neuropathy, stiff joint syndrome
o Anesthetic considerations:
 Hold Metformin and Sulfonylureas 24 to 48˚ prior to surgery  increases
risk of severe lactic acidosis
 ACE-Is and ARBs increase risk of sudden cardiac death
 Those on NPH are at increased risk of allergic reaction and death from
protamine administration
 Autonomic neuropathy increases risk of cardiovascular instability and
sudden cardiac arrest
 Delayed gastric emptying
 Diabetes insipidus (DI) – result of impairment of kidneys to concentrate or failure of
renal tubules to respond to ADH
o Central DI – reduced antidiuretic hormone secretion
 Associated with lesions in or around the hypothalamus and pituitary gland
 Dx: polydipsia, polyuria (> 6L/day) with absence of hyperglycemia
 Tx: vasopressin 5 units sq. q4˚ or DDAVP 5 to 10 mg intranasal q 12 to
24˚
o Nephrogenic DI – reduced response to circulating ADH or interference with renal
countercurrent mechanism
 Dx: kidneys fail to respond to administration of exogenous ADH
(vasopressin, DDAVP)
 Tx: treat the cause and maintain adequate fluid intake
 Hypothyroidism – reduced T4 as a result of autoimmune disease (Hashimoto’s
thyroiditis), thyroidectomy, radioactive iodine, antithyroid medications, iodine
deficiency, hypothalamopituitary dysfunction
o Sx: weight gain, cold intolerance, muscle fatigue, constipation, hypoactive
reflexes, dull facial expression, depression, reduced HR/SV/CO, cool and mottled
extremities.
o Tx: synthetic thyroid hormone
o Myxedema coma – life-threatening complication of extreme hypothyroidism
 Sx: altered LOC, hypoventilation hypothermia, hyponatremia, CHF
 Tx: loading dose levothyroxine 300 to 500 mg IV, followed by
maintenance infusion 50 mg/day; hydrocortisone 100 mg iv q8˚; monitor
EKG for ischemia or dysrhythmia
 Anesthetic considerations: ketamine is a preferred agent for induction;
avoid hypotension and myocardial depressants; non opioid analgesics
should be used for postop analgesia; hypothermia, respiratory depression
and slow biotransformation slow recovery

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 Hyperthyroidism – caused by Grave’s disease, toxic multinodular goiter, thyroiditis,
TSH-secreting pituitary tumors, functioning thyroid adenomas, over dosage thyroid
replacement therapy
o Sx: weight loss, heat intolerance, muscle weakness, diarrhea, hyperactive reflexes,
nervousness, fine tremor, exophthalmos or goiter
o Dx: elevation free T4, total T4, or T3
o Tx: propylthiouracil, methimazole to reduce hormone synthesis; potassium or
sodium iodide to reduce hormone release; ß blocker for blood pressure control;
radioactive iodine or subtotal thyroidectomy
o Anesthetic considerations:
 Elective procedures should be postponed until euthyroid
 Propylthiouracil (PTU) and methimazole should be taken up to the time of
surgery
 Thiopental is the induction agent of choice with its antithyroid activity
 Monitor temp closely
 Avoid SNS stimulating agents – ketamine, pancuronium
 Chronic hypovolemia and vasodilation exaggerate hypotension
 Ensure adequate depth of anesthesia in avoidance of elevated heart rate,
blood pressure and ventricular dysrhythmias
 Thyroid storm – most serious complication
 Sx: hyperpyrexia, elevated heart rate, reduced blood pressure,
altered LOC
 TX: hydration, cooling, esmolol infusion or propranolol,
propylthiouracil and sodium iodide; hydrocortisone or cortisol for
adrenal suppression.
 Addison’s disease – primary adrenal (mineralocorticoid and glucocorticoid)
insufficiency as a result of adrenal gland destruction
o Sx: hypoaldosteronism – hyponatremia, hypovolemia, hypotension, hyperkalemia,
metabolic acidosis. Hypocortisolism – weakness, fatigue, hypoglycemia,
hypotension, weight loss
o Anesthetic considerations:
 Avoid etomidate as it produces adrenal suppression
 Ensure adequate steroid replacement  hydrocortisone phosphate prior to
surgery, hydrocortisone at induction.
 Cushing’s disease – glucocorticoid excess as a result of benign pituitary adenomas
o Sx: muscle wasting, weakness, osteoporosis, truncal obesity, buffalo hump,
abdominal striae, glucose intolerance, hypertension and altered LOC
o Tx: Preop K+ supplementation, spironolactone, supplemental steroids
o May have increased sensitivity to NMBAs due to muscle weakness

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 Pheochromocytoma – catecholamine-secreting vascular tumor due to chromaffin cell
hyperplasia
o Sx: paroxysmal headache, hypertension, sweating, palpitations
 Å stimulation – vasoconstriction, increased systemic vascular resistance
and elevated blood pressure
 ß stimulation – increased automaticity and ventricular ectopy
o Dx: elevated plasma catecholamine level, urine metanephrines and VMA
o Tx: å and ß blockade
 Å blockade must precede ß blockade in prevention of acute heart failure
 Å blockade - to reduce systemic vascular resistance, reduce blood
pressure, increase intravascular volume and reduce hematocrit
 Phenoxybenzamine  use for control 2 to 4 weeks preoperatively
 phentolamine  shorter duration of action than
Phenoxybenzamine, generally used intraoperative
 ß blockade – reduce myocardial work and balance MDO2 and MVO2
 Esmolol
o Anesthetic considerations:
 Avoid succinylcholine, ketamine, pancuronium, vagolytics, ephedrine,
histamine releasing medications (Atracurium, morphine), Droperidol
 Avoid hypoventilation – will increase SNS stimulation and dysrhythmias
 Blood pressure control with  phentolamine, SNP, nicardipine; SNP may
be preferred due to rapid onset
 Following tumor removal, profound hypotension generally occurs
 Acromegaly/gigantism – result of pituitary adenoma that secretes GH
o Anesthetic considerations – enhanced growth of nose, epiglottis, vocal cords,
distal extremities, osteoarthritis, TMJ instability, DM myopathies/neuropathies
 Hypoaldosteronism – reduced aldosterone production caused by adrenal suppression,
Addison’s dz, diuretics, ACE-Is or NSAID
o Sx: diuresis, hypotension
o Dx: reduced serum aldosterone and Na+ and elevated K+
o Tx: volume replacement, sodium supplementation
 Hyperaldosteronism – elevated aldosterone production caused by impaired feedback
mechanism or adrenal tumor
o Sx: edema, weight gain, hypertension
o Dx: elevated serum aldosterone and Na+ and reduced K+
o Tx: aldactone antagonists (spironolactone), antihypertensives, K+
supplementation

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Pharmacology

 Desmopressin (DDAVP) – synthetic analogue of AVP with intense antidiuretic effect and
decreased pressor effect
o Causes endothelial cells to release von Willebrand factor, tissue-type plasminogen
activator, and prostaglandins
o Administered twice daily intranasally
o Drug of choice for DI as fewer side effects than vasopressin
o Not effective in treatment of nephrogenic diabetes insipidus
o Reported to minimize intraoperative blood loss in patient undergoing cardiac
surgery or spinal fusion
o Side effects: reduction in systemic vascular resistance may lead to hypotension
 Oxytocin – selective in the stimulation of uterine smooth muscle
o Synthetic preparations are identical to the hormone normally released from the
posterior pituitary
o Clinical use: induce labor at term and decrease hemorrhage in postpartum or post
abortion period. Sensitivity of uterus to oxytocin increases as pregnancy
progresses
o Dosage: dilute solution to 10 mU/mL and administer continuously beginning at 1
to 2 mU per minute. Increase rate 1 to 2 mU per minute every 15 to 30 minutes
until optimal response (uterine contraction every 2 to 3 minutes) is obtained.
Average dose to induce labor is 8 to 10 mU per minute. May increase to 40 mU
per minute for uterine atony initially after delivery
o Side effects: direct relaxant effect on vascular smooth muscle, reflex tachycardia,
increased cardiac output
 Phenoxybenzamine – haloalkylamine derivative that acts as a nonselective alpha-
adrenergic antagonist by combining covalently with alpha-adrenergic receptors
o Onset: slow  60 minutes to reach peak effect
o Elimination half-time ~ 24 hours
o Clinical use: administered preoperatively to control blood pressure in patient with
pheochromocytoma, treatment of peripheral vascular disease characterized by
intermittent claudication, in conditions with cutaneous vasoconstriction (i.e.
Raynaud syndrome)
o Side effects: orthostatic hypotension, sedation, nasal stuffiness
 Phentolamine – substituted imidazoline derivative that produces transient nonselective
alpha-adrenergic blockade
o Produces peripheral vasodilation and decrease in systemic blood pressure that
manifests within 2 minutes and lasts ~ 10 to 15 minutes
o Enhances neural release of norepinephrine manifesting as increased heart rate and
cardiac output
o Clinical use: acute hypertensive emergencies
o Metabolism: Hepatic
o Side effects: cardiac dysrhythmias, angina pectoris, hyper peristalsis, abdominal
pain, diarrhea

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 Vasopressin – exogenous preparation of AVP used for AVP-sensitive diabetes insipidus,
evaluation of urine-concentrating abilities of the kidney, management of uncontrolled
hemorrhage, hemodynamic stabilization in the presence of hemorrhagic and septic shock,
management of refractory cardiac arrest
o TX of DI: administered IV for initial evaluation of patients with suspected DI.
Oral administration is followed by rapid inactivation by trypsin, which cleaves a
peptide linkage. IV administration results in brief effect because of rapid
enzymatic breakdown of peptides
o Side effects: vasoconstriction, increased system blood pressure, facial pallor,
elevated pulmonary artery pressures, may produce selective vasoconstriction of
the coronary arteries, stimulation of GI smooth muscle, reduced platelet count.

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 Endocrine Disease & Anesthesia
Diabetes Mellitus

 Liver is primary source of endogenous glucose production via glycogenolysis and

gluconeogenesis.
 After a meal, plasma glucose level rises stimulating an increase of plasma insulin
secretion to promote glucose utilization (brain, GI tract, RBC’s). Hyperglycemia
producing hormones (glucagon, epinephrine, growth hormone, and cortisol) comprise
other half of regulatory system for balance of blood sugar.
 Diabetes Mellitus results from inadequate supply or response to insulin which leads to
elevated glucose levels causing micro vascular and macro vascular complications
 Type 1a – autoimmune destruction of beta cells within pancreatic islets resulting in
complete absence or minimal circulating levels of insulin
 Type 1b – rare disease of absolute insulin deficiency that is not immune mediated
 Type 2 – not immune mediated; result of defects in insulin receptors and post receptor
intracellular signaling pathways
 Signs & Symptoms
o Type 1 – caused by T-cell mediated autoimmune destruction of pancreatic beta
cells
 Long pre-clinical period (9-13 yrs) with antibodies to beta cell antigens
and loss of beta cell function (80-90% loss before hyperglycemia occurs)
 Clinical presentation – sudden, severe hyperglycemia (fatigue, weight
loss, polyuria, polydipsia, blurring of vision, hypovolemia)
 Diagnosis – spot blood sugar > 200 and HbA1C > 7 (ketoacidosis
represents severe insulin deficiency and unrestrained lipolysis)
o Type 2 – characterized by relative beta cell insufficiency and insulin resistance
 Disease usually present 4-7 yrs before diagnosis
 Peripheral tissue insulin insensitivity → increased insulin secretion
→pancreatic cell function decrease and unable to compensate →
hyperglycemia
 3 defects seen in DM II
 ↑ rate of hepatic glucose release (normally insulin inhibits this)
o Insulin resistance inherited with obesity and sedentary
lifestyle contributing
 Impaired basal and stimulated insulin secretion
 Inefficient use of glucose by peripheral tissues (resistance)
 Metabolic Syndrome (insulin-resistance syndrome)
 Constellation of symptoms associated with DM II
o HTN, dyslipidemia, procoagulant state, obesity, premature
atherosclerosis and then CV disease
o Affects 25% of people in US

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 Diagnosis
o Symptoms of DM plus random plasma glucose > 200
 Polyuria, polydipsia, unexplained weight loss
o Fasting plasma glucose > 125
o 2 hr plasma glucose level > 200 during oral glucose tolerance test
o HgbA1C normal = 4-6
 Treatment
o Dietary adjustments, exercise therapy and oral antidiabetic drugs, weight control
o Oral Anti-diabetic drugs
 4 classes
 Secretagogues – increase insulin availability (sulfonylureas,
meglitinides)
o ↑ insulin secretion from pancreatic beta cells
o Possibly ↓ protective cardiac ischemic preconditioning by
Potassium adenosine triphosphate channels in the
myocardium
 Biguanides – suppress excessive hepatic glucose release
(metformin)
o Also enhance glucose utilization in skeletal muscle and
adipose
o ↓ triglyceride and LDL levels and ↓ postprandial
hyperlipidemia and plasma free fatty acids
o Risk of lactic acidosis > in renal insufficiency; less
common with metformin than phenformin
 Thiazolidinediones or glitazones – improve insulin sensitivity (rosi
or pio)
o Bind to peroxisome proliferator – activated receptors
located in skeletal muscle, liver and adipose tissue
 α glucosidase inhibitors – delay GI glucose absorption (acarbose,
miglitol)
o inhibit α glucosidase enzymes in the brush border of
enterocytes in the proximal small intestine – delay
intraluminal production and subsequent absorption of
glucose
o Insulin added at hs if combo therapy of above ineffective as overnight hepatic
glucose production typically greatest
 Necessary to treat all DM I and 30% DMII
 Basal insulin - (wt in kg x 0.3) /24 hrs = hourly insulin requirement
 intermediates – NPH,lente, lispro, aspart) – twice daily
 long-acting (ultra-lente, glargine) – once daily
 Short-acting (regular) or rapid acting (lispro, aspart)

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 o Hypoglycemia – most frequent complication of therapy
 Exacerbated by simultaneous administration of: alcohol, sulfonylureas,
Biguanides, Thiazolidinediones, ACE inhibitors, MAOI’s, and non-
selective BB’s
 BBs inhibit lipolysis of adipose tissue which is an alternate fuel during
hypoglycemia
 Symptoms – sweating, tachycardia, palpitations, restlessness, pallor
(adrenergic) or fatigue, confusion, HA, somnolence, convulsions, coma
(neuroglycopenic)
 Complications
o Diabetic Ketoacidosis (DKA)
 More common in DMI precipitated by infection or acute illness
 Glucose levels exceed threshold for renal tubular absorption → significant
osmotic diuresis and hypovolemia
 Gluconeogenesis and ketogenesis tightly coupled = overproduction of
ketoacids by liver
 Anion gap metabolic acidosis
 Treatment – volume (NS) and insulin with electrolyte supplementation (K,
Na, Phos)
o Hyperglycemic Hyperosmolar syndrome
 Severe hyperglycemia, hyperosmolarity (>340 mOsm/L), dehydration,
more common in DMII – elderly with acute illness; evolves over days to
weeks
 No ketoacidosis
 Treatment – significant fluid resuscitation (hypotonic for hyperosmolar),
insulin administration and electrolyte supplementation
o Microvascular Complications – nonocclusive, microcirculatory disease and
impaired autoregulation of blood flow and vascular tone
 Nephropathy
 35% DM I & 10% DMII develop ESRD
 HTN, albuminuria, peripheral edema, progressive ↓ in GFR
 When GFR < 20 ml/min – kidneys unable to excrete potassium and
acids = hyperkalemia and metabolic acidosis
 HTN, hyperglycemia, hypercholesterolemia and microalbuminuria
accelerate the ↓ in GFR
 ACE inhibitors – retard progression of proteinuria and ↓ GFR
 Peripheral Neuropathy
 50% who have had DM > 25 yrs
 Significant morbidity results from recurrent infection, foot
fracture, amputations
 TX – NSAIDS, antidepressants, anticonvulsants for pain control

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  Retinopathy
 Result of microvascular blood vessel occlusion, dilation, increased
permeability and micro aneurysm formation resulting in
hemorrhage, exudation and growth of abnormal blood vessels and
fibrous tissue
 Autonomic Neuropathy
 Affects any part of the ANS – result of damaged vasoconstrictor
fibers, impaired baroreceptor function and ineffective CV
reactivity
 Abnormalities in heart rate control and vascular dynamics,
dysrhythmias may result in death, orthostatic hypotension severe in
advanced stages
 Impaired gastric motility and secretion – gastroparesis, N & V and
constipation or diarrhea
 Altered respiratory reflexes and impaired respiratory responses to
hypoxia and hypercapnia
o Macrovascular complications
 CV disease – 20-30% MI patients are diabetic
 Elevated triglycerides, low LDL and abnormally small, dense, LDL = lack
of appropriate insulin signaling
 Management of Anesthesia
o Pre-operative Evaluation
 High index of suspicion for myocardial ischemia as well as CV, renal,
neurologic and musculoskeletal symptoms
 Silent MI possible with autonomic neuropathy – stress test
 HTN, hydration status, avoid nephrotoxin, preserve renal blood flow,
limited joint mobility (intubation)
 Avoid sulfonylureas – myocardial ischemia
o Intraop Management
 Serum glucose should be maintained between 120-180, >200 = glycosuria
 1 unit regular insulin ↓ serum glucose 25-30 mg/dL
 50 ml of 50% dextrose in water ↑ serum glucose 100 mg/dL
o Postop care
 Hyperglycemia = poor outcomes
 Current guidelines – maintain glucose 140-180, initiate insulin treatment if
glucose > 180

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Insulinoma
o Rare benign insulin secreting pancreatic islet cell tumors; may be part of Multiple
Endocrine Neoplasia syndrome type I (Insulinoma, hyperparathyroidism, pituitary tumor)
o Whipple’s triad – hypoglycemic symptoms with fasting, glucose level < 50 mg/dL with
symptoms, relief of symptoms by administration of glucose
o Preop management – Diazoxide (inhibits insulin release from beta cells)
o Surgical treatment – curative (may be hypoglycemic during tumor manipulation but
hyperglycemic afterwards)
Thyroid Disease
o Thyroid hormone production reliant on exogenous iodine; T4:T3 production = 10:1
o T4/T3 bind reversibly to thyroxine binding globulin (80%), pre-albumin (10%), albumin
(5%)
o T3 4x more active than T4
o Thyroid hormones – work directly on cardiac monocytes and vascular smooth muscle
cells
o Increase myocardial contractility, decrease SVR via direct vasodilation and
increase intravascular volume
o Regulated by hypothalamus, pituitary and thyroid glands via feedback control
o TRH released from hypothalamus and TSH released from anterior pituitary
o Diagnosis:
o TSH assay – single best test of thyroid hormone action
o TRH stimulation test – asses functional state of TSH secreting mechanism
o Hyperthyroidism – hyper functioning thyroid & excess active thyroid hormones=hyper
metabolic state
o Graves Dz or Toxic diffuse goiter – typically occurs in females (7:1 ratio)
o Treatment – antithyroid drugs – methimazole or propylthiouracil (inhibit
synthesis of thyroid hormones – euthyroid state in 6-8 weeks
 Iodide – given after antithyroid drugs – inhibits thyroid hormone release
 BB – help control signs and symptoms but not actual thyroid problem
 Ablation or surgery
o Pregnancy – low dose anti-thyroid ok but higher doses cross placenta
 Usually attenuates severity of hyperthyroid state
 May need thyroidectomy in 2nd trimester if uncontrolled hyperthyroid

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 o Anesthetic Management
o Euthyroid needs to be established (6-8 weeks)
o In Emergency – BB, ipodate, glucocorticoids and PTU usually necessary
o Monitor for tracheal compression or deviation d/t goiter
o Establish adequate depth of anesthesia to avoid SNS response
o Avoid drugs that stimulate SNS – ketamine, pancuronium, atropine, ephedrine,
epinephrine)
o Thiopental (thioureylene nucleus) decreases peripheral conversion of T4 to T3
o Eye protection – eye drops, lubricant, eye pads – essential
o Increased risk of myasthenia gravis (careful titration of muscle relaxants)
o Hot – treat with direct acting vasopressor (phenylephrine)
o T4 t1/2 is 7-8 days so BB therapy may need to be continued post-op
o Thyroid Strom
o Precipitated by trauma, infection, medical illness or surgery
o Mimics MH – hyperpyrexia, tachycardia, hyper metabolism
o Results from shift from protein-bound thyroid hormone to free hormone d/t
circulating inhibitors to binding
o Most often occurs post-operatively
o Treat – IV glucose, cooling measures, BB, dexamethasone, anti-thyroid drugs
Hypothyroidism
o Slow insidious progressive course with mental and physical slowing, easy fatigue and
weight gain; ↓ CO and HR, PVR is ↑, blood volume ↓, hypercholesteremia and
hypertriglyceridemia –CAD
o Treatment – Levothyroxine – 1st evidence of therapeutic response = diuresis and ↓ TSH
o Anesthetic Management –
o Risks – airway compromise (swollen oral cavity, edematous vocal cords or goiter
 Decreased gastric emptying
 Hypo dynamic CV system - ↓CO, SV, HR, baroreceptor reflex,
intravascular volume
 Decreased ventilatory responses, hypothermia, anemia, electrolyte
imbalance, hypoglycemia, decreased neuromuscular excitability
o Treat HoT with volume resuscitation and ephedrine, dopamine or epinephrine (
NOT phenylephrine)
 For emergency surgery in presence of myxedema coma – initiate
immediate thyroid replacement
 Levothyroxine takes 10-12 days to yield peak basal metabolic rate
 IV T3 effective in 6 hrs with peak basal metabolic rate seen in 36-
72 hrs
 Levothyroxine 300-500 mcg IV or T3 25-50 mcg IV is acceptable

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 o Myxedema coma
o Rare form of hypothyroidism – delirium, unconsciousness, hypoventilation,
hypothermia, bradycardia, hypotension, severe Dilutional hyponatremia
o IV hydration with glucose containing colloids, temp regulation, correct electrolyte
imbalances, stabilize cardiac and pulmonary systems, IV L-thyroxine or L-
triiodothyronine
Goiter and Thyroid tumors
o Swelling of thyroid from compensatory hypertrophy and hyperplasia of follicular
epithelium secondary to reduction in thyroid hormone output
o Simple non-toxic goiter most common
o Use caution with sedatives, awake intubation with caution on extubation for surgical
removal
Complications of thyroid surgery
o RLN damage – 3-6 month recovery or with resection (permanent hoarseness)
o Hypoparathyroidism – damage to blood supply of parathyroid
o Hypocalcemia S & S = anxiety, circumoral numbness, tingling fingertips, muscle
cramping
o Tracheal compression – hematoma formation requires immediate evacuation
Pheochromocytoma
o Catecholamine secreting tumors that arise from chromaffin cells of the sympathoadrenal
system resulting in HTN, malignant HTN, CVA or MI
o 80% located in adrenal medulla, oragan of Zuckerkandl near the aortic bifurcation is most
common extra adrenal site
o Most secrete NE alone or in combo with Epi (85:15 which is reverse of normal secretion)
autonomously
o S&S – attacks vary (multiple daily to once monthly or less)
o HA, HTN, sweating, pallor, palpitations, orthostatic HoT (hypovolemia)
o NE (α) predominates = elevated SBP and DBP with reflex bradycardia
o EPI (β) predominates = elevated SBP, decreased DBP, tachycardia
o Cardiomyopathy – excess Ca influx, toxicity from oxidized products of
catecholamines and myocardial damage by free radicals, high catecholamine
levels result in coronary vasoconstriction thru alpha adrenergic pathways = ↓ CBF
and ischemia
o Elevated blood sugar d/t catecholamine stimulation of glycogenolysis and
inhibited insulin release

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o Diagnosis
o 24 hr urine collection or plasma measurement of metanephrines (catecholamines
are metabolized to free metanephrines within tumor cells)
o Clonidine Test – alpha agonist - lowers plasma catecholamine levels in patients
without pheo but has no effect on catecholamine levels in patients with pheo
o CT and MRI
o Anesthetic Management
o Preoperatively
 Alpha blockade to lower BP and increase intravascular volume
 Phenoxybenzamine – noncompetitive alpha 1 antagonist
 BB to treat tachycardia after alpha blockade initiated
 Propranolol, atenolol, metoprolol and labetalol
 Calcium Channel blockers and ACE inhibitors
 Ca triggers catecholamine release from tumor
o Intraoperatively
 HTN with pneumoperitoneum and tumor manipulation or HoT with
ligation of tumors venous drainage
 A-Line and CVP to monitor closely with no cardiac involvement
 Add TEE, PA cath for cardiac involvement
 Minimize catecholamine release – avoid histamine releasers (Morphine &
Atracurium)
 Treat HTN – nitroprusside, Mag inhibits release of catecholamines from
adrenal medulla and peripheral nerve terminals, reduces sensitivity of
alpha receptors to catecholamines, is a direct vasodilator and
antiarrhythmic
 Have Lidocaine, Esmolol, diltiazem and phentolamine handy
 Significant HoT with tumor vein ligation – volume resuscitation, decrease
anesthetic depth
o Postoperatively
 Continued HTN – d/t slow release of stored catecholamines from
peripheral nerves
 HoT – d/t poorly responsive vasculature to reduced levels of
catecholamines, may require steroid supplementation if hypoadrenalism is
present; dextrose fluid therapy with plasma glucose monitoring

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Adrenal Gland dysfunction
o Adrenal Gland – 2 compartments
o Adrenal cortex
 Glucocorticoids – Zona Fasciculata
 Mineralcorticoids (aldosterone) – Zona Glomerulosa
 Androgens (sex hormones) – Zona reticularis
o Adrenal medulla – synthesis of catecholamines
o Anterior pituitary releases corticotropin in response to corticotropin releasing hormone
from the hypothalamus
o Cortisol – supports BP by converting NE to Epi in the adrenal medulla
 Hyperglycemia response reflects gluconeogenesis and inhibition of
peripheral use of glucose by cells
 Retention of sodium and excretion of potassium
 Anti-inflammatory effects
o Activation of the HPA axis (hypothalamic pituitary adrenal)
o Most potent cause = surgery
Hypocortisolism (Cushing’s syndrome)
o 2 forms:
o ACTH dependent – inappropriately high plasma ACTH concentrations stimulate
the adrenal cortex to produce excessive amounts of cortisol
 Benign or malignant adrenocortical tumors are most common
o ACTH independent – excessive production of cortisol by abnormal adrenocortical
tissue that is not regulated by secretion of CRH and ACTH (these are actually
suppressed)
o Cushing’s disease – reserved for excessive secretion of ACTH by pituitary ACTH
tumors
 Acute ectopic ACTH syndrome is another form, most often associated
with small cell lung carcinoma
o Diagnosis
o Sudden onset of weight gain with thickening of facial fat which rounds the facial
contour along with florid complexion resulting from telangiectasia
o Systemic HTN, glucose intolerance, osteoporosis, obesity, poor wound healing,
oligomenorrhea or amenorrhea, ↓ libido, spontaneous ecchymosis, skeletal muscle
wasting and weakness, depression and insomnia
o 24 hr urine shows cortisol hypersecretion along with plasma ACTH
o Treatment
o Transsphenoidal microadenomectomy of microadenoma treatment of choice
o Resection of anterior pituitary, pituitary irradiation, bilateral total adrenalectomy

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 o Anesthetic Management
o Preop – eval BP, electrolytes, blood glucose
o Intraop-osteoporosis considerations when positioning
o Etomidate may transiently decrease the synthesis and release of cortisol by
adrenal cortex
o Decrease doses of muscle relaxants due to skeletal muscle weakness
(hypokalemia)
o Plasma cortisol levels decrease rapidly after microadenomectomy or bilateral
adrenalectomy so replacement therapy is recommended (cortisol 100 mg/day IV);
may also see transient diabetes insipidus or meningitis
Primary Hyperaldosteronism (Conn’s Syndrome)
o d/t excess secretion of aldosterone from a functional tumor (aldosteronoma) that acts
independently of physiologic stimulus
o Male > Female occurrence; rare in children; occasionally associated with
pheochromocytoma, 1 hyperparathyroid or acromegaly
o Secondary hyperaldosteronism - ↑ serum levels of renin = renovascular HTN which
stimulates the release of aldosterone
o Signs & Symptoms
o Nonspecific – HA (HTN-fxn of aldosterone induced Na retention), hypokalemia
(polyuria, nocturia, skeletal muscle cramps, skeletal muscle weakness)
o Aldosterone promotes renal excretion of K –hypokalemic metabolic acidosis
o Diagnosis
o Spontaneous hypokalemia in patients with systemic HTN suggestive
o A syndrome resembling hyperaldosteronism (HTN, hypokalemia, RAA
suppression) may result from long term ingestion of licorice
o Treatment – K supplementation, aldosterone antagonist (spironolactone)
o Anesthetic Management
o Correct hypokalemia (may modify NDMB responses), avoid hyperventilation (↓
K+)
o CVP measurement useful; hypovolemia from pre-op correction leading to HoT
from vasodilators, positive pressure ventilation, body position changes and blood
loss

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Hypoaldosteronism
o Hyperkalemia in the absence of renal insufficiency suggestive of hypoaldosteronism
o Hyperkalemia is sometimes abruptly enhanced by hyperglycemia
o Hyperchloremic metabolic acidosis is a predictable finding
o Other causes – congenital deficiency of aldosterone synthetase, hyporeninemia (defects
of juxtaglomerular apparatus or treatment of ACEI), chronic renal disease or DM leading
to hyporeninemic hypoaldosteronism in patients > 45 yrs old; indomethacin induced
prostaglandin deficiency is reversible cause
o Treatment – liberal sodium intake and daily admin of fludrocortisone (0.1 mg/day
independent of body size)
Adrenal Insufficiency
o Signs & Symptoms
o 2 types
 Primary (Addison’s Dz) – adrenal glands unable to elaborate sufficient
quantities of glucocorticoid, mineralocorticoid and androgen hormones
 Most common cause – bilateral adrenal destruction from
autoimmune disease (>90% gland involvement)
 Insidious onset – fatigue, weakness, anorexia, N & V, cutaneous
and mucosal hyperpigmentation, hypovolemia, hyponatremia,
hyperkalemia
 Secondary – results from failure in production of CRN or ACTH d/t HPA
disease or suppression
 Only glucocorticoid suppression; usually iatrogenic (pituitary
surgery, pituitary irradiation, synthetic glucocorticoids)
 Lack hyperpigmentation and may have only mild electrolyte
abnormalities
o Cortisol – essential hormone of life
 Participates in CHO and protein metabolism, fatty acid mobilization,
electrolyte and water balance, anti-inflammatory response
 Facilitates catecholamine synthesis and action, modulates B receptor
synthesis, regulation, coupling and responsiveness
 Contributes to normal vascular permeability, tone and cardiac contractility
 Accounts for 95% of adrenal glands glucocorticoid activity
 Estimated daily cortisol secretion is equivalent to 15-25 mg/day of
hydrocortisone or 5-7 mg/day of prednisone
o Diagnosis – baseline plasma cortisol concentrations of < 20 mcg/dL
o ACTH stimulation test reliable for integrity of HPA

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 o Treatment
o Causes – exogenous steroid treatment (arthritis, bronchial asthma, malignancies,
allergies, collagen vascular disease, inflammatory conditions
o Baseline steroid therapy – may require supplementation during surgery
 Methylprednisolone may be substituted for hydrocortisone when dose >
100 mg/day (lower mineralocorticoid activity – less fluid retention, edema
and hypokalemia)
o Management of Anesthesia
o Acute AI should be in differential diagnosis of hemodynamic instability
o Treat the cause – replete circulating glucocorticoids, replace Na and water deficits
 Dexamethasone preferred when ACTH stimulation testing required
 Does not alter cortisol levels
 Hydrocortisone bolus followed by infusion until condition stabilized
 Hemodynamic support with vasopressors
o Avoid Etomidate – inhibits synthesis of cortisol transiently
Parathyroid Gland Dysfunction
o Hypocalcemia stimulates release of parathyroid hormone; hypercalcemia inhibits both
synthesis and release of parathyroid hormone
o Parathyroid hormone promotes movement of Ca across three interfaces (GI tract, renal
tubules, bone)
o Primary Hyperthyroidism
o Results from excessive secretion of parathyroid hormone due to a benign
parathyroid adenoma, carcinoma of the PTH gland or hyperplasia of one or more
parathyroid glands
o Diagnosis:
 Hypercalcemia is hallmark (serum Ca > 5.5 or ionized Ca > 2.5 mEq/L)
 Urinary excretion of cAMP is increased
o Signs & Symptoms
 Skeletal muscle weakness, polyuria, polydipsia, ↓ GFR, kidney stones,
anemia, prolonged PR, shortened QT, systemic HTN, vomiting,
abdominal pain, peptic ulcer, pancreatitis, skeletal demineralization,
collapse of vertebral bodies, pathologic fractures, somnolence, decreased
pain sensation, psychosis, calcification (band keratopathy) conjunctivitis

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 o Treatment
 Medical means followed by surgical removal of diseased or abnormal
PTH gland
 Medical – Saline infusion (150 ml/hr) to replace volume deficit
 Loop diuretics (inhibit Na and therefore Ca reabsorption in the
proximal loop of Henle); goal of 3-5 L urine output/day
 Biphosphonates (Disodium etidronate) IV for life threatening
hyperCa
o Bind to hydroxyapatite in bone and act as potent inhibitors
of osteoclastic bone reabsorption
 Surgical – Ca normalizes in 3-4 days along with decreased urinary
excretion of cAMP
 Complications – hypocalcemic tetany
o Hypomagnesemia aggravates hypocalcaemia
o Hyperchloremic metabolic acidosis r/t renal fxn
deterioration
o Acute arthritis
o Anesthetic Management
 Maintain hydration and urine output
 Careful positioning – osteoporosis, pathologic fractures
 Sevo with renal dysfunction – impaired urine concentrating ability
associated with polyuria and hypercalcemia could be confused with
anesthetic induced fluoride nephrotoxicity
 Titrate NMB to effect – muscle weakness vs hypercalcemia antagonism
o Secondary Hyperparathyroidism
o PTH reacting to disease process that causes hypocalcaemia
 Chronic renal disease (impaired phos elim)
o Rarely causes hypercalcemia – treat underlying cause to correct
o Ectopic hyperparathyroidism
o Hymoral hypercalcemia of malignancy, pseudohyperparathyroidism – d/t
secretion of PTH by tissues other than the PTH glands
 Carcinoma of breast, lung, pancreas, kidney or lumphoproliferative
disease
 Indomethacin inhibits prostaglandin synthesis and lowers Ca

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Hypoparathyroidism
o Causes
o Decreased or Absent PTH
 Accidental removal of PT glands during thyroidectomy
 Parathyroidectomy to treat hyperplasia
o Resistance of Peripheral tissues to effects of PTH
 Congenital – pseudohypoparathyroidism
 Acquired – hypomagnesemia, Chronic renal failure, malabsorption,
anticonvulsive therapy, osteoblastic metastases, acute pancreatitis
o Diagnosis
o Measure serum Ca (<4.5 mEq/L) and ionized Ca (<2.0 mEq/L)
o Signs & Symptoms
o Acute – perioral paresthesia, restlessness and neuromuscular irritability,
inspiratory stridor
o Chronic – fatigue, skeletal muscle cramps, ECG changes (prolonged QT),
lethargy, personality changes, cataracts, calcification involving the subcutaneous
tissues and basal ganglia, thickening of the skull and chronic renal failure
o Treatment
o IV Calcium (10 ml 10% Ca gluconate or Ca Cl)
o Vitamin D
o Thiazide diuretics – cause Na depletion without proportional potassium
excretions=increase serum Ca Concentrations
o Anesthetic Management
o Prevent further decrease in serum Ca and treat adverse effects of hypocalcaemia
o Avoid iatrogenic hyperventilation
o Monitor Ca with whole blood administration d/t citrate
Pituitary Gland Dysfunction
o Located in sella turcica at the base of the brain; consists of the anterior and posterior
pituitary.
o Anterior pituitary –
o secretes 6 hormones under hypothalamus control
 Corticotropin-releasing hormone (stimulates secretion of cortisol and
androgens)
 Thyrotropin releasing hormone (stimulates secretion of thyroxine and T3
 Gonadotropin releasing hormone (stimulates secretion of estradiol and
progesterone – ovulation, testosterone secretion, spermatogenesis)
 Growth hormone-releasing hormone (stimulates production of insulin like
growth factor
 Dopamine – inhibits prolactin which stimulates lactation
 Somatostatin – inhibits secretion of growth hormone and TSH, suppresses
release of GI and pancreatic hormones

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 o Overproduction by Anterior pituitary usually result of hypersecretion of ACTH
o Underproduction of a single hormone less common
o Posterior pituitary – storage of vasopressin (ADH) and oxytocin which are synthesized in
the hypothalamus
Acromegaly
o Due to excessive secretion of growth hormone in adults (most often adenoma in anterior
pituitary)
o Signs & Symptoms
o Parasellar extension of anterior pituitary adenoma and peripheral effects produced
by excess growth hormone
o Parasellar tumor – enlarged sella turcica, HA, visual field defects, rhinorrhea
o Excess Growth hormone – skeletal overgrowth, soft tissue overgrowth (lips,
tongue, epiglottis, vocal cords), connective tissue overgrowth (RLN paralysis),
peripheral neuropathy (carpal tunnel syndrome), visceromegaly, glucose
intolerance, osteoarthritis, osteoporosis, hyperhidrosis, skeletal muscle weakness
o Treatment
o Transsphenoidal surgical excision of pituitary adenoma
o Medical treatment – bromocriptine – suppressant drugs
o Anesthetic Management
o Changes of upper airway – distorted facial anatomy make mask ventilation and
DL difficult
o Preop history of SOB or dyspnea, stridor or hoarseness
o Inadequate collateral flow in wrist when placing art line possible
Diabetes Insipidus
o Reflects the absence of vasopressin (ADH) either from destruction of posterior pituitary
(neurogenic DI) or failure of renal tubules to respond to ADH (nephrogenic DI)
o Desmopressin (DDAVP) concentrates the urine in neurogenic but not
nephrogenic DI
o Manifestations – polydipsia with high output unconcentrated urine despite increased
serum osmolality
o Treatment – IV infusion of electrolyte solutions to offset polyuria
o Chlorpropamide potentiates effects of ADH on renal tubules (tx nephrogenic DI)
o Neurogenic DI – ADH IM q 2-4 days or by intranasal admin of Desmopressin
o Anesthetic management – monitor electrolytes and urine output
Inappropriate Secretion of ADH
o May occur d/t intracranial tumors, hypothyroidism, porphyria, carcinoma of the lung
o Increased urine Na in the presence of hyponatremia and water reabsorption
o SIADH treatment – restrict oral fluid intake
o Antagonize effects of ADH on renal tubules with demeclocycline and IV NaCl
o Hypertonic Na to increase serum Na by 0.5 mEq/L/hr

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Geriatric Considerations:
o DM II more likely to occur in the middle to older age group
o Aging leads to a progressive ↓ ability to handle IV glucose
o Increases in total body lipid content enlarge Vd
o Affects drugs that are more lipid-soluble: inhaled anesthetics, barbiturates,
benzos
o Lipid storage acts as reservoir for continued maintenance of plasma drug
concentrations
 May delay recovery in elderly in addition to ↓ hepatic, renal clearance
o Neurons in sympathoadrenal pathways undergo significant cellular attrition
o Adrenal tissue & cortisol secretion ↓ 15% by 80 yr
o Plasma norepi concentrations in elderly > young
 Effects of ↑ plasma catechol’s not clinically apparent since aging causes ↓
end-organ responsiveness
 Impairment of β agonists to enhance velocity/flow cardiac contraction
 Aging produces endogenous β blockade
 Aging produces little change in α adrenergic or muscarinic
cholinreceptor activity
Pediatric Considerations
DM I more likely to arise in childhood but DM II is becoming more rampant in peds, usually
those who are overweight and have a family history of DMII
Many considerations are the same as for adults, however there are some variations:
o Be sure the patient is metabolically stable before surgery (Blood glucose, electrolytes,
ketones, volume, normal HgbA1C)
o To calculate expected drop in blood glucose from 1 u regular or aspart insulin, use the
1500 rule. Take the child’s normal daily dose and divide 1500 by it (1500/30u = 50 so 1
unit insulin would drop blood glucose by 50 mg/dL)
DI – pediatric considerations
o minor procedures; child should receive usual morning dose of DDAVP
o Restrict fluid to 1 L/m2/24hr to match insensible free water losses
o Major procedures
o Should be scheduled as first case of the day
o Day before, normal AM dose but only 50% of PM dose DDAVP, AM of
surgery – hold
o Art line and urinary catheter with admission post-op to ICU
o Infusion of aqueous vasopressin started at beginning of case (1.5 mU/kg/hr)
o Correct fluid losses for insensible loss, blood and surgical fluid and third
space loss, not for urine output

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Hypothyroid – child should be euthyroid before surgery
o T4 replacement – 10-15 µg/kg/day for neonates BUT 2-4 µg/kg/day for children and
adolescents
Pharmacology
Phentolamine – nonselective alpha blockade; Used mostly in pheochromocytoma resection or in
situations of extravascular infiltration of sympathomimetic
o Nonselective blockade, so decreased blood pressure and peripheral vasodilation (alpha 1
blockade), but increased heart rate and increased cardiac output (alpha 2 blockade)
Clonidine – alpha 2 agonist
o Alpha 2 receptors in the CNS (medullary vasomotor center) and spinal cord (substantia
gelatinosa)
o In the CNS, clonidine decreases SNS outflow via alpha 2 agonism
o Useful in patients with severe hypertension
o Sedation, decreased anesthetic requirements (via modification of K+ channels?) ,
and analgesia are properties of clonidine
o The sedative effects of clonidine are different from drugs that act on GABA
receptors>>calm, easily aroused patient as opposed to a consciousness-clouded patient or
a paradoxically agitated patient
o 150 – 400 mcg can be added neuraxially, producing dose-dependent analgesia,
without the side effects of opioids
o Neuraxial placement of clonidine inhibits substance P release
o Hypotension, dry mouth, and sedation are side effects
o Oral Clonidine 5mcg/kg prior to surgery decreases SNS response to laryngoscopy,
decreases plasma catecholamine levels, decreases MAC requirements
o Augments the pressor response to ephedrine
o Decreased risk of myocardial ischemia, infarction and mortality following CABG
o Ineffective in the setting of pheochromocytoma (no effect on tumor diffusion of
catecholamines)
o Can be used as an adjunct in the management of acute ETOH withdrawal
o 75mcg IV can be used to stop shivering, as clonidine inhibits central thermoregulatory
control
o Decrease in SBP>DBP
o Maintenance of CV reflexes & Minimal depressant effects on ventilation, and no
potentiation of opioids in this regard
o Abrupt discontinuation produces rebound hypertension in 8-36 hours since last dose

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Phenoxybenzamine - nonselective alpha blockade with irreversible covalent bonding; a prodrug
that needs to be activated, so onset time is slow (45 min to 1 hour)
o This drug lasts 24 hours (covalent bond)
o Significant hypotension if the patient is hypovolemic or has preexisting hypertension.
o Other noncardiac effects include miosis and nasal stuffiness
Cardizem (Diltiazem a benzodiazepine) targets cardiac cells, coronary vasodilation > peripheral
o Increase the time that Ca2+ channels are closed (treat SVT and essential HTN)
o Relaxation of the arterial smooth muscle but not much effect on venous smooth muscle
o Significant reduction in afterload but not preload
o Cardiac muscle requires Ca2+ influx through L-type Ca2+ channels
o contraction (fast response cells)
o upstroke of AP (slow response cells)
o Vascular smooth muscle requires Ca2+ influx through L-type Ca2+ channels for
contraction
Insulin: promote glucose utilization
Short-acting Onset Peak Duration
Regular 30 min 2-4 hr 5-8 hr
Lispro & Aspart 10-15 min 1-2 hr 3-6 hr
Intermediate
NPH & Lente 1-2 hr 6-10 hr 10-20 hr
Long-Acting
Glargine (Lantus) 1-2 hr ---- 24 hr

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Endocrine:
Hypocortisolism (Cushing’s syndrome)
a. Two categories
i. ACTH dependent
1. Inappropriately high plasma ACTH concentrations stimulate the
adrenal cortex to produce excessive amounts of cortisol.
2. Cushing’s disease is reserved for Cushing’s syndrome caused by
excessive secretion of ACTH by pituitary ACTH tumors
(microadenoma).
ii. ACTH independent
1. Excessive production of cortisol by abnormal adrenocortical tissue
that is not regulated by secretion of CRH and ACTH. CRH and
ACTH levels in this form of the disease are actually suppressed.
b. Signs and symptoms
i. The most common symptom is the relatively sudden onset of weight gain,
which is usually central and often accompanied by thickening of the facial
fat, which rounds the facial contour (moon faces), and a florid complexion
resulting from telangiectasia.
ii. Systemic hypertension
iii. Glucose intolerance
iv. Oligomenorrhea or amenorrhea in premenopausal women
v. Decreased libido in men
vi. Spontaneous ecchymosis
vii. Skeletal muscle wasting and weakness
viii. Depression and insomnia
c. Diagnosis
i. Cortisol hypersecretion based on 24-hour urinary secretion of cortisol
ii. Determining whether a patient’s hypercortisolism is ACTH dependent or
ACTH independent requires reliable measurements of plasma ACTH
using immunoradiometric assays
iii. High dose dexamethasone suppression test distinguishes Cushing’s
disease from ectopic ACTH syndrome
d. Treatment
i. Transsphenoidal microadenomectomy (Cushing’s disease)
ii. Resection of the anterior pituitary
iii. Pituitary irradiation
iv. Bilateral total adrenalectomy
e. Management of anesthesia
i. Preoperative evaluation of systemic blood pressure, electrolyte balance,
and blood glucose concentration
ii. Osteoporosis is a consideration when positioning patients for the operative
procedure
iii. The choice of drugs for preop, induction and maintenance of anesthesia is
NOT influenced by the presence of hypercortisolism.

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 iv. Etomidate may transiently decrease the synthesis and release of cortisol by
the adrenal cortex
v. Dose of muscle relaxants should probably be decreased initially in view of
the skeletal muscle weakness that frequently accompanies
hypercortisolism.
vi. Mechanical ventilation of the patient’s lungs during surgery is
recommended, because skeletal muscle weakness may decrease the
strength of the muscles of breathing.
vii. Regional anesthesia is acceptable, but the likely presence of osteoporosis,
with possible vertebral body collapse, is a consideration.
viii. Plasma cortisol concentrations decrease promptly after
microadenomectomy or bilateral adrenalectomy, and replacement therapy
is recommended. A continuous infusion of cortisol (100mg/day IV) may
be initiated intraoperative.
ix. Patients with metastatic disease involving the adrenal glands may develop
acute adrenal insufficiency, which requires the initiation of supplemental
therapy.
x. Transient diabetes insipidus and meningitis may also occur after
microadenomectomy

2.) Primary Hyperaldosteronism (Conn’s disease)

a. Description
i. Excess secretion of aldosterone from a functional tumor (aldosteronoma)
that acts independently of a physiologic stimulus. Aldosteronoma occur
more often in women than in men and only rarely in children.
ii. Occasionally, primary aldosteronism is associated with
pheochromocytoma, primary hyperparathyroidism, or acromegaly
iii. Secondary hyperaldosteronism is present when increased circulating
serum concentrations of renin, as are associated with renovascular
hypertension, stimulate the release of aldosterone.
b. Signs and symptoms
i. s/s are not specific and some patients are completely asymptomatic
ii. systemic hypertension (headache)
1. diastolic blood pressure is often 100-125 mm Hg
2. is a function of aldosterone-induced sodium retention and increase
in extracellular fluid volume
3. resistant to treatment
iii. hypokalemia (polyuria, nocturia, skeletal muscle cramps, skeletal muscle
weakness)
1. renal excretion of potassium results in hypokalemic metabolic
alkalosis
iv. hypomagnesemia and abnormal glucose tolerance may also be present

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c. Diagnosis
i. Spontaneous hypokalemia in patients with systemic hypertension is highly
suggestive of aldosteronism
ii. Plasma renin activity is suppressed in almost all patients with untreated
primary aldosteronism
iii. With secondary aldosteronism, however, the plasma renin activity is high
iv. A syndrome exhibiting all the features of hyperaldosteronism (systemic
hypertension, hypokalemia, suppression of the renin-angiotensin system)
may result from long-term ingestion of licorice (glycyrrhizin acid)
d. Treatment
i. Initial treatment consists of potassium supplementation and administration
of a competitive aldosterone antagonist such as spironolactone.
ii. Systemic hypertension is treated with antihypertensive drugs
iii. Definitive treatment: surgical excision. Bilateral adrenalectomy may be
necessary if multiple aldosterone-secreting tumors are found.
e. Management of anesthesia
i. Preoperative correction of hypokalemia and treatment of systemic
hypertension.
ii. Persistence of hypokalemia may modify responses to nondepolarizing
muscle relaxants. Intraoperative hyperventilation of the patient’s lungs can
decrease the plasma potassium concentration and should be avoided.
iii. The use of sevoflurane is questionable if hypokalemic nephropathy and
polyuria are present preoperatively.
iv. Measurement of cardiac filling pressures via a right atrial or pulmonary
artery catheter may be useful during surgery for adequate evaluation of the
intravascular fluid volume and the response to intravenous infusion of
fluids.
v. Aggressive preoperative preparation can convert the excessive
intravascular fluid volume status of these patients to unexpected
hypovolemia, manifesting as hypotension in response to administration of
vasodilating anesthetic drugs, positive pressure ventilation, changes in
body position, or surgical blood loss. The detection of orthostatic
hypotension during the preoperative evaluation is a clue to underlying
hypovolemia.
vi. Acid-base status and plasma electrolyte concentrations should be measure
frequently
vii. Supplementation with exogenous cortisol is probably unnecessary for
surgical excision of a solitary adenoma in the adrenal cortex. A continuous
IV infusion of cortisol (100mg/day) may be initiated on an empirical basis
if transient hypocortisolism resulting from surgical manipulation is a
consideration

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3.) Acromegaly
a. Definition
i. Excessive secretion of growth hormone in adults, most often by an
adenoma in the anterior pituitary gland.
ii. Failure of plasma growth hormone concentration to decrease 1-2 hours
after ingestion of 75-100 g of glucose is presumptive evidence of
acromegaly, as are growth hormone concentrations higher than 3ug/mL.
iii. A skull radiograph and CT are useful for detecting enlargement of the
sella turcica, which is characteristic of anterior pituitary adenomas
b. Signs and Symptoms
i. Headache and papilledema reflect increased intracranial pressure resulting
from expansion of the anterior pituitary adenoma
ii. Visual disturbances are due to compression of the optic chiasm by the
expanding overgrowth of surrounding tissues
iii. Overgrowth of soft tissues of the upper airway (enlargement of the tongue
and epiglottis) makes patients susceptible to upper airway obstruction.
iv. Hoarseness and abnormal movement of the vocal cords or paralysis of a
recurrent laryngeal nerve may result from stretching caused by overgrowth
of the surrounding cartilaginous structures
v. Involvement of the cricoarytenoid joints can result in alterations in the
patient’s voice resulting from impaired movement of the vocal cords
vi. Peripheral neuropathy is common and likely reflects trapping of nerves by
skeletal, connective, and soft tissue overgrowth.
vii. Half of patients have inadequate collateral blood flow through the ulnar
artery in one or both hands
viii. Glucose intolerance
ix. Incidence of systemic hypertension, ischemic heart disease, osteoarthritis,
and osteoporosis seems to be increased in these patients.
x. Lung volumes are increased, and ventilation/perfusion mismatching may
be present
xi. Patient’s skin becomes thick and oily
xii. Skeletal muscle weakness, fatigue
c. Treatment
i. Transsphenoidal surgical excision of pituitary adenomas
ii. Medical treatment with bromocriptine

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d. Management of anesthesia
i. Distorted facial anatomy may interfere with placement of an anesthesia
face mask
ii. Enlargement of the tongue and epiglottis predisposes to upper airway
obstruction and interferes with visualization of the vocal cords by direct
laryngoscopy
iii. Distance between the lips and the vocal cords is increased
iv. The glottis opening may be narrowed because of enlargement of the vocal
cords. This may necessitate use of a tracheal tube with a smaller internal
diameter.
v. Nasal turbinate enlargement may preclude the passage of nasopharyngeal
or nasotracheal airways
vi. Awake fiberoptic tracheal intubation may be necessary
vii. When catheter is placed in the radial artery, it is important to consider the
possibility of inadequate collateral circulation at the wrist.
viii. Monitoring blood glucose concentrations is useful if diabetes mellitus or
glucose intolerance accompanies acromegaly
ix. The skeletal changes associated with acromegaly may make the use of
regional anesthesia technically difficult or unreliable

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 Endocrine Pathophysiology

 Enzyme activation- Hormones affect target cells by inducing this, which is a catalytic
reaction- inducing a more widespread cellular response
 Types of Hormone Receptors
1. Cell Surface Receptors (on plasma membrane)
a. Hormone classes here- Proteins, peptides, eicosanoids and catecholamines
i. These generate 2nd messengers- enzymatic activity
2. Intracellular Receptors (in cytoplasm and/or nucleus)
a. Hormone classes- Steroids and thyroid hormones
i. These alter transcriptional activity of responsive genes
Thyroid Gland- Isthmus located over 2nd-4th tracheal rings
 Major regulator of cellular metabolic activity
 Secretes Thyroxine- T4, and 3, 3’, 5 triiodothyroine- T3.
 Thyroid Metabolism and Function
1. Production of T3, T4- initiated by iodide.
2. Dietary iodine- reduced to iodide in GI tract
3. Iodide- taken up by thyroid- bound to tyrosine- formation of iodotyrosines- mono or
di- iodotyrosines – then coupled by thyroid peroxidase – formation of either T3 or T4
4. T3 orT4 are bound thyroglobulin
5. TSH release from adenohypophysis, whose regulation is by TRH in hypothalamus, is
responsible for uptake of iodide and release of T3 or T4.
6. Excess iodine inhibits T3 and T4 secretion
7. T4- Thyroxine-
a. Increases speed of biochemical reactions
b. Increases total body O2 consumption
c. Increases energy- heat production
8. T3- stimulates mRNA synthesis, controls protein synthesis, and stimulates oxidative
phosphorylation with ATP formation.
9. Thyroid hormones act directly on cardiac myocytes and vascular smooth muscle cells
10. Thyroid hormone- increases myocardial contractility, decreases SVR, and increases
intravascular volume

- Negative Feedback Loop/Mechanism

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 Thyroid Hormones
1. T4 half-life is 6-7 days. T3 half-life is 24-30 hours- much shorter- T3 is four times
more potent than T4.
2. The process by which iodine is transported into thyroid cell is called iodine trapping
3. 80% of T3 is made by the extra thyroidal deiodination of T4. 20% by direct thyroid
secretion.
4. 97% of hormone released from thyroid is T4 and 7% T3.
5. Major fraction of hormone- bound to thyroxine binding hormone, smaller fraction to
albumin, thyroid-binding prealbumin- Point here- changes in serum-binding protein
concentrations have a major effect- more free hormone- more active.
The CRNA is most concerned with the CV manifestations of thyroid disease
1. B-Adrenergic receptors increase in number, and a-adrenergic receptors are
decreased by thyroid hormone.
 The best initial test of thyroid function is serum TSH.

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 Parathyroid Glands

 Regulates Calcium and Phosphate

 Parathyroid hormone increases plasma calcium concentration- by increasing absorption
of calcium from intestine, increasing reabsorption of calcium from renal tubule, and by
increasing reabsorption of calcium from bone.
 Parathyroidectomy complications
1. Hypocalcemia- paresthesia, muscle spasm, laryngospasm, bronchospasm, apnea.
2. Unilateral or bilateral RLN damage
3. BILATERAL RLN DAMAGE REQUIRES INTUBATION
4. Hematoma with airway compromise
5. Pneumothorax
 Calcitonin is secreted from Parafollicular C Cells- this has been on multiple test
questions we have had. Calcitonin is a relatively weak regulator of calcium homeostasis
 Calcitonin decreases calcium ions- decreases osteoclastic (bone breakdown) and
increases osteoblastic (bone deposition). Know that calcitonin has OPPOSITE effects of
parathyroid hormone

344
 Thyroid Disease

 Graves’ Disease
1. Most common form of hyperthyroidism
2. S/S- 1. The high state of exit ability, intolerance to heat, increased sweating, mild
extreme weight loss, varying degrees of diarrhea, muscle weakness, nervousness or
other psychic disorders, extreme fatigue but inability to sleep, tremor of the hands.
3. The clinical manifestations that are classic and Graves' disease is characterized by
multi nodular goiter and classic triad of hyperthyroidism, exophthalmos, and
dermopathy.

Hyperthyroidism and anesthetic considerations

 Most importantly is to make the patient you thyroid before any surgery, if possible.
 PTU, medication the decreases the peripheral conversion of T4 to T3.
 The drugs propyl thiol uracil and methimazole are thio urea derivatives inhibit
organification of iodide and the synthesis of thyroid hormone.
 Hyperthyroid patients are unlikely to be regulated to a euthyroid state with anti-thyroid
drugs in less than 6 to 8 weeks.
 Beta-adrenergic antagonists are effective at attenuating the manifestations of excessive
sympathetic activity and should be used in all hyperthyroid patients unless
contraindicated.
 Propranolol is a specific beta adrenergic antagonist that has specifically the ability to
impair the peripheral conversion of T4 to T3 in 1 to 2 weeks.
 Propranolol plus calcium iodide is frequently used before surgery to ameliorate
cardiovascular symptoms and reduce circulating concentrations of T4 and T3.
 If a hyperthyroid patient with clinically apparent disease requires emergency surgery,
beta-adrenergic blockade should be administered to achieve a heart rate less than 90 bpm.
 Glucocorticoids such as dexamethasone are used in the management of severe
thyrotoxicosis because the reduced thyroid hormone secretion and the peripheral
conversion of T4 to T3.
 All anti-thyroid medications or continue through the morning of surgery. The goal of
intraoperative management and a hyperthyroid patient is to achieve a depth of anesthesia
that prevents an exaggerated sympathetic response the surgical stimulation while
avoiding the administration of medication that stimulates the sympathetic nervous
system. AVOID KETAMINE AND PANCURONIUM.
 Hypotension occurs during surgery is best treated with direct acting vasopressors rather
than a medication such as ephedrine that provokes the release of catecholamines.
 The incidence of myasthenia gravis is increase in hyperthyroid patients so the initial dose
of muscle relaxant should be reduced.
 If regional used avoid epinephrine containing solutions.

345
 Thyroid storm

 Severe exacerbation of hyperthyroidism or thyrotoxicosis due to sudden excessive release

of thyroid gland hormones into the circulation.
 Most likely occurs in the first 6 to 18 hours postoperatively and is usually abrupt in onset.
 Manifestations include hyperthermia, tachycardia, congestive heart failure, dehydration,
shock, and hyperglycemia.
 It must be distinguished from, or considered with, pheochromocytoma, malignant
hyperthermia, and light anesthesia.
 Treatment involves large doses of propyl thiol uracil and supportive measures to control
fever and restore intravascular volume.
 Treatment consists of cold crystalloid solutions containing glucose and aggressive
amounts to replace fluid loss during hyperthermia. Digitalis is administered to treat high
output heart failure. Specific drugs to treat specific manifestations of excessive thyroid
gland activity Arden ministered including sodium iodide cortisol propranolol and propyl
thiol uracil.
 The drug of choice to treat ventricular arrhythmia is in the hyperthyroid patient is
specifically a combined beta-1 and beta-2 adrenergic antagonists such as propranolol.

Hypothyroidism

 Results from inadequate circulating levels of T4 or T3, or both. The development is often
slow and progressive, making the clinical diagnosis difficult.
 Hypothyroidism causes cretinism and the infant or child and myxedema and the adult.
 Signs and symptoms of hypothyroidism include slow mental function, slow movements,
dry skin, cold intolerance, depressed ventilatory responses, abnormal cardiac
conductance, and renal disease. Anesthesia requirements are decreased
 Big concerns include intraoperative hypothermia, delayed or impaired drug metabolism,
and cardiovascular instability and/or collapse.
 Very sensitive to the hypotensive effects of anesthetic drugs, and are very prone to
drug induced respiratory depression.
 Management of myxedema includes tracheal intubation and control ventilation as needed,
levothyroxine, hydrocortisone, and fluid electrolyte therapy is indicated by serum
electrolytes, and cover to conserve body heat.

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 Anesthesia and Parathyroid Disease

 Preoperative preparation including the correction of intravascular volume and electrolyte

irregularities.
 Very important to evaluate the patient with chronic hypercalcemia for
abnormalities of the renal, cardiac, or CNS systems.
 An element in treating hypercalcemia is the correction of hypophosphatemia.
 A conservative approach to muscle paralysis makes sense because of the unpredictable
response to neuromuscular blocking drugs and the hypercalcemia patient.
 The hallmark in patients with hyperparathyroidism includes increased ionized calcium
concentration and hypercalcemia.
 The main perioperative goal in these patients is to correct intravascular volume and
electrolyte abnormalities. Normal saline and a loop diuretic usually Lasix is ad ministered
to increase calcium excretion by means of hydration and diuresis. Avoid LR.
 General anesthesia is most common for parathyroid surgery, but cervical plexus block
and LA with hypnosis has been used.
 Some centers use and intraoperative rapid PTH assay to determine when a hyper
functioning gland has been removed.
 RLN monitoring may be done with NIM tube so neuromuscular blockade is not
warranted.
 Postoperative complications include RLN injury, bleeding, and transient or complete
hypoparathyroidism.
 After parathyroidectomy, a decrease in the serum calcium level should be or is observed
within 24 hours.

ADRENAL GLAND- Cortex

 The adrenal cortex functions to synthesize and secrete three types of hormones.
 Great mnemonic to use- “Go find rex, make good sex” - Glomerulosa-
Mineralocorticoids. Fasciculata- Glucocorticoids Zona Reticularis- Sex hormones
 Zona Glomerulosa- Mineralocorticoid- outer layer of cortex- Aldosterone

Mineralocorticoid- Aldosterone- Glomerulosa

 Aldosterone @ the distal tubules and collecting duct to increase reabsorption of sodium
and to increase the secretion of potassium promoting a sodium retention and potassium
excretion respectively.
 If aldosterone levels decrease potassium concentrations will be increased intracellularly
 The two most potent stimuli triggering the release of Aldosterone from the adrenal cortex
includes angiotensin II and potassium.
 The hormone that most regulates extracellular fluid volume is aldosterone.

347
 Excess Mineralocorticoid- Conn syndrome

 With excess mineralocorticoid aldosterone, it would make sense to see that there would
be increased renal tubular exchange of sodium for potassium and hydrogen ions.
 With this this would lead to hypertension, hypokalemia alkalosis, skeletal muscle
weakness, and fatigue.
 High incidence of diastolic hypertension secondary to increase in sodium reabsorption
and extracellular fluid volume expansion.
 Preoperative preparation includes restoring the intravascular volume and electrolyte
concentrations. Treat hypertension and hypokalemia by controlling sodium intake and
administration of spironolactone. The usual complications of chronic hypertension need
to be assessed.

Addison’s disease

 A disease caused by the destruction of adrenal gland resulting in a combined

mineralocorticoid and glucocorticoid deficiency.
 This is secondary to autoimmune destruction of the adrenal cortex.
 Signs and symptoms of Addison's disease include hypotension, hyponatremia,
hyperkalemia, hypoglycemia, hemo concentration, skin pigmentation, weight loss,
skeletal muscle weakness, abdominal or back pain.
 Hypoglycemia as a result of diminished cortisol secretion from the adrenal cortex.
 The two electrolyte imbalances occur include hyponatremia and hyperkalemia secondary
to hypoaldosteronism.
 Hypotension is almost always encountered in the disease process.
 Treatment includes glucocorticoid therapy. Mineralocorticoid replacement is also
administered on a daily basis and this is with fludrocortisone.
 For acute adrenal insufficiency hydrocortisone 100 mg IV bolus, followed by
hydrocortisone 100 milligrams q six hours for 24 hours, with fluid electrolyte
replacement is indicated by vital signs, serum electrolytes, and serum glucose.
 The supplement that is key to management of patients with Addison's disease is with
glucocorticoid.

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 Glucocorticoid- Cortisol- Fasciculata

 Cortisol is the most potent endogenous glucocorticoid and this produced by the inner
portions of the adrenal cortex.
 The daily production of endogenous cortisol is approximately 20 mg with a maximal
output a modern 50 to 300 mg.
 Most of the circulating hormone cortisol is bound to alpha globulin transcortin
 Cortisol secretion is directly controlled by ACTH, which in turn is regulated by the
corticotropin releasing factor from the hypothalamus.
 ACTH is synthesized in the pituitary gland from a precursor molecule that also produces
be Lippo troponin and be endorphins.
 The secretion of ACTH and corticotropin releasing factor is governed chiefly by
glucocorticoids, the sleep wake cycle, and stress.
 Cortisol is the most potent regulator of ACTH secretion, this is another negative feedback
mechanism.
 Cortisol’s effects include intermediate carbohydrate, protein, and fatty acid metabolism,
maintenance and regulation of immune and circulatory function.
 Glucocorticoids enhance gluconeogenesis, elevated blood glucose, and promote hepatic
glycogen synthesis.
 In excessive amounts, glucocorticoids suppress the growth hormone secretion and
impairs somatic growth.
 Of all the synthetic corticosteroids- There is NO mineralocorticoid potency in
dexamethasone, betamethasone, and triamcinolone.

Cushing’s syndrome

 Caused by the overproduction of cortisol by the adrenal cortex or exogenous

glucocorticoid therapy.
 Signs and symptoms are truncal obesity, hypertension, hyperglycemia, increased
intravascular fluid volume, hypokalemia, fatigability, abdominal striae, osteoporosis,
muscle weakness.
 Remember excessive cortisol increases sodium reabsorption and sodium retention. This
in turn causes water retention which leads to hyperkalemia and hypertension. Cortisol
also promotes potassium secretion and excretion, so there is development of
hypokalemia. Hyperglycemia makes sense since excessive cortisol stimulates
gluconeogenesis and blocks entry of glucose into skeletal muscle cells and adipose tissue.
 Preoperative preparation includes treating hypertension and diabetes and normalizing
intravascular fluid volume and electrolyte concentrations.
 Diuresis with spironolactone.

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 Adrenal Gland- Medulla

 As a specialized part of the sympathetic nervous system, the adrenal medulla synthesizes
and secretes the catecholamines epinephrine 80% and norepinephrine 20%.
 Preganglionic fibers of the SNS bypass the paravertebral ganglia and pass directly from
the spinal cord to the adrenal medulla
 SNS Pregang- DIRECTLY TO ADRENAL MEDULLA
 The Adrenal Medulla can be considered analogous to a postganglionic neuron- but
excreting hormones, not neurotransmitters.


 The synthesis of norepinephrine begins with hydroxylation of tyrosine to dopa.
 Norepinephrine is converted to epinephrine by the enzyme phenylethanolamine-N-
methyltransferase.
 The adrenal Medulla secretes epinephrine norepinephrine and dopamine.
 The triggering event in the release of epinephrine and norepinephrine from the adrenal
Medulla is the release of acetylcholine by preganglionic cholinergic fibers of the
sympathetic division of the autonomic nervous system.
 Chromaffin cells of the adrenal medulla synthesize and release catecholamines-
Chromaffin- Catecholamines- Adrenal Medulla
 The final metabolic product of catecholamines is vanillylmandelic acid- VMA.
Somehow I remember that vanilla and catecholamines go together.

350
 Pheochromocytoma

 The only important disease process associated with the adrenal medulla.
 This is a catecholamine secreting tumor of chromaffin tissue.
 The HALLMARK of pheos are HTN associated with diaphoresis, headache, palpitations,
tremulousness, and weight loss.
 The 3 SIGNS AND SYMPTOMS- TRIAD- Diaphoresis, headache, and tachycardia.
 Most pheos secrete both epinephrine and norepinephrine with the percentage of secreted
norepinephrine being greater than that secreted by the normal gland.
 Diagnosis s through urinary vanillylmandelic acid and unconjugated norepinephrine and
epinephrine levels are measured in a 24-hour urine collection and are expressed as a
function of the creatinine clearance.
 ECG, chest radiograph, and complete CVC can provide valuable information the
clinician who entertains the diagnosis.
 An adrenergic blockade is initiated once the diagnosis of pheochromocytoma is
established.
 Phenoxybenzamine, long-acting, noncompetitive presynaptic alpha-2 and postsynaptic
alpha-1 blocker, has been used at doses of 10 MG every eight hours.
 Begin alpha blockade therapy at least 10 to 14 days before the proposed surgery however,
periods as short as 3 to 5 days have been used.
 Beta blockade is occasionally added after alpha blockade has been established. This
edition is considered in patients with persistent tachycardia or cardiac dysrhythmias the
may be caused by nonselective alpha blockade or epinephrine secreting tumors.
 Beta blockers should not be given until adequate alpha blockade is insured to avoid the
possibility of unopposed alpha mediated vasoconstriction.

351
 Pancreas

 Both exocrine and endocrine

 Sphincter of Oddi is formed from the pancreatic duct and common bile duct, which
empties into the duodenum.
 Insulin and glucagon are secreted by the islets of Langerhans. Insulin is secreted by beta
cells, Glucagon is secreted by alpha cells
 Pancreatic islet delta cells produce somatostatin- this inhibits GI motility and secretions
including secretion of Hydrochloric acid by the stomach.
 The tissues that DO NOT need insulin to utilize glucose- CNS and RBCs
 Insulin receptors- two alpha units, two beta units. The receptor is a tyrosine kinase. -
The insulin receptor intracellular protein is the IRS-1.
 Another test question we have had- The only way cells take up glucose is through
facilitated diffusion by a transporter called GLUT 4. Just relate Glucose to GLUt. And
think… to eat a lot of Glucose, you would have to be a GLUTtton.
 Insulin also works to stimulate the liver to store glucose in the form of glycogen. It also
promotes the synthesis of fatty acids in the liver, and inhibits breakdown of fat in adipose
tissue, also increases the permeability of many cells to K, Mg and PO4. Insulin causes a
flux of K into cells.

Type 1 Diabetes- Need insulin to survive- IDDM

 5-10 percent of all cases

 Diagnosed be4 age 40.
 Caused by a T-cell mediated autoimmune destruction of beta cells of pancreas. Unknown
mechanism, postulated viruses, dietary proteins, drugs/chemicals.
 At least 80-90 percent beta cell function must be lost be4 hyperglycemia occurs.
 Patients demonstrate hyperglycemia over several days to weeks associated with fatigue,
weight loss, polyuria, polydipsia, blurring of vision and signs of intravascular fluid
depletion
 Diagnosis is based on blood glucose >200, and an HbA1c> 7%.

Type II Diabetes, Do not need insulin- NIDDM

 Responsible for 90 percent of all cases of DM in the world.

 Typically middle age to older group and obese.
 Characterized by relative beta cell insufficiency and insulin resistance.
 Three important defects – increased rate of hepatic glucose release, impaired basal and
stimulated insulin secretion, and inefficient use of glucose by peripheral tissues.

352
 Diabetes and Anesthesia

 Three ketones produced by the diabetic patient are acetoacetic acid, beta-hydroxybutyric
acid and acetone. They are produced because when glucose cannot be utilized as energy-
fatty acids are then used, and when they are they are oxidized to ketones as described.
 A thorough preoperative search MUST be done for any end-organ complications of
diabetes.
 There are very important concerns in the DM patient with autonomic neuropathy since
they are at a higher risk of morbidity/mortality- orthostatic hypotension, silent MI, and
gastroparesis.
 DM patients are at a much higher risk of nerve injury, since they commonly present with
neuropathy.
 There are many CV manifestations of autonomic neuropathy associated with DM- and
these include- Orthostatic hypotension, resting tachycardia, absence of beat to beat
variability in HR, dysrhythmias, silent MI.
 We all know by now the DM is associated with retinopathy, CAD, PVD, PAD, CVA,
autonomic neuropathy, gastroparesis and renal disease.
 Realize diabetic stiff joint syndrome is associated with the prayer sign, and these patients
may be very difficult to DL with intubation.
 Hypoglycemia- activation of SNS- anxiety, diaphoresis, tachycardia, tremulousness

DKA

 Complication of decompensated DM.

 Diagnostic features- Glucose >300, pH<7.3, HCO3<18, positive ketones and <320
mOsm/L.
 DKA occurs more commonly in type 1 DM.
 Usually precipitated by infection or acute illness.
 Overproduction of ketoacids by the liver-metabolic acidosis from B-hydroxybutyrate,
acetoacetate, and acetone.
 There will be an increased anion gap with deficits in water, K and PO4.
 TX is giving large amounts of NS, doses of insulin, and electrolyte supplementation.

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 Hyperglycemic Hyperosmolar Syndrome

 Characterized by severe hyperglycemia, hyperosmolarity, and dehydration

 Usually older than 60 years of age type 2 DM patients get this, live alone, socially
isolated, and experience an acute illness such as infection, MI, CVA, renal failure, burn
pancreatitis, etc.
 The syndrome occurs over days to weeks with a persistent glycosuric diuresis.
 Patient presents with polyuria, polydipsia, hypovolemia, hypotension, and tachycardia
and organ hypoperfusion.
 Hyperosmolarity over 340 is responsible for mental status changes- obtundation, coma.
 DIC, vascular occlusions, low flow states are all important complications of HHS.
 Tx- significant fluid resuscitation, insulin and electrolyte supplementation
 Common features- Glucose >600, pH>7.3 HCO3 >15, mOsm/L>340.

Insulinoma

 Insulin secreting tumor of pancreatic beta cells manifested as fasting hypoglycemia.

 Principal anesthetic challenge is maintenance of normal blood glucose. Profound
hypoglycemia can occur intraop, followed by hyperglycemia after removal of tumor.
 Frequent measurement q15min of blood glucose intraop may be necessary.

Pituitary Gland- Master Gland

 Located in the sella turcica of the sphenoid bone at the base of brain
 The posterior pituitary (neurohyphophysis) is solely controlled by neural impulses, and
releases ADH and oxytocin. It is connected to the hypothalamus and is OUTSIDE the
blood brain barrier. It is a direct extension of the hypothalamus
 The anterior pituitary (adenohypophysis) hormones are ACTH, TSH, GH, prolactin, LH,
FSH, and PRL- and ALL are controlled by negative feedback.
 ADH- or vasopressin- controls water secretion and ECF osmolality. ADH target sites are
the collecting tubules of kidneys.
 The primary stimulus for release of ADH is an increase in serum osmolality.
 The anterior pituitary hormonal secretion is controlled by hypothalamus- hypophyseal
artery to the pituitary- then drain by way of the hypothalamic-hypophyseal portal veins

354
 Diabetes Insipidus

 Absence of ADH from destruction of the neurohyphophysis OR failure of renal tubule to

respond to ADH.- neurogenic vs. nephrogenic
 DI is seen in patients who undergo neurosurgical procedures, particularly those involving
the pituitary.
 Relate DI to transphenoidal hypophysectomy. Fluid and electrolyte replacement is
critical and Desmopressin as indicated.
 Classic manifestations are polydipsia, and a high output of poorly concentrated urine
despite high serum osmo.

SIADH

 This can occur in the presence of intracranial tumors, hypothyroidism, porphyria,

SMALL CELL LUNG CA.
 Inappropriately increased urinary Na concentration and osmolality in the presence of
hyponatremia and decreased serum osmo are suggestive of SIADH.
 What occurs in this disease is excessive reabsorption of water from renal tubules
secondary to high levels of ADH.
 Tx of SIADH- remove the underlying cause, restrict water intake, antagonize the effects
of ADH on renal tubule by giving democolcine, and giving hyperosmotic saline with or
without diuretics.

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Carcinoid Tumor

 A slowly growing neuroendocrine tumor (originating from neuroendocrine

cells) secreting bioactive substances:
o Serotonin:
 Metabolized to 5-HIAA acid. ↑levels of 5-HIAA in urine is a
marker for ↑serotonin levels
 Causes vasoconstriction or vasodilation → ↑BP or ↓BP
 ↑ gut motility, secretion of water, Na, K, Cl, by small intestine
 Vomiting, bronchospasm, ↑BS, prolonged drowsiness following
GETA.

o Histamine
 Bronchospasm, flushing
o Kinins
 Vasomotor relaxation → ↓BP and flushing; bronchospasm
 If these substances reach the systemic circulation they can produce carcinoid
syndrome → hemodynamic instability
 Normally the liver rapidly inactivates the bioactive substances → if the tumors do
not drain in the portal circulation, therefore bypassing the liver → capable of
producing carcinoid syndrome
 Carcinoid tumors originate in the GI tract or lungs (less common)
o Foregut carcinoids: from esophagus to duodenum
o Midgut carcinoids: from jejunum to mid-transverse colon; most likely to
produce carcinoid syndrome
o Hindgut carcinoids: from mid-transverse colon to rectum; usually do not
present w/ carcinoid syndrome, but present w/ GI bleeding
 Symptoms of carcinoid tumors:
o Hypotension or hypertension
o Cutaneous flushing
o Bronchoconstriction (wheezing)
o GI hypermotility: Diarrhea (dehydration, ↓Na, ↓K, ↓Cl, abd pain, nausea)
o Carcinoid heart disease
 Carcinoid syndrome: episodic flushing, diarrhea, wheezing, abd. Pain, R/L sided
heart disease.
o Triggering agents: stress, exercise, foods high in serotonin (bananas,
alcohol, cheese, coffee, avocados, tomatoes, plums, kiwis, eggplant,
walnuts)
 Carcinoid crisis: life-threatening
o Triggered by: physical tumor manipulation, induction, intubation,
chemical stimulation, tumor necrosis from chemotherapy
o Presentation: severe flushing, dramatic BP changes, ↑HR, cardiac
arrhythmias, bronchoconstriction, mental status changes

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  Diagnosis:
o 5-HIAA assay > 25mg per 24hrs → indicative of carcinoid tumor
o Chromogranin A (CgA): a protein found of neuroendocrine cells;
indicative of neuroendocrine tumors
 Treatment:
o Bowel resection and mesenteric lymphadenectomy (most effective)
o Somatostatin: ↓serotonin release from tumor
 Inhibits GI motility, gastric acid production, pancreatic enzyme
secretion, bile and colonic secretion, insulin, glucagon
 Short T1/2 1-3 min → administered as continues IV infusion
o Octreotide: (synthetic somatostatin analog) is drug treatment of choice for
symptoms
 Suppresses release of serotonin & other vasoactive substances
from tumor
 SQ T1/2 1.5-2 hrs; Tx symptoms and prevents intraoperative ↓BP
 IV injection or IV infusion T1/2 50 min; Tx carcinoid crisis
 50-200 mcg IV rapidly reverses severe ↓BP and
bronchospasm
 Infusion 50 mcg/hr following induction
 Inhibits insulin secretion
 Can be given SQ or IV (10-100 µg 1 hr preop)

Anesthesia management
Preop management
o Assess for presence or severity of carcinoid syndrome and triggering
factors
o Labs: CBC, BMP, liver f-n panel, BS, EKG, 5-HIAA
o Correct fluid and electrolyte abnormalities (especially w/ history of
diarrhea)
o Bronchodilators for wheezing
o Premedication:
 Maintenance medications continued
 Anxiolytics like benzodiazepines to ↓stress
 Antihistamines: diphenhydramine, ranitidine
 Octreotide 100mcg SQ/IV can be given before induction to prevent
mediator release

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Intraop management
o Avoid triggering release of bioactive substances from tumor → smooth
induction
o General anesthesia to avoid the sympathectomy w/ neuraxial anesthesia
o Octreotide 100 µg IV at induction
o Avoid histamine-releasing drugs
o Arterial line since potential exists for labile BP, placed prior to induction
due to potential for induction induced ↓BP triggering carcinoid crisis
o CVP can help exclude hypovolemia as a cause for ↓BP
o Temp monitoring and warming devices as hypothermia is a trigger for
bioactive substance release
o W/ coexisting cardiac dysfunction:
 Left ventricular f-n can be monitored w/ pulm artery catheter
 Right ventricular f-n can be monitored w/ TEE
Induction:
o Propofol best in suppressing sympathetic response, but be careful with
↓BP; can also use thiopental and etomidate
o No succinylcholine: ↑ Intraabdominal pressure from fasciculation’s may
trigger substance release
o Avoid histamine releasing drugs (avoid morphine)
 Fentanyl is ok
 Vecuronium (cardiovascular stability) is ok
 Rocuronium is ok
Maintenance w/ volatile agent & opioid or TIVA
o Sympathomimetic, e.g., ephedrine, can cause mediator release from tumor
o ↓ BP due to carcinoid crisis → Rx: ↓ anesthetic depth, fluids, pressors
like phenylephrine, octreotide (slowly IV)
 Have the surgeon stop operating until hemodynamic control is
restored
 Aprotinin (kallikrein inhibitor) to treat ↓BP refractory to octreotide
o Hypertensive carcinoid crisis →Rx: ↑volatile agent or octreotide gtt
o Bronchospasm → IV bolus octreotide 200 µg IV & nebulized
ipratropium
o Monitor blood sugar for hyperglycemia
o ↑ risk of bleeding due to abd carcinoids having rich vascular supply

 Postop management:
o If octreotide was taken prior to surgery, it should be weaned over 7 days
o Monitor x 24o for effects of carcinoid mediators → intensive or acute care
unit
o Ensure analgesia to prevent sympathetic stress (Fentanyl)

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 Renal Review:

Renal
Basic functions: The kidneys are responsible for, or contribute to, a number of essential functions
including water conservation, electrolyte homeostasis, acid base balance, and several
neurohumoral or hormonal functions. When the kidneys are involved in a disease process, some
or all of these functions may be affected. Knowledge of how the kidneys perform these important
functions aids in the understanding of the clinical presentation, signs and symptoms, and
treatment of renal diseases.
Each kidney consists of approximately a million nephrons, each of which has distinct anatomic
parts: Bowman's capsule, proximal tubule, loop of Henle, distal tubule, and collecting duct. A
glomerulus, which is a tuft of capillaries, is surrounded by Bowman's capsule and is supplied by
an afferent arteriole and drained by a slightly smaller efferent arteriole. The glomeruli filter the
plasma at a rate of 180 L/day, allowing all but protein and polysaccharides to pass into the
nephron. The glomerular filtration rate (GFR) is calculated from the clearance of either
endogenous or exogenous substances (creatinine and inulin, respectively). Normal values for
GFR are 125 mL/min but vary with gender, body weight, and age, and GFR decreases by
approximately 1% per year after the age of 20. The GFR may be calculated from timed urine
volumes plus urinary and serum creatinine concentrations (creatinine clearance), or,
alternatively, a number of formulas exist that estimate the GFR from serum creatinine, As the
plasma flows along the nephron, virtually all the fluid and solutes are reabsorbed by a number of
active and passive transport systems. The main function of the kidneys is water and sodium
homeostasis, which is intimately linked and regulated by a number of feedback and hormonal
systems.
Basic Renal Patho:
Acute kidney injury (AKI), previously called acute renal failure (ARF), is a rapid loss of kidney
function.
Its causes are numerous and include low blood volume from any cause, exposure to substances
harmful to the kidney (e.g. some drugs), and obstruction of the urinary tract. AKI is diagnosed on
the basis of characteristic laboratory findings, such as elevated blood urea nitrogen and
creatinine, or inability of the kidneys to produce sufficient amounts of urine. AKI may lead to a
number of complications, including metabolic acidosis, high potassium levels, uremia, changes
in body fluid balance, and effects to other organ systems. Management includes supportive care,
such as renal replacement therapy, as well as treatment of the underlying disorder.
Chronic renal failure is the progressive, irreversible deterioration of renal function that results
from a wide variety of diseases. Diabetes is the leading cause of end-stage renal disease (ESRD)
followed closely by systemic hypertension. The clinical manifestations of chronic renal failure
are typically independent of the initial insult that damaged the kidneys and instead reflect the
overall inability of the kidneys to excrete nitrogenous waste products, regulate fluid and
electrolyte balance, and secrete hormones. In most patients with chronic renal disease, regardless
of the etiology, a decrease in the GFR to less than 25 mL/min is characterized by progressive
deterioration in renal function that eventually leads to end-stage renal failure requiring dialysis or
transplantation. Intrarenal hemodynamic changes (glomerular hypertension, glomerular hyper
filtration and permeability changes, glomerulosclerosis) are likely responsible for progression of
359
renal disease. Systemic hypertension may be a primary cause of renal failure and is also a major
risk factor for progression of renal disease. Genetic factors may be important in determining
whether renal disease develops in hypertensive patients. Decreases in glomerular hypertension
and in systemic hypertension can be achieved by the administration of ACE inhibitors and/or
angiotensin receptor blocker (ARB). In addition to beneficial effects on intraglomerular
hemodynamics and systemic pressures, the renoprotective effects of ACE/ARB inhibitors
manifest as reductions in proteinuria and slowing of the progression of glomerulosclerosis in
patients with diabetic and nondiabetic nephropathy. Other antihypertensive drugs that lower the
systemic pressure to similar degrees do not provide the renoprotective effects seen with
ACE/ARB inhibitors.

Signs and symptoms of CRI may be undetectable until the later stages of the disease and even
then often continue to be nonspecific and vague, appearing insidiously as fatigue, general
malaise, and anorexia. Volume overload (peripheral edema and dyspnea) and electrolyte or acid
base disturbances are late signs of CRI. CRI and cardiac disease are intimately linked, and as
CRI progresses, coronary artery disease and congestive heart failure contribute to symptoms.
More than 70% of diabetic ESRD patients have congestive heart failure, while almost 70% have
ischemic heart disease. In nondiabetic ESRD patients, congestive heart failure and ischemic heart
disease occur less frequently, just more than 40% for both diagnoses. Seventy-five percent of
older patients beginning ESRD therapy carry a diagnosis of five or more comorbidities,
contributing to complex clinical presentation. It is well established that anemia develops in the
course of chronic kidney disease and is nearly universal in patients with kidney failure. Other
symptoms associated with CRI include cognitive impairment, peripheral neuropathy, infertility,
and increased susceptibility to infection.

Sources:
Clinical Anesthesiology, 4th Edition, G. Edward Morgan, Jr., Maged S. Mikhail, Michael J.
Murray
Hines & Marschall: Stoelting's Anesthesia and Co-Existing Disease, 5th Ed.

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Anesthetics and Renal Function:

Most drugs are weak electrolytes and lipid-soluble in the un-ionized state; thus, they are
extensively reabsorbed by renal tubular cells. Termination of their action is not dependent on
renal excretion; redistribution and metabolism produce this effect. After biotransformation, these
drugs are excreted in the urine as water-soluble, polar forms of the parent compound. They are
usually pharmacologically inactive, and their retention is not harmful. The majority of drugs
with prominent central and peripheral nervous system activity fall into this category, including
most narcotics, barbiturates, Phenothiazines, Butyrophenone derivatives, benzodiazepines,
ketamine, and local anesthetics. However, several drugs are relatively lipid-insoluble or are
highly ionized in the physiologic pH range and are eliminated unchanged in the urine. Their
duration of action may be extended in patients with impaired renal function. Drugs in this
category include muscle relaxants, cholinesterase inhibitors, thiazide diuretics, digoxin, and
many antibiotics. Because patients with severe renal disease often are debilitated, caution should
be exercised when administering any therapeutic agent; dosage reductions of 25 to 50 percent are
appropriate in most cases. At times, it may not be possible to avoid the administration of certain
nonanesthetic drugs, such as digitalis or aminoglycoside antibiotics, excreted primarily or solely
by the kidney. Blood concentration determinations of many of these agents are regularly
performed in many institutions. When levels cannot be determined, formulas have been derived
for calculation of dosage, based on serum creatinine concentration or creatinine clearance, so that
nontoxic therapeutic levels may be maintained. In patients with chronic renal disease who are not
dependent on hemodialysis or in those vulnerable to renal dysfunction because of advanced age
or the need for major thoracic or abdominal vascular surgery, anesthesia is often maintained with
nitrous oxide combined with isoflurane, desflurane, or short-acting opioids. Sevoflurane may be
avoided because of concerns related to fluoride nephrotoxicity or production of compound A,
although there is no evidence that patients with co-existing renal disease are at increased risk of
renal dysfunction following administration of sevoflurane. Isoflurane or desflurane combined
with nitrous oxide provides sufficient potency to suppress excessive increases in systemic blood
pressure due to surgical stimulation, to avoid the controversy related to fluoride nephrotoxicity,
and to decrease the dose of nondepolarizing muscle relaxants needed to produce skeletal muscle
relaxation. Total intravenous anesthesia with Remifentanil, propofol, and Cisatracurium has been
recommended for patients with end-stage renal failure. Potent volatile anesthetics are useful for
controlling intraoperative systemic hypertension and decreasing the doses of muscle relaxants
needed for adequate surgical relaxation. The high incidence of associated liver disease in patients
with chronic renal disease should be considered, however, when selecting these drugs.
Furthermore, excessive depression of cardiac output is a potential hazard of volatile anesthetics.
Decreases in tissue blood flow must be minimized in the presence of anemia to avoid
jeopardizing oxygen delivery to the tissues. Opioids decrease the likelihood of cardiovascular
depression and avoid the concern of hepatotoxicity or nephrotoxicity.

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Nevertheless, opioids do not reliably control intraoperative systemic blood pressure elevations.
Furthermore, prolonged sedation and depression of ventilation from small doses of opioids have
been described in anephric patients. Conceivably, pharmacologically active metabolites of
opioids accumulate in the circulation and cerebrospinal fluid when renal function is absent.
Selection of nondepolarizing muscle relaxants for maintenance of skeletal muscle paralysis
during surgery is influenced by the known clearance mechanisms of these drugs. Renal disease
may slow excretion of Vecuronium and rocuronium, whereas clearance of mivacurium,
Atracurium, and Cisatracurium from plasma is independent of renal function. Renal failure may
delay clearance of laudanosine, the principal metabolite of Atracurium and Cisatracurium.
Laudanosine lacks effects at the neuromuscular junction, but at high plasma concentrations, it
may stimulate the central nervous system. Regardless of the nondepolarizing, neuromuscular-
blocking drug selected, it seems prudent to decrease the initial dose of the drug and administer
subsequent doses based on the responses observed using a peripheral nerve stimulator. The
diagnosis of residual neuromuscular blockade after apparent reversal of nondepolarizing
neuromuscular blockade with anticholinesterase drugs should be considered in anephric patients
who manifest signs of skeletal muscle weakness during the early postoperative period. Renal
excretion accounts for approximately 50% of the clearance of neostigmine and approximately
75% of the elimination of Edrophonium and pyridostigmine. As a result, the elimination half-
time of these drugs is greatly prolonged by renal failure. Even in anephric patients, there is some
protection because renal elimination of anticholinesterase drugs is delayed as long as, if not
longer than, that of the nondepolarizing neuromuscular blocking drugs. In addition, other
explanations (antibiotics, acidosis, electrolyte imbalance, diuretics) should be considered when
neuromuscular blockade persists or reappears in patients with renal dysfunction. Patients with
severe renal dysfunction but not requiring hemodialysis and those without renal disease
undergoing operations associated with a high incidence of postoperative renal failure may benefit
from preoperative hydration with administration of balanced salt solutions. Most patients come
to the operating room with a contracted ECF volume unless corrective measures are taken.
Lactated Ringer's solution (potassium 4 mEq/L) or other potassium-containing fluids should not
be administered to anuric patients. Administration of balanced salt solutions (3–5 mL/kg per
hour IV), is often recommended to maintain acceptable urine output. Rapid infusion of a bolus of
balanced salt solutions to restore circulating volume (500 mL IV) should increase urine output in
the presence of hypovolemia. Stimulation of urine output with osmotic (mannitol) or tubular
(furosemide) diuretics in the absence of adequate intravascular fluid volume replacement is
discouraged. The most likely etiology of oliguria is an inadequate circulating fluid volume,
which can only be further compromised by drug-induced diuresis. Furthermore, although
administration of mannitol or furosemide predictably increases urine output, there is no evidence
of corresponding improvements in the GFR. Patients dependent on hemodialysis require special
attention with respect to perioperative fluid management. An absence of renal function narrows
the margin of safety between insufficient and excessive fluid administration to these patients.
Noninvasive operations require replacement of only insensible water losses with 5% glucose in
water (5–10 mL/kg IV). The small amount of urine output can be replaced with 0.45% sodium
chloride. Thoracic or abdominal surgery can be associated with loss of significant intravascular
fluid volume to the interstitial spaces. This loss is often replaced with balanced salt solutions or
5% albumin solutions. Blood transfusions may be considered if the oxygen-carrying capacity
must be increased or if blood loss is excessive

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 Renal Review

Good pasture’s Syndrome

‐ Rare autoimmune disease that manifests as rapidly progressing glomerulonephritis in
combination with pulmonary hemorrhage.
‐ Occurs most often in young males.
‐ Anti-glomerular basement membrane antibodies account for renal dysfunction and
also react with similar antigens in the lungs, producing alveolitis and subsequent
hemoptysis
‐ Hemoptysis precedes clinical evidence of renal disease.
‐ Plasmapheresis is sometimes used to remove the disease-causing antibodies.
Corticosteroids are also employed to reduce inflammatory damage.
‐ Prognosis is poor, and most patients develop renal failure within a year of diagnosis.
Interstitial Nephritis
‐ Allergic reaction to drugs, including sulfonamides, allopurinol, phenytoin, and
diuretics.
‐ Other less common causes include autoimmune diseases (lupus) and infiltrative
diseases (sarcoidosis).
‐ Patient’s exhibit decreased urine concentrating ability, proteinuria, and systemic
hypertension.
‐ Renal failure is often reversible after withdrawal of the offending agent or treatment
of the underlying disease.
Polycystic Kidney Disease
‐ Genetic disorder most commonly inherited as an autosomal dominant trait
‐ Disorder is marked by the development of cysts in the kidney, as well as in other
organs such as the liver and pancreas. Intracranial aneurysms and cardiac valve
abnormalities may also be present.
‐ Mild systemic hypertension, hematuria, kidney stones, and urinary tract infections are
common.
‐ Disease progresses slowly until renal failure occurs during middle age.
‐ Hemodialysis or renal transplantation is eventually necessary

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Anesthetic Management of patient with renal disease
‐ Preop
o Evaluate pt renal function
 Trends in creatinine
o Assess blood sugar and BP
o Serum K+ concentrations should not exceed 5 mEq/L on the day of surgery
o Assess for anemia
o Coagulopathy may be addressed with administration of Desmopressin.
o Gastric aspiration prophylaxis, especially in diabetic pt.
o Dialysis should be done within 24 hours of surgery
o
‐ Induction
o Induction and intubation can be safely accomplished with most of the IV
drugs (propofol, etomidate, thiopental)
o Likelihood of hypotension is increased by uremia
o Exaggerated central nervous system effects of anesthetic induction drugs d/t
uremia-induced disruption of the BBB.
o Succinylcholine ok if K+ less than 5.5
o Nondepolarizing MR with a short onset of action, such as rocuronium, may be
selected
o Attenuated sympathetic nervous system activity impairs compensatory
peripheral vasoconstriction; thus, small decreases in blood volume, institution
of PP ventilation, abrupt changes in body position or drug-induced myocardial
depression can result in an exaggerated decrease in BP.
‐ Maintenance
o Elimination of volatile anesthetics is not dependent on renal function.
o Sevoflurane may be avoided because of concerns related to fluoride
nephrotoxicity or production of compound A
o Decrease dose of MR to maintain surgical paralysis
o Clearance of Cisatracurium from plasma is independent of renal function.
o Morphine and meperidine undergo metabolism to potentially neurotoxic
compounds that rely on renal clearance.
o Elimination half-life of fentanyl may be prolonged in patients with CKD.
o To preserve blood vessels for future dialysis access, venipuncture should be
avoided entirely in the non-dominant arm as well as in the upper part of the
dominant arm.
o Radial and ulnar artery cannulation be avoided in case these vessels are
needed for an AV fistula in the future

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 o Venous pressure monitoring is often extremely helpful since a volume load is
not well tolerated by patients with even modest decreases in renal function.
o Special attn. to positioning: poor nutritional status renders the skin particularly
prone to bruising and sloughing.
o Fistulas must be protected. BP cuffs should not be applied to the arm with
fistula.
o Preoperative hydration with balanced salt solution if patients do not require
dialysis or operation associated with high incidence of postoperative renal
failure.
o LR or other potassium containing fluids should be used with caution.
o Maintain UO of at least 0.5ml/kg/hr is generally considered reasonable.
o Patients on hemodialysis require special attention to fluid management. An
absence of renal function narrows the margin of safety between insufficient
and excessive fluid administration.

Loop Diuretics
 Furosemide, Bumex and Ethacrynic Acid
 Inhibit Na+, K+ and Cl- reabsorption in the medullary portion of the
ascending loop of Henle.
 Responsiveness to Lasix is directly related to GFR
 Tx of cardiac failure, acute pulmonary edema, increased ICP
 Most important side effect is hypokalemia, which increases the potential for
digoxin toxicity and potentiates nondepolarizing relaxants
 Also trigger release of renal prostaglandins →venodilation→ ↓ BP 2° decreased
preload
Osmotic Diuretics
 Mannitol and Urea
 Mannitol is freely filtered at the glomerulus and not reabsorbed. This creates
increased osmolality in the renal tubule. Free water follows mannitol, diminishes
Na reabsorption.
 Works at the Proximal tubule
 SE: hypokalemia, dehydration
 Mannitol is contraindicated if the BBB has been disrupted since Mannitol may
enter the brain and bring fluid with it, increasing ICP. Mannitol may cause
vasodilation of vascular smooth muscle if administered too rapidly and cause
increased ICP.
 Don’t give with an open head injury

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Potassium Sparing Diuretics (aldosterone antagonists)
 Spironolactone (Aldactone) is the prototype aldosterone antagonist.
 Inhibits aldosterone, blocks Na reabsorption, and results in K retention
 Works in Distal tubule
 Spironolactone acts by competing with aldosterone in the late distal tubule and
mostly the collecting duct, and leads to hyperK+.
 K+ sparing diuretics which act independently of aldosterone include Amiloride or
triamterene.
Carbonic Anhydrase Inhibitors
 Acetazolamide
 Inhibit carbonic anhydrase, blocks H ion secretion and reabsorption of Na
and HCO3
 Works in proximal tubule
 SE: Hypokalemia, systemic acidosis, alkaline urine
 Inhibits the reabsorption of bicarbonate and prevents the secretion of H+ (dumps
bicarbonate) and leads to a hypokalemic acidosis.
 Cells of the proximal and distal renal tubules normally secrete hydrogen ions.
Carbonic anhydrase is an enzyme which converts carbon dioxide and water to
carbonic acid. This dissociates into bicarbonate which is reabsorbed and
hydrogen ions which are secreted. The secretion of hydrogen is accompanied by
the reabsorption of sodium and water.
DIURETICS: CARBONIC
 Acetazolamide is the prototype carbonic acid inhibitor, inhibiting acid secretion and
sodium reabsorption.
 It has the following effects: increased diuresis of a more alkaline urine, and a
hyperchloremic, hypokalemic metabolic acidosis.
 Thiazides
 Chlorothiazide, HCTZ, Metolazone
 Thiazides inhibit sodium and chloride reabsorption primarily in the cortical
portion of the ascending loop of Henle and in the early distal tubule.
 Hypokalemia results

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HCO3-
 HCO3- is normally not excreted.
 Reabsorption of existing bicarbonate is one of the major functions of the kidneys,
 Employing the Na+-H+ exchange which permits bicarbonate ions to be
reabsorbed and acids to be excreted.
 Most of the filtered HCO3- (90%) is reabsorbed in the PT; the other 10% is
reabsorbed in the later segment of the renal tubule.
 H+ ions are actively exchanged for Na ions in the tubular lumen.
 The H+ ions then combine with HCO3- in the tubular lumen to form
H2CO3
 which rapidly disassociates to CO2 and H2O then diffuse into the tubular
cell
 Where carbonic anhydrase catalyzes the CO2 and H2O to form HCO3-
and H+.
 HCO3- combines with Na and is reabsorbed to the peritublar capillary
blood.
 The H+ is not excreted but is again exchanged for Na and reenters the
lumen to recombine with HCO3-.
 Thus, in the PT, for every H+ ion secreted into the tubular lumen, a
HCO3- ion enters the blood.

ACID-BASE BALANCE
 From the PaCO2 & HCO3-, determine if primary disturbance is respiratory or metabolic;
or if a compensation has occurred ( pH restored)
 If PaCO2 change is compatible with the change in pH, disturbance is primarily
respiratory
 If HCO3- change is compatible with the change in pH, the disturbance is primarily
metabolic.
 Respiratory disturbances can be fully compensated , but not metabolic problems
 pH 7.35-7.45
 paCO2 35-45
 HCO3 22-26

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ANION GAP
The anion gap is used to aid in the differential diagnosis of metabolic acidosis.
Determined from plasma measurements of Na+, Cl-, & HCO3-
A representative of the unmeasured ions in the plasma or serum.
The 'measured' cations are Na+, K+, Ca2+ and Mg2+.
The 'measured' anions are Cl−, HCO3− and PO3−, with the 'unmeasured' anions as SO4 ²- .
Normal: 10-12 mEq/L
When non-chloride acids are added to the body fluids, there will be an increase in the
anion gap because HCO3- that reacts with the H+ is replaced by the unmeasured anion of
the acid. The Cl- usually does not change (normochloremic)
When HCO3 – is lost from the body fluids, Cl- replaces the lost HCO3-. The anion gap
does not decrease because Cl- increases (hyperchloremia)

HIGH ANION GAP

A high anion gap indicates that there is loss of HCO3− without a concurrent increase in
Cl−.
Electro neutrality is maintained by the elevated levels of anions like lactate, beta-
hydroxybutyrate and acetoacetate, PO4−, and SO4−. These anions are not part of
the anion-gap calculation and therefore a high anion gap results.

Thus, the presence of a high anion gap should result in a search for conditions
that lead an excess of these substances.

Here, bicarbonate concentrations decrease, in response to the need to buffer the

increased presence of acids (as a result of the underlying condition). The
bicarbonate is replaced by the unmeasured anion resulting in a high anion gap.

Lactic acidosis, ketoacidosis (DKA, ETOH abuse)

Toxins: ethylene glycol, methanol, propylene glycol, ASA, cyanide, iron,

isoniazid

Propylene glycol: preservative for diazepam and Lorazepam; subsequently

converted to lactate and pyruvate causing lactic acidosis

NORMAL
 The drop in HCO3− is compensated for almost completely by an increase in Cl− and hence
is also known as hyperchloremic acidosis.
 The HCO3− lost is replaced by a chloride anion, and thus there is a normal anion gap.
 GI loss of HCO3- (diarrhea) (note: vomiting causes hypochloremic alkalosis)
 Renal loss of HCO3- ( proximal RTA)
 Renal dysfunction ( RF, hypoaldosteronism, distal RTA
 Ingestions: ammonium chloride,acetazolamide,even TPN

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LOW ANION GAP
 Largely associated with hypoalbuminemia
 Albumin is a negatively charged protein and its loss from the serum results in the
retention of other negatively charged ions such as Cl- & HCO3-. As bicarbonate and
chloride anions are used to calculate the anion gap, there is a subsequent decrease in the
gap.
 Common conditions that reduce serum albumin in the clinical setting are hemorrhage,
nephrotic syndrome, intestinal obstruction and liver cirrhosis.

NEPHRON
 25% CO ( 1.25 L/min)
 Is the functional unit of the kidney and is made up of the
o glomerulus
 The glomerulus is a capillary tuft intimately associated with Bowman’s
capsule.
 The glomerulus is supplied by the Afferent arteriole and drained by the
Efferent arteriole, then to the peritubular capillary
 Juxtaglomerular cells are located around the Afferent arteriole
o Renal tubule.
 is formed from Bowman’s capsule,
 proximal convoluted tubule, and loop of Henle,
 Most of filtered sodium, potassium, bicarbonate, chloride, protein,
and water are reabsorbed from the proximal convoluted tubule and
loop of Henle back into peritubular capillaries.
 Cortical and distal convoluted tubule.
 Several distal convoluted tubules come together to form the
collecting ducts.
Afferent arteriole Glomerulus Efferent arteriole Peritubular Capillaries

 2 Types of Nephrons
o Cortical and medullary
o Peritubular capillaries arise from the Efferent arteriole and engulf the renal tubule.
o Vasa recta are the peritubular capillaries of the loop of Henle, and constitute the
countercurrent exchange system
o The inner stripe of the outer medulla is most vulnerable to ischemia ( probably
secondary to hypotension)

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 o Reabsorption: A substance may be transported from the tubule to the capillary
 Tubular reabsorption:
 Function of epithelial cells making up the tubule
 Passive diffusion
 Primary active transport: Sodium
 Secondary active transport (depending on the Na gradient): sugars
and amino acids
o Secretion: from the capillary to the tubule
o RAAS
 Stimulates Na reabsorption in the distal and collecting tubules
 Aldosterone can cause 99.5% retention of Na
o Inhibited by the natriuretic peptide
 Distal Convoluted tubules and collecting ducts
o ADH acts here causing reabsorption of free water and concentration of urine
 Principal cells resorb Na and H2O, secreted K
 Intercalated cells resorb K, and secrete either H+ or HCO3-
 Proximal Tubule
o Active reabsorption of Na is the primary function
o Reabsorbs the bulk of filtered fluid and its dissolved constituents, preliminary
control of ECF volume and concentration.
o HCO3- ( 90%) is reabsorbed in the PT
 Loop of Henle
o Establish a hyperosmotic state/gradient with in the medullary interstitial fluid
(this is achieved by absorbing more solute the water into the interstitium) by
means of a countercurrent multiplier system
o Descending limbs, both thin and thick segments, have
 Low permeability to ions and urea, while being highly permeable to water.
o Ascending limbs:
 The thin ascending limb is not permeable to water, but it is permeable to
ions.
o The loop of Henle is supplied a series of straight capillaries called the vasa recta,
which also have a countercurrent exchange mechanism that prevents washout of
solutes from the medulla, thereby maintaining the medullary concentration.
o As water is osmotically driven from the descending limb into the interstitium, it
readily enters the vasa recta.
o The low blood flow through the vasa recta allows time for osmotic equilibration.
o Also, the vasa recta provides an oncotic pressure for ions to enter the vasa recta
from the interstitium.
o The main function of the Loop of Henle is to set up a concentration gradient.

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HORMONES AND OTHER FACTORS
RAA SYSTEM
o Increase systemic arterial pressure, change RBF, and increase Na reabsorption.
o Rennin, an enzyme formed and stored in the granular cells of the afferent arterioles of the
JGA.
o Angiotensin II stimulates secretion of Aldosterone by the adrenal cortex, it is a potent
vasopressor, inhibits renin release, and stimulates ADH secretion and thirst.
Atrial Natriuretic Peptide
o When the heart dilates during volume expansion or heart failure, ANP and BNP inhibit
secretion of renin, inhibit angiotensin induced secretion of aldosterone, vasodilators’ the
afferent and constrict the efferent glomerular arterioles, and inhibit Na and water
absorption by kidney tubules.
Catecholamines
o Nor Epi and Epi promote afferent arteriolar vasoconstriction and decrease GFR and RBF.
ADH
o Secreted from the posterior pituitary
o Increases water permeability in the last segment of the distal tubule and along the entire
length of the collecting ducts.
o In the presence of ADH water reabsorption is high. Most of the water is reabsorbed in the
medullary collecting ducts.
RENAL FAILURE
May be "prerenal", "renal", or "postrenal".

Prerenal azotemia results from under perfusion of the kidney due to:
 dehydration, hemorrhage, shock, congestive heart failure ; glomerulonephritis is likely
also to be "prerenal" if mild, since it compromises renal blood flow more than tubular
function
 absolute decrease in blood volume (acute hemorrhage, GI fluid loss, trauma, surgery,
burns), relative decreases in blood volume (sepsis, hepatic failure, allergic reaction)

Renal azotemia (intrinsic) has several familiar causes:

 acute tubular necrosis, chronic interstitial nephritis, glomerulonephritis
 acute glomerulonephritis, interstitial nephritis, acute tubular necrosis (85% of cases—
comprised of ischemia, nephrotoxic drugs, solvents, contrast dyes)

Postrenal azotemia (obstructive) results from obstruction of urinary flow:

 prostate trouble, stones, surgical mishaps, tumors
 upper urinary tract obstruction (ureteral), and lower urinary tract obstruction (bladder
outlet)

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ACUTE RENAL FAILURE
– Increases in serum creatinine concentrations of more than 0.5 mg/dl compared
with baseline,
– 50% decrease in calculated creatinine clearance,
– or decreased function that results in the need for dialysis
– BUN increases around 20 mg/dL each day
– May be oliguric (< 400 ml day) or nonoliguric
– Prerenal and intrinsic renal failure due to ischemia or nephrotoxins are
responsible for most episodes of ARF.
ARF RISK FACTORS
– Co-existing renal disease
– Advanced age
– CHF and symptomatic CV disease associated with renovascular disease
– Major operative procedures (CABG, AAA resection), sepsis,
– Multi system organ failure
– Inadequate fluid replacement
– Delayed treatment of sepsis
– Non maintenance of systemic blood pressure
ARF COMPLICATIONS
– Neurologic – confusion, asterixis, somnolence, and seizures. May be ameliorated
by dialysis
– Asterixis (also called the flapping tremor, or liver flap) is a tremor when the wrist
is extended (dorsiflexion)
– CV – systemic HTN, CHF, pulmonary edema from sodium and water retention,
hypotension, anemia (Hct between 20-30%)
– GI – anorexia, nausea, vomiting, and ileus, GI bleeding in as many as 1/3 of
patients
– Infection – respiratory and urinary, and sites in which normal barriers have been
interrupted (owing to indwelling catheters). Impaired immune responses due to
uremia. Careful asepsis!
ARF MGT
– Associated with high morbidity and mortality
– Most often the first treatment perioperatively is a fluid challenge, with a possible
addition of a loop diuretic (diuretic therapy should stop if oliguria persists)
– Dopamine infusion (controversial)
– Hemodialysis
– Adequate protein and caloric intake because protein catabolism is excessive. A
negative nitrogen balance may result in malnutrition and impaired immune
defense mechanisms. Possible TPN.

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PERI-OP ARF
• Most common complication of critical surgical illness
• Surgery related ARF (incidence: 18%-47%) is 9x greater than overall incidence of ARF
(2%-5%) for other inpatients.
• Periop ARF accounts for ½ of all patients requiring acute dialysis
• Periop ARF is associated with 40-90% mortality

• CHRONIC RENAL FAILURE

Pathogenesis
– Multifactorial –not corrected RF
– Intrarenal hemodynamic changes (glomerular HTN, glomerular hyper filtration,
and permeability changes, glomerulosclerosis, systemic HTN)
– ACE Inhibitors are renal protective (reduce HTN, reduce proteinuria, and slow
progression of glomerulosclerosis in patients with diabetic and nondiabetic
nephropathy)
– Strict control of blood glucose can delay the onset of proteinuria and slow disease
progression
• Adaptations to chronic renal failure
– Patients can remain asymptomatic until renal function is <10% of normal
– As GFR decreases, creatinine and urea begin to increase, but is not directly
proportional to the degree of GFR impairment.
• when the renal reserve is exhausted, further decreases in GFR can result in
significant increases in serum creatinine and urea concentrations
– Serum K+ is maintained within normal limits until the decrease in GFR
approaches 10% of normal.
– K+ is secreted by the distal renal tubules, and as nephrons are lost, the remaining
nephrons increase their secretion of K+ through increased blood flow and
increased Na++ delivery to the collecting tubules. In addition, because
aldosterone secretion increases in patients with renal failure, there is a greater loss
of K+ through the GI tract.
– Third stage adaptation seen in sodium homeostasis and regulation of ECF volume.
S/S
– Electrolyte imbalance – hyperkalemia, hypermagnesemia, hypocalcemia
– Metabolic acidosis
– Unpredictable intravascular fluid volume status
– Anemia – increased CO, O2/Hgb curve right shifted
– Uremic coagulopathies – platelet dysfunction
– Neurologic changes – encephalopathy
– CV changes – systemic HTN, CHF, attenuated SNS activity due to
antihypertensive meds
– Renal osteodystrophy
– Pruritis

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 GFR Symptoms Labs
mL/min

Normal 125 none none

Decreased Renal 50-80 none none
Reserve
Renal Insufficiency 12-50 nocturia ↑ BUN & serum
creatinine levels
Uremia <12 Uremic syndrome multiple

 Uremic syndrome – a constellation of anorexia, N/V, pruritis, anemia, fatigue,

coagulopathy that reflects the kidney’s progressive inability to perform its excretory,
secretory, and regulatory functions.
– BUN is a good indicator of the extent, while serum creatinine (while a good
measure of GFR) poorly correlates with symptoms.
 HYPERKALEMIA
o Restrict dietary K+, avoid drugs that affect K+ homeostasis (triamterene,
spironolactone, NSAIDs, B-Blockers). Severe acidosis, acute infection with
marked catabolism, acute hemolysis, and marked hyperglycemia can result in
rapid development of life-threatening hyperkalemia. If the serum K+ is greater
than 6.5 meq/L or if ECG changes are present, immediate therapy must be
considered.
o Avoid LR : contains 4mEq/L K+; avoid elective sx unless K+ is < 5.5 mEq/L
o To lower K+: can also hyperventilate ( 10 mmHg decrease in PaCO2 will lower
K+ by 0.5 mEq/L; insulin-glucose; calcium
 ACIDOSIS
o The kidneys remove acid produced by dietary protein metabolism, and pH is
maintained until GFR decreases below 50 ml/min. Chronic metabolic acidosis
produces symptoms of fatigue and lethargy, increases respiratory work and
catecholamine responsiveness, stimulates protein degradation, and exacerbates
renal osteodystrophy.
o TX slowly with sodium bicarbonate.
 HYPERMAGNESEMIA
o Caused by magnesium retention and possibly excessive ingestion of magnesium
containing antacids
o Signs & symptoms: coma, hypoventilation, hypotension
o NMBs are potentiated by hypermagnesemia

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 RENAL OSTERODYSTROPHY
o Renal osteodystrophy – a complex interaction of secondary hyperparathyroidism
and decreased Vitamin D production by the kidneys. As GFR declines, there is a
parallel decrease in phosphate clearance and an increase in serum phosphate that
results in reciprocal decreases in serum calcium.
o Hypocalcemia stimulates parathyroid hormone, which leads to bone reabsorption
and calcium release. Because of decreased Vitamin D production, intestinal
absorption of calcium decreases, which adds to the above problem. TX is to
restrict dietary phosphate (antacids), administration of oral calcium and Vitamin
D therapy.
 ANEMIA / UREMIC BLEED
o Anemia – responsible for many of the undesirable symptoms (fatigue, weakness,
decreased exercise tolerance). Primarily due to decreased erythropoietin
production by the kidneys. Tx with epoetin and iron
o Uremic bleeding – increased tendency to bleed despite normal coags. The
bleeding time is the screening test that best correlates with the tendency to bleed.
Hemorrhagic episodes (GI bleeding, epistaxis, hemorrhagic pericarditis, subdural
hematoma) remain major factors contributing to the M/M of anemia. TX with
cryoprecipitate, DDAVP—but these treatments last only a few hours.
 CV CHANGES
o HTN presents in 80% of patients with ESRD
o HTN contributes to MI, CHF, CAD, and cerebrovascular disease. Dialysis is the
indicated TX for HTN due to hypervolemia (salt and water retention), whereas
dialysis is unlikely to control HTN due to activation of the RAA system (TX is
with drugs). Uremic pericarditis is a significant problem that can lead to
pericardial effusion, cardiac tamponade and hemodynamic instability.
 NEURO CHANGES
o Neurologic changes – early manifestations of renal insufficiency. Mild symptoms
(impaired abstract thinking, insomnia, and irritability) can progress with disease
to more significant changes (increased deep tendon reflexes, seizures,
obtundation, and uremic encephalopathy coma). A polyneuropathy develops
commonly in advanced renal failure, similar to restless leg syndrome.
 HEMODIALYSIS
o Diffusion of solutes between the blood and dialysis solution results in removal of
metabolic waste products and replenishment of body buffers.
o Goals are adequate dialysis, adequate nutrition, maintaining vascular access, and
prolonging life.
o The annual mortality rate for patients on dialysis is near 25% and is most often
attributed to cardiovascular causes or infection.
o INFECTION IS THE MOST COMMON CAUSE OF DEATH IN RENAL
PATIENTS!!

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PRIMARY KIDNEY DISEASE

 Glomerulonephritis
o Deposition of antigen-antibody complexes in the glomeruli from exogenous (post
streptococcal infection) or endogenous (collagen disease) processes.
o Manifestations include hematuria, proteinuria, HTN, edema, and increased plasma
creatinine concentration
o RBC casts are suggestive of glomerular disease
o TX’s: immunosuppressant’s, possible antibiotics

 Nephrotic Syndrome
o Most commonly due to diabetic nephropathy, or neoplasms (carcinoma, sarcoma,
lymphoma, leukemia), HIV, and Pregnancy-Induced Hypertension
o Manifestations include sustained and heavy proteinuria, hypoalbuminemia, edema
and ascites, hypovolemia, hyperlipidemia, and hypercoagulability
o TX’s: Managing edema and reducing proteinuria, so loop diuretics, ACE
inhibitors, steroids, cyclosporine

 Interstitial Nephritis
o Caused by allergic reaction to drugs (sulfonamides, allopurinol, phenytoin, and
diuretics), and less commonly from lupus and sarcoidosis.
o Decreased urine concentrating ability, proteinuria, and systemic hypertension
o Renal failure due to acute interstitial nephritis is usually reversible after
withdrawal of the offending drug or treatment of underlying disease.
o Steroids may be helpful

 Polycystic Renal Disease

o Autosomal dominant
o Progresses to and manifests as renal failure during middle ages
o Mild systemic HTN, proteinuria are common
o Cysts may be present in the liver and CNS as intracranial aneurysms
o Hemodialysis or renal transplantation is necessary in most of these patients

 Hereditary Nephritis (Alport Syndrome)

o Often accompanied by hearing loss and ocular abnormalities
o Males are afflicted more often than females
o Disease culminates in systemic HTN and renal failure
o No drug therapy successful

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 Renal Hypertension
o The appearance of systemic HTN in young patients suggests renal rather than
essential HTN
o Chronic pyelonephritis, glomerulonephritis and parenchymal diseases are risk
factors
o Tx with renal artery endarterectomy or nephrectomy

 Hepatorenal Syndrome
o Acute oliguria in patients with decompensated liver cirrhosis, which is associated
with decreased GFR and renal blood flow
o Renal failure in these patients may reflect hypovolemia caused by vigorous
attempts to treat ascites
o Saline and albumin may aggravate ascites, so PRBCs may be more appropriate
o A peritoneal to venous shunt may be necessary
o Hemodialysis has not been reliable

 Fanconi Syndrome
o Inherited or acquired disturbances of proximal renal tubular function, causing
hyperaminoaciduria, glycosuria, and hyperphosphaturia
o Renal loss of K+, HCO3-, and H2O
o Symptoms include polyuria, polydipsia, metabolic acidosis (loss of HCO3-), and
skeletal muscle weakness (loss of K+)
o Dwarfism and osteomalacia, reflecting loss of phosphate, is prominent in these
patients
o Management of fluids and electrolytes, and appreciation of LV failure secondary
to uremia

 Good pasture Syndrome

o A combination of pulmonary hemorrhage and glomerulonephritis, occurring most
often in young males
o Antigen-antibody deposits in kidneys and lungs
o Poor prognosis, with progression to renal failure usually within 1 year of
diagnosis

 Bartter Syndrome (congenital hypokalemia alkalosis)

o May be inherited as an autosomal recessive trait
o Characterized by hypokalemic, hypochloremic metabolic alkalosis in the presence
of increased circulating concentrations of renin and aldosterone and the
paradoxical absence of systemic HTN
o Due to a defect in Cl- reabsorption resulting in increased NaCl load to the distal
renal tubules, where the Na+ is reabsorbed in exchange for K+, resulting in
increased urinary K+ loss
o Increased arterial pH causes of left shift of the O2/Hgb curve with less oxygen
unloading to the tissues

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  Bartter Syndrome
o Management of acid-base and lytes, effects of hypokalemia (neuromuscular
blockade, cardiac arrhythmias)
o May need supplemental K+
o Nephrolithiasis
o Multifactorial causes
o Most stones are calcium oxalate (consider hyperparathyroidism, sarcoidosis,
cancer in these patients)
o Hematuria is common
o Ureteral obstruction may lead to s/s of renal failure

RENAL FUNCTION TESTING

• GFR
– BUN 7-18 mg/100cc
– Creatinine 0.6 -1.2 mg/100cc
– Creatinine Clearance 107-139 cc/min
• Tubular Function
– Specific Gravity 1.016 -1.022
– Osmol 40-1400 mosm/L
– Na+ 136-145 meq/L

BUN
 Urea is a relatively nontoxic substance made by the liver as a means of disposing of
ammonia from protein metabolism.
 Normal blood urea nitrogen is 7-18 mg/dL (2.9-8.2 mmol/L).
 Urea is filtered by the glomerulus. If the glomerular filtrate is flowing slowly through the
proximal tubule, urea tends to be passively reabsorbed and return to the bloodstream.
 Blood urea levels are sensitive indicators of renal disease, becoming elevated when renal
function drops to around 25-50% of normal
 BUN is altered by a number of variables:
 Increased protein intake, GI bleeding, and dehydration
 The capacity of the liver to form urea from amino acids
 Rate of incorporation of amino acids into tissue protein
 Rate of release of amino acids from tissue protein, altered, for example, by sepsis
or trauma
 Increased BUN is, by definition, azotemia due either to increased protein catabolism or
impaired kidney function.

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  Increased protein catabolism results from:
 a really big protein meal
 severe stress (myocardial infarction, high fever)
 upper GI bleeding (blood being digested and absorbed)
 Decreased BUN
 Lack of protein (celiac disease, some patients with nephrotic syndrome)
 Severe liver disease (end-stage cirrhosis, yellow atrophy, hepatitis, halothane or
acetaminophen toxicity, enzyme defects)
 Over hydration (iatrogenic, psychogenic water-drinking)

CREATININE
 This breakdown product of creatine phosphate is released from skeletal muscle at a
steady rate.
 It is filtered by the glomerulus, and a small amount is secreted into the glomerular filtrate
by the proximal tubule
 If the urine volume goes up, the serum creatinine does go down slightly.
 Creatinine is generally considered a more sensitive and specific test of renal function than
BUN.
 Normal serum creatinine is 0.6-1.2 mg/dL
 Increased creatinine is due to any cause of impaired kidney function listed above, a lot of
meat in the diet, or a very large muscle mass (bodybuilders, anabolic steroid users, giants
and acromegaly patients).
 A few drugs block the tubular secretion of creatinine, and will increase serum creatinine
levels even though they have not damaged the kidney. This will be important if, and only
if, the GFR is already very low. Remember probenecid, cimetidine, triamterene,
trimethoprim, and Amiloride.
 In massive rhabdomyolysis / crush injury, there is so much creatine released that the
creatinine will rise.
 Athletes taking oral creatine may have slight increases in serum creatinine levels for the
next day or so, but the effect is slight and unlikely to take a person above the normal
range

CREATININE CLEARANCE
 Creatinine clearance is widely used to approximate GFR , measured following a 24 hour
urine collection
 You remember that the clearance of a substance is the volume of plasma "cleared" of that
substance per unit time.
 The most definitive test of GFR
 Normal: 107-139 ml/min
 Creatinine clearance decreases with age. It approaches 70 ml/min at 70 years of age.

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PRERENAL VS. RENAL AZOTEMIA
 A very common clinical problem is to distinguish prerenal azotemia (due to shock,
dehydration, CHF -- also "hepatorenal syndrome") from renal azotemia (acute tubular
necrosis, "renal shutdown".)
 Either could be the cause when a patient has been hypotensive and now is azotemia and
oliguric but the management is different.
 One older technique is to calculate the BUN/creatinine ratio, which is normally around
10.
 Values over 10, especially over 20, suggest prerenal azotemia rather than acute
tubular necrosis.
 High values are also seen postrenal azotemia and upper GI bleeding.
 In fact, a high BUN/creatinine ratio is a common finding, especially in the elderly,
and a marker for ill-health

URINE SODIUM
 In prerenal azotemia, urine sodium is low (the kidney responds to low blood flow by
"trying to retain all the sodium it can.")
 In acute tubular necrosis, urine sodium is higher (the renal tubules are unable to
concentrate or dilute the glomerular filtrate effectively.)
 Urinary sodium under 20 mEq/L suggests prerenal azotemia (or hepatorenal syndrome,
etc.); urinary sodium over 40 mEq/L suggests acute tubular necrosis

FENa
 A further refinement, currently popular, is to measure the fractional excretion of filtered
sodium (FeNa), approximated by:
 Values less than 1% indicate prerenal azotemia; values over 2% indicate acute tubular
necrosis

URINE SPECIFIC GRANITY

 Provides information about tubular function and hydration.
 We drink relatively little fluid. Thus "normal" people have fairly concentrated urine (SG
greater than 1.010). The same is true of patients in prerenal azotemia (high urinary
specific gravity, low or zero urinary sodium).
 Patients with tubular disease ("renal azotemia", i.e., acute tubular necrosis, really bad
bilateral pyelonephritis or interstitial nephritis, or on diuretics, or with end-stage kidney)
will have isosthenuria. This is a fancy word for fixed SG of around 1.010 because the
kidney cannot form urine with a higher or lower specific gravity.
 Patients getting lots of fluid by IV, or with diabetes insipidus, or enthusiastic water-
drinkers will have low urine specific gravity.
 This test is unreliable in the setting of diuretic administration or in the presence of
glycosuria.
 If SG is > or = to 1.025, the patient is volume constricted, “dry”.

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URINE MICROSCOPY
 If there is proteinuria, this indicates or suggests parenchymal disease
 If there are RBCs, this indicates trauma, tumor or infection
 If there are WBCs or bacteria, this indicates infection
 If there are fatty casts, this indicates nephrotic syndrome
 If there are ketones, this indicates DKA or starvation
URIC ACID
 This breakdown product of purine metabolism is filtered by the glomeruli and then
reabsorbed and secreted by the renal tubules. Serum levels are highly variable from day
to day.
 Indications: include suspected gout and suspect uric acid nephropathy. However, it is
generally measured as part of an automated chemistry profile.
 Increased serum uric acid is often seen in:
 renal failure
 gout (remember all patients with gout have hyperuricemia, but most patients with
hyperuricemia do not have symptomatic gout)
 liver-and-sweetbread gourmets ("organ meats" are rich in purines)
 increased breakdown of nucleoprotein (burns, crush injuries, very severe
hemolytic anemia, plasma cell myeloma, myeloproliferative disorders, and
especially leukemia’s under treatment)
 lead poisoning
 patients receiving thiazide diuretics or high doses of aspirin
 idiopathic
PRE RENAL RENAL

UOP cc/kg/hr <0.5 <0.5

Urine sodium : mEq/L <20 >40

FENa+ <1 >2

Urine Osm : mOsm/L >400 250-300

BUN/ Crea ratio >20 <20

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ANESTHETIC IMPLICATIONS
 In general, volatile anesthetics decrease renal blood flow and GFR, thus urine output.
 They also disturb autoregulation so that decreases in MAP are reflected by falls in urine
output.
 Thus, renal blood flow becomes pressure dependent.
 ADH increases with volatile anesthetics, fluid loss, and positive pressure ventilation.
Postoperatively, the ADH influence is felt more strongly than the aldosterone influence,
the reason hyponatremia develops.
 Spinal in the presence of renal failure should only be undertaken when coagulopathy has
been ruled out.
 Succinylcholine should be avoided when serum potassium is > or = to 5.5 meq/L. K+
increases 1 meq/L after the administration of succinylcholine and increases the risk of
cardiac standstill when the baseline level is high.
 The actual rise in K+ with succinylcholine is no greater in renal failure patients
than in other patients. Some consider it the drug of choice, because of its
metabolism, as long as the potassium level is not initially elevated.
 **Atracurium is an excellent choice because of Hoffman elimination and ester hydrolysis
(non-organ dependent mechanisms of elimination). Less than 10% is excreted unchanged
by renal and biliary routes.
 *Cisatracurium (Nimbex) metabolism is independent of renal or liver function and is also
a good choice in end-organ failure.
 Vecuronium (Noruron) is an acceptable choice in the setting of CRF as its elimination is
largely biliary. While renal elimination is not insignificant (25%), it is generally
considered acceptable for renal failure patients. However, it must be understood that the
duration of this drug is somewhat prolonged in the setting of renal failure.
 Rocuronium (Zemuron) is not significantly metabolized. It is eliminated primarily by the
liver and slightly by the kidney; liver failure prolongs metabolism but renal failure does
not.
 Metocurine (a derivative of Tubocurarine) is not a good choice as it is largely excreted by
the kidneys, so duration of action is prolonged in renal failure.
 Neostigmine, an anticholinesterase drug used to reverse the effects of neuromuscular
blockade, relies upon renal excretion. Dose should be reduced 50-75% in patients with
renal failure.
 Thiopental is generally 85% bound to plasma proteins. In uremia, with decreased protein
amounts, there is less binding to albumin and other plasma proteins and thiopental is
therefore available at receptor sites in greater amount.
 Since thiopental is a weak acid, the acidosis of renal failure results in more
unionized, nonbound, and active drug. This is another reason for administering
less.
 Morphine has an active metabolite, Morphine-6-glucuronide, that has an increased
duration of action in patients with chronic renal failure. Dose should be decreased, and
adjustments to dosing intervals may be necessary.

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DIALYSIS
 Dialysis should be performed from 6-24 hours before surgery.
 If it is done too close to surgery, volume depletion can be present. However, if it is done
too remote from surgery, electrolyte disturbances can be present.
 Consult your institution’s policy, but it is general practice to draw a serum K+
preoperatively on dialysis-dependent renal failure patients.

383
 Renal Study Guide

Renal Functions
1. Maintain Extracellular Composition
a. Regulation of ionic composition
i. Acid-Base (H+, HCO3)
ii. Electrolytes (Na, K, Ca, Mg, Cl)
b. Osmolality
i. Regulating Na concentration (90% ECF osmolality from Na salts)
ii. Concentration=amount/volume (kidneys regulate concentration by
regulating volume)
iii. Normal osmolality = 300 mOsm/kg (270-310 mOsm/kg)
1. Osmolality = measure of solute concentration (# of osmoles of
solute/L of solution)
2. Osmolality = measure of osmoles of solute / kg of solvent
c. Regulation of non-ionic plasma components (glucose, amino acids, proteins,
water)
d. Elimination of non-volatile end products of metabolism (phosphates, sulfates,
urea, creatinine, uric acid, lactic acid)
2. Maintain Extracellular Fluid Volume
a. Regulate Na and H2O excretion
3. Endocrine Functions
a. Erythropoietin (chronic renal failure →anemia)
b. RAAS (Renin Angiotensin Aldosterone System)
i. Enzyme-hormone system for blood pressure regulation, K & Na excretion
ii. Stimulates Sodium reabsorption in the distal and collecting tubules
iii. Inhibited by natriuretic peptide → ANP also inhibits Na Reabsorption
iv. Aldosterone causes 99.5% sodium retention → if absent, 20 mg Na/day
excreted
Renin stimulated by ↓renal perfusion, ↓ Na, SNS stimulation
Liver produces Angiotensin → Juxtaglomerular apparatus produces renin which converts
angiotensin to angiotensin I →the lungs produce a converting enzyme (ACEI make you cough
d/t leukotriene’s) to then produce angiotensin II which stimulates the adrenal cortex to produce
Aldosterone (may also be secreted if hyperkalemia present) which leads to increase Na
reabsorption (and K excretion) to help correct low Na, ECF volume and Arterial BP
If there is increased plasma potassium or low Na, low ECF volume or Low BP, Aldosterone
secretion will ↑ to increase tubular Secretion and increase urinary K excretion, increase tubular
Na Reabsorption and decrease urinary Na excretion
c. Convert Vit D to active forms (Vit D3 to 1,2,5 dihydrocholecalciferol)
i. Chronic renal failure →hypocalcemia

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 4. Arterial Blood Pressure Regulation
Urinary System (blood supply –arteries & veins, kidneys, ureter, urinary bladder, urethra
1. Bladder → stores the urine
a. Gravity & peristalsis propel the urine in the ureter
b. PSNS contracts the bladder causing micturition if both sphincters relax
i. The external sphincter is under voluntary control
c. Reflex →bladder filling →bladder contraction →internal sphincter opens →
stretch receptors send inhibitory impulses to external sphincter which is
voluntary→ cortex can override reflex or allow it to take place
2. Kidney → uses 25% of the CO (1.25 L/min) and most of the blood flow goes to the renal
cortex
a. Renal Blood flow + GFR are auto regulated over a MAP of 60-160
b. Inner Stripe of outer medulla is the most vulnerable to ischemia from hypotension
c. GFR decreases sharply at a MAP of 50 or less (hypovolemia, sepsis, after bypass
pump) and there are no β receptors in the kidney
3. Nephron→ functional unit of the kidney made of glomerulus and renal tubule
a. Glomerulus → capillary tuft is intimately associated with Bowman’s capsule
i. Glomerular Filtration
1. Function Test = BUN (norm 7-18 mg/100 cc), Creatinine (0.6-1.2
mg/100cc) Creatinine Clearance (107-139 cc/min)
2. Filtered blood in tubule forms primitive urine
3. Entire plasma volume filtered 65 x/day, proteins are not filtered,
180 L/day or 120 ml/min
4. Tubular Reabsorption →absorption of substances needed into the
tubular cells, interstitium or peritubular capsules
a. By passive diffusion, by primary active transport (Na), by
secondary active transport depending on the sodium
gradient across the membrane (sugars & amino acids)

5. Tubular Secretion →Secretion of substances to be eliminated from

the body into the renal tubule
6. Forces of Glomerular Filtration
a. Glomerular Capillary Hydrostatic Pressure (47)
b. Glomerular Capillary oncotic pressure (-25)
c. Bowman’s Capsule Hydrostatic Pressure (-10)
d. Net Filtration Pressure (12)
b. Renal Tubule is formed by:
i. Bowman’s capsule
ii. Proximal convoluted tubule
a. Glucose actively reabsorbed here, if concentration > 180 mg/dL
→ glucose spills into urine

385
 b.
iii. Loop of Henle →establishes osmotic gradient in medulla
a. Countercurrent multiplier system that utilizes Na pumps to
produce hyperosmolar urine by the kidney
i. Derived form and process (Function) of LoH which has
two parallel limbs of renal tubules running in opposite
directions, separated by interstitial space of renal
medulla. Water flows from tubular fluid of descending
limb on LoH into the medullary space
ii. Proximal tubule osmolality is iso-osmolar to plasma
1. Ascending limb (impermeable to H2O) Na and Cl
are actively transported into medullary space so
filtrate becomes hypotonic

2. Active transport creates osmotic pressure drawing

H2O from descending limbs into hyperosmolar
medullary space
iii. Countercurrent flow between ascending and descending
limbs increases or multiplies osmotic gradient between
tubular fluid and interstitial space.
1. Countercurrent multiplication is a hypothesis
describing the mechanism whereby urine is
concentrated in the nephron
2. Mechanisms of countercurrent multiplication and
vasa rectas countercurrent exchange help prevent

386
 wash out of salts → maintaining a high osmolality
in inner medulla
b. Creates and area of high Na concentration deep in the medulla
near the collecting duct
c. Water in filtrate of collecting duct flows thru aquaporin channels
out of collecting duct, moving passively decreases its
concentration gradient
i. Reabsorbs H2O and creates a concentrated urine for
excretion
d. Descending limbs (thin & thick segments) have low permeability
to ions and urea but are highly permeable to H2O
e. Ascending Limbs
i. Thin ascending limb is not permeable to H2O, it is
permeable to ions
ii. Thick medullary ascending limb reabsorbs Na, K, Cl by
active transport
1. K transported thru K channel across concentration
gradient and takes other ions with it (Mg, Ca, Na)
iii. Cortical thick ascending limb drains urine into distal
collecting tubule
f. Main Function is to set up a concentration gradient
iv. Cortical and distal convoluted tubule
a. Several distal convoluted tubules form collecting ducts
i. Make final adjustments in urine osmolality, ionic
composition, pH → depending on body’s current
metabolic needs
ii. ADH controls H2O reabsorption while Aldosterone
controls Na reabsorption and K secretion
iii. ADH increases the permeability of the distal tubule and
collecting duct to H2O → H2O reabsorbed → small
volume high concentrate urine formed

iv. Distal Tubule and collecting duct are final control in

renals of ECF volume and composition
a. Tubular Function Tests = specific gravity
(normal 1.016-1.022), osmolality (normal 40-
1400 mOsm/L), Na (normal 136-145 mEq/L)
b. ADH acts at Distal convoluted tubules and collecting ducts,
released from posterior pituitary
i. Rate of Release is proportionate to the osmolality of the
ECF, ↓ vascular volume (↑ osmolality) → ADH release,
thirst mechanism activated = ↑ H2O ingestion
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 ii. Other triggers → HoT, pain, trauma, CPAP, PEEP, VA’s
1. +ADH →1200-1500 mOsm urine
osmolality→0.5 ml/kg/hr of urine volume
2. –ADH → 50-100 mOsm urine osmolality→2-25
ml/kg/hr urine volume
iii. SIADH
1. Inappropriate ADH secretion caused by surgery,
intracranial tumor, hypothyroidism, porphyria,
small cell lung CA
2. Findings → inappropriately increased urine
sodium concentration and increased urine
osmolality which leads to ↓ plasma osmolality
3. Treatment= limit fluid intake, 3% NaCl slowly, if
Na < 120 seizure threshold is ↓
c. Filter Na, K, HCO3, Cl, protein, H2O which are reabsorbed from the proximal
convoluted tubule and loop of Henle to go back into peritubular capillaries
i. Peritubular capillaries arise from the afferent arteriole and engulf the renal
tubule
ii. Vasa Recta → straight peritubular capillaries in the loop of Henle that
constitute the countercurrent exchange system
1. Maintains medullary concentration
2. H2O is osmotically driven from descending limb into interstitium
and readily enters vasa recta
3. Low blood flow thru vasa recta allows for osmotic equilibrium
4. Provides oncotic pressure for ions to enter vasa recta from intertie
d. Types → Cortical & Medullary
4. Proximal Tubule (PT) → reabsorbs the bulk of filtered fluid and dissolved constituents
which leads to preliminary control for renal regulation of ECF volume and composition

388
Renal Failure
Acute=sudden onset, rapid reduction in urine output, usually reversible
Chronic= progressive, not reversible
General Assessment with RF = anemia and heart failure, acidosis, coagulopathies, electrolyte
problems, infection, hypertension, hyperglycemia, hyperparathyroidism
Pre-Renal; Renal; Post Renal AZOTEMIA
Pre-Renal AZOTEMIA: result from under perfusion to the kidney (dehydration, hemorrhage,
shock, CHF, glomerulonephritis, trauma, surgery, burns, sepsis, hepatic failure, aortic or renal
artery clamping, thromboembolism), compromises renal blood flow > tubular function
Absolute decrease in blood volume (acute hemorrhage, GI fluid loss, trauma, surgery,
burns) or Relative decreases in blood volume (sepsis, hepatic failure, allergic reactions)
Renal Azotemia: Intrinsic, caused by acute tubular necrosis, chronic interstitial nephritis,
glomerulonephritis (aminoglycosides are nephrotoxic antibiotics)
Acute glomerulonephritis, interstitial nephritis, acute tubular necrosis (85% → ischemia
from nephrotoxic drugs, solvents, contrast dyes)
Post-renal Azotemia: Obstructive → urinary flow →prostate trouble, stones, surgical mishaps,
tumors
Upper urinary tract obstruction (ureteral) and lower urinary tract obstruction (bladder
outlet) (nephrolithiasis, BPH, clot retention, bladder carcinoma)
ACUTE RENAL FAILURE
Increased serum creatinine (more than 0.5 mg/dL than baseline; normal is 0.6-1.2 mg/100 cc),
50% decrease in calculated creatinine clearance or decreased fsn leading to dialysis
1. BUN increases (range 10-50 mg/dL daily)
2. May be oliguric (< 400 ml/day) or non-oliguric
3. Pre-renal and intrinsic renal failure due to ischemia or
nephrotoxins are responsible for most ARF episodes

389
 ARF Risk Factors:
Co-existing Dz, Advanced Age, CHF & symptomatic CV Dz associated with
renovascular Dz, Major operative procedures (CABG, AAA resection), Inadequate fluid
replacement, Non-maintenance of systemic blood pressure, sepsis, delayed treatment of
sepsis, multisystem organ failure
ARF Complications:
1. Neurologic: confusion, asterixis (motor disorder with jerky movements),
somnolence & seizures, may be ameliorated by dialysis
2. Cardiovascular: systemic HTN, CHF, pulmonary edema (Na & H2O
retention), Hypotension, anemia (Hct 20-30%)
3. GI: anorexia, nausea and vomiting, ileus (GI bleeding in up to 1/3 of patients)
4. Infection: respiratory and urinary or sites where normal barriers are
interrupted, Impaired immune responses due to uremia
ARF Management:
1. Treat with fluid challenge and possibly loop diuretic
2. Dopamine infusion (controversial)
3. Hemodialysis
4. Adequate protein and caloric intake (excessive protein catabolism) – negative
nitrogen balance may result in malnutrition and impaired immune defense
mechanisms – TPN?
Peri-op ARF:
1. Most common complication of critical surgical illnesses
2. Surgery related ARF (18-47% incidence) is 9x greater than overall ARF
incidence (2-5%) for in patients
3. Periop ARF accounts for ½ of patients requiring acute dialysis
4. Associated with 40-90% mortality
Chronic Renal Failure
A. Pathogenesis – multifactorial
a. Intrarenal hemodynamic changes (glomerular HTN, glomerular hyperfiltration,
permeability changes, glomerulosclerosis, systemic HTN)
b. ACE Inhibitors are renal protective (↓ HTN, ↓ proteinuria and slow progression of
glomerulosclerosis in pts with DM nephropathy or non-DM nephropathy)
c. Strict blood glucose control can delay onset of proteinuria and slow progression
of disease

390
B. Adaptions to CRF
a. Pt may remain asymptomatic until renal function < 10%
i. As GFR ↓ plasma concentrations of urea and creatinine begin to increase,
altho they are not directly proportional
ii. When renal reserve is exhausted, further ↓ in GFR can result in significant
↑ in serum creatinine and urea concentrations
b. Serum K+ maintained within norm limits until GFR ~10% normal
i. Normally, K secreted by distal renal tubules
ii. Aldosterone increased Na reabsorption and H2O and ↑ secretions of K+
1. As nephrons lost, remaining nephrons ↑ secretion of K
a. Increased blood flow
b. Increase Na delivery to collecting tubules
2. Aldosterone secretion ↑ in renal failure
a. Greater loss of K thru GI tract
c. Third Stage Adaption seen in Na homeostasis and regulation of ECF volume
C. Symptoms
a. Electrolyte imbalance – hyperkalemia, hypermagnesemia, hypocalcemia
b. Metabolic Acidosis
c. Unpredictable intravascular fluid volume status
d. Anemia - ↑CO – oxyhemoglobin curve shifted right
e. Uremic coagulopathies – platelet dysfunction
f. Neurologic changes – encephalopathy
g. CV changes→ systemic HTN, CHF, attenuated SNS activity d/t antihypertensive
meds
h. Renal osteodystrophy
i. Pruritis (uremic scales)

GFR ml/min symptoms labs

Normal 125 none none
↓ renal reserve 50-80 none none
Renal insuff. 12-50 nocturia ↑ BUN, creatinine
Uremia <12 uremic syndrome multiple

D. Uremic Syndrome
a. A constellation of anorexia, N/V, pruritis, anemia, fatigue, coagulopathy that
reflects the kidney’s progressive inability to perform its excretory, secretory and
regulatory functions
b. BUN is a good indicator of extent while serum creatinine (while good measure of
GFR) poorly correlates with symptoms

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E. Hyperkalemia & Chronic Renal Failure
a. Restrict dietary K and avoid drugs that affect K homeostasis
i. Triamterene, spironolactone, NSAIDS’s, BB’s
ii. Avoid LR – contains 4 mEq/L K+
b. Severe acidosis, Acute infection with marked catabolism, acute hemolysis,
marked hyperglycemia – rapid development of life threatening hyperkalemia
c. If serum K > 6.5 mEq or if ECG changes present, immediate therapy must be
considered – avoid elective surgery unless K < 5.5 mEq/L
d. To lower K – hyperventilate (10 mmHg ↓PaCO2 = ↓ K+ by 0.5 mEq/L)
i. Insulin/glucose
ii. Calcium
F. Chronic Renal Failure Acidosis
a. Treat slowly with sodium bicarb (pushes K out)
b. Kidney remove acid produced by dietary protein metabolism
c. pH is maintained until GFR ↓ below 50 ml/min
d. Chronic metabolic acidosis → symptoms of fatigue & lethargy, increases
respiratory work and catecholamine responsiveness, stimulates protein
degradation and exacerbates renal osteodystrophy
G. Hypermagnesia
a. Caused by magnesium retention and possibly excessive ingestion of magnesium
containing antacids (Hypocalcemic)
b. S & S – coma, hypoventilation, hypotension
c. Hypermagnesia potentiates NMBA’s
H. Renal Osteodystrophy – a complex interaction of 2̊ hyperparathyroidism and ↓ Vit D
production by the kidneys
a. GFR declines – parallel ↓ in phosphate clearance - ↑ serum PO4 – reciprocal ↓ in
serum Ca++
b. Hypocalcemia stimulates parathyroid hormone – bone reabsorption & Ca release
i. ↓ Vit D production = ↓ intestinal absorption of Ca
ii. Treatment with oral Ca and Vit D therapy – avoid dietary phosphates
(antacids)
I. Chronic Renal Failure Anemia –d/t ↓ erythropoietin production by the kidneys
a. Causes fatigue, weakness, decreased exercise tolerance
b. Treat with epoietin and iron
J. Uremic Bleeding – increased tendency to bleed despite normal coags
a. Bleeding time best correlates with bleeding tendency
b. Hemorrhagic episodes remain major factors contributing to anemia
i. GI bleeds, epistaxis, hemorrhagic pericarditis, subdural hematoma
c. Treatment with cryoprecipitate (10 u over 30 min) which has a duration of 12-18
hrs, DDAVP (0.3 mcg/kg IV) which has a duration of 6-8 hrs

392
K. CRF Neuro Changes
a. Early manifestations of renal insufficiency
b. Mild symptoms – impaired abstract thinking, insomnia, irritability – can progress
with dz process to more significant changes – increased deep tendon reflexes,
seizures, obtundation, uremic encephalopathy coma
c. Polyneuropathy develops in advanced renal failure i.e. Restless Leg Syndrome
L. CV Changes
a. HTN in 80% of patients with ESRD
i. Contributes to MI, CHF, CAD, cerebrovascular Dz
ii. Dialysis indicated Tx for hypervolemia (Na & H2O retention)
iii. Drugs used to treat HTN d/t activation of RAA system
b. Uremic pericarditis can lead to pericardial effusion, cardiac tamponade (pulses
paradoxes, bradycardia and HoT) and hemodynamic instability
c. Dyslipidemia are common, increase risk of cardiovascular morbidity and
mortality
i. Therapy advised when fasting triglyceride levels >500 mg/dL or LDL >
100 mg/dL
M. Hemodialysis
a. Diffusion of solutes between blood and dialysis solution results in removal of
metabolic waste products and replenishment of body buffers
b. Goals – adequate dialysis, adequate nutrition, maintain vascular access, prolong
life
c. Annual mortality rate for dialysis pt = 25%/yr – most are attributed to CV causes
or infection
d. Vascular Access
i. Surgically created from cephalic vein anastomosis to radial artery as an
effective hemodialysis site
ii. Complications – thrombosis (despite adequate heparinization) infections,
aneurysm formation and limb ischemia
1. Infection – most serious problem in Renal Failure patients
2. Sepsis is most common cause of death in RF patients
N. BUN – normal blood urea nitrogen is 7-18 mg/dL
a. Urea is relatively non-toxic. Liver creates urea as a means to dispose NH4 from
protein metabolism
b. Urea is filtered thru glomerulus. If glomerular filtrate is flowing slowly thru
proximal tubule – urea passively reabsorbed to blood stream
c. BUN level sensitive indicator of renal Dz (elevated when fxn 25-50%)
d. BUN altered by many variables
i. ↑ protein intake, GI bleeding, anemia, intravascular fluid volume status
ii. Capacity of the liver to form urea from AA
iii. Rate of incorporation for AA – tissue protein

iv. Rate of AA release from tissue protein – altered by sepsis or trauma

393
 e. Increased BUN – AZOTEMIA – due to ↑ protein catabolism or ↓ kidney fxn
i. Increased protein catabolism result of – a really big protein meal, severe
stress (MI, high fever) upper GI bleed (blood is digested and absorbed)
f. Decreased BUN
i. Lack of protein – celiac disease, nephrotic syndrome
ii. Severe liver disease – end stage cirrhosis, yellow atrophy, hepatitis,
halothane or acetaminophen toxicity, enzyme defects
g. Over hydration – iatrogenic, psychogenic water drinking

O. Creatinine – normal = 0.6-1.3

a. A breakdown product of creatinine phosphate – released from skeletal muscle at a
steady rate
b. It is filtered by the glomerulus – small amount secreted into glomerular filtrate by
proximal tubule
c. If urine volume foes ↑, serum creatinine goes ↓ slightly
d. Creatinine is generally considered a more sensitive and specific test of renal
function than BUN
e. Increased Creatinine
i. Due to any cause of impaired kidney function – lots of meat in diet, body
builders/large muscle mass, anabolic steroid users, giants and acromegaly
patients
ii. Drugs may block tubular secretion of creatinine - ↑ creatinine even though
no kidney damage (probenecid, cimetidine, triamterene, trimethoprim,
Amiloride)
iii. In massive rhabdomyolysis/crush injury – lots of creatinine released - ↑
creatinine
iv. Athletes take oral creatinine – may have slight increase but not usually out
of normal range
P. Creatinine Clearance – normal 110-140 ml/min
a. Widely used to measure approximate GFR – 24 hr urine collection
b. Creatinine is an endogenous marker of renal filtration produced at a relatively
constant rate by hepatic conversion of skeletal muscle creatinine.
c. THE MOST DEFINITIVE TEST OF GFR
d. Creat Clearance decreases with age -70 yr – 70 ml/min
Q. Renal Function Tests
a. Prerenal vs Renal AZOTEMIA
i. Common clinical problem to distinguish pre-renal azotemia (shock,
dehydration, CHF, hepatorenal syndrome from renal azotemia) acute
tubular necrosis, renal shutdown
ii. Could be either cause with HoT, azotemia, oliguric but treatments are
different

394
 iii. Older technique-calculate BUN/Creatinine ration – norm = 10
1. Values over 10, especially over 20 – pre-renal azotemia
2. High values – postrenal azotemia & GI bleeding
3. Common finding in elderly – marker for ill health
iv. Urine Sodium
1. Pre-renal Azotemia – Na is low (<20 mEq/L)
a. Kidneys respond to decreased blood flow by retaining Na
2. Acute Tubular Necrosis – Na is higher (>40 mEq/L)
a. Renal tubules unable to concentrate or dilute filtrate
effectively
R. FeNa = fraction excretion of filtered Na
a. FeNa = (Urine Na) (Serum Creat)/(Serum Na) (Urine Creatinine)
b. Values < 1% suggest pre-renal azotemia while values > 2% suggest acute tubular
necrosis
Prerenal Renal
Urine output (cc/kg/hr) <0.5 < 0.5
Urine Sodium (mEq/L) <20 >40
FeNa <1 >2 (↑ Na excretion)
Urine Osm (mOsm/L) >400 250-300
BUN/Creat ration >20 <20
S. Urine Specific Gravity gives info on tubular function and hydration
a. Normal – fairly concentrated – 1.010
b. Prerenal – normal SG to high SG and low urine Na
c. Acute Tubular Disease – fixed SG around 1.010
i. Isosthenuria – fixed SG
ii. Kidney cannot form urine with higher or lower SG
iii. i.e. renal azotemia, acute tubular necrosis, bad bilateral pyelonephritis,
interstitial pyelonephritis, on diuretic, ESRD
d. patients with lots of IV fluid, DI, enthusiastic H2O drinkers = ↓ SG
e. Unreliable test with diuretics or glycosuria
f. IF SG > 1.025, pt is dry

395
T. Urine Microscopy
a. Proteinuria – parenchymal Dz
b. RBC’s from trauma, tumor or infection
c. WBC’s or bacteria from infection
d. Fatty casts from nephrotic syndrome
e. Ketones d/t DKA or starvation
U. Uric Acid
a. Breakdown product of purine metabolism (Filtered by glomeruli, reabsorbed and
secreted by renal tubules) – highly variable from day to day
b. Increased serum uric acid is often seen in:
i. Renal Failure
ii. Gout (hyperuricemia)
iii. Liver and sweet bread gourmets (organ meat has high purines)
iv. Increased breakdown of nucleoprotein (burns, crush injuries, severe
hemolytic anemia, plasma cell myeloma, myeloproliferative disorders –
leukemia under treatment
v. Lead Poisoning
vi. Thiazide Diuretics or high doses of ASA
vii. Idiopathic
V. Primary Kidney Disease (PKD)
a. Glomerulonephritis
i. Deposition of antigen-antibody complexes in glomeruli from exogenous
(post streptococcal infection) or endogenous (collagen Dz) processes
ii. Manifestations – hematuria, proteinuria, HTN, edema, increased plasma
creatinine concentration
iii. RBC casts are suggestive of glomerular Dz
iv. Treatments – immunosuppressant’s, possible antibiotics
b. Nephrotic Syndrome
i. Defined as daily urinary protein excretion exceeds 3.5 g associated with
sodium retention, hyperlipoproteinemia and thromboembolic infection
complications
ii. Due to diabetic nephropathy, neoplasms (sarcoma, carcinoma, lymphoma,
leukemia) HIV, pregnancy induced HTN
iii. Manifestations –sustained and heavy proteinuria, hypoalbuminemia,
edema ascites, hypovolemia, hyperlipidemia, hypercoagulability
iv. Treatments – manage edema, reduce proteinuria (Loop diuretics, ACE
Inhibitors, steroids, cyclosporine)

396
c. Interstitial Nephritis
i. Caused by allergic reaction to drugs (sulfonamides, allopurinol, phenytoin,
diuretics) and less commonly by lupus or sarcoidosis
ii. Manifestations – decrease urine concentrating ability, proteinuria,
systemic HTN
iii. Renal failure d/t intestinal nephritis usually reversible – withdraw drug,
treat Dz
iv. Steroids may even be helpful
d. Polycystic Kidney Disease
i. Autosomal dominant disease progresses to renal failure in middle age
ii. Mild HTN, proteinuria are common, cysts in liver and CNS (intracranial
aneurysms)
iii. Hemodialysis and/or renal transplantation to treatment
e. Hereditary Nephritis (Alport Syndrome)
i. Often accompanied by hearing loss, ocular abnormalities
ii. Males > Females, Dz culminates to systemic HTN and renal failure
iii. No drug therapy is successful
f. Renal HTN
i. Appearance of systemic HTN in young patient that leads to renal rather
than essential HTN
ii. Risk factors include chronic pyelonephritis, glomerulonephritis,
parenchymal Dz
iii. Treatment is with artery endarterectomy or nephrectomy
g. Hepatorenal syndrome
i. Decompensated liver cirrhosis – acute oliguria associated with decreased
GFR and renal blood flow
ii. Renal Failure may reflect hypovolemia (vigorous treatment for ascites)
iii. PRBC are appropriate treatment because saline and albumin may lead to
ascites
iv. May need peritoneal to venous shunt
v. HD not reliable treatment
h. Fanconi Syndrome
i. Inherited or Acquired Disturbances of proximal renal tubular function
ii. Manifestations:
1. Hyperaminoaciduria, glycosuria, hyperphosphaturia
2. Polyuria (loss of H2O), polydipsia, metabolic acidosis (loss of
HCO3), skeletal muscle weakness (loss of K+)
3. Dwarfism + osteomalacia – loss of PO4
iii. Management: Fluid & Electrolytes, LV failure 2̊ to uremia

397
 i. Goodpasture Syndrome
i. Combo of pulmonary hemorrhage + glomerulonephritis (mostly young
males)
ii. Antigen-Antibody deposits in kidneys & lungs
iii. Poor prognosis – renal failure, usually within 1 yr
iv. Treatment – Plasmapheresis, corticosteroids
j. Bartter Syndrome (Congenital hypokalemia alkalosis)
i. Inherited – autosomal recessive trait, salt wasting
1. Defect in Cl- reabsorption – increased NaCl load to distal renal
tubules – Na absorbed in exchange for K+ - increased urinary K+
excretion
ii. Manifestation – hypokalemic, hypochloremic metabolic alkalosis with
increased renin and aldosterone but no systemic HTN
iii. Increased arterial pH causes left shift of O2/Hgb curve – less O2
unloading to tissues
iv. Management – treat acid base and electrolytes, effects of hypokalemia
(NM block & cardiac arrhythmias)
k. Nephrolithiasis
i. Multifactorial causes
ii. Most stones CaOxalate (hyperparathyroidism, sarcoidosis, CA)
iii. Hematuria
iv. Ureteral Obstruction – signs and symptoms of renal failure
W. Anesthetic Implications in Renal Failure
a. Volatile Anesthetics
i. Decrease renal blood flow and GFR which leads to decreased urine output
ii. Disturb autoregulation – decreased MAP = decreased urine output
1. Renal blood flow is pressure dependent
iii. ADH increases with VA, fluid loss, positive pressure ventilation which
leads to hyponatremia
iv. *Sevo may produce Compound A which is an alkene but is nephrotoxic
unless there is increased O2 flow
b. Spinal Anesthesia
i. Only if RF coagulopathy ruled out
c. NMBA’s
i. Succinylcholine – increases serum K by 1 mEq/L in all patients
1. Avoid when serum K > 5.5
2. Increased risk of cardiac standstill if baseline K is high
ii. Atracurium
1. Hoffman elimination and ester hydrolysis
a. Non organ dependent mechanisms of elimination
2. Less than 10% is excreted unchanged by renal and biliary routes

398
 iii. Cisatracurium (Nimbex; 0.1 mg/kg) only uses Hoffman Elimination
1. Metabolism is independent of renal or liver function
iv. Vecuronium
1. Elimination largely biliary
2. Renal elimination (25%) generally acceptable for renal failure
3. However, duration of drug prolonged d/t renal failure
v. Rocuronium
1. Eliminated primarily by the liver, slightly by the kidney
2. Liver failure prolongs metabolism, renal failure does not
d. Anticholinesterase
i. Neostigmine (Prostigmine; 0.05 mg/kg) – relies on renal excretion so
reduce dose by 50-75%
e. Thiopental – 85% bound to plasma protein
i. Uremia leads to decreased protein amount which means less binding to
albumin and other plasma proteins so that thiopental has increased
availability at receptor sites
ii. Weak Acid that adds to renal failure acidosis due to increased unionized,
nonbound, active drug
iii. Administer less for same effect in hypoproteinemia
f. Morphine
i. Active metabolite – morphine 6 glucuronide leads to increased duration of
action in chronic renal failure
ii. Dose should be decreased and doing interval adjustments may be
necessary
g. Anesthetics that depend largely on renal elimination
i. Induction agents – Phenobarbital & Thiopental
ii. Muscle Relaxers – Pancuronium, Vecuronium
iii. Cholinesterase inhibitors – Edrophonium, Neostigmine
iv. Cardiovascular drugs – atropine, digoxin, glycopyrrolate, hydralazine,
milrinone
v. Antimicrobials – Aminoglycosides, cephalosporins, PCN, sulfonamides,
Vancomycin
vi. Analgesics – codeine, meperidine, morphine
X. Dialysis
a. Should be performed 6-24 hrs pre-op
i. Too close to surgery = volume depletion
ii. Too remote from surgery = electrolyte disturbances
b. Draw serum K+ pre-op on dialysis dependent renal failure pt per institution

399
Y. Diuretics ACTION SITE
a. Loop (Lasix, Bumex causing cortical vasodilation, Ethacrynic Acid)
i. Treatment of cardiac failure, acute pulmonary edema, increased ICP
ii. Action site = thick ascending limb of Henle loop
iii. Inhibit Na, K, Cl reabsorption in medullary portion of the ascending Loop
of Henle
iv. Most important side effect – hypokalemia
1. Increases the potential for digoxin toxicity and potentiates non-
depolarizing relaxants
v. Triggers release of renal prostaglandins leading to vasodilation and
decreased BP 2̊ decreased preload
vi. Responsiveness to Lasix is directly related to GFR
b. Osmotic Diuretics – mannitol and urea
i. Mannitol is filtered at glomerulus and not reabsorbed
1. Creates osmolality in proximal tubule so that water follows
mannitol
ii. Mannitol contraindicated if BBB disrupted so that mannitol enters brain
and brings fluid with it which increases ICP
1. Mannitol may cause vasodilation if administered too rapidly and
cause increased ICP
c. Potassium Sparing Diuretics – Aldosterone Antagonists
i. Spironolactone (Aldactone) acts by competing with aldosterone in the late
distal tubule and mostly in collecting duct which leads to hyperkalemia
ii. Amiloride And Triamterene have K sparing but act independently of
Aldosterone which blocks Na reabsorption and inhibits K excretion
d. Carbonic Anhydrase Inhibitors
i. Inhibits reabsorption of HCO3 and prevents secretion of H which leads to
hypokalemic acidosis
ii. Cells of proximal and distal tubules that normally secrete H. Carbonic
anhydrase is an enzyme that converts CO2 and H2O to H2CO3. Then
carbonic acid dissociates into H and HCO3. HCO3 is reabsorbed but H is
secreted in exchange for Na and H2O
e. Acetazolamide – carbonic acid inhibitor – inhibits acid secretion and Na
reabsorption
i. Leads to diuresis, alkaline urine, hyperchloremic, hypokalemic metabolic
acidosis
f. Thiazides – HCTZ , metalozone, Chlorothiazide
i. Inhibit Na & Cl reabsorption primarily in the cortical portion of the
ascending Loop of Henle and in the early distal tubule
ii. Results = hypokalemia

 Minimize the amount of muscle relaxants and limit their use within the last hour of
surgery, to maximize the probability of extubating the trachea.

400
 References

Lonnqvist, P., & Lerman, J. (2009). General Abdominal and Urologic Surgery. In A Practice of
Anesthesia for Infants and Children (4th ed., pp. 591-592). Philadelphia, PA: Asunders
Elsevier.
Schwartz, J. J. (2008). Skin and Musculoskeletal Diseases. In Anesthesia and Co-existing
Disease (5th ed., p. 463). Philadelphia, PA 19103: Churchill Livingstone.

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 RENAL pathophysiology

 RENAL FUNCTIONS:
1. Maintenance of extracellular fluid composition= electrolyte balance and acid-base
balance, also regulation of osmolality. Sodium Salts Account for 90% of the Total
Osmolality of the ECF
Kidneys Regulate Volume Not Amount
What is normal sodium osmolality? 300mOsm/kg- range is 270-310
2. Endocrine functions: erythropoietin, RAAS, vitamin D conversion to vitamin D3.
Chronic renal failure results in hypocalcemia- due to poor calcium absorption, lack of
vitamin D.
3. Regulation of arterial blood pressure
4. Maintenance of ECF Volume- BY REGULATING Na and H2O excretion
 URINARY BLADDER
1. Parasympathetic contracts bladder.
2. The external sphincter is the one under voluntary control- stretch receptors send
inhibitory impulses to external sphincter
 KIDNEYS
1. Receives 20-25% of the CO or 1.25LPM- 80% to cortical nephrons, 10-15% to
juxtamedullary nephrons.
2. Each kidney is composed of 1 million nephrons
3. Rework ECF once every 2 hours. Dialysis can only do this one every 8-12hours.
4. Renal blood flow, GFR auto regulated over MAP 60-160, with sharp decrease GFR is
MAP<50
 Neural regulation
1. Kidney innervation primarily from the celiac ganglion and greater splanchnic nerve.
2. Renal blood flow directly related to systemic arterial pressure. Renal arteriolar
vasoconstriction from sympathetic activity creates a decreased renal blood flow and
decreased GFR. This decreased diminishes excretion of sodium and water promotes an
increase in blood volume subsequently an increase in systemic pressure.
 ENDOCRINE FUNCTIONS
1. Renin angiotensin aldosterone system. Major regulator of RBF. Fall in BP sodium
ECF -renin release from juxtaglomerular apparatus- cleaves angiotensinogen
produced in liver-- to form angiotensin I,-ACE produced in renal and pulmonary and
of helium converts to angiotensin II-stimulates arteriolar vasoconstriction,
aldosterone release from adrenal cortex, stimulates ADH secretion and thirst.

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 2. Aldosterone-produced in zona glomerulosa of the adrenal cortex. Axon late distal
tubule and collecting duct. Increases rate of sodium reabsorption and decreases the
rate of sodium excretion. Increases potassium secretion into the late distal tubule and
collecting duct and increases potassium excretion. -
3. Aldosterone secretion stimulated by potassium, Bolan sodium, ECF volume, blood
pressure.
4. Aldosterone is the most important hormone for regulating extracellular fluid
volume.
5. Aldosterone acts on the late distal tubule and collecting duct to alter two renal tubular
functions simultaneously- again increases Na reabsorption, decreasing excretion, and
increases K secretion, which increases excretion. Aldosterone acts primarily on the
principal cells of the collecting ducts.
6. Natriuretic peptides- ANP- secreted from right atrium. BNP secreted from cardiac
ventricles. CNP from vascular endothelium. Urodilantin secreted by DT and CD.
ANP and BNP secreted during volume expansion of CHF- this inhibits renin,
aldosterone, dilates the afferent and constricts the efferent glomerular arterioles. CNP
is a vasodilator, and urodilantin promotes NaCl excretion.
 NEPHRONS- cortical and medullary
1. Functional unit of kidney.- Made of glomerulus, renal tubule- Glomerulus ----
associated with Bowman’s Capsule
2. BLOOD is delivered to glomerulus via AFFERENT and exits via EFFERENT
arterioles.

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  BLOOD FLOW OF NEPHRON
Blood passes through the afferent arterioles- the glomerular capillaries- the efferent arterioles
and the peritubular capillaries before drains into the venous system.
1. The efferent arteriole goes to a capillary network- this entwines the renal tubule.
2. The vasa recta are the peritubular capillaries of the loops of Henle of the
juxtamedullary nephrons.
3. The vasa recta are the countercurrent exchange system.

4. Reabsorption- substance going from the tubule to capillary

5. Secretion- substance going from the capillary to the tubule.
Glomeruli, proximal tubules, and distal tubules are found in the cortex, whereas the loops
of Henle and collecting ducts are in the medulla.

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 THE INNER STRIPE OF THE OUTER MEDULLA- most vulnerable to ischemia.

 BASIC NEPHRON FUNCTIONS- ultrafiltration

1. Glomerular filtration, tubular reabsorption, and tubular secretion
a. Glomerular filtration- capillary pressure and electrical charge have an effect on it.
Hydrostatic pressure major force for filtration. That filtration pressure is the sum
of forces favoring or opposing filtration. Average GFR is 180 L a day or 120
mL a minute. Changes in afferent or efferent arteriolar resistance alters
glomerular capillary hydrostatic pressure and GFR. If the afferent arterial
constricts blood flow decreases, withdraw and glomerular pressure. The GFR then
decreases, and body fluids are conserved. If the efferent arteriole constricts- RBF
is reduced and so is GFR-

2. Proximal Tubules: sodium reabsorption. Reabsorbs the bulk of the filtered fluid.
Reabsorbs 67% of filtered water. All of the glucose that is filtered is completely
reabsorbed by the PT through active transport. In DM filtered glucose exceeds
maximum transport so then some is excreted. In the PT- the osmolality is iso-
osmolar to plasma- 300mOsm.
a. Reabsorbs- 67% Na and H2O, 90% or more of K, glucose, HCO3, Ca, PO4, amino
acids, uric acid- ALL BY ACTIVE TRANSPORT. WHEN GLUCOSE EXCEEDS
180, - the threshold is surpassed for reabsorption and spills over into the urine.

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 Loop of Henle- ESTABLISHES AND MAINTAINS OSMOTIC GRADIENT in
medulla of kidney. It is a COUNTERCURRENT MULTIPLIER. Deposits NaCl in
medullary interstitium- producing a gradient in osmolality. Utilizes the Na K 2CL
symporter- creates area of high Na deep in medulla near collecting duct.

1. Osmotic gradient is required for making urine concentrated or dilute.

2. Descending limbs- thin and thick segments are HIGHLY PERMEABLE TO H2O.
3. Ascending limbs- Thin ascending limb- NOT PERMEABLE TO H2O, but to IONS.
Medullary thick ascending limb reabsorbs Na K Cl Mg Ca. Cortical thick ascending
limb drains urine into DCT.
 COUNTERCURRENT SYSTEM-
1. Countercurrent multiplier- loop of henle- again a gradient is set up along the flow
pathway- increases osmotic gradient in the interstitium surrounding the loops.
2. Countercurrent exchange- transfer of matter or energy between inflow and outflow
limbs- think vasa recta- exchanges solutes and water along with the loop of henle to
maintain gradient in interstitium.
 Distal Tubule and collecting duct- Make final adjustments on urine pH, osmolality and
ionic composition. Water present in filtrate in collecting duct goes through
AQUAPORIN channels.
 Regulation of Extracellular Fluid Osmolality-
1. Antidiuretic Hormone- Its release is directly related to the osmolality of the
extracellular fluid.
2. ADH release also is stimulated through pain and decrease in vascular volume.
3. ECF osmolality and hand sodium concentration is regulated by ADH.
4. ADH is synthesized in the periventricular and super optic nuclei of the hypothalamus.
5. It is then transported to the posterior pituitary. Nerve action potential stimulate
release of ADH. An increase in the ECF osmolality is the most powerful stimulus
triggering the release of ADH. ADH reaches the distal tubule collecting duct and
increases the reabsorption of water. If there's a decrease in ECF osmolality cells of
the periventricular and super optic nuclei swell and nerve action potentials are
inhibited to ADH release is depressed. In the absence of ADH a large volume of
dilute urine is formed.

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 6. When ADH is high small volume of urine is formed with 1200 to 1500 mOsm
concentration.
7. When ADH is low a large volume of dilute urine is formed 50 to 100 mOsm.
8. ADH increases the permeability of the distal tubules and collecting ducts to H2O.
9. Rate of release ( from ?) is proportionate to the osmolality of the ECF
10. ↓ vascular volume (↑ osmolality )→ ADH release
11. Thirst mechanism activated→↑ water ingestion
12. Other triggers: hypotension, pain, trauma, CPAP, PEEP, volatile agents

 TESTS of renal function

1. GFR
o BUN 7-18 mg/100cc
o Creatinine 0.6 -1.2 mg/100cc
o Creatinine Clearance 107-139 cc/min
2. Tubular Function
o Specific Gravity 1.016 -1.022
o Osmol 40-1400 mosm/L
o Na+ 136-145 meq/L
3. The most definitive test of GFR is creatinine clearance.
4. BUN is a better indicator with CRF patients.
5. FENa- Values less than 1 % indicate prerenal azotemia values over 2% indicate acute
tubular necrosis.
6. Urine specific gravity provides information about tubular function hydration. Normal
people have a specific gravity greater than 1.010 patients with tubular disease such as
renal azotemia such as acute tubular necrosis really bad pyelonephritis or with end-
stage renal disease will have fixed urine specific gravity of around 1.010
7. If the SG is over or equal to 1.025, the patient is volume constricted, dry.

 SIADH
1. inappropriate ADH secretion
2. Caused by surgery, intracranial tumors, hypothyroidism, porphyria, small cell lung
CA
3. Sx- inappropriately increased urine sodium concentration, increased urine osmolality,
decreased plasma osmolality.

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 ACUTE RENAL FAILURE- sudden onset, rapid reduction in UO, reversible
1. Common complication of critical surgical illness.
2. Mortality of 40 to 90%.
3. BUN increases around 20 mg/DL each day.
4. Prerenal Causes include acute hemorrhage, G.I. fluid loss, trauma, surgery, burns,
sepsis, hepatic failure, allergic reaction.
5. Renal (intrinsic) causes include acute glomerulonephritis, interstitial nephritis, ATN,
nephrotoxic drugs, solvents, contrast dyes.
6. Postrenal causes include urinary tract obstruction, and lower urinary tract obstruction.

 ETIOLOGY OF PERIOP OLIGURIA

1. Prerenal- decreased RBF, hypovolemia, decreased CO.
2. Renal-ATN, renal ischemia due to prerenal, causes, nephrotoxic drugs, release of
hemoglobin and myoglobin.
3. Post-renal-obstruction of urine flow bilateral ureteral obstruction or extravasation due
to bladder rupture.
 PRERENAL FAILURE
1. Triggered by hypoperfusion of the kidneys resulting in deterioration of renal function
and accumulation of nitrogenous wastes.
 PRERENAL VS. RENAL
1. In ARF Na reabsorption sucks so lots of Na goes to the pee- then the FENa is HIGH.
If its prerenal, well the filtered Na EXTENSIVELY resorbed since flow is slow- so
then the FENa is LOW.
2. The BEST TEST to differentiate between prerenal and renal is to get a
Fractional excretion of filtered sodium.
 CHRONIC RENAL FAILURE

1.
The best test of renal reserve is creatinine clearance which measures GFR.
2. Patients can be asymptomatic until renal function is under 10% of normal. Serum K is
maintained until GFR is 10% of normal.

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 CRF Pathophys
1. Chronic anemia occurs- Decreased production of renal erythropoietin- TX
recombinant erythropoietin.
2. Pruritus- occurs in most patients with ESR D, administer erythropoietin lowers
concentration of histamine and may decrease the incidence of pruritus.
3. Electrolyte imbalance-hyperK, Mg, hypo Ca. Met. Acidosis. Anemia, Uremic
coagulopathies, Neuro changes, systemic HTN, CHF, renal osteodystrophy

4. INFECTION IS THE MOST SERIOUS PROBLEM, WITH SEPSIS BEING

THE MOST COMMON CAUSE OF DEATH IN CRF PATIENTS.
5. Hypocalcemia with CRF cause hyperphosphatemia. Also since is a diminished renal
production of vitamin D3, there is no promoted intestinal absorption of Ca.
6. Avoid LR- it has K, the CRF pt is unable to excrete K.
7. Atracurium, Vecuronium, Cisatracurium and Mivacurium are best for CRF- They do
not depend on renal excretion for clearance.
8. AVOID SUX IN CRF PATIENT THAT HAS HYPER K.
9. The BUN is BEST indicator of extent of CRF, NOT CREATININE. On the other
hand creatinine is generally considered a more sensitive and specific test of renal
function overall than BUN.
10. Uremic bleeding-increased tendency to bleed, the bleeding time best correlates with a
tendency to bleed in CRF patients.

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 RENAL OSTEODYSTROPHY
1. Complex interaction of secondary hyperparathyroidism and decreased vitamin D
production. As GFR goes down, there is a decrease in phosphate clearance, increase
in serum phosphate, and decreases in serum calcium.
2. Hypocalcemia stimulates parathyroid hormone, which leads to bone reabsorption,
calcium release. Decreased vitamin D intestinal absorption.
3. Restrict dietary phosphate, administer oral calcium and vitamin D.
 GLOMERULONEPHRITIS
1. Antigen-antibody deposits in glomeruli from post-strep or collagen disease processes
2. hematuria, proteinuria, HTN, edema, and increased plasma creatinine concentration
3. RBC casts are suggestive of glomerular disease
4. TX’s: immunosuppressant’s, possible antibiotics
 NEPHROTIC SYNDROME
1. From diabetic nephropathy, neoplasms, HIV, Preg-induced-HTN.
2. Sx- sustained and heavy proteinuria, hypoalbuminemia, edema and ascites,
hypovolemia, hyperlipidemia, and hypercoagulability
3. Tx with loop diuretics, ACE-Is, steroids, cyclosporine
 INTERSTITIAL NEPHRITIS
1. From allergic reaction to drugs, lupus, sarcoidosis
2. There is decreased urine concentrating ability, proteinuria, systemic HTN
3. Renal failure from this reversible after taking away offending drug, tx underlying
disease
4. Steroids
 POLYCYSTIC RENAL DISEASE
1. Autosomal Dominant, progresses to renal failure during middle age
2. Sx mild HTN, proteinuria
3. Cysts in liver and CNS as aneurysms
4. Tx HD or renal transplant
 HEREDITARY NEPHRITIS AKA ALPORT SYNDROME
1. I always related it to sounding like an airport- you can go deaf and blind at airports,
somehow this stuck with me- Alport sx is associated with ocular issues and hearing
loss.
2. Of course more Males get it- dumb males go to airports and go blind and deaf
3. Systemic HTN and RF. NO SUCCESSFUL DRUG THERAPY
 HEPATORENAL SYNDROME
1. Acute oliguria with decompensated liver failure/cirrhosis
2. Renal failure may be from hypovolemia from vigorous/excessive ascites removal
3. Tx with peritoneal to venous shunt

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 FANCONI SYNDROME
1. “Fanconi the weak floppy dwarf drinks and pees a lot”
2. Basically a syndrome that is acquired disturbance of PCT- loss of K, HCO3, H20,
hyperaminoaciduria, glycosuria, and hyperPO4, met. acidosis, - muscle weakness
3. Dwarfism and osteomalacia from hypophosphatemia
4. Manage with fluid, electrolytes, potential for LV failure from uremia
 GOODPASTURE SYNDROME
1. Pasture- I think of some young farmer guy that is coughing up blood with
glomerulonephritis.
2. Young males affected- pulmonary hemorrhage, glomerulonephritis.
3. This is due to antigen-antibodies depositing on kidneys and lungs.’
4. VERY POOR prognosis- renal failure in a year.
 BARTTER SYNDROME
1. Congenital autosomal recessive hypokalemic alkalosis.
2. Defect in Cl reabsorption which increases NaCl to DCT, so if Na is not resorbed
(exchanged) for K, there is increased K loss. There is increased arterial pH, less O2
unloading to tissues.
 NEPHROLITHIASIS
1. Most stones are calcium oxalate
2. Hematuria common
3. Ureteral obstruction may lead to postrenal failure s/s
 RENAL AND ANESTHESIA CONSIDERATIONS
1. Volatiles decrease RBF and GFR- decreased urine output. Also volatiles disturb
autoregulation- if MAP goes down, so does urine.
2. RBF is pressure dependent under anesthesia
3. ADH goes up with all we do- so urine concentration, oliguria- volatiles, fluid loss and
PPV does this.
4. IF RENAL FAILURE- question coagulopathy if you are considering a spinal
5. If renal disease what immediately should come to mind is where is this patients K,
and can I give SUX if I want/have to.
6. The rise in K in renal disease patients after SUX isn’t any greater than any other
patient
7. Thiopental- in uremia there is hypoalbuminemia- STP is 85% protein bound this
means there will be greater free STP available at receptors in renal disease patients.
Also since STP is a weak acid- acidosis of renal disease will mean more unionized
active drug. Point- give less STP to renal disease patients
8. Morphine- metabolite- Morphine-6-glucuronide increased DOA in renal disease.
Decrease dose of morphine or avoid.

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 RENAL DRUGS

 LOOP DIURETICS
1. Furosemide, Bumex, Ethacrynic acid
2. Work by inhibiting Na/K/Cl reabsorption- in the medullary portion of ascending loop
of Henle.
3. Side effect hypokalemia, triggers release of renal prostaglandins- venodilation, low
BP from low preload
 OSMOTIC DIURETICS- MANNITOL AND UREA
1. Mannitol- filtered freely at glomerulus, NOT REABSORBED. This increases
osmolality- free water follows mannitol
2. DO NOT GIVE if the BBB is compromised since mannitol can bring fluid to brain
increasing ICP.
 POTASSIUM SPARING DIURETICS (ALDOSTERONE ANTAGONISTS)
Spironolactone
1. ACTS on the late DT, since this is where aldosterone chills- if it is blocking
aldosterone, you guessed it, can lead to hyperK.
2. AMILORIDE AND TRIAMTERENE are independent of aldosterone activity
 CARBONIC ANHYDRASE INHIBITORS- ACETAZOLAMIDE
1. As you know this enzyme converts CO2 and H20 to H2CO3- which dissociates to
HCO3- gets resorbed, and H- which gets secreted. The PCT and DCT secrete H ions.
The secretion of H also is accompanied reabsorption of Na and H20.
2. If you are inhibiting this enzyme- Na and H20 aren’t reabsorbed- and you pee more,
right. But, if you preventing the secretion of H- you guessed it, you will have a
hypokalemic acidosis.
3. Since you are inhibiting H secretion- the urine will be alkaline, and again there will
be a hyperCl, hypoK, met. Acidosis.
 THIAZIDES- ACT ON THE CORTICAL ASCENDING LOOP OF HENLE AND
EARLY DT.
1. HCTZ, Chlorothiazide, Metolazone. When acting on loop of Henle, and DT, HypoK
results.

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 NEURO Review:

The cerebral cortex is a thick layer of neural tissue that covers most of the brain. This layer is
folded in a way that increases the amount of surface that can fit into the volume available. The
pattern of folds is similar across individuals, although there are many small variations. The
cortex is divided into four "lobes", called the frontal lobe, parietal lobe, temporal lobe, and
occipital lobe. Within each lobe are numerous cortical areas, each associated with a particular
function such as vision, motor control, language, etc. The left and right sides of the cortex are
broadly similar in shape, and most cortical areas are replicated on both sides. Some areas,
though, show strong lateralization, particularly areas that are involved in language. In most
people, the left hemisphere is "dominant" for language, with the right hemisphere playing only a
minor role. There are other functions, such as spatiotemporal reasoning, for which the right
hemisphere is usually dominant. Despite being protected by the thick bones of the skull,
suspended in cerebrospinal fluid, and isolated from the bloodstream by the blood–brain barrier,
the human brain is susceptible to many types of damage and disease. The effects of anesthetic
agents on cerebral metabolism, blood flow, cerebrospinal fluid (CSF) dynamics, and intracranial
volume and pressure are often profound. In some instances, these alterations are deleterious,
whereas in others they may actually be beneficial. The brain is normally responsible for
consumption of 20% of total body oxygen. Most of cerebral oxygen consumption (60%) is used
in generating adenosine triphosphate (ATP) to support neuronal electrical activity. The cerebral
metabolic rate (CMR) is usually expressed in terms of oxygen consumption (CMRO2), which
averages 3–3.8 mL/100 g/min (50 mL/min) in adults. CMRO2 is greatest in the gray matter of
the cerebral cortex and generally parallels cortical electrical activity. Because of the relatively
high oxygen consumption and the absence of significant oxygen reserves, interruption of
cerebral perfusion usually results in unconsciousness within 10 s as oxygen tension rapidly drops
below 30 mm Hg. If blood flow is not reestablished within minutes (3–8 min under most
conditions), ATP stores are depleted and irreversible cellular injury begins to occur. The
hippocampus and cerebellum appear to be most sensitive to hypoxic injury. Neuronal cells
normally utilize glucose as their primary energy source. Brain glucose consumption is
approximately 5 mg/100 g/min, of which over 90% is metabolized aerobically. CMRO2
therefore normally parallels glucose consumption. This relationship does not hold during
starvation, when ketone bodies (acetoacetate and -hydroxybutyrate) also become major energy
substrates. Although the brain can also take up and metabolize some lactate, cerebral function is
normally dependent on a continuous supply of glucose. Acute sustained hypoglycemia is equally
as devastating as hypoxia. Paradoxically, hyperglycemia can exacerbate global and focal hypoxic
brain injury by accelerating cerebral acidosis and cellular injury. Cerebral blood flow (CBF)
varies with metabolic activity. Studies have shown that regional CBF parallels metabolic activity
and can vary from 10–300 mL/100 g/min. For example, motor activity of a limb is associated
with a rapid increase in regional CBF of the corresponding motor cortex. Similarly, visual
activity is associated with an increase in regional CBF of the corresponding occipital visual
cortex.

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Although total CBF averages 50 mL/100 g/min, flow in gray matter is about 80 mL/100 g/min,
whereas that in white matter is estimated to be 20 mL/100 g/min. Total CBF in adult’s averages
750 mL/min (15–20% of cardiac output). Flow rates below 20–25 mL/100 g/min are usually
associated with cerebral impairment, as evidenced by slowing on the electroencephalogram
(EEG). CBF rates between 15 and 20 mL/100 g/min typically produce a flat (isoelectric) EEG,
whereas values below 10 mL/100 g/min are usually associated with irreversible brain damage.
Cerebral perfusion pressure (CPP) is the difference between mean arterial pressure (MAP) and
intracranial pressure (ICP) (or central venous pressure [CVP], whichever is greater). MAP – ICP
(or CVP) = CPP. When CVP is significantly greater than ICP, perfusion pressure becomes the
difference between MAP and CVP. CPP is normally 80–100 mm Hg. Moreover, because ICP is
normally less than 10 mm Hg, CPP is primarily dependent on MAP. Moderate to severe
increases in ICP (> 30 mm Hg) can significantly compromise CPP and CBF even in the presence
of a normal MAP. Patients with CPP values less than 50 mm Hg often show slowing on the
EEG, whereas those with a CPP between 25 and 40 mm Hg typically have a flat EEG. Sustained
perfusion pressures less than 25 mm Hg result in irreversible brain damage. Similar to the heart
and kidneys, the brain normally tolerates wide swings in blood pressure with little change in
blood flow. The cerebral vasculature rapidly (10–60 s) adapts to changes in CPP, but abrupt
changes in MAP will lead to transient changes in CBF even when autoregulation is intact.
Decreases in CPP result in cerebral vasodilation, whereas elevations induce vasoconstriction. In
normal individuals, CBF remains nearly constant between MAPs of about 60 and 160 mm Hg.
Beyond these limits, blood flow becomes pressure dependent. Pressures above 150–160 mm Hg
can disrupt the blood–brain barrier and may result in cerebral edema and hemorrhage. The most
important extrinsic influences on CBF are respiratory gas tensions—particularly PaCO2. CBF is
directly proportionate to PaCO2 between tensions of 20 and 80 mm Hg. Blood flow changes
approximately 1–2 mL/100 g/min per mm Hg change in PaCO2. This effect is almost immediate
and is thought to be secondary to changes in the pH of CSF and cerebral tissue. Because ions do
not readily cross the blood–brain barrier but CO2 does, acute changes in PaCO2 but not HCO3–
affect CBF. Thus, acute metabolic acidosis has little effect on CBF because hydrogen ions (H+)
cannot readily cross the blood–brain barrier. After 24–48 h, CSF HCO3– concentration adjusts to
compensate for the change in PaCO2, so that the effects of hypocapnia and hypercapnia are
diminished. Marked hyperventilation (PaCO2 < 20 mm Hg) shifts the oxygen–hemoglobin
dissociation curve to the left and, with changes in CBF, may result in EEG changes suggestive of
cerebral impairment even in normal individuals. CBF changes 5–7% per 1°C change in
temperature. Hypothermia decreases both CMR and CBF, whereas pyrexia has the reverse effect.
Between 17°C and 37°C, the Q10 for humans is approximately 2—that is, for every 10° increase
in temperature, the CMR doubles. Conversely, the CMR decreases by 50% if the temperature of
the brain falls by 10°C, e.g., from 37°C to 27°C, and another 50% if the temperature decreases
from 27°C to 17°C.

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At 20°C, the EEG is isoelectric, but further decreases in temperature continue to reduce CMR
throughout the brain. Above 42°C, oxygen activity begins to decrease and may reflect cell
damage. Intracranial vessels are innervated by sympathetic (vasoconstrictive), parasympathetic
(vasodilatory), and noncholinergic noradrenergic fibers; serotonin and vasoactive intestinal
peptide appear to be the neurotransmitters for the latter. The normal physiological function of
this innervation is uncertain, but it may play an important role in some pathological states. This
is particularly true for the innervation of large cerebral vessels by sympathetic fibers originating
in the superior cervical sympathetic ganglia. Intense sympathetic stimulation induces marked
vasoconstriction in these vessels, which can limit CBF. Autonomic innervation may also play an
important role in cerebral vasospasm following brain injury and stroke. Cerebral blood vessels
are unique in that the junctions between vascular endothelial cells are nearly fused. The paucity
of pores is responsible for what is termed the blood–brain barrier. This lipid barrier allows the
passage of lipid-soluble substances but restricts the movement of those that are ionized or have
large molecular weights. Thus, the movement of a given substance across the blood–brain barrier
is governed simultaneously by its size, charge, lipid solubility, and degree of protein binding in
blood. Carbon dioxide, oxygen, and lipid-soluble substances (such as most anesthetics) freely
enter the brain, whereas most ions, proteins, and large substances such as mannitol penetrate
poorly. Water moves freely across the blood–brain barrier as a consequence of bulk flow,
whereas movement of even small ions is impeded to some extent (the equilibration half-life for
sodium is 2–4 h). As a result, rapid changes in plasma electrolyte concentrations (and,
secondarily, osmolality) produce a transient osmotic gradient between plasma and the brain.
Acute hyper tonicity of plasma results in net movement of water out of the brain, whereas acute
hypo tonicity causes a net movement of water into the brain. These effects are short-lived, as
equilibration eventually occurs, but, when marked, they can cause rapid fluid shifts in the brain.
Thus, marked abnormalities in serum sodium or glucose concentrations should generally be
corrected slowly. Mannitol, an osmotically active substance that does not normally cross the
blood–brain barrier, causes a sustained decrease in brain water content and is often used to
decrease brain volume. The blood–brain barrier may be disrupted by severe hypertension,
tumors, trauma, strokes, infection, marked hypercapnia, hypoxia, and sustained seizure activity.
Under these conditions, fluid movement across the blood–brain barrier becomes dependent on
hydrostatic pressure rather than osmotic gradients.
CSF is found in the cerebral ventricles and cisterns and in the subarachnoid space
surrounding the brain and spinal cord. Its major function is to protect the CNS against trauma.
Most of the CSF is formed by the choroid plexuses of the cerebral (mainly lateral) ventricles.
Smaller amounts are formed directly by the ventricles' ependymal cell linings and yet smaller
quantities from fluid leaking into the perivascular spaces surrounding cerebral vessels (blood–
brain barrier leakage). In adults, normal total CSF production is about 21 mL/h (500 mL/d), yet
total CSF volume is only about 150 mL.

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CSF flows from the lateral ventricles through the interventricular foramina (of Monro) into the
third ventricle, through the cerebral aqueduct (of Sylvius) into the fourth ventricle, and through
the median aperture of the fourth ventricle (foramen of Magendie) and the lateral aperture of the
fourth ventricle (foramina of Luschka) into the cerebellomedullary cistern (cisterna magna).
From the cerebellomedullary cistern, CSF enters the subarachnoid space, circulating around the
brain and spinal cord before being absorbed in arachnoid granulations over the cerebral
hemispheres. CSF formation involves active secretion of sodium in the choroid plexuses. The
resulting fluid is isotonic with plasma despite lower potassium, bicarbonate, and glucose
concentrations. Its protein content is limited to the very small amounts that leak into perivascular
fluid. Carbonic anhydrase inhibitors (acetazolamide), corticosteroids, spironolactone,
furosemide, isoflurane, and vasoconstrictors decrease CSF production. Absorption of CSF
involves the translocation of fluid from the arachnoid granulations into the cerebral venous
sinuses. Smaller amounts are absorbed at nerve root sleeves and by meningeal Lymphatics.
Although the mechanism remains unclear, absorption appears to be directly proportionate to ICP
and inversely proportionate to cerebral venous pressure. Because the brain and spinal cord lack
Lymphatics, absorption of CSF is also the principal means by which perivascular and interstitial
protein is returned to blood.
The cranial vault is a rigid structure with a fixed total volume, consisting of brain (80%),
blood (12%), and CSF (8%). Any increase in one component must be offset by an equivalent
decrease in another to prevent a rise in ICP. ICP by convention means supratentorial CSF
pressure measured in the lateral ventricles or over the cerebral cortex and is normally 10 mm Hg
or less. Minor variations may occur depending on the site measured, but, in the lateral recumbent
position, lumbar CSF pressure normally approximates supratentorial pressure. Intracranial
compliance is determined by measuring the change in ICP in response to a change in intracranial
volume. Normally, increases in volume are initially well compensated. A point is eventually
reached, however, at which further increases produce precipitous rises in ICP. Major
compensatory mechanisms include (1) an initial displacement of CSF from the cranial to the
spinal compartment, (2) an increase in CSF absorption, (3) a decrease in CSF production, and (4)
a decrease in total cerebral blood volume (primarily venous). The concept of total intracranial
compliance is useful clinically even though compliance probably varies in the different
compartments of the brain and is affected by arterial blood pressure and PaCO2. Increases in
blood pressure can reduce cerebral blood volume because autoregulation induces
vasoconstriction in order to maintain CBF. In contrast, hypotension can increase cerebral blood
volume as cerebral vessels dilate to maintain blood flow. Cerebral blood volume is estimated to
increase 0.05 mL/100 g of brain per 1 mm Hg increase in PaCO2. Compliance can be
determined in patients with interventricular catheters by injecting sterile saline. An increase in
ICP greater than 4 mm Hg following injection of 1 mL of saline indicates poor compliance. At
that point, compensatory mechanisms have been exhausted and CBF is progressively
compromised as ICP rises further. Sustained elevations in ICP can lead to catastrophic herniation
of the brain. Herniation may occur at one of four sites: (1) the cingulate gyrus under the falx
cerebri, (2) the uncinate gyrus through the tentorium cerebelli, (3) the cerebellar tonsils through
the foramen magnum, or (4) any area beneath a defect in the skull (transcalvarial).

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Overall, most general anesthetics have a favorable effect on the CNS by reducing electrical
activity. Carbohydrate metabolism decreases, whereas energy stores in the form of ATP,
adenosine diphosphate, and phosphocreatine increase. Determination of the effects of the
specific agents is complicated by the concomitant administration of other drugs, surgical
stimulation, intracranial compliance, blood pressure, and CO2 tension. For example, hypocapnia
or prior administration of thiopental blunts the increases in CBF and ICP that usually occur with
ketamine and volatile agents. Halothane, desflurane, sevoflurane, and isoflurane produce dose-
dependent decreases in CMR. Isoflurane produces the greatest depression (up to 50% reduction),
whereas halothane has the least effect (< 25% reduction). The effects of desflurane and
sevoflurane appear to be similar to isoflurane. Unlike hypothermia, no further reduction in CMR
is observed once the EEG is isoelectric. Moreover, the reduction is not uniform throughout the
brain; isoflurane reduces metabolic rate mainly in the neocortex. Volatile anesthetics dilate
cerebral vessels and impair autoregulation in a dose-dependent manner. Halothane has the
greatest effect on CBF; at concentrations greater than 1%, it nearly abolishes cerebral
autoregulation. Moreover, the increase in blood flow is generalized throughout all parts of the
brain. At an equivalent minimum alveolar concentration (MAC) and blood pressure, halothane
increases CBF up to 200%, compared with 20% for isoflurane. Unlike halothane, isoflurane
increases blood flow primarily in subcortical areas and the hindbrain. Qualitatively and
quantitatively, desflurane and sevoflurane may be closest to isoflurane. The effect of volatile
agents on CBF also appears to be time dependent because, with continued administration (2–5
h), blood flow begins to return to normal. The response of the cerebral vasculature to CO2 is
generally retained with all volatile agents. Hyperventilation (hypocapnia) can therefore abolish
or blunt the initial effects of these agents on CBF. The timing of the hyperventilation is
important because this effect is observed only if hyperventilation is initiated prior to the
administration of halothane. In contrast, simultaneous hyperventilation with administration of
either isoflurane or sevoflurane can prevent increases in ICP. Hypocapnia may be less effective
in decreasing ICP with desflurane compared with other volatile agents. Increases in cerebral
blood volume (10–12%) generally parallel increases in CBF, but the relationship is not
necessarily linear. Expansion of cerebral blood volume can markedly elevate ICP in patients with
reduced intracranial compliance. Studies indicate that cerebral blood volume increases to the
same extent with all volatile agents, suggesting that each affects cerebral venous capacitance to a
variable degree. Moreover, these studies demonstrate that hypocapnia most effectively blunts the
increase in cerebral blood volume during isoflurane anesthesia. As is apparent from the
discussion above, volatile agents alter but do not uncouple the normal relationship of CBF and
CMR. The combination of a decrease in neuronal metabolic demand with an increase in CBF
(metabolic supply) has been termed luxury perfusion. This state may be desirable during induced
hypotension and supports the use of a volatile agent, particularly isoflurane, during this
technique.

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In contrast to this potentially beneficial effect during global ischemia, a detrimental circulatory
steal phenomenon is possible with volatile anesthetics in the setting of focal ischemia. Volatile
agents can increase blood flow in normal areas of the brain but not in ischemic areas, where
arterioles are already maximally vasodilated. The end result may be a redistribution of blood
flow away from ischemic to normal areas. The net effect of volatile anesthetics on ICP is the
result of immediate changes in cerebral blood volume, delayed alterations on CSF dynamics, and
arterial CO2 tension. Based on these factors, isoflurane appears to be the volatile agent of choice
in patients with decreased intracranial compliance. Animal studies suggest that desflurane may
increase ICP more than other volatile agents. The effects of nitrous oxide are generally mild and
easily overcome by other agents or changes in CO2 tension. Thus when combined with
intravenous agents, nitrous oxide has minimal effects on CBF, CMR, and ICP. Adding this agent
to a volatile anesthetic, however, can further increase CBF. When given alone, nitrous oxide
causes mild cerebral vasodilation and can potentially increase ICP. With the exception of
ketamine, all intravenous agents either have little effect on or reduce CMR and CBF. Moreover,
with some exceptions, changes in blood flow generally parallel those in metabolic rate. Cerebral
autoregulation and CO2 responsiveness are preserved with all agents.
Barbiturates have four major actions on the CNS: (1) hypnosis, (2) depression of CMR, (3)
reduction of CBF due to increased cerebral vascular resistance, and (4) anticonvulsant activity.
These properties make barbiturates, particularly thiopental (when it was available), the most
commonly used induction agents in neuroanesthesia. Barbiturates produce dose-dependent
decreases in CMR and CBF until the EEG becomes isoelectric. At that point, maximum
reductions of nearly 50% are observed; additional barbiturate does not further reduce metabolic
rate. Unlike isoflurane, however, barbiturates reduce metabolic rate uniformly throughout the
brain. CMR is depressed slightly more than CBF, such that metabolic supply exceeds metabolic
demand (as long as CPP is maintained). Because barbiturate-induced cerebral vasoconstriction
occurs only in normal areas, these agents tend to redistribute blood flow from normal to ischemic
areas in the brain (Robin Hood, or reverse steal phenomenon). The cerebral vasculature in
ischemic areas remains maximally dilated and is unaffected by the barbiturate because of
ischemic vasomotor paralysis. Barbiturates also appear to facilitate absorption of CSF. The
resultant reduction in CSF volume, combined with decreases in CBF and cerebral blood volume,
makes barbiturates highly effective in lowering ICP. Their anticonvulsant properties are also
advantageous in neurosurgical patients who are at increased risk for seizures. The metabolic
demand imposed by seizure activity promotes secondary injury in ischemic areas. Small doses of
methohexital can activate seizure foci in patients with epilepsy, but higher doses are
anticonvulsant like other barbiturates. Other possible actions of barbiturates include blockade of
sodium channels, reduction of intracellular calcium influx, scavenging or suppression of free
radical formation, and retardation of cerebral edema following ischemic brain injury. All these
actions represent the theoretic justification for the controversial use of barbiturates for cerebral
protection. Studies suggest that barbiturate prophylaxis is effective in preventing brain injury
during focal but not global ischemia.

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 All opioids generally have minimal effects on CBF, CMR, and ICP, unless PaCO2 rises
secondary to respiratory depression. Increases in ICP have been reported in some patients with
intracranial tumors following administration of sufentanil and, to a lesser degree, Alfentanil. The
mechanism appears to be a precipitous drop in blood pressure; reflex cerebral vasodilation likely
increases intracranial blood volume and potentially ICP. Although hypotension may be more
likely with sufentanil and Alfentanil than with fentanyl, significant decreases in blood pressure
can adversely affect CPP regardless of the opioid selected. In addition, small doses of Alfentanil
(< 50 mg/kg) can activate seizure foci in patients with epilepsy. Morphine is generally not
considered optimal in neuroanesthesia due to poor lipid solubility. The latter results in slow CNS
penetration and prolonged sedative effects. Normeperidine, a metabolite of meperidine, can
induce seizures, particularly in patients with renal failure. The accumulation of normeperidine
and the associated cardiac depression limit the use of meperidine during the perioperative period.
Etomidate decreases the CMR, CBF, and ICP in somewhat the same way as thiopental.
Its effect on CMR is nonuniform, affecting the cortex more than the brain stem. Its limited effect
on the brain stem may be responsible for greater hemodynamic stability in unstable patients
when compared with the effect of barbiturates. Etomidate also decreases production and
enhances absorption of CSF. Concern over adrenal suppression limits its long-term use.
Induction with etomidate is associated with a relatively high incidence of myoclonic movements,
but these movements are not associated with seizure activity on the EEG in normal individuals.
The drug has been used to treat seizures, but reports of seizure activity following etomidate
suggest that the drug is best avoided in patients with a history of epilepsy. In fact, small doses of
etomidate can activate seizure foci in patients with epilepsy.
Propofol reduces CBF and CMR similar to barbiturates and etomidate; however, the
decrease in CBF may exceed that in metabolic rate. The drug also appears to be useful in the
CMR. Although it has been associated with dystonic and choreiform movements, propofol
appears to have significant anticonvulsant activity. Moreover, its short elimination half-life
makes it a useful agent for neuroanesthesia. Unfortunately, excessive hypotension and cardiac
depression in elderly or unstable patients can compromise CPP.
Benzodiazepines lower CBF and CMR but to a lesser extent than barbiturates, etomidate,
and propofol. Benzodiazepines also have useful anticonvulsant properties. Midazolam is the
benzodiazepine of choice because of its short half-life. Midazolam induction frequently causes
significant decreases in CPP in elderly and unstable patients and may prolong emergence in
some instances, particularly in patients with renal failure or if used as a continuous infusion
throughout the case.
Ketamine is the only intravenous anesthetic that dilates the cerebral vasculature and
increases CBF (50–60%). Selective activation of certain areas (limbic and reticular) is partially
offset by depression of other areas (somatosensory and auditory) such that total CMR does not
change. Seizure activity in thalamic and limbic areas is also described. Ketamine may also
impede absorption of CSF without affecting formation. Increases in CBF, cerebral blood volume,
and CSF volume can potentially increase ICP markedly in patients with decreased intracranial
compliance.

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 Intravenous lidocaine decreases CMR, CBF, and ICP but to a lesser degree than other
agents. Its principal advantage is that it decreases CBF (by increasing cerebral vascular
resistance) without causing other significant hemodynamic effects. The risks of systemic toxicity
and seizures, however, limit the usefulness of repeated dosing.
Droperidol has little or no effect on CMR and minimally reduces CBF. When used with
an opioid as part of a neuroleptic technique, Droperidol may cause undesirable prolonged
sedation. Reversal of opioids or benzodiazepines with naloxone or flumazenil, respectively, can
reverse any beneficial reductions in CBF and CMR. Severe hypertension may also follow the use
of naloxone but not flumazenil.
With normal autoregulation and an intact blood–brain barrier, vasopressors increase CBF
only when mean arterial blood pressure is below 50–60 mm Hg or above 150–160 mm Hg. In the
absence of autoregulation, vasopressors increase CBF by their effect on CPP. Changes in CMR
generally parallel those in blood flow. Adrenergic agents seem to have a greater effect on the
brain when the blood–brain barrier is disrupted; central 1-receptor stimulation increases CMR
and blood flow. Adrenergic blockers generally have no direct effect on CMR or CBF, whereas
adrenergic agonists produce cerebral vasoconstriction. Excessive elevations in blood pressure
with any agent can disrupt the blood–brain barrier. In the absence of hypotension, most
vasodilators induce cerebral vasodilation and increase CBF in a dose-related fashion. When these
agents decrease blood pressure, CBF is usually maintained and may even increase. The resultant
increase in cerebral blood volume can significantly elevate ICP in patients with decreased
intracranial compliance.
Neuromuscular blocking agents (NMBAs) lack direct action on the brain but can have
important secondary effects. Hypertension and histamine-mediated cerebral vasodilation increase
ICP, while systemic hypotension (from histamine release or ganglionic blockade) lowers CPP.
Succinylcholine can increase ICP, possibly as a result of cerebral activation associated with
enhanced muscle spindle activity, but the increase is generally minimal if an adequate dose of
thiopental or propofol is given and hyperventilation is initiated at induction. Moreover, a small
(defasciculating) dose of a nondepolarizing NMBA appears to blunt the increase, at least
partially. Agents that are likely to release histamine include Tubocurarine, Atracurium,
Metocurine, and mivacurium. Tachycardia and hypertension may follow large doses of
pancuronium, whereas ganglionic blockade may be seen following the use of Tubocurarine. In
the majority of instances, increases in ICP following administration of an NMBA are the result
of a hypertensive response due to light anesthesia during laryngoscopy and tracheal intubation.
Acute elevations in ICP will also be seen if hypercapnia or hypoxemia results from prolonged
apnea.
Sources:
Clinical Anesthesiology, 4th Edition, G. Edward Morgan, Jr., Maged S. Mikhail, Michael J.
Murray
Hines & Marschall: Stoelting's Anesthesia and Co-Existing Disease, 5th Ed.

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 Neurophysiology Review

Cerebral Blood Flow

 normally 50 ml/100 g brain tissue/min over a CPP range of 50-150 mmHg (15% CO)
 Governed by cerebral metabolic rate, CPP (MAP-ICP), PaCO2, PaO2, the influence of
various drugs and intracranial abnormalities
 Normally auto regulated or constant over a range of CPP
Cerebral Metabolic Rate (CMRO2) – rate of oxygen consumption of brain tissue

 3.0-3.8 ml O2/100 g brain tissue/min

 may be decreased by reductions in temperature or various anesthetic agents
 increased by temperature increases and seizures
Cerebral Blood Volume along with CBF, are responsible for intracranial volume and pressure

 Vasodilating anesthetics, hypercapnia produce parallel increases in CBV & CBF

 Moderate systemic HoT leads to ↓CBF but compensatory vessel dilation ↑ CBV
 Partial occlusion of an intracranial artery (embolic stroke) ↓ regional CBF with distal
vessel dilation in an attempt to restore circulation which causes ↑CBV
PaCO2 produces changes in CBF

 CBF ↑ 1 ml/100 g/min for each 1 mmHg ↑ PaCO2 and a similar ↓ occurs with ↓ PaCO2
 Impact of PaCO2 on CBF mediated by variations of pH of CSF around the walls of
arterioles
o ↑ CSF pH = vasoconstriction; ↓ CSF pH = vasodilation
 CBV ↓ dependent on anesthetic. Vasoconstrictors attenuate effects of PaCO2 on CBV.
 ------ PaO2; ------PaCO2; _____ MAP

 Hypocapnia acutely decreases CBF, CBV and ICP (PaCO2 <20 mmHg)
o ↓ CBV and thus ICP attenuated by CSF pH return to normal after prolonged
period
o Above adaptive change from active transport of bicarbonate ions into or out of the
CSF and takes about 6 hrs for the CSF to return to normal

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PaO2 - ↓ does not affect CBF until threshold of 50 mmHg reached;

 abrupt cerebral vasodilation and ↑ CBF

 combination of arterial hypoxemia and hypercarbia are synergistic
CPP and Cerebral Autoregulation (maintenance of CBF despite changes in CPP)

 Autoregulation characterized by: arterial constriction when BP ↑, arterial dilation in

response to ↓ BP (below threshold, vessels maximally dilated-CBF dependent on CPP)
o CPP 30-45 mmHg = symptoms of cerebral ischemia (Nausea, dizziness, slow
cerebration)
o CPP > 50 mmHg = cerebral vessels maximally constricted; CBF ↑ and is pressure
dependent
 Vessels over distended = fluid forced across the vessel walls into brain
tissue producing cerebral edema
 Chronic HTN – autoregulation displaced to the right
o Develops over time (not true in acute HTN – glomerulonephritis or PIH)
o Lower limit also shifts so that ↓ in BP normally well tolerated are not tolerated in
HTN
 Rapidly lowering BP to “normal” levels may precipitate a stroke in HTN
pts
o May gradually return to normal over time with antihypertensive therapy
 Autoregulation lost or impaired – intracranial tumors, head trauma, volatile anesthetics
Venous Blood Pressure on CBF

 Direct changes - ↑ venous pressure leads to ↓ in arterial/venous pressure gradients

 Indirect changes - ↑ venous pressure leads to ↑ CBV and ICP which ↓ CPP
 ↑ venous pressure can contribute in ↑ brain bulk during IC surgery
 Causes: venous sinus thrombosis, jugular compression (improper neck position),
superior vena cava syndrome, coughing
Anesthetic Drugs

 CMRO2 changes lead to CBF changes – CBF-CMRO2 coupling

 Isoflurane, Sevoflurane, Desflurane at MAC > 0.6 = potent cerebral vasodilators; ↑ CBF
↓CMRO2
o Increased MAC can lead to ↑ CBF, CBV and possibly ICP
 Halothane – direct vasodilatory effects - ↑↑ CBV at same doses as other VA’s = ↑ ICP
 Thiopental (Barbiturates), Propofol, Etomidate & opioids – cerebral vasoconstrictors
which attenuate CBV and ICP (if no hypercapnia from resp depression)

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  Nitrous Oxide – less effect on CBF and autoregulation; tension pneumocephalus –
delayed awakening from GETA after craniotomy
 Ketamine – cerebral vasodilator
 NMBD – muscle relaxation may prevent acute ↑ ICP (movement, DL, coughing)
o Histamine release may produce cerebral vasodilation -↑ CBV & ICP
o Succinylcholine – may ↑ ICP but can be attenuated with induction of deep
anesthesia with cerebral vasoconstricting anesthetic
Increased Intracranial Pressure

 Normal brain tissue, IC CSF and IC blood combined volume = 1200-1500 ml

o If one ↑, another must ↓ to compensate or cerebral ischemia will eventually result
 Normal ICP usually 5-15 mmHg
 CSF and ICP
o CSF produced by ultrafiltration and secretion by the cells of the choroid plexus
and the passage of water, electrolytes and other substances across the BBB at a
constant rate of 500-600 ml/day in adults
o CSF contained within the ventricular system of the brain, the central canal of the
spinal cord and the subarachnoid space, extracellular compartment of the CNS
o CSF absorbed from microscopic arachnoid villi and macroscopic arachnoid
granulations within the dura mater and bordering venous sinusoids and sinuses
 Intracranial vault is compartmentalized: meningeal barriers separate the falx cerebri
(separates two cerebral hemispheres) tentorium cerebelli (dura mater that lies rostral to
cerebellum, marks border between supratentorial and infratentorial spaces)
o Regional ↑ ICP may cause herniation into the other compartments
 Herniation under falx cerebri = subfalcine herniation – compression of
anterior cerebral artery (midline shift)
 Herniation of supratentorial content past tentorium cerebelli =
transtentorial herniation – brainstem compression occurs in rostral to
caudal manner - ↓LOC
 Uncus (medial portion of the temporal lobe) herniates over the tentorium
cerebelli – transtentorial herniation called uncal herniation – ipsilateral
oculomotor nerve dysfunction due to compression of oculomotor nerve
compression against brainstem (pupillary dilation, ptosis, lateral deviation
of affected eye)
 Cerebellar tonsils herniate through foramen magnum – medullary
dysfunction – cardiorespiratory instability and death

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 o Nonspecific ICP S & S
 HA, N & V, papilledema, ↓ LOC, coma
o CT or MRI may show third but not fourth ventricle enlargement = aqueductal
stenosis
o Measure and Monitor ICP: subdural bolt (pressure transducer in subdural space,
brain parenchyma), ventriculostomy (transducer in ventricle which allows CSF
drainage), lumbar SA catheter (drain CSF but ↑ risk of tonsillar herniation)
o ICP waveform – pulsatile with cardiac impulse and spontaneous ventilation
Methods to Decrease ICP (> 20 mmHg)

 Elevate Head – optimal venous drainage, 30̊ above heart ↓ ICP, extreme flexion or
rotation of head can obstruct jugular veins and restrict venous outflow, avoid head down
position=↑ ICP
 Hyperventilate – recommended PaCO2 30-35 mmHg, lower than this may not ↓ ICP
further, effect will diminish after 6-12 hours and rebound ↑ ICP potential problem
 CSF Drainage -↓ IC volume and ICP, Lumbar CSF drain reserved for ↑ surgical exposure
needs (pituitary or IC aneurysm), if chronic ↑ ICP – shunt CSF from IC ventricle or CSF
drained to R atrium (ventriculoatrial) or peritoneal cavity (ventriculoperitoneal shunt)
 Hyperosmotic Drugs – (Mannitol; 0.25-0.5 g/kg IV over 15-30 min) produce transient
increase in osmolality of plasma to draw water from tissues producing diuresis and lower
BP.
o Avoid hypovolemia – jeopardizes CPP,
o monitor electrolytes (K+) and replace,
o BBB must be intact so that Mannitol does not exert effects in brain – cerebral
edema,
o brain adapts to chronic hyperosmotic drugs – short term effectiveness
 Diuretics –
o Mannitol – removes 100 ml from brain, ↓ ICP in 30 min-2 hrs with significant
diuresis, ↑ intravascular volume – monitor CHF or ↓ cardiac reserve patients,
Mannitol vasodilates (transient ↑ CBV in normal ICP but not with ↑ ICP), and
duration 6 hrs.
o Loop Diuretics (Lasix) helpful for ↑ intravascular volume and pulmonary edema –
systemic diuresis and dehydration to improve arterial oxygenation and ↓ ICP, may
produce hypokalemia
 Corticosteroids – (Dexamethasone & Methylprednisolone) ↓ ICP that is caused by
localized vasogenic cerebral edema around brain tumors thru stabilization of capillary
membranes and ↓ production of CSF, ↑ neurologic status and ↓ HA within 12-36 hours,
also effective in pseudo tumor cerebri(benign IC HTN); not effective for closed head
injury, ↑ blood sugar which adversely affects cerebral ischemia
 Cerebral vasoconstricting Anesthetics –High doses of Barbiturates treat ↑ ICP after acute
head injury, Propofol also useful, however long infusions may cause metabolic acidosis-
may be fatal

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Surgical Decompression
Specific Causes of ↑ ICP

 Tumors – size, edema in surrounding tissue, obstruction to CSF flow (3rd ventricle)
 Intracranial hematomas
 Blood in CSF (SAH) – lead to obstruction of CSF reabsorption
 Infection – meningitis or encephalitis – edema or obstruction of CSF reabsorption
 Aqueductal Stenosis
o Common cause of obstructive hydrocephalus caused by congenital narrowing of
cerebral aqueduct that connects 3rd and 4th ventricle
 May present during infancy when narrowing is severe
o Lesser narrowing – slower progression of hydrocephalus may not be evident until
adulthood
o Symptoms – seizures (30%)
o Treatment – ventricular shunting (anesthesia focus on managing ICP)
 Benign IC HTN – syndrome characterized by ICP > 20 mmHg, normalCSF composition,
normal sensorium and absence of local IC lesions
o Typically occurs in obese women with menstrual irregularities, HA and bilateral
visual disturbances, symptoms may be exaggerated in pregnancy
o No cause of ICP usually found but prognosis is excellent
o Acute treatment – remove 20-40 ml CSF from lumbar SA space, administer
acetazolamide to ↓ CSF production, corticosteroids, surgery
 Indication for treatment is loss of visual acuity
 Long term acetazolamide = acidemia (inhibition of H+ secretion by renal
tubules)
 Lumboperitoneal shunt or optic nerve fenestration – anesthesia includes
avoid hypoxia and hypercarbia, spinal anesthesia is option however CSF
may drain into peritoneal space resulting in inadequate block, GETA may
be best
 Normal Pressure Hydrocephalus
o Presenting Triad = dementia, gait changes, urinary incontinence developing over
weeks to months
o r/t compensated but impaired CSF absorption from previous insult (SAH,
meningitis, head trauma) or unidentified cause
o Normal to low CSF pressure with large ventricles – ventriculoperitoneal or
ventriculoatrial shunt

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Intracranial Tumors

 Primary (arising from brain and its coverings) or metastatic

 Supratentorial more common in adults – HA, seizure, neurologic deficits
 Infratentorial more common in children – obstructive hydrocephalus and ataxia
 Tumor types
o Astrocytoma – neuroglial cells in CNS
 young adults with new onset seizures;
 pilocytic affect children and young adults (cerebellum, cerebral
hemispheres, hypothalamus, optic pathways;
 Anaplastic poorly differentiated, disrupt BBB and evolve to glioblastoma
multiforme;
 Glioblastoma M. (grade IV glioma), 30% of all adult brain tumors
o Oligodendroglioma – myelin-producing cells in CNS (6% IC tumors); seizures
many years before tumor visualized on imaging
o Ependymona – from cells lining ventricles and central canal of spinal cord
(childhood or young adults), most common in floor of 4th ventricle; obstructive
hydrocephalus, HA, N & V, ataxia
o Primitive neuroectodermal tumor – includes retinoblastoma, medulloblastoma,
pineoblastoma, neuroblastoma from neurectodermal cells; medulloblastoma most
common pediatric primary malignant brain tumor and may disseminate via the
CSF to the spinal cord
o Meningioma – extra axial (Arise out of brain proper), slow growing, well
circumscribed, benign tumors from arachnoid cap cells; most commonly in
sagittal sinus, falx cerebri and cerebral convexity, receive blood supply thru
external carotid artery
o Pituitary tumor – may occur as part of endocrine neoplasia type I (PTgland and
pancreatic islet cells), functional (hormone secreting) or nonfunctional
o Acoustic neuroma – result of benign schwannoma involving CN VIII in auditory
canal; hearing loss, tinnitus, disequilibrium
o CNS lymphoma – Primary most common in supratentorial locations (deep gray
matter or corpus callosum); SLE, Sjogrens’ syndrome, rheumatoid arthritis,
immunosuppressed states, Ebstein Barr infection; very sensitive to steroids (tumor
lysis)
o Metastatic Tumor – Primary sites usually lung or breast, malignant melanoma,
hypernephroma, carcinoma of colon; usually more than one IC lesion, bleed more

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 Management of Anesthesia
o Goals: maintain adequate cerebral perfusion and oxygenation of normal brain;
optimize operative conditions to facilitate resection; ensure rapid emergence from
anesthesia to facilitate neuro assessment; accommodate intraop electrophysiologic
monitoring prn
o Preoperative Management: ID presence or absence of elevated ICP
 S&S – N & V, altered LOC, mydriasis and ↓ reactivity of pupils to light,
papilledema, bradycardia, systemic HTN, breathing disturbances
 Opioids and Sedatives: IC pathology= ↑ sensitivity to CNS depression,
hypoventilation, mask alterations in LOC that accompany IC HTN,
o Induction of Anesthesia:
 Thiopental, Etomidate or Propofol followed by NDMB to adequate depth
before DL that may abruptly ↑ CBF, CBV and ICP
 DL response further blunted with Lidocaine (1.5 mg/kg), esmolol or
opioid
 HTN = ↑ CBF, CBV and ICP – cerebral edema whereas HoT should be
avoided to prevent brain ischemia, PEEP has variable effect on ICP
o Maintenance of Anesthesia
 Combo of N2O, VA, opioids, barbiturates, propofol to achieve desired
cerebrovascular effects
 N2O – controversial d/t possibility of VAE
 If VAE detected, DC N2O to avoid VAE expansion
 N2O and VA’s may ↑ CBV and ICP d/t vasodilation but low MAC (0.6-1)
will blunt BP changes d/t noxious surgical stimulation
 Nitroglycerin or SNP may ↑ CBV and ICP despite ↓ BP = ↓ CPP; use only
after craniotomy and opening of the dura
 Avoid patient movement - ↑ ICP, surgical bleeding, IC volume, direct
injury to head and brain
o Fluid Therapy
 Iso-osmolar solutions (0.9% NS, LR) do not adversely affect brain water
or edema formation as long as BBB intact
 Free water/ hypo-osmolar solution (0.45% NS) rapidly distributed, may
↑ICP
 Hyper-osmolar (3% NS) tends to ↓ brain water d/t ↑ osmolality of plasma
 Avoid hypervolemia, maintain euvolemia
 Intravascular volume depletion (blood loss) should be corrected with
PRBC or colloid supplemented with BSS.
 Glucose containing solutions – use with caution- exacerbates neuronal
injury with CNS ischemia

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o Monitoring
 Arterial line – BP and blood sampling
 Capnography – facilitate ventilation and PaCO2 management, detect VAE
 Continuous ICP – not routine but quite helpful
 Temperature – prevent hyperthermia or uncontrolled hypothermia
 Bladder catheter – management of periop fluid balance (diuresis, DI,
SIADH)
 IV access – large bore to replace blood loss
 CVL – CVP, aspiration of VAE
 TEE – VAE and cardiac function monitoring
 PA catheter for patients with cardiac disease
 PNS (paralysis d/t brain tumor resistant to NDMR proliferation of Ach
responsive receptors after denervation)
 ECG – changes d/t IC tumors, may reflect ↑ ICP; arrhythmias range from
sinus arrhythmias to PVC’s or Vtach
o Postoperative Management
 Anesthetic and muscle relaxant effects ideally dissipated for immediate
neuro status monitoring
 Awake with little response to ETT – intraop narcotic, lidocaine (may
produce CNS depression), and extubate
 If consciousness depressed pre-op, delay extubation until airway reflexes
confirmed and SV sufficient to prevent CO2 retention
 Hypothermia may cause slow awakening as might NMB, sedatives (narcs,
benzos, VAs) OR primary CNS event – ischemia, hematoma, tension
pneumocephalus
 If persistent new deficit does not quickly resolve – investigate further
o Sitting position and VAE
 Craniotomy for SUPRATENTORIAL tumor performed supine with 10-
15 ̊ elevation of head to facilitate cerebral venous drainage
 INFRATENTORIAL tumors require lateral, prone or sitting positions
 Sitting position
 Advantages – excellent surgical exposure, enhanced cerebral
venous and CSF drainage, minimizes blood loss and ↓ ICP,
 Disadvantages - ↓ BP & CO, hazard of VAE
 Considerations:
o Hydrostatic pressure gradient on CPP (difference between
heart and brain) – transduce arterial line zeroed at external
auditory meatus (approx. location of Circle of Willis) or
patient may be at risk for cerebral hypoperfusion

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 o Venous air embolism – pressure in exposed veins is
subatmospheric, may occur in neurosurgery, neck, thorax,
abdomen or pelvis surgery and during open heart surgery,
repair of liver and vena cava lacerations, obstetric or
gynecologic procedures, THA.
 S&S=↓EtCO2, gasp reflex, ↑EtNitrogen, HoT,
tachycardia, cardiac dysrhythmias and cyanosis
o Air entering RA or ventricle = interference with R sided
CO and blood flow into PA. If air enters PA = pulmonary
edema and reflex bronchoconstriction or even death from
air lock in R ventricular outflow tract (R CO plummets,
acute cor pulmonale (indicated by ↑ RA or PA pressure),
hypoxemia)
o Air may pass through pulmonary vessels to coronary or
cerebral circulations, through R to L intracardiac shunts
o Known PFO or other cardiac defect causing R to L shunt =
relative contraindication to sitting position
o Reversed interatrial pressure gradient predisposes pt to
paradoxical air embolism
 VAE detected: surgeon should flood operative site with fluid and
apply occlusive material to all bone edges
o Attempt air aspiration through RA catheter
o 100% FiO2, DC Nitrous if used at all (this will↓ PA
pressure)
o Direct jugular venous compression may increase venous
pressure at the surgical site (PEEP not proven effective)
o Extreme HoT requires BP support with sympathomimetic
(inotropic and vasoconstrictive properties), Bronchospasm
treated with Albuterol aerosol,
o Place pt left lateral Trendelenburg if possible (may not be
with craniotomy)
o Hyperbaric treatment may be beneficial after VAE or
paradoxical air embolism within 8 hrs
 Postoperative complications for posterior fossa craniotomy:
o Apnea d/t hematoma formation
o Tensionpneumocephalus
o CN injury
o Macroglossia – d/t impaired venous and lymphatic drainage
from the tongue (assoc with excess neck flexion)

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Disorders Related to Vegetative Brain Function

 Coma – a state of profound unconsciousness produced by drugs, disease, injury of CNS

o Dysfunction of brain region responsible for consciousness – pontine reticular
activating system, midbrain or cerebral hemispheres
o Causes: Structural lesions (tumor, stroke, abscess, IC bleeding) or diffuse
disorders (hypothermia, hypoglycemia, hepatic or uremic encephalopathy, post-
dictal state, encephalitis or drugs)
o Assessed with Glasgow Coma scale
o Management:
 Establish patent airway with adequate oxygenation, ventilation, circulation
 Determine cause – medical history, exam, diagnostics, vitals, breathing
pattern
 Ataxic breathing = random pattern of Vt- medulla pathway
interrupted
 Apneustic = prolonged end inspiratory pauses – pons lesion or
basilar artery occlusion leading to pontine infarction
 Cheyne-Stokes=breaths of progressively increasing then
decreasing Vt (crescendo-decrescendo pattern) followed by periods
of apnea – cerebral hemisphere or basal ganglia injury, arterial
hypoxemia, CHF (delay in circulation time from pulmonary
capillaries to carotid bodies is presumed to be cause in CHF)
 Central Neurogenic Hyperventilation=spontaneous, may be so
severe that PaCO2 < 20 mmHg - acute neurologic insults assoc
with cerebral thrombosis, embolism, closed head injury
 Pupil exam – normal pupils 3-4 mm equal bilaterally with brisk
reflex
o Compression of Diencephalon or thalamic structures =
small (2mm) but reactive pupils, likely from interrupted
descending sympathetic fibers
o Unresponsive midsize pupils (5 mm) indicate brain
compression
o Fixed and Dilated pupil (7 mm) Oculomotor nerve
compression – also seen with herniation, anticholinergic or
sympathomimetic drug intoxication
o Pinpoint pupils (1mm) indicate opioid or organophosphate
intoxication, focal pontine lesions or neurosyphilis

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  Extraocular muscle function allows brainstem functioning test via
CN III, IV and VI (Oculomotor, trochlear, abducens)
o Using passive head rotation in comatose patient
(oculocephalic reflex or doll’s eye maneuver) - produces
full conjugate horizontal eye movements
o Cold water on tympanic membrane (oculovestibular reflex
or cold caloric testing) If normal brainstem fxn – results in
tonic conjugate eye movements toward the side of cold
water irrigation
o Unilateral oculomotor nerve or midbrain lesions result in
failed adduction but intact contralateral abduction
o Complete absence of response – pontine lesion or diffuse
disorders
 Motor response to Painful stimuli
o Mild to moderate diffuse brain dysfunction above
diencephalon=purposeful reaction; unilateral response may
indicate unilateral lesions (stroke, tumor)
o Decorticate response=flexion of elbow, adduction of
shoulder, extension of knee and ankle – indicates
diencephalic dysfunction
o Decerebrate response=extension of elbow, internal rotation
of forearm, leg extension – indicates more severe brain
dysfunction
o Pontine or medullary lesion – likely no response to painful
stimuli
o Management of Anesthesia
 Be aware of cause of coma
 Goals – secure airway, provide adequate cerebral perfusion and
oxygenation, avoid ↑ICP
 Monitoring – arterial line, ICP monitoring
 Brain Death And Organ Donation
o Brain death Defined – permanent cessation of total brain function
o Coma cause established with irreversible cause
 Pt lacks spontaneous movement (spinal reflexes may be intact)
 Lacks CN reflexes and function (HR fails to ↑ in response to atropine)
 Apneic – lack of function of respiratory control nuclei in brainstem
 EEG isoelectricity or absence of CBF

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 o Management of Anesthesia
 Goal – optimize oxygenation and perfusion to harvestable organs
 Commonly HoT – hypovolemia, DI, 3rd space losses, drugs – fluid
resuscitation while avoiding hypervolemia; avoid vasoconstrictive drugs
and use inotropes instead – dopamine or dobutamine
 Minimize catecholamine release for heart retrieval, monitor ECG,
dysrhythmias from electrolyte abnormalities, loss of vagal function, ↑ ICP,
cardiac contusion
 Hypoxemia d/t ↓ CO, aspiration, edema, contusion atelectasis
 DI occurs frequently in brain dead patients – replace with hypotonic
solutions, consider inotropes, vasopressin or Desmopressin to treat DI
 Brain dead become poikilothermic – Avoid hypothermia
 Rule of 100’s: SBP > 100 mmHg, UO > 100 ml/hr, PaO2>100 mmHg,
Hgb>100g/L
Cerebrovascular Disease

 Stroke – characterized by sudden neurologic deficits resulting from ischemia or

hemorrhage
o 3rd leading cause of death in US, leading cause of disability
 Cerebrovascular Anatomy
o Blood supply (20% CO) via internal carotids and vertebral arteries

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 o CIRCLE OF WILLIS – inferior surface of the brain to provide collateral
circulation to multiple areas of the brain
o Only 20-25% of people have a normal, intact Circle of Willis

 Acute Ischemic Stroke

o Sudden onset of neurologic dysfunction or evolving over minutes to hours
o TIA – vascular related focal neuro deficit that resolves promptly
 Evidence of impending ischemic stroke
o Systemic HTN most significant risk factor for acute ischemic Stroke, other risks =
cigarette smoking, hyperlipidemia, DM, excess alcohol consumption, increased
serum homocysteine concentrations
o Stroke suspected – Diagnostic imaging (non contrast CT) reliably distinguishes
acute intracerebral hemorrhage from ischemia
o Most likely reflects embolism from cardiac cause (a fib, ventricular akinesis
following MI, dilated cardiomyopathy, valvular heart disease, large vessel
atherothromboembolism or small occlusive disease (lacunar infarction)
 Management of Acute Ischemic Stroke
o ASA initial therapy to prevent recurrent stroke, IV infusion of recombinant tissue
plasminogen activator, Infusion of thrombolytic drugs
o Manage airway, oxygenation, ventilation, BP, blood glucose and body temp
o Cerebral edema and ↑ ICP – may cause focal or diffuse mass effects that peak 2-5
days following stroke onset
o Malignant middle cerebral artery syndrome – edematous infarcted tissue causes
compression of anterior and posterior cerebral arteries resulting in secondary
infarctions
o Surgical decompression - craniotomy with cerebellar resection
o MAINTAIN BP – perfuse ischemic regions, may use small dose of Labetolol to
keep BP < 185/110 and decrease myocardial workload and irritability
o Hyperglycemia=poor outcomes in acute ischemic stroke
 Cellular hypoxia or anoxia – glucose metabolized to lactic acid which
leads to tissue acidosis and increased tissue injury
o Hypothermia may improve outcome d/t decreased neuronal O2 demands, cerebral
edema, neurotransmitter toxicity; still controversial but AVOID FEVER
o Heparin 5000 u SC q 12 hrs or pneumatic compression stockings

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Acute Hemorrhagic Stroke – from intracerebral hemorrhage or SAH

 Intracerebral hemorrhage – 4x more likely to cause death

o Interventricular Hemorrhage occludes CSF drainage
o Factor VII may lessen hematoma and improve outcome
o Maintain MAP < 130 in essential HTN
 SAH and IC aneurysms
o SAH – most common from rupture of IC aneurysm
 Causes - HTN, coarctation of aorta, polycystic kidney disease,
fibromuscular dysplasia
 Risk of rupture – HTN, cigarette smoking, cocaine abuse, female sex and
oral contraceptive use
o Unruptured aneurysm – HA, new focal deficit, seizures
o SAH diagnosis – with CT and symptoms (worse HA of my life, photophobia, stiff
neck , ↓ LOC, focal neuro changes)
 ST changes (depression or T wave inversion) d/t catecholamine release,
also dysrhythmias, pulmonary edema
o Treatment of aneurysm – localizing aneurysm and surgically excise or clip
 Prevent vasospasm – triggered by Hgb on a luminal surface of cerebral
arteries & treat with Triple H (hypertension, hypervolemia and passive
hemodilution)
 Nimodipine-CCB- protective effect from consequences of
vasospasm
 Management of Anesthesia
o Goals – limit risk of aneurysm rupture, prevent cerebral ischemia and facilitate
surgical exposure, provide anesthetic depth to offset surgical stimulation,
facilitate surgical exposure through optimal brain relaxation, maintain CPP,
prompt awakening
o Induction – prevent ↑ in transmural pressure of aneurysm sac
o Avoid hyperventilation (↓ ICP which decreases tamponading force on external
surface of aneurysm)
o Avoid HTN during DL – esmolol, lidocaine, propofol, barbiturates opioids
o Monitoring – Arterial line, CVP, PA or TEE may be considered, EEG or SSEP or
MEP
o Intraoperative Rupture – Volume resuscitation to maintain normovolemia,
controlled HoT with Nitroprusside to limit hemorrhage, once clipped, ↑ BP to ↑
collateral flow
o Use VA’s, fentanyl bolus or Remifentanil infusion or TIVA; Barbiturates and
Propofol cause vasoconstriction and may offer neuronal protection against
ischemia, muscle paralysis essential to prevent movement during aneurysm
clipping

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 o Optimize Brain Relaxation – CSF drainage, mild hyperventilation, loop and/or
osmotic diuretics, proper positioning to facilitate venous drainage; intraop fluids
guided by blood loss, UO, cardiac filling pressures, avoid hyperthermia
o Controlled HoT – used less d/t impairment of autoregulation concerns; now using
regional HoT with clamp on parent artery < 10 min
Arteriovenous Malformations

 AVM- abnormal collections of blood vessels in which multiple direct arterial to venous
connections exist without intervening capillaries
o typically, high flow, low resistance shunts with vascular intramural pressure <
systemic arterial pressure
o congenital, adult onset with hemorrhage or seizures
 seizure d/t cerebral steal (shunt blood from normal brain tissue to low
resistance AVM) or fliosis from hemosiderin deposits from previous
hemorrhage
o most are supratentorial
o Neonate or childhood presentation = Vein of Galen (hydrocephalus or
macrocephaly with prominent forehead veins, high CO or heart failure)
o Treatment – surgical resection, highly focused Gamma Knife irradiation, radiation
or embolization therapy
 Venous Angioma
o Consist of tufts of veins, rarely found as hemorrhage or seizure
o Low flow, low pressure lesions containing intervening brain parenchyma w/i
nidus
 Cavernous Angioma
o Benign lesions of vascular channels without large feeding arteries or large veins,
no brain parenchyma
o Low-flow, well circumscribed lesions present as new onset seizures or less often,
hemorrhage
o Treatment – surgical resection; do not respond to irradiation, not amenable to
embolize
 Capillary Telangiectasia
o Low flow, enlarged capillaries
o Low hemorrhage risk unless in the brainstem; not treatable
 Arteriovenous fistula
o Direct communications between arties and veins without intervening nidus
o Occur between meningeal vessels within dura mater or b/w carotid artery and
venous sinuses within the cavernous sinus (present with orbital or retro-orbital
pain)
o Treatment – embolization or surgical ligation (risk of rapid significant blood loss)

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  Management of Anesthesia
o Pre-operatively – evaluate for cerebral ischemia or ↑ ICP
 Other treatments, nature of malformation (size, location), mechanism of
venous drainage
 Medications (antiepileptic’s) should be administered pre-operatively
 If preoperative angiography – may be fluid/electrolyte imbalances 2 to
hypertonic contrast material
o Intra-operatively
 Monitor with A-line – hypotension = ischemia; hypertension = risk of
rupture, worsen ICP
 Thiopental, propofol and etomidate are safe, effective inductions agents
 Avoid SNS response to DL, pinion placement & incision with lidocaine,
esmolol or SNP, deepen anesthesia
 Adequate IV access in case of aneurysm rupture; CVP may be helpful to
monitor volume status; PA cath or TEE may be useful if concurrent
cardiac disease
 Mild hyperventilation will help surgical exposure (PaCO2 30-35)
 Avoid cerebral edema (hypotonic or glucose containing solutions, tx with
diuretics and ↓ BP)
Moya Moya Disease

 “puff of smoke” – progressive stenosis of IC vessels with the secondary development of

an anastomotic capillary network (cluster of small abnormal blood vessels)
 Causes – familial, head trauma, neurofibromatosis, tuberous sclerosis, fibromuscular
dysplasia
 Affected arteries – thickened intima, thin media; similar pathologic findings in other
organs
 Ischemia – TIA or CVA – present in children; hemorrhage – present in adults
 Management of Anesthesia:
o Document pre-existing neuro deficits, history of hemorrhage or presence of IC
aneurysm; discontinue anticoagulant or antiplatelet therapy to avoid bleeding
o Induction goals: ensure hemodynamic stability, avoid vasoconstriction, facilitate
rapid emergence to assess neuro fxn
o Post-op complications include – stroke, seizure, hemorrhage

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Traumatic Brain Injury

 Initial management – immobilize cervical spine, establish patent airway, protect lungs
from aspiration, maintain perfusion by treating HoT
 Perioperative Management – consider risks of ongoing injury to the brain as well as co-
existing injuries to organs and other body structures
o Poor outcomes contributed to: ↑ ICP, MAP < 70 mmHg as normal autoregulation
is impaired in acute head injury
o Hyperventilation will ↓ ICP but may contribute to cerebral ischemia
o Barbiturate coma to control IC HTN may be useful, hypertonic saline and
mannitol may decrease brain volume
o Lung injury may impair ventilation – require mechanical ventilation
o Neurogenic pulmonary edema – hyperactivity of SNS results in alterations in
Starling forces in the lung which result in pulmonary edema
o DIC may result after severe head injury – brain release of thromboplastin into
systemic circulation which activates coag cascade – replace clotting factors
 Management of Anesthesia
o Optimize CPP, minimize occurrence of cerebral ischemia, avoid drugs and
techniques that could increase ICP
o Maintain CPP > 70 mmHg
o Adequate fluid resuscitation and replacement are important
o Induction & Maintenance
 Stable patient – IV induction with NDMR acceptable
 Moribund patient – safe effective airway takes precedence over anesthetic
drug selection
 Avoid Nitrous oxide – risk of pneumocephalus or pneumothorax
 If acute brain swelling occurs – rule out hypercapnia, arterial hypoxemia,
HTN and venous obstruction
o Postoperatively – maintain skeletal muscle paralysis to facilitate mechanical
ventilation
Hematomas

 Epidural Hematomas
o Results from arterial bleeding into space between skull and dura from tear in
meningeal artery associated with skull fracture
o Usually pt losses consciousness with injury with variable lucid periods following
o Hemiparesis, mydriasis and bradycardia suddenly develop a few hours after head
injury reflecting uncal herniation and brainstem compression
o Treatment = prompt drainage

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  Traumatic subarachnoid Hematoma
o Most often follows rupture of an IC aneurysm, or trauma, bleeding from cortical
vessels
o May evolve over time, associated with cerebral vasospasm
 Subdural hematoma
o Results from laceration or tearing of bridging veins that bleed into the pace
between the dura and arachnoid
o CSF clear; confirmed by CT
o Trauma most common cause, most view as trivial incident or even forget it
happened, occasionally, subdural hematoma forms spontaneously (HD or
anticoagulant therapy)
o S&S – develop slowly over days (slow venous bleed) – HA, drowsiness,
obtundation, hemiparesis, hemianopsia, language disturbance, progressive
dementia
o TX – medical management, drain via burr holes or craniotomy, normocapnia to
tamponade any further venous bleeding
 Intraparenchymal hematoma
o Abnormal collection of blood located within the brain tissue proper
o Difficult to treat d/t location; acutely increase in size
Congenital Anomalies of the Brain

 Chiari Malformation
o Group of disorders consisting of congenital displacement of the cerebellum
 Chiari I – downward displacement of cerebellar tonsils over the cervical
spinal cord
 Occipital HA at any age, cutaneous dysesthesias; pain aggravated
by coughing or moving head, visual disturbances, intermittent
vertigo, ataxia; signs of syringomyelia present in 50% of patients
 Chiari II downward displacement of cerebellar vermis; often assoc. with
meningomyelocele
 Present in infancy with obstructive hydrocephalus plus lower
brainstem and CN dysfunction
 Chiari III – extremely rare; represent displacement of the cerebellum into
occipital encephalocele
o Treatment – surgical decompression by freeing adhesions and enlargement of
foramen magnum
Anesthetic considerations - ↑ ICP, significant intra-op blood loss (Chiari II)

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Tuberous Sclerosis (Bourneville’s disease

 Autosomal dominant disease characterized by mental retardation, seizures, facial

angiofibromas
 Pathologically – condition in which a constellation of benign hamartomatous (local tissue
growing in disorganized fashion) lesions and malformations occur in almost every organ
of the body
o Brain – cortical tubers, giant cell astrocytoma’s
o Cardiac rhabdomyoma – associated with Wolf-Parkinson White syndrome
o Kidneys – angiomyolipomas and cysts resulting in renal failure
o Oral – nodular tumors, fibromas, papilloma’s on tongue, palate, pharynx, larynx
 Anesthesia Management
o Consider mental retardation (seizure disorders)
o ID upper airway abnormalities pre-operatively
o Select drugs appropriate for renal function impairment
o Cardiac involvement may be associated with cardiac dysrhythmias intra-op
Von Hippel-Lindau Disease

 Familial disease transmitted by an autosomal dominant gene with variable penetrance

 Characterized by retinal angiomas, hemangioblastomas, CNS and visceral tumors (benign
but may cause bleeding), ↑ incidence of pheochromocytoma, renal cysts, renal cell
carcinoma
 Anesthetic Management – consider involvement (pheochromocytoma) – exaggerated
HTN during DL may require esmolol, labetalol, SNP or combo
Neurofibromatosis

 Autosomal dominant mutation – affects both sexes; categorized as classic, acoustic or

segmental
 Disease progresses over time;
 S&S=café au lait spots (diagnosing feature),
o neurofibroma-cutaneous, vascular or neural,
o IC tumor (5-10% with ↑ mortality), spinal cord tumor,
o pseudarthrosis (spontaneous fracture that progresses to nonunion),
o kyphoscoliosis (2%), short stature,
o CA (neurofibrosarcoma, malignant schwannoma, Wilms tumor,
rhabdomyosarcoma, leukemia),
o endocrine abnormalities (pheochromocytoma-1%, disturbed sexual development,
medullary thyroid carcinoma, hyperparathyroidism)
o learning disability (40%), seizures-idiopathic or r/t tumors

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  May be nodular and discrete or diffuse with extensive interdigitations into surrounding
tissues; although benign in and of themselves, invasive nature may cause functional
compromise
 Treatment – therapy to treat symptoms – antiepileptic’s, surgery
 Anesthetic Management – look at S & S, variable response to NMB
Degenerative diseases of the Brain
Alzheimer’s disease

 Chronic neurodegenerative disorder, most common cause of dementia (>65 yr)

 Diffuse amyloidrich senile plaques and neurofibrillary tangles are hallmark pathologic
findings
 Changes in synapses – Ach and CNS nicotinic receptors
o Early onset – before age 60, due to missense mutations in several genes
(autosomal dominant)
o Late onset – after age 60, related to genes
 Progressive cognitive impairment – memory, apraxia, aphasia, agnosia; diagnosed post-
mortem
 Use shorter-acting sedative-hypontic drugs, anesthetic agents and narcotics are preferred
 Be aware – use of cholinesterase inhibitors (tacrine, donepezil, rivastigmine,
galantamine) for Alzheimer’s may prolong effect of succinylcholine and add relative
resistance to NDMR’s
Parkinson’s disease

 Neurodegenerative disorder of unknown cause; aging single risk factor for development
 ID’d relation between manganese exposure (welders) and genetic associations
 Characteristic loss of dopaminergic fibers that are normally present in the basal ganglia =
regional dopamine concentrations are depleted (dopamine inhibits firing of neurons that
control extrapyramidal motor system – unopposed stimulation by Ach = Parkinson’s)
 Triad – skeletal muscle tremor, rigidity and akinesis.
o Rigidity – loss of arm swing with walk, infrequent blinking
o Tremor – rhythmic, alternating flexion and extension of the thumbs
o Seborrhea, oily skin, diaphragmatic spasms, oculogyric crisis, dementia &
depression often present
 Treatment – Levodopa combined with decarboxylase inhibitor (prevents peripheral
conversion to dopamine to optimize levodopa concentrations)
o Levodopa may cause: dyskinesia’s, psychiatric disturbances, increased
myocardial contractility and heart rate, orthostatic hypotension, GI SE’s – N&V,
o Amantadine – antiviral – control symptoms

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 o Selegiline – MAOI type B – inhibits catabolism of dopamine in CNS without
tyrosine related HTN of MAOI
o Surgical – disabling and medically refractory symptoms
 Implanted deep brain stimulator to control tremor (awake, MAC or
GETA)
 Pallidotomy – improves levodopa induced dyskinesia
 Fetal tissue transplantation – embryonic dopaminergic neurons can survive
in recipients
 Management of Anesthesia
o Interruption of drug therapy may lead to skeletal muscle rigidity (ventilation
issues) d/t elimination ½ time of levodopa (short – 6-12 hrs)
o HoT and cardiac dysrhythmias possible
o Butyrophenone (Droperidol, haloperidol) should be available to antagonize
dopamine in basal ganglia
o Acute dystonic reactions – ALFENTANIL – opioid induced decrease in central
dopaminergic transmission
o Ketamine – controversial – exaggerated SNS response but has been safely
administered to patients treated with levodopa
o Muscle relaxant type not affected
o Deep Brain Stimulator Implantation
 Skip AM dose of levodopa to facilitate return of tremor and enhance
sensitivity in detecting the efficacy of DBS during procedure
 Difficult IV access with tremor
 GABA NT involved in normal circuitry of basal ganglia – avoid
propofol, benzos – may alter characteristic microelectrode
recordings of specific nuclei
 Opioids and Dexmedetomidine good alternatives
o Remifent – avoid resp depression, short acting
 Patient in sitting position = risk of air embolism
 Pre-cordial Doppler, US
 If VAE- pt should NOT take deep breath as lower intrathoracic
pressure may cause more air entrainment – surgeon should flood
field with saline
 Other Risks – HTN, seizures, bleeding (sudden alteration of
consciousness)

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Hallervorden-Spatz Disease

 Rare autosomal recessive disorder of the basal ganglia; slowly progressive from late
childhood onset to death in 10 yrs
 Dementia, dystonia with torticollis, scoliosis are commonly present
o Dystonia disappears with induction of general anesthesia but skeletal muscle
contractures/ bony changes = immobility of TMJ and cervical spine, even in deep
GA
o Awake intubation likely to intensify dystonia – mask induction with SV preferred
 Succinylcholine – dangerous d/t muscle wasting and diffuse axonal changes in the brain
involving upper motor neurons that would accentuate the release of potassium, NDMR’s
are best
Huntington’s disease

 Degenerative disease of the CNS marked by atrophy of the caudate nucleus and the
putamen and globus pallidus; autosomal dominant with delayed appearance (35-40 yr
olds)
 Basal ganglia deficiencies – Ach (and synthesizing enzyme choline acetyltransferase) and
GABA
 Progressive dementia with choreoathetosis; depression, aggressive outbursts, mood
swings; pharyngeal muscle involvement ↑ susceptibility to pulmonary aspiration; onset to
death avg 17 yrs
 Treatment – symptomatic – directed at ↓ choreiform movements (Haldol)
o Most useful therapy – Haldol or Fluphenazine (interfere with NT effects of
dopamine by antagonizing dopamine); or Reserpine; tetrabenazine (deplete
dopamine stores)
 Anesthesia – limited recommendations
o Pre-op: Haldol or Droperidol to limit choreiform movements
o Use of Nitrous and Volatile anesthetics are acceptable
o Decreased plasma cholinesterase may prolong succinylcholine action but these
patients may also be sensitive to NDMR effects
Torticollis

 Disturbance in basal ganglia function; spasmodic contraction of nuchal muscles which

progresses to limb and girdle muscles
o SCM hypertrophy, spasm may involve cervical muscles of vertebral column
(lordosis, scoliosis, impaired ventilation)

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  Treatment –
o not very effective – surgical bilateral anterior rhizotomy at C1 and C3 with
sectioning of the spinal accessory nerve
 May cause postop diaphragm paralysis – respiratory distress
o Selective peripheral denervation of affected cervical musculature
o Spasm of nuchal muscles may interfere with maintenance of patent upper airway
 Sudden appearance of torticollis after administration of Anesthesia has been reported
o Treatment = Diphenhydramine 25-50 mg IV to produce dramatic reversal of
torticollis
Transmissible Spongiform Encephalopathy’s

 Include Creutzfeldt-Jakob disease, kuru, Gerstmann-Straussler-Scheinker syndrome and

fatal familial insomnia; non-inflammatory diseases of CNS (Bovine = mad cow disease)
 Transmitted by prions (slow acting infectious protein pathogens that lack RNA and DNA
and do not produce immune reaction)
 Diagnosis- based on clinical and neuropathologic findings (presence of diffuse or focal
clustered small round vacuoles, familial progressive subcortical gliosis, inherited
thalamic dementia)
 CJD – most common at 1/million worldwide;
o 10-15% diagnosed also have family history of disease so there may be genetic
factor
o Abnormal protein accumulation acting as NT develops producing dementia with
ataxia and myoclonus
o Diagnosis requires brain biopsy; differential diagnosis = Alzheimer’s
o Special precautions – especially when handling CSF
Multiple Sclerosis

 Autoimmune disease affecting CNS in genetically susceptible persons

o Diverse combinations of inflammation, demyelination and axonal damage in
CNS; loss of myelin covering axons is followed by formation of demyelinated
plaques
o Peripheral nerves not affected by MS
 Clinical Manifestations – multifocal involvement leads to subacute-acute, relapses and
remissions, chronic and progressive course
o Increased body temp can exacerbate symptoms/ increased incidence of seizure
disorders in patients with MS
o Onset after 35 yrs usually suggests slow disease progression

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  Treatment (nothing curative)
o Corticosteroids – immunomodulatory and anti-inflammatory that restore BBB,
decrease edema and possibly improve axonal conduction
o Interferon B – for relapsing/remitting MS with SE of transient influenza like
symptoms
o Glatiramer acetate is a mix of random synthetic polypeptides synthesized to
mimic myelin basic protein – useful in patients resistant to Interferon B
o Mitoxantrone – immunosuppressive and inhibits lymphocyte proliferation
 Cardiotoxic; used for rapidly progressive MS
o Azathioprine – depresses cell-mediated and humoral immunity; decreases relapses
but has no effect on progression
o Methotrexate – relatively nontoxic, inhibits both cell mediated and humoral
immunity d/t anti-inflammatory effects
 Anesthetic Management:
o Surgical stress likely to cause exacerbation of MS
o Increase in body temp of even 1̊ C can exacerbate MS
o Spinal anesthesia implicated in exacerbations but epidural/peripheral is not
 May be d/t local anesthetic neurotoxicity (demyelination of spinal cord=
more susceptible)
o GETA most common anesthetic for MS
 Possibility of exaggerated potassium release with Succinylcholine
 Prolonged response to NDMR – skeletal muscle weakness, decreased
skeletal muscle mass – d/t proliferation of extrajunctional cholinergic
receptors characteristic of upper motor neuron lesions
o Corticosteroids perioperatively – especially if on chronically
Post-polio Sequelae

 Poliomyelitis – caused by enterovirus infecting reticuloendothelial system; enters CNS

and targets motor neurons in brainstem and anterior horn of spinal cord
 Post-polio Sequelae – fatigue, skeletal muscle weakness, joint pain, cold intolerance,
dysphagia and sleep and breathing problems (OSA)
 Polio may damage reticular activating system making these patients exquisitely sensitive
to sedative effects of anesthetics and delayed awakening
 Sensitive to NDMR is common
 Postop shivering can be profound –very sensitive to cold; as well as post-op pain d/t
endogenous opioid secreting cells in brain and spinal cord
 At risk for post-op complications r/t respiratory muscle weakness and dysphagia

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Seizure Disorders

 Caused by transient, paroxysmal and synchronous discharge of groups of neurons in the

brain or hypoglycemia, hyponatremia, hyperthermia and drug toxicity
 Epilepsy – recurrent seizures resulting from congenital or acquired factors (cerebral
scarring)
 Classification – Loss of Consciousness AND Focus of seizure activation
o Simple (no loss of consciousness); complex (altered LOC); Partial (single
hemisphere); Generalized (diffuse activation of neurons in both hemispheres)
o EEG used to determine foci; videography, electrocorticography also used
 Pharmacologic Treatment
o Antiepileptic’s – dose guided by clinical response rather than serum levels
 Decrease neuronal excitability or enhance neuronal inhibition
 Partial Seizures – carbamazepine, phenytoin, eslicarbazepine, valproate
 Generalized Seizures – carbamazepine, phenytoin, valproate, barbiturates,
gabapentin, levetiracetam, lamotrigine
 Consider altered metabolism of other drugs
 Side Effects – depression of cerebral function with sedation
 Phenytoin – hypotension, cardiac dysrhythmias, gingival
hyperplasia, aplastic anemia, erythema multiforme, Stevens-
Johnson syndrome; Significant vasoconstriction on IV
extravasation = purple glove syndrome
o Fosphenytoin – prodrug – does not share toxicity profile
 Valproate – hepatic failure (idiosyncratic hypersensitivity
reaction), pancreatic, increased surgical bleeding with long-term
use (thrombocytopenia or ↓ factor VIII vW
 Carbamazepine – diplopia, dose related leukopenia, hyponatremia
and altered hepatic metabolism of various drugs
 Hematologic – mild anemia to aplastic anemia – most common
with carbamazepine, phenytoin and valproate
 Surgical Treatment
o Consideration if seizures do not respond to antiepileptic drugs or cannot tolerate
SE’s
 Resection of pathologic region (tumor, hematoma, scar tissue); corpus
callosotomy to prevent generalization of partial seizure to opposite
hemisphere; hemishperectomy for persistent catastrophic seizures
 Preparation – seizure focus located by imaging
o Implantation of left vagal nerve stimulator (left chosen d/t right significant cardiac
innervation)

Mechanism unclear but patient’s tolerate well; occasional hoarseness

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 Status Epilepticus
o Life threatening condition that manifests as continuous seizure activity or two or
more seizures occurring in sequence without recovery of consciousness between
them
o Goal of Treatment – prompt IV access to treat and support of airway, ventilation
and circulation
 Rule out hypoglycemia – routine glucose admin potentially dangerous as
hyperglycemia = cerebral ischemia
 Secure Airway – avoid NDMR
 Use propofol or Thiopental to temporarily halt seizure
 ABG to check for metabolic acidosis (common sequela) and treat with
sodium bicarbonate
o Anesthetic Management
 Consider impact of antiepileptic drugs on anesthetic drug
pharmacokinetics and pharmacodynamics
 Methohexital may activate epileptic foci
 Alfentanil, ketamine, enflurane, isoflurane and sevoflurane may cause
epileptiform spike and wave EEG activity in patients without a history of
seizure but are also known to suppress epileptiform and epileptic activity
 Propofol – has produced seizures and opisthotonos (severe back spasm
causing hyperextension of body and head)
 Cisatracurium and Atracurium produce laudanosine – a proconvulsant
metabolite
 NDMR – duration shortened by antiepileptic’s (phenytoin and
carbamazepine)
 Maintain antiepileptic therapy through operative course
 Thio-barbiturates, opioids, Benzos, Isoflurane, desflurane and sevoflurane
are acceptable for seizure disorders
 For epileptiform activity:
 Avoid Benzos, propofol, VA’s, barbiturates – suppress activity
 Use narcotics, Nitrous oxide, Droperidol, diphenhydramine or
Dexmedetomidine
 Accentuate activity with high-dose short acting opioids,
methohexital or etomidate but may cause intraop awareness
 Maintain muscle paralysis
 Despite GETA – patient may still have seizure activity
 Unexplained changes in heart rate, BP, increases in EtCO2
 Treat:
o barbiturate, propofol or Benzo – may cause somnolence,
hypoventilation, airway obstruction, apnea
o direct application of cold saline to brain

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 Neuro Pharm

 Esmolol (0.5 mg/kg): minimal effects on CBF and ICP;

o selective β1 antagonist; half-life 9 mins;
o useful to blunt SNS to DL and HTN on emergence (preferred to Labetolol-less
bradycardia);
o crosses BBB;
o used by itself for management of thyrotoxicosis, PIH, cocaine toxicity;
o metabolized by plasma esterases and is independent of organ function
Nicardipine: can increase CBF and ICP by direct cerebral vasodilation if MAP is maintained;
used in treatment of cerebral vasospasm
o 1,4 dihydropyridine CCB; treatment of angina, HTN, supraventricular arrhythmias
o Increase time Ca++ channels are closed
o Relaxation of arterial smooth muscle but not venous smooth muscle
o Significant reduction in afterload but not preload
o Greater peripheral vasodilation than with other CCB’s; Greatest coronary vasodilator of
all CCB’s
o No conduction changes, may be used with BB
o Side effects: Flushing, headache, and pedal edema
o Used for tocolytic, SAH management (Nimodipine more lipid soluble – better for brain),
prior to DL and pneumoperitoneum for hemodynamic management
Nitroprusside (0.3-10 mcg/kg/min): increases CBV and ICP
o Reduces peripheral vasoconstriction through arterial dilation
o Nipride is the prodrug while NO is the active drug
o Toxicity – Cyanide, Methemoglobin, thiocyanate
o Decreased SBP may cause renin release leading to higher blood pressure when infusion
stopped
Remifentanil: opioids cause minimal changes in cerebral hemodynamics and are useful in
blunting responses to intubation and craniotomy; intubation, placement of head pins and
craniotomy represent most stimulating periods but allows for rapid emergence
o Metabolized by hydrolysis by non-specific esterases, elderly 2x as sensitive
o Metabolite renally excreted
o Rapid onset (1 min), rapid offset (5-10 min), rapid steady state attainment (5-10 min)
o Minimal effect on ICP, modest effect on MAP
Propofol: decreases CBF and cerebral O2 demand; can produce isoelectric EEGs (500
mcg/kg/min); may reduce focal ischemic cerebral injury; ↑latency, no effect on amplitude of
SSEP’s;

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 o Isopropylphenol; 1% solution (10 mg/kg); 10% soybean oil, 2.25% glycerol, 1.2% egg
lecithin
o Decreases rate of GABA dissociation from its receptor
o Antiemetic, antipruritic, anticonvulsant
o Clearance from plasma > hepatic blood flow
o Tissue uptake (possibly into lungs) important in transfer from plasma; Elimination t1/2 ~
1 hr
o ↓MAP > comparable amt of thiopental, Negative inotrope, Systemic vasodilation, Direct
myocardial depression, Resetting or inhibition of arterial baroreceptor tone
Geriatric Considerations

 Age-related changes in organ function highly variable

o Change significantly altered by activity level, social habits, diet, genetic
background
 CNS changes with aging
o Loss of neural tissue
o Decreased number of serotonin, acetylcholine & dopamine receptors
o Reduction in cerebral blood flow
o Decline in memory, reasoning, perception
o Disturbed sleep/wake cycle
 Liver metabolism may be age & gender specific
o Elderly men don’t metabolize benzos as well as women;
o Elderly women may have ↓ plasma cholinesterase
 Aging decreases brain size
o Neuronal attrition in gray matter
o Neurons that synthesize neurotransmitters (dopamine, norepi, tyrosine, serotonin)
most affected
o CBF decreases proportionately w/brain size; Autoregulation maintained
 Comprehension & long-term memory maintained
o ↓ short-term memory, visual/auditory reaction time
o Impaired cognition may be secondary to Hypothalamic Pituitary Axis
deregulation, ↑ cortisol leading to ↑ cognitive decline w/ ↓CNS tissue & ↓ NT
 MAC requirements decrease linearly w/increasing age
 Thought to be neurophysiologic (pharmacodynamics) rather than
pharmacokinetic response
 ↓ MAC parallels ↓ brain NT activity
 EEG:
o Aging ↑ brain sensitivity to injected drugs
o Median effective concentration to produce same effect in old vs young pts not
changed

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 Elderly pts less likely to experience PONV
 More likely to experience mental confusion following outpatient surgery
o Return of cognitive function to preop level may require 5-10 days
o ↓CNS functional reserve d/t anesthetics affecting metabolic & neurotransmitter
functions of neuronal tissue
 Most common cause for delayed emergence
o Too much anesthesia or too many anesthetic drugs
o Nerve palsies secondary to regional anesthesia more frequent in elderly
 Post-operative Delirium of Elderly – Acute disorder of attention and cognition
o Can be superimposed on dementia or other neurological disorders
o Course varies considerably & depends on resolution of causative factors
 Aging process in brain
 Structural brain disease
 ↓ capacity for homeostatic regulation
 Resistance to stress, visual/hearing impairment, high prevalence of chronic
disease,
 ↓ resistance to acute disease
 Age-related changes in pharmacokinetics, dynamics
 Precipitants: Sleeping disorders, sensory deprivation or overload,
psychological stress from bereavement/relocation to unfamiliar
environment
o Recommendations to ↓ delirium:
o Minimize # medications used
o Avoid hypoxemia, extremes of ↓/↑ PaCO2
o Provide adequate postop analgesia

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 Neuro Review

Terminology review;

 Circle of Willis: provides collateral blood flow to brain if major vessel becomes
obliterated, middle cerebral art, internal carotid art, and basilar art.
o Stump pressure: pressure transmitted through Circle back to carotid artery for
which a carotid endarectomy is done. >60mmHg means brain perfusion adequate
during procedure
o
 Autonomic Dysreflexia: Injury T6 or above, unopposed sympathetic discharge below
injury
 Stimulus -> afferent NS-> massive sympathetic response causing widespread
vasoconstriction and elevated BP-> Baroreceptors detect HTN crisis-> signal brain to
slow HR, descending inhibitory signal blocked at spinal cord
o Spinal anesthesia especially effective in prevention
o Goal prevention, 1st line treatment remove noxious stimuli
o Deepen anesthesia
 Spinal Shock: sudden transection of cord, vasodilate secondary to SVR, hypotension,
bradycardia unopposed parasympathetic, hypothermia
 Ventral roots Motor Efferent
 Dorsal roots Sensory Afferent
 Basal Ganglia: primarily crude motor movements, damage here can cause
 RAS: influence attention, motivation, keeps brain conscious, circadian rhythms
controlled by internal clock in suprachiasmatic nucleus. Sleep 2 stages –REM –Slow
wave
o Damage to RAS can cause coma associated with decerebrate and decorticate
posturing
o Delta waves: deep sleep anesthesia
o Theta waves: General anesthesia
o Alpha waves: during sedation, resting awake adult
o Beta waves: during light anesthesia, during concentration
 Cerebral Blood Flow: 750ml/min, 15% of cardiac output
o Brain tissue; 50ml/100g of brain tissue/min
o CBF: CPP/CVP
 CPP: MAP(CVP/RAP) – ICP use whichever is higher between CVP and ICP
 CSF; total volume 150mL, produced at ~30mL/hr
 Autoregulation MAP 50-150
 CMRO2 and CBF coupled
o Increased CMRO2; hyperthermia, seizures, shivering
o Decreased CMRO2; hypothermia, anesthetics

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 Hypoventilation-> increase C02->lower pH(acidic)->increase CBF r/t vasodilation-
>lower seizure threshold (Ketamine increased CBF and ICP)
 Hyperventilate->lower C02->increase pH (alkalotic)->decrease CBF r/t vasoconstriction
(why neuro pt’s hypervent)->increase seizure threshold
 ICP 5-15 A waves of Plateau waves seen with elevated ICP, Cushing’s low HR, HTN,
ireg RR- Mannitol, corticosteroid, hyperventilate, HOB up
 Reverse Steal ( robin hood) damaged ischemic areas vessels have no tone and are
maximally dilated all the time in an attempt to increase perfusion to the area
 Steal Syndrome (luxury perfusion) when a vasodilator is given or hypoventilation and
increase C02 causes dial. The healthy area of brain responds and vasodilates increasing
perfusion to healthy and decrease perfusion to already ischemic area
 Total Body Water: ICF- 40% (28L), ECF 20% (14L) TBW decreases with age
 Adrenergic NT Epi 80% Norepi 20%, 1st step in cessation of adrenergic receptor
stimulation is diffusion of norepi away. Effects terminated by reuptake, metabolism,
diffusion
 GABA is the receptor for Chloride
o Major NT inhibitor in CNS (Glycine in spinal cord)
o Major post synaptic inhibitor is Chloride
o **Cystic Fibrosis: defect in Chloride transport, Autosomal recessive
 Autosomal recessive: abnormal genes from both parents 25% recurrent
o CF
o Phenylketonuria: metabolic disorder toxic build up
o Sickle cell anemia
 Autosomal Dominant: 1 abnormal gene in pair 50% recurrent parent usually has disease
o Neurofibroma
o Huntington’s disease: defect in basal ganglia (similar. to Parkinson’s but with
intellectual deteriation)
 X-linked: mainly on X Chromosome M>F
o Hemophilia A, B
o Muscular dystrophy
 Downs Syndrome: trisomy 21
o Hypotonia, macroglossia: big tongue, micrognathia: short neck crowed face,
laryngomalacia: soft immature cartilage of larynx, cardiovascular shunts 40%,
always check cervical ROM

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 Dermatomes:
o Sympathetic block 2 above Sensory
o Sensory Block
o Motor Block 2 below Sensory
 C5: thumb
 C8: pinkie fingers numb
 T2: clavicle
 T4: Nipple line
 T6: Xiphoid
 T10: Umbilicus
 S3: Pubis
 T5-6 or higher ->hypotension
 T10-L1 early labor pain, S2-4 late
 C 3, 4, 5 keeps the diaphragm alive
 T 1, 2, 3, 4 keeps the Heart rate more
 Motor is the last to go and the first to come back
 CRPS Chronic Regional Pain Syndrome
o Sympathetically mediated, so relieved by sympatholytic drugs or nerve blocks,
can do epidural post op for pain control
 Type 1 Reflex Sympathetic Dystrophy: affects extremities after trauma,
no underlining peripheral nerve damage
 Type 2 Causalfia: diagnosable nerve damage, occurs after a high velocity
injury (GSW), or from uncontrolled post op pain, more serious
 Chronic pain: sensitization repetitive stimulation of dorsal root
leading to increase frequency of discharge. Receptor: NMDA
 Somatic: Motor, Conscious, Skeletal muscle, no synapse
o Single neuron from CNS terminates in skeletal muscle
o Always excitatory and cause contraction
o Nicotinic/Muscarinic receptors
 NT: Ach
 Autonomic: Smooth Muscle, Unconscious, endocrine
o Autonomic ganglion synapse, para/sympathetic

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 Sympathetic
o Adrenergic, Receptors are G protein coupled
 Alpha :
 Beta
o NT
 ??Ach: sympathetic postganglionic neuron to sweat glands and muscles
 Norepi : sympathetic postganglionic neuron to viscera hear lung smooth
muscle
o Thoracolumbar: pathways originate in the thoracic and lumbar regions
o Effects Motor efferent, preganglionic nerves originate in itermediolateral horns of
the **gray matter T1-L3 sympathetic
 Parasympathetic
o Cholinergic receptors on cell bodies of para/sympathetic postganglionic neurons,
motor end plate
 Muscarinic (antagonist Atropine, Scopolamine)
 Nicotinic
o NT
 Ach
o Craniosacral: preganglionic arise from CN 3 oculomotor ,7 facial ,9
glossopharyngeal ,10 vagus (75% of all PNS fibers)
o SLUDD, 3 decreases HR, diameter of airway and pupil
 Up/Down Regulation:
o Up: increase number of receptors to be able to be more responsive and receive as
much stimuli as possible. Beta Blocks, Denervation
o Down: decrease number of receptors r/t continuous abundance of stimuli Ex.
Pheochromocytoma
 Horner’s Syndrome: blockade of stellate ganglion with LA. Can be side effective
interscalene or supraclavicular brachial plexus
o S/Ipsilateral (same side) Ptosis(droopy eye), Miosis (constricted Pupil), flushed
 Myofibrils
o **Thick
 Myosin
o Thin
 Actin
 Troponin
 Tropomyosin

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 o Actin Myosin cross bridge movement
 Calcium binds with troponin which displaces tropomyosin that is blocking
myosin site
 Actin and myosin now have a direct path to each other and the muscle
contracts
o Muscle fibers store energy for contraction in the form of Phosphocreatine
o Calcium: Skeletal released from sarcoplasmic reticulum, Smooth muscle Ca
diffuses in from ECF
o Fast Twitch: Oxidative-glycolytic Fiber, most fatigue resistant
o Isotonic Contraction: creates force and moves a load
 Reflexes
o Autonomic: polysynaptic, smooth and cardiac muscle
o Somatic: Monosynaptic, skeletal, stretch, flexion
o Spinal: no brain in put
o Cranial: integrated within brain
 Spinal Cord ends at L1 in most adults
o T12 in 30% and L3 in 10%
 Inhibitory Neurotransmitters
o Spinal Cord: Glycine,
o CNS: GABA
 Skin
o Epidural Space (subatmospheric pressure)
o Dura mater
o Subdural space
o Arachnoid mater
o Subarachnoid space
o Pia mater
 Adamkiewicz: largest artery supplying spinal cord, 75%, thoracolumbar T8 to conus.
o Ischemia to this region can cause paraplegia during a AAA
 Monro-Kellie Doctrine : contents of cranial vault
o Blood, Brain, CSF -> pressure/volume relationship
 Spinal: decrease pain impulse to brain
o **Mu-2 (spinal opioid, analgesia by neuraxial opioid: morphine fentanyl,
sufentanil, Alfentanil) dominate receptor
 Supra spinal: alters pain, felt but not cared about, works on limbic, thalamus and
hypothalamus
o Mu-1 dominate receptor (kappa, delta)

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 Neuromuscular disorders;

Myasthenia Gravis:
Autoimmune mediated disease of NMJ
- postsynaptic Ach receptors destroyed
- Skeletal muscle weakness
‐ exacerbated by exercise, improved by rest
‐ abnormal thymus
Bulbar involvement my cause resp insuff and dysphagia
Myasthenia Syndrome: Eaton-Lambert
Acquired immune disorder of NMJ

‐ release of Ach from motor nerve terminal

Reduced
Frequently assoc with small cell lung CA
Exercise improves muscle function
DX: EMG
Patients are sensitive to both Succ and nondepolarizers
Where weakness may persist for days

Muscular dystrophy
Volatile anesthetics are associated with extreme elevations in CK,
Myoglobinuria, and cardiac arrest.
Succinylcholine & inhalation agents should be avoided

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Guillain Barre
Inflammatory polyneuropathy of motor, sensory, autonomic, and cranial nerves
Affected axons undergo lymphocyte infiltration and demyelination
IgM antibodies in myelin sheaths
Disease evolves over 3-4 weeks
Full recovery: 80%, 5% permanently handicapped, 3% relapse rate
Preceded by acute viral infection
Ascending, symmetric muscle weakness of lower extremities
Rapid progression to flaccid quadriplegia can occur
Proximal muscle pain & transient paresthesia common
Bulbar & respiratory muscles involved
Progression to respiratory failure, weakness of forced exhalation, impaired cough
Tracheostomy indicated early in course
Autonomic dysfunction can be severe in patients with quadriparesis & respiratory failure
Rx: supportive; Plasmapheresis; IV Ig

Duchene Syndrome: Coexisting problems

Cardiomyopathy
CK markedly elevated
Contractures and scoliosis
Respiratory insufficiency is the most common cause of death

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Avoid with MS
Succinylcholine – hyperkalemia in severe disease
Limit perioperative stress
Avoid hyperthermia
Spinal anesthesia may cause neurotoxicity (Epidural OK)

Pulmonary complications associated with neuromuscular disorders

Guillain-Barre: muscle weakness occurs early, is reversible
Myasthenia gravis: muscle weakness reversible with drugs
ALS: relentlessly progressive deterioration
Multiple sclerosis: relapsing respiratory muscle weakness

Mannitol:

 0.25-0.5g/kg
 osmotic diuretic agent and a weak renal vasodilator; filtered by the glomeruli of
the kidney but is incapable of being resorbed from the renal tubule, resulting in
decreased water and Na reabsorption via its osmotic effect; increased H2O and Na
excretion). This creates increased osmolality in the renal tubule. Free water
follows mannitol, diminishes Na reabsorption.

 Works at the Proximal tubule

 SE: hypokalemia, dehydration
 Contraindicated if the BBB has been disrupted since Mannitol may enter the brain
and bring fluid with it, increasing ICP. Mannitol may cause vasodilation of
vascular smooth muscle if administered too rapidly and cause increased ICP.
 Don’t give with an open head injury

457
Nicardipine (Cardene);

 0.5-2 mg IVP loading dose

 1-4mcg/kg/min
 Duration 10-15 min.
 Calcium channel blocker, treat vasospasms, HTN, supraventricular dysrhythmias
 Works on SA and AV nodes with minimal myocardial depression (so it can be used
with a BB)
 More arterial smooth muscle relaxation then venous
 The greatest vasodilating effects of all the CCB, vasodilation being prominent in the
coronary arteries
 NMB can be potentiated by CCB
Nitroglycerin (Nitrol);

 0.1-7 mcg/kg/min
 Peripheral vasodilator, coronary artery dilator, pulmonary vasodilation
 Generates NO which stimulates the production of cGMP to cause peripheral
vasodilation
 Control HTN during induction and emergence
 Duration 3-5 min.
Esmolol (Brevibloc);

 0.5-1.0mg/kg IVP
 50-300 mcg/kg/min infusion
 duration of action 10 minutes
 Beta 1 antagonist
 metabolized by plasma esterases
 Control HTN during induction and emergence

Brevitol (Methohexitol);

 1-2mg/kg IVP
 50-100 mcg/kg/min
 Works through interaction with GABA receptor, mimic GABA by directly activating
Cl- channels
 Depress RAS system
 Decrease ICP by decreasing cerebral blood volume (only in normal regions, not
ischemic ones) secondary to cerebral vasoconstriction and decreased CBF
 Can cause an isoelectric ECG
 Decreases cerebral CMRO2
 Can cause myoclonus

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 Neuro System

Anatomy/ Pathophysiology

 Neurons
o Unipolar  Sensory
o Bipolar  Interneuron
o Multipolar  Motor neuron
 Neuron action potential

 Divisions of the nervous system

 Cranial nerves

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 Circle of Willis – arterial supply to the brain
o Arise from the internal carotid artery and basilar artery
 Internal carotid – supplies 80% (anterior and
middle)
 Basilar artery - supplies 20% (posterior)

 Cerebral spinal fluid

o Production ~ 450 ml/day
o Turnover ~ 3 x per day
 Brainstem  midbrain, pons and medulla
o Midbrain contain optic nuclei and substantia nigra (produce
dopamine), crucial for fine motor movement and reward
o Pons  secondary respiratory centers
 Pneumotaxic center (inhibitory)  inhibits
inspiration and reduces respiratory rate

460
  Apneustic center (excitatory)  stimulates inspiration  respiratory rate
and tidal volume
 Herring-Breuer reflex  pulmonary stretch receptors  reduce
inspiration
o Medulla  contains primary respiratory centers
 Dorsal respiratory group (DRG)  controls inspiratory cycle (phrenic and
external intercostal nerves)
 Ventral respiratory group (VRG)  controls expiratory cycle (internal
intercostal nerves)
 Cardiac center
 Chemoreceptor trigger zone (CTZ) in the Area Postrema (controls
vomiting reflex)
 Triggers  hypotension, Ach, DA, 5-HT, histamine, substance P,
pain, anxiety, medications
 Vasomotor zone
 Spinal cord
o 31 spinal nerves:
 C1-8
 T1-12
 L1-5
 S1-5
 Co1
o Termination spinal cord:
 Adult ~L1, Dural sac ends at ~S2
 Children ~L3, Dural sac ends at ~S3
o Segmented into dorsal (sensory), itermediolateral (autonomic) and ventral (motor)
horns
o Blood supply  3 spinal arteries
 1 anterior spinal artery  supplies anterior 2/3
 2 posterior spinal arteries (supply posterior 1/3
 Rexed laminae
o I-II: Fibers A∂, C  for pain
and temperature
o III-IV: Fibers Aß, A∂  for
mechanoreceptors/proprioception
o V: Fibers Aß, A∂, C  for
mechanoreceptors
(proprioception), light pressure, 1˚
visceral input, wind-up
phenomenon
o VI: Fibers Aß, Aå  for

461
 o mechanoreceptors/proprioception
o VII: Fibers Aß, Aå  preganglionic SNS neurons
o VIII-IX: Fibers Aß, Aå  efferent motor output
o X: Fibers Aß, Aå  none
 Rami communication
o Grey rami communicates with all levels  unmyelinated postganglionic
sympathetic fibers (located medically)
o White rami communicates with T1 – L2  myelinated preganglionic fibers
(located laterally)
 Somatic reflex  3 neuron system
o 1st neuron  sensory (afferent)
o 2nd neuron  interneuron
o 3rd  motor (efferent)
 Autonomic nervous system  2 types of fibers
o Sympathetic (SNS)  adrenergic
o Parasympathetic (PSNS)  cholinergic

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Physiology

 Cerebral metabolic rate of oxygen consumption (CMRO2)

o Consumes ~20% of total body oxygen
o ~60% CMRO2 is dedicated to production of ATP for neuronal activity
 ATP stores depleted in 3 – 8 min
o CMRO2 ~50 ml/min (3 - 3.5 ml/100g/min)
o Brain glucose consumption ~ 5 mg/100g/min
 Cerebral blood flow (CBF)  parallels CMRO2
o CBF ~15 – 20% CO
o CBF ~750 ml/min (50 ml/100g/min)
 CBF 20 – 25 ml/100g/min  slowing of EEG
 CBF 15 – 20 ml/100g/min  isoelectric EEG
 CBF < 10 ml/100g/min  irreversible brain damage
 Intracranial pressure (ICP)
o Normal ICP ~ < 10 mmHg
o S/S of elevated ICP: HA, N/V, LOC ∆, papillary ∆, high-pitched cry
 Cerebral perfusion pressure (CPP)
o CPP = (MAP – (ICP or CVP))
o CPP normal ~ 80 – 100 mmHg
 CPP < 50 mmHg  slowing of EEG
 CPP < 25 – 40 mmHg  isoelectric EEG
 CPP < 25 mmHg  irreversible brain damage

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 Cerebral autoregulation
o Occurs between 50 – 150 mmHg
 Respiratory effects on autoregulation
o PaO2 < 50 mmHg  vasodilation and increased CBF to preserve O2 and glucose
supply
o PaCO2 > 80 mmHg  vasodilation and increased CBF to preserve O2 and
glucose supply
 For every 1 mmHg increase in PaCO2, CBF increases 1 – 2 ml/100g/min
 Temperature effects on autoregulation
o Every 1˚C increase in temperature, CBF increases 5 – 7 ml/100g/min
o Every 10 ˚C increase in temperature, CMRO2 doubles
 > 42˚ C  O2 activity  cell damage
o Cooling  decreases CMRO2 and CBF
 20˚C  isoelectric EEG
 Cerebral ischemia
o Cerebral steal syndrome (Luxury Perfusion) – causes redistribution of CBF from
ischemic areas to nonischemic areas
 Detrimental during focal ischemia
 Vasodilators (SNP, hydralazine) and hypoventilation (increase PaCO2 and
acidosis) promote cerebral steal
o Inverse steal (Robin Hood/Reverse Steal)
 Ischemic areas are maximally dilated to improve blood flow
 Causes redistribution of CBF from nonischemic to ischemic areas
 Beneficial during focal ischemia
 Hyperventilation reduces PaCO2, causing alkalosis which increases SVR,
shunting blood to ischemic areas
 Cerebral protection
o Reduce CMRO2  barbiturates, etomidate, propofol, volatiles
 Barbiturates are the drug of choice for focal ischemia
o Ensure adequate profusion
o Control cerebral edema
 Mannitol 0.5 – 1 g/kg IV +/- furosemide 10 – 20 mg IV
 Avoid hyperglycemia  exacerbates cerebral edema
 Ideal glucose 70 – 110 mg/dl
o Reduce ICP
 Avoid increased PaCO2, which will increase cerebral steal
 Ideal PaCO2 30 – 35 mmHg
 Ideal EtCO2 27 – 30 mmHg
 Head midline to maintain venous drainage
 Control HTN

464
 o Hypothermia is most effective protective mechanism during both local and global
ischemia
 Every 1˚C reduction temperature  7% reduction in CMRO2
o Reduce seizure potential – barbiturates, benzodiazepines, phenytoin
o Ketamine may be beneficial due to blocking glutamate activity at NMDA
receptors
o Nicardipine and Nimodipine reduce neurologic injury following hemorrhage and
ischemic CVA, but do not improve outcomes
o Methylprednisolone reduces neurologic injury if given within 8 hours of SCL
o Mg++, Dexmedetomidine, dextromethorphan and vit E may also be protective
Central nervous system and aging

 Brain mass begins to decline slowly beginning at ~ age 50 and decreases more rapidly
later, such that an 80-year-old brain has typically lost 10% of its weight.
 Neurotransmitter functions suffer more significantly, including dopamine, serotonin, g-
aminobutyric acid, and especially the acetylcholine system.
 Response time’s increase, and learning more difficult, but vocabulary, “wisdom,” and
past knowledge better preserved.
 Individuals age 85 and older, nearly half have significant cognitive impairment
 The aged brain does make new neurons and is capable of forming new dendritic
connections
 Implications to practice:
o Approximately 6% decrease in MAC per decade after age 40
o Age is a major risk factor for postoperative delirium and/or cognitive decline
 Potentially related to exacerbation of central cholinergic insufficiency by:
narcotics, sedatives, anticholinergics
 Additional contributory factors: stress of surgery, fever, pain, emesis,
sleep deprivation, loss of routine
 Pre-existing conditions that predispose the patient to postoperative
cognitive dysfunction:
 Advanced age
 Lower educational levels
 Stroke
 Cognitive abnormalities
 Organic brain syndrome (i.e. Dementia)
 Hearing/visual impairment
 High ASA physical status – Comorbidities
 Lack of stress response to surgery
 Post-operative cognitive dysfunction (POCD) generally evident during 1st
to 3rd day postoperatively

465
  Persistent POCD suggests perioperative injury to the brain resulting in
prolonged cognitive dysfunction
 The rate of cognitive decline is positively correlated with the risk of
mortality  with rapid decline associated with the highest death rates
o Other pertinent brain aging phenomenon is pharmacodynamics  in which case
the target organ is more sensitive to a given drug tissue level, or the cause can be
pharmacokinetic, in which case a given dose of drug commonly produces higher
blood levels in older patients
Pharmacology

 Volatile agents
o All volatile agents  dose-dependent reduction in CMRO2
 Isoflurane (50%) > sevoflurane > desflurane > halothane (< 25%)
o All volatile agents  vasodilate  increase CBF through the brain
 Halothane (200%) > sevoflurane > desflurane > isoflurane (20%)
o Cerebral steal: volatiles increase CBF to normal areas, but not ischemic areas,
which is detrimental during focal ischemia
o Halothane reduces reabsorption of CSF  increased ICP
o Isoflurane reduces CSF production  reduces ICP
o Desflurane increases ICP more than the other volatile agents
o N2O has minimal effects on CMRO2, CBF, and ICP when used as adjunct
 Methohexital (Brevitol)  Barbiturates
o MOA: produce their sedative-hypnotic effects through an interaction with the
inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the CNS.
GABAa receptors consist of up to five glycoprotein subunits. When GABAa
receptors are activated, transmembrane chloride conductance increases, resulting
in hyperpolarization of postsynaptic cell membranes and functional inhibition of
postsynaptic neurons. The interaction of barbiturates with specific membrane
components of GABAa receptors appears to decrease the rate of dissociation of
GABA from these receptors, thereby increasing the duration of the GABAa-
activated opening of chloride channels
o Clinical use: produce hypnosis and raise seizure threshold (reduce seizure
potential), may be used to create an isoelectric EEG
o Robin Hood Syndrome (inverse steal)  redistribute CBF from normal to
ischemic areas  is beneficial for focal, but not global ischemia
o Assist with reabsorption of CSF
o May block Na+ channels and reduce influx of Ca+, as well as scavenging free
radicals and reduce free radical production

466
 Etomidate (Amidate)
o MOA: relatively selective as a modulator of GABAa receptors. Stereoselectivity
of etomidate supports the concept that GABAa receptors are the site of action of
etomidate. Etomidate is believed to exert its effects on GABAa receptors by
binding directly to a specific site or sites on the protein and enhancing the affinity
of the inhibitory neurotransmitter (GABA) for these receptors
o Potent direct vasoconstrictor that decreases CBF and CMRO2 35 – 45%
o Reduce CSF production and increase CSF reabsorption  additive reduction in
ICP
o Causes myotonic activity, but is not associated with seizure activity
o Small doses may activate seizure foci in epileptic patients
 Ketamine (Ketanest, Ketaset, Ketalar)
o MOA: binds noncompetitively to the phencyclidine recognition site on N-methyl-
D-aspartate (NMDA) receptors. Ketamine may also exert effects at other sites
including opioid receptors, monoaminergic receptors, muscarinic receptors, and
voltage-sensitive sodium and L-type calcium channels. Ketamine has only weak
actions on GABAa receptors. Inflammatory mediators produced locally by
compression of nerve roots can activate neutrophils that then adhere to blood
vessels and impair blood flow. Ketamine suppresses neutrophil production of
inflammatory mediators and improves blood flow. Direct inhibition of cytokines
in blood by ketamine may contribute to the analgesic effects of the drug
o Produces a dissociative amnesia
o CMRO2 remains unchanged
o Increased CBF (50 – 60%)  increased CBV  increased ICP
o May reduce CSF reabsorption  increasing ICP
o Seizure activity has been noted in the thalamic and limbic systems
 Succinylcholine (Anectine)
o MOA: SCh attaches to one or both of the alpha subunits of nAChRs and mimics
the action of acetylcholine (partial agonist), thus depolarizing the postjunctional
membrane. Compared with Acetylcholine, the hydrolysis of Sch is slow, resulting
in sustained depolarization (opening) of the receptor ion channels. Neuromuscular
blockade develops because a depolarized postjunctional membrane cannot
respond to subsequent release of acetylcholine. Sch has presynaptic effects, but
these are considered minor when compared with postsynaptic effects. Sustained
opening of receptor ion channels and resulting depolarization of postjunctional
membranes produced by SCh is associated with leakage of potassium ions from
the interior of cells sufficient to produce an average 0.5 mEq/liter increase in
serum potassium concentrations
o May experience HTN and histamine release  SCh, Atracurium, dTc  can
increase ICP
o Reduction of BP  lowers CPP
o Defasciculating doses of ND-NMBAs blunt the response to succinylcholine

467
 MEPs & SSEPs

Motor evoked potentials (MEPs)

 Evaluates the descending motor pathways – i.e. from the cerebral cortex, past the
neuromuscular junction, to peripheral muscle groups
 Stimulus is applied in a transcranial fashion over the motor cortex
o The deflection, is an electromyography signal, that is detected by electrodes
embedded in the muscle belly
o The signal is usually delivered as a rapid train of four or more stimuli
 Transcranial magnetic stimulation is obliterated under anesthesia
o Obliteration particularly with inhalation anesthetics - with reduce amplitude and
increase latency
o Some centers avoid muscle relaxants as to avoid compromise of the signal
 Bite block is mandatory to prevent injury to the tongue during transcranial stimulation
Somatosensory evoked potentials (SSEPs)

 A signal that is detectable on EEG and is generated in a time-locked fashion in response

to applied sensory input, typically a cutaneous electrical stimulation – i.e. of a peripheral
sensory nerve, but also of a cranial nerve with a sensory pathway
o An intact neural pathway from the periphery to the cerebral sensory cortex is
essential for a signal to be generated
o Summation followed by signal averaging of repetitive stimuli is necessary in
order to extract meaningful signals
o Stimulation is typically done in the regions of the median, ulnar, and posterior
tibia nerves to generate predictable and reliable signals
o Disruption of the neural pathway at any point will result in complete loss of SSEP
 A 50% decrease in signal amplitude is generally accepted as clinically
significant, as is a 10% increase in latency
o Avoid MAC > 0.5
 Brainstem auditory evoked potentials (BAEP)
o A standardized sound (click) is applied to the eighth cranial nerve via the auditory
apparatus.
o A recognized series of peaks are generated with respect to the integrity of various
parts of the auditory pathway
 Visual evoked potential
o Are generated via light stimulation of the retina
o Typically, goggles that emit LED lights are worn
o Useful to monitor the integrity of the optic nerve
o They are difficult to record in a consistent fashion during anesthesia

468
 Somatosensory Evoked Potentials & Motor Evoked Potentials

Sensory Evoked Potentials:

 Travel from periphery to the brain and can be recorded by electrodes placed over the
scalp and along the transmission pathway
 Normal response = conduction pathway intact
 Damaged pathway = ↓ amplitude & ↑ latency
 Classified according to nerve tract being evaluated
o Somatosensory Evoked Potentials (SSEP)
 Stimulation at peripheral nerve (median or post tib) and response recorded
over spinal cord (Spinal SSEP) or cerebral cortex (cortical SSEP’s)
 Monitors spinal cord function during spinal cord or vertebral column
surgery
 SSEP’s conducted through dorsal column of spinal cord = concerns about
ischemia to motor portion (anterior spinal cord) may lead to “wake-up”
test or more sensitive MEP’s
 Anesthetics:
 N2O, Volatile agents, Ketamine & Etomidate = ↓ amplitude & ↑
latency
 Barbiturates, Propofol, Fentanyl/Remifentanil are compatible with
effective monitoring of cortical SSEPs
o Brainstem-auditory evoked potentials (BAEP)
 Auditory stimulus to one ear, recorded in posterior fossa to avoid
brainstem or auditory (VIII) nerve damage
 Anesthetics:
 More resistant to depressant effects of VA’s than SSEP or MEP
 Barbiturates, Propofol, Fentanyl/Remifentanil are compatible with
effective monitoring

469
Motor Evoked Potentials (MEP)

 Motor impulses are generated by transcranial electrical stimulation and the evoked
responses are measured as a potential over the spinal cord below the surgical field and in
the muscle of interest
o May be more reliable than SSEP’s when monitoring the integrity of motor tracts
during spinal cord surgery (Ventral motor columns may be more susceptible to
ischemia than the posterior proprioceptive fibers)
 Anesthetics:
o N2O & Volatile agents can abolish motor evoked potentials (TIVA preferred, no
NMB’s)
Barbiturates, Propofol, Fentanyl/Remifentanil are compatible with effective monitor

470
 SSEPs- Somatosensory Evoked Potentials

 SSEPs assess the integrity of the dorsal column of the spinal cord
1. More precisely- the Cuneatus and Gracilis tracts of the dorsal-lemniscal
system
 So SSEPS assess Touch, Pressure, and Vibration- This is all SENSORY- Remember
SAD- sensory/afferent/dorsal
 What is the purpose of all this? SSEPS evaluate the INTEGRITY of the brain or spinal
cord during certain types of surgery
 Dorsal spinal cord integrity is assessed in spine operations, CEA, aortic surgery or
intracranial aneurysm repair.
 IF there is dorsal cord or brain ischemia- transmission of action potentials obviously goes
down- so there is decreased intensity and arrival of action potentials reaching cortex- so
SSEP will be altered.
 SSEP Anatomical Pathways
1. Tibia, median or ulnar nerves may be stimulated usually bilaterally, and the
SSEP recording is from the SCALP.
2. To record tibia nerve- the electrode at MIDLINE of scalp- TIBIAL-
MIDLINE
3. To record ulnar or median nerve- the electrode placed lateral to midline of
scalp- ULNAR or MEDIAN- LATERAL
4. IN all cases- Electrode placed peripherally and read centrally
 Measuring SSEP
1. Early peak of SSEP from DIRECT route- which is dorsal cord. Late peak of SSEP is
from INDIRECT route- Reticular activating system- RAS.
2. Latency and amplitude are measured are measured in SSEP monitoring- A decrease
in amplitude suggests damage, if there is increase in latency, this suggests damage.
 SSEP and Anesthesia
1. Volatiles increase latency, decrease amplitude
2. Hypotension bellows levels of cerebral autoregulation affect SSEP
3. Changes in PaCO2, since it affects cerebral blood flow- affects SSEP
4. Temperature of either extreme affect SSEP
5. PaO2 affects SSEP= changes in O2 delivery to neural structures.
 What drugs don’t affect SSEP?
1. Ketamine, etomidate, opiates, Precedex- have no to little effect
2. NMBs okay to use

471
 Motor Evoked Potentials- MEPS

 Used to monitor the ANTERIOR CORDS, and for any ischemia- the efferent motor
division.
 The most common technique- stimulation over motor cortex or c-spine with sensing over
popliteal nerve.
 Monitors electromyography signal- EMG
 Again MEPs evaluates descending motor pathways
 Types of stimulation
1. Transcranial- electric or magnetic
2. Train of electrical stimulation
3. Magnetic stimulation
4. Neurogenic- direct spinal cord stimulation
 Measurement
1. Measures amplitude- a 50% decrease is significant
 MEP Problems/Anesthetic Implications
1. Can’t use magnetic in OR- too large, not practical
2. Mastication muscles stimulated- use bite block
3. More sensitive to depression from volatiles- even a low MAC can obliterate signal
4. MEP is not affected by Etomidate, Ketamine, Opiates, Precedex
5. AVOID Inhaled anesthetics
6. TIVA Preferred- better signal results. Limit bolusing during critical monitoring
periods
7. NMB use is RARE. IF used- maintain T1 twitch height around 30%
8.
Visual Evoked Potentials- VEP

 LED lighted goggles are used- flashes of light are emitted.

 VEP monitors the optic nerve CN II integrity.
 Electrodes are over occipital, parietal, and central scalp
 May be useful if surgery is near optic nerve- such as trans-spheroidal approach to anterior
pituitary tumor.
 Rarely used.
 Problems
1. Highly variable- due to type of stimulation, part of retina stimulated, pupil dilation,
and patient’s attention level
 Anesthetic Implications
1. Most sensitive to changes caused by volatiles of all SEPs.
2. Increased latency, possible change in amplitude with VEPs.
3. Signals NOT affected by opiates, Precedex.
4. HIGH VARIABILITY- monitoring with any anesthetic technique difficult

472
 Brainstem Auditory Evoked Potentials- BAEP

 Peripheral stimulation through headphones or foam insert- clicking sound applied to ear
 Used to monitor CN VIII- Vestibulocochlear
 Useful in acoustic neuroma surgery, posterior fossa surgery, brainstem prognosis.
 Monitoring- Recording electrodes on ear lobe and top of head
 Measures amplitude, absolute and interpeak latencies.
 Problems
1. Use with brainstem monitoring, low sensitivity and specificity

 Anesthetic Implications
1. Barely sensitive to volatile anesthetics
2. Increased latency without affecting amplitude
3. NOT affected by Barbiturates, benzos, ketamine, propofol, N20, or NMBs
4. BAEPs ARE affected by hypothermia- prolongs interpeak intervals.
5. Low PCO2 exaggerates signal, increases latency

473
 Somatosensory evoked potentials

 Monitors the Dorsal side of spinal cord that carries the sensations of touch pressure and
vibration via a direct route up the ipsilateral side of the SC and crosses over in the
brainstem to the contralateral thalamus and primary sensory cortex.
o Reticular activating system is the indirect route of sensory information
 SAD; Sensory/Afferent/Dorsal
 SSEP’s monitor the integrity of the dorsal side of the sc during certainoperations such as
spinal surgery, carotid endarterectomy, aortic surgery or repair of intracranial aneurysms.
 Posterior cord ischemia or brain ischemia; transmission of impulses will be diminished,
reducing intensity and delaying the speed the action potentials reach the cerebral cortex.
 Tibia, Median or Ulnar nerves can be stimulated peripherally and the SSEP is recorded
form electrodes on the scalp
o Recording electrode is place midline to record tibia nerve and laterally for ulnar
and median nerve potentials
 Latency; the time it takes for the action potential to traverse the peripheral nerves, spinal
cord and inner brain structures before arriving at the cerebral cortex
 Decrease in Amplitude and an Increase in Latency  suggests that damage id occurring
in the neural pathway being monitored
o Alterations to amplitude and latency can be caused by…..
 Hypo and Hyperthermia
 BP (HoTN below levels of autoregulation)
 PaCO2 (via changes in CBF)
 PaO2 (reflection of the change in O2 delivery to neural structures)

 Volatile anesthetics; Decrease amplitude and Increase latency

o Keep under 0.5 MAC to decrease effect
o VEP; Visual EP; elicited by flashes of light, this monitors the integrity of the
optic nerve.
o BAEP; Brainstem Auditory EP; elicited by auditory clicks, this monitors the
integrity of CN VII
o Sensitivity to volatile anesthetic (most to least)
 VEP (“v” very sensitive)
 SSEP (“s” somewhat sensitive)
 BAEP (“b” barely sensitive)
 Drugs that do NOT affect SSEP’s; Ketamine, Etomidate, Opiates, Precedex, and NMB

474
Motor Evoked Potentials- MEPS

 Monitor the anterior (motor/efferent/descending) side of the SC

 Stimulation; motor cortex or c-spine
 Sensing; popliteal nerve.
 Types of stimulation
 Transcranial- electric or magnetic
 Train of electrical stimulation
 Magnetic stimulation
 Neurogenic- direct spinal cord stimulation
 Affected by volatile anesthetics! Even low MAC’s
 No NMB
 TIVA is the anesthetic of choice. Etomidate, Ketamine, Opioids and Precedex OK

Somatosensory Evoked Potentials & Motor Evoked Potentials

Sensory Evoked Potentials:

 Travel from periphery to the brain and can be recorded by electrodes placed over the
scalp and along the transmission pathway
 Normal response = conduction pathway intact
 Damaged pathway = ↓ amplitude & ↑ latency
 Classified according to nerve tract being evaluated
o Somatosensory Evoked Potentials (SSEP)
 Stimulation at peripheral nerve (median or post tib) and response recorded
over spinal cord (Spinal SSEP) or cerebral cortex (cortical SSEP’s)
 Monitors spinal cord function during spinal cord or vertebral column
surgery
 SSEP’s conducted through dorsal column of spinal cord = concerns about
ischemia to motor portion (anterior spinal cord) may lead to “wake-up”
test or more sensitive MEP’s
 Anesthetics:
 N2O, Volatile agents, Ketamine & Etomidate = ↓ amplitude & ↑
latency
 Barbiturates, Propofol, Fentanyl/Remifentanil are compatible with
effective monitoring of cortical SSEPs
o Brainstem-auditory evoked potentials (BAEP)
 Auditory stimulus to one ear, recorded in posterior fossa to avoid
brainstem or auditory (VIII) nerve damage
 Anesthetics:
 More resistant to depressant effects of VA’s than SSEP or MEP
 Barbiturates, Propofol, Fentanyl/Remifentanil are compatible with
effective monitoring

475
Motor Evoked Potentials (MEP)

 Motor impulses are generated by transcranial electrical stimulation and the evoked
responses are measured as a potential over the spinal cord below the surgical field and in
the muscle of interest
o May be more reliable than SSEP’s when monitoring the integrity of motor tracts
during spinal cord surgery (Ventral motor columns may be more susceptible to
ischemia than the posterior proprioceptive fibers)
 Anesthetics:
o N2O & Volatile agents can abolish motor evoked potentials (TIVA preferred, no
NMB’s)
Barbiturates, Propofol, Fentanyl/Remifentanil are compatible with effective monitoring

476
 Cardiac Review…

Equations;
CPP = aortic DBP – LVEDP
AKA  CPP = (driving pressure)-(impeding pressure)
SVR = (MAP – CVP) x 80
CO
CVP aka RAP
Measures resistance to Left heart
Normal range 900-1500 dynes/sec/cm-5
Not BP! It is an fxn of MAP and CO
PVR = (MPAP – PCWP) x 80
CO PVR: Pulmonary vascular resistance
MPAP: mean pulmonary artery pressure
PCWP or LAP (left atrial pressure)
Measures resistance to Right Heart
Cardiac Index
CI = CO .
Body surface area
Cardiac Output
CO = HR x SV
Stroke Volume (fxn of Preload, Afterload, and Intrinsic inotropic state)
SV = EDV - ESV
Ejection fraction
EF % = EDV – ESV x 100
EDV

477
Flow velocity
Q = ∆ Pressure
Resistance
Resistance affected byLength, Viscosity, RADIUS
Flow = CO

Afterload and Laplace: P = 2T/R

Is the tension, or force per unit of cross-sectional area in the ventricular wall during ejection
Is a function of ventricular size & arterial pressure
Changes during systole as the radius changes
The greater the wall thickness -the lower the afterload (protective measure of the heart)

 is a function of ventricular size & arterial pressure

 changes during systole as the radius changes
 Afterload: is a function inherent to heart muscle
 Both Intrinsic and Extrinsic
  NOT ABSOLUTE! IT IS DYNAMIC!!!
 The thicker the muscle the lower the afterload, it is nature’s way of protecting
the heart

FRANK-STARLING RELATIONSHIP

478
  Preload is the loading of the heart prior to ventricular filling.
 During early & mid-diastole, filling is rapid but passive. Late diastole filling is active
(atrial contraction, 15 -20%)

The FS relationship shows that up to a point, the more a sarcomere is stretched, the greater the
force of the contraction
NTG ↓ LVEDP = ↓ impedance of perfusing coronary arteries
Preload for L heart
↓preload and ↓curve

Right atrial pressure wave form analysis

 “a” wave atrial contraction (correlates with P waves)

 “x” wave atrial relaxation
 “c” wave  bulging of the tricuspid valve into the right atrium with its closure (end
of QRS, valve bulges b/c of back pressure with systole)
 “v” wave atrial filling during atrial diastole (while ventricle is contracting) (end of
T wave)
 “y” wave  atrial collapse due to passage of blood into the RV (before P wave)

479
What happens in complete heart block?
“A” waves dramatically increased “Cannon waves” because atrium is contracting against a
closed tricuspid valve
Tricuspid Regurgitation
”C” wave and “X” decent will be replaced by large + waves of regurgitation as blood flows
back into the R atrium during Ventricular contraction
? C not as positive, very pronounced V wave
What are canon waves?
Exaggerated waves associated with
Pressure in Atria increases when A and v contract at the same time
A, C, V, are the + waveforms where there is an ↑ in pressure within Atrium
This happens during…
Contraction
Filling
Valve closure

Myocardial Action Potentials

 In cell, change in membrane potential from Na+ influx & increased Ca++ causes
sarcoplasmic reticulum to release Ca++
 Ca++ binds w/troponin & tropomyosin
 Myosin & actin interact and cross-bridges between them bend, resulting in
contraction
 Relaxation involves return of Ca++ to sarcoplasmic reticulum

480
 o Absolute refractory period comprises phases 0, 1, 2, and part of 3
o Ability of non-pacemaker cells to become pacemaker cells in hypoxic
conditions=>>>arrhythmias
o True resting potential, like other cells
 Phase 4 – resting; open K+ channels, closed and L-type slow Ca++
channels, closed Na
 Phase 0 – depolarization; fast Na+ channels open, K+ channels closing
 Phase 1 – partial repolarization; outward K+ channel open
 Phase 2- plateau; L-type Ca++ slow inward channels open
 Phase 3 – repolarization; K+ increases, Ca++ channels inactivated

Myocytes:

 Initiation of muscle contraction by Ca++

 When Ca++ binds to troponin, tropomyosin is displaced
 Exposes binding site for myosin on actin
 Hydrolysis of ATP changes conformation of myosin head and fosters its binding
to an exposed site

Pacemaker cells action potentials

 Fast Na++ channels are absent

 Rapid phase 0 depolarization not observed in SA & AV nodal cells
 These cells characterized by increased automaticity from rapid spontaneous phase 4
depolarization
 Combination of reduced outward K+ flow and inward flow of Na+ and Ca++ via
specialized channels responsible for changes in membrane potentials
 Pacemaker cells
 No resting potential->spontaneous action potentials
 Slow inward Ca currents instead of fast Na channels for depolarization
 3 Phases
 Phase 4- pacemaker potential
 Phase 0-depolarization
 Phase 3- repolarization

481
  PHASE  PACEMAKER CELL  VENTRICULAR CELL

 0  Ca++ influx, some Na+  Na+ influx

influx

 1  Cl- influx, K+ efflux

 2  Ca++ influx, K+ efflux

 3  K+ influx  K+ efflux

 4  K+ efflux, slowing; Na+  Na+ efflux & K+ influx by the ATPase

influx, increasing
 Ca++ influx during last part
 ( these ionic movements are
responsible for spontaneous
depolarization= auto
rhythmicity

EKG findings in A/L/I/S MIs

o Anterior (LAD) Elevation – V3, V4
o Lateral (Circumflex) Elevation – V5, V6, I, AvL
o Inferior (RCA) Elevation – II, III, AvF
o Septal (LAD) Elevation – V1, V2

482
Pressure Volume Loops

Phase 1: N  O is ventricular filling during diastole. During early and mid-diastole, filling is
passive. In late diastole the atrium contracts and results in final end-diastolic volume. The
mitral valve closes as the end-diastolic pressure exceeds left atrial pressure

Phase 2: O  P is isovolumic contraction. The pressure inside the ventricle is progressively

rising without change in volume because the mitral and aortic valves are closed.

Phase 3: P  M is when ventricular pressure exceeds aortic diastolic pressure and the
aortic valve opens and ejection begins. At point M, the aortic valve closes.

Phase 4: M N is isovolumic relaxation when no change in volume in the left ventricle occurs
until the pressure inside the LV becomes less than the LAP.
Think about what happens to the point on the graph where the mitral valve opens and diastolic
filling begins when the LV has severe systolic, or diastolic dysfunction.

SV = EDV – ESV (width of the Pres. Vol. curve) SV on slide is 90

483
N  Mitral valve is open, ESV
N to O  Flow from LA to LV
O Mitral valve closes, S1, EDV
O to P  Isovolemic contraction (generating tension of muscle, no ∆ in volume)
P Aortic valve opens
P to M Ejection
M  Aortic valve closes, S2
M to N  Isovolemic relaxation
N  Mitral valve is open, ESV

484
 Aortic Regurgitation and Perianesthetic Considerations

Results from failure of aortic leaflet coaptation- by disease of the aortic leaflets or of the aortic
root.
Causes of leaflet abnormalities- infective endocarditis, rheumatic fever, bicuspid aortic valve,
and the use of anorexigenic drugs.
Causes of aortic root abnormalities- idiopathic aortic root dilation, hypertension induced
aortoannular ectasia, aortic dissection, syphilitic aortitis, Marfan syndrome, Ehlers-Danlos
syndrome, rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis.
Acute aortic regurgitation usually follows infective endocarditis, trauma, or aortic dissection.
Either congenital or due to rheumatic fever- (Valley, 2012).
Pathophysiology- Decrease in CO from regurgitation of some ejected SV from the aorta back
into the LV during diastole. Volume and pressure overload ensue from the regurgitated volume
back into the LV.

 Regurgitant volume depends on HR and the diastolic pressure gradient across the aortic
valve.
 Over time the LV will retain a large regurgitant volume, and there will be no room for
atrial volume.
 Left ventricular volume overload- large aortic valve orifice, increased pressure gradient
between left ventricle and aorta, with diastolic portion of cardiac cycle being prolonged,
resulting in bradycardia.
 Stroke volume is reduced from backward flow of blood into LV during diastole.
 Over time, eccentric LV hypertrophy – since the ventricle experiences a large increase in
volume with a small increase in pressure; LV compliance is large, but when massively
overloaded, is less compliant- leading to small changes in filling pressure making large
changes in preload/CO.
 ANGINA can occur in the absence of coronary disease from increased myocardial O2
demand in response to muscular hypertrophy and dilation, and reduction in blood supply
due to low diastolic pressures in the aorta.
 Ventricular function eventually deteriorates- LVEDP and end-systolic volume increase.
LV failure occurs LATE in disease process.
 Pulmonary congestion can occur with progressively increasing LVEDP.
 INITIAL SX are exertional dyspnea, orthopnea, and paroxysmal nocturnal dyspnea.

485
Severity of Aortic Regurgitation Graded by Echo:

Regurgitant jet width Mild 25-46% Moderate 47-64% Severe >65%

as percentage of
LVOT width
Regurgitant jet area Mild 4-24% Moderate 25-59% Severe >60%
as percentage of
LVOT area
Aortic diastolic flow None Holodiastolic
reversal retrograde flow in
the descending aorta
(LVOT- Left ventricular outflow tract)
Acute aortic regurg presents as the sudden onset of pulmon. Edema and hypotension,
reflecting CV collapse and pts have severe dyspnea, hypotension and weakness.

Chronic aortic regurg presents as CHF. Sx minimal if regurgitant volume is under

40% SV, but severe if it exceeds 60% of SV. Manifestations are diastolic murmur, best
heard at left sterna border. Widened pulse pressure, decreased diastolic pressure,
bounding peripheral pulses and mitral regurg.
Treatment- Chronic AR usually takes 10-20 years before symptomatic. Digitalis, diuretics
and afterload reducing with ACE-Is, for chronic condition. Will require surgery- AV
Replacement. Acute AR requires Inotropes and vasodilator, followed by early surgery as it
carries a high mortality rate.
Anesthesia Concerns-
1. Maintain normal HR (minimizes regurg) and keep SVR LOW (favors forward flow).
Bradycardia and increases in SVR will increase regurgitant volume.
2. Avoid tachycardia as this promotes myocardial ischemia- increased O2 demand,
decreased delivery.
3. Avoid myocardial depression.
4. Maintain preload. Too much volume may lead to pulmonary edema.
5. Spinal and epidural tolerated- so long as intravascular volume is maintained.
6. EXCESSIVE LV VOLUME LEADS TO PULMONARY EDEMA.

486
 Monitoring/Agents

 Large V-wave suggests mitral regurg secondary to dilation of LV. Arterial pressure
line reflects wide pulse pressures. The more distal the holodiastolic flow reversal is
detected, the more severe the regurgitation.
 Forane or Suprane (vasodilators) good choices as they reduce SVR
 OPIOID-BASED general anesthesia
 Pancuronium useful- prevents bradycardia
 Ephedrine, if vasopressor needed.

Bibliography
Morgan, G., Mikhail, M. S., & Murray, M. J. (2006). Clinical Anesthesiology. New York:
McGraw-Hill.
Sauvage, T. R., & Schaus, S. S. (2012). Valley Anesthesia Sweat Book. Clive: Valley Anesthesia.
Stoelting, R. K., & Hillier, S. C. (2006). Valvular Heart Disease. In R. K. Stoelting, & S. C.
Hillier, Pharmacology and Physiology in Anesthetic Practice (pp. 27-42). Philadelphia:
Lippincott Williams and Wilkins.

487
 Aortic Stenosis

Etiology;

 A progressive calcification and narrowing of a normal valve preventing the valve from
opening completely, often a process of aging.
 A contributing factor to developing Aortic stenosis (AS) is the presence of a bicuspid rather
that a tricuspid aortic valve. This produces turbulence that traumatizes the valve and
eventually leads to stenosis.
o AS develops earlier in life (30–50 years of age) in individuals with a bicuspid aortic
valve than in those with a tricuspid aortic valve (60–80 years of age).
 AS can be congenital, rheumatic or degenerative
 Less commonly due to hypertrophic cardiomyopathy, discrete congenital subvalvular
stenosis or rarely supravalvular stenosis
Pathophysiology;

 AS causes a chronic obstruction of the outflow path (chronically high afterload) of the left
ventricle (LV) due to decreased valve area
 The chronic high afterload requires an increase in the transvalvular pressure to maintain forward
flow resulting in concentric ventricular hypertrophy. The increased thickness of the LV and
septum decrease wall tension.
 Diastolic dysfunction; the result of increased ventricular muscle mass, fibrosis, or myocardial
ischemia
 Almost always associated with some degree of aortic regurgitation.
 Concentric LV hypertrophy  increased myocardial work to offset the increased afterload
increased myocardial oxygen demand Angina pectoris may occur in patients with AS despite
the absence of coronary disease.
 AS is almost always associated with some degree of aortic regurgitation.
 Myocardial oxygen demand increased due to ventricular hypertrophy and the delivery is
decreased because of compression of subendocardial blood vessels by the increased left
ventricular pressure.
 Patients with AS have an increased risk of perioperative mortality and of nonfatal myocardial
infarction regardless of the presence of risk factors for coronary artery disease.
 5 reasons why aortic stenosis causes ischemia
o Demand problem
 1. ⇑ Afterload
 2. ⇑ Muscle Mass (Laplace ↓ wall ten., ↑O2 demand)
 3. Vascular bed: muscle mass imbalance (↑ muscle but no ↑ vessels that supply it)
o Supply problem
 4. ⇑ time for systole (which ↓ time for diastole when LV is perfused)
 5. ⇑ LVEDP aka PCWP
 The normal valve area is 2.5 to 3.5 cm2
 Guideline for the severity of AS

488
 Valve area (cm2) Maximum aortic Mean pressure
velocity (mmHg) gradient (mmHg)
Mild 1.5-2 2.5-3.0 <25
Moderate 1.0-1.5 3.0-4.0 25-40
Severe 0.6-1.0 >4.0 >40
Critical <0.6
Symptoms/Diagnosis

 Triad of classic clinical symptoms of critical AS

o Dyspnea on exertion, angina, orthostatic or exertion syncope
o Onset of symptoms to death can average 2-5 years
 Physical examination
o Characteristic systolic murmur heard best in the aortic area (R sternal border, 2nd IC
space), which may radiate to the neck and mimic a carotid bruit.
o Chest radiography may show a prominent ascending aorta due to poststenotic aortic
dilation.
o The ECG may demonstrate left ventricular hypertrophy.
o Echocardiography with Doppler;
 Trileaflet versus a bileaflet aortic valve, thickening and calcification of the
aortic valve, decreased mobility of the aortic valve leaflets, left ventricular
hypertrophy, and systolic or diastolic dysfunction.
 Aortic valve area and transvalvular pressure gradients can be measured.
 Cardiac catheterization and coronary angiography may be necessary when the
severity of aortic stenosis cannot be determined by echocardiography.

Treatment

 Asymptomatic;
o Medical management; digoxin, sodium restriction, diuretics, annual monitoring
o Small risk of sudden death or rapid progression of symptoms
 Symptomatic
o Percutaneous balloon valvuloplasty; usually for younger patients with congenital or
rheumatic AS, but is an option for an older patient that is not a valve replacement
candidate.
o Valve replacement
 Mortality approaches 75% within 3 years after symptoms develop unless the
aortic valve is replaced.
Anesthetic management

 Maintain normal sinus rhythm and heart rate;

o Ventricular filling is severely impaired without an atrial kick. Loss of NSR may
produce a dramatic decrease in SV and BP.
o Tachycardia decreases the time for left ventricular filling and ejection and reduces
cardiac output as well as increasing oxygen demands.
o A decrease in heart rate can cause over distention of the left ventricle.
 Maintain afterload, prevent hypotension, increase preload to maintain SV.
o Hypotension reduces coronary blood flow and results in myocardial ischemia and

489
 further deterioration in left ventricular function and cardiac output.
o The reduced ventricular compliance makes the patient very sensitive to abrupt
changes in intravascular volume.

Other anesthetic considerations;

 Epidural or spinal anesthesia is contraindicated in severe AS

 Epidural anesthesia is preferable to spinal because of its slower onset of hypotension and
may be tolerated by patients with mild to moderate AS.
 General anesthesia
o Induction;
 choose drugs that decrease systemic vascular resistance the least;
Etomidate, Ketamine and Benzo
 A primarily opioid based technique typically results in minimal cardiac
depression.
o Volatile anesthetic
 Carefully titrate the concentration to avoid myocardial depression,
vasodilation, or loss of NSR.
 May combine with nitrous oxide
o Interventions
 Junction rhythm or bradycardia glycopyrrolate, atropine
 Persistent tachycardia  β-antagonists such as esmolol
 Supraventricular tachycardia  promptly terminated with electrical
cardioversion.
 Hypotension alpha agonist Phenylephrine
 Monitoring
o ECG;
 Monitor for ischemia can be difficult due to baseline ST segment and T
wave abnormalities.
 Frequent ventricular ectopy often reflects ischemia
o Intra-arterial monitoring
o Pulmonary artery catheter
 Prominent a waves visible on PAWP waveform
 A higher PAWP is needed to maintain adequate LVED volume and
cardiac output.
o TEE
 Monitoring ischemia, ventricular preload, contractility, valvular function
and the effects of therapeutic interventions.

490
 References
Herrera, A. (2008). Valvular Heart Disease. In Stoelting’s Anesthesia and Co-Existing Disease
(5th ed., pp. 36-38). Philadelphia, PA: Churchill Livingstone.
Morgan, G., Mikhail, M. S., & Murray, M. J. (2006). Clinical Anesthesiology (4th Ed.). New
York: McGraw-Hill.

491
 AORTIC STENOSIS

 Common valvular lesion in US with and increasing incidence

 Two factors a/w development of AS
o Degeneration and calcification of the aortic leaflets leading to subsequent
stenosis; common process with aging
o Bicuspid vs tricuspid valve. AS develops earlier in life (ages 30-50) in those with
bicuspid valve vs those with a tricuspid valve (ages 60-80)
 Other causes include rheumatic heart disease and invective endocarditis.
 Pathophysiology
o Obstruction to ejection of blood into the aorta caused by a decrease in the aortic
valve area
o Requires an increase in LV pressure to maintain stroke volume

Normal AV Mild Moderate Severe AS

AS AS
Peak AV velocity (m/s) <1.7 <3.0 3.0-4.0 >4.0
Peak transvalvular gradient (mmHg) <36 36-64 >64
Mean transvalvular gradient (mmHg) <25 25-40 >40
Aortic valve area/AVA (cm2) >2.5 1.5- 1.0-1.5 <1.0/0.8
2.5

 Diagnosis
o Classic symptomsangina, syncope, and dyspnea on exertion
o About 75% of symptomatic pts will die within 3 years without a valve
replacement
o Systolic murmur, heard best in aortic area, may radiate to the neck and mimic a
carotid bruit
 Anesthetic considerations for pts with AS having non-cardiac surgery
o Pts often have accompanying CAD
o Anesthetic mgmt.
 General anesthesia is often preferred over epidural of spinal because of the
sympathetic blockade a/w regional can lead to significant hypotension
 Avoid hemodynamic changes that will decrease cardiac output
 Maintain NSR
 Avoid bradycardia or tachycardia
 Avoid hypotension
 Optimize intravascular fluid volume to maintain venous return and
left ventricular filling
 Induction

492
  IV drugs that do not decrease SVR
 Opioids useful with induction if LV function is compromised
 Benzos good
 Etomidate good
 Ketamine avoid, may cause tachycardia
 Maintenance
 Combo of N20/volatile/opioids
 Maintain SVR and cardiac output
 If LV function is impaired, avoid drugs that can cause additional
myocardial depression, use opioids alone in high doses or N2O
plus opioids
 NMB’s with minimal hemodynamic effects
 Maintain intravascular fluid volume, pts are preload dependent
 Treat hypotension with α agonists, phenylephrine, that do not
cause tachycardia, thus they maintain diastolic filling time
 Treat episodes of junctional rhythm or bradycardia with glycol,
atropine, or ephedrine.
 Treat persistent tachycardia with β blockers, esmolol
 Have lidocaine, amiodarone, and a defibrillator readily available as
these pts are prone to ventricular dysrhythmias.
 Base need for invasive monitoring on pts status and type of surgery
being performed.

493
 Aortic Stenosis/Regurgitation

AS Pathology
 Normal Aortic valve area 3.5-4 cm2
 Critical Aortic stenosis: valve area < 1.0 cm2
 Peak transvalvular pressure gradient can be > 80 mmHg
 LV wall thickness
 Concentric hypertrophy develops in response to ↑ afterload from outflow
obstruction due to decreased valve area
 compliance
 LVEDP
Causes
 Congenital
 unicuspid, bicuspid
 abnormal flow leads to fibrosis, calcification
 symptoms develop before age 30
 Rheumatic
 Tissue inflammation results in adhesion & fusing of commissures.
 abnormal flow leads fibrosis and calcification of leaflet
 symptoms develop between age 30-70
 Degenerative
 leaflets become inflexible 2o Ca++ deposition at bases
 most likely cause of Ao stenosis in pts > 70

5 reasons why aortic stenosis causes ischemia

Demand problem
1. ⇑ Afterload
2. ⇑ Muscle Mass (Laplace ↓ wall ten., ↑O2 demand)
3. Vascular bed: muscle mass imbalance (↑ muscle but no ↑ vessels that supply it)
Supply problem
4. ⇑ time for systole (which ↓ time for diastole when LV is perfused)
5. ⇑ LVEDP

494
AR Pathology
 Can be chronic or acute
o Chronic: long latent period
 Compensatory mechanisms fail  LV failure
o Acute: no compensatory mechanisms
 SOB, pulmonary edema, hypotension, CV collapse can occur quickly
o PE: hyper dynamic pulses w/ murmurs
 High-pitched early diastolic, diastolic rumble, S3
o May be due to valvular or aortic root anomalies
o
o Places volume load on LV
 Heart responds to increased diastolic pressure by fiber elongation and
replication of sarcomeres in series
 Leads to ventricular volumes
 Wall thickens and eccentric hypertrophy develops
o Chronic AR leads to huge ventricular volumes
 Handles large EDV & SV w/ little increase in LVEDP
 Ao pulse pressure widens

 LV SV due to regurgitant volume flowing back into the LV

 Magnitude of regurgitant volume depends on HR and pressure gradient across the
 valve
o – Tachycardia and peripheral vasodilation = less regurgitation
o – Bradycardia and high afterload = more regurgitation
 Maintain normal to high HR
 Often see a wide pulse pressure and bounding pulses

495
 Anesthesia management

AS Diastolic Dysfunction

-Can’t ↓ afterload because ↓ preload would cause ischemia

AR  need to help heart eject forward by ↓afterload which will improve forward flow

496
 Mitral Stenosis

Etiology:

 Most common cause: rheumatic heart disease

 Primarily affects females (two-thirds of patients)
 MS is typically a diffuse thickening of the mitral leaflets and subvalvular apparatus,
commissural fusion and calcification of the annulus and leaflets. This takes 20-30 yrs
after rheumatic heart disease.
 Thickening and calcification causes stenosis which leads to CHF, pulmonary HTN and
RV failure
 Symptoms typically include dyspnea on exertion, orthopnea and paroxysmal
nocturnal dyspnea as a result of high left atrial pressure
 LV contractility is usually normal unless MS is accompanied by mitral or aortic
regurgitation.
Pathophysiology:

 Normal mitral valve orifice area is 4-6 cm2. Symptoms usually develop when mitral
valve area < 1.5 cm2 or when area decreased by 50%
 MS is characterized by mechanical obstruction to LV diastolic filling from decrease size
of mitral valve orifice which leads to an increase in left atrial volume and pressure.
 Stroke volume decreases during stress-induced tachycardia or if effective atrial
contraction lost.
 Over time, MS leads to increased pulmonary venous pressure which leads to fluid in the
pulmonary interstitial space, decreased pulmonary compliance and increased work of
breathing and progressive dyspnea on exertion.
 Pulmonary vasculature changes result in pulmonary HTN and right sided heart failure.
 Acute episodes of pulmonary edema can occur with atrial fibrillation, sepsis, pain or
pregnancy.
Diagnosis:

 Echocardiography will show degree of leaflet thickening, calcification, and changes in

mobility, involvement of subvalvular apparatus, calculate mitral valve area and measure
transvalvular pressure gradient.
 If mitral valve area is < 1 cm2, a mean atrial pressure of 25 mmHg is needed for LV
filling and resting CO.
 Normal mitral transvalvular pressure gradient is < 5 mmHg, if > 10 mmHg suggests
severe MS. Pulmonary HTN will develop if pressure gradient >/= 25 mmHg over a
period of time

497
  Early MS has characteristic opening snap early in diastole or by diastolic murmur heard
at apex or in left axilla. Calcification and reduced leaflet mobility leads to snap
disappearance.
 On radiograph, one may see LA enlargement which is a straightening of the L heart
boarder and elevation of the left main stem bronchus.
 On ECG, broad notched P waves suggest LA enlargement. A-fib is present in about 1/3
of patients with severe MS.

Treatment:

 Diuretics to reduce LA pressure and relieve symptoms.

 Heart rate control for a fib with digoxin, BB, CCB’s, or a combination – rate control
critical as tachycardia impairs LV filling and increases LA pressure.
 Anticoagulation – with a fib and MS, risk of stroke 7-15%/yr. Target INR is 2.5 to 3.0.
 Surgically – may be fixed with percutaneous balloon valvotomy or surgical
commissurotomy, valve reconstruction or valve replacement.
Management of Anesthesia:

 Prevent and Treat events that may decrease CO or produce pulm edema with
cardioversion, amiodarone, BB, CCB’s or digoxin.
 Excess periop fluid administration, Trendelenburg, autotransfusion via uterine
contraction may precipitate CHF.
o Sudden ↓ in SVR with hypotension leads to reflex ↑ HR which ↓ CO.
o Maintain SVR with phenylephrine (preferred over Ephedrine d/t ↓ B agonist
activity), vasopressin (limited effects on pulm artery pressure)
 Hypercrabia, hypoxemia, lung hyperinflation or increased lung water may lead to
pulmonary HTN or RV failure
o RV failure can be supported with inotropes or pulmonary vasodilating drugs
Pre-operatively:

 Decrease anxiety and associated tachycardia cautiously as MS patients more susceptible

to ventilator depressant effects
 Anticholinergics not recommended preop d/t tachycardic response
 Continue rate control meds, treat hypokalemia, hypovolemia and continue anticoagulants
only if blood loss from surgery not expected.
 Neuroaxial anesthesia is acceptable in absence of anticoagulation.
o Epidural may be better than Spinal for MS patients due to decreased
sympathectomy and its associated symptoms (hypotension, decreased preload or
tachycardia).

498
Anesthesia Induction:

 Avoid Ketamine – increased heart rate

 Muscle relaxants – avoid those that cause tachycardia or hypotension from histamine
release (Succinylcholine, Pancuronium, Atracurium, Mivacurium)
 BB may be required to treat episodes of tachycardia during induction
Maintenance:

 Use drugs with minimal effects on heart rate, myocardial contractility or systemic and
pulmonary vascular resistance.

499
Mitral regurgitation and Management of Anesthesia

Causes

‐ Rheumatic fever
‐ Ischemic heart disease
‐ Papillary muscle dysfunction
‐ Mitral annular dilation
‐ Rupture of chordae tendinae
‐ Endocarditis
‐ Mitral valve prolapse
‐ Trauma
‐ Congenital heart disease
‐ Left ventricular hypertrophy
‐ Cardiomyopathy
‐ Myxomatous degeneration
‐ Systemic lupus erythematosus
‐ Rheumatoid arthritis
‐ Ankylosing spondylitis
‐ Carcinoid syndrome
Pathophysiology

‐ Decrease in forward left ventricular stroke volume and cardiac output

‐ Left atrial volume overload and pulmonary congestion
‐ MR produces a V wave on the pulmonary artery occlusion pressure waveform.
Changes in the V wave amplitude can assist in estimating the magnitude and direction
of changes in the degree of mitral regurgitation.
Management of Anesthesia

‐ Noncardiac surgery
o Prevention and treatment of events that may further decrease cardiac output
o Goal: improve forward left ventricular stroke volume and decrease the
regurgitant fraction.
 Maintain normal to slightly increased heart rate
 Bradycardia may result in severe left ventricular volume overload
 Increases in SVR->decompensation of the left ventricle
 Afterload reduction with a vasodilator such as nitroprudide
with or without an inotropic drug will improve left ventricular
function
 Regional anesthesia beneficial

500
Oculocardiac reflex

The oculocardiac reflex is a decrease in heart rate associated with traction applied to
extraocular muscles and/or compression of the eyeball. The reflex is mediated by nerve
connections between the ophthalmic branch of the trigeminal cranial nerve via the cilliary
ganglion, and the vagus nerve of the parasympathetic nervous system. Nerve fibers from the
maxillary and mandibular divisions of the trigeminal nerve have also been documented. These
afferents synapse with the visceral motor nucleus of the vagus nerve, located in the reticular
formation of the brain stem. The efferent portion is carried by the vagus nerve from the
cardiovascular center of the medulla to the heart, of which increased stimulation leads to
decreased output of the sinoatrial node. This reflex is especially sensitive in neonates and
children, particularly during strabismus correction surgery. However, this reflex may also occur
with adults. Bradycardia, junctional rhythm and asystole, all of which may be life-threatening,
can be induced through this reflex.

Treatment

The reflex can be blocked by injecting peribulbar or retrobulbar local anesthetics prior to
stimulation, or with intravenous injection of an anti-muscarinic acetylcholine (ACh) antagonist,
such as atropine or glycopyrrolate. If bradycardia does occur, removal of the stimulus is
immediately indicated. This often results in the restoration of normal sinus rhythm of the heart. If
not, the use of atropine or glycopyrrolate will usually be successful and permit continuation of
the surgical procedure. In extreme cases, such as asystole, cardiopulmonary resuscitation may be
required.

Cremasteric reflex

The cremasteric reflex is a superficial reflex observed in human males. This reflex is elicited
by lightly stroking the superior and medial part of the thigh regardless of the direction of stroke.
The normal response is an immediate contraction of the cremaster muscle that pulls up the
ipsilateral testis. More specifically, the reflex utilizes sensory and motor fibers of the
genitofemoral nerve, formed by fibers from both the L1 and L2 spinal nerves. When the inner
thigh is stroked, sensory fibers of the femoral branch of the genitofemoral nerve and the
ilioinguinal nerve are stimulated. These synapse in the spinal cord and activate the motor fibers
of the genital branch of the genitofemoral nerve which causes the cremaster muscle to contract
and elevate the testis. In boys, this reflex may be exaggerated which can occasionally lead to a
misdiagnosis of cryptorchidism. The cremasteric reflex may be absent with testicular torsion,
upper and lower motor neuron disorders, as well as a spine injury of L1-L2. It can also occur if
the ilioinguinal nerve has accidentally been cut during a hernia repair.

The cremasteric reflex can be helpful in recognizing testicular emergencies. The presence of the
cremasteric reflex does not eliminate testicular torsion from a differential diagnosis, but it does
broaden the possibilities to include epididymitis or other causes of scrotal and testicular pain. In
any event, if testicular torsion cannot be definitively eliminated in an expeditious manner, a
testicular Doppler ultrasound or exploratory surgical intervention is usually implemented to
prevent possible loss of the testicle to necrosis.

501
Vagal reflex

The vagal reflex refers to GI tract reflex circuits where afferent and efferent fibers of the vagus
nerve coordinate responses to gut stimuli via the dorsal vagal complex in the brain. The
parasympathetic vagus nerve carries signals from stretch receptors, osmorreceptors, and
chemoreceptors to dorsal vagal complex where the signal may be further transmitted to
autonomic centers in the medulla. Efferent fibers of the vagus carry signals to the GI tract up to
2/3 of the transverse colon. See occulocardiac reflex for s/s and treatment.

Chem 20: Normal Results

 Albumin: 3.9 to 5.0 g/dL

 Alkaline phosphatase: 44 to 147 IU/L
 ALT (alanine aminotransferase): 8 to 37 IU/L
 AST (aspartate aminotransferase): 10 to 34 IU/L
 BUN (blood urea nitrogen): 7 to 20 mg/dL
 Calcium: 8.5 to 10.9 mg/dL
 Chloride: 96 - 106 mmol/L
 CO2 (carbon dioxide): 20 to 29 mmol/L
 Creatinine: 0.8 to 1.4 mg/dL **
 Glucose test: 70 to 100 mg/dL
 Potassium test: 3.7 to 5.2 mEq/L
 Sodium: 136 to 144 mEq/L
 Total bilirubin: 0.2 to 1.9 mg/dL
 Total protein: 6.3 to 7.9 g/dL

Albumin- Low albumin (hypoalbuminemia) may be caused by liver disease, nephrotic

syndrome, burns, protein-losing enteropathy, malabsorption, malnutrition, late pregnancy,
artefact, genetic variations and malignancy. High albumin (hyperalbuminemia) is almost always
caused by dehydration. In some cases of retinol (Vitamin A) deficiency, the albumin level can be
elevated to high-normal values (e.g., 4.9 g/dL).

Alkaline phosphatase-

High level

 Biliary obstruction
 Bone conditions
 Osteoblastic bone tumors
 Osteomalacia
 Liver disease or hepatitis
 Leukemia
 Lymphoma
 Paget's disease
 Sarcoidosis
 Hyperparathyroidism

502
Low level

 Hypophosphatasia, an autosomal recessive disease

 Postmenopausal women receiving estrogen therapy because of osteoporosis
 Men with recent heart surgery, malnutrition, magnesium deficiency, hypothyroidism, or
severe anemia
 Children with achondroplasia and cretinism
 Children after a severe episode of enteritis
 Pernicious anemia
 Aplastic anemia
 Chronic myelogenous leukemia
 Wilson's disease

ALT

Significantly elevated levels of ALT (SGPT) often suggest the existence of other medical
problems such as viral hepatitis, diabetes, congestive heart failure, liver damage, bile duct
problems, infectious mononucleosis, or myopathy.

AST

AST may be elevated also in diseases affecting other organs, such as myocardial infarction, acute
pancreatitis, acute hemolytic anemia, severe burns, acute renal disease, musculoskeletal diseases,
and trauma

BUN

The main causes of an increase in BUN are: high protein diet, decrease in Glomerular Filtration
Rate (GFR) (suggestive of renal failure) and in blood volume (hypovolemia), congestive heart
failure, gastrointestinal hemorrhage,[3] fever and increased catabolism.

The main causes of a decrease in BUN are severe liver disease, anabolic state, and syndrome of
inappropriate antidiuretic hormone

Calcium

Common causes of hypocalcemia include hypoparathyroidism, vitamin D deficiency, and

chronic kidney disease. Symptoms of hypocalcemia include neuromuscular irritability (including
tetany as manifested by Chvostek's sign or Trousseau's sign, bronchospasm),
electrocardiographic changes, and seizures.

Causes of hypercalemia- Primary hyperparathyroidism and malignancy account for about 90% of
cases of hypercalcaemia. Also lithium use, familial hypocalciuric hypercalcaemia/familial
benign hypercalcaemia, hypervitaminosis D (vitamin D intoxication), renal failure, aluminium
intoxication, and milk-alkali syndrome

503
Chloride

Low levels- hypoventilation, chronic respiratory acidosis, vomiting, hyponatremia or elevated

bicarbonate concentration and cystic fibrosis.

High levels- Elevations in chloride may be associated with administration significant amounts of
IV normal saline, diarrhea, certain kidney diseases as type 2 renal tubular acidosis, type 1 renal
tubular acidosis, and overactivity of the parathyroid glands. Hyperchloremia is often comorbid
with diabetes or hyponatremia. Certain drugs, especially diuretics such as carbonic anhydrase
inhibitors, hormonal treatments, and polypharmacy, may contribute to this disorder.

Creatinine

High levels- kidney disease, dehydration, large muscle mass, large protein intake

Glucose

High levels- DM, Drugs- Certain medications increase the risk of hyperglycemia, including
corticosteroids, octreotide, beta blockers, epinephrine, thiazide diuretics, niacin, pentamidine,
protease inhibitors, L-asparaginase, and some antipsychotic agents. The acute administration of
stimulants such as amphetamine typically produces hyperglycemia; chronic use, however,
produces hypoglycemia. Some of the newer psychotropic medications, such as Zyprexa
(Olanzapine) and Cymbalta (Duloxetine), can also cause significant hyperglycemia. Critical
illness.

Potassium

High levels

 Renal insufficiency
 Medication that interferes with urinary excretion:
o ACE inhibitors and angiotensin receptor blockers
o Potassium-sparing diuretics (e.g. amiloride and spironolactone)
o NSAIDs such as ibuprofen, naproxen, or celecoxib
o The calcineurin inhibitor immunosuppressants ciclosporin and tacrolimus
o The antibiotic trimethoprim
o The antiparasitic drug pentamidine
 Mineralocorticoid deficiency or resistance, such as:
o Addison's disease
o Aldosterone deficiency
o Some forms of congenital adrenal hyperplasia
o Type IV renal tubular acidosis (resistance of renal tubules to aldosterone)
 Gordon's syndrome (pseudohypoaldosteronism type II) ("familial hypertension with
hyperkalemia"), a rare genetic disorder caused by defective modulators of salt
transporters, including the thiazide-sensitive Na-Cl cotransporter.

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Excessive release from cells

 Rhabdomyolysis, burns, or any cause of rapid tissue necrosis, including tumor lysis
syndrome
 Massive blood transfusion or massive hemolysis
 Shifts/transport out of cells caused by acidosis, low insulin levels, beta-blocker therapy,
digoxin overdose, or the paralyzing agent succinylcholine
 Box jellyfish venom
 Digoxin toxicity decreases sodium potassium ATPase activity preventing potassium from
entering cells.

Excessive intake

 Excessive intake with salt-substitute, potassium-containing dietary supplements, or

potassium chloride (KCl) infusion. Note that, for a person with normal kidney function
and normal elimination (see above), hyperkalemia by potassium intake would be seen
only with large infusions of KCl or oral doses of several hundred milliequivalents of KCl.

Low levels

‐ Inadequate potassium intake

‐ Gastrointestinal/integument loss
‐ Urinary loss
‐ Certain medications can cause excess potassium loss in the urine. Blood pressure
medications such as thiazide diuretics (e.g. hydrochlorothiazide) and loop diuretics
(e.g. furosemide) commonly cause hypokalemia. Other medications such as the
antifungal, amphotericin B, or the cancer drug, cisplatin, can also cause long-term
hypokalemia.
 diabetic ketoacidosis
 A low level of magnesium in the blood
 An increase in the pH of the blood
 Disease states that lead to abnormally high aldosterone levels can cause hypertension and
excessive urinary losses of potassium. These include renal artery stenosis and tumors
(generally nonmalignant) of the adrenal glands, e.g., Conn's syndrome (primary
hyperaldosteronism).
 Cushing's syndrome
 Rare hereditary defects of renal salt transporters, such as Bartter syndrome

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Sodium

High levels

 Hypovolemic
o Inadequate intake of free water associated with total body sodium depletion.
Typically in elderly or otherwise disabled patients who are unable to take in water
as their thirst dictates and also are sodium depleted. This is the most common
cause of hypernatremia.
o Excessive losses of water from the urinary tract, which may be caused by
glycosuria, or other osmotic diuretics - leads to a combination of sodium and free
water losses.
o Water losses associated with extreme sweating.
o Severe watery diarrhea
 Euvolemic
o Excessive excretion of water from the kidneys caused by diabetes insipidus,
which involves either inadequate production of the hormone vasopressin, from the
pituitary gland or impaired responsiveness of the kidneys to vasopressin.
 Hypervolemic
o Intake of a hypertonic fluid (a fluid with a higher concentration of solutes than the
remainder of the body) with restricted free water intake. This is relatively
uncommon, though it can occur after a vigorous resuscitation where a patient
receives a large volume of a concentrated sodium bicarbonate solution. Ingesting
seawater also causes hypernatremia because seawater is hypertonic and free water
is not available.
o Mineralcorticoid excess due to a disease state such as Conn's syndrome usually
does not lead to hypernatremia unless free water intake is restricted.
o Salt poisoning (this condition is most common in children).

Low levels

Hypervolemic hyponatremia —both sodium & water content increase: Increase in sodium
content leads to hypervolemia and water content to hyponatremia. Total body water and sodium
are regulated independently.

 cirrhosis of the liver

 congestive heart failure
 nephrotic syndrome in the kidneys
 massive edema of any cause

Euvolemic hyponatremia — there is volume expansion in the body, no edema, but hyponatremia
occurs

 states of severe pain or nausea

 in the setting of trauma or other damage to the brain
 SIADH (and its many causes)

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  Hypothyroidism
 Glucocorticoid (steroid) deficiency

Hypovolemic hyponatremia — the hypovolemia (extracellular volume loss) is due to total body
sodium loss. The hyponatremia is caused by a relatively smaller loss in total body water.

 any cause of hypovolemia such as prolonged vomiting, decreased oral intake, severe
diarrhea
 diuretic use (due to the diuretic causing a volume depleted state and thence ADH release,
and not a direct result of diuretic-induced urine sodium loss)
 Addison's disease and congenital adrenal hyperplasia in which the adrenal glands do not
produce enough steroid hormones (combined glucocorticoid and mineralocorticoid
deficiency)

Miscellaneous causes of hyponatremia that are not included under the above classification
scheme include the following:

 factitious hyponatremia (due to massive increases in blood triglyceride levels, extreme

elevation of immunoglobulins as may occur in multiple myeloma, and very high level of
blood glucose)
 Hypothyroidism and adrenal insufficiency (both thyroid hormone and cortisol are
required to excrete free water)
 Beer potomania and other malnourished states where poor dietary protein intake leads to
inadequate urine solute formation thereby impeding the kidney's ability to excrete free
water
 Primary polydipsia (where the amount of urine solute required to excrete huge quantities
of ingested water exceeds the body's ability to produce it; this typically occurs when 12
or more liters of water are ingested per day)

A prolonged period of exercise may be a cause.

Bilirubin

High levels

Mild rises in bilirubin may be caused by the following:

 Hemolysis or increased breakdown of red blood cells

 Gilbert's syndrome – a genetic disorder of bilirubin metabolism that can result in mild
jaundice, found in about 5% of the population
 Rotor syndrome: non-itching jaundice, with rise of bilirubin in the patient's serum,
mainly of the conjugated type.

Moderate rise in bilirubin may be caused by:

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  Pharmaceutical drugs (especially antipsychotic, some sex hormones, and a wide range of
other drugs)

Sulfonamides are contraindicated in infants less than 2 months old (exception when used
with pyrimethamine in treating toxoplasmosis) as they increase unconjugated bilirubin
leading to kernicterus.

 Hepatitis (levels may be moderate or high)

 Chemotherapy
 Biliary stricture (benign or malignant)

Very high levels of bilirubin may be caused by:

 Neonatal hyperbilirubinaemia, where the newborn's liver is not able to properly process
the bilirubin causing jaundice
 Unusually large bile duct obstruction, e.g. stone in common bile duct, tumor obstructing
common bile duct etc.
 Severe liver failure with cirrhosis (e.g. primary biliary cirrhosis)
 Circler–Najjar syndrome
 Dubin–Johnson syndrome
 Choledocholithiasis (chronic or acute).

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 Mitral Regurgitation/Mitral Stenosis
Mitral Stenosis
 Mechanical obstruction to left ventricular filling (which makes blood back up into the
lungs causing…)
 Increased pulmonary venous pressure
o – Pulmonary edema
o – Dyspnea on exertion
 Pulmonary hypertension when LA pressure chronically above 25 mmHg (massive LA)

 Increasingly rare due to better management of infections.

 Must ensure control of heart rate, because if you decrease the time for diastolic filling
of the left ventricle you will increase the volume of blood remaining in the left atrium and
increase the back-up into the pulmonary veins.
 These patients have a high incidence of biventricular failure.

Mitral Regurgitation
 Main patho: pulmonary venous pressure and ↑ right sided pressures
 LA volume overload, LA pressures become elevated
 ⇓ antegrade SV
 ⇑ LA size & LVH
 V wave on PCWP
 Much more common than mitral stenosis.
 Chronic
o Symptoms develop over time, s/s: dyspnea, easy fatigability, palpitations
o Inflammatory
 RHD, collagen vascular disease
o Infection
 Infective endocarditis
o Degenerative
 Myxomatous or calcific damage to valve
o Rupture

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 Acute
o L-sided CHF, SOB, orthopnea, shock, CP when MR assoc w/ CAD
o Ruptured chordae tendinae
 Infective endocarditis, trauma, acute rheumatic fever
o Rupture or dysfunctional papillary muscles
 Ischemia, MI, trauma, myocardial abscess
o Perforated leaflet
 PE: pan systolic regurgitant murmur
o Heard best at apex, radiates to axilla
o Possible S3
 Functional MR
o Associated with annular dilation & eccentric cardiomyopathy. The valve gets
stretched so they don’t touch in the middle and you get jet flow in the middle, can
go south quickly

 Will hear a holosystolic murmur at the apex.

 Treatment is afterload reduction & diuretics.
 MR is often associated with a fib.

510
ACC/AHA risk factors for perioperative cardiac events
A. Major –Cancel case if elective
1. Acute (<7 days) or recent MI (> 7 days and < 1 month)
2. Decompensated Heart Failure
3. Dysrhythmias
4. Unstable Angina
5. Severe Valvular heart disease
B. Intermediate
1. Mild Angina
2. Q waves
3. Compensated heart failure
4. Chronic renal failure (creatinine > 2.0)
5. Diabetes mellitus
C. Minor
1. Age > 70
2. EKG – LVH, LBBB, ST-T changes
3. Rhythm other than sinus
4. Low functional capacity
5. History of CVA
6. Uncontrolled hypertension
Most importantly current management considers whether or not the patient has potential for
residual myocardium to be at risk if surgery occurs. Current management also considers whether
or not the HF is adequately compensated if the patient
Sustained a large MI, as well as volume management considerations
 Is this patient at risk for perioperative HF and or ischemia????
 DBP => risk of ischemia
Stents
Types
a. Drug eluding stent
a. double anti-platelet therapy for 12 months
b. Bare metal stent
a. double anti-platelet therapy for 4-6 weeks at a minimum
Management of perioperative thrombolytic therapy

511
 o DO NOT have the patients with DES discontinue dual antiplatelet therapy
preoperatively if less than 12 mos. This MUST be managed by the cardiologist.
o If greater than 12 months recommendation is to continue aspirin.
o Elective non-cardiac surgery should be delayed for 4 to 6 weeks after an MI. Main
consideration should be – Is there still myocardium at risk?

CHF
 SNS activation (good short-term fix, bad in the long-run)
 arteriolar and venous constriction cause a reduction in renal blood flow
(RBF)
 reduced renal blood flow activates RAAS
 RASS causes increased absorption of sodium and water
 increased blood volume results in increased cardiac output by Frank-
Starling relationship
 Down-regulation of Beta receptors
o Increased levels of catecholamines (Nor Epi) are directly cardiotoxic and promote
myocytes necrosis and cell death (remodeling)
 Pathophysiologic changes assoc. with Heart Failure
o Myocardial changes
 Systolic dysfunction
 Diastolic dysfunction
o Neurohumoral changes
 SNS activation
 RAAS activation
 Vasopressin release
 Cytokine release
o Cellular changes
 Inefficient intracellular Ca++ handling
 Adrenergic desensitization
 Myocytes hypertrophy
 Reexpression of fetal phenotype proteins
 Cell death (apoptosis)
 Fibrosis
 Neurohumoral changes & CHF
o ↑ secretion of neurohormones (Epi, Aldosterone) & cytokines (proteins secreted
by macrophages with tissue injury)
 Interleukins and TNF-a involves in CHF
 Endothelin (vasoconstrictor) released from endothelial cells

512
 o Increased SNS activity early in CHF
 NE levels
o Reduced renal BP  release of renin, angiotensin II
 vasopressin release from post pituitary
 Cellular changes with CHF
o Delivery of Ca++ to contractile apparatus and Ca++ reuptake by sarcoplasmic
reticulum slowed
o a1 receptors important for induction of myocardial hypertrophy
 Levels of α1 receptors ↑ in CHF
o b1 receptor down regulation
 Downstream uncoupling of signal transduction pathway
 Up regulation of inhibitory G proteins
o In response to CHF hemodynamics, angiotensin II, TNF-α, norepi induce protein
synthesis
o Heart enlarged 2o continued hemodynamic stress
 CHF related changes in heart size/shape referred to as LV remodeling
 Mediated by apoptosis w/ holes left in myocardium, increased
interstitial fibrous tissue, and ventricular dilation
 RV failure
o Symptoms: pedal edema, abd pain
o Findings: + JVD; blue face
o Most common cause: LV failure. Also:
 Precapillary obstruction
 Congenital, e.g., shunts, obstruction
 Idiopathic pulmonary HTN
 1o RV failure
 RV infarction
 Cor pulmonale  Right sided HF, an enlargement of the RV due to Pulm
HTN
 Hypoxia-induced vasoconstriction
 PE
 COPD
o Elevated R sided pressure leads to fluid accumulation in systemic venous
circulation
o Venous congestion manifested by generalized edema (anasarca), ascites (fluid
collection in peritoneal space) & dependent edema (swelling of feet, legs)
o Hepato Jugular Reflex: Pressing on liver for ~ 5 sec can lead to blood
displacement into vena cava
 When increase in JVP, H-J reflux is seen
o Liver expansion from fluid accumulation causes distension of liver capsule w/
RUQ pain

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Hypertrophic Cardiomyopathy
 The left ventricle and interventricular septum hypertrophy and become stiff, non-
compliant and unable to relax during ventricular filling.
 As the ventricle’s ability to fill ↓ the pressure ↑ and LA and pulmonary venous pressures
rise.
 The LV forcefully contracts buy can’t sufficiently relax.
 The anterior leaflet of the mitral valve is drawn toward the interventricular septum as the
blood is forcefully ejected. Early closure of the out flow tract results because of the ↓EF
 Diastolic dysfunction is a result of the Hypertrophy,
o The muscle gets too thick and can’t relax and fill appropriately.
o This is what causes sudden death in athletes

Dilated Cardiomyopathy
 Results from damage to cardiac muscle fibers.
 The resulting loss of muscle tone grossly dilates all four chambers of the heart giving the
heart a globular shape
 LV is at risk with an elevated DBP because the vessel in the myocardium and
endocardium are compressed during systole secondary to the increased pressure
(impeding pressure/afterload) and the RV is supplied because it is pumping against a low
pressure system in the lungs

Myocardial Oxygen Supply: demand factors

o GOAL IS TO INCREASE SUPPLY & DECREASE DEMAND
Decreased Supply
 Decreased time for diastole
 Decreased diastolic pressure
 Decreased CO2
 Coronary artery spasm
 Anemia
 Hypoxemia
 Left shift on oxy-hemoglobin curve
 Increased preload (wall tension)
Increased Demand
 Increased heart rate
 Increased afterload
 Increased inotropy
 Aortic stenosis
 Left ventricular hypertrophy

514
o GOAL IS TO INCREASE SUPPLY & DECREASE DEMAND
 O2
 Make sure hemoglobin WNL
 Preload
 Nitro:
 1. Dilates coronary arteries
 2. Vasodilation ↓ preload (decreases preload by dilating venous
bed and decreasing the starling curve)
 Impeding pressure by EDV (impeding pressures) which will
increase coronary perfusion (CPP = Driving pres. – LVEDP
(imped. P)
 give high doses of nitro to lower LVEDV and give neo (Alpha
Agonist) to increase SVR if it drops too much
  decreases preload by dilating venous bed, starling's law will
increase SV and dilate coronary arteries to increase O2 to said
arteries, this will decrease the impeding pressure which will then
increase coronary perfusion pressure in endocardium
 Beta Blocker=> Heart Rate => demand=> time for coronary filling
 Aspirin  platelet aggregation


515
 Murmurs

Anesthetic management of aortic valve lesions

AS AR
Afterload Maintain SVR Decrease SVR
Preload Maintain EDV Restrict EDV
Heart Rate slow SR High normal
Inotropes No Yes (LV)
Go to drug Phenylephrine Dobutamine
Anesthetic Management of mitral valve lesions
MS MR
Afterload Maintain SVR &↓PVR ↓SVR & ↓PVR
Preload Tight control tight control
Heart rate slow normal High normal
Inotropes Yes (RV) Yes (LV)
Rescue Drug Phenylephrine Dobutamine

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Grade Description
Grade 1 Very faint, heard only after listener has “tuned in”. May not be heard in all positions
Grade 2 Quiet, but heard immediately after placing the stethoscope
Grade 3 Moderately loud
Grade 4 Loud with palpable thrill
Grade 5 Very loud with thrill. May be heard when stethoscope is party off the chest.
Grade 6 Very loud with thrill. May be heard when stethoscope is entirely off the chest

Extra Heart Sounds:

S4 - may be heard in such pathologic states as uncontrolled hypertension; described as
“Tenn-ess-ee” cadence
Pericardial Friction Rub – resembles squeaky leather and is caused by pericarditis; best heard at
left lower sternal border
S3 - “Ken-tuck-y” cadence
 Normal in childhood and physically active young adults, the third heart sound is felt to
arise from vigorous elastic recoil of the left ventricle in early diastole, causing the heart to
impact the chest wall
 The third heart sound is a physical sign specific for left ventricular failure due to a
dilated, hypocontractile LV or Mitral Regurgitation
 Origin of the third heart sound is thought to be the sudden cessation of early, rapid left
ventricular filling impelled by high left atrial pressure
 A brief period of exercise for the patient will augment the amplitude, making detection
easier

517
 Systolic Murmurs
Aortic Stenosis
Chronic obstruction to LV ejection results in concentric (thickened walls shrink LV) ventricular
hypertrophy
Makes heart susceptible to ischemia even in absence of CAD; Ventricle is stiff
Critical stenosis: 1. Mean transvalvular gradient > 50 mmHg
2. Aortic valve area <.8 cm2
Pathophys: Aortic stenosis usually occurs due to calcium deposits that narrow the valve, more
common in bicuspid valves; another cause is rheumatic fever, a condition that may develop after
strep throat or scarlet fever. Valve problems do not develop for 5 - 10 years or longer after
rheumatic fever occurs; AS occurs more frequently in males than females
Symptoms: usually occur later → breathlessness, dizziness, fainting, angina like chest pain
Mitral Insufficiency – “leaky valve”
Quite common, 20% of population > age 55, more common in females
Causes: Mitral Valve prolapse, rheumatic fever, marfan’s, Ischemic heart Dz, Degeneration
Acute phase- sudden rupture of a chorda tendinae or papillary muscle, ↑ LA volume leads to
pulmonary congestion
Compensated phase: LV develops eccentric hypertrophy, RA enlargement leads to ↓ pressure
and pulmonary congestion
Decompensated phase: Due to Ca++ overload of cardiac myocytes, leads to ↓ SV of LV and
CHF; dilated LV → worsens regurgitation; LVEF maintained until late decompensated phase
Symptoms: shortness of breath, coughing while lying flat, fatigue with activity, swollen feet or
ankles, heart palpitations, atrial arrhythmias

518
 Diastolic Murmurs

Mitral Stenosis

 You can hear the opening snap near the cardiac apex, or more easily along the lower left
sternal border.
 Main cause – valve scarring from rheumatic fever
 Produces mechanical obstruction to left ventricular filling leading to increased pulmonary
venous pressure
o Pulmonary edema
o Dyspnea on exertion
 Pulmonary HTN when LA pressure chronically above 25 mmHg
 S & S – fatigue, SOB, swollen ankles, coughing, hemoptysis, frequent URI’s
Aortic Regurgitation

 Results in eccentric (dilated) LV hypertrophy

 Heard best at left sternal boarder
 S & S – CHF (fatigue, SOB, swollen ankles), angina, fainting, arrhythmias or palpitations
 Causes – Congenital defects (uni or bi-leaflet valve), deterioration with age, endocarditis,
rheumatic fever, Diseases (Marfan’s, ankylosing spondylitis, syphilis), Trauma, HTN

519
 Cardiac Study Guide
Ischemic Heart Disease
Risk Factors – aging, male, hypercholesterolemia, HTN, cigarette smoking, DM, obesity,
sedentary lifestyle, family history

 Stable Myocardial Ischemia (Angina Pectoris)

o An imbalance between coronary blood flow and myocardial oxygen demand
o Partial occlusion or significant chronic narrowing of a segment of coronary artery
o Release of adenosine, bradykinin and other substances that stimulate cardiac
nociceptive and mechanosensitive receptors→afferent neurons converge with
upper five thoracic sympathetic ganglia and somatic nerve fibers in spinal cord to
produce thalamic and cortical stimulation → chest pain
 Also slow AV nodal conduction and ↓ contractility to improve
supply/demand balance
o Diagnosis: retrosternal chest discomfort, pain, pressure or heaviness that often
radiates to the neck, left shoulder or arm or jaw and occasionally to the back
 Stable – does not change in severity for two months
 Unstable – angina at rest, new onset or increasing severity without
increase in cardiac markers
 Pericarditis – sharp, retrosternal pain exacerbated by deep
breathing, coughing or change in position
 ECG – MI 12 lead shows ST segment depression
 Variant Angina (coronary vasospasm) shows ST elevation during
angina
 ECG most likely to indicate ischemia when there is at least 1 mm
of horizontal or down sloping ST segment depression during or
within 4 minutes after exercise
 Nuclear Stress imaging
 Use atropine, dobutamine or pacing to stress heart
 Coronary vasodilator (adenosine or dipyridamole) to see where
dilation does not occur (Atherosclerotic area)
 Echocardiography
 Wall motion analysis – either after exercise or stress
 Valvular function assessment

520
 o Treatment:
 Comprehensive Management
 ID and treat Dz that precipitates or worsens ischemia (fever,
infection, anemia, tachycardia, thyrotoxicosis, heart failure,
cocaine use)
 Reduce risk factors for CAD (↓ LDL, HTN)
 Lifestyle modification
 Pharmacologic management of angina (antiplatelet drugs, nitrates,
BB, CCB’s, ACEI)
 Revascularization by CABG or PCI with or without stents
 Acute Coronary Syndrome
o Hypercoagulable state – focal disruption of an athermanous plaque triggers the
coagulation cascade with subsequent generation of thrombin and partial or
complete occlusion of the coronary artery by a thrombus
 Chest pain with ST elevation on 12 lead ECG = STEMI
 Chest pain, ST depression or normal with elevation of cardiac markers =
NSTEMI or without cardiac marker change =unstable angina
o STEMI
 Nearly all are caused by thrombotic occlusion of a coronary artery
 Long term prognosis determined by: severity of LV dysfunction, presence
and degree of residual ischemia, presence of malignant V dysrhythmias
 Pathophysiology
 Atherosclerosis (inflammatory process) that ruptures creating an
environment that favors thrombogenesis
 Platelet monolayer forms at site of rupture, various chemical
mediators (collagen, ADP, epinephrine, serotonin) stimulate
platelet aggregation.
 Thromboxane A2 released (potent vasoconstrictor) and
Glycoprotein IIb/IIIa receptors activated followed by fibrin
deposition
 Diagnosis:
 Requires typical rise and fall of cardiac markers + one of the
following:
o Ischemic symptoms
o Development of pathologic Q waves on ECG
o ECG changes (ST elevation or depression)
o Imaging evidence of a new loss of viable myocardium or
regional wall motion abnormality
 Differential diagnosis – PE, aortic dissection, spontaneous
pneumothorax, pericarditis, cholecystitis
 S&S
 Anxious, pale, diaphoretic with tachycardia, HoT or dysrhythmias,
rales (CHF), murmur (ischemic mitral regurg)
 Labs – troponin (↑ within 3 hrs of myocardial injury for 7-10 days)

521
 o More specific than CK-MB
 Imaging – Echo if LBBB or abnormal ECG with uncertain MI
 Treatment
 Administer O2,
 pain relief and ↓ catecholamine release (IV morphine or SL
nitroglycerin),
 ASA or Plavix to further ↓ thrombus formation)
 BB – relieve ischemic chest pain, infarct size and dysrhythmias
 GOAL – reestablish blood flow in obstructed coronary artery ASAP
 Reperfusion therapy – thrombolytic therapy
 PCI – to open occluded vessel
 CABG – reserved for those in whom angiography reveals coronary
anatomy precludes PCI, patients with a failed angioplasty and
those with evidence of infarction related ventricular septal rupture
of mitral regurg.
 Adjunctive therapy – IV heparin, BB (↓ infarct size), ACEI
(anterior wall MI with LV failure, DM)
o Unstable Angina/NSTEMI
 Results from reduced myocardial oxygen supply d/t to 5 processes
 Rupture or erosion of coronary plaque that leads to nonocclusive
thrombosis
 Dynamic obstruction due to vasoconstriction
 Worsening coronary luminal narrowing due to progressive
atherosclerosis, in-stent restenosis, or narrowing of coronary artery
bypass grafts
 Inflammation (vasculitis)
 Myocardial ischemia due to increased O2 demand
 Microvasculature clot fragments lead to microcirculatory ischemia
and infarction that elevates cardiac markers but does not change
ST on ECG
 Diagnosis
 3 presentations:
o Angina at rest (> 20 min)
o Chronic angina pectoris that becomes more frequent
o New onset angina that is severe, prolonged, disabling
o Hemodynamic instability or CHF
 Treatment
 Directed at decreasing myocardial oxygen demand and limiting
thrombus formation
o Bed rest, supplemental O2, analgesia, BB

522
Complications of Acute Myocardial Infarction

 Cardiac Dysrhythmias
o Ventricular fibrillation (usually within 4 hours)
 Rapid defibrillation with 200-300 J necessary
 Amiodarone – most effective Ventricular antidysrhythmics
 BB early may prevent V-fib
 Hypokalemia is a risk factor for Vfib
o Ventricular tachycardia
 Sustained or hemodynamically significant – cardioversion
 Asymptomatic – IV lidocaine or Amiodarone
 ICD placement for recurrent Vtach
o Atrial Fibrillation and Atrial Flutter
 Occur in about 20% of patients after MI
 Precipitated by hypoxia, acidosis, heart failure, pericarditis, sinus node
ischemia
 Atrial ischemia or ↑ L atrial pressure d/t LV dysfunction
 If hemodynamically significant – cardioversion
 Well tolerated – BB or CCB to control V response
o Sinus Bradycardia
 Common with inferior wall MI
 May be due to ↑PSNS activity or acute ischemia of sinus or AV node
 Treatment – atropine or temporary pacing if hemodynamically
compromised
 Pericarditis
o Occurs 1-4 days post MI in 10-15% patients
o Chest pain – pleuritic (worse with inspiration or laying down, relieved by changes
in posture)
o Treatment – in absence of significant effusion – aim to relieve chest pain
 ASA or indomethacin
 Corticosteroids for refractory cases at least 4 weeks post MI
 Mitral Regurgitation
o d/t ischemic injury to papillary muscles or V muscles to which papillary muscles
attach
o more likely after inferior wall MI than after anterior wall MI
o results in pulmonary edema and cardiogenic shock
o Total papillary muscle rupture – prompt surgical repair or death within 24 hrs
o Treatment - ↓ LV afterload and ↑ coronary perfusion (IABP, IV nitroprusside)
 Ventricular Septal Rupture
o More likely after an anterior wall rather than an inferior wall MI
o Characteristic holosystolic murmur of V septal rupture
o As soon as diagnosis made – IABP should be initiated
o Emergency surgery if hemodynamically compromised

523
  Congestive Heart Failure and Cardiogenic Shock
o Cardiogenic shock – advanced heart failure – CO insufficient to maintain
perfusion to brain, kidneys and other vital organs
o Oliguria and HoT persist even after angina is relieved, hypovolemia is corrected,
SNS activity abated and dysrhythmias treated
o SBP is low, associated pulmonary edema and arterial hypoxemia
o Usually a manifestation of MI > 40% of L V myocardium
o Treatment – dependent on blood pressure and peripheral perfusion
 NE, dopamine, vasopressin or dobutamine
 If BP adequate, Nitro to ↓ preload and afterload
 If pulmonary edema – morphine, diuretics and mechanical ventilation
 Thrombolytic therapy to restore blood flow to infarct
 LVAD or IABP
 Myocardial rupture
o Usually causes acute cardiac tamponade
o Typically occurs in first week after MI – sudden hemodynamic collapse or death
 Right Ventricular infarction
o 1/3 of inferior wall MI
o Kussmaul’s sign (distention of jugular vein on inspiration)
o Treatment – fluids, inotropes (NOT diuretics or vasodilators)
 Stroke
o Anterior wall infarct due to thrombus in 1/3 of patients
o Presence of thrombus = immediate thrombolytic therapy
 Hemorrhagic stroke in 0.3-1% patients
Perioperative Implications of Percutaneous Coronary Intervention

 Alternative to CABG to open stenosis of coronary arteries (BMS and DES)

 PCI stent and Thrombosis
o Mechanically opening a vessel = vessel injury and makes the vessel prone to
thrombosis
o Acute – within 24 hrs of stent placement
o Subacute – between 2-30 days
o Late – between 30 days and 1 yr
o Very late – after a year
o Platelets – the cause of thrombosis
 Antiplatelet drugs – multiple triggers so need to block multiple pathways
 ASA and Plavix
 Increase the risk – DM, low EF, renal impairment, advance age, CA
 Surgery and Risk of Stent Thrombosis
o Bare Metal Stents
 Surgery within 6 weeks of BMS placement increases risk of death, MI,
stent thrombosis and urgent revasc by 5-30%

524
 o Drug Eluting Stents
 Chance of late stent thrombosis higher after placement of DES than after
BMS
 Risk of Bleeding with Antiplatelet Agents
o Antiplatelet drugs clearly increase the risk of bleeding during the perioperative
period
o ASA – increases risk of bleeding during surgery by 1.5 x
 Bleeding versus stent thrombosis in the perioperative period
o Risk of adverse coronary, cerebrovascular and peripheral vascular events must be
weighed against the risk of bleeding
 Management of Patients with Stents
o Timing of the operation after PCI
o Continuation of dual antiplatelet therapy
o Perioperative monitoring strategies
o Anesthetic technique
o Immediate availability of an interventional cardiologist
Perioperative Myocardial Infarction

 Usually appear within 24-48 hrs postop

 MI usually preceded by tachycardia and ST depression
 Diagnosis
o Nonspecific ECG changes, new onset dysrhythmias, noncardiac hemodynamic
instability
o Acute increase in troponin levels
 Relationship of ECG leads to areas of myocardial ischemia
o II, III, AvF Right coronary artery R atrium, RV, SA node, Inf aspect of
LV, AV node
o I, AvL Circumflex coronary artery Lateral aspect of LV
o V3-V5 LAD coronary artery anterolateral aspect of LV
Cardiac Transplantation

 Mostly performed in patients with end-stage heart failure d/t idiopathic or ischemic
cardiomyopathy, EF often < 20%, commonly coagulation disturbances due to passive
congestion of the liver d/t CHF
 Contraindications – irreversible pHTN, age > 65 (depending on hospital), active
infection, recent PE

525
  Anesthetic Management
o Full stomach
o Hemodynamically stable before induction – use Etomidate to keep stable on
induction
o Use NDMB without histamine release, pancuronium may be desirable (↑ HR and
BP)
o Maintain with opioids as VA’s may produce undesirable myocardial depression
o Avoid Nitrous – pHTN, air embolism in large blood vessels opened during
procedure
o Immunosuppressive drugs may be started preoperatively
o Inotropic support may be needed briefly postoperatively to maintain myocardial
contractility and heart rate
o Denervated heart usually assumes HR of 110 (no vagal tone), tolerate
hypovolemia poorly, depend on preload for SV, not responsive to direct acting
catecholamines but rather indirect mechanisms of action (Ephedrine), may require
vasopressin to treat HoT that is unresponsive to catecholamines
o ¼ develop bradycardia (transplanted heart unresponsive to anticholinergics and
anticholinesterases) so they require insertion of permanent pacemaker
Valvular Heart Disease

 See prior write ups on Aortic stenosis & regurg and Mitral Stenosis & regurg
Murmurs

526
Risk factors for CAD

 Family history
 DM
 HTN
 Cigarettes
 Dyslipidemia
 Obesity
 Sedentary lifestyle
 Stress
 Male gender
 Increased age
Clinical predictors of increased perioperative cardiovascular risk (2007)
Major:

 Acute or recent MI
 Decompensated HF
 Dysrhythmias
 Unstable angina
 Severe valvular heart disease
Intermediate

 Mild angina
 Q waves
 Compensated CHF
 CRF
 DM
Minor

 Age > 70
 EKG (LVH, LBBB, ST-T changes)
 Rhythm other than sinus
 Low functional capacity
 H/O CVA
 Uncontrolled HTN

527
Cardiac related Equations

 coronary perfusion pressure = the driving pressure (aortic diastolic pressure) - impeding
pressure (LVEDP)
 SVR=(MAP-CVP)*80/CO
 CI=CO/BSA
 CO=HRxSV
 SV=(EDV-ESV)*100/EDV
 MAP=DBP + 1/3PP
Pharmacology
Inotropes

 Dobutamine
o Mostly a beta 1 agonist, some beta2 and alpha stimulation
o Useful in improving cardiac output when heart rate and SVR are increased
o Increases SV with small changes in HR and BP
o Used in combination with vasodilators to decrease afterload
o No important vasoconstrictor activity
o Coronary artery vasodilator
o Absence of endogenous catecholamine release
 Isoproterenol
o Most potent beta 1 and beta 2 agonist (but not used for asthma due to
arrythmogenic effects)
o Has taken a back seat to drugs such as dobutamine and phosphodiesterase
inhibitors in the management of failing hearts
o Useful in patients with Denervated hearts to increase heart rate. A “chemical”
pacemaker.
o Effects are increased heart rate, contractility and automaticity and decreased SVR
(from skeletal muscle vasodilation). Net effect is increased CO and slightly
decreased MAP
o Not great in patients with CAD>>decreased DBP decreases coronary flow and
tachycardia and increased CO increase oxygen demands
 Dopamine
o Endogenous catecholamine that is an immediate precursor of norepinephrine
o Nonspecific agonist at both dopamine 1 and dopamine 2 receptors, and alpha and
beta receptors
o Dopamine 1 receptors are located postsynaptically and cause vasodilation when
stimulated. These are located in the kidney, brain, heart and mesentery. Mediated
by adenylate cyclase.

528
 o Dopamine 2 receptors are located presynaptically and inhibit adenylate cyclase
and release of norepinephrine. Nausea and vomiting are also possibly induced via
these receptors
o Lower dose stimulates dopamine 1 receptors in the kidney
o Moderate dose stimulates dopamine and beta 1 receptors in the heart
o High dose stimulates dopamine, beta 1, and alpha receptors in the peripheral
vasculature
o Unique in being able to simultaneously increase contractility, renal blood flow,
GFR, excretion of Na and urine output
o “Renal-dose” dopamine is a fallacy in terms of preventing ATN
o Increases CO via beta 1 stimulation. Increased CO is also due to stimulation of
norepinephrine release. This is an indirect action.
o Used in combination with dobutamine as infusion for failing hearts
o Dysrhythmias possible
o Must be given as an infusion to achieve and maintain therapeutic plasma
concentrations
Vasodilators

 Nitroglycerin
o Principally a vasodilator
o Can be sublingual, transdermal, or IV
o Generates NO in the presence of thio-containing compounds
o Not a good choice in Aortic Stenosis > venous pooling > syncope
o Metabolite capable of producing methemoglobinemia (esp. high doses in liver
dysfunction)
o Tolerance to vasodilating effects that is dose and duration dependent; tx is to d/c
drug for at least 12 hours and restart
o Relaxes airway and biliary/GI tract smooth muscle (can relax sphincter of Oddi
spasm)
o Cerebral vasodilator
o Decreased CO due to decreased venous return
o Baroreceptor mediated tachycardia and increased contractility, especially if
hypovolemic
o SVR relatively unchanged
o Increased coronary flow to subendocardial layers > good
o Good for patients with HTN and CAD
o 0.3 mg sublingual for angina
o Decreases the area of cardiac muscle injury in MI by preferentially diverting flow
to the ischemic area
o Side effects: Headache, facial flushing, tolerance (not with intermittent
sublingual)
o Not to be used in patients taking drugs for ED (potentiation of hypotensive effects
via inhibition of c-GMP catabolism)

529
  Nitroprusside
o Direct acting, nonselective potent vasodilator
o Ferrous ion center together with 5 cyanide ions and a nitrosyl group
o Immediate onset, requires continuous infusion
o Need an arterial line for safety
o SNP interacts with oxyhemoglobin to form methemoglobin, releasing cyanide and
NO
o NO is the active mediator and SNP is the prodrug
o One of the 5 cyanide ions reacts with methemoglobin to form
cyanmethemoglobin
o The other 4 cyanide ions are converted to thiocyanate by the Rhodanase enzyme
in the liver and kidneys
o Cyanmethemoglobin remains in dynamic equilibrium with free cyanide and is
nontoxic
o SNP Toxicity: Cyanide Toxicity, Methemoglobinemia, High plasma
concentrations of thiocyanate
 Hydralazine (Apresoline)
o Direct arterial vasodilator that activates guanylate cyclase and generates NO
o Decreased BP (DBP>SBP)
o Reflex-mediated increase in heart rate
o Increased SV and CO
o In 10-20% of patients, SLE-like syndrome occurs
o Can cause angina via increased heart rate
o Onset is about 20 minutes; lasts for hours
o Vial is 20 mg, dose can vary 2mg-20mg
Phosphodiesterase 3 inhibitors

 Milrinone
o Action is to decrease the hydrolysis of c-AMP and c-GMP, which in turn leads to
protein kinase phosphorylation of other substances that increase inward
movement of calcium ions.
o Overall effect of this is positive inotropy (via increased c-AMP) and vascular and
airway smooth muscle relaxation
o Will increase contractility in beta-blocked patients
o Synergistic response with catecholamines
o Management of acute CHF/post-MI CHF
o a positive inotrope and a vasodilator, so the effect is increased CO and decreased
LVEDP

530
 Geriatrics

Cardiovascular system - LV hypertrophy & ↓ compliance, ↑vascular rigidity, ↓ compliance of

venous vessels; ↓PNS tone, ↑ sympathetic neuronal activity, Desensitization of β adrenergic
receptors, ↑ SVR, BP, ↓ SV, CO, Diastolic LV dysfunction, ↓ maximally attainable heart rate
Modest ↓ in resting CI seen in most elderly
Not indicative of degenerative cardiac change
Response to ↓ need for perfusion, metabolism r/t skeletal muscle atrophy & ↓ tissue mass
Demand for cardiopulmonary function maintained in elderly by daily exercise
Short-term ↑ CO achieved w/modest ↑ HR, ↑ SV
Aging ↓ inotropic & chronotropic responses to neutrally-mediated adrenergic stimulation
Maximum HR & inotropic responses are age-limited
Passive ventricular filling in early diastole ↓ in elderly 2o stiffer, less compliant ventricle
Age-related diastolic dysfunction makes elderly more dependent on synchronous atrial
contraction for complete ventricular filling
Small decreases in venous return (positive pressure ventilation, hemorrhage, vasodilators) may
significantly compromise stroke volume, especially when arrhythmias present
Perioperative hypotension more common in elderly
Pediatrics
Simple L to R shunts
Shunt depends on relationship between SVR: PVR
Preop: Pulmonary HTN, RV failure
Postop: May have persistent pulmonary HTN, May need LV inotropic support
Examples of dependent shunts: PDA 10% of CHD (volume overload to pulmonary circulation),
ASD 10% of CHD, VSD 20% of CHD (can easily lead to volume overload of the right heart),
AVSD 3% of CHD, AP window 0.1% of CHD

531
Anesthetic Management:
Presentation: CHF - No cyanosis
SpO2 Monitor - For repair of PDA or coarctation of aorta: 1st probe on R hand digit for
preductal oxygenation, 2nd probe on toe or foot for postductal pulse detection
Pre bypass management: Minimize fluids, manage right heart failure - maintain status
quo, Reduce SVR
Post bypass management: Provide left heart inotropic support prn, Decrease PVR if child
has persistent pulm HTN with RV failure, Provide RV inotropic support prn
Children with CHF are at increased risk for cardiac instability on induction
–Anesthetic implications for induction: Easy to overdose on inhalation agent
(bradycardia and hypotension), therefore IV induction is preferred, IV induction with fentanyl
(2-3 ug/kg) and pavulon (0.1mg/kg) with low dose inhalation will maintain CO and HR, IV
Etomidate (0.2-0.3 mg/kg) induction maintains hemodynamics, but does not blunt response to
laryngoscopy, IV Ketamine 1-2 mg/kg maintains CO, HR, B/P but may be a poor choice in
patients with catecholamine depletion
Simple shunts: R to L (obligatory)
Shunt - Increased resistance to flow in the R heart causes movement across a
communication to the L heart.
Preop: Cyanosis, Beware of “tet” spells, Beware of air emboli to L side
Postop: May have persistent pulmonary HTN, May need LV inotropic support
Examples of R to L shunts: Tetralogy of Fallot (11%- VSD, Overriding aorta, RVOTO, RVH),
Pulmonary atresia (Blood gets into the pulmonary circulation by way of the PDA & L to R VSD)
, Tricuspid Atresia (Blood gets into the pulmonary circulation by way of the PDA & L to R
VSD) , Ebstein anomaly
Anesthesia management of R to L shunt
Presentation: Cyanotic
Pre-repair management: Reduce PVR / shunt, 100% oxygen, Hyperventilation (pH = 7.6),
Prevent crying, Consider Inderal (propranolol) for RVOTO, Increase SVR, Phenylephrine (5 ug
bolus), Norepinephrine (0.5 [Link]/m)
Post-repair management: Assess and manage PVR, Inotropic support, Low dose epi, DTX
Compensatory mechanisms increase delivery of oxygen to tissues in cyanotic defects: Increase
hematocrit > 65 (increased erythropoietin production), Increased 2, 3, DPG, Increased blood
volume

532
Complex Shunts: In complex shunts there is mixing of the pulmonary and systemic circulation
with cyanosis
Examples of complex shunts: Transposition of great vessels (6%), Truncus arteriosus (1%-
Common outflow tract for the RV and LV with a large VSD.), double outlet RV, Hypoplastic
left heart syndrome, Total anomalous pulmonary venous drainage

Types of Heart Failure

3 categories of myopathies:
 Systolic= dilated cardiomyopathy; results from
chronic volume overload from regurgitation or
an acute myocardial infarction)
 Diastolic= hypertrophied (thick walled)
cardiomyopathy (Patients with diastolic
dysfunction have impaired lusitropy or impaired
ventricular relaxation during diastole, which
causes impaired passive filling and increased
reliance on atrial kick.)
 Restrictive (rarely encountered and results in
biventricular under-filling and biatrial
enlargement )

533
 Systolic Diastolic
Dilation Hypertrophy (Nonelastic, stiff
Eccentric/Serial fibers)
Concentric/Parallel)

LV Chamber ↑(lots of volume to pump out) ↓

Size
Chronic volume overload Chronic pressure overload
Failure of the pump f-n of the heart Ventricle can’t relax (↑wall
thickness)
Causes Regurgitation Aortic stenosis
Maintenance ↓afterload →↓flow back (Nipride, Keep them where they are
cardine, inhalational agents, Maintain preload/afterload
epidurals, spinals) Avoid ↑HR (70-80 goal)
↑HR (80-100)→↓time in diastole to Maintain NSR
↓time for flow back No beta agonists
Phenylephrine (↑HR, ↓afterload)

534
Aortic Stenosis
• Critical stenosis is defined as:
– Aortic valve area <0.8 cm2
– *Mean transvalvular gradient > 50 mm Hg
• Note the  in the RV chamber size a/w LVH
• AS is predominantly characterized as diastolic dysfunction, with + systolic dysfunction
• Note septal wall thickness at diastole on TEE report (normal is .6-1.0 cm)
• LV Hemodynamic Effects
• ↑LV afterload
• LVH
• Increased LVEDP:LVEDV
• Decreased lusitropy
• ↓myocardial O2 supply
• Increased MVO2
• Angina
• ↓SV
• Pulmonary HTN
• Dyspnea on exertion
• RV Hemodynamic Effects
• Pulmonary HTN increases afterload to RV
• Can ultimately lead to RV failure
• AS is a/w increased risk for ischemia despite normal coronary arteries due to of the
unique effect of AS on myocardial oxygen supply and demand.
• Net increased in oxygen demand
• afterload due to valve area (normal is 2.5-3.5 cm2)
• LV muscle mass
• Decrease in oxygen supply
• for any given HR, there is time for diastole
• LVEDP decreases CPP to the endocardium
• muscle outgrows blood supply
Aortic Regurgitation

 LV Hemodynamic Effects (Initial stage)

o Increased LVEDV
o Increased LVEDP (+)
o Dilated LV
o Increased SV (CO)
o Systolic HTN
o Low DBP (Wide pulse pressure)
o LVH
o Compensatory to reduce wall stress

535
  RV Hemodynamic Effects (Later stage)
o Syncope
o Dyspnea
o S3
o Pulmonary HTN
o Increased afterload to RV
o RV failure
o RAE
o JVD
o Hepatic congestion
o Leg edema

Mitral Stenosis

 L Heart Hemodynamic Effects

o Increased LA Volume
o Gross LA dilation
o Increased LA pressure
o Atrial dysrhythmias
o Stroke
o Gross pulmonary HTN
o Dyspnea
 R Heart Hemodynamic Effects
o Increased afterload to RV
o RV failure
o RAE
o Increased CVP
o Neck vein distention
o Hepatic congestion
o Edema

536
Mitral Regurgitation

 LV Hemodynamic Effects
o Increased LA volume during systole
o LA dilation
o Atrial fibrillation
o Stroke (AF = LA appendage thrombus)
o Increased LVEDV
o Dilated LV & hypertrophy
o Gradual increase in the degree of MR secondary to annular dilation
 RV Hemodynamic Effects
o Pulmonary HTN
o Dyspnea
o Increased afterload to RV
o RV failure
o RA dilation
o JVD
o Hepatic congestion
o Edema

IHSS idiopathic hypertrophic sub aortic stenosis.

 Most commonly inherited cardiac disorder
 Characterized by:
• Thickened septum
• LV outflow track obstruction
• Decreased LV compliance
• Decreased lusitropy
 Worsens with:
• Increased inotropy
• Decreased preload
 At risk for sudden death due to ventricular-fibrillation

Right Heart Failure

• Blue face & neck is a telltale sign of right heart dysfunction
• Extremely rare to be a/w pulmonic valve disease
• Typically caused by acute or chronic increase in afterload a/w:
– Hypoxic pulm vasoconstriction
– COPD, cystic fibrosis, ARDS
– L heart disease
– Saddle pulmonary embolus

537
High Output Heart Failure
 Increased cardiac output is unable to meet the metabolic demand
 Etiology
 Hyperthyroidism
 Anemia
 Septicemia
 Beriberi: a thiamine deficiency usually caused by alcoholic malnutrition.
 Thiamine deficiency causes impaired myocardial cellular metabolism that
leads to decreased inotropy
 Thiamine deficiency also caused vasodilation (decreased SVR).
 Decreased SVR creates a demand for increased CO

538
 The Heart and Anesthesia:

 Basic function: preload determined by volume status and venous return to the right
atrium. Flow from right atrium to right ventricle through tricuspid valve. Through
pulmonic valve at low pressure and high volume (entire cardiac output goes through
pulmonary bed) via the pulmonary arteries. From pulmonary bed to left atrium via 4
pulmonary veins. Left atrium to left ventricle through the mitral valve. Ejected from left
ventricle through aortic valve to ascending aorta.
 Cardiac output is determined by preload, afterload, contractility and heart rate. Coronary
perfusion pressure determined by aortic diastolic pressure and left ventricular end
diastolic pressure. Perfusion occurs during diastole when aortic leaflets close and the
RCA and LM are perfused. SVR = (MAP – CVP) * 80 / CO
 Conduction system starts with sinoatrial (SA) node to atrioventricular (AV) node to left
and right bundles of HIS to Purkinje fibers. Heart rate determined by pacer maker cells
with funny channels that have a baseline leak of sodium inward that brings the membrane
potential closer to threshold potential resulting in depolarization and myocytes
contraction.
 Problems that can occur with the heart in many ways:
o Supply / demand mismatch (oxygen) resulting in ischemia as with a myocardial
infarction or increased heart rate with aortic stenosis. Remember that heart rate is
the major determinant of oxygen demand of the heart and that increased heart rate
will cause ischemia before high blood pressure will.
o Impaired inotropy as seen with volume overload and over-stretched sarcomeres.
Or after an MI and having hypokinetic, akinetic or dyskinetic wall motion.
Dyskinetic wall motion seen with Takotsubo cardiomyopathy and resultant apical
ballooning.
o Patients with systolic dysfunction will need to volume restriction and inotropic
support, whereas patients with diastolic dysfunction have impaired lusitropy and
rely heavily on volume status and atrial kick to maintain adequate filling of the
ventricles. LV hypertrophy is compensatory mechanism of increased pressures as
evidenced by the law of La Place – pressure * radius / wall thickness. Wall
tension is inversely proportional to wall thickness.
 Putting it all together:
o Imagine a patient with diastolic dysfunction and an EF of 30%. What will happen
with volatile anesthetic delivery, propofol induction dose or anything that will
reduce preload? They rely heavily on preload as a function of left ventricular
filling pressures. Without that they will have a dramatic decrease in cardiac output
and oxygen delivery to vital organs. Preload has to be maintained. What will
positive pressure ventilation with PEEP do to your preload??

539
o A patient with severe aortic stenosis (valvular area less than 1 cm squared)
presenting for a total hip replacement. How will they respond to a sympathectomy
after that T 10 spinal you administered? Without afterload a patient with AS will
not have coronary perfusion and will have an MI. How will they respond to
tachycardia? More time is spent in systole in order to eject blood through the
smaller area and flow is more turbulent (Poiselle’s law: Flow = pressure drop * pi
* r ^4 / 8ln). This means the heart has to work harder to pump that blood through
that area and it is taking longer, so less time is spent in diastole where the heart is
perfused. With an increase in heart rate, there is not nearly enough time spent in
diastole and ischemia will result. Also, this patient may likely have a hypertrophic
LV that is outgrowing its blood supply. More time is needed in diastole to perfuse
the increased muscle mass. Anyone have esmolol drawn up?
o We don’t have that, but we have Brevibloc… what do you say? Of course you
know they are the same thing. And of course you know it is metabolized by non-
specific red blood cell ester hydrolysis. How about we use pancuronium and
desflurane in our anesthetic?? Both can increase heart rate right??? So we want to
avoid these in this type of patient. You’re so keen, you RFUMS SRNA.
o What was that magic cocktail for hearts? Nitroglycerine and phenylephrine.
Nitroglycerine to maintain adequate preload and Neo to maintain afterload makes
the heart happy.
o How about the 6 weeks post-partum patient that presents with shortness of breath
and prominent bilateral points of maximum impulse. Do you want to provide a
general anesthetic for her or do you want to see an echo first? Smells like
pregnancy induced cardiomyopathy. May need some inotropic support.
o A couple little things to think about: What do you do if you look up at the monitor
and you see ST elevation in leads II and V5 (we always monitor those, standards
right??). First, don’t panic… but seriously what do you do??? Think MONA, turn
off your air and deliver 100 % oxygen. Decrease afterload with nitroglycerine. All
the while having communicated with the surgical team to abort procedure and
consult cardiology ASAP. Get the pads on and get ready.

540
Pulse Pressure (PP)
• PP = SBP-DBP
• Normal PP in the brachial artery is 40 mm Hg
• Why care about pulse pressure?
– It helps us to assess cardiac disease
– It is affected by acute illness not directly related to the heart
Decreased (narrow) Pulse Pressure
• Etiology
– Increased SVR
– Decreased inotropy
– Decreased intravascular volume
– i.e. low cardiac output states
• Examples
– Cardiogenic shock (pump failure)
– Cardiac tamponade
– Hypovolemic shock
Increased (wide) Pulse Pressure
• Etiology
– Increased stroke volume
– Increased ejection velocity
– Decreased arterial compliance
• Examples
– Aortic regurgitation
– Bradycardia
– Fever
– Anemia
– Exercise
– Hyperthyroidism
– Atherosclerosis

Pulse Waves & Tidal Waves

• Pulse waves (driving pressure)
– Characterizes the antegrade flow
– A function of the force velocity
– SBP = pulse wave effect + tidal wave effect
• Tidal wave (impeding pressure)
– Characterizes the retrograde flow
– A function of resistance in the system
– Under normal conditions, 80% of the pulse wave is reflected back as the tidal
wave
• Clinical implications
– Timing of coronary perfusion
– Increased afterload effect

541
Monitoring Location & Waveform Characteristics

542
Peripheral A-line waveform will have an:
• Increased systolic pressure
• Decreased diastolic pressure
• More prominent dicrotic notch
• Exception to the rule
• Cardiac surgery – radial artery systolic pressure will be significantly lower than
the femoral or aortic systolic pressure in the first 20 – 45 minutes post separation
from CPB secondary to disproportionate dilatory effects caused by rewarming.

Pulses Tardis/Pulses Parvus

Aortic Stenosis

Pulses Paradoxes

543
 • > 10 – 15 mmHg drop in blood pressure during exhalation and negative pressure
ventilation
• > 10 – 15 mmHg drop in blood pressure during inspiration and positive pressure
ventilation
• In clinical practice, simply focus on the change in pressure - generally
• Commonly relied on in anesthesia practice as an assessment of hypovolemia
Theories
1. Increase in negative intrathoracic pressure causes in RVEDVLVEDV secondary to
septal wall bulge into the LV cavity
2. Increase in negative intrathoracic pressure causes either or both of the following:
• pulm vasc compliance LVEDV
• in afterload to the LV LVEF
3. Increase in positive intrathoracic pressure a/w positive pressure ventilation leads to a
decrease in afterload LVEF
4. Right lung hyperinflation on inspiration increases pressure on the outside of the right
ventricle and either:
• Inhibits right ventricular filling LVEDV and SV
• Causes a septal wall bulge into the LV that LVEDV
At risk patients
• Hypovolemic
• Less than optimal mechanical ventilation modes
• Cardiac tamponade (82% sensitivity)
• Restrictive pericarditis
• COPD with hyperinflation
• Severe asthma
• Severe heart failure

544
Abnormal Waveform: Bisferiens
• Aortic Regurgitation

• IHSS

Abnormal waveform: Technical

545
546
Abnormal Waveform: Abducens

Abnormal Waveform: Premature Beat

547
 The Law of Laplace

P=2T/R for spheres

(P)Pressure =the pressure within the bubble required to keep it inflated
(T)Surface tension = force outside the bubble, somewhat like a rubber band being stretched
(R)Radius=the radius of the bubble
If we plug in a few generic numbers, we see that as the radius decreases, the pressure required to
keep the balloon inflated increases, especially when surface tension remains the same. This
explains why a balloon is difficult to start blowing up but gets easier as the balloon gets bigger.
P=2(10)/10=2 compared to P=2(10)/5=4
This also explains why, when two bubbles share a communicating surface, the smaller bubble
will collapse and the big bubble will get larger. Less pressure is required to maintain the larger
bubble than the smaller bubble. See illustration at [Link]
[Link]/content/75/2/[Link]
Alveoli & Laplace
Alveoli also have a fluid/gas interface which makes them behave like bubbles. The gas within
the alveoli however, communicates with the atmosphere via the airway.
The alveoli also have surfactant which tempers surface tension and helps to prevent alveolar
collapse:
1. When the alveoli are small (those more towards the base of the lung in the upright
lung and after expiration), surface tension is decreased by thickened surfactant.
P=2(5)/5=2
2. And when the alveoli are larger (as are those towards the apex of the upright lung and
on inspiration), surfactant is thin and surface tension is increased to prevent over
distension. P=2(10)/10=2
3. Without surfactant or in ARDS, smaller alveoli are inclined to empty into larger
alveoli.
Of course, the change is surface tension is not directly proportional to the change in radius.

548
Laplace & the Heart:
Laplace’s law can also be applied to the LV. Greater filling during diastole leads to greater wall
tension at end diastole

Laplace & Anesthesia

Inhalational agents tend to induce shallow rapid breathing while Nitrous and opioids result in
slower, deeper respirations. With the greater pressure of deeper respirations, the smaller alveoli
will be kept open as well as the larger alveoli.
Laplace’s law explains why the addition of PEEP (Positive End Expiratory Pressure) can be
helpful in preventing alveolar collapse. The alveolar radius is smaller on expiration and more
pressure is required to prevent its collapse.
1. But in COPD where expiratory flow is limited, adding PEEP may cause over distension
of the alveoli and barotrauma.
2. And, as the alveoli are distended, blood flow is impeded (as in Wes Zone 1
pAlveolus>pArterial>pVenous) which may decrease venous return and BP.

References:
Ault, M., & Stock, M. (2009). Respiratory Function. In P. Barash, B. Cullen, R. Stoelting, M.
Cahalan, & M. Stock, Clinical Anesthesia, sixth edition (pp. 233-253). Philadelphia:
Lippincott Williams & Wilkins.
Morgan Jr., G., Mikhail, M., & Murray, M. (2006). Clinical Anesthesiology, fourth edition. New
York: McGraw-Hill.

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 Illegal Drugs and Anesthesia

Common theme- Almost all drugs of abuse share the ability to increase synaptic levels of
dopamine particularly in the nucleus accumbens- cocaine, amphetamine, nicotine, ethanol,
opioids and marijuana all share this feature.

Marijuana

 Pot, reefer, hash, bong, doobie, bammy, chillums, Buddha, skank, fire up a fatty, ganja,
good shiznazzle, loco, moocah, muggles, paca lolo, philly blunt, weed- yeah you get the
message
 Comes from plant Cannabis sativa. Cultivated for centuries for production of hemp,
medicinal and psychoactive properties.
 Most commonly used illicit drug
 Pharmocokinetics
1. Rapidly absorbed through lungs to CNS- peak effect 15 min lasts 2-4 hrs
2. Oral- 1st pass metabolism through liver- but longer lasting effect- Peak 1 hour, lasts
5-6 hours
3. T1/2 life- 56 hours for occas. users. 28 hrs for chronic users
4. Very lipophilic, accumulates in adipose
5. Elimination takes up to 30 days for complete elimination
 MOA: 2 receptors- CB1, CB2
1. CB1 in CNS and PNS- effects memory, emotion, movement
2. CB2 is peripheral- think immune system- spleen, macrophages- decreases resistance
to infection
 There are 61 different cannabinoids found- Delta-9-THC produces the most of the
characteristic pharm effects.
 Effects- Euphoria, anxiety, dizziness, altered gait, bloodshot eyes, cotton mouth, time
distortion, short term memory loss, appetite increase.
 Low dose effect- Increased SNS activity, decreased PaSNS activity
 High dose effect- Decreased SNS, Increased PaSNS
 Chronic effects-Memory problems, low testosterone, Increased Bronchitis risk and lung
cancer risk

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 Anesthetic Implications
 CV- Tachycardia may suggest acute intoxication. Reports of myocardial depression
 Pulm- 5x the level of carboxyhgb as tobacco users
 Potential for Airway hyperreactivity, laryngospasm, bronchospasm. Reports of uvular
edema leading to upper airway obstruction.
 Pulmonary issues- regional better choice if it’s an option.
 Potential antiemetic, analgesic and anticonvulsant. Reduces IOP in glaucoma. However
no clear advantage as these benefits come at cost of the psychoactive effects that impair
normal activities
 Dronabinol (Marinol)—oral capsule containing delta-9-THC approved for anorexia,
weight loss in HIV, Cancer patients, and for cancer chemo induced N/V.
 Studies have shown that marijuana users need higher doses of Propofol on induction than
nonusers.
 It would seem prudent to avoid medications that would potentiate tachycardia or
histamine release i.e.- D-tubo (Good luck finding), Atracurium, succinylcholine,
pancuronium, ketamine
 Can potentiate hypnotic and sedative effects of ETOH, barbiturates, opiates, benzos,
Phenothiazines
Pregnancy and Mary Jane
 THC crosses placenta easily- reduces uteroplacental perfusion
 IUGR, preterm delivery, SIDS, cognitive delay have all been reported

Cocaine

 Yeyo, Zip, tardust, white horse, white lady, teeth, toke, toot, snort a line, pearl, paradise
white, mama coca, love affair, lady, lady caine, line, birdie powder, etc.
 Adding HCO3 or ammonia and H2O converts to hardened alkalinized form- crack or
free base
 Second most common cause of acute drug related visits to ER- Chest pain most common
presenting sign.
 Most common cause of drug related death, and most common illicit drug in those seeking
rehab.
 Comes from the leaves of Erythroxylon coca. At one point- late 1800s Sigmund Freud
advocating use for ETOH and morphine addiction
 In studies, when given the choice between food, sex, and IV cocaine- monkeys will
always pick the cocaine.
 Popularity grew for local anesthetic properties- 1884- ophthalmologist used for eye
surgery and presented findings to Ophthalmologic Congress

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 Pharmacokinetics- Ester
1. Very lipid soluble- rapid absorption IV and inhaled- Peak effect 1-20 min.
2. Oral and snorted lower plasma concentration - slower absorption rates
3. T1/2 life- 0.5-1.5 hours
4. Metabolism by plasma and liver Cholinesterases.
5. Metabolites- Benzoylecgonine, Ethyl methylecgonine.
6. Detection in urine 15-60min after intake. Can be detected 2-5 days after binge.
7. When coke and alcohol are together- cocaethylene- which is equipotent to cocaine in
blocking reuptake of dopamine
 MOA- Slow Na channel blocker
1. Interferes with presynaptic uptake of Norepinephrine, Dopamine, and Serotonin.
Dopamine causes the “high”
 Effects
1. Nasal septal perforation. Anxiety, restlessness, movement disorders,
2. Seizures
3. Coronary vasospasm, MI, ventricular cardiac dysrhythmias, V-Fib,
4. There is a 24x increase chance in MI first hour after cocaine use
5. Aortic, coronary dissection possible, accelerated atherosclerosis
6. Consider myocardial hypertrophy in chronic cocaine users- due to increased
afterload- law of Laplace, right?
7. Acute- Bronchospasm, pulm. Hemorrhage, pneumothorax. Chronic- Pulm edema,
pulm HTN, crack lung
8. ARF, renal infarctions
 Cocaine and Anesthesia
1. Airway edema, bronchospasm- Difficult airway management and ventilation
2. Since cocaine competes for pseudocholinesterase metabolism- prolonged action of
succinylcholine
3. Arrhythmias- exacerbated by volatiles.
4. Tachycardia- avoid ketamine, pancuronium
5. MI risk- monitor EKG closely. Benzos and NTG as tx
6. HTN- preop anxiolysis. Severe response to laryngoscopy. Preop arterial line
consideration.
7. Increased anesthetic requirement with acutely intoxicated patient.
8. Consider potential for thrombocytopenia with regional anesthesia
9. Unopposed alpha block with beta blocker- SEVERE HTN. Labetalol may still cause
it. Studies show beta-blockade with cocaine NOT A GOOD IDEA- cocaine induced
coronary vasoconstriction potentiated by beta-blockade.
10. Hypotension resistant to tx with ephedrine- depleted catecholamine stores

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 Amphetamines/Methamphetamines

 Amp, blue belly, crystal, crank, la glass, speed, white cross, baggers, chalk, chicken
flippin, chittle, crunk, crystal meth, go-go, hillbilly crack, pootananny, powder monkeys,
satan dust, etc.
 Similar/Related agents- dextroamphetamine, methamphetamine, phenmetrazine,
methylphenidate (Ritalin, anyone?), diethylpropion.
 1930s- Wide use for asthma, hangover, narcolepsy, weight reduction, hyperactivity in
kids, and N/V.
 This drug can be made easily from legal ingredients- all you have to be able to do is do
simple math, use Google, a few household supplies, etc., crazy huh? “Shake and Bake”
 Still prescribed for narcolepsy, obesity, ADHD, Parkinson’s in various forms
 MOA-Increases synaptic dopamine, norepi, and serotonin by stimulating presynaptic
release, rather than by blockade of reuptake like in cocaine.
 Pharmocokinetics
1. Onset- injected immediate, snorted- 3-5minutes, oral- 15-20 minutes
2. T1/2 life 11-12 hours. Renal excretion
 Acute Effects- Elevated body temp, increased activity, euphoria, wakefulness, increased
alertness, decreased appetite, dilated pupils, dry mouth, HTN, Tachycardia, Arrhythmia,
Tachypnea, Hostility or paranoia, MI, bronchodilation, hyperglycemia, Pulm HTN,
Dehydration and HoTN.
 Chronic Effects- Psychological (many), lethargy, weight loss, memory disturbances,
dental problems (Meth head, Meth Mouth- easy sign to catch) cardiac arrhythmias,
repetitive motor activity, convulsions, coma, death.
 It has been shown to be a neurotoxin to dopaminergic neurons- use can lead to psychosis
resembling schizophrenia.
 Stimulants and Anesthetic Implications
1. Acute intoxication increases anesthetic requirements
2. Chronic use decreases anesthetic requirements- depletion of CNS catecholamines.
3. Consider using Direct Acting vasopressors

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 Heroin

 Horse, Smack, H, Chiba, Junk, Brown Sugar, China White, White nurse, White Lady,
Mexican Brown, etc.
 Most frequently abused opiate. However one must still consider the staggering statistical
increases in prescription opiate abuse of oxycodone, hydrocodone. Others include,
codeine, meperidine, fentanyl, pentazocine, propoxyphene, methadone, morphine, all
have been abused at one point or another. Also consider opium- less common
 Use may lead to tetanus, botulism, multiple skin infections, hepatitis B and/or C,
HIV/AIDS, pneumonia, endocarditis by S. aureus, osteomyelitis, fat necrosis,
lipodystrophy, skin atrophy, PUD, amenorrhea, and many more, all of which can be
encountered in pts needing surgery.
 Heroin- opioid analgesic synthesized from morphine. Used still for TX of severe pain.
 Injection of Heroin- intense sensations such as warmth, taste, high, intense pleasure.
However double blind studies show even experience opioid addicts cannot distinguish
between heroin and hydromorphone- interesting.
 IV effects- less than 1 minute. Very lipophilic. Crosses BBB quick. Deacetylated to
active metabolites 6 monoacetyl morphine and morphine.
 Pharmocokinetics
1. Hepatic Metabolism
2. T1/2 Life less than 10 minutes
3. Excretion 90% Renal, 10% biliary
 Compulsive drug seeking and use, physical dependence, higher doses needed to achieve
same effect.
 Rapid tolerance as well as respiratory depressant, analgesic, sedative and emetic effects.
 Miosis- indicator of user of opioids- this is via stimulation of Edinger-Westphal nucleus
of the oculomotor nerve.
 Withdrawal S/S
1. - Symptoms- Craving for more, restlessness, irritable, nausea, pain, cramps, dysphoria,
insomnia, anxiety.
2. Signs- pupil dilation (mydriasis), sweating, piloerection, tachycardia, HTN, yawning,
fever.
 Withdrawal treatment- Opioid withdrawal syndrome- usually lasts 5-10 days. Switching
addict to long-acting opioid such as methadone. Or tx with a2-receptor agonist clonidine
 Autonomic signs seen- from the loss of opioid induced suppression of the adrenergic
neurons in the locus coeruleus- clonidine restores this inhibition.

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 Recently- buprenorphine- partial mu agonist, kappa antagonist
 Long term management- Stabilize with methadone. Naltrexone- blocks MuOpioid
Receptors preventing effects of heroin-for highly motivated individuals
 I have seen Suboxone- buprenorphine and naloxone combination for withdrawal
treatment- Oral stops withdrawal symptoms. However if user attempts to inject-
produces withdrawal symptoms. Nice in that user cannot attempt to convert oral form to
IV form for rush.
 Anesthetic Implications
1. Regional is safe, although increased tendency for hypotension. Also increased
incidence of spinal, epidural and disc-space infections have been reported.
HIV/AIDS- should be okay but make sure there is no CNS HIV infection.
2. Difficult peripheral and central vein access. May be underlying sepsis, coagulopathy,
hemodynamic instability.
3. May have liver disease concomitant, malnutrition, reduced intravascular volume
which require adjustments in anesthetic drug doses.
4. These patients NEED often much higher doses of opioids perioperatively.
5. Patients coming in acutely high on opioids have lower MAC requirements
6. Chronic opioid users- chronic receptor stimulation and down-regulation, and
decreased production of endogenous opioids- EXAGERRATED PAIN.
7. Very challenging perioperative management- ethical issue between liberal vs.
conservative, managing pain vs. encouraging addict.
Hallucinogens and Other Club Drugs

 LSD

 Lysergic Acid diethylamide- chemical found in morning glory seeds and ergot- a rye
fungus. Colorless, odorless, tasteless.
 MOA- Thought to produce hallucinogenic effects by activating several subtypes of
serotonin receptors
 Pharmocokinetics
1. Psychedelic effects with less than 100mcgs.
2. Route- Oral, IV, Ocular, IM
3. Hepatic metabolism, renal elimination
4. T1/2 Life- 3-6 hours
5. Not addictive
6. Rapid absorption orally- onset 40-60min, peak 2-4 hours, duration 8 hours
 S/S- Mydriasis, reduced appetite, tachypnea, bradypnea, hallucinations, psychosis, coma,
death, N/V, numbness, weakness, hyperthermia, hyperglycemia, piloerection, jaw
clenching, hyperreflexia, seizures, tremors, sleeplessness.

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 PCP- Sernyl

 Angel dust.
 Originally developed as an anesthetic- but unfortunately found to produce severe
delirium and hallucinations
 MOA- dissociative anesthetic by working on NMDA receptor. Also on D-2 receptor-
psychosis effects. Many different interactions not fully understood- effects nicotinic,
muscarinic cholinergic, noradrenergic and serotonergic neurotransmission.
 Smoked, oral, insufflation
 T1/2 Life 6-48 hours
 Ketamine in same family- 1/20 the strength
 Paranoia, Schizophrenia, delirium, disorientation, many psychological effects,
hallucinations, suicidal ideation, aggression
 Many common CV and sympathomimetic effects- Tachycardia, HTN, diaphoresis,
lacrimation, increased bronchial secretions
 Acute/Chronic issues- Seizures, hyperthermia, intracranial hemorrhage, apnea,
rhabdomyolysis- ARF, hypotension, circulatory collapse
 Haldol treatment of choice for psychotic reactions from PCP. There is no treatment for
overdose.
MDMA- 3, 4- methylenedioxmethamphetamine

 X, E, XTC, Ecstasy, love drug.

 First synthesized as appetite suppressant
 Swallowed or rectal insertion- absorbed readily in GI tract.
 Effects- 3-6 hours. Stimulant and Hallucinogenic properties. Ability to provide feelings
of warmth and empathy.
 MOA- increases the release of serotonin in the neocortex, limbic system and spinal cord.
 Acute Effects- Elevated mood, reduced appetite, disturbed behavior, clouded thinking,
sweating, polydipsia, hyperthermia, tachycardia, hypertension, muscle spasms- jaw
clenching. High or repeated doses- cardiac arrhythmia, acute rhabdomyolysis leading to
ARF, malignant hyperthermia, liver damage, DIC, liver failure.
 These effects are related to MDMA-induced dysfunction of the hypothalamus- which
regulates HR BP fluid retention, kidney function, body temperature, etc.
 Seizures- attributed to severe hypoNa and cerebral edema that occurs from profuse
sweating and polydipsia. (water intoxication)

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 Rohypnol (flunitrazepam) and GHB (gamma-Hydroxybutyrate)

 GHB binds to GABA-B. Rohypnol is a benzodiazepine.

 Date rape drugs
 Both active orally. At high doses GHB can induce sleep, coma, death
 Rohypnol can be fatal if mixed with ETOH or other CNS depressants
 Rohypnol onset 30min, peak 1-2 hours, duration 8-10 hours. Causes anterograde
amnesia, short-term memory loss.
 GHB, AKA liquid ecstasy- once used as anesthetic- declined due to side effects- severe
nausea, seizures.
 GHB- another easy one to make at home- [Link]
 GHB onset 10-20 minutes, last up to 4 hours.

Fry

 An altered form of marijuana that is soaked in PCP laced, formaldehyde-soaked papers.

 Primary effect- toxic psychosis. Also hallucinations, delusions, panic, paranoia
 Side effects obviously with embalming fluid- memory loss, disorganized thoughts,
psychomotor agitation, up regulation of the SNS. Bronchitis, brain, lung damage,
inflammation.

Anesthetic Considerations- hallucinogens and/or club drugs

 Anticipate autonomic deregulation- HTN, HoTN, Tachycardia should all be anticipated

and prevented- increased risk of MI, coronary and cerebral vasospasm.
 Use extreme caution with vasopressors. Ephedrine may not work- catecholamine
depletion
 Exaggerated response to sympathomimetic drugs- arrhythmias common.
 Hallucinogens may prolong analgesic and ventilator depressant effects of opioids.
 Ecstasy and polydipsia, hypoNa- think pulmonary edema. Monitor labs
 LSD and PCP may prolong succinylcholine effects due to inhibition of plasma
cholinesterase activity.
 Consider- MDMA related hyperthermia- AVOID volatile agents and suxx, just like you
would in an MH patient.

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 Solvents

 Inhalants- variety of substances such as organic solvents, volatile agents.

 Toluene most commonly used- major component of household paints, glue, rubber
cement, cleaning agents.
 Most common in the teenage group. Ease of obtaining and transient euphoria.
 Complications- cardiac arrhythmias, bronchial irritation, ARDS, liver failure, pulm HTN,
methemoglobinemia, death from cerebral or pulmonary edema.
 Long term- cerebellar degeneration, diffuse brain atrophy.
 Anesthetic considerations- MI, labile blood pressures, cardiac arrhythmias. Acute
intoxicated patients- GA best option. Potential for difficulty ventilating- increased
airway resistance.

558
 Review of the Immune System

 There are two PRIMARY lymphoid tissue- Thymus and Bone Marrow
 SECONDARY lymphoid tissue- spleen, lymph nodes, tonsils, gut-associated lymphoid
tissue (GALT)
 Key features- Specificity and Memory- self vs. oneself
 There are 2 categories of immune response- non-specific innate, and specific acquired

Cellular Components of Immunity

 Phagocytes
1. PMNs- phagocytosis and destruction of microorganisms, contain bactericidal
substances/produce bactericidal reactive oxygen molecules
2. Monocytes- Circulating cells of mononuclear phagocyte system- after entering tissue,
monocytes mature into macrophages
3. Macrophages- Mobile and fixed tissue cells of the mononuclear phagocyte system-
perform phagocytosis, destroys microorganisms. Presents antigen to helper t cells and
secrete cytokines
4. Eosinophil’s- Provide defense against parasites and perform phagocytosis of allergen-
antibody complexes formed in an allergic response
 Lymphocytes
1. NK cells- Destroys virus infected “self” cells and tumor cells; secretes cytokines
2. B lymphocytes- Differentiate into plasma cells that secrete antibodies; present antigen
to T helper cells.
3. Helper T lymphocytes- secrete cytokines the stimulate T helper cell proliferation and
activation of B lymphocytes, cytotoxic T lymphocytes, and macrophages.
4. Cytotoxic T lymphocytes- engage antigen and secrete pore forming proteins known
as perforins into foreign cell membrane; secrete granzymes that destroy the targeted
cell.
 Auxiliary Cells
1. Mast cells and basophils- release histamine and other pro-inflammatory mediators
responsible for hyperemia, increased vascular permeability, pain.
2. Dendritic cells- Present antigen to T helper cells
3. Platelets- participate in coagulation and walling off of areas of inflammation; secrete
pro-inflammatory mediators.

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 Innate Immunity

 Nonspecific- Provides defense against a large number of pathogens. EARLY FIRST

LINE OF DEFENSE. Begins defense within minutes to hours.
 Components of Innate Immunity-
1. FIRST line of Defense- Barriers- Physical- skin hair mucous Chemical- sweat
tears saliva urine stomach acid
2. Cellular Response- Phagocytosis, inflammatory reaction, NK cells, mast cells
3. Cells involved- NK cells, phagocytes, Mast cells, Basophils and eosinophil’s
4. Soluble Factors- complement
 Innate Immunity- Present since your birth
 Phagocytes- patrol the body. Ingest foreign material. Act as scavengers ridding body of
worn out cells
1. The primary phagocytes- PMNs and Macrophages. Neutrophils are the MOST
ABUNDANT circulating leukocyte
2. This group altogether- neutrophils, eosinophil’s, macrophages and monocytes
3. Recognize molecules- PAMPS- associated with microorganisms
4. Attracted to areas of invasion through chemotaxins- chemical signals such as
bacterial toxins, products of tissue injury
5. After phagocyte engulfs material- makes a phagosome- then lysosome joins- making
phagolysosome so digestive enzymes kill it.
6. Another group of phagocytes- antigen-presenting cells (APCs) - include
macrophages, monocytes, dendritic cells. After eating invader- these wear pieces of
it called antigens to tell others what to look for.
 NK cells- Natural killer cells-BOTH INNATE AND ACQUIRED IMMUNE SYSTEM
Develop in bone marrow- potent killer of virus infected cells. They bind to infected cell-
secrete a pore producing protein- perforin- puts holes in cell- aptosis occurs since water
rushes in cell.
 NK cells – MAIN immune cell in pregnant uterus- protect uterus and fetus from virus.
Also they look out for tumor cells and destroy some of them. Release cytokines
 IFN-y, or IFN-gamma is released by NK cells.
 Soluble factors- Interferon
1. A chemical (cytokine) produced by virus-infected cells, inhibits synthesis of viral
proteins.
 Soluble factor- Acute Phase protein- made in liver- increase during infection and
inflammation- act as opsonins- coat pathogens for recognition and phagocytosis
 Complement System--- BOTH INNATE and ACQUIRED
1. Collection of plasma proteins produced in liver
2. Cascade of reactions- particular complement catalyzes production of next component
in cascade and so on.
3. Main proteins- C1 through C9.
4. Antigen-antibody reaction- classical pathway. Lectin pathway- activated by bacterial
carbohydrate.
5. Final products cause opsonization, chemotaxis, activation of mast cells and basophils.

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 Inflammatory Response- Hallmark Reaction of Innate Immunity

 - steps- Damaged tissue- then immune cells and chemical mediators go to site, these
produce a physical barrier, promotes tissue repair once infection is under control.
 It is created when activated tissue macrophages release CYTOKINES- which attract
other immune cells, increase capillary permeability, and cause fever.
 Cytokines- TNF-a, IL-1, IL-6, IL-2.
 TNF-a stimulates production of endothelial adhesion molecules and chemokine’s.
 Overproduction of TNF-a is CHARACTERISTIC OF Systemic Inflammatory Response
Syndrome
 Immediately after injury or infection- Acute phase proteins come in- these act as
opsonins, antiprotease molecules, and C-REACTIVE PROTEIN
 Putting it together- CRP that is high is associated with CAD since atherosclerosis is an
inflammatory response from macrophages in blood vessels eating cholesterol and
becoming foam cells.
 Inflammation and HISTAMINE-found in MAST CELLS and BASOPHILS- this initiates
inflammatory response when mast cells degranulate.
1. Histamine brings more leukocytes to injury site to kill bacteria-
2. Histamine opens pores in capillaries causing edema and swelling.
3. Histamine dilates blood vessels increasing blood flow to area
4. RESULT- Hot, Red, Swollen area around wound or infection
5. Mast cells activated after antigen binds to IgE. Mast cells degranulate Histamine,
heparin, chondroitin sulfate, chemotactic factors such as serotonin which signal
neutrophils, eosinophil’s to site of inflammation.
Acquired Immunity- Antigen Specific Response

 B lymphocytes, T lymphocytes and NK cells.

 B Cells-Humoral/Antibody- develop into plasma cells- that secrete antibodies. And
Memory Cells
 B cells develop in bone marrow- B with b.
 T Cells-cell mediated- attack or destroy virus infected cells or envelop into
 Natural Passive- Mommy passing antibodies to fetus- IgG. Also found in breast mile
 Fetal/Neonatal immune- Immature, cell-mediated capabilities all functional
1. IgM production, unable to produce IgG response- that is why mommy gives to uterus
2. IgG level in cord at adult level in birth
3. Think baby- innate immune system.
 Natural Active- When infection leads to activation of B and T cells- and you develop
immunity
 Artificial Active- Think vaccinations
 ANTIBODIES- proteins secreted by plasma cells
1. IgG- most abundant in body- only antibody that crosses into placenta
2. IgA- localized protection- found in mucosal – gut, resp. tract, urogen. Tract, - IgA-
think saliva, tears, breast milk

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 3. IgM- Complement fixation- expressed on B cells. IgM helps kill pathogens early in
B cell immunity before IgG kicks in.
4. IgD- Activates Mast and Basophils
5. IgE- binds to allergens triggers histamines, and protection against parasitic worms.
 Antibody Proteins-Polypeptide linked into a Y shape- top of “Y”- both sides have heavy

and light chain-

 Antibody Functions- Act as opsonins, make antigens clump, inactivate bacterial toxins,
enhance inflammation by- activate complement, and mast cells. Also- final role is that
the antigen bound antibody activates immune cells.
 T- Cell Response to Antigens
1. Needs presentation of antigen to T lymphocytes by infected cells or APCs.- The
APCs such as dendritic cells, macrophages, and B cells
2. Antigen fragment presented bound to a major histocompatibility (MHC) molecule on
presenting cell surface
3. T-cell receptors on T cells- recognize and bind to antigen MHC complex.
 MHC-
1. Two types- Class 1- present on surface of all nucleated cells. Class 2- Present on
surfaces of APCs
2. MHC also known as human leukocyte antigen (HLA). - HLA-A, HLA-B, HLA-C.
3. Genetic variability in HLA type influences susceptibility to infection, autoimmune
disease, and rejection of transplanted tissue- organs, blood.
 Hypersensitivity Reactions
1. Type 1- Immediate Anaphylactic Reaction- IgE- Mast Cells and Basophils- IgE-
Histamine
2. Type 2- Antibodies bind to antigens on patient’s own cells- antibody-dependant or
cytotoxic hypersensitivity- IgG, IgM or IgA. Type 2 is GAM. Think type 2-
transfusion reactions, myasthenia gravis, Goodpasture syndrome
3. Type 3- Immune Complexes- GAM- IgG, IgA, IgM. Usually IgA- Antibody-
Antigen- A. Think 3 Glomerulonephritis, SLE, Rheumatoid Arthritis
4. Type 4- Cell-mediated= delayed- takes 2-3 days to develop- T cells, Macrophages-
Involves contact dermatitis, TB skin test, poison ivy, metals, LATEX. Type 4-
LATEX REACTIONS

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 TX of Allergic Type 1 Reactions

Intraop Anaphylaxis- - Combo of cutaneous resp and CV s/s- bronchospasm,

circulatory collapse, wide spread flushing.
1. STOP EXPOSURE
2. D/C ALL ANESTHETIC AGENTS
3. Fluid Resuscitate NS, LR, Voluven, Plasmanate
4. Epinephrine 100-500mcg SQ or IM up to max of 1mg. Kids- 10mcg/kg up to max of
500mcg.
5. Know that Epi- 5-10mcg IV boluses for HOTN. 100-500mcg for CV collapse. Mast
and Baso degranulation- attenuated by B-agonists- that is why Epi
6. Benadryl 1-2mg/kg or 25-50mg/dose oral.
7. Glucocorticoids.
8. CPR is loss of circulation or respiration- obviously- BLS, ACLS, and PALS.
9. O2, monitors. HOTN- Pressors, IV crystalloid vs. colloid. Bronchospasm- B2
agonists, antimuscarinics, theophylline. NaHCO3 for refract HOTN and determined
by ABGs. Glucagon for refractory hypotension, IV Calcium

 Latex allergy- Type IV vs Type I. Know that Type IV is delayed. Mediated by

histamine and tryptase. Most common type of latex allergy is Type IV Hypersensitivity.
At Risk Groups- Banana, avocado, kiwi, apricot, chestnut, grape, passionfruit, pineapple,
peaches, cherries.

HIV

 Infection involving depletion of CD4 lymphocytes.

 Glycoprotein on viral envelope binds to CD4 antigen to allow virus to enter T Cell
 Retrovirus- two strands of single stranded RNA. Once virus enters cell- RNA- reverse
transcription- complementary DNA that incorporates into host DNA.
 Transmission through bodily fluids- primary blood, sex, and perinatal.
 Acute HIV infection- mono like illness- release of inflammatory mediators- IL-1, TNF-a-
malaise fever rash.
 Gradual progressive fall in CD4.
 Can progress to AIDS- defined as CD4 count less than 200cells/uL.
 Treatment modalities- “a cocktail” of several med classes= refer to big pharm too
extensive
1. Nucleoside reverse transcriptase inhibitors- Zidovudine- AZT.
2. Non-nucleoside reverse transcriptase inhibitors-
3. Protease Inhibitor
4. Fusion Inhibitors- Enfuvirtide

563
 Anesthesia and Immune System

 No clear picture how anesthetic agents alter immune function

 Surgical Stress and Immune Function
1. Surgical trauma- provoke or inhibit cytokines- cause immunosuppression- depressed
cell-mediated immunity
2. Tissue trauma from surgery- stimulates HPA axis- release of cortisol from adrenal
cortex- immunosuppression.
3. SNS increases catecholamine secretion from adrenal medulla. - Activation of B
adrenergic receptors suppress monocytes and TNF-a, IL-1, PMN. And lymphoid
receives SNS innervation.
4. Magnitude of surgical stress influences postop immune responses i.e. - laparoscopy
better immune function vs. laparotomy.
5. Wound healing impaired- IL-1, TNF-an essential in wound healing- they regulate
ability of fibroblasts and epithelial cells to remodel damaged tissue.
6. Post-op Pain- Increased plasma epi- B receptors suppress monocytes TNF-a, IL-1,
PMN. Also increased cortisol, endorphin reflecting SNS and HPA axis activation.
7. SO with above- If you block nociception locally or at spinal cord (RA) then you
decrease neuroendocrine and immune response. LA infiltration, epidural vs. GA all
lower incidence of postop wound infections.
8. Studies suggest opioids/narcotic anesthesia suppresses hormonal response to surgery.
 Anesthetic Agents and Immune Function
1. Volatile agents may suppress effector functions of innate and adaptive immunity.
2. LAs block neurons and are potent anti-inflammatory drugs.
3. Morphine has immunosuppressive function not shared by synthetic opioids.
4. Studies have proven perioperative O2 improves postop outcomes- FiO2 of 0.8
doubles subcut O2 tension- halves postop wound infections.
5. Studies have shown craniotomy cases- T cell ratios are less reduced with
TIVA/propofol vs. isoflurane.
6. Propofol may be more appropriate in HIV patients some studies suggest less decrease
in T cell ratio.
7. Know that neuraxial anesthesia may prevent or reduce the degree of perioperative
immune dysfunction.
8. Periop hypothermia- surgical wound infection secondary to vasoconstriction and
decreased O2 tension- impairs oxidative killing by neutrophils, impairs immune
function.

564
 Bleeding & Clotting Cascade

Clotting Cascade

Coagulation Factors

Vitamin K Present in
Factor Name Pathway Notes
Dependent Cryo

I Fibrinogen Common - Yes -

II Prothrombin Common Yes - AT3 inhibits factor IIa

III Tissue Factor Extrinsic - - -

All Required for all

IV Calcium _ _
Pathways pathways

V Proaccelerin Common - - APC inhibits factor Va

N/A (formerly factor

VI - - - -
Va)

VII Proconvertin Extrinsic Yes - -

565
 Antihemophilic APC inhibits factor
VIII Intrinsic - Yes
factor VIIIa

IX Christmas factor Intrinsic Yes - -

X Stuart factor Common Yes - AT3 inhibits factor Xa

Plasma
XI thromboplastin Intrinsic - - -
antecedents

XII Hageman factor Intrinsic - - -

Fibrin-stabilizing
XIII Common - Yes -
factor

Pathogenesis of Hemorrhage – Primary Hemostasis

 Primary Hemostasis
o Requires ability to maintain hemostasis
 Hemostasis – arrest of bleeding
o Result of hemostasis:
 Volume
 Pressure
 Flow
o Triad of hemostasis:
 Vasculature (endothelial cells and subendothelial matrix)
 Platelets
 Blood proteins (clotting factors)
 Hemostasis
o Sequence of events in hemostasis
 Vascular injury  arteriolar vasoconstriction
 Endothelial cell lining damage  platelet adherence and activation and
formation of a hemostatic plug
 Tissue factor + platelet factors + activated platelets  activation of
coagulation
 Regulatory pathways are activated
 Platelet Activation
o Vascular damage initiates process of platelet activation:
 Increased platelet Adhesion to the damaged vascular wall
 Activation leads to secretion of chemicals from platelet granules, which
stimulates a change in platelet shape and biochemistry
 Aggregation, which leads to activation of the clotting system and
development of an immobilizing meshwork of platelets and fibrin

566
 Adhesion
o Platelets become adherent to the site of endothelial damage where the
subendothelial matrix is exposed and endothelial cells have released von
Willebrand factor (vWF)
o Adhesion is primarily mediated by the binding of platelet surface receptor
glycoprotein-Ib (in a complex with factors IX and V) to vWF
 Activation
o Activation results in dynamic changes in platelet shape from smooth spheres to
those with spiny projections and degranulations (platelet release reaction)
o The changes the platelet plasma membrane undergoes causes them to be ruffled
and sticky
o Platelets contain 3 types of granules:
 Lysosomes
 Dense Bodies – contain ADP, serotonin, calcium.
 ADP – recruits and activates other platelets through specific
receptors
 Alpha Granules
o Platelets also initiate production of prostaglandin derivative thromboxane-A2
(TXA2), which counters the effects of prostacyclin (PGI2)
 TXA2 – promotes degranulation of platelets, increases expression of
platelet fibrinogen receptors, and stimulates platelet aggregation
 Aggregation
o Platelet aggregation is stimulated primarily by thromboxane-A2 (TXA2) and
ADP, which induce functional fibrinogen receptors on the platelet
o The GPIIb-IIIa complex undergoes conformational change during activation to
become a calcium-dependent factor receptor for fibrinogen
 The GPIIb-IIIa-fibrinogen pathway is essential for the formation of a
thrombus and is an important therapeutic target for blockage by
antiplatelet drugs

567
Pathogenesis of Hemorrhage – Secondary Hemostasis

 Formation of a fibrin clot

o Fibrin network binds and strengthens the platelet plug
o Fibrin formed via two pathways:
 Intrinsic
 Extrinsic
o Result  conversion of fibrinogen to fibrin

568
 Fiber Size and Function-Regional:
α: (dia 12-20um; conduction velocity 70-120m/s) largest, afferent to and efferent from
muscles and joints. Actions: motor function, proprioception, reflex activity.

β: (dia 5-12um; 30-70m/s) large as A-alpha, afferent to and efferent from muscles and
joints. Actions: motor proprioception, touch, pressure, touch and pressure.

δ: (dia 2-5um; 12-30m/s) thinnest, pain and temperature. Signal tissue damage.
B fibers: (dia – 2-5um) Myelinated preganglionic autonomic. Innervate vascular smooth
muscle. Though myelinated, they are more readily blocked by LA than C fibers.

C fibers: (dia 0.4-1.2 um) Nonmyelinated, very small nerves. Smallest nerve fibers, slow
transmission. Transmit dull pain and temperature, post-ganglionic autonomic.

* Both A-d and C fibers transmit pain and are blocked by the same concentration of LA.

Order of sensory function block

1. Pain B (first blocked) not really pain Sympathetic
2. Cold C, A-Delta Pain, Temp, Touch
3. Warmth A-Gamma—Well?? Spindle Tone
4. Touch A-Beta Touch, Pressure
5. Deep pressure A-Beta More Pressure
6. Motor A-Alpha Motor-Proprioception

569
 Recovery in Reverse Order

Lipid Rescue for Local Toxicity:

20% lipid solution
1.5 ml/kg over 1 minute
Follow immediately by an infusion at rate of 0.25ml/kg/min (17.5 ml/min for a 70 kg
adult)
Repeat dose if no improvement – and double the infusion rate
Max of 10 ml/kg???
[Link]
Airway Management
TX seizures
ACLS------limit epi----Weinberg work!
What about Propofol? (Propofol is 1%) Lipid based? –Notice concentration! Need 20%

570
 Many classes of compounds bind and inhibit Na channels

Local anesthetics
Ca channel blockers

2 agonists
Tricyclic antidepressants
Substance P antagonists
Many nerve toxins
Benadryl
Droperidol????

571
 Regional Anesthesia

Baricity:

 equal to the density of the local anesthetic divided by the density of the CSF
 main determinant of how the local anesthetic is distributed when injected into the CSF
 Local anesthetics can be…..when compared to CSF:
o Hypobaric: Baricity<1.0, Med in H2O, ↓ density than CSF → rise; positioning
of pt after injection is important (for perineal/anal sx, in prone/jackknife)
o Isobaric: Baricity = O, remains in the level of the injection; positioning does
not affect spread of LA
o Hyperbaric: Baricity > 1, med in dextrose, ↑ density than CSF → “fall”,
positioning is important

Density, Specific Gravity, and Baricity of Different Substances and Local Anesthetics
Density Specific Gravity Baricity
Water 0.9933 1.0000 0.9930
CSF 1.0003 1.0069 1.0000
Hypobaric
Tetracaine 0.33% in water 0.9980 1.0046 0.9977
Lidocaine 0.5% in water N/A 1.0038 0.9985
Isobaric
Tetracaine 0.5% in 50% CSF 0.9998 1.0064 0.9995
Lidocaine 2% in water 1.0003 1.0066 1.0003
Bupivacaine 0.5% in water 0.9993 1.0059 0.9990
Hyperbaric
Tetracaine 0.5% in 5% dextrose 1.0136 1.0203 1.0133
Lidocaine 5% in 7.5% dextrose 1.0265 1.0333 1.0265
Bupivacaine 0.5% in 8% dextrose 1.0210 1.0278 1.0207
Bupivacaine 0.75% in 8% dextrose 1.0247 1.0300 1.0227

Levels for major procedures:

Body Landmark Dermatome Level Procedure
Little finger C8 (All cardio
accelerator fibers
blocked)
Nipples T4 Upper abdominal surgery
Xiphoid T6 Intestinal, gynecologic, and urologic
surgery
Inferior edge of T7
Scapula
Umbilicus T10 Vaginal delivery of a fetus, and hip surgery

572
 L1 Thigh surgery and lower leg amputations
L2 Foot and ankle surgery
Spinal cord ends at L1-2, place spinals below this level.
Superior iliac crest L4
Inferior iliac crest S2
S2 to S5 (saddle Perineal and anal surgery
block)

Spinal Epidural
Smaller doses of LA (mg) → mg block → Larger doses of LA (ml) → Volume block →
→Lower potential for toxicity →Higher potential for toxicity
Faster onset Slower onset
Limited Duration Flexible duration
Lower failure rate (CSF is definitive for Higher failure rate
location)
Baricity has an effect Baricity has no effect (no CSF to create
Baricity)

Doses for Spinal Blocks:

Dose, Duration, and Onset of Local Anesthetics Used in Spinal Anesthesia
Dose (mg) Duration (min) With 0.2mg
Onset (min)
to T10 to T4 Plain Epinephrine
Commonly Used

Lidocaine 5% 50–75 75–100 60–70 75–100 3–5

Bupivacaine 0.75% 8–12 14–20 90–110 100–150 5–8

Less Commonly Used

Tetracaine 0.5% 12–16 70–90 120–180 3–5

Mepivacaine 2% 6–10 60–80 140–160 N/A 2–4
Ropivacaine 0.75% N/A 18–20 140–200 N/A 3–5
Levobupivacaine 0.5% 15–17 N/A 135–170 N/A 4–8
Chloroprocaine 3% 10–15 45 80–120 130–170 2–4
30

Drug Onset Maximum Dose Duration

(with epinephrine); (with Epinephrine)
Max mg dose
Lidocaine Rapid 4.5 mg/kg (7 mg/kg) 120 min (240 min)

573
 300mg (500 mg)

Bupivacaine Slow 2.5 mg/kg (3 mg/kg) 4 hours (8 h)

175mg (225mg)
Chloroprocaine Rapid 10 mg/kg (15 30 min (90 min)
(short mg/kg)
duration) 800mg (1000mg)

Doses for spinal blocks depend on:

 Height of pt → determines the volume of the subarachnoid space

 Segmental level of anesthesia desired
 Duration of anesthesia desired

Doses for Epidural blocks (Volume blocks): the volume depends on the location the catheter
tip in the epidural space as the size of the segmental epidural spaces increases down the spinal
cord as the spinal cord occupied less and less space.
Site of procedure Dose in ml
Chest T12-L2 8-12ml
Upper Abdomen L2 12-16ml
(Cholecyctectomy, gastric
resection)
Lower Abdomen
Colon resection, aortic L2 12-16ml
aneurysm, retro pubic
prostatectomy
Herniorrhaphy L3 8-12ml
hysterectomy L3 10-14ml
Lower Extremities
Anesthesia L4 10-14ml
Sympathetic block L2 8-12ml
Perineum (TURP, vaginal L4 8-12ml
hysterectomy)
Back and flank (nephrectomy) L2 10-14ml
Vaginal delivery
1st stage labor L3 5-7ml
nd rd
2 and 3 stage labor L3 10-12ml
Nagelhout p. 1067

574
 Opioids in Regional Anesthesia:

Epidural anesthesia:
Hydrophilic opioids (Morphine) spread easily within CSF and can enhance surgical
anesthesia and provide postoperative pain control.
Lipophilic opioids (Fentanyl) rapidly absorbed into systemic circulation → no strong
effect.
Epidural Opioids Bolus Dose Onset Peak Duration
Morphine 2-5mg 20-30min 30-60min 12-24hr
Hydromorphone 1 mg 10-15min 20-30min 8-15hrs
Nagelhout p.1069

Spinal anesthesia: Spinal doses are approximately 10 times less than the epidural doses.
Morphine: 0.1-0.5mg can provide pain control for ~24hrs, but necessitates in-hospital
monitoring for respiratory depression → is the traditional opioid for prolonged pain
management.
Fentanyl: 25mcg for short surgical procedures, pts can be discharged home the same day.

575
Transient neurological symptoms (TNS) syndrome of pain and dysesthesias that may occur
in up to 1/3 of pts receiving intrathecal doses of lidocaine.

 Pathogenesis of TNS is believed to represent concentration dependent neurotoxicity of

local anesthetics
 Rarely occurs with other local anesthetics
 Mechanism responsible is unknown
 Increased incidence in pts in lithotomy position, positioning for knee arthroscopy, and
outpatient procedures
 Symptomstypically include back pain, weakness, and numbness radiating to one or
both buttocks and down the legs, or both. Does not consistently manifest with
sensory/motor deficits or reflex abnormalities.
o Appear within first 12-24 hours after surgery
o Exclusively a pain syndrome, no bowel or bladder dysfunction
o All neuro, MRI and Electrophysiologic examinations are normal
o Most often resolve within 3 days, rarely last a week.
 Pain is often more severe than the surgical procedure.
 TreatmentNSAIDs, possibly opioids if severe pain, and trigger point injections, time to
allow symptoms to pass

Caudal equina syndromeresult of an injury below the level of the conus, or caudal end of the
cord, typically below L2. Persistent paresthesia and limited motor weakness are the most
common injuries

 Nerve roots within the subarachnoid space are highly vulnerable to chemical damage,
particularly the sacral roots which are poorly myelinated.
 Typically results from compression within the lumbar spinal canal or from chemical
damage
Risk factors

 Poor subarachnoid dispersion of LA

o Block failure, followed by a repeat injection
o Fine-gauge or pencil point needle
o Spinal micro catheter
o Continuous infusion
o Hyperbaric anesthetic solution
o Lithotomy position
 Unintentional intrathecal injection of a large volume intended for the epidural space
 Incorrect formulation, with unsuitable preservative or antioxidant
 Intrathecal LIDOCAINE, particularly 5%
 Can be caused by an epidural hematoma
Treatmentsteroids, anti-inflammatory medications, decompression if related to hematoma

576
Epidural hematomadamage to vessel or anticoagulation can cause a hematoma to form in
epidural space. Incidence <1 in 150,000
Symptoms includecan initially be hard to see in pts with an epidural or spinal block

 Severe, localized back pain with delayed radicular radiation that may mimic disk
herniation
 Weakness
 Numbness
 Urinary incontinence
 Fecal incontinence
Risk factors

 Difficult or traumatic epidural needle/catheter placement or spinal placement

 Coagulopathy or therapeutic anticoagulation
 Spinal deformity
 Spinal tumor
Early recognition is critical as delay of more than 8 hours in decompressing the spine reduces the
odds of good recovery. Treatment is surgical removal of the pressure on the spine.
Important to review what meds the pt is onepidural/spinals should not be done on pts taking
antiplatelet drugs unless they have been held for a specific time frame. Also pts on LMWH at
high risk. Timing of catheter removal is crucial as removal can cause hematoma formation as
well.

Blood patchregarded by many as the gold standard treatment for PDPH. Blood is drawn using
sterile technique. All air is removed from the syringe. It is then injected into the epidural space
near the area of the where the dura was inadvertently punctured.

 Idea is that the blood will help “patch” the hole in the dural space preventing continued
leak of CSF
 Possibly blood in epidural space helps more to tamponade the leak of CSF vs actually
seal the puncture.
 Exact volume used is debatable, average 12-15 mL is used, but can inject up to 20 mL.
With larger volume. The injection is terminated when volume is instilled or pt complains
of severe back, leg, or neck pain or pressure.
 Headache is often relieved immediately
 After procedure pt should lie flat and rest for 1-2 hours. Pt may resume ambulation after
2 hours but should avoid vigorous physical activity, heavy lifting, or any activity
involving a valsalva maneuver.

577
 Procedure may be repeated if first fails. Often second procedure provides relief. If second
fails to relieve PDPH, get neuro consult.
 Two main complications
o Infection
o Neurologiclow back pain with neuro impairment of the lower extremities,
subdural hematoma, arachnoiditis, radicular back pain, pneumocephalus, seizures,
and acute meningeal irritation.

578
 Regional Review
Interscalene block

 Anatomy
o Landmarks
 Clavicular head of the
sternocleidomastiod muscle
 Clavicle
 External jugular vein

 Nerves blocked

Nerve stimulation
 Twitch of the pectoralis, deltoid, arm, forearm, or hand muscles at 0.2-0.4
mA current

579
 Response
Interpretation Problem Action
Obtained
Direct stimulation of the Needle pass is in the
Withdraw the needle to
Local twitch of anterior scalene or wrong plane; usually
the skin level and reinsert
the neck muscles sternocleoidomastoid anterior and medial to the
15o posteriorly
muscles plexus
The needle is inserted too
Needle contacts
posteriorly; the needle is Withdraw the needle to
bone at 1-2 cm The needle is stopped by
contacting the anterior the skin level and reinsert
depth; no the transverse process
tubercles of the transverse 15o anteriorly
twitches are seen
process
This is the result of
Twitches of the The needle is inserted too Withdraw the needle and
stimulation of the phrenic
diaphragm anteriorly reinsert 15o posteriorly
nerve
Withdraw the needle and
Arterial blood
Puncture of the carotid The needle insertion and keep a steady pressure 2-3
noticed in the
artery (most common) angulation is too anterior minutes; reinsert 1-2 cm
tubing
posteriorly
Pectoralis muscle Brachial plexus Accept and inject local
twitch stimulation (C4-5) anesthetic
Twitch of the serratus
Needle position is Withdraw the needle to
Twitch of the anterior muscle;
posterior/deep to the the skin level and reinsert
scapula stimulation of the
brachial plexus the needle anteriorly
thoracodorsal nerve
Trapezius muscle Accessory nerve Needle posterior to the Withdraw the needle and
twitches stimulation brachial plexus reinsert
Twitch of:
pectoralis,
deltoid, triceps, Stimulation of the Accept and inject local
None
biceps, forearm, brachial plexus anesthetic
and hand
muscles

580
  Medications
o Local anesthetic volume 35-40 ml
Onset Anesthesia Analgesia
(min) (hrs) (hrs)
3% 2-Chloroprocaine (+HCO3 + epinephrine) 5-10 1.5 2.0
1.5% Mepivacaine (+HCO3) 10-20 2-3 2-4
1.5% Mepivacaine (+HCO3 + epinephrine) 5-15 2.5-4 3-6
2% Lidocaine (+ HCO3) 10-20 2.5-3 2-5
2% Lidocaine (+ HCO3 + epinephrine) 5-15 3-6 5-8
0.5% Ropivacaine 15-20 6-8 8-12
0.75% Ropivacaine 5-15 8-10 12-18
0.5% Bupivacaine (+ epi) 20-30 8-10 16-18

 Benefits
o Indications for shoulder, arm and elbow surgery
 Risks/side effects
o Infection – strict aseptic technique
o Hematoma – avoid multiple needle insertions, keep 5-minute steady pressure
when carotid artery is inadvertently punctured,
o Vascular puncture – is not common, steady pressure of 5 minutes duration should
be maintained when the carotid artery is punctured
o Local anesthetic toxicity – is rare. Most commonly occurs during or shortly after
injection and is most commonly caused by an inadvertent intravascular injection.
o Nerve injury – local anesthetic injection should never be injected when the patient
complains of severe pain or exhibits a withdrawal reaction on injection
o Total spinal anesthesia – when stimulation is obtained with current intensity of <
0.2 mA, the needle should be pulled back to obtain the same response with the
current > 0.2 mA before injection
o Horner’s syndrome – occurrence of ipsilateral ptosis, hyperemia of the
conjunctiva, and nasal congestion is common and it is dependent on the site of
injection, and total volume of local anesthetic injected
o Diaphragm paralysis – avoid interscalene blockade or use of a large volume of
local anesthetic in patients who have severe, chronic respiratory disease and use
accessory respiratory muscles during breathing at rest

581
Popliteal

 Anatomy
o Landmarks
 Popliteal crease
 Laterally – tendon of biceps femoris
 Medially – tendons of semitendinosus and semimembranosus

 Nerves blocked
o Block of the sciatic nerve at the level of the popliteal fossa
 Consists of two separate nerve trunks, tibia and common peroneal nerves
 As the sciatic nerve descends toward the knee, the two components
diverge in the popliteal fossa between 50 to 120 mm proximal to the
popliteal fossa crease
 Common peroneal nerve continues along the head and neck of the fibula,
branching to the knee joint and cutaneous branches that form the sural
nerve with its terminal branches as the superficial and deep peroneal
nerves
 Tibial nerve continues through the popliteal fossa with terminal branches
that are the medial and lateral plantar nerves with collateral branches that
give rise to the cutaneous sural nerves, muscular branches to the muscles
of the calf and articular branches of the ankle joint
o Results in anesthesia of the entire distal two thirds of the lower extremity, with
exception of the medial aspect of the leg

582
 o Pearls:
 When local stimulation of the biceps muscle, the needle should be
redirected medially
 Local twitches of the semitendinosus muscle indicates too medial insertion
and the needle should be withdrawn to the skin level and reinserted
laterally
o Goal: Visible/palpable twitches of the foot or toes at 0.2-0.5 mA current
 Common peroneal nerve stimulation results in dorsiflexion and eversion
 Tibial nerve stimulation results in plantar flexion and inversion

 Medications
o Requires larger volume of local anesthetic 35-45 ml to achieve anesthesia of both
divisions of the nerve

Onset Anesthesia Analgesia

(min) (hrs) (hrs)
3% 2-Chloroprocaine (+ HCO3) 10-15 1 2
3% 2-Chloroprocaine (+HCO3 + epinephrine) 10-15 1.5-2 2-3
1.5% Mepivacaine (+ HCO3) 15-20 2-3 3-5
1.5% Mepivacaine (+ HCO3 + epinephrine) 15-20 2-2 3-8
2% Lidocaine (+ HCO3 + epinephrine) 10-20 2-5 3-8
0.5% Ropivacaine 15-30 4-8 5-12
0.75% Ropivacaine 10-15 5-10 6-24
0.5 Bupivacaine (or l-bupivacaine) 15-30 5-15 6-30
o Typical onset time 10-25 minutes
o Signs of blockade: patient reported “foot feels different” or an inability to wiggle
toes

583
 o Sensory anesthesia of the skin is often the last to develop and may take up to 30
minutes
 Benefits
o Clinical use: foot surgery and Achilles tendon repair
 Risks/side effects
o Systemic toxicity and vascular punctures are rare
o Infection – use of strict aseptic technique
o Hematoma – avoid advancement of needle when the patient reports pain - may
indicate the needle is inserted through the hamstrings muscles
o Nerve injury – rare
 Do not inject when the patient complains of pain or high pressures on
injection
 Do not inject when stimulation is obtained at < 0.2 mA current
 Avoid combination of epinephrine in local anesthetic and application of
tourniquet over the injection site to decrease the risk of prolonged
ischemia of the nerve
Spinal

 Anatomy

584
 o Midline approach
 Skin
 Subcutaneous fat
 Supraspinous ligament
 Interspinous ligament
 Ligamentum flavum
 Dura mater
 Subdural space
 Arachnoid mater
 Subarachnoid space
o Paramedian approach
 Skin
 Subcutaneous fat
 Ligamentum flavum
 Dura mater
 Subdural space
 Arachnoid mater
 Subarachnoid space

 Dermatome
o The fourth thoracic (T4)
dermatome corresponds to the
nipples.
o The sixth thoracic (T6)
dermatome corresponds to the
xiphoid.
o The tenth thoracic (T10)
dermatome corresponds to the
umbilicus.

585
Table 1. Dermatomal Levels of Spinal Anesthesia for Common Surgical Procedures
Procedure Dermatomal Level
Upper abdominal surgery T4
Intestinal, gynecologic, and urologic surgery T6
Transurethral resection of the prostate
Vaginal delivery of a fetus, and hip surgery T10
Thigh surgery and lower leg amputations L1
Foot and ankle surgery L2
Perineal and anal surgery S2 to S5 (saddle block)

 Medications
Table 4. Dose, Duration, and Onset of Local Anesthetics Used in Spinal Anesthesia

Dose (mg) Duration

With 0.2 mg Onset
(min)
Epinephrine (min)
to T10 to T4 Plain

Commonly Used

Lidocaine 5% 50–75 75–100 60–70 75–100 3–5

Bupivacaine 0.75% 8–12 14–20 90–110 100–150 5–8

Less Commonly Used

Tetracaine 0.5% 6–10 12–16 70–90 120–180 3–5

Mepivacaine 2% N/A 60–80 140–160 N/A 2–4

Ropivacaine 0.75% 15–17 18–20 140–200 N/A 3–5

Levobupivacaine 0.5% 10–15 N/A 135–170 N/A 4–8

Chloroprocaine 3% 30 45 80–120 130–170 2–4

586
 o Additives
 Vasoconstrictors – epinephrine and phenylephrine – limit systemic
reabsorption and prolong duration of action by keeping the local anesthetic
in contact with the nerve fibers
 Alpha-2-adrenergic agonists enhance pain relief and prolong sensory
block and motor block
 i.e. clonidine
 Acetylcholinesterase inhibitors prevent the breakdown of acetylcholine
and produce analgesia when injected intrathecally
 i.e. neostigmine
o Factors determining spinal level blockade and spread
 Baricity of the local anesthetic solution
 Position of the patient during and just after injection
 Dose of the anesthetic injected
Table 2. Determinants of Local Anesthetic Spread in the Subarachnoid Space
Properties of local anesthetic solution

Baricity

Dose

Volume

Specific gravity

Patient characteristics

Position during and after injection

Height (extremely short or tall)

Spinal column anatomy

Decreased CSF volume (increased Intraabdominal pressure due to increased

weight, pregnancy, etc.)

Technique

Site of injection

Needle bevel direction

587
 Risks/side effects
o Contraindications
 Absolute
 Patient refusal
 Sepsis at the site of injection
 Hypovolemia
 Coagulopathy
 Indeterminate neurological disease
 Increased intracranial pressure
 Relative
 Infection distinct from the site of injection
 Unknown duration of surgery
o Complications
 Permanent neurologic injury - can occur after needle introduction into the
spinal cord or nerves, spinal cord ischemia, bacterial contamination of the
subarachnoid space, or hematoma formation
 After low-molecular-weight heparin (LMWH) administration,
delay spinal anesthesia for 10 to 12 hours
 If blood is noted during needle placement, delay LMWH therapy
for 24 hours
 In cases of continuous spin anesthesia and accidental LMWH
therapy, remove the catheter 10-12 hours after the last dose of
LMWH
 Avoid spinal anesthesia for 14 days after the last dose of
ticlopidine (Ticlid) and 7 days after clopidogrel (Plavix)
 Patients should not receive glycoprotein IIb/IIIa inhibitors for 4
weeks after surgery, and do not attempt spinal anesthesia until
platelet function returns to normal
 Caudal equina syndrome – associated with the use of continuous spinal
micro catheters. Use of hyperbaric 5% lidocaine for spinal anesthesia is
also associated with an increased incidence of cauda equina syndrome
 Arachnoiditis – known to occur after intrathecal steroid injection. Causes
include infection, myelograms from oil-based dyes, blood in the
intrathecal space, neuroirritant, neurotoxic/neurolytic substances, surgical
interventions in the spine, intrathecal corticosteroids, and trauma
 Meningitis – bacterial or aseptic
 Post dural puncture headache – result of loss of CSF with incidence up to
25% after spinal anesthesia. Headache is characteristically worse when the
head is elevated and becomes milder or completely relieved when the
patient is supine.

588
  High spinal – can result in profound respiratory impairment, most likely
due to brainstem ischemia. If the blood pressure and cardiac out become
too low due to vasodilation, cerebral blood flow can be impaired
 Cardiovascular collapse – rare event. Bradycardia usually precedes cardiac
arrest, and early aggressive treatment of bradycardia is warranted.
Treatment with atropine, ephedrine, and epinephrine with ACLS protocol
initiated
Wrist

 Anatomy

o Ulnar nerve – passes between the ulnar artery and tendon of the flexor carpi
ulnaris
o Median nerve – is located between the tendons of the Palmaris longus and the
flexor carpi radialis
o Radial nerver – superficial branch runs along the medial aspect of the
brachioradialis muscle. Then passes between the tendon of the brachioradialis and
radius to pierce the fascia on the dorsal aspect. Just above the styloid process to
the radius, it gives digital branches for the dorsal kin of the thumb, index finger,
and lateral half of the middle finger

589
 Nerves blocked
o Ulnar – supplies digital branches of the skin of the medial 1½ digits
 Deep branch accompanies the deep palmar arch and supplies innervation
to the three hypothenar muscles, the medial two lumbricals, all the
interossei, adductor pollicis, palmar brevis
o Median – supplies the lateral 3½ digits and lateral two lumbricals
 The recurrent branch of the median nerve supplies the three thenar
muscles
o Radial
 External branch supplies skin of the radial side and base of the thumb and
joins the anterior branch of the musculocutaneous nerve
 Internal branch communicates with the posterior branch of the
musculocutaneous nerve

590
 Medications
o Typical onset is 10-15 minutes
o Placement of an Esmarch or a tourniquet at the level of the wrist is well tolerated
and does not require additional blockade
Onset Analgesia
Anesthesia (hrs)
(min) (hrs)
1.5% Mepivacaine (+ HCO3) 15-20 2-3 3-5
2% Lidocaine (+ HCO3) 10-20 2-5 3-8
0.5% Ropivacaine 15-30 4-8 5-2
0.75% Ropivacaine 10-15 5-10 6-24

0.5% Bupivacaine (or l-bupivacaine) 15-30 5-15 6-30

 Benefits
o Common use for carpal tunnel and hand/finger surgery
 Risks/side effects
o Systemic toxicity is rare
o Infection – is rare with strict aseptic technique
o Hematoma – avoid multiple needle insertions for superficial blocks, use a 25-
gauge needle and avoid puncturing superficial veins
o Vascular puncture – do not use epinephrine with wrist and finger blocks
o Nerve injury – do not inject when the patient complains of pain or high pressure
on injection is detected and do not inject again into the medianus and ulnaris
nerves

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 Ankle Blocks – 5 nerves

1. Posterior Tibial; L4-5, S1-3

a. Sensation to skin of heel and medial side of the sole
2. Sural;
a. Branch of tibial
b. Sensation to posterior lateral aspect of lower calf and lateral side of foot and 5th
toe
3. Saphenous:
a. branch of femoral
b. Sensation on medial side of the legs, ankles and onto the foot
4. Deep peroneal: L4-5, S1-2
a. Continuation of the common peroneal nerve
b. Innervates toe extensors and provides sensation to the medial half of the dorsal
foot, especially the first and second digit
5. Superficial peroneal: L4-5, S1-2
a. Branch of the common peroneal
b. Sensation to dorsum of foot and adjacent sides of the 1-5 toes

-This is a volume block

-Epinepherine should be avoided due to potential of inducing ischemia distal to the site of
injection.

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 Procedure--Regional

• **OBTAIN CONSENT**
• Place patient monitors, including blood pressure cuff, ECG, pulse oximeter.
• Appropriate resuscitation equipment, including suction and resuscitation medications, should be immediately
available.
• Patient should have an IV catheter in place, connected via tubing to an appropriate IV fluid, such as normal
saline or lactated Ringer’s.
• Place the patient in the supine position, with the foot on a padded support to elevate the ankle
Clinical Pearls: Although some authors prefer to block the posterior tibial and sural nerves with the patient in
supine position, the posterior tibial nerve can be blocked from the supine position by flexing the knee and placin
the ankle to be blocked on top of the contralateral shin.

Clinical Pearls: Four of the five nerves are sensory, and nerve stimulation is useful only for location of the
posterior tibial nerve. If a nerve stimulator is used, movement of the big toe is the physical sign to look for. This
procedure is described here without use of a nerve stimulator.

• **TIME OUT** Confirm with the patient and surgical staff which limb is the correct limb and mark the site.
• Consider sedation in anxious patients: administer oxygen by mask or nasal cannula, particularly if sedation is
anticipated.
• Wash hands, wear mask and sterile gloves. **STERILE TECHNIQUE**
• Prep the area using betadine or other appropriate surgical prep.
• Deep peroneal nerve
◦ Have the patient dorsiflex the foot
◦ Identify the extensor hallucis longus and extensor digitorum longus tendons.
◦ Palpate the pulsation of the dorsalis pedis artery at the level of the line connecting both malleoli,
between the first and second metatarsals.
◦ Raise a small wheal under the skin with local anesthetic just lateral to the arterial pulsation.
◦ Advance the needle gently perpendicular to the skin until the needle encounters bone.
◦ Slightly withdraw the needle.
◦ Always aspirate prior to injection to avoid intravascular injection of local anesthetic.
◦ Inject 3–5 mL of local anesthetic deep to the fascia.
Clinical Pearls: Inject on both sides of the arterial pulsation to increase the chance of the success of your block
This is done by withdrawing the needle to the level of the skin, advancing in a more medial direction, and
repeating the steps listed above.

593
• Superficial peroneal nerve
◦ After blocking the deep peroneal nerve, withdraw the needle to just beneath the skin.
◦ Turn the needle toward the lateral malleolus.
◦ Infiltrate 5 mL of local anesthetic subcutaneously in a line between the lateral malleolus and the anter
border of the tibia.
• Saphenous nerve
◦ After injecting the superficial peroneal nerve, again withdraw the needle to just beneath the skin (this
will now be at your original injection site), and turn the needle toward the medial malleolus.
◦ Infiltrate 5 mL of local anesthetic subcutaneously while slowly advancing the needle in a line toward
the medial malleolus. The great saphenous vein lies in this area, just anteromedial to the medial
malleolus. To infiltrate around the vein without puncturing it, it may be necessary to make a
further skin puncture lateral to the vein.
◦ Remove the needle.
• Posterior tibial nerve
◦ Using the local anesthetic syringe and needle, raise a small skin wheal of local anesthetic along the
medical aspect of the Achilles tendon at the upper border of the medial malleolus.
◦ Advance the needle anteriorly toward the posterior border of the tibia (the nerve lies just posterior to t
posterior tibial artery).
◦ If a paresthesia is encountered, inject 3–5 mL of local anesthetic.
◦ If no paresthesia occurs, advance the needle to contact the tibia, withdraw the needle 0.5 cm and injec
5–7 mL of local anesthetic.
◦ Withdraw the needle.
• Sural nerve
◦ Raise a small skin wheal of local anesthetic along the lateral border of the Achilles tendon at the uppe
border of the lateral malleolus.
◦ Infiltrate 5–10 mL of local anesthetic subcutaneously while slowly advancing the needle anterior towa
the tibia.

594
595
 Supraclavicular

INDICATIONS
• Anesthesia for surgery of the arm, forearm, and hand
• Analgesia for the arm, forearm, and hand
Post-surgical
Post-traumatic
Complex regional pain syndrome
Post-amputation pain
Vascular disease (ischemic limb pain)
Tumor-related pain
• Vasodilation for some upper-extremity procedures
Vascular flaps
Reimplantation of forearm, hand, digits

CONTRAINDICATIONS
• Absolute contraindications
◦ Patient refusal
◦ Allergy to local anesthetics
◦ Local infection at or near the needle insertion site
• Relative contraindications
◦ Uncooperative patient
◦ Severe respiratory compromise
◦ The need for bilateral upper-extremity anesthesia (and risk for bilateral phrenic nerve blockade or pneumothorace
◦ Coagulopathy or medical anticoagulation
◦ Traumatic nerve injury in the upper extremity or neck
◦ Preexisting neurodeficits in the distribution of the block
◦ Previous surgery in the neck that may distort brachial plexus anatomy

596
ANATOMY-Supraclavicular
The posterior triangle of the neck has well-described borders corresponding to the collarbone at the base, the posterior
margin of the sternocleidomastoid muscle anteriorly, and the trapezius muscle posteriorly, creating the supraclavicular
fossa.4 The supraclavicular fossa is covered by skin and subcutaneous tissue and the supraacromial and supraclavicular
cutaneous branches of the superficial cervical plexus. The anterior scalene muscle originates from the anterior
tubercles of the transverse processes of the fourth, fifth, and sixth cervical vertebrae and inserts onto the anterior aspect
of the first rib. At its insertion, the anterior scalene muscle separates two important vascular structures, the subclavian
artery and vein, respectively, located posterior and anterior to the muscle

Cephaloposterior to the subclavian artery is found the brachial plexus, which rests upon the anterior belly of the middle
scalene muscle. The middle scalene muscle originates in the posterior tubercles of the transverse processes of the first four t
five cervical vertebrae and inserts in the external margin of the first and second ribs. Important vascular relationships are
found in this anatomic region. The subclavian artery emerges to the right from the brachiocephalic trunk and from the
Left of the aortic arch. The subclavian artery is a basic reference for US-guided brachial plexus anesthesia. It, in turn, gives
rise to the vertebral artery, which penetrates the intertransverse foramina (from the sixth cervical vertebra) located
Anterior to the path of the spinal nerves through the neural foramen, and which is of interest when interscalene anesthetic
techniques are performed.

The supraclavicular techniques focus on the supraclavicular fossa, where the superior, middle, and inferior primary trunks
divide into their anterior and posterior branches. The plexus runs superficially at this level, and high-frequency transducers
(10 MHz) are thus needed to identify the structures. Technical difficulties are encountered in studying the supraclavicular
region due to the presence of the supraclavicular depression, which complicates both manipulation of the probe and
Needle puncture. Finally, although the primary trunks of the brachial plexus are easily identified between the scalene
Muscles in the interscalene space, the plexus is more difficult to locate in the supraclavicular zone. Although color
Doppler pulsing is not required to identify the subclavian artery, it greatly facilitates identification of the brachial
Plexus by allowing the differentiation of nerves (hypoechogenic in the absence of Doppler effect) from the arterial and
venous branches found in the zone (hypoechogenic with Doppler effect). The US anatomy of the supraclavicular
Region is shown in. The pleura is identified as a hyperechoic fine line outlining the anechoic lung tissue.

597
PROCEDURE »
• **OBTAIN CONSENT**
• Be sure the patient has an established IV in the nonoperative arm, connected via tubing to an
• IV solution (such as normal saline or lactated Ringer’s solution) that runs freely.
• Select and draw up anesthetic solution for injection into the 30-mL syringe. Connect the syringe and IV
extension tubing to the stopcock. Flush the IV tubing with anesthetic solution by injecting several
milliliters from the syringe into the tubing. Connect the nerve stimulator needle to the IV tubing.
• Attach the wire from the nerve stimulating needle to the stimulator, and ground to an electrode placed
• On the patient’s trunk.
• Apply routine patient monitors, including blood pressure cuff, pulse oximetry, and ECG.
• Have patient lie supine with their head turned away from the side to be blocked.
• Consider IV sedation.
• Administer oxygen by nasal cannula, particularly if sedation is being considered.
• Arrange the US screen, transducer, and needle on the side to be blocked so that all are in one view of the
operator—in the case of the supraclavicular block, this is often to the patient’s side below the
• Arm on the side to be blocked, with the screen facing the operator at the patient’s head. Room lights
• Should be dimmed to enhance US viewing. Be sure the US screen is made to look like a scanning field;
• That is, the right side of the screen represents the right side of the patient. Optimize the US variables
• Such as scanning mode, depth of field, and gain prior to beginning the procedure.
• Wash hands; wear sterile gloves and mask. **STERILE TECHNIQUE**
• Stand or sit on above the shoulder of the patient, on the same side as the one to be blocked.
• Apply sterile prep solution to the neck, clavicle, and infraclavicular space on the side to be blocked
• Drape with sterile towels or fenestrated drape—be sure the elbow is visible.
• Apply sterile sheath over US transducer with US gel, and place another layer of US gel to the patient’s neck.
• Hold the US transducer between the thumb, index, and ring fingers of the non-dominant hand. Place
• The little finger and ulnar aspect of the hand on the patient to stabilize the transducer. Apply firm, even
• Surface pressure with the transducer to produce the best images.
• Apply the transducer to the skin above the clavicle, and orient the US transducer in a coronal
• Oblique axis to the neck. This is the transverse probe orientation. Such transverse imaging facilitates
identification of nerves and associated relations. It also allows verification of circumferential
• Spread of local anesthetic around nerves. (A curvilinear transducer can also be used for this block.)
• Scan the neck from cephalad to caudad. Identify the trachea, common carotid, and internal jugular
• Veins, and sternocleidomastoid muscle. Move the transducer laterally to identify the lateral edge of the
sternocleidomastoid muscle. Beneath this muscle edge lie the anterior and middle scalene
• Muscles, with the roots of the brachial plexus between them.

598
Clinical Pearls: Ask the patient to sniff—this makes the scalene muscles stand out further for identification.

The brachial plexus roots will appear as large hypoechoic (dark) structures. Scan the roots to just above the
clavicle. Here the brachial plexus appears as a cluster of hypoechoic nodules lateral to the subclavian
Artery, lying on top of the hyperechoic first rib. Identify the pleura as a hyperechoic fine line outlining the
anechoic lung tissue.
• Using the small gauge needle and syringe, raise a small wheal of local anesthetic in the skin beyond
• The lateral aspect of the transducer to maintain sterility and allow a shallow angle of approach to improve
visualization of the needle.
• Maintaining position of the US transducer with the non-dominant hand, insert the nerve-stimulating
• needle (connected via tubing and stopcock to the local anesthetic syringe) parallel to the axis of the
• beam of the US probe with the bevel facing the active face of the transducer to improve visibility
• of the needle tip
• Slowly advance the needle under “real time” imaging until the needle reaches the side of the
• target neural structures

Clinical Pearls: Manipulation of the transducer or redirection of the block needle may be necessary
To bring the needle tip into the plane of imaging. Patients tolerate transducer manipulation better than needle
redirection.
Needle placement should be very superficial.
• Once the needle tip has been confirmed by US to lie in close proximity to the nerve roots, its position can be
further confirmed by using a nerve stimulator.
• See Axillary Block for further details on using a nerve stimulator. Characteristic motor activity in the
forearm and hand is seen.
Clinical Pearls: Be sure that the motor twitch involves the forearm and hand;
Shoulder movement may be due to stimulation of local structures.
• Aspirate the syringe to be sure the needle is not intravascular.
• Inject a small “test” volume (0.5 to 2 mL) of local anesthetic. If the local anesthetic spread
• Is not seen on the ultrasound screen, stop injection. During injection of the block (15 to 25 mL of local
anesthetic), readjust the needle to allow complete encirclement of the nerve roots with local
anesthetic. Local anesthetic solution appears as a hypoechoic image.
Clinical Pearls: Typically a decreased volume of local anesthetic is required compared to non-guided
supraclavicular blocks.

599
• Note: Continuous supraclavicular block is similar to the single shot technique. An 18-gauge needle designed for
introduction of an indwelling catheter is used. Once the local anesthetic is injected, the catheter is
carefully inserted some 5 cm beyond the tip of the cannula while keeping the cannula immobile. The
needle is withdrawn while simultaneously advancing the catheter to prevent its dislodgment. The catheter
is secured with a transparent dressing. With this approach, a 2 to 3 cm tunnel can also help to optimize
catheter fixation. The position of the catheter tip is confirmed by injecting 1 to 2 mL of air and observing
its echodense spread. The catheter is secured with a clear, transparent dressing. Compared to the
interscalene approach, this part of the body is minimally exposed to movement, which decreases the risk
for catheter displacement.

600
Infraclavicular block was first described by Bazy in the early 20th century.1 In 1973, Raj and colleagues2
described an infraclavicular approach to brachial plexus anesthesia. The needle pointed posterolaterally, thereby
decreasing the likelihood of pneumothorax, which was often encountered while administering the supraclavicular
block. Since then, several modifications have been reported.3-5 Whiffler and colleagues4 described a subcoracoid
lateral vertical approach.

The infraclavicular approach is particularly useful as all surgical procedures below the shoulder can be
accommodated. Surgical indications include elbow, forearm, and hand surgery. Nonsurgical indications include
complex regional pain syndrome, post-amputation pain, vascular disease and injuries, and tumor-related pain. The
infraclavicular approach allows blockade of the upper extremity where the brachial plexus is most compactly
arranged; therefore a lower volume of local anesthetic is required, and onset of the block is rapid. The location of
the block avoids complications associated with supraclavicular block, such as phrenic nerve paralysis, recurrent
laryngeal nerve, or stellate ganglion block. In addition, the technique can be used with the arm placed in virtually
any position: patients who have difficulty abducting the arm due to pain, trauma, or anatomic restriction can still
undergo infraclavicular block. Ultrasound (US) guidance allows visualization of the pleura and a probable
decreased risk for pneumothorax or intravascular injection with infraclavicular blocks. US also has been used when
traumatic injury to the upper extremity, face, and neck has obscured landmarks for direct-visual performance of
other brachial plexus blocks.6

INDICATIONS
• Anesthesia for surgery of the arm, forearm, and hand
• Analgesia for the arm, forearm, and hand
Post-surgical
Post-traumatic
Complex regional pain syndrome
Post-amputation pain
Vascular disease (ischemic limb pain)
Tumor-related pain
• Vasodilation for some upper-extremity procedures
Vascular flaps
Reimplantation of forearm, hand, digits

601
CONTRAINDICATIONS
• Absolute contraindications
◦ Patient refusal
◦ Allergy to local anesthetics
◦ Local infection at or near the needle insertion site
• Relative contraindications
◦ Non-cooperative patient
◦ Severe respiratory compromise
◦ The need for bilateral upper-extremity anesthesia (and risk for bilateral phrenic nerve blockade or
pneumothoraces)
◦ Coagulopathy or medical anticoagulation
◦ Traumatic nerve injury in the upper extremity or neck
◦ Preexisting neurodeficits in the distribution of the block
◦ Previous surgery in the neck that may distort brachial plexus anatomy

EQUIPMENT
• Appropriate resuscitation equipment, including oxygen, suction, emergency airway equipment, and resuscitation
medications
• Local anesthetic, typically 2% lidocaine with bicarbonate and 1:200,000 epinephrine
• Sterile gloves and mask
• Sterile fenestrated drape or sterile towels for draping
• Sterile prep solution
• A 5-mL sterile syringe and small gauge (25 or 30 gauge) needle for local anesthetic infiltration of the skin
• Two 20-mL syringes, IV extension tubing, and a 3-way stopcock
• 17-gauge Tuohy needle
• Ultrasound (US) machine and transducer sterile ultrasound gel

ANATOMY
The brachial plexus passes behind the clavicle to enter the axilla. In the infraclavicular region, it lies superolateral
to the axillary vessels and cephalad to the chest wall. The plexus lies deep to skin, pectoralis major, and
clavipectoral fascia, which splits to enclose the pectoralis minor muscle. Above the clavicle the trunks have formed
divisions that continue to form the cords of the plexus in the axilla. The cords of the plexus form around the second
part of the axillary artery. The divisions of the artery are named in relation to the pectoralis minor muscle. The
axillary artery becomes the subclavian artery at the lateral edge of the first rib.

602
The US-guided infraclavicular technique is performed over the pectoral region. In view of the increased depth at
which the brachial plexus is found at this level with respect to other techniques, the US transducer should be of
lower frequency (4-7 MHz). Scanning is performed laterally in proximity to the coracoid process (see Figure 5).
The US transducer (curvilinear held in a sagittal orientation) is placed near the lower edge of the clavicle, and a
transverse view of the axillary artery and vein is obtained. Curvilinear, phased-array, or linear transducers can be
used, but the needle is more poorly imaged with linear transducers during an infraclavicular block. The color
Doppler mode facilitates identification of the vascular structures and decreases the risk for vascular puncture, the
most frequent complication associated with US-guided infraclavicular techniques.4 The pleura or chest wall is
identified as a hyperechoic fine line outlining the anechoic lung tissue if the transducer is moved too medially. It
moves with respiration. The plexus is usually found at a depth of 2-6 cm. The cords of the plexus are located
adjacent to the artery in medial, lateral, and posterior positions. Upper limb position influences these relationships.
The pectoralis major muscles, pectoralis minor muscles, and clavipectoral fascia are visualized and further
identified by appropriate resisted movements.

603
 Infraclavicular

ROCEDURE »
• **OBTAIN CONSENT**
• **MARK SITE**
• Be sure the patient has an established IV in the nonoperative arm, connected via tubing to an IV solution, such
as normal saline or lactated Ringer’s solution that runs freely.
• Select and draw up anesthetic solution for injection into the 20-mL syringes, and connect each to the stopcock.
Attach the extension tubing to the stopcock. Lidocaine 2% mixed with epinephrine 1:200,000 and sodium
bicarbonate 8.5% (0.10 mL of lidocaine) produces a block lasting 3-4 hours in adults. A solution mixture
containing 8 mL of tetracaine, 32 mL of lidocaine 2%, and 200 mcg of epinephrine can be used to prolong
anesthesia.
• Remove the stylet from the 17-gauge Tuohy needle, and connect the syringe and IV extension tubing directly to
the Tuohy needle. Flush the IV tubing with anesthetic solution by injecting several milliliters from the
syringe into the tubing and needle.
• Apply routine patient monitors, including blood pressure cuff, pulse oximeter, and ECG.
• Have patient lie supine with the head turned away from the side to be blocked.
• **TIME OUT** Confirm patient identity and correct surgical side.
• Consider IV sedation—for example, midazolam, 2 mg, and fentanyl, 50 mcg IV.
• Administer oxygen by nasal cannula, particularly if sedation is being considered.
• Arrange the US screen, transducer, and needle on the side to be blocked so that all are in one view of the
operator. In the case of the infraclavicular block, this is often to the patient’s side below the arm on the
side to be blocked, with the screen facing the operator at the patient’s head. Room lights should be
dimmed to enhance US viewing. Be sure the US screen is made to look like a scanning field—that is, the
right side of the screen represents the right side of the patient. Optimize the US variables such as scanning
mode, depth of field, and gain prior to beginning the procedure.

• Stand or sit on above the shoulder of the patient, on the same side as the one to be blocked.
• Apply sterile prep solution to the neck, clavicle, and infraclavicular space on the side to be blocked.
• Drape with sterile towels or fenestrated drape—be sure the elbow is visible.
• Apply sterile sheath over US transducer with US gel, and apply another layer of US gel to the patient’s neck.
• Hold the US transducer between the thumb, index, and ring fingers of the non-dominant hand. Place the little
finger and ulnar aspect of the hand on the patient to stabilize the transducer. Apply firm, even surface

604
 pressure with the transducer to produce the best images.
• Scan the deltopectoral region with a 4-7 MHz probe on a line drawn from the mid-clavicular point to the
axillary pulse to obtain an image of the axillary artery and vein.

• Optimize adjustable US variables such as scanning mode, depth of field, and gain.
• Move the transducer cephalad or caudad to bring the axillary artery to the center of the image. Then start
sliding the transducer laterally while maintaining the axillary artery in the center of the image to a point
when the three cords wrap around the artery on three sides. Moving further laterally, two branches from
the medial and lateral cords are seen lying anterior to the axillary artery, and further lateral still, they join
to form the median nerve.
• Mark the outline of the US transducer on the skin.
• **STERILE TECHNIQUE**Wash hands, and wear sterile gloves and a mask.
• Disinfect the skin with antiseptic solution, and drape the field with sterile towels or a fenestrated drape.
• Apply a sterile sheath over the US transducer with sterile ultrasound gel. Apply another layer of sterile gel
between the sterile sheath and the skin.
• Using the small syringe and small gauge needle, raise a skin wheal of local anesthetic a small distance from the
transducer to facilitate sterility and allow a shallow angle of approach to improve needle visualization.
• Insert the needle 1-2 cm cephalad to the final curvilinear transducer position.
• Advance a 25-gauge needle under real-time US guidance and deposit local anesthetic along the needle entry
path.
• Use a 17-gauge Tuohy needle in a freehand technique. (This needle is chosen as it gives good tissue feel and
has advantages for ultrasound visualization).
• Insert the Tuohy needle under the skin and visualize it with the US transducer. This may require needle or
transducer adjustment. Do not advance the needle without US visualization.
• Direct the needle between the axillary vein and artery. A loss of resistance will be felt and observed as the
needle pierces the clavipectoral fascia.
• Inject 1-2 mL of 2% lidocaine, with epinephrine 1:200 000 and sodium bicarbonate (0.9 mEq/10 mL), to ensure
correct placement. Once correct placement is seen, inject 10 mL of local anesthetic around the medial
cord.
• Withdraw the needle partially, and redirect it between the lateral cord and the superior aspect of the axillary
artery. Inject 1-2 mL of local anesthetic to ensure satisfactory position, and then inject 10 mL of local
anesthetic around the lateral cord.
• Advance the needle slightly deeper than the posterior aspect of the artery, and shift the needle shaft into a more
horizontal position, placing its tip between the artery and posterior cord. Inject an additional 10 mL of
local anesthetic around the posterior cord. During all maneuvers keep the image of the entire needle in
view.

605
• Routinely, a total of 35-40 mL of local anesthetic solution is used. However, successful block can be produced
with 15-20 mL.
• Note: Continuous infraclavicular block can be done by threading a catheter through the Tuohy needle between
the posterior cord and the axillary artery
Clinical Pearls: A 19-gauge flexible-tip epidural catheter can be easily imaged with US due to the presence of a
metal spring in the tip.

• The position of the catheter tip can be confirmed by injecting 1-2 mL of air and observing its echodense spread
around the posterior cord. A multi-orifice catheter should not be used because the local anesthetic will
flow preferentially from an orifice located in low-resistance tissue.
• Secure the catheter with a transparent dressing. If the catheter is to be retained for pain control for longer
periods, it may be tunneled subcutaneously.

606
 Epidural Block

Patient Selection

-cooperative
-can also be used in the cervical and thoracic areas as well—levels at which spinal anesthesia is
not advised.
-a continuous technique has been found to be helpful in providing epidural local anesthesia or
opioid analgesia after major surgical procedures.
Pharmacologic Choice
Chloroprocaine, an amino ester local anesthetic, is a short-acting agent that allows efficient
matching of the length of the surgical procedure and the duration of epidural analgesia, even in
outpatients. 2-Chloroprocaine is available in 2% and 3% concentrations; the latter is preferable
for surgical anesthesia and the former for techniques not requiring muscle relaxation.
Lidocaine is the prototypical amino amide local anesthetic and is used in 1.5% and 2%
concentrations epidurally. Concentrations of mepivacaine necessary for epidural anesthesia are
similar to those of lidocaine; however, mepivacaine lasts from 15 to 30 minutes longer at
equivalent dosages. Epinephrine significantly prolongs (i.e., by approximately 50%) the
duration of surgical anesthesia with 2-chloroprocaine and either lidocaine and mepivacaine. Plain
lidocaine produces surgical anesthesia that lasts from 60 to 100 minutes.

Bupivacaine, an amino amide, is a widely used long-acting local anesthetic for epidural
anesthesia. It is used in 0.5% and 0.75% concentrations, but analgesic techniques can be
performed with concentrations ranging from 0.125% to 0.25%. Its duration of action is not
prolonged as consistently by the addition of epinephrine, although up to 240 minutes of surgical
anesthesia can be obtained when epinephrine is added.

Ropivacaine, another long-acting amino amide, is also used for regional and epidural anesthesia.
For surgical anesthesia it is used in 0.5%, 0.75%, and 1% concentrations. Analgesia can be
obtained with concentrations of 0.2%. Its duration of action is slightly less than that of
bupivacaine in the epidural technique, and it appears to produce slightly less motor blockade
than a comparable concentration of bupivacaine.

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In addition to the use of epinephrine as an epidural additive, some anesthesiologists recommend
modifying epidural local anesthetic solutions to increase both the speed of onset and the quality
of the block produced. One recommendation is to alkalinize the local anesthetic solution by
adding bicarbonate to it to achieve both these purposes. Nevertheless, the clinical advisability of
routinely adding bicarbonate to local anesthetic solutions should be determined by local practice
protocols.

Placement
Anatomy

 When a lumbar approach to the epidural space is used in adults, the depth from the skin
to the ligamentum flavum is commonly near 4 cm; in 80% of patients the epidural space
is cannulated at a distance of 3.5 to 6 cm from the skin. In a small number of patients the
lumbar epidural space is as near as 2 cm from the skin.
 In the lumbar region, the ligamentum flavum is 5 to 6 mm thick in the midline, whereas
in the thoracic region it is 3 to 5 mm thick.
 In the thoracic region, the depth from the skin to the epidural space depends on the
degree of cephalad angulation used for the paramedian approach as well as the body
habitus of the patient.
 In the cervical region the depth to the ligamentum flavum is approximately the same as
that in the lumbar region, 4 to 6 cm.


Needle Puncture: Lumbar Epidural

 identify the midline structures, and the bony landmarks

 If a single-shot epidural technique is chosen, a Crawford needle is appropriate; if a

608
 continuous catheter technique is indicated, a Tuohy or other needle with a lateral-facing
opening is chosen.


 The midline approach is most often indicated for a lumbar epidural procedure.
 The needle is slowly advanced until the change in tissue resistance is noted as the needle
abuts the ligamentum flavum.
 At this point, a 3- to 5-mL glass syringe is filled with 2 mL of saline solution, and a small
(0.25 mL) air bubble is attached to the needle, and if the needle tip is in the substance of
the ligamentum flavum, the air bubble will be compressible. If the ligamentum flavum
has not yet been reached, pressure on the syringe plunger will not compress the air
bubble.


 Once compression of the air bubble has been achieved, the needle is grasped with the
nondominant hand and pulled toward the epidural space, while the dominant hand
(thumb) applies constant steady pressure on the syringe plunger, thus compressing the air
bubble. When the epidural space is entered, the pressure applied to the syringe plunger
will allow the solution to flow without resistance into the epidural space.
 An alternative technique is the hanging-drop technique for identifying entry into the
epidural space. In this technique, when the needle is placed in the ligamentum flavum a
drop of solution is introduced into the hub of the needle. No syringe is attached, and
when the needle is advanced into the epidural space, the solution should be “sucked into”
the space.
 The incidence of unintentional intravenous cannulation with an epidural catheter may be
decreased by injecting 5 to 10 mL of solution before threading the catheter. If a catheter
is inserted, it should be inserted only 2 to 3 cm into the epidural space because threading
it farther may increase the likelihood of catheter malposition. Obstetric patients require

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 catheters to be inserted to 3 to 5 cm into the epidural space to minimize dislodgement
during labor analgesia.

Needle Puncture: Thoracic Epidural

 In this technique, the paramedian approach is preferred because it allows easier access to
the epidural space because the spinous processes in the mid-thoracic region overlap each
other from cephalad to caudad.
 The loss-of-resistance technique and insertion of the catheter are carried out in a manner
identical to that used for lumbar epidural block. Again, the hanging-drop technique is an
alternative method of identifying the thoracic epidural space, although the classic
Bromage needle–syringe grip is my first choice for the thoracic epidural block (Fig. 41-
10).

Needle Puncture: Cervical Epidural

 In the cervical epidural technique, the patient is typically in a sitting position with the
head bent forward and supported on a table.
 The spinous processes of the cervical vertebrae are nearly perpendicular to the long axis
of the vertebral column; thus, a midline technique is applicable for the cervical epidural
block.
 The most prominent vertebral spinous processes, those of C7 and T1, are identified with
the neck flexed. The second (index) and third fingers of the palpating hand straddle the
space between C7 and T1, and the epidural needle is slowly inserted in a plane
approximately parallel to the floor (or parallel to the long axis of the cervical vertebral
spinous processes). Abutment of the needle onto the ligamentum flavum will be
appreciated at a depth similar to that seen in the lumbar epidural block (i.e., 3.5 to
5.5 cm), and needle placement is then performed using the loss-of-resistance technique as
in the other epidural methods. The hanging-drop method is also an option for
identification of the cervical epidural space.

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Potential Problems

 systemic toxicity resulting from intravenous injection of the intended epidural anesthetic
o One way to minimize intravenous injection of the pharmacologic doses of local
anesthetic needed for epidural anesthesia is to verify needle or catheter placement
by administering a test dose before the definitive epidural anesthetic injection.
The current recommendation for the test dose is 3 mL of local anesthetic
solution containing 1:200,000 epinephrine (15 µg of epinephrine).
o Even if the test dose is negative, the anesthesiologist should inject the epidural
solution incrementally, be vigilant for unintentional intravascular injection, and
have all necessary equipment and drugs available to treat local anesthetic–induced
systemic toxicity.

611
 o

 Unintentional administration of an epidural dose into the spinal fluid.

o Blood pressure and heart rate should be supported pharmacologically and
ventilation should be assisted as indicated.
o Usually atropine and ephedrine will suffice to manage this situation, or at least
will provide time to administer more potent catecholamines. If the entire dose (20
to 25 mL) of local anesthetic is administered into the cerebrospinal fluid, tracheal
intubation and mechanical ventilation are indicated because it will be
approximately 1 to 2 hours before the patient can consistently maintain adequate
spontaneous ventilation.
o When epidural anesthesia is performed and a higher-than-expected block
develops after a delay of only 15 to 30 minutes, subdural placement of the local
anesthetic must be considered. Treatment is symptomatic, with the most difficult
part involving recognition that a subdural injection is possible.
 If neurologic injury occurs after epidural anesthesia, a systematic approach to the
problem is necessary.
 The performance of cervical or thoracic epidural techniques demands special care with
hand and needle control because the spinal cord is immediately deep to the site of both
these epidural blocks.
 Epidural hematoma created with the needles or catheters.
o Concern about epidural hematoma formation is greater in patients who have been
taking antiplatelet drugs such as aspirin or who have been receiving preoperative
anticoagulants.
o Perioperative anticoagulant regimens that demand special consideration are the
use of low–molecular-weight heparin (LMWH) or potent antiplatelet drugs
concurrently with epidural block.

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 o It is currently recommended that no procedure, including withdrawal or
manipulation of an epidural catheter, should occur within 12 hours after a dose of
LMWH, and the next dose of LMWH should be delayed for at least 2 hours after
atraumatic epidural needle or catheter insertion or manipulation. The antiplatelet
drugs (e.g., ticlopidine, clopidogrel, and platelet glycoprotein IIb/IIIa receptor
antagonists) are sometimes combined with aspirin and other anticoagulants.
 Post–dural puncture headache can result from epidural anesthesia when unintentional
subarachnoid puncture accompanies the technique.
o When using the larger-diameter epidural needles (18 and 19 gauge), it can be
expected that at least 50% of patients experiencing unintentional dural puncture
will have a postoperative headache

Pearls

 Epidural catheters can be malpositioned in a number of ways. If a catheter is inserted too

far into the epidural space, it can be routed out of foramina, resulting in patchy epidural
block.
 The catheter can also be inserted into the subdural or subarachnoid space or into an
epidural vein. Similarly, the use of epidural catheters may be complicated by a prominent
dorsomedian connective tissue band (epidural septum or fat pad), which is found in some
patients.
 Another means of facilitating the success of epidural anesthesia is to allow the block
enough “soak time” before beginning the surgical procedure.
 There appears to be a plateau effect in the doses of epidural local anesthetics; that is, once
a certain quantity of local anesthetic has been injected, more of the same agent does not
significantly increase the block height but rather may make the block denser, perhaps
improving quality.

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 Regional Anesthesia: Femoral, Saphenous, Axillary and Digit blocks

Femoral Block
Anatomy: The femoral nerve comes from the roots of L2, L3 and L4. They combine to form
the femoral nerve which then travels through the pelvis in the groove between the psoas and
iliacus muscles, emerging beneath the inguinal ligament, posterior and laterally to the femoral
vessels. At that point, the femoral nerve divides into its branches.
Local Anesthetics and Doses: 20 mL of 1% Lidocaine or 0.25-0.5% Bupivicaine will produce
sufficient sensory blockade of the femoral nerve. To produce motor blockade as well, higher
concentrations of the local anesthetic will be required.
Nerves Blocked: When the femoral nerve is blocked, the saphenous nerve (sensory only) is also
blocked as it is a branch of the femoral nerve.
Risks & Benefits: A patient with PVD may require a lower extremity block. If a recent
prosthetic femoral artery has been placed, use extra caution to avoid the prosthesis. However,
the vessels are actually in a different compartment than the femoral nerve. They are separated by
the fascia iliaca.
Some benefits with this block are that the patient just needs to lay supine for placement, which
they will likely need to do for surgery anyway and the patient need not be awake for placement
of a femoral block.
The femoral block does require “soak time” to set up as it is a field block.
Here are some common complications with the femoral block, but many of them also apply to
other blocks (i.e. infection, hematoma, vascular puncture with systemic toxicity and nerve
injury).

 Just like with any other procedure, use a strict aseptic technique
 Catheters at his location are difficult to keep sterile and should probably
Infection
remove after 48 hours

 Avoid advancement of the needle when the patient reports pain; this may
indicate insertion of the needle through the illiopsoas or pectineus muscles
 When the femoral artery or vein are punctured, the procedure should be
stopped and a firm and constant pressure applied over the femoral artery
Hematoma for 2-3 minutes before proceeding with the blockade.
 In a patient with difficult anatomy or severe peripheral vascular disease,
use a single-shot smaller gauge needle to localize the femoral nerve before
proceeding with a larger gauge needle for the continuous technique.

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  Never redirect the needle medially!
 The needle is first inserted just lateral to the femoral artery and the
Vascular
consequent insertions and redirections should all be progressively more
Puncture
lateral

 Use nerve stimulation and slow needle advancement

 Distinct paresthesia is almost never elicited with femoral nerve block and
should not be sought
Nerve Injury
 Do not inject when the patient complains of pain or when high pressures
on injection are met

 Instruct the patient on the inability to bear weight on the blocked extremity
Other

Indications: knee surgery, thigh surgery

Contraindications: infection at the site of injection as the environment will likely be too acidic
to allow enough local anesthetic to be in the ionized portion which is required to block the nerve
channel and be effective.
Dermatome spread: Although this doesn’t really have dermatome spread, analgesia arises to
the anterior and medial aspects of the thigh, anterior aspect of the knee and medial aspect of the
calf as a result of the femoral block.
Femoral Branches
Anterior division:
Posterior division:
 Middle
cutaneous  Saphenous nerve (most medial)
 Medial  Muscular (individual heads of the
cutaneous quadriceps muscle)
 Muscular  Articular branches (hip and knee)
(sartorius)

615
Saphenous Block
Anatomy: When using ultrasound and holding transducer in the transverse position on the
anteromedial middle thigh, a triangle of structures is seen around the femoral artery and
saphenous nerve. The roof of the triangle, which points down, is composed of the Sartorius
muscle. On the medial side of the triangle, the adductor longus or magnus is seen. On the lateral
side of the triangle, the vastus medialis is seen. The femoral artery generally runs more laterally,
on the vastus medialis side, than the saphenous nerve. So, this block is placed medially to the
femoral artery.

616
Or, the block may be placed just below the knee on the medial aspect at the level of the tibial
tuberosity.
Local Anesthetics and Doses: Because the saphenous nerve provides sensory only and not
motor, lower doses of anesthetic are required. Five to 10 mL of 1% Lidocaine, 1% mepivacaine,
0.25% to 0.5% Bupivacaine or 0.2% to 0.5% Ropivacaine are effective.
Nerves Blocked: The Saphenous nerve is a branch of the femoral nerve. When just the
saphenous nerve is blocked, the infrapatellar branch and medial crural cutaneous branches of the
saphenous nerve are also blocked. The saphenous nerve courses superficially, anterior to the
medial malleolus, providing cutaneous innervation in the area of the medial ankle and foot.
Risks and Benefits: Because local anesthetic is distributed in the adductor canal with the
saphenous block, the local anesthetic may partially cause motor block in the vastus medialis.
This is a concern as ambulation may be impaired. Other risks also include infection, hematoma
and nerve injury.
Indications: The saphenous block may be used for saphenous vein striping or harvest or as a
supplement for medial foot or ankle surgery in combination with a sciatic block.
Contraindications: Other than the contraindications for performing any block, there are no
specific contraindications to the saphenous block.

617
 Axillary Block
Anatomy: Four nerves, or branches from the brachial plexus, run alongside the axillary artery
on the proximal medial aspect of the upper arm. If you look at the artery as the center or clock
face, the musculocutaneous nerve lies between 9 and 12 o’clock in the coracobrachialis muscle,
the median nerve lies between 12 and 3 o’clock along the artery, the ulnar nerve is then between
3 and 6 o’clock while the radial nerve lies under the artery between 6 and 9 o’clock.

This Axillary artery is quite superficial

and the nerves are not is the text book clock positions. This is why ultrasound can be so helpful
in producing an effective block, you no longer have to assume they are in the text book positions.
Local Anesthetics and Doses: Common concentrations of local anesthetics used for Axillary
blocks are 1% to 1.5% Lidocaine or Mepivacaine, 0.5% Bupivacaine or 0.5% to 0.75%
Ropivacaine. Again, with lower concentrations of local anesthetic, sensory block is provided but
there may only be weak motor blockade. 15-20 mL of local anesthetic is usually used for this
block. The addition of Epinephrine (with the exception of Ropivacaine which has its own
vasoconstricting properties) or dexamethasone will prolong the duration of the block.
Nerves Blocked: The musculocutaneous, ulnar, median and radial nerves are commonly
blocked with one stick in an axillary block. When a tourniquet is applied to the upper arm, it is
also nice to block the intercostobrachial cutaneous nerve which lies just under the skin of the
axilla.

618
Risks & Benefits: Because the musculocutaneous nerve is not always reachable with the first
needle stick and multiple sticks may be required, it is important to monitor the amount of local
anesthetic administered to prevent toxicity as well as sterile technique to prevent infection.
This block is relatively safe to place (no risk of pneumothorax as with supra and infraclavicular
blocks) and provides adequate analgesia for hand and forearm surgery. Of course, strict sterile
technique is required to prevent infection. Other risks include hematoma, vascular puncture with
systemic toxicity and nerve injury.
Indications: The Axillary block is indicated in the patient who can abduct their arm enough to
place the block and who is having hand or forearm surgery.
Contraindications: This block should not be used in the patient who cannot abduct their arm or
who is having a surgical procedure above the elbow.
Digit Blocks
Anatomy: The common digital nerves are derived from the median and
ulnar nerves and divide in the distal palm into the volar aspect, tip, and
nail bed area.
The main digital nerves, accompanied by digital vessels, run on the
ventrolateral aspect of the finger immediately lateral to the flexor tendon
sheath. Small dorsal digital nerves run on the dorsolateral aspect of the
finger and supply innervation to the back of the fingers as far as the
proximal joint.
Local Anesthetics and Doses: Infiltration of both the dorsal and ventral branches of the digital
nerve is carried out bilaterally and a total of 1 to 2 mL at each site should be sufficient for the
digital block. Lower concentrations of any amide local anesthetic are appropriate but no
epinephrine should be used.

Onset (min)Anesthesia (hrs)Analgesia (hrs)

1.5% Mepivacaine (+ HCO3) 15-20 2-3 3-5
2% Lidocaine (+ HCO3) 10-20 2-5 3-8
0.5% Ropivacaine 15-30 4-8 5-12
0.75% Ropivacaine 10-15 5-10 6-24
0.5 Bupivacaine (or I-bupivacaine)15-30 5-15 6-30

Risks and Benefits: These blocks are commonly used in the emergency department for digit
injuries to provide pain relief. Epinephrine should be avoided with this block due to its
vasoconstricting properties.

619
  This should be very rare with use of an aseptic technique
Infection
 Avoid multiple needle insertions
Hematoma  Use 25-gauge needle (or smaller) and avoid puncturing superficial veins

 Avoid puncturing the greater saphenous vein at the medial malleolus

Vascular  Intermittent aspiration should be performed to avoid intravascular
puncture injection

 Instruct the patient on the care of the insensate finger

Other
 Avoid epinephrine-containing solution for this block
 Limit the injection volume to 2mL on each side
 The mechanical pressure effects of injecting solution into a potentially
Gangrene of confined space should always be borne in mind, particularly in blocks at
the digit(s) the base of the digit
 In patients with small vessel disease, perhaps an alternative method
should be sought in addition to avoidance of digital tourniquet

 Residual paresthesias are likely due to an inadvertent intraneuronal

injection
 Systemic toxicity is rare because of the distal location of the blockade
Nerve injury
 Do not inject when the patient complains of pain or when high
pressures on injection are met

620
 Practice Questions:
1. Important landmarks for performing a sciatic nerve block (classic approach of Labat)
include:
a. Iliac crest, sacral hiatus, greater trochanter
b. Iliac crest, coccyx and greater trochanter
c. Posterior superior iliac spine, coccyx and greater trochanter
d. Posterior superior iliac spine, greater trochanter and sacral hiatus
e. Posterior superior iliac spine and greater trochanter
2. An axillary block utilizing the transarterial approach with 0.5% Bupivacaine and epi
(1:200,000) is performed in a 70 kg patient. Thirty mL is injected posterior to the
axillary artery and 30 mL anterior to it. How many mg have been injected and was the
maximum recommended dose exceeded?
a. 150 mg bupivacaine, 150 mcg epi did not exceed maximum dose
b. 150 mg bupivacaine, 150 mcg epi exceeded maximum dose
c. 300 mg bupivacaine, 300 mcg epi did not exceed maximum dose
d. 300 mg bupivacaine, 300 mcg epi exceeded maximum dose
e. Transarterial blocks should never contain epi and the block should not be done
3. Which of the following observations, after nerve injury, is correctly paired with the
appropriate nerve?
a. Inability to flex the forearm – ulnar nerve
b. Numbness in the thumb – radial nerve
c. Inability to extend the forearm – musculocutaneous nerve
d. Numbness in the little finger – median nerve
e. All are correctly paired
4. Nerves that originate from the sacral plexus include each of the following EXCEPT:
a. Femoral nerve
b. Tibial nerve
c. Superficial peroneal nerve
d. Deep peroneal nerve
e. Sural nerve
5. An axillary block is performed on a healthy 19 yr old athlete. Thirty ml of 0.75%
bupivacaine is injected incrementally. Fifteen minutes after the bupivacaine injection,
the patient has a seizure and experiences a ventricular fibrillation arrest. Which of the
measure below is NOT indicated?
a. Begin chest compressions at 100/minute
b. Ventilate with 100% oxygen
c. Bolus propofol to bind local anesthetic
d. Infuse 20% lipid emulsion
e. Repeat emulsion infusion if fibrillation continues

621
Answers:
1. D
2. D
3. B
4. A
5. C
And a little Local anesthetic review . . .
Lidocaine (Xylocaine)

 Rapid onset;
 Max dose 4.5 mg/kg (with epi 7);
 Duration in min 120 (240)
 Anticonvulsant and Anti-dysrhythmic properties
 1-2% for peripheral nerve blocks
 2% for epidural
 4% for mucosal analgesia
 5% for spinal is most likely to cause transient neurologic injury and cauda equina
syndrome
Cocaine - Rapid onset; max dose 200 mg; used for ENT topical vasoconstriction
Mepivacaine (Carbocaine, Polocaine)

 rapid onset;
 max dose 5 mg/kg (300 mg) or 7 mg/kg (500 mg) with epi,
 duration 180 min (360 with epi)
 mild vasodilator
 poorly metabolized in utero, not good choice for OB
Bupivacaine (Marcaine, Sensorcaine)

 Slow onset
 Max dose 2.5 mg/kg (175 mg) or 3 mg/kg (225 mg) with epi
 Duration 4 hours to 8-24 hrs
 More hydrophobic than mepivacaine or lidocaine which means a slower onset but longer
duration
 Should not be used for continuous IV Regional as it is the most cardiotoxic local
anesthetic
 For infiltration – 0.25%
 Peripheral nerve blocks – 0.375-0.5%
 Spinal/Epidural – 0.5-0.75%

622
Procaine (Novacaine)

 Slow onset
 Max dose 8 mg/kg or 10 mg/kg with epi (1000 mg max)
 Duration 45-90 min, metabolized by plasma esterases
 Provides an “unreliable block”
Chloroprocaine (Nesacaine)

 Rapid onset
 Max dose 10 mg/kg (800 mg) or 15 mg/kg (1000 mg) with epi
 Duration 30 min (up to 90 with epi)
 Used for “crash” epidural
 Has lowest risk of toxicity
Ropivacaine (Naropin)

 Rapid onset
 Max dose 2.5 mg/kg or 300 mg
 Produces vasoconstriction so addition of epi has little effect on increased duration
 Equivalent potency to bupivacaine with less cardiotoxicity
Tetracaine (Pontocaine)

 Slow onset
 Max dose 1.5 mg/kg or 2.5 mg/kg (200 mg) with epi
 Duration 3-10 hrs (longest ester block)
 1% for spinal, also used for ophthalmic procedures
 Needs to be refrigerated
Epinephrine – max dose to prolong block 3-5 mcg/kg or 200-250 mcg
Dexamethasone – 8-10 mg added to brachial plexus block increases the duration of the block
Bicarb – alkalinizes local anesthetic which is more effective in epidural application than
peripheral; dose of 1 ml: 10 mL of Lidocaine or 0.1 mL: 10 mL of Bupivacaine
Clonidine – prolongs duration and density, -0.5 mcg/kg, provides lower incidence of CPRS,
direct inhibitory effect on peripheral nerves

623
IN CASE OF TOXICITY:
20% Lipid Rescue – 1.5 ml/kg over 1 min bolus followed by infusion at 0.25 mg/kg/min
ORDER of BLOCKADE:
PAIN → COLD →WARMPTH→ TOUCH →DEEP PRESSURE → MOTOR

624
 TAP, Rectus Abdominal, Bier Block, and Ilioinguinal

Transversus Abdominis Plane Block (TAP)

Anatomy/Innervation- As illustrated in the picture, innervation of the

anterolateral abdominal wall comes from the anterior rami of spinal nerves T7-L1. This
innervation includes- Intercostal (T7-T11), Subcostal Nerve (T12), also the iliohypogastric and
ilioinguinal nerves (L1).

‐ T7-T11 Anterior- enter between internal oblique and transversus abdominis muscles until
they reach rectus abdominis, - perforate it and end supplying the skin at front of
abdomen. Midway in their course they pierce external oblique- leading to lateral
cutaneous branch- divides into ant. and post. Branches- supplying external oblique and
latissmus dorsi.

‐ Iliohypogastric (L1) - goes in between internal oblique and transversus abdominis near
iliac crest- lateral- skin of gluteal region. Anterior- hypogastric region
‐ Ilioinguinal nerve (L1) - Supplies upper and medial part of thigh and part of skin
covering genitalia.
+++The Goal of the TAP block is to target the spinal nerves described above++++
Indications- Appendectomy, Hernia Repair, C-Section, TAH, Prostatectomy. Also any lap
surgery with bilateral blocks.

625
Dermatome Spread- Controversial. Some literature- T7-L1, while others show that there is a
spread to T10 upwards suggesting it more suitable for lower abdominal procedures.
However- T10-L1 spread with single posterior injection. Subcostal TAP can augment with a
block up to T7.
Pharmacologic Choice- Ropivicaine (Naropin) 0.2-0.5% most common. Bupivicaine 0.25%
also option. Midline incisions- Max 20ml to each side. Unilateral TAP block- just 20ml on side
to be blocked.
Continuous catheter- 7-10ml per hr of any of the above.
Complications- Rare. Intravascular injection potential, allergy to LA, or if needle is inserted too
deeply- possibility of intrahepatic injection, intraperitoneal injection, bowel hematoma. Potential
for LA toxicity due to large volumes of LA used- especially if bilateral block.

626
 Rectus Abdominis Block

Anatomy- As described previously- intercostal nerves- T7-T11 anterior rami supply sensory
inneration to rectus abdominis and overlying skin.

What is the Difference between a TAP, and Rectus Abdominis Block???

TAP block is performed laterally on the abdomen, between the internal oblique and transversus
abdominis muscles In the Rectus Abdominis Block, LA is deposited within the
posterior rectus sheath, usually bilateral to umbilicus in subcostal region with needle tip
advanced just posterior to rectus muscle and above underlying rectus sheath- with injection
hydrodissection the muscle away from the sheath-
Rectus Abdominis block provides sensory block to whole midline of abdomen. Compared to
TAP, rectus abdominis continuous catheter has much denser analgesia of shorter duration.

627
Dermatome Spread-
As shown in this pic- Sensory dermatome block of rectus abdominis is the large black circle over
midline, the bilateral TAP is grey semicircle over lower abdomen and the unilateral oblique
subcostal TAP is the shaded gray in upper abdomen.

Indications- For any midline or paramedian incision extending above the umbilicus- lap cases,
bowel surgeries, and laparotomy. This block and the TAP are wonderful for patients in which an
epidural is contraindicated such as those with coagulopathy, those on anticoagulants, sepsis
patients who need emergent laparotomies, hypotensive patients.
Pharmacologic Agents- This block is usually a catheter directed/continuous catheter technique.
0.25% Bupivicaine or 0.375% Ropivicaine with a 20ml bolus every 6 hours will provide
effective continuous analgesia.
Complications- Intravascular injection- realize the superior and inferior epigastric vessels run in
the posterior rectus sheath. Rectus sheath hematoma, intra-abdominal, intra-hepatic injection all
complications. Risk of infection.

628
 Intravenous Regional Block (Bier Block)
This block can be performed for procedures that are 45-60 minutes or less on the hand, forearm,
or even the leg. Most common- carpal tunnel release.
Anatomy- Peripheral nerve endings of the extremities are nourished by small blood vessels. So
if you inject local anesthetic into a venous system, this results in diffusion of LA into the nerve
endings with the development of anesthesia- this is true, as long as the concentration in the
venous system remains high- this is why it is important to exsanguinate it to prevent dilution of
LA.
Technique- Place tourniquet on proximal arm (or leg), using a double cuff technique. Place
22ga PIV into dorsum of hand of arm to be anesthetized (or leg, foot). Elevate extremity
involved for 1 minute for passive exsanguination. Then 5” Esmarch bandage applied
systematically from finger tips to distal cuff. Then inflate distal cuff, followed by proximal cuff,
then deflate distal cuff. Cuff should be at least 100mmHg above SBP or at least 300mmHg.
Then unwrap Esmarch and check for radial arterial pulse occlusion.
Local Anesthetic choice/Pharm- Lidocaine – 12-15ml of 2%, or 50ml of 0.5%. Onset is
usually within 5 minutes.
Complications etc- Usually patients c/o tourniquet pain after 20-30 minutes- inflate lower
tourniquet, deflate upper tourniquet- another 15-20min usually tolerated.
Very short procedures- Leave tourniquet inflated at least 15-20 minutes to avoid rapid IV
systemic bolus of LA that can cause a seizure. Gradual release of tourniquet in several steps
within 2 minute intervals allows for lower chance of systemic toxicity of LA.
Also with this procedure, risk of hematoma, engorgement of extremity, exchomoses and subq
hemorrhage.

629
 Ilioinguinal Block

Anatomy/Innervation-
Primarily used for inguinal herniorrhaphy. Both the iliohypogastric and ilioinguinal n. come
from L1 spinal root. Superomedial to the ASIS, these nerves pierce the transversus abdominis to
lie between it and the internal oblique. Their ventral rami pierce the external oblique to give
cutaneous sensation. The ilioinguinal nerve runs then anteroinferiorly to the superficial inguinal
ring, where it supplies the skin on the superomedial aspect of thigh.
Considerations- As mentioned previously in TAP block- the ventral rami of T11-T12 also lie
between the transversus abdominis and internal oblique- blocking these nerves as well as the
iliohypogastric and ilioinguinal nerves is essential if one wants to provide anesthesia to lower
abdominal wall.
With knowledge of this anatomy- the ASIS is palpated, and a mark is placed 3cm superomedially
to ASIS. Injection is made first after needle passes and in between external and internal oblique-
2ml injection. Then after passing between internal oblique and transversus abdominis- 2ml
injection. After this, redirect needle 45 deg. Angle medially- and above step is repeated.
Redirect again 45 degree laterally, repeat steps again- so a total of 12ml of LA is placed in a fan-
like matter between external and internal oblique and between the internal oblique and
transversus abdominis muscles.

630
Dermatome Spread- As shown in this pic

Indications- Primarily for inguinal herniorrhaphy.

Pharm Choice- Ropivacaine 0.5-1% is sometimes used. Brown states lower concentrations of
intermediate to long acting LA such as 1% lidocaine or mepivacaine, or 0.25% bupivacaine or
0.2% Ropivicaine.
Complications- Since proper performance of ilioinguinal/iliohypogastric blocks require multiple
small volume injections, in combination with potential other blocks- possibility of LA toxicity is
there, however is remote. There has been reports of perf of small and large bowels, and creation
of pelvic hematoma.
References/Links/Great Articles
Brown, D. Atlas of Regional Anesthesia
[Link]
33)[Link]
[Link]
[Link]
[Link]
bier_block.html
[Link]
ilioinguinal_and_iliohypogastric_blocks.html

631
 The Oncology Patient and Anesthesia

 Medical, nursing, and anesthetic management of these patients focuses on their specific
cancer, treatments, chronic pain, systemic effects of their cancer, and pain management
 Staging of Cancer
The TNM system is based on the extent of the tumor (T), the extent of spread to the lymph
nodes (N), and the presence of metastasis (M). A number is added to each letter to indicate the
size or extent of the tumor and the extent of spread.
Common Cancers Encountered
 Lung Cancer
Can be of squamous cell, adenocarcinoma, large or small cell origin
Small cell lung cancer has a widespread metastatic feature and associated metabolic
abnormalities  EATON LAMBERT SYNDROME
The most effective treatment is surgical resection
Evaluate underlying pulmonary and cardiac function
 Colorectal cancer
More than 99% of these cancers are adenocarcinomas
Usually presents in the 5th decade
About 25% of patients have a familial incidence
First metastatic site is usually the liver
SCREENING!!!!!!!
 Prostate Cancer
Vascular gland
SCREENING!! With PSA and digital rectal exam
Treatment with brachytherapy, transurethral resection, radical prostatectomy (associated
impotence and incontinence)
 Breast Cancer
Systemic therapy, radiation, excision
Lymphedema occurs after lymph node removal>no IVs, BPs in the ipsilateral arm
SCREENING!!!!! Mammography

Metabolic Changes of Malignancy

 Abnormal Carbohydrate Metabolism
• Insulin resistance & Glucose intolerance
• Increased glucose production
 Abnormal Protein Metabolism leading to extreme muscle wasting
• Decreased protein synthesis
• Increased protein catabolism
• Tumor derived products like PIF (proteolysis inducing factor) and endogenous
factors like TNF-alpha cause increased protein catabolism

632
  Abnormal fat and carbohydrate metabolism leading to Wasting Syndrome (Cachexia)
 Stimulation of nausea / vomiting contributing to malabsorption
 Anemia leading to fatigue
 Increased resting energy expenditure also leading to fatigue
 Ectopic Hormone Production depending on the cancer. This can produce conditions such
as: Cushing’s, Water Intoxication, altered electrolytes
 Spread of cancer into the mediastinum or great vessels can cause Superior Vena Cava
Syndrome (Obstruction)
 Anemia and bone marrow suppression, pancytopenia

Chemo Agents
Antimetabolites:
 Interrupt the cell cycle by preventing DNA synthesis - the “S” phase.
 They interfere with the production of key molecules with the cell – nucleic acids, RNA &
DNA.
 Examples of Antimetabolites:
o Folate Antagonists such as MTX. MTX binds to and inhibits dihydrofolate
reductase (DHFR), meaning Folate stays in its inactive form.
o Purine Antagonists such as 6-MP (6-Mercaptopurine). 6-MP inhibits purine
nucleotide production thus halting DNA synthesis.
o Pyrimidine Antagonists such as 5-FU (5-fluorouracil). 5-FU inhibits the
production of pyrimidine nucleotides, thus halting DNA synthesis.

Alkylating Agents
o Cyclophosphamide, Cisplatin, Carboplatin
o DNA alkylation produces a variety of defects that disrupt DNA replication and
transcription by modifying DNA bases and their bonds.
o Defects caused include depurination, double-stranded and single-stranded breaks, as well
as inter-strand cross-links which cell destruction and mutations.

Plant Alkaloids
o Vinca Alkaloids (derived from the periwinkle plant) - halt the mitosis phase of the cell
cycle by binding to tubulin, thus preventing the assembly of microtubules responsible for
chromosome migration. Example: vincristine, vinblastine
o Paclitaxel or Taxol (isolated compound from the Pacific Yew tree) – binds to
microtubules and prevents their breakdown. Without the ability to breakdown,
microtubules cannot pull chromosomes to opposite ends of the dividing cell.
o Etoposide (a derivative of the mandrake plant) – inhibits topoisomerase II, an enzyme
which normally unwinds DNA during replication to relieve tension on the unwinding
strand. The DNA which has been nicked by topo II, is unable to unwind and eventually
breaks under tension.

633
Antitumor Antibiotics
o All derivatives of species Streptomyces (Actinomycin D, bleomycin, mitomycin C, ect.).
o Act by either interfering with DNA, RNA and protein synthesis or by altering membranes
surrounding the cells.
o Adriamycin is cardiotoxic
o Bleomycin is pneumotoxic
o Cisplatin is nephrotoxic.

TABLE 20-1 -- Principal Toxicities of Commonly Used Cancer Chemotherapeutic Drugs

Drug Effect
Bleomycin (Blenoxane) Interstitial pneumonitis/pulmonary fibrosis
Busulfan (Myleran) Interstitial pneumonitis/pulmonary fibrosis
Cisplatin (Platinol) Ototoxicity, peripheral neuropathy, renal failure
Cyclophosphamide (Cytoxan) Plasma cholinesterase inhibition, hemorrhagic cystitis
Doxorubicin (Adriamycin) Dose-dependent cardiomyopathy
L-Asparaginase (Elspar) Hypersensitivity reactions/anaphylaxis, pancreatitis
Melphalan (Alkeran) Development of secondary leukemias, sterility
Mitomycin Hemolytic uremic syndrome
Paclitaxel (Taxol) Hypersensitivity reactions, peripheral neuropathy
Vincristine (Oncovin) Peripheral neuropathy, autonomic neuropathy

Radiation Therapy and the Cell Injury Effect

o Cancer cells grow without appropriate external signals and do not exhibit contact
inhibition; therefore they grow much more rapidly than do normal cells.
o Radiation Therapy uses both x-rays and gamma rays to target cancerous growth. The
high energy waves cause damage to DNA (break the hydrogen bonds linking DNA
strands, disrupt cellular processes and division, and ultimately kill the cell).
o Simply put, damage caused by radiation (and by chemotherapy) is manifest much
more quickly in tissues where the cells are dividing rapidly.

The fast-growing normal cells likely to be affected are:

 Blood cells resulting in anemia, fatigue, and a higher susceptibility to infection
 Cells of the digestive tract, resulting in mouth ulcers, changes in the sense of taste, gum
& throat problems, diarrhea, constipation
 Cells of the reproductive system, resulting in permanent or temporary infertility, ED in
men, and menopausal symptoms in women
 Hair follicles resulting in hair loss

634
Leukemia
Acute leukemia
 uncontrolled production of immature leukocytes
 crowding out of normal red bone marrow cells by production of immature WBC
 prevents production of RBC & platelets
o Leukocytes have surface proteins (as do erythrocytes), called major
histocompatibility antigens (MHC), and are unique for each person (except for
identical siblings) and can be used to identify a tissue.
o Leukocytosis is a high white blood cell count
 – microbes, strenuous exercise, anesthesia or surgery
o • Leukopenia is low white blood cell count
 – radiation, shock or chemotherapy
o • Only 2% of total WBC population is in circulating blood at any given time; the
rest is in lymphatic fluid, skin, lungs, lymph nodes & spleen

Chronic leukemia
 accumulation of mature WBC in bloodstream because they do not die
 Classified by type of WBC that is predominant---monocytes, lymphocytic.
o Lymphocyte Function
o B cells
 destroy bacteria and their toxins
 turn into plasma cells that produces antibodies
o T cells
 attack viruses, fungi, transplanted organs, cancer cells & some bacteria
o Natural killer cells
 attack many different microbes & some tumor cells
 destroy foreign invaders by direct attack
o Monocyte
 • Largest WBC in circulating blood
 differentiate into macrophages
o fixed group found in specific tissues
 alveolar macrophages in lungs
 kupffer cells in liver
 wandering ( once they leave the capillaries) group gathers at sites of
infection

635
**Nitrous Oxide
o DO NOT USE IN CANCER KIDS!!
o Long term exposure can cause bone marrow depression (megaloblastic anemia) and
neurological deficiencies (peripheral neuropathies and pernious anemia)

Graft vs. Host

o Graft-versus-host disease is a life-threatening complication of bone marrow
transplantation manifesting as organ system dysfunction most often involving the skin,
liver, and gastrointestinal tract. Severe rash, even desquamation, jaundice, and diarrhea
are usually seen. This response occurs when immunologically competent cells in the graft
target antigens on the recipient's cells

PARANEOPLASTIC SYNDROMES
o Paraneoplastic syndromes manifest as pathophysiologic disturbances that may
accompany cancer (Table 20-2). Certain of these pathophysiologic disturbances (superior
vena cava obstruction, increased intracranial pressure, pericardial tamponade, renal
failure, and hypercalcemia) may manifest as life-threatening medical emergencies.
o TABLE 20-2 -- Pathophysiologic Manifestations of Paraneoplastic Syndromes
Fever
Anorexia
Weight loss
Anemia
Thrombocytopenia
Coagulopathy
Neuromuscular abnormalities
Ectopic hormone production
Hypercalcemia
Hyperuricemia
Tumor lysis syndrome; caused by sudden destruction of tumor cells
by chemo leading to the release of uric acid, potassium, and
phosphate. Occurs most often after treatment of hematologic
neoplasms, such as ALL. Acute renal failure can accompany the
hyperuricemia, Hyperkalemia and resulting cardiac dysrhythmia are
more likely in the presence of renal dysfunction. Hyperphosphatemia
can lead to secondary hypocalcemia, which increased the risk of
cardiac dysrhythmias from hyposkalemia and can cause
neuromuscular symptoms such as tetany.

Adrenal insufficiency

636
Nephrotic syndrome
Ureteral obstruction
Pulmonary hypertrophic osteoarthropathy and digital clubbing
Pericardial effusion
Pericardial tamponade
Superior vena cava obstruction
Spinal cord compression

Placenta Accreta

637
  Abnormally adherent placenta
 Characterized by amount of invasion into the uterine wall
Placenta Accreta Vera
Adheres to myometrium without involvement of uterine wall
“A’s” Accreta Adheres
Placenta Increta
Invades the uterine myometrium into the muscle
“I’s” go together Increta Invades
Placenta Percreta
Most problematic
Invades uterine serosa or other structures outside of the pelvis, it penetrates
“P’s” Percreta Penetrates


 Without prenatal diagnosis placenta accreta may be found after delivery of the baby
Surgeon will be unable to remove the placenta
History of cesarean section and placental previa increases risk
Anesthetist should be highly suspicious of presenting parturient with history of cesarean and
current placenta previa
 Attempting to remove placenta can result in hemorrhage
Treatment usually requires hysterectomy
Prenatal diagnosis allows the obstetrician to proceed to peripartum hysterectomy, decreasing
incidence of hemorrhage

Two obstetricians maybe present for high risk accreta

 Diagnosis of previa and accreta are both done with trans vaginal ultra sound

638
 Advancement in diagnoses decrease the occurrence of double set up exams
If unable to dx with ultrasound, obstetrician and anesthesia set up for possible cesarean
section
Obstetrician performs a vaginal exam
If placental previa dx or bleeding begins, the teams continue with cesarean delivery

Intubation of the OB pt.

639
 • Airway difficulties are often unexpected and are 3x more likely!!
• Changes in the airway
• Airway edema
• Decreased FRC Increased closing capacity= desat quickly
• Increased O2 consumption
• Weight gain
• Enlarged breasts
• Decreased LES tone, increased intragastric pressure
• Decreased emptying
• Always considered to be a full stomach and 6 weeks post delivery
• Decreased GI motility, decreased food absorption and decreased LES pressure are
d/t elevated levels of circulating progesterone.
• Elevated gastrin produced by the placenta increases intragastric pressure resulting
in higher risk for reflux→ always considered full stomach. Also, gastric acid
secretion increases secondary to gastrin secretion.
Parameter: % Change:

Diaphragm excursion ↑

Chest wall excursion ↓

Pulmonary resistance ↓ by 50%

FEV1 No change

FEV1/FVC No change

Flow volume loop No change

Closing capacity No change

Pitocin (Oxytocin)
640
  Drug of choice for labor induction, and prevention/treatment of uterine atony
 Routine use of oxytocin has been shown to reduce the incidence of PPH by as much as 40
percent
 Exogenous oxytocin stimulates the force and frequency of uterine contractions
 MOA:
Enhances the activation of voltage-gated calcium channels, and increases local prostaglandin
production
 Oxytocin IV infusion is started after placenta delivery in vaginal birth, or
immediately after umbilical cord clamping in cesarean delivery
20-30 U added to 1L NS, in continuous IV infusion
 Bolusing oxytocin IV causes peripheral vasodilation, which can result in hypotension
 Various EKG changes may occur with oxytocin administration, but they are transient
due to oxytocin’s short plasma half-life

OB ANESTHESIA

641
 Respiratory-----
-Since the diaphragm pushes up against the lungs by expanding uterus- There is a 20% decrease
in FRC (Valley) Chestnut claims 25% in ERV and 15% RV- 45% decrease all the way up to
80% of prepreg. Capacity at term!!
-There is NO CHANGE in TLC, VC, and Insp. Capacity cause of increase in thoracic anteropost.
Diameter. – How can the body do this? -- Relaxin – relaxes ligamentous attachments of ribs.
-Tidal volume increases by 45%- half of this occurs during first trimester- so with this- increase
in minute ventilation obviously
-ESTROGEN plus more blood-----Airway edema!!!!- Capillary engorgement of larynx- begins
early- MOST EVIDENT during third trimester, ironic as this is the time we are usually screwing
around w/their airway.
- PROGESTERONE is a direct respiratory stimulant- increases MV, increases chemo sensitivity
to CO2-
- SO… PROGESTERONE helps cause left-shift of CO2 curve
-There is a respiratory alkalosis- PaCO2 30- metabolic acidosis keeps pH normal.
-PaO2 is higher- higher alveolar ventilation. –CO2 lower- Progesterone, higher PaO2
-ENHANCED uptake of inhaled anesthetics- Increase in O2 consumption- higher alveolar vent
and MV, TV, RR- faster uptake of gas
SOOO... challenging airway, prone to mucosal bleeding. Engorge breasts, full dentition and
weight gain- good luck with DL. Difficult airway algorithm, have LMA, advanced airway
techniques. Better yet, don’t DL at all!
-LOWER MAC- increased MV, decreased FRC. Decreased by 40%.
-Ventilation during general anesthesia adjust so that PaCO2 is maintained at 30mmHg-
remember that is their normal level, AND they have a reduced serum bicarb level- so increasing
PaCO2 to nonpreg levels will make Acidosis.
Have a smaller ETT 6.5 or 7 and always have 6.0 ready if needed.
DESATURATE FAST!!!! Why? — Less FRC, Increase O2 consumption, and their swollen
airways obstruct easy. Why else? --- When lying flat may get venocaval compression- reduction
in O2 delivery.

-AIRWAY complications are the LEADING cause of anesthesia related mortality in OB, and the
rest of the population for that matter.

642
PRE-ECLAMPSIA----- Now we are talking retention of extra fluid, low plasma oncotic, ----
TISSUE EDEMA- --- AIRWAY EDEMA, narrowing all the way up to airway compromise.
O2-Hgb dissociation curve lie to right- P50 30.4mmHg vs. normal 26.7mmHg
Higher P50 aids DO2 to uteroplacental unit.
Resp. alkalosis of Preg. Pushes O2-Hbg dissociation to left- increase in 2, 3, DPG- brings curve
back to right.

Cardiac changes OB

643
Pregnancy- Cardiac Hypertrophy- Greater blood volume increased stretch and force of
contraction. Eccentric LV hypertrophy- bigger existing cardiomyocytes.
3rd heart sound in 3rd trimester. Benign. S1 accentuation. Elevation of diaphragm- heart
shift anterior and to left- PMI displaces to 4th ICS and left to midclavic. Line.
-CO INCREASES to 30-40% during 1st trimester due to increase in HR, decrease in afterload.
-CO during LABOR-

Latent phase 15% increase

Active phase 30% increase
Second stage 45% increase
POSTPARTUM 80% INCREASE

-Changes in CV System-

Blood volume 35%increase

Plasma volume 45% increase
RBC volume 20% increase

Increase in blood volume, however, bigger increase in plasma volume---- Relative Anemia seen
in pregnancy
Decrease in PVR seen so HTN doesn’t occur from increased blood volume
Hemodynamics at Term----
CO 50% increase SV 25% increase HR 25% increase LVEDV increase+LVESV
unchanged =EF% increase SVR 20% decrease
-Rise in CO- more perfusion to uterus, kidneys, extremities- higher skin temp
Uterine blood flow increase from 50ml/min to 700-900ml/min at term- 90% of this goes to the
intervillous space.
Why decrease in SVR? --- Development of low-resistance vascular bed (intervillous space) and
vasodilation from prostacyclin, estrogen, and progesterone

644
-Maternal supine hypotensive syndrome---- Compression of IVC decreases venous return-
decreases CO- decreases BP- hypotension.
SOOO----- Venodilation- increase risk of epidural vein puncture
Healthy parturient tolerates up to 1500 blood loss. Transfusion rare.
Higher Hgb of 14 or up- consider low-volume state from pathology- HTN, pre-eclampsia, too
much diuretic
- There is a gestational thrombocytopenia- enhanced plt turnover, clotting and fibrinolysis.
A state of accelerated, compensated intravascular coagulation Factors XI and XIII
DECREASE, Factor I and V unchanged.

GI SYSTEM OB

645
-Stomach displaced up and to left, axis rotation to left- Esophageal displacement INTO
THORAX-
-This REDUCES ton of the lower esophageal high-pressure zone (LEHPZ)
PROGESTINS decrease this zone, and the LES tone, decreases GI motility, food absorption and
LES pressure
GASTRIN elevation- Increases gastric acid. Intragastric pressure increase, decreases oblique
angle of GE-junction- High risk of GERD.
30-50% pregnant patients get GERD.
-Changes in GI physiology during Pregnancy

Parameter First Second Third Labor Postpartum

trimester trimester trimester
Barrier Decrease Decrease Decrease Decrease
pressure
Gastric Unchanged Unchanged Unchanged Delayed Unchanged
emptying
Gastric acid No change or No change or No change or ?? increase
secretion decrease decrease decrease
Amount of Unchanged Unchanged Unchanged Increased No change
women with
gastric
volume
>25ml
Amount with Unchanged Unchanged Unchanged Decreased No change
pH<2.5
gastric

These patients are ALWAYS considered full stomach and risk for aspiration!!!
ON top of this, narcotics, valium and atropine all further decrease LES tone and increase GI
emptying-

Renal OB

646
Increase in total vascular volume--- renal vascular volume and interstitial volume increase-
Enlarged Kidneys
-Hydronephrosis may occur in 80% of women by mid-pregnancy
-GFR and renal plasma flow INCREASE MARKEDLY. GFR increase 50%, plasma blood flow
increase 75%.
-GFR does not decrease until 3 months postpartum.
With the above- creat. Clearance increased to 150-200ml/min- this is up from normal
`120ml/min.
With the above- reduction in nitrogenous metabolites- BUN decreases to 8-9mg/dlring
Proteinuria also occurs during pregnancy
-GREATER BICARBONATE EXCRETION--- metabolic acidosis- this is a compensatory
response to the resp. alkalosis
- With the above- there is a decreased ability to buffer an acid load

Drugs Passing Placenta Review

647
• The transfer mechanisms used for the transfer of substances across the placental barrier:
simple diffusion; simple diffusion through channels; facilitated diffusion; active
transport; endocytosis.
• Drug dose.
• Maternal protein binding- reduces the amount of available drug (only free drug will
transfer).
• Non-ionized drugs cross the placenta.
• Highly charged drugs do not cross placenta easily NDMR do not cross.
• Rapid biotransformation & excretion speed the decline of drug levels & limit transfer;
i.e.: Succinylcholine.
• Route is important ( less drug transfer epidurally than intravenously)
• Dependent on uterine blood flow
• Placental blood flow decreases with uterine contractions
• Molecular weights - heavier molecules do not cross as easily as lighter molecules
• Lipid solubility: the more lipid soluble the molecule, the faster it crosses the placental
membrane.
- Fetal academia can result in the ion trapping of both local anesthetics and opioids.
- Drugs that pass placenta - Drugs that don’t pass placenta
Anticholinergics- atropine scopolamine Anticholinergic- Glycopyrrolate
AntiHTN agents- B-antagonists, nipride, nitroglycerin Heparin
Benzos- Diazepam, Midazolam Succinylcholine
Induction- Propofol, STP, ketamine, methohexital, etomidate All NDMRs
All inhalational
Local anesthetics----

Amides greatest to least ability to cross-

Mepiv>Etidocaine>Lidocaine>Ropivicaine>Bupivicaine

Ester LAs don’t transfer as much due to metabolization by

plasma pseudochol.
Opioids
MEPERIDINE- neonate and CNS depression
Ephedrine

OB Review

648
Stages of labor review,

 1st (cervical): perception of regular contractions → complete cervical dilation (10 cm)
o Allows fetal movement from uterus to vagina
o Active phase, 1st stage: nullipara should dilate cervix at 1.2 cm/hr, parous at 1.5
cm/hr
o –If pt doesn’t dilate at appropriate rate during active phase, said to have 1o
dysfunctional labor
o Membranes generally rupture at onset of labor or near full cervical dilation
 2nd (pelvic): complete cervical dilation to birth of baby
o Cervix completely retracted to form lower uterine segment
o –Full dilation
o When complete, increased bloody show and vomiting may occur
o Strong uterine contractions w/pushing cause fetal presenting part to descend
through pelvis, resulting in delivery
o 2nd stage > 2 hrs prolonged for nullipara w/out epidural, 3 hrs w/epidural
o Cord arterial pH varies inversely w/length of 2nd stage duration
 3rd (placental): birth of baby to placental delivery
o Time from delivery of baby to delivery of placenta
o •Placenta usually separates from uterine wall w/in few contractions after delivery
of baby
o •Signs of placental separation:
 Uterus rises in maternal abdomen
 Shape of uterus changes from discoid to globular
 Umbilical cord lengthens
 Gush of blood
o •If no separation of placenta after 30 min, or significant bleeding, manual removal
indicated
 If placenta can’t be separated from uterine wall, may have some retention
and ↑ bleeding
o •After placenta removed, uterotonic given to decrease bleeding
o •Oxytocin 20U/1L
 Bolus doses cause hypotension
o •If uterus doesn’t respond, consider methergine 0.2 mg IM
 Contracts vascular smooth muscle
o •15-methylprostaglandin F2α (Hemabate)
 Ecbolic agent
 0.25 mg IM can be effective uterotonic

 4th (1st 60 minutes after delivery of placenta)

649
 o 60 min post delivery
o Pt must be watched closely for bleeding
o >90% of postpartum hemorrhage due to uterine atony
Regional in OB...Included how the uterine blood flow is affected,
Neuraxial anesthesia:

 Regional strongly preferred

 Neonatal APGAR scores no different at 5 min, but maternal M&M decreased with
regional
 Considerations:
o Pre-hydration
o FHT monitoring
o LUD
o Vasopressors : ephedrine ( β sympathetic, α indirect) > Neosynephrine ( pure α ₁
agonist)
o T4 sensory block
 Local Anesthetics and Uterine Blood flow
o Pregnancy may enhance uterine vascular reactivity to local anesthetic agents.
Exact mechanism is unknown.
o Clinical experience with the use of local anesthetics; clinical concentrations do
not adversely affect the uterine vasculature.
o All local anesthetics can reduce uterine blood flow at plasma concentrations that
greatly exceed those occurring during the routine practice of obstetric anesthesia
o Regulatory mechanisms that control flow through the umbilical vessels are poorly
understood.
o Local anesthetics constrict at lower doses and relax vessels at higher doses. ↓↓
Flow with IV administration.
o Local anesthetics exert direct effects on uterine smooth muscle.
o Local anesthetics cross the placenta.
o Local anesthetics are weak bases; they have a relatively low degree of ionization
and considerable lipid solubility at physiologic pH.
o Maturation of the placenta may affect the rate of drug transfer. Drugs cross the
placenta more rapidly in late pregnancy.
 Maternal hypotension= >20% decrease in CO
 > 2 mins of severe hypotension→ fetal acidosis, lower APGAR scores, prolonged time to
sustain respiration
 SAB for elective or urgent cesarean delivery
 Epidural→ when rapid blockade is contraindicated : hypovolemia, hemorrhaging patient;
good control over duration

650
Spinal for C-section:

 Metoclopramide 10 mg IV
 Oral antacid
 IV volume expansion w/LR or NS 15-20 ml/kg
 Apply monitors
 Supplemental O2
 Prophylactic IM ephedrine
 L3-L4:24 or 22 G Sprotte; 25 or 27 G Whitacre
 Hyperbaric bupivacaine 12 mg +/- morphine 0.25-0.4 mg for postop analgesia ( or 20
mcg fentanyl or 200 mcg astromorph)
 Aggressive rx hypotension
 *Exaggerated L uterine displacement
 *IV fluids
 *Ephedrine
 Complications
o Pruritus
o Nausea/vomiting
o Urinary retention
o Uterine hyper stimulation and fetal bradycardia: presumably due to decrease in
maternal catecholamines with opioids causing uterine hypotonicity
o Maternal respiratory depression
Epidural for C-section:

 Metoclopramide 10 mg IV
 Oral antacid
 Volume expansion w/LR or NS, 10-20 ml/kg
 Supplemental O2
 Epidural catheter at L2-3 or L3-4
 L uterine displacement
 Test dose: why? what to expect, what to give
 Therapeutic dose
o 5 ml boluses of 2% lido with 1:200K/1:400K epi, or
o 5 ml boluses of 0.5% bupivacaine or 3% Nesacaine
o Boluses of lidocaine or Nesacaine q 1-2 min
o Boluses of bupivacaine q 2-5 min
 Aggressive rx hypotension
o Exaggerated LUD
o IV fluids
o Ephedrine

651
Nerve and dermatome during stages and pain blocking mechanisms
1st Stage – uterine contraction & cervical dilation

 Pain initially @ T11-T12, then progresses to T10-L1 with active labor via visceral
afferent nerves
 Dilating cervix & lower uterine segment along with myometrial contraction against
resistance of cervix and perineum play major role in pain
2nd Stage – from end of first stage to delivery of baby

 Onset of perineal pain @ end of first stage is signal of fetal descent

 Pudendal nerves (S2-4) provides the sensory innervation of the perineum via somatic
nerve fibers, therefore the 2nd stage of labor involves T10-S4 dermatomes.
3rd Stage – delivery of baby until placenta & membranes expelled
Pain perception involves a complex series of nociceptive transmissions that begin with
stimulation of sensory nerves in the periphery, resulting in generation of action potentials within
the spinal cord and synaptic transmission to other supraspinal sites.
Intraspinal administration of an opioid exploits the pharmacology of pain-modulating and pain-
relieving systems that exist within the spinal cord.
Preeclampsia and magnesium
Magnesium as tocolytic:

 Decreases uterine activity during labor

 Has infrequent cardiovascular side effects, thus is widely used.
 Although actual mechanism is unknown, calcium antagonism appears to play a role
 Extracellular Mg++ affects uptake, binding, distribution of cellular Ca++ in vascular
smooth muscle→ ↑ intracellular cAMP which inhibits light chain kinase activity and
actin-myosin interaction
 Loading dose = 4 g x 15-20 min
 Continuous gtt: 1-4 g/hr
 Serum concentration of 5-7 mg/100 ml needed to inhibit uterine activity
 •Adverse effects: chest pain, palpitations, nausea, hypotension ( from ↑ed muscle
relaxation including vascular smooth muscle), blurred vision, sedation ( hence, there is a
20% decrease in MAC requirements), pulmonary edema
 •Hypermagnesemia results in abnormal neuromuscular function
o Decreases release of ACh at NMJ and sensitivity of endplate to ACh, thus
potentiates the action of both depolarizing and non-depolarizing MRs ( titrate
NDMR; avoid defasciculating dose)
o May have an effect on platelet function due to calcium antagonism

652
  •Affects action of phenylephrine by increasing uterine vascular resistance →↓UBF; use
ephedrine instead
 •D/C MgSO4 before epidural (2-4 hrs prior) due to more pronounced hypotension.

Anesthetic Implications of MgSO4

 Regional
o Titrate epidural block carefully
o Higher block level + MgSO4 may impair maternal MAP and UBF
 •Neuromuscular function
o At motor end plate, Mg++ inhibits Ca++ facilitated presynaptic transmitter
release, enhancing sensitivity to nondepolarizers
o Mg++ also potentiates activity of depolarizers
Pre-Eclampsia:

 Pregnancy-induced HTN
o Preeclampsia
 Mild
 Severe
o Eclampsia
 Pre-eclampsia
o HTN, proteinuria and/or pathologic edema after 20th week
 HTN–Diastolic BP at least 90, systolic BP at least 140
 Rise of 15 mm Hg diastolic or 30 mm Hg systolic on at least 2
occasions 6 hrs apart
 Magnesium as treatment:
o Peripheral effects at neuromuscular junction
o Central anticonvulsant effect mediate via NMDA receptors
in hippocampus
o Beneficial effects:
 Vasodilation, increased cGMP production,
attenuation of vascular responses to pressor
substances, decreased PRA and ACE levels,
increased production of PGI2 by endothelial cells

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  Severe refractory HTN
o Most preeclampsia pts respond well to intermittent boluses
of hydralazine
 SNP, labetalol, Ca++ channel blockers may all be
useful for rx of severe refractory HTN
o ACE inhibitors useful in postpartum period
o Magnesium produces vasodilation
 1st line drug before anti-HTN agent
 Plus proteinuria
 ≥ 300 mg protein in 24 hr urine collection or ≥ 1 g/L in at least 2
random specimens 6 or more hrs apart
 And/or edema
 Generalized fluid accumulation (> 1+ pitting edema) after 12 hrs
bed rest
 Wt gain of ≥ 5 # (2.27 kg) in 1 wk.
o Severe Symptoms:
 SBP ≥ 160, DBP ≥ 110 on 2 occasions 6 hrs apart
 Proteinuria ≥ 5 g in 24 hr urine specimen or 3+-4+ on UA
 Oliguria: urine output < 400 ml/24hrs
 Cerebral or visual disturbances
 H/A, blurred vision, altered LOC
 Pulmonary edema, cyanosis
 Epigastric or RUQ pain 2o stretching of Glisson’s capsule by hepatic
edema
 Hepatic rupture (rare)
 Impaired liver function
 Thrombocytopenia 2̊ platelet adhesion to exposed collagen at sites of
endothelial damage
 Check Coags before inserting epidural – just because they have
platelets doesn’t mean they work well in pre-eclampsia
 HELLP syndrome: Hemolysis, Elevated Liver enzymes, Low Platelets
 Eclampsia:
o convulsions w/out coincidental neurologic disease in pt who meets criteria for
preeclampsia
o Etiology unknown
o 85% of preeclampsia cases in 1st pregnancy. Also associated with:
 Higher body mass, multiple gestation, chronic HTN

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Magnesium Sulfate is cornerstone of seizure prophylaxis
 Loading dose 4-6 g IV over 20 min followed by infusion of 1-2 g/hr

o Pts monitored clinically, e.g., patellar reflexes, respiratory rate, urine output
o Therapeutic range: 4-7 mEq/L
 Loss of patellar reflexes: 10 mEq/L
 Respiratory arrest: 12-16 mEq/L
 Asystole: > 20 mEq/L
 If suspected toxicity, D/C immediately & treat w/ IV calcium gluconate or
chloride

Acceleration – Abrupt increase above the baseline, duration of >/= 15 seconds but </= 2 minutes
from onset to return to baseline. Accelerations are usually associated with either spontaneous
fetal activity, stimulation, or uterine activity. Acceleration are GOOD

655
Decelerations- NOT good, ↓ in HR, shows fetal distress, can’t tolerate the contractions
Periodic (occurring associated with contractions)
Episodic (occurring without an association to contractions)

Early deceleration occur simultaneously w/ uterine contractions

Gradual decrease and return to baseline associated with a contraction; the onset, nadir and offset
occur coincidentally with the contraction, with the nadir of the deceleration occurring at the peak
of the contraction.

Variable Deceleration

Abrupt decrease in FHR of ≥ 15 bpm lasting ≥

15 seconds but < 2 minutes. May be periodic
or episodic. When associated with uterine
contractions (periodic), variable decelerations
may vary in onset, depth, and duration from
contraction to contraction.

Change in maternal position (e.g., Return of

Transient umbilical cord Variable left or right lateral or umbilical blood
compression decelerations Trendelenburg position), flow toward
amnioinfusion normal

Return of
Head compression,
Variable Pushing only with alternate umbilical blood
usually during the
decelerations contractions flow toward
second stage of labor
normal

Late Deceleration → begin after the onset of a uterine contraction.

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Hypotension (e.g., Bradycardia, Intravenous fluids, position
Return of uterine blood
supine hypotension, late change, vasopressor
flow toward normal
neuraxial anesthesia) decelerations (phenylephrine or ephedrine)

Bradycardia, Decrease in oxytocin, lateral

Excessive uterine Return of uterine blood
late position, tocolysis (e.g.,
activity (tachysystole) flow toward normal
decelerations terbutaline, nitroglycerin)

 Return of uterine
blood flow toward
 Change in maternal
normal, increase in
Decreased uterine position (e.g., left
maternal-fetal O 2
blood flow associated lateral position),
gradient
with uterine Late administration of
 Decrease in
contractions, below decelerations supplemental oxygen
contractions or
limits of fetal basal  Tocolysis (e.g.,
uterine tone, thus
oxygen needs terbutaline,
abolishing the
nitroglycerin)
associated drop in
uterine blood flow

Baseline Variability-fluctuations in the baseline FHR of two cycles per minute with peak to
trough amplitude.

657
 Absent variability = undetectable amplitude range-> sign of fetal compromise
 Minimal variability = undetectable but ≤ 5 bpm → sign of fetal compromise
 Moderate variability = amplitude 6-25 bpm → OK
 Marked variability = amplitude > 25 bpm → bad, baby is working hard

Sinusoidal baseline

‐ Regular oscillations with an amplitude range of 5-15 bpm. Frequency of

undulations of 2-5 cycles per minute. Minimal to absent short term variability.
Rhythmic oscillation of a since wave above and below baseline. Absence of FHR
accelerations. Extreme regularity and smoothness.
‐ Is known to occur in the presence of fetal hypoxia, fetal anemia, and chronic fetal
bleeds.

658
Uterine Emergencies

Staging Scheme to Assess Obstetric Hemorrhage

Severity of Findings % blood loss
Shock
None None <15%-20%
Mild Tachycardia (< 100), mild hypotension 20-25%
Peripheral vasoconstriction
Moderate Tachycardia (100-120) Moderate
Hypotension (SBP 80-100), Restlessness, oliguria
Severe Tachycardia (> 120), Hypotension (SBP < 60), altered > 35%
consciousness, anuria

Placenta Previa
Placenta Previa: Anesthetic Management
• All pts admitted w/antepartum vaginal
bleeding should be evaluated by anesthesia
provider on admission
– Airway exam, volume status
– At least 1 large-bore IV
– Check hgb & hct, type & crossmatch
– Volume resuscitation w/crystalloid
• Double set-up
– U/s exam results?
– Examine pt in OR – all team members present & set up for C-section
– Full monitors, 2 large bore IVs, 2 U PRBCs,
– C-section if significant bleeding during exam
• RSI preferred for bleeding pts
– Ketamine 0.5-1 mg/kg IV
• No hallucinations when < 1 mg/kg
• Causes myocardial depression if pt hypovolemic
– Etomidate 0.2-0.3 mg/kg IV
• Minimal cardiac depression
• Venous irritation, myoclonus, poss adrenal suppression

659
 • Maintenance of anesthesia
– Severe fetal distress – no N2O
– Low concentration inhalation agent – D/C after delivery 2o effects on uterus &
increase N2O to 70% w/opioids
– Add Pitocin 20U/1L after delivery

Placental Abruption
• Separation of placenta before delivery of fetus.
• Acute bleeding from exposed decidual vessels.
• Fetal distress occurs due to loss of area for maternal-fetal gas exchange.

Anesthetic Management: Placental Abruption

• Epidural analgesia if coags and volume status OK
• If C-section for fetal distress:
– GA w/RIS, etomidate or ketamine induction
– Aggressive volume resuscitation
• Crystalloid, colloid, Level I infuser
• Consider invasive monitoring lines
– Risk for persistent hemorrhage 2o uterine atony or coagulopathy
• After delivery, add oxytocin 20U/1 L
Uterine Rupture: Etiologies
• Previous uterine surgery
• Trauma
– Indirect: blunt, e.g., seat belt, excessive manual fundal pressure, extension of
cervical laceration
– Direct: penetrating wound, intrauterine manipulation, forceps application &
rotation, postpartum curettage, manual placental extraction, version & extraction,
external version

• Inappropriate oxytocin use

• Grand multiparity
• Uterine anomaly
• Placenta Percreta
• Tumors
– Trophoblastic disease, cervical carcinoma
• Fetal problems
– Macrosomia, malposition, anomaly

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Anesthetic Management: Uterine Rupture
• Hysterectomy is definitive procedure for most cases of uterine rupture
• Pt evaluation/preparation begun while pt prepared for emergency laparotomy
• If rupture antepartum, fetal distress likely
• GA often necessary
• Aggressive volume replacement & maintenance of urine output essential
• Invasive monitoring if unsure re: adequacy of volume replacement

Vasa Previa
• Umbilical vessels separate in membranes distant from placental margin
• Some of fetal vessels cross internal os and occupy position ahead of presenting fetal part
• Rupture of membranes may be accompanied by tear of fetal vessel leading to
exsanguination
• Obstetric emergency
– C-section
– Ensure fetal survival
– Aggressive neonatal resuscitation

661
 Placental Abruption

What is it?Complete or partial separation of the placenta from the uterine wall before delivery
of the baby. Maternal hemorrhage may be revealed by vaginal bleeding or may be concealed
behind the placenta. Fetal compromise occurs because of the loss of placental surface area for
maternal-fetal exchange of oxygen and nutrients.

Risk factorshypertension, pre-eclampsia, advanced maternal age/parity (high number of

pregnancies), tobacco use, cocaine use, premature rupture of membranes, chorioamnionitis
(infection between maternal and fetal edges of the amniotic membrane), bleeding in early
pregnancy and a history of previous abruption.

Incidence0.4-1% of pregnancies, higher in African American women.

DiagnosisPAINFUL VAGINAL BLEEDING, although bleeding may be hidden, uterine

tenderness, idiopathic preterm labor

Fetal impactnon-reassuring fetal heart rate (FHR) patterns including bradycardia, late or
variable decels, and/or loss of FHR variability, fetal hypoxia, fetal compromise or demise.

Maternal complicationshemorrhagic shock, acute renal failure, & coagulopathy. Most

common cause of DIC in pregnancy.

Curedefinitive treatment=delivery of baby, degree of maternal and fetal compromise

determine the timing and route of delivery. Most often, non-reassuring FHR pattern necessitates
immediate delivery.

662
Anesthetic considerations

If mom and baby are stable enough to warrant an attempt at a vaginal delivery adequate volume
status and baseline CBC/coagulation panel are essential. Epidural anesthesia will cause a
sympathectomy which may impact the maternal response to hemorrhage.

If procedure is urgent d/t fetal distress, general anesthesia is required. RSI should be done with
all pregnant patients along with gastric acid neutralization-30mL bicitra. Avoid propofol and
thiopental with induction as they may precipitate severe hypotension in hypovolemic patients.
Ketamine and etomidate are better options for the hypovolemic patient.

 Large gauge IV catheter

 T/C x at least 2 units, baseline CBC & coags
 Oxygen
 Left uterine displacement
 Aggressive volume resuscitation with crystalloid and colloids.
 If severe hemorrhage CVC (if coagulopathy present, use an antecubital vein to place 14 g
PIV) and arterial line

Patients are at a high risk for persistent hemorrhage from uterine atony or coagulopathy once the
baby is delivered. Immediate infusion of oxytocin (20-30 U/L) should be infused. Can also use
misoprostol, methergine or Hemabate for severe uterine atony.

663
 Umbilical Cord Prolapse

Situation in which the umbilical cord passes through the cervix leading to cord compression
resulting in fetal hypoxia. Compression of the cord cuts off the supply line for oxygen/nutrients
exchange for the baby.

Diagnosiscan be visibly seen protruding out of the vagina or can be found on digital cervical
examination. FHR patterns can include decels, variables and/or late, or prolonged bradycardia.

TreatmentDELIVERY

 Place the mom on her hands and knees and have a practitioner manually displace the fetal
head away from the cervix, relieving pressure on the cord. Do not touch the umbilical
cord itself as manipulation of the cord will cause the vessels to vasospasm. The
practitioner “rides the bed” with the patient to the OR and does not remove their hand
until the fetus is delivered by the surgical team.
 If unable to immediately proceed to the OR, place the patient in Trendelenburg and place
a foley catheter. Instill the maternal bladder with 500 mL of saline and clamp. This will
cause the bladder to displace the baby’s head and keep it from compressing on the cord.
Continuous FHR monitoring.
Anesthetic considerations

 If patient was laboring, dose epidural, if unable to achieve an adequate surgical block,
may have to convert to a general. Can try 5-10 mg of ketamine to make it to delivery of
the baby then you can give more narcotics/benzos. Must not sedate patient too much so
that they are unable to protect their airway as they are high risk for aspiration.
 If patient does not have regional anesthesia already in place, proceed with GETA with
RSI and gastric acid neutralization.

Retained Placenta
• Placenta accreta vera:
– Adherence to myometrium w/out invasion
into/through uterine muscle
• Placenta increta
– Invasion in myometrium
• Placenta percreta
– Invasion into uterine serosa or other pelvic
structures

664
Retained placenta: anesthetic management
• Depends on presence/absence of hemorrhage
• Epidural block used for labor/delivery
– Add 2% Nesacaine or lidocaine PRN
• SAB good choice for pts not bleeding who don’t have epidural in place
• In some cases, 50% N2O adequate or ketamine 10 mg boluses up to 0.5 mg/kg, fentanyl
50-100 μg
• May require GA
• Consider NTG

Treatment of massive blood loss

• Postpartum hemorrhage can lead to massive blood loss
• BP may remain close to normal until EBL 1500 ml
• Initial resuscitation
– Warmed LR, NS, Hespan
– 1 unit RBCs increases hgb by 1.5 g/dL, hct 4-5%
– FFP: replaces coag factors in clotting disorders. Doesn’t decrease blood loss in
massive EBL situations.
– Platelets: beneficial if platelet count < 50K
• Coagulopathy can develop rapidly
– Observe for microvascular bleeding on surgical field

Coagulopathy
• Dilutional `
– Results from replacement of blood loss w/ crystalloid and PRBCs
• Concentrations of coag factors diluted
• Develops gradually after > 1 blood volume loss
• Responds to FFP & platelets
• Disseminated
– Dramatic decline in coag factors & platelets 2o clotting factor and platelet
consumption
– Develops rapidly in OB pts, e.g., w/ AFE or abruption
– Multiple coag components required (FFP, platelets, cryo)

665
Labs:
Magnesium

 Magnesium is involved in energy production, oxygen uptake, central nervous system

function, electrolyte balance, glucose metabolism and muscle activity, including the
heart. Magnesium plays an essential role in many of the functions of energy
production itself. It is an integral part of the energy (ATP) and protein (enzymes - as
co-factor and as a structural component of the muscle protein, myosin) molecules—
without which the energy to contract and relax the heart does not occur properly.
Magnesium is also an essential element in the construction of the cell membrane and
vitally important to the electrolyte balance of cells. In that the heart is composed of
cells, magnesium plays a role in the integral strength of the heart muscle itself. When
magnesium levels begin to get too low the body tries very hard to adapt, but these
basic functions of energy production and cell structure can be affected, and when they
are, symptoms of heart or cardiovascular disease can begin to manifest.
 Without enough magnesium, the cell is no longer able to keep up the proper number
of high-energy molecules (ATP) to healthfully function. Once magnesium falls down
below a certain level, just about everything starts to go. The sodium balance starts to
go and the electrolyte balance starts to go. The cell is not able to have a fully and
optimally functional membrane system. Calcium and sodium start to rush into areas
where they normally would not be and the cell begins to lose its ability to properly
alternate of "wave" between active and inactive states. Spending too much time in an
"over-active" biochemistry, and if no "balance" is possible unless there is an influx of
essential magnesium in proper balance with other electrolytes, the cell just starts to
get weaker and weaker because it doesn’t have the energy to do all the things it needs
to do.

Effects of Low Magnesium Levels

 Increased blood clotting. When this clotting occurs within blood vessels, it creates the
risk of heart attack or stroke.
 The secretion of adrenaline increases abnormally.
 Cells begin to over respond to the stimulation of adrenaline stimulation.
 Cholesterol production and metabolism become abnormal.
 All muscle cells, including those in the heart and blood vessels, tend to contract and
become unable to relax. In myocardial cells, magnesium is a cofactor for the sodium-
potassium adenosine triphosphates enzyme and antagonizes both the L-type and T-
type calcium channels in the atria. Magnesium is often given as an antiarrhythmic
 There is increased production of free radicals and susceptibility to oxidative stress.
 Arteries stiffen and develop a buildup of plaque as a result of too much bad
cholesterol and too much calcium.
 Glucose is not properly processed as a result of insulin resistance, which can lead to
type II diabetes and a whole spectrum of other disorders, all leading to heart disease.

666
Magnesium and OB

 Magnesium sulfate is most commonly used for the treatment of preeclampsia during
pregnancy. Magnesium sulfate is effective in reducing the risk of seizures in women
who have severe preeclampsia. It also prevents repeat seizures in women who have
eclampsia. It is not known exactly how magnesium prevents or stops seizures during
pregnancy. But it may work by antagonizing NMDA receptors. Magnesium sulfate is
sometimes used as a tocolytic medicine to slow uterine contractions or to help protect
the baby's brain during preterm labor. Magnesium is thought to affect the action of
calcium in the body, and calcium must be present for the muscles of the uterus to
contract.

Common side effects of Magnesium:

 Muscle weakness and lack of energy. Decreased reflexes (reflexes must be monitored
ever 2-4 hours)
 Blurry vision.
 Slurred speech.
 Headache.
 Nausea and vomiting.
 Flushing.
 Stuffy nose.

Magnesium and pain control

 NMDA antagonist
 Hypermagnesemia can impair the release of acetylcholine and decrease motor end
plate sensitivity of acetylcholine in the muscle.
 Dose 1-2 grams over 30 minutes.
 Avoid in patients with renal failure
 Blocks bradykinin release in the local vasculature.
 How to treat low magnesium (normal Mag 1.5 - 2.5 mg/dL)
 1-2 grams IV over 30 min.

Diet

 Green vegetables such as spinach are good sources of magnesium, which is contained
in the chlorophyll molecule. Some legumes (beans and peas), nuts and seeds, and
whole, unrefined grains are also good sources of magnesium.

667
High levels of magnesium

 Hypermagnesemia occurs rarely because the kidney is very effective in excreting

excess magnesium. It usually develops only in people with renal failure who are
given magnesium salts or who take drugs that contain magnesium (e.g. some antacids
and laxatives). It is usually concurrent with hypocalcemia and/or hyperkalemia.
 Arrhythmia and Asystole are possible cardiac complications of hypermagnesemia.
Magnesium acts as physiologic calcium blocker, which results in electrical
conduction abnormalities.

Clinical consequences related to serum Magnesium concentration:

 4.0 mEq/l hyporeflexia

 >5.0 mEq/l Prolonged atrioventricular conduction
 >10.0 mEq/l Complete heart block
 >13.0 mEq/l Cardiac arrest

o Note that the therapeutic range for the prevention of the pre-eclampsic uterine
contractions is: 4.0-7.0 mEq/L

Treatments for hypermagnesemia:

 Intravenous calcium gluconate, because the actions of magnesium in neuromuscular

and cardiac function are antagonized by calcium.
 Definitive treatment of hypermagnesemia requires increasing renal magnesium
excretion through:
 Intravenous diuretics, in the presence of normal renal function
 Dialysis, when kidney function is impaired and the patient is symptomatic from
hypermagnesemia

Lactate

 Lactate is one of the main components of lactated Ringer's solution and Hartmann's
solution. These intravenous fluids consist of sodium and potassium cations along with
lactate and chloride anions in solution with distilled water, generally in concentrations
isotonic with human blood. It is most commonly used for fluid resuscitation after
blood loss due to trauma, surgery, or burn injury.

668
One liter of lactated Ringer's solution contains:

 130 mEq of sodium ion = 130 mmol/L

 109 mEq of chloride ion = 109 mmol/L
 28 mEq of lactate = 28 mmol/L
 4 mEq of potassium ion = 4 mmol/L
 3 mEq of calcium ion = 1.5 mmol/L
 Lactated Ringer’s is not for use for the treatment of lactic acidosis or severe
metabolic acidosis.
 Lactated Ringer’s should not be administered simultaneously with citrate
anticoagulated/preserved blood through the same administration set because of the
likelihood of coagulation.
 Lactated Ringer’s should be administered with particular caution, if at all, to patients
with hyperkalemia or conditions predisposing to hyperkalemia (such as severe renal
impairment or adrenocortical insufficiency, acute dehydration, extensive tissue injury
or burns), cardiac disease, to patients with alkalosis or at risk for alkalosis (because
lactate is metabolized to bicarbonate, administration may result in, or worsen,
metabolic alkalosis), severe renal impairment, hypervolemia, or conditions that may
cause sodium and/or potassium retention, fluid overload, or edema.

669
Anion Gap

Used to identify the cause of metabolic acidosis. If the gap is greater than normal, then high
anion gap metabolic acidosis is diagnosed.
The anion gap (AG) was introduced to help establish the cause of a metabolic acid–base
disturbance. To maintain electrical neutrality, cations and anions must be balanced: measured
anions + unmeasured anions = measured cations + unmeasured cations. Routinely measured
anions are Cl− and HCO3−, and routinely measured cations are Na+ and K+. Unmeasured cations
include calcium, magnesium, lithium, and immunoglobulin G. Other serum proteins, phosphate,
sulphate, and organic anions (e.g. lactate and ketoacids) account for the unmeasured anions.
The AG is mainly due to the negative charge of plasma proteins, predominantly albumin:

Example: The anion gap is affected by changes in unmeasured ions. A high anion gap indicates
acidosis. In uncontrolled diabetes, there is an increase in ketoacids due to metabolism of ketones.
Ketoacids are unmeasured anions, so there is a resulting increase in the anion gap. In these
conditions, bicarbonate concentrations decrease, in response to the need to buffer the increased
presence of acids (as a result of the underlying condition). The bicarbonate is consumed by the
unmeasured cation (H+) (via its action as a buffer) resulting in a high anion gap.

Reference range is 8 to 16 mmol/l.

Major Clinical Uses of the Anion Gap
 To signal the presence of a metabolic acidosis and confirm other findings
 Help differentiate between causes of a metabolic acidosis: high anion gap versus normal
anion gap metabolic acidosis. In an inorganic metabolic acidosis (e.g. due HCl infusion),
the infused Cl- replaces HCO3 and the anion gap remains normal. In an organic acidosis, the
lost bicarbonate is replaced by the acid anion which is not normally measured. This means
that the AG is increased.
 To assist in assessing the biochemical severity of the acidosis and follow the response to
treatment
The anion gap is useful especially if very elevated or used to confirm other findings. Causes of
a high anion gap acidosis can be sorted out more specifically by using other investigations in
addition to the history and examination of the patient. Investigations which may be very useful
are:
 Lactate
 Creatinine
 Plasma glucose
 Urine ketone test

670
Key Fact: Hypoalbuminemia causes a low anion gap
Albumin is the major unmeasured anion and contributes almost the whole of the value of the
anion gap. Every one gram decrease in albumin will decrease anion gap by 2.5 to 3 mmoles. A
normally high anion gap acidosis in a patient with hypoalbuminemia may appear as a normal
anion gap acidosis. A lactic acidosis in a hypoalbuminemia ICU patient will commonly be
associated with a normal anion gap.

To understand the context read the following:

Bicarbonate on the chemistry panel gives you an indication of acid-base status, but does not
replace blood gas measurement as it does not supply information about the respiratory
component of acid-base maintenance. Bicarbonate values should always be interpreted with
the anion gap, which is a calculated parameter. The anion gap provides useful information
for delineating causes of metabolic acidosis and can give you an indication of a mixed acid-
base disturbance.

Acid-base status
In health, blood pH (which is taken as the same as ECF pH) is maintained within a narrow
range of approximately 7.4 to 7.5. Traditional interpretation of acid-base status involves the
Henderson-Hasselbach equation, where pH is determined by the ratio of bicarbonate to
carbon dioxide. Blood pH is normal when the ratio of HCO3- to pCO2 is 20:1. Respiratory
factors affect pCO2, whereas non-respiratory, or metabolic factors, affect the HCO3-.
The major extracellular buffer of acids in the body is bicarbonate followed by plasma
proteins and bone. Intracellular buffers include proteins, organic phosphate, inorganic
phosphate and hemoglobin (in erythrocytes). Regulation of acid-base involves chemical
buffering with intra- and extra-cellular buffers, control of partial pressure of carbon dioxide
by altering respiration and control of bicarbonate and hydrogen excretion by the kidneys. In
general, rapid changes in acid-base can be achieved by changing respiration, whereas the
kidney is involved in slower, more long-term regulation of acid-base status. The kidney is
central to acid-base regulation. Filtered bicarbonate is absorbed in the PCT of the kidney
and regenerates the bicarbonate lost in buffering acids produced by normal body
metabolism. Hydrogen is excreted by the PCT and DCT of the kidney. Excretion of H+ by
the PCT is dependent on filtered phosphates and urea generated by the tubular epithelial
cells. Excretion of H+ by the DCT is dependent on sodium reabsorption and exchanges for
K+.

There are four primary types of acid-base disorders: metabolic acidosis, respiratory acidosis,
metabolic alkalosis, and respiratory alkalosis. The majority of patients with acid-base
imbalance have either metabolic acidosis or metabolic alkalosis or a mixed disorder of both.

671
Acidosis
Acidosis can be primary metabolic (decreased HC03) or respiratory (hypercapnea) or
secondary in compensation for a primary alkalosis. Acidosis has profound effects on the
body, resulting in arrhythmias, decreased cardiac output, depression, and bone
demineralization.

 Primary metabolic acidosis: This can be due to loss of bicarbonate (hyperchloremic

metabolic acidosis) or titration of bicarbonate (high anion gap metabolic acidosis).

 Primary respiratory acidosis: This is due to increased pCO2 from decreased effective
alveolar hypoventilation. Any disorder interfering with normal alveolar ventilation
can produce a respiratory acidosis. The most common causes are primary pulmonary
disease, ranging from upper airway obstruction to pneumonia. Diseases or drugs that
inhibit the medullary respiratory center also produce a profound respiratory acidosis,
e.g. general anesthesia.

Alkalosis
Alkalosis can be primary metabolic (increased HCO3) or respiratory (hypocapnea) or
secondary in compensation for a primary acidosis. Usually respiratory alkalosis is the
compensatory mechanism for a primary metabolic acidosis. Alkalosis results in tetany and
convulsions, weakness, polydipsia and polyuria.

 Primary metabolic alkalosis: This is usually due to loss of chloride with retention of
HCO3 in place of chloride.

 Primary respiratory alkalosis: This is due to hyperventilation and is associated with

decreased pCO2. Hyperventilation is usually stimulated by hypoxia associated with
pulmonary disease, congestive heart failure, or severe anemia. Psychogenic
disturbances, neurologic disorders, or drugs that stimulate the medullary respiratory
center, will also stimulate hyperventilation.

Compensation

In general, changes in bicarbonate produce compensatory changes in carbon dioxide and

vice versa. Compensation causes parallel changes in pCO2 and bicarbonate.
In a primary metabolic acidosis, HCO3 will be decreased. The compensatory response is
reduction of pCO2 by alveolar hyperventilation (i.e. a secondary respiratory alkalosis), e.g.
dogs with a lactate acidosis from hypovolemia often hyperventilate. The maximum
respiratory compensation expected for a primary metabolic acidosis is estimated from the
following formula:

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Decrease in pCO2 = 1.5 [HCO3) + 8
The compensatory response for a primary respiratory acidosis is renal retention of
bicarbonate (a secondary metabolic alkalosis).
In a primary metabolic alkalosis, HCO3 is increased. Chemoreceptors in the respiratory
center sense the alkalosis and trigger hypoventilation, resulting in increased pC02 or a
compensatory respiratory acidosis.
The compensatory response to a respiratory alkalosis is initially due to a decrease in ECF
bicarbonate from cellular buffering. Then renal reabsorption of bicarbonate is reduced. The
decline in bicarbonate is offset by retention of chloride (to maintain electro neutrality), thus
producing a secondary hyperchloremic metabolic acidosis. The pH can revert to normal
from compensation in chronic respiratory alkalosis.

Rules for compensation:

 Compensation does not produce a normal pH (except for compensation of chronic

respiratory alkalosis, in which compensatory metabolic acidosis does correct the
pH).
 Overcompensation does not occur.
 Sufficient time must elapse for compensation to reach steady-state, approximately 24
hours.

Characteristic findings in the different primary acid-based disorders with appropriate

compensatory changes are illustrated in the table below.

Conditions pH H+ Primary Compensation

Metabolic acidosis Low High Low HCO3 decrease pCO2 (hyperventilation)

Metabolic alkalosis High Low High HCO3 increase pCO2 (hypoventilation)

Respiratory acidosis Low High High pCO2 kidneys retain HCO3

Respiratory alkalosis High Low Low pCO2 kidneys excrete HCO3

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Mixed acid-base disturbances

These are quite common and can be detected by non-parallel changes in HCO3 and the
anion gap, chloride and pCO2. The following features give you an indication that a mixed
acid-base disturbance is present:

1. The pH is normal but there is an abnormal pCO2 and/or bicarbonate. (Remember

that compensation rarely results in a normal pH.)
2. Changes in pCO2 and bicarbonate occur in opposing directions. (Remember that
with compensation, changes in pCO2 and bicarbonate parallel each other.)
3. Change in pH is opposite to that predicted from the pCO2 and HCO3.
4. Compensation exceeds upper or lower limits.

There are easy formulas used to determine if there is a mixed acid-base disturbance present.
These formulas depend on whether there is an elevated anion gap or not. For all these
formulas, the change in the parameter is compared to the midpoint of the reference range for
the parameter (normal), i.e.

 Change in AG (anion gap) = Measured AG - Normal AG

 Change in bicarbonate = Measured bicarbonate - Normal bicarbonate
 Change in chloride = corrected chloride concentration - Normal chloride

Remember that all of these are generalizations. There are exceptions to every rule.

High anion gap

In an uncomplicated high anion gap acidosis, the change in AG is equivalent to the change
in bicarbonate. If the change in anion gap is greater or less (usually by 2:1) than the change
in bicarbonate, a mixed acid-base disturbance is present.

 If the decrease in bicarbonate is greater than the increase in anion gap, this indicates
that there is a mixed disturbance, with something lowering the bicarbonate greater
than expected. In this instance, this is compatible with a mixed high anion gap and
hyperchloremic (normal anion gap) acidosis, e.g. renal failure, resolving diabetic
ketoacidosis, diarrhea with a high anion gap acidosis (e.g. lactic acidosis).

 If the decrease in bicarbonate is less than the increase in anion gap, this indicates that
there is a mixed disturbance, with something preventing the bicarbonate from being
as low as it should be. This is compatible with a mixed high anion gap acidosis and
metabolic alkalosis, e.g. GDV (lactic acidosis with sequestration of chloride-rich
fluid), renal failure with vomiting/diuretics, vomiting and diarrhea/diabetic
ketoacidosis/lactic acidosis. In this case, the bicarbonate and chloride will be low
and the anion gap will be high.

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Normal anion gap acidosis or alkalosis

In an uncomplicated normal anion gap acidosis or a metabolic alkalosis, the change in

chloride is equivalent to the change in bicarbonate. If the change in chloride is greater or
less (usually by 2:1) than the change in bicarbonate, a mixed acid-base disturbance is
present.

 If the decrease in chloride is greater than the increase in bicarbonate, this indicates
that there is a mixed disturbance, with something decreasing the bicarbonate. In this
instance, this is compatible with a mixed normal anion gap acidosis and a metabolic
alkalosis. This can occur renal failure with vomiting/diuretics, vomiting and
diarrhea, and liver disease.

 If the increase in chloride is less than the decrease in bicarbonate, this indicates that
there is a mixed disturbance, with something enhancing the decrease in bicarbonate.
This is compatible with a mixed high anion gap and normal anion gap acidosis.

In patients with a normal anion gap the drop in HCO3− is the primary pathology. Since there
is only one other major buffering anion, it must be compensated for almost completely by an
increase in Cl−. This is therefore also known as hyperchloremic acidosis. The HCO3− lost is
replaced by a chloride anion, and thus there is a normal anion gap.

 Gastrointestinal loss of HCO3− (i.e., diarrhea) (note: vomiting causes hypochloremic

alkalosis)
 Renal loss of HCO3− (i.e., proximal renal tubular acidosis(RTA) also known as type
2 RTA)
 Renal dysfunction (i.e., distal renal tubular acidosis also known as type 1 RTA)
 Renal Hypoaldosterone (i.e., renal tubular acidosis also known as type IV RTA)
characterized by elevated serum potassium.

There are three types.

1. Low Renin may be due to diabetic nephropathy or NSAIDS (and others causes).
2. Low aldosterone may be due to adrenal disorders or ACE inhibitors.
3. Low response to aldosterone maybe due to potassium sparing diuretics, Bactrim,
or diabetes (and other causes).[13]

 Ingestions
o Ammonium chloride and acetazolamide, ifosfamide.
o Hyperalimentation fluids (i.e. total parenteral nutrition)
 Some cases of ketoacidosis, particularly during rehydration with Na+ containing IV
solutions.
 Alcohol (such as ethanol) can cause a high anion gap acidosis in some patients, but a
mixed picture in others due to concurrent metabolic alkalosis.
 Mineralocorticoid deficiency (Addison's disease)

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Low anion gap

A low anion gap is frequently caused by hypoalbuminemia. Albumin is a negatively charged

protein and its loss from the serum results in the retention of other negatively charged ions
such as chloride and bicarbonate. As bicarbonate and chloride anions are used to calculate
the anion gap, there is a subsequent decrease in the gap.

In hypoalbuminemia the anion gap is decreased from between 2.5 to 3 mmol/L per 1 g/dL
decrease in serum albumin. Common conditions that reduce serum albumin in the clinical
setting are hemorrhage, nephrotic syndrome, intestinal obstruction and liver cirrhosis.

Summary

 High anion gap with change in anion gap > change in bicarbonate. This indicates:
1) Mixed high anion gap metabolic acidosis and metabolic alkalosis. Most common
causes include renal failure and vomiting, renal failure and diuretics, diabetic
ketoacidosis and vomiting, lactic acidosis and vomiting.
2) Non acidotic high anion gap with normal or increased bicarbonate. This occurs in
a pure metabolic alkalosis, carbenicillin therapy and dehydration (increased
albumin).
3) Mixed high anion gap metabolic acidosis plus respiratory acidosis, e.g.
cardiopulmonary arrest.

 High anion gap with change in anion gap < change in bicarbonate. This indicates:
1) Mixed high anion gap and normal anion gap acidosis.
2) High anion gap acidosis masked by low anion gap (decreased albumin,
paraproteins).
3) Combined high anion gap acidosis and chronic respiratory alkalosis.

Remember: There can be more than 2 mixed acid-base disturbances. There can be
three primary acid-base disturbances, e.g. mixed high and normal anion gap acidosis
and respiratory acidosis occurs with cardiopulmonary arrest.

Exceptions

The change in anion gap can be greater than the change in bicarbonate without there being a
mixed acid-base abnormality in the following situations: Alkalemia, sodium containing
drugs, changes in albumin, and changes in unmeasured cations. However the changes in
anion gap induced by these conditions are usually mild.

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 Anesthesia and Pimp Practice Type of review and Questions

Allergies and Anesthesia:

Allergic reactions are better described as hypersensitivity reactions. These reactions are then said
to be an allergy. They are mediated by an overreaction of the body’s immune response to an
interaction of an antigen (usually a protein) and antibody. Hypersensitivity reactions are
classified into 4 types. Type I is an immediate response/anaphylactic reaction, mediated by IgE
antibodies and mast cells. Type II reactions involve complement, IgG or IgM antibodies. These
reactions are referred to as, antibody dependent reactions. They are associated with interactions
of antigens on foreign cell surfaces, i.e. ABO blood incompatibility reactions or heparin-induced
thrombocytopenia. Once these reactions occur the result usually ends up with cell death by
phagocytosis or lysis from complement activation. Type III reactions are known as immune
complex reactions. They involve soluble antigens that enter the blood and interact in the plasma
to form insoluble residues that interact with microvascular endothelium. The microvascular areas
tend to localize the reaction, an example would be, and protamine induced pulmonary
vasoconstriction.
Type IV reactions are known as delayed reactions. They are the result of sensitized lymphocytes
that ultimately generate cytotoxic T cells to destroy the invading antigen. They may take a day to
develop and a week to resolve, commonly involving contact with poison ivy or graft vs. host
reactions.
Common reactions in anesthesia involve, local anesthetics, opioids, muscle relaxants, induction
agents, antibiotics, bone cement, insulin, protamine, and many others. NDNMBs like
Atracurium, Rocuronium (Zemuron) and others are the most common type of allergic reaction
involved in anesthesia. NDNMBs have a unique molecular structure that allows them to activate
IgE antibodies resulting in a type I hypersensitivity reaction. Other reactions may involve
induction agents like Propofol and patients who have egg or soy allergies, as egg and soy
proteins are present in the storage emulsion of Propofol. Patients who have an allergy to avocado
or banana, may have an allergy to latex as both bananas and avocados have latex proteins in
them. Protamine or Contrast Dye may trigger an allergic reaction with patients who have a
fish allergy as they are derived from proteins of fish. Patients with sulfa allergy may be allergic
to Lasix, Celebrex, Sulfasalazine, Bactrim, and morphine, which all contain sulfa in their active
compound or storage medium. Penicillin’s and cephalosporins have a cross sensitivity reaction
based on the beta-lactamase proteins, more specifically a side chain to the ring.

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NMDA receptors and pain:
NMDA receptors are located on secondary postsynaptic afferent neurons. Their activity is
mediated primarily by the neurotransmitter glutamate. Chiefly additional endogenous chemicals,
chiefly zinc and glycine that may allosterically open and close off the NMDA ion channel to
calcium movement also modulate them. Normally the calcium influx through the NMDA
receptor causes a central sensitivity to pain and may also be responsible for part of chronic pain
syndromes. There are a few drugs that are direct blocker of the NMDA receptor. 1) Ketamine
(Ketalar) 10mg/ml (1-2mg/kg IV) provides pain relief by directly blocking the calcium pore of
the NMDA receptor and thus blocking the normal glutamate excitation that would be a
transduction part of the pain pathway. The pain impulse may still reach the spinal column and
the brain but the brain simply does not care about it. We also refer to ketamine as a dissociative
hypnotic for this reason. 2) Memantine is an Alzheimer’s treatment to protect the brain from
self-perpetuating neural cell death associated with excessive glutamate that is present from
necrotic neural tissue. Memantine is more selective for NMDA receptors that are open and works
by blocking the channel like Magnesium, and Ketamine (Lipton, 2004). 3) Magnesium IV may
also work on keeping NMDA receptors blocked like ketamine to provide dissociative pain relief.
4) Angel dust (PCP) is the agent that Ketamine and 4) Sernyl were derived from, also a
potential NMDA receptor agent for pain control. The effects of blocking NMDA are not limited
to pain dissociative relief. They can also be tied to vivid hallucinations, hypnosis, amnesia and
sedation as well. These additional side effects are related to how long the drug acts at the
receptor. Additional NMDA receptor antagonists include 5) Dextromethorphan, 6) Nitrous
Oxide, 7) Meperidine and 8) Tramadol (Ultram). Their mechanisms of action are all similar.
Most of the fore mentioned agents would either competitively antagonize (compete for the same
site on NMDA as glutamate and thus block the receptor activation an opening for calcium influx
and associated second messaging system) or non-competitively block the ion pore. (Ketamine
and Magnesium) (Wikipedia 2013). The end result being less stimulation/excitation in the brain,
including the transduction of pain pathways.
PONV/PDNV:
Risk factors of nausea and vomiting are as follows. Females, non-smokers, patients that receive
general anesthetics with volatile agents, history of PONV, narcotic use, high levels or long
durations of nitrous oxide use (debatable may be related to the gaseous distention of the stomach
and air filled cavities, ears-vestibular- that may cause nausea), and tendency of motion sickness.
The general rule of thumb is to medicate for each risk factor up to 3-4 medications, i.e., a female,
non-smoker who receives a GETA and post op narcotics would have 4 risk factors. Typically one
would treat with maybe just Zofran. Now we know more about PONV and the benefits of
multimodal/multi receptor treatment. It would be more prudent to treat with Decadron, Zofran,
and Benadryl, and then consider, Droperidol, Compazine, and/or Reglan as rescue drugs.
Adequate hydration can also mitigate PONV following guidelines from this website-
[Link]
PDNV_Clinical_Guideline_Aug_2006_JoPAN.pdf

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Some non-traditional methods in preventing PONV/PDNV may include items that may affect
some of the triggers for PONV. Dopamine, histamine, serotonin, toxins, norepinephrine, mu
opioid, hypoxia, C02 as well as cortical sensory areas of the brain, all have inputs to the
chemoreceptor trigger zone (CTZ), which is largely responsible for the induction of nausea and
vomiting. Acupuncture or nerve stimulation may alleviate PONV via Mu receptor input into the
CTZ. Subcutaneous Propofol may provide non-traditional PONV alleviation by possibly
decreasing serotonin in the area postrema and CSF, (mimicking Zofran). Decadron may have
antiemetic effects based on decreasing para-sympathetic responses to nausea by decreasing
inflammation in the neck, which ultimately decreases the input to the CTZ. Decadron may also
inhibit serotonin production and prostaglandin synthesis associated with nausea (Fuji, 2008).
Peppermint may have some anti-nausea properties based on its pleasant smell- (cortical input)
and supposed effects on GI motility and lower esophageal sphincter tone. Isopropyl Alcohol
may also have cortical effects on PONV for acute temporary treatment; little research has been
done on this to explain the mechanism by which it may work. Ginger has long been regarded as
an anti-dyspeptic, however large doses of ginger may be needed to provide clinically effective
results. Oxygen has some anti-nausea effects, studies have found little significance in the amount
of oxygen required to treat or prevent PONV. Adequate hydration may also mitigate PONV,
possibly by diluting the concentration of toxins, or offending agents in the blood or GI tract.

Fuji, Y... 2008. The Benefits and Risks of Different Therapies in Preventing Postoperative
Nausea and Vomiting in Patients Undergoing Thyroid Surgery. Current Drug Safety.
Vol. 3 pp. 27-34

Lipton, S. 2004. Failures and Successes of NMDA Receptor Antagonists:

Molecular Basis for the Use of Open-Channel Blockers like Memantine in the Treatment of
Acute and Chronic Neurologic Insults. Neuro Rx_: The Journal of the American Society
for Experimental NeuroTherapeutics. 1(1).

Stoelting, R., Hiller, S... 2006. Pharmacology & Physiology in Anesthetic Practice. 4th ed.
Lippincott Williams and Wilkins Philadelphia.

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Allergic reaction: The hypersensitive response of the immune system of an allergic individual to
a substance. Allergic reactions have three basic characteristics:
1. immunologically mediated
2. Exhibits specificity
3. Recurrence on re-exposure
Other important distinctions:
• Pseudo allergic reaction: adverse drug effects not proven to be immune mediated but resemble
allergic reactions in clinical presentation.
• Drug Intolerance: a low threshold to the normal pharmacologic action of a drug.
• Anaphylaxis: an acute, life threatening allergic reaction involving multiple organ systems.
• Anaphylactoid reaction: synonym for pseudo allergy; resembles anaphylaxis but does not
involve the immune system
Allergies and anesthesia – allergies specifically related to anesthetic medications or to
medications or substances used during the perioperative period in during the time that anesthesia
is being administer or directly related to the administration of anesthesia and/or adjunct
treatments.
Examples:
1. Sulfonamide antibiotics/non-antibiotics (Approximately 3-5% of patients report being
allergic to sulfonamide antibiotics, mainly Bactrim). Cross reactivity - Non-antibiotic
sulfonamides include bumetanide, furosemide, glimepiride, glipizide, glyburide, HCTZ,
probenecid, and torsemide.
2. Opioids (true opioid allergy is rare – most common type is a pseudo allergy). Cross
reactivity among the three main opioid structural classes:
a. Morphine group: morphine, codeine, hydrocodone, oxycodone, hydromorphone,
nalbuphine, butorphanol, pentazocine
b. Diphenylheptanes: methadone, propoxyphene
c. Phenylpiperidines: meperidine, fentanyl, sufentanil, Remifentanil
3. Local Anesthetics “-caines” (True allergies to local anesthetics is uncommon anaphylaxis
is extremely rare. Most reactions are vasovagal, psychogenic, toxic, or a predictable side
effect of the epinephrine that commonly is included in the preparation. Other possible
causes include the preservatives in multidose vials. Cross reactivity: Two major classes
of local anesthetics
a. Benzoate esters: benzocaine, Chloroprocaine, cocaine, procaine,
proparacaine, tetracaine
b. Amides: Bupivicaine, dibucaine, lidocaine, prilocaine, and Ropivacaine
Cross reactivity only exists among the benzoate esters, not the amides. If
the patient has experienced a true allergy to a benzoate ester local
anesthetic, an amide may be considered. If the patient experienced a true
allergy to an amide, another amide or a benzoate ester may be considered.

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4. Latex - Allergic reactions to natural rubber latex comprise both delayed and immediate
(IgE-mediated) hypersensitivities, producing clinical symptoms ranging from contact
urticaria and bronchial asthma to anaphylactic shock. Cross reactivity - (degree of
association or prevalence):
a. High (4) - Banana, Avocado, Chestnut, Kiwi
b. Moderate (7) - Apple, Carrot, Celery, Papaya, Potato, Tomato, Melons
c. Low or undetermined (33) - Pear, Mango, Sweet Pepper, Peach, Rye, Cayenne
Pepper, Plum, Wheat, Shellfish, Cherry, Hazelnut, Sunflower Seed, Pineapple,
Walnut, Citrus Fruits, Strawberry, Soybean, Coconut, Fig, Peanut, Chick Pea,
Grape, Buckwheat, Castor Bean, Apricot, Dill, Lychee, Passion, Fruit, Oregano
Zucchini, Nectarine, Sage, Persimmon
5. Muscle relaxants - (e.g. succinylcholine, rocuronium, Atracurium - rocuronium has a
higher rate of IgE-mediated anaphylaxis compared with other NMBA) – responsible for
approximately 50-70% of the incidence of perioperative anaphylaxis. Cross reactivity:
Hypersensitivity can occur during the first administration of an anesthetic due to cross
sensitization from similar quaternary ammonium ions in cosmetics, personal products
(toothpastes, soaps, and shampoos), chemical additives in foods (metabisulfites,
preservatives), and drugs (cough medicines). The tertiary ions or quaternary ammonium
ions of NMBAs May cross-react with other NMBAs, morphine, acetylcholine, and
neostigmine.
6. Propofol - There is no role to contraindicate propofol in egg-allergic, soy-allergic or
peanut allergic patients. However, the administration of propofol to patients with a
documented history of true anaphylaxis to eggs is controversial.
7. Aprotinin – Even though it is no longer marketed, tissue sealants or fibrin glues may
contain Aprotinin that can trigger anaphylaxis.
8. Protamine – Cross-reactivity: insulin use ( i.e. insulin - dependent diabetes mellitus),
vasectomy, allergy to fish, prior exposure to protamine sulfate

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 NMDA Receptor

NMDA (N-methyl-D-aspartate is a receptor for the excitatory neurotransmitter glutamate, which

is released with noxious peripheral stimuli. The activation of NMDA receptors has been
associated with hyperalgesia, neuropathic pain, and reduced functionality of opioid receptors.
Hyperalgesia and neuropathic pain are a result of increased spinal neuron sensitization, leading
to a heightened level of pain. The reduced function of opioid receptors is caused by a decrease
in the opioid receptor’s sensitivity. This decreased sensitivity, in turn, translates to opioid
tolerance as patients will require higher doses of opioids to achieve the same therapeutic effects.
This being the case, the NMDA antagonists may have a role in these areas of pain management.

There are several NMDA receptor antagonists available: ketamine, methadone, Memantine,
amantadine, and dextromethorphan. Each differs in their level of activity on the NMDA
receptor. Ketamine is a strong NMDA antagonist, whereas the others are weaker NMDA
receptor blockers

1. Ketamine has several clinically useful properties, including analgesia and less
cardiorespiratory depressant effects than other anesthetic agents, it also causes some
stimulation of the cardiovascular system. Ketamine has been reported to produce general
as well as local anesthesia. It interacts with N-methyl-D-aspartate (NMDA) receptors,
opioid receptors, monoaminergic receptors, muscarinic receptors and voltage sensitive Ca
ion channels. Unlike other general anesthetic agents, ketamine does not interact with
GABA receptors.
2. Dextromethorphan is an opioid-like drug that binds to and acts as antagonist to the
NMDA glutamatergic receptor, it is an agonist to the opioid sigma 1 and sigma 2
receptors; it is also an alpha3/beta4 nicotinic receptor antagonist and targets the serotonin
reuptake pump. Dextromethorphan is rapidly absorbed from the gastrointestinal tract,
where it enters the bloodstream and crosses the blood-brain barrier. The first-pass
through the hepatic portal vein results in some of the drug being metabolized into an
active metabolite of dextromethorphan, dextrorphan, the 3-hydroxy derivative of
dextromethorphan.
3. Methadone is a mu-agonist; a synthetic opioid analgesic with multiple actions
qualitatively similar to those of morphine, the most prominent of which involves the
central nervous system and organs composed of smooth muscle. The principal therapeutic
uses for methadone are for analgesia and for detoxification or maintenance in opioid
addiction. The methadone abstinence syndrome, although qualitatively similar to that of
morphine, differs in that the onset is slower, the course is more prolonged, and the
symptoms are less severe. Some data also indicate that methadone acts as an antagonist at
the N-methyl-D-aspartate (NMDA) receptor. The contribution of NMDA receptor
antagonism to methadone's efficacy is unknown. Other NMDA receptor antagonists have
been shown to produce neurotoxic effects in animals.

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4. Memantine is an amantadine derivative with low to moderate-affinity for NMDA
receptors. It is a noncompetitive NMDA receptor antagonist that binds preferentially to
NMDA receptor-operated cation channels. It blocks the effects of excessive levels of
glutamate that may lead to neuronal dysfunction. It is under investigation for the
treatment of Alzheimer’s disease, but there has been no clinical support for the
prevention or slowing of disease progression. Memantine exerts its action through
uncompetitive NMDA receptor antagonism, binding preferentially to the NMDA
receptor-operated cation channels. Prolonged increased levels of glutamate in the brain of
demented patients are sufficient to counter the voltage-dependent block of NMDA
receptors by Mg2+ ions and allow continuous influx of Ca2+ ions into cells, ultimately
resulting in neuronal degeneration. Studies suggest that Memantine binds more
effectively than Mg2+ ions at the NMDA receptor, and thereby effectively blocks this
prolonged influx of Ca2+ ions through the NMDA channel whilst preserving the transient
physiological activation of the channels by higher concentrations of synaptically released
glutamate. Thus Memantine protects against chronically elevated concentrations of
glutamate. Memantine also has antagonistic activity at the type 3 serotonergic (5-HT3)
receptor with a potency that is similar to that at the NMDA receptor, and lower
antagonistic activity at the nicotinic acetylcholine receptor. This drug has no affinity for
γ-aminobutyric acid (GABA), benzodiazepine, dopamine, adrenergic, histamine, or
glycine receptors or for voltage-dependent calcium, sodium, or potassium channels.
5. Amantadine is an antiviral that is used in the prophylactic or symptomatic treatment of
influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions,
and for post herpetic neuralgia. The mechanisms of its effects in movement disorders are
not well understood but probably reflect an increase in synthesis and release of dopamine,
with perhaps some inhibition of dopamine uptake. The mechanism of its antiparkinsonic
effect is not fully understood, but it appears to be releasing dopamine from the nerve
endings of the brain cells, together with stimulation of norepinephrine response. It also
has NMDA receptor antagonistic effects. The antiviral mechanism seems to be unrelated.
The drug interferes with a viral protein, M2 (an ion channel), which is needed for the
viral particle to become "uncoated" once it is taken inside the cell by endocytosis.
6. Phencyclidine is a hallucinogen formerly used as a veterinary anesthetic, and briefly as a
general anesthetic for humans. Phencyclidine is similar to ketamine in structure and in
many of its effects. Like ketamine, it can produce a dissociative state. It exerts its
pharmacological action through inhibition of NMDA receptors. As a drug of abuse, it is
known as PCP and Angel Dust. Normal physiological function requires that the activated
receptor fluxes positive ions through the channel part of the receptor. PCP enters the ion
channel from the outside of the neuron and binds, reversibly, to a site in the channel pore,
blocking the flux of positive ions into the cell. PCP therefore inhibits depolarization of
neurons and interferes with cognitive and other functions of the nervous system.

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 7. Tenocyclidine (TCP) is a dissociative anesthetic drug with stimulant and hallucinogenic
effects. It is similar in effects to phencyclidine but is considerably more potent. Due to its
similarity in effects to PCP, TCP was placed into the Schedule I list of illegal drugs in the
1970s, although it was only briefly abused in the 1970s and 1980s and is now little
known. The primary interactions are as a non-competitive antagonist at the 3A-subunit
of the NMDAR in Homo sapiens. TCP is known to bind, with relatively high affinity, to
the D1 subunit of the human DAT, in addition to displaying a positive antagonistic effect
at the α7-subunit of the Nicotinic Acetylcholine Receptor (nAChR). It also binds to the
mu-opioid receptor, which seems to be a central part of the mechanism of action of drugs
in this class. (For example, Dizocilpine [MK-801] shows little appreciable analgesic
effect despite having a high specificity for the NMDA-3A and NMDA-3B subunits - this
may well be mediated by the lack of related efficacy at the mu-opioid receptor, though
the NMDAR certainly does play a role in transmission of pain signals).
8. Xenon - The anesthetic potency of Xe has been ascribed to its blocking capacity of N-
methyl-D-aspartate receptor channels. Other targets have also been identified which
might add to the anesthetic potency of Xe. These include two-pore K+ channels, nicotinic
acetylcholine receptors, as well as receptors for serotonin, glycine and GABA.

Nausea is the subjective sensation of an urge to vomit, in the absence of expulsive muscular
movements; when severe; it is associated with increased salivary secretion, vasomotor
disturbances, and sweating. Vomiting or emesis is the forcible expulsion through the mouth of
the gastric contents. Vomiting results from coordinated activity of the abdominal, intercostal,
laryngeal, and pharyngeal muscles, including retrograde giant contraction of the intestines,
relaxation of the gastric fundus, closure of the glottis, and elevation of the soft palate. This
activity is associated with increased heart rate and breathing and with sweating. Retching is an
unproductive effort to vomit. Retching and vomiting are collectively termed emetic episodes.
The vomiting center lies in the medulla oblongata and comprises the reticular formation and the
nucleus of the tractus solitarius. When activated, motor pathways descend from this center and
trigger vomiting. These efferent pathways travel within the 5th, 7th, 9th, 10th, and 12th cranial
nerves to the upper gastrointestinal tract, within vagal and sympathetic nerves to the lower tract,
and within spinal nerves to the diaphragm and abdominal muscles. The vomiting center can be
activated directly by irritants or indirectly following input from 4 principal areas: gastrointestinal
tract, cerebral cortex and thalamus, vestibular region, and chemoreceptor trigger zone (CRTZ).
The CRTZ is closest in proximity, lying between the medulla and the floor of the fourth
ventricle. Unlike other brain centers, it is not protected by the blood-brain barrier.

684
This is to say that the endothelium of its capillaries is not tightly joined or surrounded by glial
cells and is permeated easily by irritants regardless of their lipid solubility or molecular size.
Before vomiting occurs, there may be a period of antiperistalsis, in which rhythmic contractions
occur up the digestive tract instead of downward. This may commence as far down as the ileum,
with the antiperistalsis wave pushing contents of the lower small intestine contents upward into
the duodenum and stomach within a few minutes. Then, distention within these upper portions of
the gastrointestinal tract generates afferent impulses to the vomiting center, where the actual act
of vomiting is initiated. For this reason, an empty stomach does not preclude the expulsion of
vomitus. At the onset of vomiting, intrinsic contractions occur in both the duodenum and the
stomach, the lower esophageal sphincter relaxes, and vomitus moves from the stomach into the
esophagus. Next, the inspiratory and abdominal muscles contract and expel the vomitus into the
mouth.
Nontraditional methods to prevent/treat PONV/PDNV:
1. cannabinols such as tetrahydrocannabinol found in marijuana and Dronabinol (Marinol),
a synthetic derivative, have proven efficacy only for chemotherapy-induced nausea and
vomiting
2. Acupuncture has been fairly well established in the prevention of PONV. It consists of
stimulating the so-called P6 wrist point (located on the ventral surface of the forearm
approximately 3 finger widths proximal to the wrist joint) by using acupuncture,
acupressure, and other techniques.
a. Injection of 1ml of Lidocaine at the P6 wrist point.
b. Distance- measures the width of the hand and take that length from the crease of
the wrist. Then inject at the bifurcation of the muscles on the radius.
c. Anecdotally- Worked 90% of the time during a mission trip in Columbia using
halothane. Only patient with N/V had an IV bandage on the wrist and did not
receive the block post operatively.
3. Ephedrine – anecdotal evidence only.
4. Aromatherapy with Peppermint, Isopropyl Alcohol.
5. Histamine analogue – betahistine
6. Neurokinins (substance P, NK1) antagonists - impressive antiemetic in the animal model.
However, early clinical data have been disappointing, except for aprepitant (Emend)
7. Transcutaneous electrical nerve stimulation (TENS) – shows some promise compared to
Ondansetron.
8. Ginger root – the jury is still out on this one
ASA guidelines:
[Link]
B871C2A9EF5E29C1?year=2006&index=1&absnum=2121

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 Practice Questions:

. PCN and Cephalosporins has what % cross allergy potential? What PCN is the is an
exception? Why is this? This drug also has an interaction and something to be careful
of... what is it and what drugs should you avoid... hint... think Demerol....
The frequency of adverse reactions to penicillin in the general population ranges from 0.7% to
10%, with anaphylactic reactions occurring in about 0.004% to 0.015% of patients.
Comparatively, the overall incidence of adverse reactions to cephalosporins ranges from 1% to
10%, with anaphylactic reactions occurring in less than 0.02% of patients. The incidence of cross
sensitivity between penicillin’s and cephalosporins has been reported to be as high as 10%. This
concept of increased probability of cross sensitivity between penicillin’s and cephalosporins
arose from the fact that both classes share a common beta-lactam ring and have a similar
spectrum of allergic reactions.
[Link]

Aztreonam is a Monobactams antibiotic that contains a beta lactam ring. However, unlike other
beta lactam antibiotics, Aztreonam does not contain a bicyclic-ring structure. To date,
Aztreonam has not demonstrated clinical cross-reactivity in penicillin-allergic patients.
However, there is conflicting data in the literature regarding this.
[Link]

As far as “this drug has an interaction and something to be careful of…” – I have been
completely stumped by this. I could not find any source that describes any interaction with this
drug, even when I considered Demerol?????
2. Speaking of Demerol it as a few contraindications. Tell me them and what is it heart rate
side effect and why?
Demerol (meperidine) is contraindicated in patients who are receiving MAOIs or those who have
recently received such agents. Therapeutic doses of Demerol have occasionally precipitated
unpredictable, severe, and occasionally fatal reactions in patients who have received MAOIs
within the previous 14 days. It may precipitate a serotonin syndrome reaction with agitation,
hyperthermia, diarrhea, tachycardia, sweating, tremors and impaired consciousness. In other
reactions the predominant manifestations have been hyper excitability, convulsions, tachycardia,
hyperpyrexia, and hypertension. The mechanism of these reactions is unclear, but may be
related to a preexisting hyperphenylalaninemia.
[Link]

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Additional drug interactions with Demerol:
Acyclovir: Plasma concentrations of meperidine and its metabolite, normeperidine, may be
increased by acyclovir, thus caution should be used with concomitant administration.
Cimetidine: Cimetidine reduced the clearance and volume of distribution of meperidine and also
the formation of the metabolite, normeperidine, in healthy subjects and thus, caution should be
used with concomitant administration.
Phenytoin: The hepatic metabolism of meperidine may be enhanced by Phenytoin. Concomitant
administration resulted in reduced half-life and bioavailability with increased clearance of
meperidine in healthy subjects, however, blood concentrations of normeperidine were increased.
Ritonavir: Plasma concentrations of the active metabolite normeperidine may be increased by
ritonavir, thus concomitant administration should be avoided.
Also: Opioid analgesics, including DEMEROL, may enhance the neuromuscular blocking
action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
[Link]

3. Speaking of that: what NDML does this same thing and why?

Large doses of pancuronium may cause hypertension and tachycardia. Pancuronium can induce
tachycardia due to its vagolytics and sympathomimetic actions.
[Link] [Link]
[Link]/content/79/3/[Link]
4. If I am allergic to the flu shot, what induction agent should I not be getting and why?

You should not receive Propofol. Both the flu vaccine and Propofol have egg products in their
preparations. If one is allergic to the flu shot, it may be the egg products in the preparation.
Therefore one should not receive other medications also containing egg products, i.e. Propofol.
[Link] [Link]
allergy/AN02033/

5. If I have an allergy to shellfish what does this mean for prep soln?

This means I should not have any prep soln that contains iodine.

6. If I have sulfa allergy can I get Celebrex and why or why not? What other drugs should I
avoid?

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Celecoxib (Celebrex) contains a SO2NH2 compound. However, it is not identical to the structure
of sulfonamide antimicrobials so it has been suggested that it is not expected to produce allergy
symptoms as frequently. However sulfonamide allergic patients are at a greater risk for allergy
than the normal population and that for safety purposes, they should avoid celecoxib.
Other drugs to avoid: Sulfonamides (common generic sulfonamides include sulfacetamide,
sulfadiazine and sulfasalazine). Diuretics - the loop diuretics (furosemide and bumetanide).
Also, acetazolamide and methazolamide (carbonic anhydrase inhibitor class). Sulfonylureas
(common trade name sulfonylureas as Glucotrol, Amaryl, Glynase, DiaBeta and GlipiZIDE XL).
[Link]
Give me 10 foods that have cross reactivity to our anesthesia drugs....think hard... 10....you can
do it... good luck-- references of where
1. Eggs – propofol ([Link]
[Link])
2. Fish – protamine ([Link]
[Link])
3. Corn – corn based dextrose solutions
([Link] 4.
PABA – local anesthetics
([Link]
5. Chemical additives in foods (metabisulfites, preservatives) - muscle relaxants.
6. Bananas – latex
7. Avocado – latex
8. Chestnut – latex
9. Pineapple – latex
10. Cherries – latex

7. Explain Xenon....MOA, receptor cite, action... give reference

Xenon - The anesthetic potency of Xe has been ascribed to its blocking capacity of N-methyl-D-
aspartate receptor channels. Other targets have also been identified which might add to the
anesthetic potency of Xe. These include two-pore K+ channels, nicotinic acetylcholine receptors,
as well as receptors for serotonin, glycine and GABA.
([Link]
8. Explain Methadone...give reference

Methadone is an opioid pain reliever, similar to morphine. It also reduces withdrawal symptoms
in people addicted to heroin or other narcotic drugs without causing the "high" associated with
the drug addiction. Methadone is also used as a pain reliever and as part of drug addiction
detoxification and maintenance programs. ([Link]
9. Define: Pain... define acute and chronic, nociceptive and neuropathic. Give reference.

688
Pain: Unpleasant sensory and emotional experiences associated with actual or potential tissue
damage.
([Link]

Acute pain: Acute pain begins suddenly and is usually sharp in quality. It serves as a warning of
disease or a threat to the body.
([Link]
Chronic pain: Chronic pain persists despite the fact that the injury has healed. Pain signals
remain active in the nervous system for weeks, months, or years.
([Link]

Nociceptive pain - pain that arises from actual or threatened damage to non-neural tissue and is
due to the activation of nociceptors. ([Link]
Neuropathic pain - Pain caused by a lesion or disease of the somatosensory nervous system.
([Link]

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Allergies and anesthesia:

1) Ask about food allergies: Eggs, Soy, Bananas, Avocados, Hazelnuts or Chestnuts. Eggs
and soy for propofol. However, have you seen Fresenius propofol? Comes over from
Europe and has peanut oil as part of the emulsion.
2) The others foods listed are implicated in latex allergy.
3) Allergy to local anesthetics. Allergy to ester local anesthetics due to Para-aminobenzoic
acid (aka PABA). Can also be seen in amide local anesthetics with the preservative
methylparaben (a congener of PABA).
4) Previous exposure to protamine or a diabetic patient on NPH.
5) Antibiotics – anaphylaxis
6) More commonly however – anaphylaxis to NDNMBs.
7) Sulfa allergy – Lasix contains a sulfonamide compound.
8) Morphine and Atracurium cause histamine release from mast cells.

NMDA receptor and pain

1) NMDA is a receptor for the excitatory neurotransmitter glutamate, which is released with
noxious peripheral stimuli. The activation of NMDA receptors has been associated with
hyperalgesia, neuropathic pain, and reduced functionality of opioid receptors.
Hyperalgesia and neuropathic pain are a result of increased spinal neuron sensitization,
leading to a heightened level of pain. The reduced function of opioid receptors is caused
by a decrease in the opioid receptor’s sensitivity. This decreased sensitivity, in turn,
translates to opioid tolerance as patients will require higher doses of opioids to achieve
the same therapeutic effects. Therefore, NMDA antagonists may have a role in these
areas of pain management.
2) Drugs that antagonize the NMDA receptor
a. Amantadine –used to treat tremor in Parkinson’s disease
b. Dextromethorphan – a common antitussive (also inhibits reuptake of serotonin)
c. Nitrous oxide – anesthetic gas with amnestic and pain inhibitory properties.
d. Phencyclidine (PCP) – used as an anesthetic in the 1950’s, now a drug of abuse.
e. Ketamine – a noncompetitive NMDA antagonist – dissociative anesthetic
f. Xenon – would be a great anesthetic gas, difficult to obtain.
g. Magnesium – The NMDA type of ionotropic glutamate receptors plays a unique
role in synaptic functions because of high permeability for calcium and because of
a voltage-dependent block by endogenous Mg.
h. Ethanol - The ability of ethanol to inhibit responses to NMDA is dependent on the
subunit combination of NMDA receptors.

690
 Nontraditional ways to deal with PONV

The mechanisms of emesis can be divided into three components:

1. Afferent inputs go to the central nervous system (CNS), relaying the signals of emetic
stimuli;
2. These signals are received, recognized, and centrally processed. They then form
integrated emetic efferent signals coming from the CNS;
3. These motor and chemical efferent pathways relay signals that lead to the coordinated
respiratory, gastrointestinal and abdominal muscle expulsive actions of vomiting.

Central nervous system control

There are two medullary centers of vomiting in the brain known as the sensory "chemoreceptor
trigger zone (CTZ)" and the integrative center.

Chemoreceptor trigger zone (CTZ)

The CTZ is located in the medulla of the brain. It has a defensive blood-brain barrier for
detecting circulating toxins in the blood and cerebrospinal fluid (CSF), and is sensitive to a
number of circulating emetic agents, including morphine, intravenous copper sulphate, and
certain circulating metabolic emetic agents associated with uraemia, infections and radiation.
When activated, the CTZ does not initiate vomiting itself, but relays stimuli to the integrative
vomiting center which produces the actual act of emesis.

Integrative vomiting center

The integrative vomiting center coordinates activities of the nearby neural structures to produce a
complex patterned response, resulting in the processing and action of the vomiting reflex. The
center is located in the medulla. The motor component of the vomiting center is controlled by
both somatic and autonomic systems, meaning that both voluntary and involuntary systems are
involved in the process. Their inputs are coordinated by the vomiting center.

Somatic efferent pathways control respiratory and abdominal musculature, and visceral efferent
components mediating changes in gastric tone and motility, while salivation, pallor and sweating
are autonomic epiphenomena. The autonomic nervous system is not essential for the mechanical
act of vomiting, but the activation of efferent nerves of the abdominal organs in the emetic
process is proportional to the duration and intensity of the nausea that accompanies the process.

691
Afferent pathways

The vomiting center is predominantly activated by three different mechanisms:

1. By nervous impulses from the stomach, intestinal tract, and other portions of the body,
resulting in a reflexive activation;
2. By stimulation from the higher brain centers;
3. By the chemoreceptor trigger zone (CTZ) sending impulses.

Afferent impulses may also arise from other sites, such as unpleasant sights and odors, as well as
severe parietal pain. The most common afferent pathways are in the viscera, or abdominal
organs. Vomiting can be provoked by occlusion of the coronary vessels, distension of the
intestine, and irritation of the gastrointestinal mucosa. In the gastrointestinal tract,
mechanoreceptors in the intestinal wall are activated by abnormal contractions, distension or
physical damage. Potentially harmful chemical stimuli can also activate chemoreceptors located
in the intestinal wall. These receptors then release information to the vomiting center.

Efferent pathways

The neural pathways involved in the motor act of vomiting are associated mainly with the
phrenic nerve to the diaphragm, the spinal nerves to the abdominal and intercostal muscles,
efferent visceral autonomic fibers to the gut, and the viscera efferent fibers to parts of the
voluntary muscles of the pharynx and larynx. The vomiting reflex is mediated by both the
autonomic and somatic systems, and consists of two phases:

1. Prodromal phase (pre-ejection): Relaxation of gastric muscles followed by small

intestinal retrograde peristalsis;
2. Ejection phase: Comprises of retching and vomiting including expulsion of gastric
contents.

Stimuli for vomiting

Pain, sight, smell, taste, emotion

The experience of these sensations leads to information sent to the higher centers in the brain,
and then information relayed to the vomiting center and CTZ via chemicals that transmit
information to the brain, hence the name 'neurotransmitters'. The one that is most commonly
responsible is acetylcholine, or Ach. Neurotransmitters stimulate and activate the vomiting reflex
through the afferent pathways previously described.

692
Motion sickness

Motion sickness is due to labyrinth stimulation. The labyrinth is a part of the inner ear involved
in balance and perception of movement. Labyrinth stimulation leads to impulses passing along
the vestibular nerve to the central nervous system, where it activates the CTZ to produce emesis.
Neurotransmitters such as histamine or Ach are also released to the CTZ, which itself can
releases chemicals such as dopamine and serotonin (5HT) that go on to stimulate the vomiting
center, which releases Ach, which then leads to the feelings of nausea and actions of vomiting.

Opioid medications

Opioids such as codeine, morphine, pethidine, fentanyl, methadone, oxycodone, and tramadol
can cause nausea and vomiting through a number of different possible mechanisms such as
stimulation of CTZ, increased vestibular sensitivity, gastric stasis, or impaired intestinal motility
and constipation.

1) smell an alcohol pad

2) 20 mg propofol bolus as rescue
3) Haldol – cousin drug of Droperidol
4) Marinol – THC based antiemetic drug
5) Ativan or other benzodiazepine
6) Hydration
7) Acupressure
8) Hypnosis

693
 Stats: Chi-Square

Definition: A statistical test used to assess differences in proportions; symbolized as 

Chi-square () test is used to test hypotheses about the proportion of cases that fall into
different categories, as when a contingency table has been created. The chi-squared statistic is
computed by comparing observed frequencies and expected frequencies. The chi-squared test
assists in deciding whether a difference in proportions of this magnitude are likely to reflect a
real treatment effect or only chance fluctuations.

Expected frequencies are the cell frequencies that would be found if there were no relationship
between the two variables. The chi-square statistic is then computed by summarizing differences
between observed and expected frequencies for each cell. For chi-square tests, df equals the
number of rows minus 1 times the number of columns minus 1.

Example: Nurse Anesthetists implement a new instructional strategy with 100 randomly
assigned experimental patients, whereas 100 control group patients are cared for using usual
instruction.

Patient Compliance Experimental Control Total

Compliant 60 40 100

Noncompliant 40 60 100

Total 100 100 200

The observed frequencies displayed in the table identify 60 experimental subjects (60%), but
only 40 controls (40%), reported self-medication compliance after intervention. The expected
frequencies in the example are if there were no relationship between the two groups, the
expected frequency would be 50 subjects per cell because, overall, exactly half the subjects
complied. The chi-square statistic can then be computed by summarizing differences between
observed and expected frequencies for each cell. In the example,  = 8.00. For chi-square tests,
df equals the number of rows minus 1 times the number of columns minus 1. In the example
case, df = 1 x 1 = 1. With 1 df, the tabled value from a theoretical chi-square distribution that
must be exceeded to establish significance at the .05 level is 3.84. The obtained value of 8.00 is
substantially larger than would be expected by chance (the actual p = .005). It can be concluded
that a significantly larger proportion of experimental patients than control patients are compliant.
Reference
Polit, D. F., & Beck, C. T. (2008). Nursing research: Generating and assessing evidence for
Nursing practice (8th ed., pp. 600, 749). Philadelphia, PA: Lippincott Williams &
Wilkins.
694
 Pearson product-moment correlation coefficient
Pearson product-moment coefficient of correlation is the most common measure of
correlation used in statistics. The correlation coefficient quantifies the strength of the
relationship as well as the direction of the relationship between variables. This statistic is used
when there are two continuous variables that are suspected to have a linear relationship and have
normal distributions on ratio or interval scales. The symbol r is used for sample data and p (rho)
for population data.
Product-moment is based on covariance, which is a measure of how much two random
variables change together. If the greater values of one variable mainly correspond with the
greater values of the other variable, then the same holds true for the smaller values. There is a
proportional consistency in two sets of scores; a large X is associated with a large Y, and a small
X with a small Y. A strong positive correlation exists if an X score is above the mean X and is
associated with a Y score above the mean Y. A strong negative correlation exists if a low X
score that is below mean X is associated with a high Y score that is above mean Y. A moment
calculation is determined from the standard deviation of each score from its mean. The moments
for X and Y scores should be related. The degree of consistency within the distributions is
determined by the product of the moments for X and Y.
A product-moment correlation coefficient (p) of > 0 indicates a positive relationship,
coefficient < 0 indicates a negative relationship, and coefficient = 0 indicates nonexistence of
any relationship. The p values will range from -1.0 to 1.0. Coefficient values closer to -1 or 1
indicate a strong linear relationship between the two variables. The relationship between the
variables gets weaker the closer the coefficient is to 0. When interpreting Pearson product-
moment correlation coefficients, it is important to consider that p is a measure of linear
relationship. A small p value is often interpreted as nonexistence of any relationship, when
actually it only indicates a nonexistent or weak linear relationship. Under such circumstances, it
is possible that a non-linear relationship exists between the variables.

695
 Research/Statistics: Thesis Planning:

Week One: Research and Statistics

 5 steps to choosing a research topic

1. Identify a topic of interest: what you enjoy reading about, weaknesses, who do
you want to work with
2. Find a “Research Problem”: something we want to know and/or improve. Does
it pass the “who cares” test
3. State the research problem: focus inquiry, identify a single goal, use clear
language, develop complete sentence in question format using as few words as
possible to convey meaning
4. Develop Hypothesis: answer to the question. Null Hypothesis= negative language
(ex. No relationship between, is not caused by, does not result in, is not different
than. Etc.)
5. Feasibility of hypothesis: scope of project, sample size, cost, time to complete,
level of difficulty, experimental design (pro vs. retrospective)
 Types of research, research questions and corresponding research methods
o Quantitative- Measurement of the quantity of something
 Positivists would use this type of research. OBJECTIVE reality, get
standardized results and researcher remains objective and separate from
experiment (ex: double blind study).
 Methods are DEDUCIVE. Looks for cause and effect and has static
design which means categories are isolated before the research begins.
Can be generalized to larger populations.
 Uses formal language (agreed upon language) based on set definitions and
written in 3rd person.
o Qualitative- description of something depending on researcher. Hypothesis is
created (not pre-determined)
 Assumes reality is SUBJECTIVE but observable
 Researcher takes part in the experiment through direct interaction and
experience (acknowledges that they can influence behavior and
outcomes) by being a complete participant, participant as observer,
observer as participant, or complete observer (two way mirror in
room.) Methods are INDUCIVE.
 Looks for inter-relationships, has dynamic design and evolves
throughout research. Cannot be generalized to larger population.
Formal 3rd person language or personal voice
o Triangulation- uses both qualitative and quantitative to answer a research
questions.
 Quantitative methods show something exists with certain frequency
 Qualitative methods attempt to explain why
 Computerized database search engines to perform a thorough literature search include
PubMed and Psych INFO etc.

696
Week Two: Research Design and Planning

 Methods of scientific discovery

o Universality- research project could be done by anyone (and would “anyone”
find the same results)
o Reproducibility- you could repeat the experiment again and again and get the
same results. Measured by the amount of variability in results when it is repeated
and the amount of agreement in results between two or more examiners
o Control- the environmental conditions are controlled to isolate the variable being
tested
o Measurement- data should be susceptible to measurement i.e. quantifiable
(numbers) NOT subjective
 Take a research question and design research methods to test that question.
o Identify study population or sample- who’s to be included/excluded? How
representative of the population is your sample?
o Choose data collection instruments ex. Interview, survey (shouldn’t contain name,
SS# etc), observation
o Data collection procedures- sample: random vs. non-randomized
o Analysis/interpretation procedures- input information into a computer program
 Research Proposal * Difference between research proposal and a study is in an active
study you get results.*
o Has this study already been done and if so what where their findings. Can you
make a case of why this study should be performed
o Name of principal investigator (faculty advisor),Name of other investigators
(students, MDs, RNs), Affiliation with other organizations
o Title of project, research questions, formal hypothesis, significance of information
gained, is it worth the time (does it need to be finished in a certain time frame),
money and is it necessary, is there risk to human subjects, benefits, methods to
minimize risks, adherence to HIPPA guidelines
o Methods: survey, sample population (consider external validity), sample size,
instruments, what will be the independent/independent variables, what is the
proposed statistical analysis, budget and timeline
 Define and identify prospective and retrospective research designs and the
benefits/drawbacks of each
o Prospective research:
 Variables are measured through direct recording in the present and the
researcher follows subjects as they progress in their treatment or
evaluation. Researcher is able to identify factors that precede given
outcomes.
 Survey research is a type of prospective research and uses a tool to collect
objective and subjective data from people. Relies on the voluntary
participation of those people. MOST COMMON method and is easy to get
information.

697
  Designing a survey:
 Language must be clear, should be short and simple (boxes rather
than blanks, yes/no)
 Examine assumptions of each questions and do a pre-test survey on
small sample population
 Identify specific research objective and don’t ask unnecessary
questions
 Survey should look inviting and professional and identify a reason
why they might benefit from participating. Include envelope and
postage.
 Follow up survey- consider ways to contact non-respondent
Benefits:
 Not complicated- can be carried out by beginning researchers
 Less risk- IRB usually approves, not dangerous
 Drawbacks:
 Have to rely on subjective opinions of others and may not be
quantitative in nature. EX: They may not read the question and just
fill out “agree” to everything
 Rely on voluntary participation. Return rates go down as sample
size increases and may be selecting a non-random sample
 Sample may not be large enough and/or the cost of survey may
limit the size of administration, then may have low response rate.
 Need a good research tool. Good surveys are difficult to develop
and validity. All questions should measure what you are trying to
find out.
o Retrospective Research: deals with the meaning of events (primary historical
data) not just accumulation of data about the past but interpretation of those
events
 Designing retrospective study
 Develop research problems and hypothesis EX: Is there a
difference between people who had treatment a and a group that
had treatment B. How did the tx affect the condition in the patient
 Find a population that meets needs. From a clinician, medical
group, hospital, national/regional database. Examine the
population to determine demographics, illness, treatments, results.
All must start with the same condition but symptoms may change
 Is there a matched population that can be used for a control group?
Ex: Pts that came into the ER with cardiac arrest and were given
epi vs. those not given epi. (Screen population to find
inclusions/exclusions)

698
  Collect the data-recording from charts. Start with small sample and
attempt a mock analysis. Adjust collection method as needed and
then complete data collection.
 Analyze retrospective data- statistical analysis, examine
assumptions and limitations and then interpret
 Benefits:
 Events have already happened so data collection can be done by
many individuals to speed up process.
 Events have already happened so the time spent is much less= less
cost.
 There is less risk since events have already happened. The
researcher is not changing the course of treatment.
 The data is unbiased (you have no way to influence past
information)
 Drawbacks:
 Data may not be uniform (ex: charting information may vary RN
to RN) not following a research protocol and procedure may have
changed over time. Many unknowns. You were not there so you do
not know what variables may have influenced info
 Some data may be missing because info was not part of research
protocol at the time.
 Sample size may not be large enough especially if the sample size
is shrinking due to non-uniform or missing data (may consider a
larger hospital)

Week Three: The Review of Literature and Evidence based clinical practice

 What’s the importance of the literature review to the research process

o It’s a comprehensive overview of what is known about a topic thru articles to set
the stage for a research project and support an evidence based paper. You need to
get background into, find the knowledge gap and see if anyone has done similar
research and if it was done well, the sample size and population, and if it needs to
be repeated.
 Literature review:
 initial/preliminary- you just got the idea and look to see what’s been done
or patients in front of you and you need an answer (quick 5 min)
 Extensive/full- you’ve settled on an idea and are interested in what has
been performed or based on your experience (Ex: 5th pt you’ve seen with
same presentation) you want to find out why

699
  Beginning researcher- tends to focus on background info opposed to an
experienced researcher who relies on experience with patients, continuing
education, consultation with peers etc.
 Extensively researched topic (specific Science) or new technique
 Evaluating research
o Is the question clear and does the intro, problem question, and review of lit. Set
the background for the reader and consistent with the research question?
o Are key terms well defined and is the independent variable appropriate given the
question of the study? Are measurements of independent variable appropriate,
reliable and valid and is the dependent variable appropriate for the study?
o Are controls appropriate and will the outcome of the experiment be effected by
variables not controlled for
o Are methods clearly described? Do participants understand the study and are they
properly selected (no bias)
o Are the statistical tests appropriate and are assumptions reasonable? Are results
clear in tables/charts and is the discussion reasonable in view of the data.
o Do references match the citations in text and are all ethical standards upheld.
o What would you do to improve the research design? Has the lit. Review changed
your research proposal or the way you will TX a patient?
 How clinical questions are constructed- PICO
o Population: how would I describe a group of patients similar to mine? Persons
with COPD and dyspnea, patients age 77 and above, female vs. male etc.
o Intervention- which main intervention am I considering
o Comparison- what is the main alternative to compare with intervention- do
nothing, meds, surgery
o Outcome- what can I hope to accomplish? Increase pulmonary function, decrease
SOB. How will you measure results?
o Make a question out of information from PICO
 Sackett’s Classification Levels of Evidence
o I- strongest: systematic review of large randomized studies
o II- small randomized studies
o III- nonrandomized, concurrent cohort comparisons between subjects who did and
did not receive intervention
o IV- nonrandomized historical cohort comparisons between current subjects who
did receive intervention and former subjects who did not. Case controls
o V- Case series without controls/clinical expertise. Expert opinion- Not very
credible.
 Appraisal and summary recommendations
o Grade A: supported by at least one and preferably more than one Level I study
(strongly recommend tx)
o Grade B: supported by at least one Level II study
o Grade C: supported by Level III, IV or V studies

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Week Four: Research Ethics

 Institutional Review Board (IRB) - body established to protect the rights and welfare of
research participants and ensure ethical guidelines are in place for the conduct of research
involving humans. They review each research proposal, approve any modifications, and
continue to oversee the research. Consists of 5 members with expertise, diversity,
sensitivity to community attitudes. Study is approved for a max of one year and is only
completed when data collection and analysis are complete (no more contact with
subjects.)
 IRB Committee at RFUMS specific policies and procedures directed at the conduct of
research involving human participants
o Belmont report is what RFUMS follows and is agreed upon guide for human
research standards. Includes respect for persons (privacy, autonomy, consent),
beneficence, justice (vulnerable participants not targeted)
o When RFUMS wants to participate in human participant research an agreement
between the school and department of health and human services must be signed
called a Federal Wide Assurance. This requires that all research activities follow
ethical principles of Belmont report and legal requirements of government.
 Historic legal and ethical foundations for the guidelines of the IRB
 Nuremberg Code- first code to prevent exploitation and harm of human subjects
through: informed consent, stating the subject may withdraw at any time, benefits out
way risks, research is based on prior animal studies, researchers are qualified, study
designs avoid unnecessary harm, and the investigator must be able to withdraw a
participant at any time. First internationally recognized code of research ethics after trial
of Nazi physician’s sterilization experiments of prisoners.
 Thalidomide tragedy- woman in the US were given thalidomide (sedative) during
pregnancy which caused teratogenic effects leading to new legislation by Sen Hubert
Humphrey and the FDA which required special informed consent before giving a pt any
experimental drug
 Declaration of Helsinki-1964- first set of ethical guidelines written by researchers and
physicians
Week Five: Principles of Measurement, Reliability and Validity

 Scales of Measurement
o I- Nominal: only represent category label (yes/no, favorite color, blood type)
o II- ordinal: only indicates rand order, MAY have unequal intervals (ex: shirts
S,M,L, pain scale, strength)
o III- interval: equal intervals between variable but not related to any true zero- not
representing absolute quantity (age, IQ, temp, calendar years)
o IV-ratio: continuous variables measured from a true zero (Kelvin temp, decimals,
weight) * MOST complex

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  Ways to collect data- measuring, surveys, observation, conversation, experience
 Validity types:
o Face/context- is test measuring what it’s intended to measure, is sample adequate
to measure trait, and is the right research tool and construct being used
o Criterion- is there a reliable control group or normal range
o Construct- value/concept that cannot be directly measured. Results should
converge or point to same thing. Errors multiply in constructs.
o Internal- freedom from bias in forming conclusions from data. Does researcher
influence outcome? Use double-blind design or third party measures
o External- can conclusions drawn from sample be generalized to other samples?
Take large, random samples representative of larger populations
Week Six: Graphs, Tables, Distributions

 Types of distribution
o Frequency distribution: showing what you have. A way to illustrate how many of
each thing. List category then frequency (ex: people and shoe size, Number of
siblings)
o Normal distribution aka bell-shaped curve: illustration of the expectation of what
most types of data will look like-most data points are in the middle.
o Positively skewed distribution- not all data are created equal. Many data points
are near the origin of graph (towards positive side)
o Negatively skewed distribution- many data points are away from origin of graph
(toward negative end)
o Bimodal distribution: two areas under the curve with many data points. Two
modes.
o Nonnormal:
 platykurtic- flat like a plate
 Leptokurtic- up and down with high point- scores not as widely
distributed. Scores are closer to mean
 Bimodal- lumpy
o Cumulative distribution: shows how many cases (data points) have been
accounted for out of the total number of cases (data points.) Can be illustrated
with percentages and quartiles as well.

 When grouping data-

 Choose data with interval widths to 5 to 10 intervals. Interval widths must
be same and not overlap.
 Choose meaningful intervals that are easy to understand at a glance.
 Data displayed using frequency table with data points, table with intervals
or graph of data with intervals
 Measures of central tendency measures how a set of numbers is centered around a
particular point on a line scale. Includes mean (arithmetic average of a set of numbers),
median (value that divides the set of numbers in half. Half are above, half are below,)
mode (most frequently occurring number) will be bimodal if there are two values that
occur as a mode. Range (difference between highest and lowest numbers)
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 o Which measure to use depends on shape of graph?
o Positively skewed- use median=middle score
o Negatively skewed- use median
 Klinkers- something is wrong either broken equipment, language problem but the scores
do not legitimately represent anything. DON’T use the value
 Outliers- fluke. A way out there score but nothing is broke. May use it or take it out
depending on what your data is suggesting with it in vs. out.
 Standard deviation- approximate average amount that each number in a set of numbers
differs from the mean. The bigger the SD the more variability in data. Normal
distribution is 3 standard deviation above/below mean.
o 68% of all numbers in a set will fall within ONE SD (-1 to +1)
o 95% of all numbers in a set will fall within TWO SD (-2 to +2)
o 98% of all numbers in a set will fall within THREE SD (-3 to +3)
 Variance is the average of the square of the distances (deviations) of a set of numbers
from their mean.
 Standard score is a number in a set of scores where the mean and SD o that set are
already known through testing numerous participants and then doing the calculations. It
is an easy way to summarize what we know and see how an individual score compares to
the set of scores against which it is compared. EX: what does a test score of 98 mean?
Intelligent tests, MMPI
 Z score is a score that comes from a set of scores called the z distribution. This is a type
of normal distribution. EX: Mean is 0 has normal SDs. When statistician’s covert raw
scores to any other type standard score, they first convert the scores to a Z score (SD
units).
Definitions

 Deduction: start with theory then use verification

 Induction: start with observations and put them together to form a theory
 Empiricism/Verification: set out to prove/disprove something. Not quantification but
verification through observation or experience. Observation may be quantitative or
qualitative and both use logic and empiricism as the foundation.
 Epistemology: how do we know what we know? Three theories: Positivism,
Constructivism and Post-Positivism (Compromise)
o Positivism: reality is OBJECTIVE and singular, separate from observer (un-
biased) and value-free EX: Theory of gravity. It’s easy to measure, verify and
prove. “Mechanically minded.”
o Constructivism: No fixed reality, everything is SUBJECTIVE, “things are what
we make them.” EX: Heisenberg’s Uncertainty Principle- atoms always in motion
so nothing can be measured precisely

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 o Post-Positivism (Compromise): reality is singular but viewed through subjective
eyes. The observer may interact and change that which is being observed. We can
only approximate an objective reality.
 Dependent variable- depends on who it is coming from; changes. Variable being
measured. EX: B/P difference with medication
 Independent variable- does not change. EX: males vs. females, group A vs. group B
 Research- conducting an experiment to get results/conclusion
 Principle investigator- thinks up and carries out research
 Research participant- team member. Can do primary research or clinical trials
 Consumer of research- looks up information to makes clinical decision
 Primary source- statement of an idea as given in the author’s original work
 Secondary source- source is a statement of an idea as interpreted by another party
 Evidence Based Practice- integration of the best available evidence from clinical
experience, literature, and patient preferences in the process of clinical decision making
for practice.
 Randomized controlled trial- 2 groups with no bias. Control all variables other than
manipulated component
 Controlled clinical trial- can’t always control EX: B/P study- can’t control peoples salt
intake
 Cohort study- volunteers are together in another study and pull out certain data
 Human participant- living individual about whom an investigator obtains data through
intervention or interaction or obtains identifiable private information.
 Exempt research: non containing research (ex: recycling), survey, interviews of public
officials, publically available data
 Minimal risk: may undergo expedited review by IRB and means the probability and
magnitude of harm/discomfort in research are not greater in and of themselves than those
ordinarily encountered in daily life or routine physical
 Continuous variable- can take on any value in a continuum
 Discrete variable- can only be in whole units (HR, number of children)
 Dichotomous variable- can only take on two values (male/female , yes/no)
 Direct measurement- height, ROM
 Indirect measurement- temperature, EKG
 Sensitivity- likelihood that a test will indicate positive when person really is positive for
test/disease
o If low sensitivity- false negatives-lets some positives slip by
 Specificity- ability of the test to be correct about the subjects it identifies as positive
o High specificity- all positives are the same
o Low specificity- some variation among positives false positives)
 Accuracy- amount of time the test is correct. Is a combination of sensitivity and
specificity? Concerned with number of false positives and false negatives
 Precision- how much detail can the test discriminate judged by how small of units the
sample can be measured by. The smaller the units the more precise the tool.
 Validity- ability of a test to measure what is was intended to measure

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Graphs, Tables, Distributions

 Types of distribution
o Frequency distribution: showing what you have. A way to illustrate how many of
each thing. List category then frequency (ex: people and shoe size, Number of
siblings)
o Normal distribution aka bell-shaped curve: illustration of the expectation of what
most types of data will look like-most data points are in the middle.
o Positively skewed distribution- not all data are created equal. Many data points
are near the origin of graph (towards positive side)
o Negatively skewed distribution- many data points are away from origin of graph
(toward negative end)
o Bimodal distribution: two areas under the curve with many data points. Two
modes.
o Nonnormal:
 platykurtic- flat like a plate
 Leptokurtic- up and down with high point- scores not as widely
distributed. Scores are closer to mean
 Bimodal- lumpy
o Cumulative distribution: shows how many cases (data points) have been
accounted for out of the total number of cases (data points.) Can be illustrated
with percentages and quartiles as well.
 When grouping data-
 Choose data with interval widths to 5 to 10 intervals. Interval widths must
be same and not overlap.
 Choose meaningful intervals that are easy to understand at a glance.
 Data displayed using frequency table with data points, table with intervals
or graph of data with intervals
 Measures of central tendency measures how a set of numbers is centered around a
particular point on a line scale. Includes mean (arithmetic average of a set of numbers),
median (value that divides the set of numbers in half. Half are above, half are below,)
mode (most frequently occurring number) will be bimodal if there are two values that
occur as a mode. Range (difference between highest and lowest numbers)
o Which measure to use depends on shape of graph?
o Positively skewed- use median=middle score
o Negatively skewed- use median
 Klinkers- something is wrong either broken equipment, language problem but the scores
do not legitimately represent anything. DON’T use the value
 Outliers- fluke. A way out there score but nothing is broke. May use it or take it out
depending on what your data is suggesting with it in vs. out.
 Standard deviation- approximate average amount that each number in a set of numbers
differs from the mean. The bigger the SD the more variability in data. Normal
distribution is 3 standard deviation above/below mean.

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 o 68% of all numbers in a set will fall within ONE SD (-1 to +1)
o 95% of all numbers in a set will fall within TWO SD (-2 to +2)
o 98% of all numbers in a set will fall within THREE SD (-3 to +3)
 Variance is the average of the square of the distances (deviations) of a set of numbers
from their mean.
 Standard score is a number in a set of scores where the mean and SD o that set are
already known through testing numerous participants and then doing the calculations. It
is an easy way to summarize what we know and see how an individual score compares to
the set of scores against which it is compared. EX: what does a test score of 98 mean?
Intelligent tests, MMPI
 Z score is a score that comes from a set of scores called the z distribution. This is a type
of normal distribution. EX: Mean is 0 has normal SDs. When statistician’s covert raw
scores to any other type standard score, they first convert the scores to a Z score (SD
units).
Inferential Statistics: make conclusions about populations from samples of those populations.
Then make predictions about what might or might not happen, test it and interpret the results
Examining the World: test whether or not two variables are related to one another or if two or
more groups are treated differently respond differently to treatment.
o Correlation: how strongly two things are related to each other. DOES NOT tell
us if there is cause-effect relationship between variables
o Advantages of correlations: cheap, easy, and give clues at might we might want to
look at to determine cause and effect
 Finding cause and effect: experimental design- a) 2 or more different
conditions ([Link]) b) way to measure outcome c) predictions
(hypotheses)
Hypothesis testing: educated guess. Are the groups different as a result of the condition or
chance?
o Null hypothesis: use the mean scores of groups
 NO statistical significance between groups.
 There is NO relationship between the ind. Variable and dep. Variable.
 Group A and Group B have the same result
o Alternative hypothesis:
 There IS a statistical significance between groups
 There IS a relationship between the ind. Variable and the dep. Variable
 Group A and Group B DO NOT have the same result

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 o Retain or reject null hypothesis at end of experiment.
 If retain (or fail to reject) the null hypothesis, this means there are not
differences between the groups other than what would be expected by
chance
 If reject the null hypothesis, which means the groups are different, there’s
a greater than what would be expected by chance
 What is a difference that is greater than what would be expected by
chance? Need Z-scores. Use 5% or .05 as criterion.
 Type 1 error- too liberal- nothing happens but you report it does- tx is not
effective
 Type 2 error- say nothing is happening but it is- may lead to no further
study of possible effective drug
Independent T-test: determines if there is a statistically significant difference between the mean
scores of the dependent variable (what is being measured) of 2 independent groups (Independent
variable: experimental vs. control.) The greater the difference, the more different the two groups
are on the measured variable.
o How is T test used?
o Assumptions: 1) independent groups mean participants are different between
groups. 2) scores of the dependent measure are normally distributed 3) how the
scores vary from the mean will be equal within groups (more important with
small groups)
o Significance of testing: means criteria are met. Non-significant findings mean
criteria are not met. Insignificant means there’s no statistical meaning.
o Power of a test: ability of a statistical test to detect a real difference between the
mean scores of two groups. If you do not have enough statistical power, you
might get a Type II error.
 Number of participants- too few, difficult to detect difference. Too many,
detect differences resulting from chance
 Participants- make the groups as alike as possible (can be expensive,
difficult, time-consuming and results are not as generalizable.)
 Power analysis- statistical analysis that gives you an idea of how many
participants you would need to detect a group difference.
o Effect size: how much of an influence the independent variable is on the
dependent variable. Just because you reject the null hypothesis doesn’t mean
something isn’t going on. Is there anything else worth considering?
o Confidence intervals: used to estimate the amount of error in our data. EX: mean
of a sample will generally not match the population’s mean precisely.
 Value of parameter around which the confidence interval will be built
(mean, correlation coefficient etc.)
 Standard error of measure
 Desired width of confidence interval (Ex: 95% or 99%)

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Dependent T-test: examines the difference between two groups of data (scores, measurement
etc) from an experimental design where the participants in each group ARE RELATED in some
way
o Advantages
 Variability of participants is lower if the same participant is measured
before and after
 Lower variability means more powerful test

o Disadvantages
 Lower degrees of freedom- more difficult critical value to obtain
o Equation
o Assumptions: 1) no assumption of independent groups 2) scores of dependent
measure are normally distributed 3) how the scores vary from the mean will be
equal within the groups
o Designs
 Pre/Post treatment design: same participant is measures before/after
treatment
 + indication of how pt responded to tx and reduces the variability between
pre/post test scores compared to independent groups receiving placebo or
tx
 - may be a regression to the mean effect
 Matched pair design: different participants in each group but each
participant in Group A has a match in Group B (ex: twins)
 + do not have regression to mean effect and two different treatments can
be tested
 - can be expensive, matched variables must be influential and cannot
control for internal attributes of participants
 Order of presentation design: same participants tested before and after
exposure. One group gets exposed to Part A then B and the other group is
opposite
 + good for multiple part tx to see if order of presentation matters
 - participants may get bored or tired
ANOVA: comparing more than two groups without increasing possibility of committing a type I
error by just repeating t tests between groups. (Alternative is the Bonferroni solution that keeps
the overall a=0.05 by dividing it by the number of statistical tests performed)
o F statistic: when the null hypothesis is TRUE (there is at least one group that is
significantly different form at least one other mean.) F= between group variance +
within group variance/ within group variance. Compare with table of critical
values. Need to do additional test to know which mean is different from the
others.

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 o ANOVA design: completely randomized (chosen form population of
participants) with one independent variable and two or more levels or conditions
randomly assigned. Each participant can only belong to one group. Causation can
be implied between independent and dependent variable.
o Assumptions: 1) values for dependent variable are normally distributed 2)
variances about each groups means are not substantially different from each other
3) participants are randomly assigned to each group 4) scores in each group are
independent of each other
Correlation and regression: examines and quantifies the relationships between two variables.
When correlations are strong, we can guess something about the second variable by knowing the
first. Use numbers -1 to +1 to indicate strength. 0= no relationship (data points are randomly
distributed.)

 Interval and ratio data: use Pearson product-moment coefficient “R”

 Ordinal data uses Spearman rho “R”
 Scatter plots- useful for visualizing correlation. The strongest is when the data points fall
on straight line (r=+1 or -1). “r” only represents correlations where the relationship is
linear. The line of best fit on the scatter plot is the regression line.
o “r”= 0-0.25= little to no relationship
o “r”= 0.25-0.50= weak relationship
o “r”= 0.50-0.75= moderate relationship
o “r”= 0.75-1.0= strong relationship
 Pearson product-moment: ratio/interval data, R is calculated by measuring how often X
and Y are the same distance from their respective means.
 Spearman rank correlation coefficient aka Spearman rho: low ranks of X should
correlate with low ranks of Y
 Critical values of “r” are in a table and based on level of significance and degrees of
freedom
 P value for the r is calculated by the computer and tells you the probability that the
amount of correlation occurred by chance. If p<=0.05 there is statistical significance it is
not due to chance
 Regression: defines the relationship between X and Y, so that X can be used to predict Y.
o Y=a+bX (formula of a line)
o A= y-intercept (the value of y when X is 0)
o B= slope of the line (rate at which Y changes as X changes)
o When a=0, then the line hits 0,0 on the graph
o When b=0, then the line is horizontal
 Accuracy of prediction: coefficient of determination (r2) which is expressed as a
percentage of variance in Y that can be predicted by knowing X. EX: if the r for height
vs. weight is 0.87, then r2=0.76 which means that 76% of the variance in weight can be
predicted by height.

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  Nonlinear regression- described by the polynomial equation
o Y=a+bX-bX2
 Covariance= the additional variance in the dependent variable that is due to something
other than the independent variable. It is the effect of the outside factors that you are
UNABLE to control for. Come up with a new adjusted mean that may change the
significance.
o Analysis of covariance- most effective when r is greater than 0.60 and appropriate
is there is a linear relationship between the covariant and dependent variable
Comparing the Median: Nonparametric tests

 Types of nonparametric distributions

o Skewed negative or positive- tails are differently shaped and don’t have equal
AUC’s
o Rectangular distribution
o Distributions are nonparametric with pathologic conditions, small clinical samples
and with samples of convenience (may not have normal bell curve)
 Nonparametric Tests: ranking of data rather than using precise measurements. Low
power and may have too small of sample to be significant.
o Mann-Whitney U Test
 Independent groups
 Analogous to the independent t-test
 Does not require groups to be the same size (no bell curve)
 U is the measure of how often ranks in one group are lower than ranks in
the other group (uses a U table)
 U is converted to a standard z-score for each group, then a two-tailed p
value s given and compared with a pre-selected critical level for p (ex:
p=0.05)
 EX: comparing two schools- one large and one small
o Wilcoxon Signed Ranks Test
 Paired groups
 Analogous to the paired t-test
 Groups can be unequal and assumes variance is unequal
 Data is put in order and given signed ranks comparing them to the group
median
 T statistic is calculated, which measures the number of paired ranks above
and below the median
 T is converted to a standard z score and the p value is then calculated and
compared to the pre-selected critical value of p
* Tests are not appropriate for nominal data (which frequency would be used for)

710
 o Chi Squared
o Used for frequencies (individual counts, not ranks or percentages)
o All data gets assigned to a category and no data is in more than one
category
o Need to know the observed frequency and expected frequency (from
control sample)
o If observed=expected then the chi squared value is 0. If the
observed>expected, chi squared value increases
o On the computer X2 will be calculated into a p value rather than
comparing it to a critical value (ex: m/f picking their favorite color)
o Chi square is less reliable with very small samples. No more than 20% if
cells should contain expected frequencies of less than 5
 Yates correction- subtract 0.5 from each O-E calculation which
decreases the X2 making it more difficult to show statistical
difference
 Alternative to Yates correction is Fisher Exact Test-calculates the
exact probabilities given the observed frequencies.
 McNemar Test is the version of X2 used with paired data.

The t-test is a type of parametric test involving ratio or interval data. Interval and ratio data
are used with parametric tools in which distributions are predictable (normal distributions). The
t-test assesses whether the means of two groups are statistically different from each other. This
analysis is appropriate whenever comparisons of the means of two groups are required, and
especially appropriate as the analysis for the two group randomized experimental design.

There are two types of t-test, the independent-measures t-test and the matched t-test. In the
independent t-test there is a two group experimental design consisting of a control group (the
comparison group) and an experimental group (the group that receives the treatment). In the
two group experimental design, we are most interested in determining whether the two groups
are different after the program/treatment. Typically we measure the groups on one measure
(independent variable), and we compare the groups by testing for the differences between the
means using a t-test. The t-test gives an indication of the separateness of two sets of
measurements, and is thus used to check whether two sets of measures are essentially different
(and usually that an experimental effect has been demonstrated). The independent-measures t-
test (or independent t-test) is used when measures from the two samples being compared do not
come in matched pairs.

711
 In general the t-test gives an indication of how separate two sets of measurements are,
allowing you to determine whether something has changed and there are two distributions, or
whether there is effectively only one distribution. The matched-pair t-test (or paired t-test or
paired samples t-test or dependent t-test) is used when the data from the two groups can be
presented in pairs. Examples of a paired t-test include measurements before-and after
comparisons of the same people or when the group is given two different tests at different times
(egg. pleasantness of two different types of chocolate).

The formula for the t-test is a ratio: difference between the group means

Variability of the groups

The resulting ratio yields the t-value. Once the t-value is computed, the t-value is checked
within the t-test table to determine whether the t-value is large enough to be significant
(>p=0.05). If it is, you can conclude that the difference between the means for the two groups
is different.

712
 Wilcoxon test, p value
If the interval/ ratio level data do not meet the normality assumptions for a paired
samples t-test, the non-parametric alternative is the Wilcoxon signed rank test. The Wilcoxon
signed- rank test is a non-parametric statistical hypothesis test used when comparing two related
samples, matched samples, or repeated measurements on a single sample to assess whether their
population mean ranks differ. This test is the equivalent of the paired two group t-test.
Calculations involved in the Wilcoxon test involve converting the data to ranks, discarding any
variance or normality issues associated with the original values.
The Wilcoxon test can be used to analyze data from a number of different designs:
1. Repeated-measures designs with an intervention
2. Repeated- measures designs without an intervention
3. Matched –subjects with an intervention
4. Matched-subjects without an intervention
For example, a study dealing with job security and pay, concern with job security is ranked from
1- indicating no concern to 10- indicating ultimate concern and pay is defined as concern for pay
on a rating scale from 1-10, 1-indicating no concern and 10-indicating ultimate concern. The
Wilcoxon test will rank all non-zero difference scores disregarding sign, reattaching sign to the
rank, and then evaluating the mean of the positive and the mean of the negative ranks.
Certain assumptions must accepted for the Wilcoxon test
1. Each pair of observations must represent a random sample from a population and must be
independent of every other pair of observations
2. The z test yields relatively accurate results to the extent that sample size is large
3. The distribution of the difference scores is continuous and symmetrical in the population
Once data is entered into a statistical data analyzing program such as SPSS,
Descriptive statistics

N (sample Mean Std. deviation Minimum maximum

size)
Security 30 4.50 1.834 1 8
Pay 30 5.67 1.493 3 9
Ranks

N Mean Sum of ranks

rank
Pay-security negative 6 (pay<security) 12.25 73.50
ranks
Positive 20 (pay>security) 13.88 277.50
ranks
ties 4 (pay= security)
Total 30

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Test statistics

Pay security
Z -2.626
Asymp. Sig. (2-tailed) .009

These results would be reported like the following: “A Wilcoxon test was conducted to evaluate
whether employees showed greater concern for pay or security. The results indicated significant
different, z = -2.63, p <.01. The mean of the ranks in favor for pay was 13.88, while the mean of
the ranks in favor of security was 12.25. In other words, significant differential concerns for pay
were higher than job security.

References
Online:
[Link]
[Link]
Grove, S., Burns, N., & Gray, J. (2011). The practice of nursing research. (7th ed., p. 584). St.
Louis: Elsevier Saunders.

714
 Corneal Abrasion

The cornea is the clear, dome-shaped outer area of the eye. It lies in front of the colored part of
the eye (iris) and the black hole in the iris (pupil). The outermost layer of the eyeball consists of
the cornea and the white part of the eye (sclera). A corneal abrasion is basically a superficial cut
or scrape on the cornea. A corneal abrasion is not as serious as a corneal ulcer, which is
generally deeper and more severe than an abrasion

To diagnose a corneal abrasion, a topical anesthetic with a yellow dye called fluorescein is
placed into the eye. Under blue cobalt light, the part of the cornea abraded will be stained by the
dye and is easily seen by the examiner. The area and depth of the abrasion can be easily seen
under a special microscope called a slit lamp biomicroscope. If a microscope is not available,
then a blue light called a Burton lamp may be used

Topical Nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (Voltaren) and

ketorolac (Acular) are modestly useful in reducing pain from corneal abrasions

If antibiotics are used, ointment (e.g., bacitracin [AK-Tracin], erythromycin, gentamycin

[Garamycin]) is more lubricating than drops and is considered first-line treatment. In patients
who wear contact lenses, an antipseudomonal antibiotic (e.g., ciprofloxacin [Ciloxan],
gentamycin, ofloxacin [Ocuflox]) should be used, and contact lens use should be discontinued.
Clinical trial data are lacking, but it is recommended that contact lenses be avoided until the
abrasion is healed and the antibiotic course completed.

Proparacaine:

DO NOT USE TETRACAINE

715
 More Practice Scenarios and Questions?
Pt’s end tidal drops… now 19… Give me as many reasons you can think of why it would do
this…
Air leak in sample line
Leak in ETT cuff
Gas analyzer error
Low ETCO 2 with Hypocarbia (PaCO 2 < 35 mmHg)
Hyperventilation
• High minute ventilation in a mechanically ventilated patient
• Pain
• Anxiety
• Compensation for metabolic acidosis
Low ETCO2 with hypercarbia (PaCO2 >45 mmHg)
• Pulmonary thromboembolism
• Air embolus
• Fat embolus
• CO2 embolus (i.e. laparoscopic surgery)
• Amniotic fluid embolus
Obstruction
• Mechanical (kinking of tube)
• Bronchospasm
• COPD
Low cardiac output state
Esophageal intubation
Dead space ventilation
Hypothyroidism
Now their end tidal goes up… 60 to up and way… same questions, give me as many
reasons you can to as why…
Sodasorb exhausted
Sodasorb not in circuit
malignant hyperthermia
Hyperalimentation
Hyperthermia
Hyperthyroid
Hypoventilation
anesthetic getting to light
Acid load increases (i.e. tourniquet down)
IV NaHCO3 administration
CO2 insufflation

716
 Define Acute and Chronic Pain:

Chronic pain is pain that continues a month or more beyond the usual recovery period for
an injury or illness or that goes on for months or years due to a chronic condition. The
pain is usually not constant but can interfere with daily life at all levels.
[Link]
Pain that lasts beyond the term of an injury or painful stimulus. Can also refer to cancer
pain, pain from a chronic or degenerative disease, and pain from an unidentified cause.
[Link]
Acute Pain?

Pain that is usually temporary and results from something specific, such as a surgery, an injury,
or an infection. [Link]
Acute pain begins suddenly and is usually sharp in quality. It serves as a warning of
disease or a threat to the body.
[Link]
1. Pain pathways with graphs or visual material: Give me several and written paragraph on
each with 2 references;

[Link]

717
[Link]

[Link]

718
[Link]

719
First-order neurons conduct impulses from receptors of the skin and from proprioceptors
(receptors located in a join, muscle or tendon) where they synapse with second-order neurons in
the dorsal horn of the medulla and spinal cord.
Second Order Neurons - The spinal cords grey matter is divided into 10 Rexed laminae and is the
principal route of entry for primary afferents is through the dorsal root. C-fiber nociceptors
terminate mainly in lamina II (the substantia gelatinosa). Small myelinated Aδ nociceptors
terminate mainly in the superficial dorsal horn of lamina I (marginal layer) and in lamina V
(nucleus proprius). Nociceptors from joints terminate in lamina I as well as more deeply in
laminae VI and VII. Low-threshold mechanoreceptors, which transmit non-noxious information
regarding fine touch, proprioception, and vibration, terminate mainly in lamina III and IV.
Central Pain Pathways: The Spinothalamic Tract
Primary afferent nociceptors relay sensory conduction of stimuli to the dorsal horn, which
ascends various spinothalamic tracts and dorsal column of the spinal cord to terminate in the
thalamus. Along the way collaterals of the projection neurons activate multiple higher centers,
including the nucleus reticularis gigantocellularis (NGC), nucleus raphe magnus (NRM) and
periaqueductal grey (PAG) of the midbrain. Descending fibers from the PAG also project to the
NRM and adjacent reticular formations by way of the dorsolateral funiculus to terminate in the
dorsal horn of the spinal cord. Other sites such as the limbic system, amygdaloid and septal
nuclei receive projections from the spinal cord in addition to the previously mentioned structures.
Descending projections also arise from a number of brainstem sites, including the locus ceruleus.
These projections to the supraspinal third order sites are contained within the anterolateral
funiculus in the contralateral quadrant of the spinal cord, comprising various spinothalamic
tracts.
Ascending Tracts - Dorsal Column (Medial Lemniscus System) which includes the Gracile
Fasciculus that are related to proprioception of the lower limbs and trunk to the brain stem. The
Cuneate Fasciculus which transmits fine touch, fine pressure, vibration, and proprioception
information from spinal nerves located in dermatomes C1 through T6. The Spinocerebellar
Tracts which carry proprioceptive information from neuromuscular spindles of the ipsilateral
part of trunk and lower limb and also unconscious proprioceptive information. The Anterior
Spinocerebellar Tract which conveys proprioceptive information from the body to the
cerebellum. The Anterolateral System consists of the Lateral Spinothalamic Tract which carries
pain and temperature sensory information to the thalamus of the brain. It is composed primarily
of Aδ and C fibers. Finally, the Anterior Spinothalamic Tract which is primarily associated with
the conduction of soft nociceptive information to the reticular formation in the thalamus and
crude touch to the ventral posterolateral nucleus (VPL).
Third Order Neurons (Supraspinal Structures) consist of the Periaqueductal gray which activates
enkephalins releasing neurons and 5-HT is then released from the to the dorsal horn of the spinal
cord where it forms synergistic connections with the inhibitory interneurons located in Lamina
II. This then triggers the further release of either enkephalins or dynorphins which bind to mu
opioid receptors thus inhibiting the further release of substance P from first-order neurons.

720
The nociceptive signal is then inhibited before it was able to reach the cortical areas that interpret
the signal as "pain“. Also worth mentioning are the cortical structures which is the area of
perception and discrete localization of pain. Specifically, the primary somatosensory cortex
(Postcentral Gyrus) – site involved with processing of tactile and proprioceptive information and
the somatosensory association cortex – which assists with the integration and interpretation of
sensations relative to body position and orientation in space.
2. Define; BPS the behavior pain scale and VAS the visual analog scale and mean pain
intensity. Give references;
The BPS the behaviour pain scale is for patients unable to provide a self-report of pain: scored
0–10 based on clinical observation:

Face 0 1 2 Face score:

Face muscles Facial muscle Frequent to
relaxed tension, constant frown,
frown, clenched jaw
grimace

Restlessness 0 1 2 Restlessness
score:
Quiet, relaxed Occasional Frequent restless
appearance, restless movement may
normal movement, include extremities
movement shifting or head
position

Muscle tone* 0 1 2 Muscle tone

score:
Normal Increased Rigid tone
muscle tone tone, flexion
of fingers and
toes

Vocalisation** 0 1 2 Vocalisation
score:
No abnormal Occasional Frequent or
sounds moans, cries, continuous moans,
whimpers and cries, whimpers or
grunts grunts

Consolability 0 1 2 Consolability
score:
Content, Reassured by Difficult to comfort
relaxed touch, by touch or talk
distractible

Behavioural pain assessment scale total (0–10) /10

721
Assess muscle tone in patients with spinal cord lesion or injury at a level above the lesion injury.
Assess patients with hemiplegia on the unaffected side.
** This item cannot be measured in patients with artificial airways.
[Link]
url=http%3A%2F%[Link]%2Fqualitycouncil%2Fdownloads%2Fapp1_pain_
rating_scales.doc&ei=0vbpUfaFPKSVygHP8ICQCg&usg=AFQjCNG-kO-
9WhsK133N6NXKP6ATaqNMsQ&bvm=bv.49478099,[Link]
VAS the visual analog scale - a simple assessment tool consisting of a 10 cm line with 0 on one
end, representing no pain, and 10 on the other, representing the worst pain ever experienced,
which a patient indicates so the clinician knows the severity of his or her pain.
[Link]
Mean pain intensity – the use of multiple-item pain scales to derive an arithmetic mean pain
rating in chronic pain patients. ??? Not sure about this one but here is a reference:
[Link]
3. Linezolid: a very strong antibiotic that has some specific anesthesia implications: What
are they?
Linezolid: “(ZYVOX) should not be used in patients taking any medicinal product which
inhibits monoamine oxidases A or B (e.g. phenelzine, isocarboxazid) or within 2 weeks of taking
any such product. Unless patients are monitored for potential increases in blood pressure,
ZYVOX should not be administered to patients with uncontrolled hypertension,
pheochromocytoma, thyrotoxicosis and/or patients taking any of the following: directly and
indirectly acting sympathomimetic, vasopressive, and dopaminergic agents. Unless patients are
carefully observed for signs and/or symptoms of serotonin syndrome, ZYVOX should not be
administered to patients with carcinoid syndrome and/or patients taking any of the following
medications: serotonin reuptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor
agonists, meperidine, or buspirone. Spontaneous reports of serotonin syndrome have been
reported with the coadministration of ZYVOX and serotonergic agents. If signs or symptoms of
serotonin syndrome, such as cognitive dysfunction, hyperpyrexia, hyperreflexia, and
incoordination occur, discontinuation of one or both agents should be considered”.
[Link]

722
 4. Tell me about: Posidur and Exparel??
POSIDUR™ (SABER® - Bupivacaine) is a long-acting local anesthetic being developed for the
treatment of post-surgical pain. It is administered during surgery to the surgical site, where it
continuously releases therapeutic levels of bupivacaine in a controlled fashion, providing up to
72 hours of uninterrupted local analgesia. [Link]
EXPAREL is a local analgesic that utilizes bupivacaine in combination with the proven product
delivery platform, DepoFoam®. A single intraoperative injection treats pain at the source with
reduced opioid requirements for up to 72 hours. [Link]
5. Is Music…? (Not noise?) Helpful with pain control?
“Music may disrupt the brain's "pain - stress - pain" feedback loop and in doing so alter an
individual's sensitivity to pain. How might this work? We know that music effects evolutionarily
old subcortical areas of the brain, thereby influencing many different psychological and
physiological states. Music modulates the brain's limbic system, triggering numerous
accompanying neurochemical effects. The result of these changes in the brain may be to help
distract listeners from negative feelings and modify the influence of past memories associated
with pain. As a further result, music may promote relaxation by inhibiting the release of stress
hormones and weakening arousal of the pituitary-adrenal stress axis. The brain's opioid system
may also play a role. Music that listeners find emotionally engaging seems to affect the brain's
opioid system, and opioids control both physical pain and the pain of social loss”.
[Link]

6. Define Oxycodone: give reference

Oxycodone is a strong narcotic pain-reliever and cough suppressant similar to morphine,
codeine, and hydrocodone. The precise mechanism of action is not known but may involve
stimulation of opioid receptors in the brain. Oxycodone does not eliminate the sensation of pain
but decreases discomfort by increasing tolerance to pain. In addition to tolerance to pain,
oxycodone also causes sedation and respiratory depression. The FDA approved oxycodone in
1976. [Link]

723
 Anesthesia Facts:

1. Oxygen toxicity is a condition resulting from the harmful effects of breathing molecular
oxygen (O2) at elevated partial pressures. It is also known as oxygen toxicity syndrome,
oxygen intoxication, and oxygen poisoning. Historically, the central nervous system
condition was called the Paul Bert effect, and the pulmonary condition the Lorrain Smith
effect, after the researchers who pioneered its discovery and description in the late 19th
century. Severe cases can result in cell damage and death, with effects most often seen in
the central nervous system, lungs and eyes. Oxygen toxicity is a concern for underwater
divers, those on high concentrations of supplemental oxygen (particularly premature
babies), and those undergoing hyperbaric oxygen therapy.
2. Nitrous oxide is nonflammable, but it is an oxidizer and will support combustion of
flammable materials.
3. Desflurane was the 653rd compound created by Terrell and his associates at Ohio
Medical Products in the 1960s. Compound 347 (enflurane) and 469 (isoflurane) were
initially selected as the most marketable and both subsequently gained widespread
acceptance as anesthetic agents. Desflurane was known to have general anesthetic
properties, in particular, to have low blood solubility, an important criteria in the search
for an ideal anesthetic agent. Nevertheless it was rejected for several reasons.
4. Tracheal tubes used in the United States are composed of polyvinyl chloride (PVC),
nylon, Teflon or silicone rubber. PVC tubes offer several advantages over other types of
tubes and are therefore the most commonly used. PVC is somewhat rigid at room
temperature and softens once it is placed in the warm trachea. PVC used in tracheal tubes
is transparent, allowing the visualization of condensation and material in the inner part of
the tube.
5. In 1961 Dr. Brian Arthur Sellick (1918–1996), an anesthetist, published the paper Cricoid
pressure to control regurgitation of stomach contents during induction of anesthesia—
preliminary communication, describing the application of cricoid pressure for the
prevention of regurgitation. The technique involves the application of backward pressure
on the cricoid cartilage with a force of 20-44 Newtons to occlude the esophagus,
preventing aspiration of gastric contents during induction of anesthesia and in
resuscitation of emergency victims when intubation is delayed or not possible. Some
believe that cricoid pressure in pediatric population, especially neonates, improves glottic
view and aids tracheal intubation apart from its classical role in rapid sequence intubation
for aspiration prophylaxis.
6. The first patient package insert required by the FDA was in 1968, mandating that
isoproterenol inhalation medication must contain a short warning that excessive use could
cause breathing difficulties.

724
7. Insulin facilitates the transport of glucose and potassium into the cell, and is important for
the cellular uptake of glucose with the exception of the brain and liver where it does not
affect glucose transport.
8. Patients treated with aminoglycosides should be under close clinical observation because
of the potential toxicity associated with their use. As with other aminoglycosides,
Gentamicin Sulfate injection is potentially nephrotoxic. The risk of nephrotoxicity is
greater in patients with impaired renal function and in those who receive high dosage or
prolonged therapy. Neurotoxicity manifested by ototoxicity, both vestibular and
auditory, can occur in patients treated with Gentamicin Sulfate, primarily in those with
pre-existing renal damage and in patients with normal renal function treated with higher
doses and/or for longer periods than recommended. Aminoglycoside-induced ototoxicity
is usually irreversible. Other manifestations of neurotoxicity may include numbness, skin
tingling, muscle twitching and convulsions. The concurrent use of gentamicin with
potent diuretics, such as ethacrynic acid or furosemide, should be avoided, since certain
diuretics by themselves may cause ototoxicity. In addition, when administered
intravenously, diuretics may enhance aminoglycoside toxicity by altering the antibiotic
concentration in serum and tissue. Neuromuscular blockade and respiratory paralysis
have been reported in animal studies (a cat) receiving high doses (40 mg/kg) of
gentamicin. The possibility of these phenomena occurring in man should be considered if
aminoglycosides are administered by any route to patients receiving anesthetics, or to
patients receiving neuromuscular blocking agents, such as succinylcholine, tubocurarine,
or decamethonium, or in patients receiving massive transfusions of citrate anticoagulated
blood. If neuromuscular blockade occurs, calcium salts may reverse it.
9. One of the many annoying things about Joint Commission rules is their seeming lack of
common sense. Example: Waste baskets have to be five feet apart in the operating room.
10. Due to the wide variability in CSF volume, the ability to predict the level of the spinal
blockade after local anesthetic injection is very poor, even if body mass index is
calculated and used.
11. If IV Zofran is pushed too quickly some patients may develop a headache – particularly if
given preoperatively or if the patient is awake.
12. Adding 10-15 mcg of fentanyl to the spinal block local anesthetic will decrease patient
complaints of pressure and pulling during cesarean section, this is in addition to 0.3 mg
of preservative free morphine.
13. With neuraxial anesthesia one can experience a “false loss of resistance” just prior to
hitting bone.
14. A woman in labor will have an increase in their white blood cell count.
15. When do you pull back an epidural catheter? When the block is one sided.
16. Another possible solution of a one-sided epidural block is to have the patient lay on the
unblocked side to help the spread of medication to that side.
17. Why it is possible for a woman’s Mallampati to change during labor? Venous congestion
due to the pushing and contractions of labor.

725
18. Why do we give Toradol preoperatively for an Essure Procedure? It helps prevent spasm
– but be sure to ask the surgeon first.
19. If you encounter a “buttery” ligament while performing an epidural what should you do?
Start over at a different level.
20. Give two examples as to how Mg+ is useful in anesthesia (theoretically). It can be used
as an adjunct to analgesia through its action on the NMDA pathway. Also, it may reduce
the catecholamine response to DL and surgery.
21. What is the "Stop Bang" criteria and how is it used? Sleep apnea assessment tool –
Snoring, Tired, Observed apnea, Pressure (high blood pressure), BMI (obesity), Age
(over 50), Neck girth (>30 cm), Gender. This tool was originally only the "Stop" tool
with 2 or more being high risk. By adding the "Bang" if the patient has 6 positive
answers it is both sensitive and specific for sleep apnea even without a formal sleep
study.
22. The term "Kissing Ventricles" seen on TTE, refers to what physiologic condition?
Hypovolemia.
23. What is a significant cardiac side effect to the administration of cimetidine? Bradycardia
which may progress to Asystole.
24. Why is Cisatracurium and Atracurium contraindicated in a patient with an Hx of
epilepsy? They both form an active metabolite called Laudanosine, which causes
cerebral excitation and is renally eliminated.
25. What is a side effect associated with EDTA (the preservative used in propofol and
Chloroprocaine to inhibit microbial growth)? Back pain... Which is attributed to
chelation of Ca++ in the Supraspinous muscles.
26. A pt currently taking Glucophage. What is an important anesthetic consideration? Lactic
Acidosis.

726
 Second Set of Facts:

1) To use iodine or a chlorhexidine in preparation for spinal, epidural or neuraxial blockade? It

is technically off label to use chlorhexidine as a prep as it may be toxic to nerves but is
superior to iodine as a bactericide. Will you be sued for the infection or the neurotoxicity?

2) Fresenius propoven (from Europe) has been seen in the US instead of propofol. Same
efficacy, but has peanut oil as an emulsifier as well, we ask about soy allergy… should we
start asking about peanuts?

3) Higher incidence of MH susceptible patients in Marathon County, Wisconsin.

4) Which queen of England was anesthetized with chloroform during child birth? Queen
Victoria.

5) Indigo Carmine is a powerful alpha agonist with a short half-life, should be administered
slowly.

6) Who is administering my anesthesia? Many patients are unaware that there are other
specialties that provide anesthesia like CRNAs. A recent (2010) retrospective study of over
50,000 anesthetics showed no difference in outcomes between CRNAs and
Anesthesiologists.

7) I just gave my patient heparin and the ACT is still 150. I give it again…. Still 150??? What
should I do?? May be antithrombin III deficiency; in this case, counter intuitively, FFP
should be administered.

8) Crap! I just gave my Parkinson’s patient a D2 antagonist like metoclopramide. What do I

have in my top drawer that will help ameliorate these extrapyramidal symptoms???? The
central anticholinergic effects of diphenhydramine will be beneficial.

9) I am administering a spinal anesthetic for C section and my patient is nauseated, what drug
should I use as an antiemetic? Does it matter if she is planning on breast feeding? D2
antagonism with metoclopramide will assist in lactation.

10) What is the most common allergic reaction in the OR? First reaction would be to
antibiotics, but non depolarizing neuromuscular blocking drugs is the answer.

11) When is cardiac the greatest in the parturient? After delivery of the child. One would think
that CO would be greater when the needs of the fetus need to be served; however, when the
fetus is no longer compressing the great vessels, the cardiac output is the greatest because
preload is increased and afterload is decreased.

12) In the reaction of protamine sulfate and heparin sodium…, which is, the acid and which is
the base? Heparin is the acid.

727
13) What if my patient is allergic to NPH??? The P in NPH stands for protamine. Protamine
itself can cause profound histamine release if given quickly enough.

14) If your patient tests positive for cocaine but is not actively intoxicated with cocaine (AEB
normal blood pressure, heart rate and LOC), should you proceed to OR?? Studies suggest
that there is no need to delay surgery if patient is not acutely intoxicated with cocaine?

15) So what is this cauda equina syndrome and why can’t I use 5% lidocaine for spinals
anymore??? Hyperbaric 5% lidocaine is no longer recommended, however 2% lidocaine is
OK to use.

16) MAC stands for “minimum alveolar concentration”, but is actually the concentration needed
for 50% of the population to not move in response to surgical stimulus. It is actually and ED
50.

17) Curare, one of the first paralytic drugs used in anesthesia, can paralyze someone
pharmacologically if injected; but won’t work if ingested. Why? Due to the first pass effect
metabolism by the liver.

18) Should I turn my bair hugger on before or after draping? Does it matter? Some studies have
linked wound infections to bacteria that were harbored in the bair hugger unit itself. After
draping decreases the chance of wound infection.

19) You have an obstetrics patient and see MTHFR on their chart… what the??? Of course you
know that stands for methyl tetrahydrofolate reductase deficiency and that they have
increased homocysteine levels which puts them into a hypercoagulable state.

20) Give me some good reasons for low flows: less heat loss, conserves anesthetic, which
decreases cost and pollution.

21) I have a patient with a bad heart (poor EF), can I use propofol to induce? Yes, you can
induce anyone with propofol as long as you use the correct dose. Which in this case would be
decreased and would need to allow for and have the patience for increased circulation time.

728
22) I am running a TIVA on a patient and there is no Remifentanil at this institution!! What do I
do?? Why not use a fentanyl infusion with propofol. Place a BIS and titrate to effect, it can
be done!

23) How much air do I inflate the cuff of the ETT with?? To create a seal and no more. In an
effort to prevent tissue tamponade and resultant ischemia. Close the APL valve and squeeze
the bag while you inflate the cuff. When the air leak stops, there is enough air in the cuff.

24) If your patient is allergic to a non-depolarizing neuromuscular blocker, they are likely
allergic to para aminobenzoic acid as a metabolite of ester local anesthetics. Food sources of
PABA include liver and mushrooms.

25) Also, if your patient is allergic to PABA, you may want to check your amide local anesthetic
vile as it may be a multi dose containing methylparaben, a congener of PABA.

729
 Board Study Guide
1) Muscle relaxants
Nerve impulse → quanta release (1000 molecules Ach) → bind to nicotinic cholinergic receptors
on postsynaptic membranes
Causes change membrane permeability which leads to ↓transmembrane potential
- 90 mv to –45 mv → propagated action potential over skeletal muscles → muscle
contraction
Acetylcholinesterase - Situated close to cholinergic receptors (junction folds and basement
membrane)
Rapidly hydrolyzes (< 15 sec) ACh to acetic acid + choline
NMJ has 3 type of nicotinic cholinergic receptors:
2 postsynaptic on skeletal muscle surface: One junction, one extrajunctional
1 presynaptic on nerve ending
Na+ & Ca++ move into skeletal muscle, K+ leaves
2 α subunits: Binding site for Ach & Sites occupied by NMBs
Occupation of 1 or both subunits by nondepolarizers → receptor ion channel remains
closed, Ions can’t flow through channels, Depolarization can’t occur, If enough channels stay
closed, neuromuscular transmission blocked
Muscle relaxants have in common a quaternary ammonium group, SCh is 2 molecules of ACh
linked by acetate methyl groups; Nondepolarizers- Benzylisoquinolinium or amino steroid
compounds
Benzylisoquinolinium with 3o amine more likely to release histamine than amino steroids
NMBs highly ionized, water-soluble compounds
Block produced: phase I depolarizing, phase II (nondepolarizing)
Effective NMB Monitoring - Paralysis onset begins with eye muscles, followed by extremities,
trunk (neck muscles down through intercostal), abdominal muscles diaphragm, Recovery
returns in opposite manner

730
 Protective reflex muscles of pharynx & upper esophagus recover LATER than the
diaphragm, larynx, hands or face
Monitoring of the facial nerve innervating muscles of the eye:
Orbicularis oculi muscles cover the eyelids
Corrugator supercilii cause eyebrow twitch correlating well with laryngeal adductor
muscles== intubating conditions
Succinylcholine (1.5-2 mg/kg intubating dose) - Plasma cholinesterase is increased in obesity
and goiter; Plasma cholinesterase is decreased in the setting of burns, liver disease,
organophosphate poisoning, echothiopate, malnutrition, and pregnancy
Stimulates muscarinic receptors at the SA node, and this is the mechanism of bradycardia.
Contraindicated in MH, patients taking echothiopate eye drops, neuromuscular degenerative
diseases, CVA, spinal cord injury, burns, hyperkalemia;
Atracurium (0.3-0.4 mg/kg) – metabolized by Hoffman elimination, Active
metabolite=laudanosine= CNS stimulation
Cisatracurium (0.1 mg/kg) - One of 10 isomers of Atracurium, 3x as potent as Atracurium,
Eliminated by Hoffman elimination, No histamine release, compared to Atracurium
Pancuronium (0.1 mg/kg) - Long acting, highly ionized and limited lipid solubility, Undergoes
significant hepatic metabolism, 80% eliminated unchanged in the urine. Renal failure slows the
elimination of pancuronium. Accompanying increase in heart rate due to blockage of vagal
muscarinic receptors in the SA node, and activation of the SNS.
Rocuronium (0.6-1.2 mg/kg) - Chemically similar to Vecuronium, but shorter duration of action.
Onset 60-90 seconds, duration about 30 minutes, eliminated via biliary excretion, at higher doses
(1.2 mg/kg), an alternative in patients who cannot receive Suxx for RSI—due to faster peak
effect time, with an intubating dose of 0.6 mg/kg, 40% of patients will have residual NMB at
2hrs and 10% will have at 4 hrs
Vecuronium (0.08-0.1 mg/kg)-Hepatic and biliary metabolism
Factors potentiating neuromuscular blockade - Volatile anesthetics, Local anesthetics
(procaine), Anticholinesterases such as echothiopate, Antibiotics: Tetracycline, aminoglycosides
(gentamicin, tobramycin, amikacin, kanamycin), Clindamycin, Polymyxins

731
 Electrolytes: Mg++ decreases the release of Ach from the nerve terminal and decreases
the sensitivity of the end-plate to the effects of Ach—potentiating the effects of both suxx and
nondepolarizers; Increased Li, Na; Decreased Ca, K (
Hepatic dysfunction, hypothermia, acidosis, alkalosis
Erythromycin, penicillin, and cephalosporins do not potentiate neuromuscular blockade
Echothiopate - is an effective inhibitor of pseudocholinesterase. If echothiopate has been
administered within the past 4 weeks, drugs metabolized by pseudocholinesterase should be
avoided (succinylcholine, procaine, Chloroprocaine, cocaine, and tetracaine)
Dibucaine - An amide local anesthetic which is an inhibitor of pseudocholinesterase used to
determine whether atypical or normal pseudocholinesterase is present in plasma. It indicates
quality but not quantity of pseudocholinesterase.
80% inhibition indicates homozygous normal
60% inhibition indicates heterozygous atypical
20% inhibition indicates homozygous atypical
2) Volatile anesthetics;
Agent Blood/Gas Blood/Oil MAC % Boiling Point (C)
Nitrous oxide 0.47 1.4 104 - 88
Desflurane 0.42 18.7 6 23.5
Sevoflurane 0.69 47.2 2 58.5
Enflurane 1.9 98.5 1.7 56.5
Isoflurane 1.4 91 1.16 48.5
Blood: Gas Coefficients
A blood: gas partition coefficient of 2.4 for halothane means that about 70.6% (x) of halothane
delivered to the alveoli will be transferred to the blood, leaving about 29.4 % (y) remaining in
the alveolar space. (70.6/29.4 = 2.4) [The values for x & y result from simultaneously solving x
+ y = 100 % and x/y = 2.4].
x/y = 2.4, x = 2.4y, x + y = 100% OR 2.4y + y = 100%, 3.4 y = 100%, y = 29.4%

732
FA/FI

 Before we look at this particular point we want to develop a general appreciation of the
factors that influence FI.
 The anesthetic concentration in the gas circuit will rise in accord with first-order kinetics,
described in this case by the following
 relationship:
 FI = FFGO (1-e-T/τ)
 where T equals time and τ is the time constant
 which, in this case, is the volume or capacity of the breathing circuit (Vc) divided by the
fresh gas flow (FGF) [τ = Vc/FGF]
 FFGO is the fraction of inspired volatile agent in the gas leaving the fresh gas outlet (i.e.,
the vaporizer setting).
 For example is the fresh gas flow was set at 2L/minute and the volume of the circuit was
6L then the time constant would be 3 min.
 With systems that obey first-order kinetics, about 95% of the theoretical maximal value
will be reached following expiration of time
 Equal to about three x constants.
Nitrous – Des – Sevo – Iso – Halothane (fastest to slowest FA/Fi)

 Noting that τ = Vc/FGF and that Vc is a constant (6 liters), then τ decreases as FGF
increases; τ changes in accord with these ratios 6 liters/1 liter/min; 6/2liters/min;
6/4liters/min.
 Factors that tend to increase the rate of rise of FA/FI include:
o High flows!
o Relatively low blood: gas partition coefficients for the anesthetic (low λB)
o Low cardiac output (low Q) because of slowed transit time, high VA (higher
minute ventilation)
o High (PA-Pvenous), concentration gradient

733
3) Opioids
Advantages

 minimal direct myocardial depression

 no myocardial sensitization
 no increased ICP
 no hepatorenal toxicity
 predictable post-op awakening
 antagonists available
 post-op analgesia
 facilitates post-op ventilation
 no environmental pollution
 safe in malignant hyperthermia

Disadvantages

 As a sole agent, unpredictable amnesia and unconsciousness

 requires background of volatile agent, midazolam or N2O
 Does not suppress SNS response
 Addition of N2O causes CV depression
 Orthostatic hypotension
 increased venous vasodilatation (morphine)
 need for fluid replacement
 Vagal effects causing bradycardia (fentanyl, sufentanil)
 Histamine release (morphine)
 N/V from stimulation of CTZ
 Biliary tract constriction
 Muscle rigidity
 muscle relaxants may be needed
 Post-op respiratory depression
Phenanthrene

 Morphine, codeine, thebaine

 Highly ionized at physiological pH (Nonionized drugs are 1000-10,000X more lipid
soluble than ionized form)
 Water soluble at physiological pH

734
Synthetic Opioids

 Phenanthrene nucleus
 manufactured by synthesis
 phenylpiperidine derivatives (Alfentanil, Fentanyl, Naloxone, Naltrexone, Meperidine,
Sufentanil, Remifentanil)
Opioid Receptors and Endorphins

 Functions as an endogenous pain-suppression system

 Endogenous substances that mimic morphine
 Peptides in the brain with morphine like activity
o enkephalins - short acting, poor analgesia
o endorphins - long acting, potent analgesia
 However, beta-endorphins are 5 - 10 times more potent that morphine
 Opioid receptors are classified as mu, delta and kappa
 Belong to the superfamily of guanine-protein receptors
o constitute 80% of all known receptors
 CNS - brain
o periaqueductal matter of brain stem
o amygdala, corpus striatum, hypothalamus

 Spinal cord - substantia gelatinosa

o dorsal horn of the spinal cord
o first site in the CNS for integration of sensory information
 Mu
o Mu 1 - spinal (perception of pain is decreased) and supraspinal analgesia (“I feel
the pain but I don’t care), euphoria, bradycardia, hypothermia, urinary retention,
miosis, pruritis
o Mu 2 - spinal analgesia, respiratory depression, physical dependence,
constipation
 Kappa - spinal and supraspinal analgesia, dysphoria, sedation, miosis, delayed gastric
emptying
 Delta - spinal and supraspinal analgesia, respiratory depression, physical dependence,
constipation (minimal), urinary retention
 Sigma - high affinity for phencyclidine
o dysphoria, hallucination, vasomotor stimulation, tachypnea, mydriasis
 Epsilon - found in rats but not considered opioid receptors
 Most currently used opioids highly selective for μ-opioid receptors
o Coupled to K+ conductance
 Inhibits neurotransmitter release
 Hyperpolarizes cell membranes

735
  All opioid receptors coupled to G proteins
o Regulate activity of adenylate cyclase, subsequent ion channel conduction
characteristics
 Major plasma proteins to which opioids bind:
o Albumin
o α1-acid glycoprotein
10 mg of Morphine IV= 100 mcg Fentanyl (100x as potent on a mg/mg basis) IV, 100 mg
Meperidine (Demerol) IV, 1- 1.5 mg of Hydromorphone (Dilaudid) IV, 5 mg of Methadone IV,
10 mcg of Sufentanil
50 mcg Fentanyl =5 mcg Sufentanil=5 mg of Morphine
Morphine potency comparison = Sufentanil = 2000-4000 x; Remifentanil = 220 – 470 x;
Fentanyl = 50 -100 x; Alfentanil = 10 x; Meperidine = 1/10 x
Elimination t1/2 from shortest to longest: Remifentanil<<Alfentanil<<morphine<<
sufentanil<<meperidine<<fentanyl
Meperidine

 Piperidine derivative
 Structurally very similar to atropine and has a mild antispasmodic effect
 Potency: 1/10th of that of morphine (100 mg Demerol = 10 mg morphine)
 Intermediate acting: 2 - 4 hours
 Dose: 1 mg/kg
 90% metabolized by liver forming demthylated normeperidine
 normeperidine elimination half-life of 15-40 hours
 CNS stimulation
 may cause confusion, hallucinations
 Protein binding: 64-82, pKa - 8.5
 Lipid solubility: Intermediate
 Therapeutic index: 5-30 (Low)
 Side effects
o orthostatic hypotension (more profound that with MS)
o increased heart rate (atropine like effect)
o delirium and seizures (normeperidine)
o respiratory depression
o mydriasis instead of miosis
o dry mouth
 Stops shivering (kappa stimulation?)

736
  CV depression
o 20 X greater than morphine due to direct myocardial depression
o increased heart rate
o decreased cardiac output (exaggerated with N2O, valium
 60% bound to plasma proteins
o elderly manifest decreased protein binding and increased plasma concentrations
 Meperidine potentiates the CNS and circulatory depression of other opioids, sedative
hypnotics, volatile anesthetics, and TCAs
 Patients on MAOIs should NOT receive Meperidine, or the following may ensue:
hyperpyrexia, hypertension, hypotension, ventilatory depression, skeletal muscle rigidity,
seizures, coma
Morphine

 Phenanthrene derivative
 Dose: 0.1-1.0 mg/kg IV
 High dose: 1-5 mg/kg IV
 Balanced anesthesia: 0.2-0.5mg/kg IV
 Supplement inhalation anesthesia: 5-20 mg
 Potency: 10 mg Morphine = 100 μg fentanyl
 Long acting - 4 - 5 hours
 Protein binding: 26 - 36%
 Poor penetration of MS into CNS
o poor lipid solubility
o high degree of ionization
 Metabolism: 95% liver and kidneys
 Only small amount excreted unchanged
 metabolites excreted renally
 renal failure results in increased plasma concentration; use with extreme caution
 no problem with morphine in hepatic cirrhosis or anhepatic phase of orthotropic liver
transplantation due to significant renal clearance
 Side effects: Euphoria, Miosis, No amnesia, Orthostatic hypotension (due to ↓ SNS
tone), May see ↓ systemic vascular resistance, ↓ cardiac output, Bradycardia - ↑ vagal
activity, depressant effect on SA node, slow AV node conduction; Histamine release
causes hypotension, ↓ MAP, ↓ PVR, not affected by naloxone; ↓ Cerebral blood flow

737
  Respiratory effects
o ↑ CO2 threshold
o shifts CO2 response to the right
o direct depressant effect on brain stem ventilation centers
o reduces release of acetylcholine from neurons in the medullary ventilatory center
in response to hypercarbia
o physostigmine causes CNS acetylcholine
o antagonizes respiratory depression but not analgesia
o Peak onset of respiratory depression is slower than with fentanyl because of
fentanyl’s greater lipid solubility. Fentanyl gets into and out of the CNS more
quickly.
o Depressant effects can last up to 5 hours
o ↓ respiratory rate and tidal volume
o Interferes with pontine & medullary ventilatory centers that regulate rhythm of
breathing
o may see some compensatory ↑ in TV
o sighing is minimized
o prolonged pauses between breaths
o delayed exhalation and periodic breathing
o increases chance of atelectasis
o cough reflex depressed
o ↑ airway resistance
Fentanyl

 Phenylpiperidine derivative
 Potency: 75 - 125X more potent than morphine
 Therapeutic index: 277
 Rapid onset
 Short duration of action - .5 - 1 hour
 Good lipid solubility
 passes blood/brain barrier quickly
 Metabolism
o metabolized by N-demethylation producing norfentanyl
o similar to normeperidine
o excreted by the kidney
o longer elimination half-time than morphine
o due to larger volume of distribution (Vd) because of greater lipid solubility and
passage into tissues
o prolonged effect in the elderly

738
  Advantages
o lack of direct myocardial depressant effects
o absence of histamine release
o suppression of stress response to surgery
 Disadvantages
o fails to prevent SNS response to surgical stimulation
o possible patient awareness
o post-operative respiratory depression
 Routes of administration
o trans mucosal: 5-20 μg/kg lollipop
o transdermal: 75 - 100 μg/hour
 Respiratory effects
o ↑ CO2 threshold and shift of CO2 to right
o ↓ rate and TV
o Depressed cough reflex
o Respiratory depression is dose related
o Truncal rigidity
o ↓ thoracic compliance with bronchial smooth muscle rigidity
o ↓ ventilation and venous return due to ↑ mechanical ventilation pressures
o may be central effect
 Additional effects
o increased effect with liver disease
o minimal renal effects unless CV changes
o ADH not released by narcotics
o ↓ peristalsis and constipation
o ↓ biliary tone resulting in colic
o nausea and vomiting similar to morphine
Sufentanil

 5 - 10X more potent than fentanyl

 Sufentanil 0.0035 mg = fentanyl 0.05 mg
 Safe therapeutic index: 25,211
 Dose: .025 - 30 μg/kg
 Analgesic dose: 0.1 - 0.4 μg/kg IV
 Maintenance dose: 1μg/kg followed by 0.25-0.5 μg/kg/hr
 High dose: 10 - 30 μg/kg
 Faster IV induction than fentanyl
 Very lipid soluble
 Bradycardia may ↓ cardiac output
 No change in cerebral blood flow

739
Remifentanil

 Unique metabolism
 Hydrolysis by non-specific esterases
 Unaffected by age, gender, weight, hepatic or renal function
 Yet, the elderly are 2X as sensitive
 Metabolite is renally excreted
 Fast offset as it does not accumulate after long administration (5 - 10 minutes)
 Neurosurgery
o minimal effect on ICP
o modest effects on MAP
Alfentanil

 Used infrequently today

 1/5 - 1/10 as potent as fentanyl
 Alfentanil 0.2mg = Fentanyl 0.05 mg
 Safe therapeutic index - 1080
 1/3 duration of action of Fentanyl
 Rapid onset - crosses blood/brain barrier easily
 Brief duration of action due to redistribution
Antagonists (Naloxone, Nalmafene)

 High affinity for the opioid receptors

 Displace the opioid agonist from the Mu receptor
 Antagonist binds to the Mu receptor
 does not activate the receptor
Naloxone

 Dose: 1 - 4 μg/kg IV
 Half-life - 1 hour
 used to reverse opioid induced respiratory depression
 TITRATE (40 μg at a time)
 care not to reverse analgesia
 continuous infusion (5 μg/kg/hr) may offset respiratory depression of opioid neuraxial
techniques
 CNS - counteracts sedation, lethargy and analgesia
 No effect on respiratory depression of other drugs (barbiturates, alcohol, general
anesthetics)
 Short duration of action(30 - 45 minutes)
 Renarcotization may occur
 Shifts CO2 response curve to left
 ↑ respiratory rate and tidal volume

740
  Side effects
o Nausea and vomiting
o Hypertension
o Cardiac arrhythmias
o Pulmonary edema
 Etiology of side effects
o sudden pain
o stimulation of SNS
o increased catecholamines
Intraspinal & epidural opioids

 Opioid receptors identified in substantia gelatinosa of spinal cord

 Epidural dose 5 - 10X more potent than intrathecal
 Morphine
o intrathecal (0.5 - 1.0 mg)
 analgesia for an average of 20 hours
o epidural (2 - 8 mg)
 intense and long acting analgesia
 Benefits of neuraxial opioids
o No sympathetic nervous system denervation
o No skeletal muscle weakness
o No loss of proprioception
o Patients can ambulate
o Decreased risk for orthostatic hypotension
o Pain unresponsive to systemic opioids may respond to same drugs given centrally
 Analgesic activity
o k receptors in substantia gelatinosa
o Lamina II of dorsal horn
 Combined with local anesthetics
o Synergy, ↓ dose requirement

741
Ketamine – phencyclidine derivative
 Causes dissociative anesthesia (dissociation between thalamocortical & limbic systems);
the only true anesthesia drug we have
 NMDA receptor antagonist - Since NMDA receptor activation is dependent on the
binding of both glycine and glutamate, the binding of an antagonist at either of these sites
prevents activation and opening of the channel.
 NMDA plays an important role in processing pain via glutamate
 Reduces the need for opioids
 May reduce PONV??
 MH treatment = sequesters calcium
 Bronchodilator with asthma
 New concentrations
 Raises ICP; raises IOP;
 Increases mental outcome of psych patients
 Extensive metabolism by hepatic microsomal enzymes
o Active metabolite (norketamine) may contribute to prolonged duration of action

 Emergence Delirium
o Incidence: 5-30%
o Associated factors:
 Age > 15 yrs
 Female gender
 Doses > 2mg/kg IV
 History of personality problems or frequent dreaming
 Prevention
o Benzodiazepines 5 min before ketamine or mixed with it
o Prospective discussion with pt
4) Neurotransmitters

• ACh is transmitter of efferent arm of somatic nervous system

• NOREPINEPHRINE
o Associated with sleep, mood, motor function, and pleasure recognition
o First step in cessation of adrenergic receptor stimulation by norepinephrine is
diffusion of norepinephrine away from adrenergic receptor
o Effects of norepinephrine terminated by 3 mechanisms
o Reuptake (accounts for 80% of loss of efficacy)
o Metabolism (monoamine oxidase in tissues and catechol-O-methyltransferase in
blood and liver)
o Diffusion away from receptors

742
 • Proportions in which norepi and epi released from chromaffin cells of adrenal
medulla
o Norepi accounts for 20%
o Epi is 80%
• Monamine oxidase - Metabolizes amines within nerve terminals
o Neurotransmitter amines include norepi, dopamine, serotonin
• Catechol-O-methyl transferase (COMT)
o Degrades norepi and epi primarily as they circulate through liver
• CATHECOLAMINE NEUROTRANSMITTERS
o Associated with sleep, mood, motor function & pleasure recognition
o Dopamine
o Serotonin
o Endorphins: inhibits pain-type of nerve impulses
o Enkephalins: inhibits pain-type of nerve impulses
• Adrenergic receptors are G protein-coupled receptors
o α receptors respond most strongly to norepi
o β1 receptors respond equally to norepi & epi
o β 2 receptors respond most to epi
o β3 receptors respond most strongly to norepi
5) Vasopressors
Epinephrine
 Effects
o All alpha and beta receptors
o Beta receptors more sensitive than alpha receptors to epinephrine
o Increase in systolic BP, heart rate and cardiac output via beta 1 stimulation
o Modest decrease in DBP reflecting vasodilation from beta 2 stimulation
o Net= increase pulse pressure, minimal change in MAP
o Accelerates phase 4 depolarization = arrhythmias
o Alpha 1 stimulation causes vasoconstriction in the skin, mucosa, hepatorenal
vasculature
o Beta 2 effects predominate in skeletal muscle vasculature, causing vasodilation
o Beta 2 stimulation causes airway smooth muscle relaxation (bronchodilation)
 Features
o Most potent alpha adrenergic agonist; effects both beta1 and beta2 receptors
o In small doses, beta 2 effects predominate
o In larger doses, beta 1 effects also occur
o In ever larger doses, stimulation of alpha and beta receptors
o Single shot 2-10 mcg produces transient effect lasting 1-5 minutes

743
  Uses
o Addition to local anesthetics to prolong block duration and decrease systemic
absorption
o Major cases (liver transplantation, for example) to rescue hemodynamics
o Anaphylaxis treatment
o ACLS drug for CPR
o Increase myocardial contractility
 Side Effects
o Hypertension, dysrhythmias, myocardial ischemia
Norepinephrine
 Equipotent to epinephrine for beta 1 stimulation, but little effect on beta 2 receptors
 Potent alpha agonist that produces intense arterial and venous constriction
 Extravasation of this drug can cause severe necrosis
 Increased SVR leads to ↓venous return and ↑ SBP, DBP and MAP
 Decreased venous return + baroreceptor-mediated heart rate decrease (from increased
MAP) tend to decrease CO to a degree
Dopamine
 Endogenous catecholamine that is an immediate precursor of norepinephrine
 Nonspecific agonist at both dopamine 1 and dopamine 2 receptors, and alpha and beta
receptors
 Dopamine 1 receptors are located postsynaptically and cause vasodilation when
stimulated. These are located in the kidney, brain, heart and mesentery. Mediated by
adenylate cyclase.
 Dopamine 2 receptors are located presynaptically and inhibit adenylate cyclase and
release of norepinephrine. Nausea and vomiting are also possibly induced via these
receptors.
 Lower dose stimulates dopamine 1 receptors in the kidney
 Moderate dose stimulates dopamine and beta 1 receptors in the heart
 High dose stimulates dopamine, beta 1, and alpha receptors in the peripheral vasculature
 Unique in being able to simultaneously increase contractility, renal blood flow, GFR,
excretion of Na and urine output
 Increases CO via beta 1 stimulation. Increased CO is also due to stimulation of
norepinephrine release. This is an indirect action.
 Used in combination with dobutamine as infusion for failing hearts
 Dysrhythmias possible
 Must be given as an infusion to achieve and maintain therapeutic plasma concentrations

744
Ephedrine
 Structurally related to amphetamines
 Synthetic noncatecholamine that stimulates alpha and beta adrenergic receptors
 Mostly indirect acting in that in part, drug causes norepinephrine release
 Some direct acting properties
 Has been termed a “weak epinephrine”
 Mydriasis and CNS stimulation occur
 Has been used as an antiemetic at 0.5 mg/kg IM
 Useful in treatment of hypotension post spinal and from inhaled anesthetics
 OTC as a decongestant in various preparations
 SBP raised less intensely than with epi, but duration is 10 x longer
 Bolus results in increased HR, SBP, DBP and CO. Coronary and skeletal muscle flows
are increased
 Beta 1 effects predominate, except in beta-blocked patients>then the drug takes on the
characteristics of an alpha adrenergic agonist
 Side effects include tachycardia and cardiac dysrhythmias, hypertension, pulmonary
edema, anxiety, and hyperglycemia
 Use with caution in patient with HTN, ischemic heart disease, and depletion of
endogenous catecholamines (ephedrine should be avoided in cocaine-using patient

Phenylephrine
 Direct stimulation of primarily alpha 1 adrenergic receptors, but some alpha 2 stimulation
also
 Similar to norepi but less potent and longer lasting
 Usually given in 50 – 200 mcg boluses, or as an infusion in major cases
 Very useful in patients with CAD and aortic stenosis because this drug increases
coronary perfusion pressure without chronotropic side effects
 Venous > arterial venoconstriction
 Peripheral vasoconstriction
 Increased BP with a decreased CO. Decreased CO may be from increased afterload or,
more likely, to baroreceptor-mediated reflex bradycardia in response to increased DBP
 Increased SVR

745
6) Induction agents
Propofol
 Isopropylphenol
 1% solution (10 mg/kg)
 10% soybean oil
 2.25% glycerol
 1.2% egg lecithin
 Rapid IV injection of 2.5 mg/kg produces unconsciousness in 30 sec
 Awakening most rapid of available induction agents
 Mechanism of action - ecreases rate of GABA dissociation from its receptor
 Pharmacokinetics
o Clearance from plasma > hepatic blood flow
o Tissue uptake (possibly into lungs) important in transfer from plasma
o Elimination t1/2 ~ 1 hr
o Rapid metabolic clearance decreases context-sensitive t1/2
 Antiemetic, Antipruritic, Anticonvulsant - All of these actions are theorized to be due to
subcortical depression
 CNS
o ↓CMRO2/CBF/ICP
 CV
o ↓ MAP > comparable amt of thiopental
o Negative inotrope
o Systemic vasodilation
o Direct myocardial depression
o Resetting or inhibition of arterial baroreceptor tone
 Pulmonary
o Dose dependent ventilatory depression
o Apnea in 30% of patients after induction
o Potential for rapid apnea development with blousing
 Side Effects
o Proconvulsant activity
o Spontaneous excitatory movements (subcortical)
o Abuse potential
o Bacterial growth
 Discard 6 hrs after drawing up
o Tubing is good for 12 hours for continuous infusion
 Pain on injection
 With prolonged infusions, increases in serum triglycerides

746
Etomidate
 Structure: carboxylate imidazole
 Produces CNS depression by enhancing effects of GABA
 0.2% solution with propylene glycol - Pain on injection
 Pharmacokinetics
o Large Vd (considerable tissue uptake)
o Prompt awakening 2o drug redistribution from brain to inactive tissue sites
 Rapid metabolism
o Hydrolysis of ester side chain via hepatic microsomal enzymes & plasma
esterases
 Clearance 5X > thiopental
o Elimination t1/2 = 2-5 hrs
 Induction in unstable CV system
o 0.1-0.3 mg/kg
 Involuntary myoclonic movements 2o due to changes in inhibitory-excitatory influences
on thalamocortical tract
 Side Effects
 CNS
o Cerebral vasoconstriction, ↓CMRO2 ~40%
o Previously increased ICP is lowered
o EEG effects similar to thiopental
o May activate seizures – use with caution in epileptic pts
 CV
o Minimal changes in HR, SV, CO; MAP may ↓15% 2o ↓SVR
o Suggested for patients with limited cardiac reserve
 Ventilation
o Less depressant than barbiturates
 Pain on injection
 Myoclonus
o Spontaneous movement
o Dystonia, tremor
 Adrenocortical suppression
o Dose-dependent cortisol inhibition
 Significant degree of nausea

747
7) Anti-emetics
FIRST LINE
 5-HT3 antagonists
o Ondansetron
o Dolasetron
o Granisetron
o Dexamethasone
o Droperidol? (Used to be the first line agent before the Black Box!)
 SECOND LINE
o Dimenhydrinate
o Ephedrine
o Prochlorperazine
o Promethazine
o Scopolamine
o Supplemental Oxygen
 Nonpharmacologic Techniques
o Acupuncture
 Hypnosis

Pharmacologic Group Dopamine (D2) Muscarinic Cholinergic Histamine Serotonin

Anticholinergics + ++++ + –
Scopolamine
Antihistamines + +++ ++++ –
Cyclizine + ++ ++++ –
Dimenhydrinate + ++ ++++ –
Diphenhydramine + ++ ++++ –
Hydroxyzine + +++ ++++ –
Medizine ++ ++ ++++ –
Promethazine
Antiserotonins – – – ++++
Dolasetron – – – ++++
Granisetron – – – ++++
Ondansetron – – – ++++
Ramosetron
Benzamides ++++ – – +
Domperidone +++ – – ++
Metoclopramide
Butyrophenone ++++ – + +
Droperidol ++++ – + –
Haloperidol
Phenothiazines ++++ ++ ++++ –
Chlorpromazine ++++ + ++ +
Fluphenazine ++++ ++ ++ +
Perphenazine ++++ ++ ++ +
Prochlorperazine
Steroids – – – –
Betamethasone – – – –
Dexamethasone

748
 Drug Class Route Onset Duration Side effects

Ondansetron 5HT-3 receptor IV 10 min 24 hours HA, Light-headedness

(Zofran) antagonist IM 41 min abdominal pain
PO/ODT 15 min
Dolasetron 5HT-3 receptor IV 30-35 min 24 hours HA, hypotension, dizz
(Anzemet) antagonist PO 1 hour
Promethazine Phenothiazine IV 5 min 4-6 hours Dry mouth, blurred
( Phenergan) IM/PO/PR 20 min vision
Prochlorperazine Phenothiazine Extra Pyramidal
(Compazine) symptoms, Drowsiness,
Dizziness

Metoclopramide Benzamide IV 1-3 min 1-2 hours Extra Pyramidal

( Reglan) IM 10-15 min Symptoms, Drowsiness,
PO 30-60 min Lassitude

Transdermal Anticholinergic Patch 3-4 hours 24 hours Dry mouth, dizziness

Scopolamine

8) alpha/beta agonists/blockers

Receptor Effectively Binds Effect of Binding Overall Effect

Alpha 1 Via Gs protein Increased IP3 and Ca++ Vasoconstriction (reflex bradycardia
from this); ↑ BP
Alpha 2 Via Gi (inhibitory) Decreased cAMP and Decreased BP
protein Ca++
Beta 1 Via Gs protein Increased cAMP Increased contractility and heart rate
Increased Ca++
Beta 2 Via Gs protein Decreased C-amp Bronchodilation;gluconeogenesis;glyco-
genolysis;insulin secretion; coronary
Decreased Ca++ artery vasodilation

749
9) Epinephrine
Effects

 All alpha and beta receptors

 Beta receptors more sensitive than alpha receptors to epinephrine
 Increase in systolic BP, heart rate and cardiac output via beta 1 stimulation
 Modest decrease in DBP reflecting vasodilation from beta 2 stimulation
 Net= increase pulse pressure, minimal change in MAP
 Accelerates phase 4 depolarization = arrhythmias
 Alpha 1 stimulation causes vasoconstriction in the skin, mucosa, hepatorenal vasculature
 Beta 2 effects predominate in skeletal muscle vasculature, causing vasodilation
 Beta 2 stimulation causes airway smooth muscle relaxation (bronchodilation)
 Beta 1 stimulation causes glycogenolysis and lipolysis
 Alpha 1 stimulation inhibits insulin release
 Beta 2 stimulation causes hypokalemia due to K+ shift into cells
 Alpha 1 stimulation causes mydriasis
 Beta stimulation relaxes the bladder detrusor, whereas activation of alpha receptors
contracts the trigone and sphincter muscles

Features

 Most potent alpha adrenergic agonist; effects both beta1 and beta2 receptors
 In small doses, beta 2 effects predominate
 In larger doses, beta 1 effects also occur
 In ever larger doses, stimulation of alpha and beta receptors
 Single shot 2-10 mcg produces transient effect lasting 1-5 minutes
Uses

 Addition to local anesthetics to prolong block duration and decrease systemic absorption
 Major cases (liver transplantation, for example) to rescue hemodynamics
 Anaphylaxis treatment
 ACLS drug for CPR
 Increase myocardial contractility
Side Effects: Hypertension, dysrhythmias, myocardial ischemia

750
10) Anti-cholinesterase

 Law of Mass Action is responsible for displacement of NDNMBs from postsynaptic

receptors in response to an anticholinesterase
 Most commonly used is neostigmine
 MUST be given with an anticholinergic to counteract the muscarinic effects (namely,
bradycardia)
 Edrophonium has a shorter onset of action compared to neostigmine and pyridostigmine.
Muscarinic side effects are less with Edrophonium.
 The onset of Edrophonium and atropine are well matched. Typical dose of atropine
would be 10mcg/kg. Typical dose of Edrophonium is 0.5-1.0 mg/kg
 Pyridostigmine has the longest duration of action (about 90 minutes); rarely used
 Edrophonium has the shortest duration of action (about 5-20 minutes)
 Neostigmine is intermediate, with a duration of about 30-60 minutes
 Enough time must be allowed for the anticholinesterase to antagonize the block,
sometimes 15-30 minutes.
 Neostigmine is dosed 0.04-0.07 mg/kg, and is usually given with glycopyrrolate
(anticholinergic) at 0.01-0.05 mg/kg.
 Physostigmine, 1mg IV slowly, is used to treat central anticholinergic syndrome. It is a
tertiary amine which crosses the BBB
o Symptoms include: fever, blurred vision, photophobia, tachycardia, restlessness
o Scopolamine, in elderly and pediatric patients, can cause restlessness and
confusion
 Neostigmine and pyridostigmine bind covalently to acetylcholinesterase to form an
inactive carbamylated complex, which then is hydrolyzed to form regenerated
acetylcholinesterase. By contrast, Edrophonium binds electrostatically and reversibly
with acetylcholinesterase, accounting for its shorted duration
 Onset of Edrophonium is about <5 minutes, compared to neostigmine (about 5-10 min)
11) Insulin

• After a meal, plasma glucose level rises stimulating an increase of plasma insulin
secretion to promote glucose utilization (brain, GI tract, RBC’s). Hyperglycemia
producing hormones (glucagon, epinephrine, growth hormone, and cortisol) comprise
other half of regulatory system for balance of blood sugar.
• Diabetes Mellitus results from inadequate supply or response to insulin which leads to
elevated glucose levels causing microvascular and macrovascular complications
• Produced by beta cells in pancreatic islets
• Basal insulin - (wt in kg x 0.3) /24 hrs = hourly insulin requirement
o intermediates – NPH,lente, lispro, aspart) – twice daily
o long-acting (ultra-lente, glargine) – once daily
o Short-acting (regular) or rapid acting (lispro, aspart)

751
 • Insulinoma
o Rare benign insulin secreting pancreatic islet cell tumors; may be part of Multiple
Endocrine Neoplasia syndrome type I (Insulinoma, hyperparathyroidism, pituitary
tumor)
o Whipple’s triad – hypoglycemic symptoms with fasting, glucose level < 50
mg/dL with symptoms, relief of symptoms by administration of glucose
o Preop management – Diazoxide (inhibits insulin release from beta cells)
o Surgical treatment – curative (may be hypoglycemic during tumor manipulation
but hyperglycemic afterwards)
12) Dopamine

 Endogenous catecholamine that is an immediate precursor of norepinephrine

 Nonspecific agonist at both dopamine 1 and dopamine 2 receptors, and alpha and beta
receptors
 Dopamine 1 receptors are located postsynaptically and cause vasodilation when
stimulated. These are located in the kidney, brain, heart and mesentery. Mediated by
adenylate cyclase.
 Dopamine 2 receptors are located presynaptically and inhibit adenylate cyclase and
release of norepinephrine. Nausea and vomiting are also possibly induced via these
receptors.
 Lower dose stimulates dopamine 1 receptors in the kidney
 Moderate dose stimulates dopamine and beta 1 receptors in the heart
 High dose stimulates dopamine, beta 1, and alpha receptors in the peripheral vasculature
 Unique in being able to simultaneously increase contractility, renal blood flow, GFR,
excretion of Na and urine output
 “Renal-dose” dopamine is a fallacy in terms of preventing ATN
 Increases CO via beta 1 stimulation. Increased CO is also due to stimulation of
norepinephrine release. This is an indirect action.
 Used in combination with dobutamine as infusion for failing hearts
 Dysrhythmias possible
 Must be given as an infusion to achieve and maintain therapeutic plasma concentrations

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13) Preop meds

14) Cranial nerves

Sensory,
Number Name Motor, Origin Nuclei Function
or Both

Transmits the sense of

smell from the nasal
Anterior
Purely cavity.[1] Located in
I Olfactory Telencephalon olfactory
Sensory olfactory foramina in
nucleus
the cribriform plate of
ethmoid.

Transmits visual
signals from the retina
Purely Ganglion cells
II Optic Diencephalon of the eye to the
Sensory of retina[2]
brain.[3] Located in the
optic canal.

Innervates the levator

palpebrae superioris,
superior rectus, medial
rectus, inferior rectus,
and inferior oblique,
Oculomotor
which collectively
nucleus,
Mainly Anterior aspect perform most eye
III Oculomotor Edinger-
Motor of midbrain movements. Also
Westphal
innervates the
nucleus
sphincter pupillae and
the muscles of the
cilliary body. Located
in the superior orbital
fissure.

Innervates the
superior oblique
Mainly Dorsal aspect of Trochlear muscle, which
IV Trochlear
Motor midbrain nucleus depresses, rotates
laterally, and intorts
the eyeball. Located in

753
 the superior orbital
fissure.

Receives sensation
Principal from the face and
sensory innervates the muscles
trigeminal of mastication.
nucleus, Spinal Located in the
Both
trigeminal superior orbital fissure
Sensory
V Trigeminal Pons nucleus, (ophthalmic nerve -
and
Mesencephalic V1), foramen
Motor
trigeminal rotundum (maxillary
nucleus, nerve - V2), and
Trigeminal foramen ovale
motor nucleus (mandibular nerve -
V3).

Innervates the lateral

rectus, which abducts
Mainly Anterior margin Abducens
VI Abducens the eye. Located in the
Motor of pons nucleus
superior orbital
fissure.

Provides motor
innervation to the
muscles of facial
expression, posterior
belly of the digastric
muscle, and stapedius
muscle. Also receives
the special sense of
Facial nucleus,
taste from the anterior
Both Pons Solitary
2/3 of the tongue and
Sensory (cerebellopontine nucleus,
VII Facial provides secretomotor
and angle) above Superior
innervation to the
Motor olive salivary
salivary glands
nucleus
(except parotid) and
the lacrimal gland.
Located in and runs
through the internal
acoustic canal to the
facial canal and exits
at the stylomastoid
foramen.

754
 Senses sound,
rotation, and gravity
(essential for balance
and movement). More
Acoustic or specifically, the
Lateral to CN
Vestibulocochlear Vestibular vestibular branch
Mostly VII
VIII (or auditory- nuclei, carries impulses for
sensory (cerebellopontine
vestibular nerve Cochlear nuclei equilibrium and the
angle)
or acoustic nerve) cochlear branch
carries impulses for
hearing. Located in
the internal acoustic
canal.

Receives taste from

the posterior 1/3 of the
tongue, provides
secretomotor
Nucleus
innervation to the
ambiguus,
Both parotid gland, and
Inferior
Sensory provides motor
IX Glossopharyngeal Medulla salivary
and innervation to the
nucleus,
Motor stylopharyngeus.
Solitary
Some sensation is also
nucleus
relayed to the brain
from the palatine
tonsils. Located in the
jugular foramen.

Supplies
branchiomotor
innervation to most
laryngeal and
pharyngeal muscles
Nucleus (except the
Both ambiguus, stylopharyngeus,
Sensory Posterolateral Dorsal motor which is innervated by
X Vagus
and sulcus of medulla vagal nucleus, the glossopharyngeal).
Motor Solitary Also provides
nucleus parasympathetic fibers
to nearly all thoracic
and abdominal viscera
down to the splenic
flexure. Receives the
special sense of taste
from the epiglottis. A

755
 major function:
controls muscles for
voice and resonance
and the soft palate.
Symptoms of damage:
dysphagia
(swallowing
problems),
velopharyngeal
insufficiency. Located
in the jugular
foramen.

Controls the
sternocleidomastoid
and trapezius muscles,
Nucleus and overlaps with
Accessory (or
ambiguus, functions of the vagus
cranial accessory Mainly Cranial and
XI Spinal nerve (CN X).
nerve or spinal Motor Spinal Roots
accessory Symptoms of damage:
accessory nerve)
nucleus inability to shrug,
weak head movement.
Located in the jugular
foramen.

Provides motor
innervation to the
muscles of the tongue
(except for the
palatoglossus, which
is innervated by the
Mainly Hypoglossal vagus nerve) and other
XII Hypoglossal Medulla
Motor nucleus glossal muscles.
Important for
swallowing (bolus
formation) and speech
articulation. Located
in the hypoglossal
canal.

756
15) Porphyria
Porphyria is a term that refers to a group of disorders—the Porphyrias—that affect the nervous
system or skin, or both. Each type of porphyria is due to the deficiency of one of the enzymes
needed to make a substance in the body called heme. Enzymes are proteins that help chemical
reactions happen in the body. Making heme involves a series of eight different enzymes, each
acting in turn.
Heme is a red pigment composed of iron linked to a chemical called protoporphyrin. Heme has
important functions in the body. The largest amounts of heme are in the blood and bone marrow
in the form of hemoglobin within red blood cells. Hemoglobin gives blood its red color and
carries oxygen from the lungs to all parts of the body. In the liver, heme is a component of
proteins that have many functions, including breaking down hormones, drugs, and other
chemicals and generating high-energy compounds that keep liver cells alive and functioning
normally.
The body makes heme mainly in the bone marrow and the liver. The process of making heme is
called the heme biosynthetic pathway. Each step of the process is controlled by one of eight
enzymes. If any one of the enzymes is deficient, the process is disrupted. As a result, porphyrins
or its precursors—chemicals formed at earlier steps of the process—may build up in body tissues
and cause illness.
Most Porphyrias are inherited disorders, meaning they are caused by abnormalities in genes
passed from parents to children. Scientists have identified the genes for all eight enzymes in the
heme pathway. Some forms of porphyria result from inheriting an abnormal gene from one
parent. Other forms are due to inheriting two abnormal genes—one from each parent. The risk
that members of an affected family will have the disease or transmit it to their children depends
on the type of porphyria.
One type of porphyria—porphyria cutanea tarda—is most often an acquired disorder. It occurs
when factors other than genes cause an enzyme deficiency in the liver.
Porphyria can be triggered by

 •drugs such as barbiturates, tranquilizers, birth control pills, and sedatives

 •chemicals
 •fasting
 •smoking
 •drinking alcohol, especially heavy drinking
 •infections
 •excess iron in the body
 •emotional and physical stress
 •menstrual hormones
 •exposure to the sun

757
People with cutaneous forms of porphyria develop blisters, itching, and swelling of their skin
when it is exposed to sunlight. Symptoms of acute forms of porphyria include pain in the
abdomen, chest, limbs, or back; numbness, tingling, paralysis, or cramping; vomiting;
constipation; and personality changes or mental disorders. Acute attacks of porphyria can
develop over hours or days and last for days or weeks
16) CSF

 CSF produced by ultrafiltration and secretion by the cells of the choroid plexus and the
passage of water, electrolytes and other substances across the BBB at a constant rate of
500-600 ml/day in adults
 CSF contained within the ventricular system of the brain, the central canal of the spinal
cord and the subarachnoid space, extracellular compartment of the CNS
 CSF absorbed from microscopic arachnoid villi and macroscopic arachnoid granulations
within the dura mater and bordering venous sinusoids and sinuses
 Volume of CSF may be ↓ by diuretic Acetazolamide (Diamox)
17) Nerve injury

18) Ketorolac – COX 1 inhibitor (COX 1 always present while COX2 is modulated into
production)

 Very effective analgesic, anti-inflammatory, and antipyretic actions

 Available IM/IV doses are 15, 30 and 60 mg doses
 30 mg of Ketorolac = 10 mg Morphine=100 mg Meperidine
 After IM injection, peak plasma concentrations in 45-60 minutes
 Half-life of about 6 hours
 Decrease the dose in elderly patients
 Not recommended for preop>inhibits platelet aggregation and may prolong bleeding time
 Contraindications: bronchospasm, angioedema, nasal polyps, concurrent use of other
NSAIDs, known allergy or intolerance to aspirin, history of GI bleeding, renal
dysfunction, volume-depleted patients (reduces osteogenesis – not for ortho cases)
 Nice for certain surgeries, provided there are no contraindications as above: gynecologic
surgery (D and C), inguinal hernia repair, breast surgery (biopsy)

758
19) Lactic acidosis

 Lactic acidosis is when lactic acid builds ups in the bloodstream faster than it can be
removed. Lactic acid is produced when oxygen levels in the body drop.
 Causes: intense exercise, AIDS, Cancer, Kidney failure, Respiratory failure, Sepsis,
hypovolemia
o Metformin, a common medicine used to treat diabetes, can also cause lactic
acidosis
 Symptoms – nausea and weakness
20) Laryngeal muscle

 Superior Laryngeal Nerve – originates lateral to the cornu of the hyoid bone
o Interior Branch of SLN – sensory for base of tongue, epiglottis, aryepiglottic
folds, arytenoids
o External Branch of SLN – cricothyroid muscle
 Recurrent Laryngeal Nerve
o Sensory – vocal folds, trachea
o Motor – larynx

759
21) Glucocorticoid
o Adrenal Gland – 2 compartments
o Adrenal cortex
 Glucocorticoids – Zona Fasciculata
 Mineralcorticoids (aldosterone) – Zona Glomerulosa
 Androgens (sex hormones) – Zona reticularis
o Adrenal medulla – synthesis of catecholamines
o Glucocorticoids → Cortisol → Effect is Glucose homeostasis and many others
o synthesized from cholesterol through a series of enzyme-mediated
transformations
In contrast to loss of mineralocorticoids, failure to produce glucocorticoids is not acutely life-
threatening. Nevertheless, loss or profound diminishment of glucocorticoid secretion leads to a
state of deranged metabolism and an inability to deal with stressors which, if untreated, is fatal.
In addition to their physiologic importance, glucocorticoids are also among the most frequently
used drugs, and often prescribed for their anti-inflammatory and immunosuppressive properties
The vast majority of glucocorticoid activity in most mammals is from cortisol, also known as
hydrocortisone.
Cortisol binds to the glucocorticoid receptor in the cytoplasm and the hormone-receptor complex
is then translocated into the nucleus, where it binds to its DNA response element and modulates
transcription from a battery of genes, leading to changes in the cell's phenotype.
Only about 10% of circulating cortisol is free. The remaining majority circulates bound to
plasma proteins, particularly corticosteroid-binding globulin (transcortin). This protein binding
likely decreases the metabolic clearance rate of glucocorticoids and, because the bound steroid is
not biologically active, tends to act as a buffer and blunt wild fluctuations in cortisol
concentration.
Effects on Metabolism

 The name glucocorticoid derives from early observations that these hormones were
involved in glucose metabolism. In the fasted state, cortisol stimulates several processes
that collectively serve to increase and maintain normal concentrations of glucose in
blood. These effects include:
 Stimulation of gluconeogenesis, particularly in the liver: This pathway results in the
synthesis of glucose from non-hexose substrates such as amino acids and lipids and is
particularly important in carnivores and certain herbivores. Enhancing the expression of
enzymes involved in gluconeogenesis is probably the best known metabolic function of
glucocorticoids.

760
 Mobilization of amino acids from extrahepatic tissues: These serve as substrates for
gluconeogenesis.
 Inhibition of glucose uptake in muscle and adipose tissue: A mechanism to conserve
glucose.
 Stimulation of fat breakdown in adipose tissue: The fatty acids released by lipolysis are
used for production of energy in tissues like muscle, and the released glycerol provide
another substrate for gluconeogenesis.
 Effects on Inflammation and Immune Function
o Glucocorticoids have potent anti-inflammatory and immunosuppressive
properties. This is particularly evident when they administered at pharmacologic
doses, but also is important in normal immune responses. As a consequence,
glucocorticoids are widely used as drugs to treat inflammatory conditions such as
arthritis or dermatitis, and as adjunction therapy for conditions such as
autoimmune diseases.
 Glucocorticoids have multiple effects on fetal development. An important example is
their role in promoting maturation of the lung and production of the surfactant necessary
for extrauterine lung function. Mice with homozygous disruptions in the corticotropin-
releasing hormone gene (see below) die at birth due to pulmonary immaturity.
 Several aspects of cognitive function are known to both stimulate glucocorticoid
secretion and be influenced by glucocorticoids. Fear provides an interesting example of
this. Fear-inducing stimuli lead to secretion of glucocorticoids from the adrenal gland,
and treatment of phobic individuals with glucocorticoids prior to a fear-inducing stimulus
can blunt the fear response.
 Excessive glucocorticoid levels resulting from administration as a drug or
hyperadrenocorticism have effects on many systems. Some examples include inhibition
of bone formation, suppression of calcium absorption and delayed wound healing.

761
The most prevalent disorder involving glucocorticoids in man and animals is
hyperadrenocorticism or Cushing’s disease. Excessive levels of glucocorticoids are seen in
two situations:
1. Excessive endogenous production of cortisol, which can result from a primary adrenal
defect (ACTH-independent) or from excessive secretion of ACTH (ACTH-dependent).
2. Administration of glucocorticoids for therapeutic purposes. This is a common side-effect
of these widely-used drugs.
Cushing's disease has widespread effects on metabolism and organ function, which is not
surprising considering the ubiquitous distribution of glucocorticoid receptors. A diverse set
of clinical manifestations accompany this disorder, including hypertension, apparent obesity,
muscle wasting, thin skin, and metabolic aberrations such as diabetes.
Insufficient production of cortisol, often accompanied by an aldosterone deficiency, is called
hypoadrenocorticism or Addison's disease. Most commonly, this disease is a result of
infectious disease (e.g. tuberculosis in humans) or autoimmune destruction of the adrenal
cortex. As with Cushing's disease, numerous diverse clinical signs accompany Addison's
disease, including cardiovascular disease, lethargy, diarrhea, and weakness. Aldosterone
deficiency can be acutely life threatening due to disorders of electrolyte balance and cardiac
function.

762
22) Cardiac tamponade

 Two Important physical signs:

o Kussmaul’s’ sign – distention of the jugular veins during inspiration
o Pulses Paradoxes – a pulse simultaneously slight and irregular, disappearing
during inspiration and returning on expiration
 Or a decrease in SBP of more than 10 mmHg on inspiration
 Observed in 75% of patients with acute cardiac tamponade
 Represents dyssynchrony or opposing responses of the right and left
ventricles to filling during the respiratory cycle
 Beck’s Triad – observed in 1/3 of patients with acute tamponade
o Distant heart sounds
o Increased jugular venous pressure
o Hypotension
 CVP almost always increased due to SNS activation in an attempt to maintain CO and BP
with tachycardia and peripheral vasoconstriction
 Echocardiogram – finding of early diastolic inward wall motion of the RA or RV
reflecting similar intracavitary and intrapericardial pressure
 Treatment:
o Mild – conservative
 Maintain SV –
 expand intravascular volume,
 administer catecholamines (Isoproterenol) to increase myocardial
contractility
o Atropine – treat bradycardia from vagal response of
increased intrapericardial pressure
o Dopamine infusion – increase SVR
 correct metabolic acidosis
o results from low CO, should be treated to correct
myocardial depression seen with severe acidosis and
improve the inotropic effects of catecholamines
o If CVP increased (then fluid must be removed by pericardiocentesis or surgical
techniques – subxiphoid pericardiostomy, thoracoscopic pericardiostomy,
thoracotomy with pericardiostomy)
o Anesthetic Management

763
  GETA and positive pressure ventilation with significant tamponade =
severe, life threatening hypotension (peripheral vasodilation, direct
myocardial depression, decreased venous return)
 Local anesthetic for pericardiocentesis
 Induction and maintenance with ketamine or benzodiazepine in combo
with N2O, pancuronium effects beneficial
 Monitors – A-line and CVP
23) Cyanide toxicity
Seen with prolonged and/or high dose infusions of Sodium Nipride

 Can occur with infusion rates > 2 mcg/kg/min

 Can occur when sulfur donors and methemoglobin are exhausted (accumulation of
cyanide radicals)
 Free cyanide radicals bind to cytochrome oxidase and prevent oxidative phosphorylation
(life-sustaining process)
 Increased cyanide concentrations may precipitate tissue anoxia, anaerobic metabolism,
and lactic acidosis
When to suspect cyanide toxicity

 Resistance to the hypotensive effects of the drug at maximum infusion rates (10
mcg/kg/min)
 Or Tachyphylaxis (most commonly children)
 Mixed Venous PO2 is increased in cyanide toxicity, reflecting inability of tissues to
utilize O2
 Metabolic acidosis
 CNS-mental status changes & seizures in awake patients
 Toxic blood level > 40 micromoles
Treatment of cyanide toxicity

 Stop infusion
 100% oxygen
 NaHCO3 to correct metabolic acidosis
 Sodium thiosulfate at 150 mg/kg IV over 15 minutes (sulfur donor to convert cyanide to
thiocyanate)
 If severe, sodium nitrate at 5mg/kg IV slowly (converts hemoglobin to methemoglobin,
which converts cyanide to cyanmethemoglobin)
 Hydroxycobalamin (Vitamin B12) binds cyanide to form cyanocobalamin (expensive,
reddish skin discoloration)

764
 Basic Board Prep!
CO2 absorbers

Rebreathing alveolar gas conserves heat and humidity. Soda lime contains hydroxide salts
capable of neutralizing carbonic acid (CO2 + H2O). Reaction end product = heat, water and
calcium carbonate. Capable of absorbing 23 liters of CO2 per 100 grams absorbent.

CO2 + H2O = H2CO3

H2CO3 + 2 NaOH -> Na2CO3 + 2H2O + heat
Na2CO3 + Ca (OH) 2 -> CaCO3 + 2NaOH

pH indicator – ethyl violet (changes at a critical pH of 10.3)

The dryer the soda lime, the more likely it will absorb and degrade volatile anesthetics.
Desflurane can be broken down to carbon monoxide by dry barium hydroxide.
Absorb = less degradation of volatile anesthetic
2 canisters stacked = less resistance and more complete absorption.
Signs of exhausted absorber – increase ETCO2 and not getting back to base line, respiratory
acidosis, hyperventilation, increased sympathetic outflow, bleeding increased, color of indicator.
Later would see increase then a decrease in heart rate, dysrhythmias.

765
Breathing circuits

Most commonly used in anesthesia is the circle system, Bain system, a coaxial modification of
the Mapleson D, is occasionally used.
With the Mapleson systems, remember (All Do Continuous Breathing) for spontaneous breathing
and (Dead Babies Can’t Assist) for Controlled Ventilation.
Circle system can be semi-open, semi-closed or closed.
Semi-open – enough FGF to prevent rebreathing of CO2.
Semi-closed – some rebreathing of gasses (FGF < Ve)
Closed – oxygen flow matches MVO2
Circle system 7 primary components
1)fresh gas source 2) unidirectional valves 3) inspiratory and expiratory corrugated tubes 4) a
Y-piece connector 5) APL valve 6) reservoir bag 7) CO2 absorbent
Most efficient if unidirectional valves are near patient and APL valve just downstream of
expiratory valve.
If expiratory valve sticks – barotrauma can result.

766
Monitoring (EKG, CVP, A-line)

EKG standard monitoring – leads II and V5. (5th intercostal space at anterior axillary line)

CVP – a wave = atrial contraction, c wave = begin systole and tricuspid closure,
X descent = RV systole and emptying resulting in “sucking” of tricuspid valve down and
negative pressure. V wave = passive filling of right atrium. Y descent = tricuspid opening and
passive filling of right ventricle. A, C, X, V, Y.

Arterial monitoring – as move further from heart, systolic pressure increases and diastolic
decreases with MAP staying relatively the same. Dicrotic notch = closure of aortic valve. Over
dampened = underestimate SBP, Under dampened = overestimate SBP
Zero to atmosphere, level at phlebostatic axis.

767
OSHA acceptable limits for contaminants

OSHA directs that no worker be exposed to no more than 2 ppm halogenated agents (or 0.5 ppm
if used with nitrous oxide). And no more than 25 ppm nitrous oxide, based on time-weighted 8
hour average concentration.

Ventilators

Most likely locations of a breathing circuit leak – right angle connector and ETT. (Frank
disconnection). Leaks most commonly at base plate of CO2 absorber. Leak may be around
uncuffed tracheal tube.
Inspiratory phase and expiratory phase
Double circuit system – tidal volume delivered from a bellows assembly. Standing “ascending”
bellows or hanging “descending” bellows (descending rarely used due to the fact that they will
continue to fill by gravity in the event of a disconnect). Fresh gas fills the bellows and the plastic
canister which then drives the gas into the circuit.
If oxygen is being used to pneumatically drive the bellows, it will be consumed at a rate of at
least the minute volume. (If Ve = 6L/min and FGF = 2L/min, total used is 8L/min)
A leak in the bellows can transmit high pressures to patient and barotrauma. (If oxygen is driving
gas would also see a sharp increase in FiO2.
Also will see increase in tidal volume with increase in FGF compared to what is set.
FGF * I: E ratio (I percentage is 33% in 1:2) / breaths per minute.
Peak airway pressure = highest pressure achieved during PPV
Plateau pressure = pressure measured during an inspiratory pause and mirrors static compliance.
Piston systems “decouple” with the FGF delivering a more exact tidal volume.
When O2 flush valve is depressed, APL valve is excluded and 600-1200 ml/sec are delivered,
recipe for barotrauma.

768
Metabolic alkalosis

Metabolic Alkalosis occurs when fixed acid loss is increased or when the intake of bases is
abnormally high. Can be caused by vomiting or diuretic administration. Above normal increases
in bicarbonate level when the PCO2 is maintained at approximately 40 mmHg is termed
uncompensated metabolic alkalosis. The combination of resp and meta is termed mixed. With
hypoventilation and normal pH is termed compensated metabolic alkalosis.
Causes a left shift in the oxyhemoglobin dissociation curve and may lead to tissue hypoxemia.

Methemoglobin

Methemoglobin results when the iron in heme is oxidized to its trivalent form and FE3+ is
formed. Cannot unload oxygen, causes a left shift of the hemoglobin dissociation curve.
Reduction to normal hemoglobin by methylene blue or ascorbic acid.
In pulse oximetry, methemoglobin absorbs both red and infrared light equally resulting in a
reading of 85%. Thus, causing a false low (or high) reading.
Metabolites of prilocaine (o-toluidine) after large doses (>8-10mg/kg) can cause
methemoglobinemia. Benzocaine, a common ingredient in local anesthetic sprays can also cause
methemoglobinemia.

Line isolation monitor

To reduce the chance of two coexisting faults, a line isolation monitor measures the potential for
current flow from the isolated power supply to the ground. Basically, it determines the degree of
isolation between the two power wires and the ground and predicts the amount of current that
could flow if a second short circuit were to develop. Alarm will develop at around 2 mA. No
ground fault interrupter in the OR. It warns of the existence of a single fault.

769
Micro shock

100 uA – ventricular fibrillation

10 uA – Recommended maximum for 60 Hz leakage current
Small amounts of current (via a CVC of Swan) may result in lethal arrhythmias.
1 mA is perception – therefore a patient can be “electrocuted” with 1/10th the current of
perception.

O2 analyzer

Three types of oxygen analyzers are available: polarographic (Clark electrode), galvanic (fuel
cell) and paramagnetic. The first two utilize electrochemical sensors that contain cathode and
anode electrodes. As oxygen reacts with the electrodes, a current is generated that is proportional
to the oxygen partial pressure. Paramagnetic are more expensive, but have no consumable parts
and are self-calibrating. Should be placed on the inspiratory or expiratory limb, but NOT in the
FGF line.

770
Lung volumes

Volumes are alone, capacities are sums of more and 1 volume.

IRV – 3000 Inspiratory capacity – IRV + TV

TV – 500 Vital capacity – IRV + TV + ERV
ERV – 1200 FRC – ERV + RV
RV – 1200 TLC – IRV + TV + ERV + RV

771
SVO2, O2 content, dissociation curve

Oxygen carrying capacity = (hgb * 1.37 * SpO2) + (PaO2 * 0.003)

SVO2 – saturation of oxygen in the pulmonary artery, lower than ScVO2 due to deoxygenated
blood from the heart (remember heart extracts 70 % of O2 and empties back into right atrium).
Gives an idea of oxygen delivery to body.
Dissociation curve (Hgb)
Left shift – methemoglobin, cyanide toxicity, hypothermia, decreased 2, 3 DPG, fetal
hemoglobin, alkalosis, decrease pCO2
Right shift – acidosis, hyperthermia, increased 2, 3 DPG, increase pCO2

Gas laws

1) Charles Law: at a constant pressure, temperature and volume are directly related. If a
compressed gas gets hot, volume will want to increase.

2) Boyle’s Law: At a constant temperature, pressure and volume are INVERSELY related.

3) Gay Lussac’s Law: At a constant volume, temperature and pressure are directly related.

Remember “Can These Guys Possibly Be Virgins” in a triangle…. We deal with compressed
gasses on a daily basis, knowing how these substances will behave is necessary to our
profession.

4) Universal Gas Law: PV = nRT were P = pressure, V = volume, n = moles of gas, T =

temperature and R is the gas constant. Essentially a combination of the 1st 3 laws.

772
5) Dalton’s : In chemistry and physics, Dalton's law (also called Dalton's law of partial
pressures) states that the total pressure exerted by the mixture of non-reactive gases is equal to
the sum of the partial pressures of individual gases. This empirical law was observed by John
Dalton in 1801 and is related to the ideal gas laws. This is applied when we look at percentage of
gasses or vapors in our anesthetic delivery and allows us to know what partial pressure is being
exerted.
6) Henry: Henry’s law states that at a constant temperature, the amount of a given gas dissolved
in a given liquid is directly proportional to the partial pressure of the gas in contact with the
liquid. According to Henry’s law the partial pressure of anesthetic agent dissolved in the blood is
proportional to the partial pressure exerted by the anesthetic vapor in the alveoli.
7) Graham: The rate of diffusion of gases is inversely proportional to the square roots of their
densities, or molecular weights. As anesthetists, we are concerned about how quickly our agents
will diffuse across the alveolar membrane. Put simply, this states the smaller the molecule, the
faster it will diffuse down its concentration gradient.
Bernoulli – The Bernoulli principle states that as the speed of a fluid (or air) increases, the
pressure exerted by the fluid decreases. This phenomenon is called the Bernoulli Effect (the
Bernoulli Effect provides the lift for airplanes).

Ohm’s law

E = I * R (or V = A*O)
E = electromotive force (measured in volts)
I = current (measured in Amperes)
R = resistance (measured in ohms

Ohm’s law forms the basis for the physiological equation BP = CO * SVR
Also, W = E * I (wattage = volts * amps)

773
Scavenging system

These dispose of waste gases that have been vented from the breathing circuit by the APL valve.
Adjust float to between lines, this will allow for ~ 10-15 L/min of waste gas to be evacuated.

Laminar vs. turbulent flow

Reynolds number = velocity * density * diameter of tube / viscosity

Reynolds number < 2000 is laminar, 2000-3000 is transitional, and > 3000 is turbulent.
Equation for resistance is Poiselle’s inverted without change in pressure.

8ln / pi * r ^ 4

Laminar flow through a tube exists as concentric circles flowing over each other.
Viscosity is the only physical gas property relevant under conditions of laminar flow.
Helium will not improve flow if flow is already laminar

High flow rates, especially through branched or irregularly shaped tubes, disrupt the orderly flow
of laminar gas. When resistance to gas flow is significant, turbulent flow occurs and is usually
audible. Four conditions that will change laminar flow to turbulent:
1) high flow rates
2) sharp angles within the tube
3) branching in the tube
4) decrease in tubes radius

774
Volatile agents (Fa/Fi), MAC

FA = alveolar concentration – increase with increasing Ve (minute volume)

Fi = inspired anesthetic – increase by increasing FGF (fresh gas flow)
FA/Fi ratio: The faster FA rises relative to Fi, the faster the speed of induction since FA is
proportional to partial pressure in CNS.
The smaller the partition coefficient, the faster the onset (nitrous is fastest, does not follow rule)
N20: MAC 104%, PC 0.47
Desflurane: MAC 6%, PC 0.42 vapor pressure 660 (boils at 23 degrees Celsius) TEC 6 vaporizer
operates at 2 atm and 39 degrees Celsius. Has to be calibrated at what elevation it will be used
at. Example: if calibrated at sea level and used in the mountains, it will deliver an overdose.
Sevoflurane: MAC 2%, PC 0.69, vapor pressure 160
Isoflurane: MAC 1%, PC 1.46, vapor pressure 238,

Remember MAC is an ED 50, and 1.3 MAC is ED 95.

Anaphylaxis
Is an exaggerated response to an allergen that is mediated by a type I hypersensitivity reaction.
The syndrome appears within minutes following exposure to a specific antigen. Antibiotics are
the most common cause of anaphylaxis, but latex is on the rise. Most important factors are
histamine, leukotrienes, BK-A and platelet activating factor. They increase vascular
permeability and contract (bronchial H1) smooth muscle. H2 activation causes venodilation,
enhanced mucous secretion, tachycardia and increased contractility. BK-A cleaves bradykinin
from kininogen; bradykinin increases vascular permeability. Leukotrienes may preferentially
effect smaller airways.
Anaphylactoid reactions resemble anaphylaxis, but are not IgE mediated.

Primary treatment: maintain airway and administer 100% oxygen, D/C all anesthetic drugs,
provide volume expansion, administer epinephrine.
Secondary treatment: Treat with H1, H2 blockers, epinephrine, bronchodilators, corticosteroids,
bicarbonate. Cromolyn sodium prevents mast cell histamine degranulation.

775
Critical temperature

The temperature above which a substance cannot be liquefied no matter how much pressure is
applied to it. At critical temperature, critical pressure = vapor pressure.
Because the critical temperature of N2O is above room temperature, it can be kept liquefied
without an elaborate refrigeration system.

Vapor pressure

Vapor pressure is the pressure exerted by a vapor when it is in equilibrium with its associated
liquid. In anesthesia the term saturated vapor pressure (SVP) is also frequently used, although the
term ‘saturation’ incorrectly implies that vapor is ‘dissolved’ in the atmosphere.

Malignant hyperthermia

Sudden increase in ETCO2, exhausted absorber, masseter muscle rigidity, tachycardia, acidosis,
rhabdomyolysis.
Offending agents are volatile anesthetics or suxx, Genetic defect in RYR ryanodine receptor,
allows for mass exodus of calcium for sarcoplasmic reticulum and decrease in reuptake. Results
in hyper metabolic state (hence the sudden increase in ETCO2)
1) Discontinue agent, call for help
2) Hyperventilate with 100% oxygen, don’t waste time changing anesthesia machine, can use
inline filters if available.
3) Dantrolene 2.5 mg/kg (20 mg vials in 50 ml bacteriostatic sterile water). Poorly soluble,
helps if H2O is 41 degrees Celsius.
4) Manage BP, heart rate and temperature (no calcium channel blockers)
5) Cool patient however possible.

776
ASA classification

ASA class 1: no organic, physiologic, biochemical, or psychiatric disturbance.

ASA class 2: Mild to moderate systemic disturbances that may not be related to the reason for
surgery.
ASA class 3: Severe systemic disturbance that may or may not be related to the reason for
surgery.
ASA class 4: Sever systemic disturbance that is life threatening with or without surgery.
ASA class 5: Moribund patient who has little chance for survival but is submitted to surgery as a
last resort (resuscitative effort)
ASA class 6: organ donor
Emergency: an E is added for any patient whom the operation is an emergency.

777
Airway assessment

I) soft palate, fauces, uvula, pillars

II) Soft palate, fauces, uvula
III) Soft palate, uvular base
IV) Hard palate only

Assess thyromental distance (greater than 6 cm (3 normal finger breadths)

Neck range of motion
Upper lip bite test (prognathia)
Look at patient from side (micrognathia)
Interincisor gap (if prominent upper incisors, may be less than 3 cm)
Thick or short neck
May have difficulty with narrow high arched hard palate.
Overbite

778
Post intubation croup

Post intubation croup caused by glottis, laryngeal or tracheal edema is particularly serious in
children. The efficacy of corticosteroids in preventing postextubation airway edema remains
controversial. In pediatrics, the cricoid cartilage is the most susceptible area because it is the
narrowest. Uncuffed tube helps and gas leak at 20 cmH2O helps. Risks include repeated
instrumentation, large tube, prolonged surgery, head and neck procedures and tube manipulation.
Treat with Decadron and nebulized racemic epinephrine. Usually appears within 3 hours of
extubation.
Cricoid pressure

Use for any full stomach or emergency situation. Use of the thumb and fore finger, apply force
until the fingers blanch. BURP (backward, upward, rightward pressure) since the esophagus is to
the right of the trachea in approximately 75% of patients should occlude the upper esophagus to
prevent aspiration of gastric contents during laryngoscopy and intubation. Recommended
pressure before loss of consciousness in 20 Newtons (or 2 kg) of pressure. On loss of
consciousness, the pressure must be increased to 44 Newtons (or 4 kg) of pressure.
Warning, this may mimic the pressure of a bolus of food and decrease LES tone by 9-12 mmHg.
Assistant may not release cricoid pressure until instructed by anesthetist. ETT must be secured
and placement confirmed.

Laryngospasm

Forceful, involuntary spasm of the laryngeal musculature occurs through sensory stimulation of
the superior laryngeal nerve and afferent responses from the recurrent laryngeal nerve.
Laryngospasm can be caused by either secretions or stimulation of the larynx while the patient is
in a light plane of anesthesia. In the awakening patient, it can be lessened by extubation when the
patient is either in a deeper plane of anesthesia or fully awake. Extubate during exhalation.

2 phases of laryngospasm – a “shutter” phase with partial obstruction (adduction of the vocal
cords), then a “ball valve” phase with full obstruction (constriction of false cords and
supraglottic tissue). Treatment of “shutter” spasm includes gentle PPV with 100% oxygen (20
cm H2O) don’t force air into esophagus. If condition persists, administer lidocaine or 0.1 mg/kg
suxx. Treatment of a full or “ball valve” obstruction requires an intubating dose of suxx.

779
LMA

Laryngeal Mask Airway or “Let Me Aspirate”. Inserted blindly into posterior pharynx until
resistance is met. Inflate until no leak at 20 cm H2O. If cuff is overinflated it can actually open
the upper esophageal sphincter. Pressure on posterior wall of pharynx can result in the epiglottis
closing the glottic opening. In the airway algorithm, attempt LMA prior to Cricothyroidotomy.
ProSeal LMA has a second port that allows for passage of a gastric tube. ProSeal allows for
pressures up to 30 PSI and can be used with a ventilator.

780
PA waveform

LBBB relative contraindication. Pulmonary artery pressures should be continuously monitored

for wedge position as this can infarct tissue. Note the increase in diastolic pressure as the tell-tale
that the catheter tip has exited the right ventricle and entered to pulmonary artery. Remember
how to tell which pulmonary artery, right or left, the catheter is in? West zones of the lung. . . .
Hint.

781
Hemodynamic calculations

MAP = DBP + 1/3 pulse pressure

Coronary perfusion pressure = DBP – LVEDP
Cerebral perfusion pressure = MAP – ICP
CO = HR * SV (stroke volume consists of preload, afterload and contractility)
CI = CO/BSA
SVR = (MAP – CVP)*80/CO
SV = CO * 1000 / HR

Frank-Starling’s curve

782
The most important determinant of right ventricular preload is venous return. In the absence of
significant pulmonary or right ventricular dysfunction, venous return is also the major
determinant of left ventricular preload. Ventricular filling becomes impaired at high rates and
time spent in diastole becomes proportionally greater. Atrial fibrillation can decrease ventricular
filling by 20 – 30 %.

783
Capnogram below appears to be obstructive

Determination of ETCO2 concentration to confirm adequate ventilation is useful during all

anesthetic procedures, but particularly so for general anesthesia. A rapid fall of ETCO2 is a
sensitive indicator of air embolism. There are no contraindications. Infrared light is the
mechanism used to measure content of CO2. What is the first indicator of malignant
hyperthermia???

784
Positioning

Ulnar nerve injury is the most common. It is susceptible to compression between the medial
epicondyle of the humerus and the olecranon. A retinaculum is the roof of this structure where it
can compress the ulnar nerve. Pad the elbow.

Brachial plexus stretching is possible if arms are abducted greater than 90 degrees, this can
stretch the plexus around the humeral head. This can happen in any position. Also, shoulder
straps and steep Trendelenburg can stretch the plexus.

Postoperative visual loss – as a result of decreased perfusion and increased intraocular pressure.
Prone position.

Lithotomy- the common fibular (peroneal) nerve is susceptible to compression due to its
superficial course and fixation against the fibular head posteriorly and inferiorly. Elevate both
legs at same time (can cause postoperative back and hip pain). Acute abduction and external
rotation of the hips can cause femoral nerve or lumbosacral plexus stretch injuries.

Lateral decubitus position – ensure arms are parallel to floor and each other. Axillary roll is
placed under the dependent side of the thorax, slightly caudad, not directly on the axilla to
decompress the shoulder, axillary vessels and brachial plexus of dependent arm.

Sitting position – Hypoperfusion of the brain and resultant anoxic injury. Risk for VAE.
Correction of blood pressure for the difference in height between the site of measurement and the
brain (1 cm height = 0.77 mmHg or 1 mmHg = 1.25 cm height)

785
Dextran

Available as dextran 70 and dextran (refers to molecular weight in thousands). Dextran 70 is a

better volume expander, and dextran 40 improves blood flow through the microcirculation.
Infusions greater than 20 ml/kg per day can have an antiplatelet effect and prolong bleeding time.
It is also large macro-molecule that is a complete antigen, anaphylaxis is a possibility. Dextran 1
may be administered prior to 40 or 70, it acts as a hapten and binds any circulating dextran
antibodies.

Dead space

The volume of the conducting airways is called the anatomic dead space and normally equals
approximately 2 ml /kg of body weight. The conducting airways create dead space because their
relatively thick walls do not allow the gas they contain to be exchanged with the gas contained in
the blood. Alveoli that are ventilated but not perused are known as alveolar dead space and
contribute nothing to gas exchange with the blood. The sum of the anatomic dead space plus the
alveolar dad space is the physiologic volume of dead space (Vds) and can be calculated with the
Bohr equation. (PaCO2 – PECO2) / PaCO2.

786
Board Review Prep!
Drugs:
Coumadin:

 inhibits synthesis of vitamin - k dependent factors II, VII, IX, X and protein C & S
 Reversal:
o stopping medication and waiting for ~4 days for PT normalization
o vitamin K PO or IV (1-2mg)
o immediate: rFVIIa, FFP (1-2 units), Prothrombin complex concentrate
 check PT prior to surgery
 biphasic effect on PT and INR
o initial ↑: ↓ F VII (shortest t ½) to 55 % of normal
o subsequent ↑: ↓ F II and X – therapeutic anticoagulant
 Discontinuation
o return to normal: F VII followed by F II & X
o caution: INR =/< 1.4 no assurance of normal coagulation
o In patients with mechanical valves, IV heparin may administered following
discontinuation of warfarin up until 24 hours prior to surgery
Tests: Prothrombin Time (PT)

 test of extrinsic pathway activity

 measures vitamin K - dependent factors activity (factors II, VII, IX, X)
 thromboplastin + Ca+2 to plasma = clotting time
 normal values: 12-14 seconds
 International Normalized Ratio (INR)
o standardizes PT reporting
 normal values: 0.8 -1.2 seconds
 most sensitive to alteration in F VII levels
o prolonged: 55 % ↓ of normal F VII activity
 antithrombotic activity: reduction of factor II and factor X activity (after several days)

787
Nitroprusside:
Sodium Nitroprusside (arterial dilatation) reduces peripheral vasoconstriction effects

 Arterial vasodilators decrease blood pressure via decreased SVR

 Mechanism of Action:
o Generation of intracellular Nitric Oxide (NO) produces vasodilation
o NO generation leads to stimulation of guanylate cyclase and increased c-GMP,
producing smooth muscle relaxation
o C-GMP leads to a decreased Ca++ ion concentration intracellularly
o Diseases or Conditions Associated with Abnormal NO Production and
Bioavailability
 Hypertension
 Obesity
 Dyslipidemias (particularly hypercholesterolemia and
hypertriglyceridemia)
 Diabetes (both type I and II)
 Heart failure
 Atherosclerosis
 Aging
 Cigarette smoking
 SNP solution
o Must be mixed in 5% glucose in water and must be wrapped in a light-protecting
cover (SNP converts to aquapentacyanoferrate in the presence of light with
release of hydrogen cyanide)
o Dose range is 0.3 - 10 mcg/kg/min, and the max rate should not be infused for >
10 min
o To lessen the likelihood of cyanide toxicity, use other drugs such as volatile
agents, possibly beta-blockers to help decreased BP
 Mechanism of action:
 Direct acting, nonselective potent vasodilator
 Ferrous ion center together with 5 cyanide ions and a nitrosyl
group
 Immediate onset, requires continuous infusion
 Need an arterial line for safety
 SNP interacts with oxyhemoglobin to form methemoglobin,
releasing cyanide and NO
 NO is the active mediator and SNP is the prodrug
 One of the 5 cyanide ions reacts with methemoglobin to form
cyanmethemoglobin

788
  The other 4 cyanide ions are converted to thiocyanate by the
Rhodanase enzyme in the liver and kidneys
 Cyanmethemoglobin remains in dynamic equilibrium with free
cyanide and is nontoxic
 CV system:
 Direct arterial and venous dilation, resulting in decreased BP
 SVR decreased because of arterial dilation
 Venodilation produces decreased venous return (decreased
preload)
 Baroreceptor response to decreased BP include increased heart rate
and contractility
 No direct inotropic or chronotropic effects on the heart
 Decreased systemic blood pressure may cause renin release,
contributing to a spike in blood pressure once the infusion is
stopped
 May increase the area of an MI due to coronary steal
 Decreased DBP contributes to myocardial ischemia by decreasing
coronary perfusion pressure and flow (theoretically could cause
angina) Increased CBF and CBV
 Not a good choice if increased ICP of significant carotid disease
 Decreased PaO2 via attenuation of Hypoxic pulmonary
vasoconstriction
 SNP Toxicity
o Cyanide Toxicity
 Seen with prolonged and/or high dose infusions
 Can occur with infusion rates > 2 mcg/kg/min
 Can occur when sulfur donors and methemoglobin are exhausted
(accumulation of cyanide radicals)
 Free cyanide radicals bind to cytochrome oxidase and prevent oxidative
phosphorylation (life-sustaining process)
 Increased cyanide concentrations may precipitate tissue anoxia, anaerobic
metabolism, and lactic acidosis
 Symptoms:

789
  Resistance to the hypotensive effects of the drug at maximum
infusion rates (10 mcg/kg/min)
 Or Tachyphylaxis (most commonly children)
 Mixed Venous PO2 is increased in cyanide toxicity, reflecting
inability of tissues to utilize O2
 Metabolic acidosis
 CNS-mental status changes & seizures in awake patients
 Toxic blood level > 40 micromoles
 Treatment:
 Stop infusion
 100% oxygen
 NaHCO3 to correct metabolic acidosis
 Sodium thiosulfate at 150 mg/kg IV over 15 minutes (sulfur donor
to convert cyanide to thiocyanate)
 If severe, sodium nitrate at 5mg/kg IV slowly (converts
hemoglobin to methemoglobin, which converts cyanide to
cyanmethemoglobin)
 Hydroxycobalamin (Vitamin B12) binds cyanide to form
cyanocobalamin (expensive, reddish skin discoloration)
o Methemoglobinemia
 Unlikely even in patients with a congenital inability to convert
methemoglobin to hemoglobin
 High SNP doses would be required
 If pt receiving high doses and presents with impaired oxygenation despite
adequate CO and arterial oxygenation should have methemoglobinemia
included in differential
 Measurement via co-oximetry may be helpful
o High plasma concentrations of thiocyanate
 Rare event
 Thiocyanate is 100-fold less toxic than cyanide
 Thiocyanate is cleared slowly by the kidneys, so CRF patients (not on
dialysis) with prolonged infusions may be at risk
 Is cleared by dialysis
 Nonspecific symptoms include tinnitus and N&V
 Hyper-reflexia, confusion, psychosis, miosis, seizure, coma

790
Benzodiazepines: Benzodiazepine: benzene ring fused to a 7-membered diazepine ring

Five Principal Effects of Benzodiazepines

1. Sedation
2. Anxiolysis
3. Anticonvulsant actions
4. Spinal cord-medicated skeletal muscle relaxation
5. Anterograde amnesia
Synergy with other CNS depressants, including other hypnotics, sedating antidepressants,
neuroleptics, anticonvulsants, antihistamines, and ETOH
Tolerance: to the hypnotic effects. Good for daytime but long-term management of insomnia
difficult. After 4 to 6 months, BZDs lose efficacy with long-term use
Dependence develops sooner in patients taking high-dose, high-potency agents (alprazolam
(Xanax))
Short-term withdrawal symptoms: autonomic instability and anxiety
Benzodiazepines replaced barbiturates for preoperative sedation & use during monitored
anesthesia care (MAC)

 The barbiturate binding site also modifies the effects of GABA, but is capable of opening
the ionophore by itself -- something that benzodiazepines can't do, and almost certainly
what makes them so much safer than barbiturates.
 Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter and GABA
receptors are found throughout the Central Nervous System. Depending on the brain
region, as many as ten to fifty percent of all central synapses possess GABAA receptors
o Cerebral cortex and hippocampus
 Mental confusion and amnesia
o Amygdala, orbitofrontal cortex & insula
 Alleviation of anxiety, agitation and fear
o Spinal cord, cerebellum & brain stem
 Muscle relaxation (also anxiolytic)
o Cerebellum and hippocampus
 Antiepileptic action
o Ventral tegmentum and nucleus accumbens
 Rewarding behavioral effects (depend/abuse)
 Two alpha 1, two beta 2, and one gamma subunit
o Binding site for benzodiazepines is between the alpha 1 and the gamma 2 subunit
 Benzodiazepines allosterically alter (potentiate) the GABAa, so that it has a greater
binding affinity for GABA

791
  Benzodiazepines with high affinity for the α1 subunit are associated with sedatives and
those with affinity for α2 or α3 subunits demonstrate anti-anxiety activity.
 Mechanism of Action:
o Facilitate actions of GABA
o Benzodiazepines do this by binding to specific site of GABAA receptor and
increasing affinity for GABA leading to enhanced opening of Cl- gating channels
which increases Cl- conductance leading to hyperpolarization of postsynaptic
membrane which makes postsynaptic neurons become resistant to excitation
o Resistance to excitation is mechanism for sedation, anxiolysis, skeletal muscle
relaxation & anticonvulsant properties
o 20% benzodiazepine receptor occupancy: anxiolysis
o 30-50% receptor occupancy: sedation
o >60% receptor occupancy: unconsciousness
 On postsynaptic endings in CNS
o Minimal circulatory effects which makes them more CV stable
 Highest density in cerebral cortex
o Hypothalamus > cerebellum > hippocampus > medulla > spinal cord
Midazolam

 Water soluble with imidazole ring

o Replaced diazepam for preop & conscious sedation
o 2-3X > potency than diazepam
 No propylene glycol, so not painful on injection
 Can be mixed with opioids & anticholinergics
 Pharmacokinetics
o Rapid absorption from GI tract, prompt passage across BBB (more lipid soluble
than other benzos)
o ~50% of oral dose reaches systemic circulation secondary to significant first pass
hepatic effect
o Short duration 2̊̊ liposolubility & rapid redistribution
o T1/2 : 1-4 hrs
 May double in elderly 2o hepatic blood flow
o Vd similar for midazolam & diazepam
o Similar lipid solubility & protein binding
o Clearance fast due to fast context-sensitive t1/2
 Drugs that inhibit cytochrome P-450 may decrease hepatic clearance
 Hepatic clearance rate 5X > Ativan, 10X > diazepam

792
  Renal failure doesn’t increase t1/2β secondary to extensive metabolism
 Extensive hydroxylation by hepatic microsomal enzymes
o water soluble metabolites excreted in urine as glucuronide conjugates
 Effects on Organ Systems
o Decrease CMRO2 & CBF
o Can’t produce flat EEG
o Minimal changes in ICP
o Effective anticonvulsant
 Dose-dependent ventilatory depression
 Decreases SBP & Increases HR with 0.2 mg/kg IV
o CO unchanged
 Synergy with opioids, propofol
o Potential effects on oxygenation & ventilation
 Induction dose: 0.1-0.2 mg/kg IV
Diazepam

 Highly lipid soluble with longer duration than midazolam

 Contains propylene glycol
o Painful injection
 Kinetics
o oral dose rapidly absorbed
o highly lipid soluble
o Large Vd = Slower onset & longer duration than 3-4 mg/kg thiopental
 Extensively protein bound since it’s highly lipid soluble
 cirrhosis & CRF associated with incidence side effects
 Metabolized by hepatic microsomal enzymes - active metabolites
 Cimetidine:
o delays hepatic clearance 2o inhibition of microsomal enzymes
o prolongs t1/2β of diazepam/metabolites
 T1/2β : 21-37 hrs
o Cirrhosis increases 5X
o Other factors that increase β elimination half-life: Vd, age
 Metabolite has t1/2β of 48-96 hrs
 Minimal effects on ventilation at 0.2 mg/kg IV
o Synergy with opioids & other CNS depressants
 Minimal change in BP, SVR, CO
o SVR & BP will decrease when fentanyl added
 Skeletal muscle relaxation 2o effects on spinal internuncial neurons

793
Lorazepam

 More potent amnestic than midazolam or diazepam

 Kinetics
o Conjugated with glucuronic acid to form pharmacologically inactive metabolites
o Elimination t1/2 = 10-20 hrs
 less lipid soluble than diazepam
 less dependent on hepatic microsomal enzymes
o >80% of injected dose excreted in urine
 Reliable absorption after oral & IM doses
o Oral: 50 mcg/kg, peaks in 2-4 hrs
 Slow onset limits usefulness for:

o IV induction of anesthesia
o IV sedation during regional anesthesia
o Use as an anticonvulsant
 Contains solvent (propylene glycol)
Flumazenil (Romazicon)

 Specific benzodiazepine antagonist

 Prevents or reverses dose-dependent benzodiazepine agonist effects
 Reverses respiratory depression from combined administration of benzo & opioid
 Dose: 0.2 mg IV (8-15 g/kg) - peaks in 2 min
o Further doses of 0.1 mg q 60 sec can be given to a total of 1 mg
 Duration: 30-60 min
o May need repeat doses or infusion of 0.1-0.4 mg/hr
 No rebound anxiety, agitation, HTN
o Weak intrinsic agonist
 Doesn’t precipitate withdrawal seizures when given to patients with seizure disorders
 Also doesn’t affect MAC of volatile anesthetics
Clonidine:

 Alpha 2 receptors in the CNS (medullary vasomotor center) and spinal cord (substantia
gelatinosa – in lamina II and some sources say lamina III)
 In the CNS, clonidine decreases SNS outflow via alpha 2 agonism
 Useful in patients with severe hypertension
 Sedation, decreased anesthetic requirements (via modification of K+ channels?) , and
analgesia are properties of clonidine
o The sedative effects of clonidine are different from drugs that act on GABA
receptors>>calm, easily aroused patient as opposed to a consciousness-clouded
patient or a paradoxically agitated patient

794
  150 – 400 mcg can be added neuraxially, producing dose-dependent analgesia, without
the side effects of opioids
o Neuraxial placement of clonidine inhibits substance P release
 Hypotension, dry mouth, and sedation are side effects
 Oral Clonidine 5mcg/kg prior to surgery decreases SNS response to laryngoscopy,
decreases plasma catecholamine levels, decreases MAC requirements
 Augments the pressor response to ephedrine
 Decreased risk of myocardial ischemia, infarction and mortality following CABG
 Ineffective in the setting of pheochromocytoma (no effect on tumor diffusion of
catecholamines)
 Decreased risk of myocardial ischemia, infarction and mortality following CABG
 Ineffective in the setting of pheochromocytoma (no effect on tumor diffusion of
catecholamines)
 Can be used as an adjunct in the management of acute ETOH withdrawal
 75mcg IV can be used to stop shivering, as clonidine inhibits central thermoregulatory
control
 Decrease in SBP>DBP
 Maintenance of CV reflexes
 Minimal depressant effects on ventilation, and no potentiation of opioids in this regard
 Side effects: sedation and xerostomia (dry mouth)
 Abrupt discontinuation produces rebound hypertension in 8-36 hours since last dose
 Symptoms of SNS irritation often precede BP increase
 Beta blockade is not wise as a treatment because blockade of beta2 vasodilating effects
leave unopposed alpha1 vasoconstriction. However, Labetolol can be used carefully
because of its alpha1 antagonism
 If you need to treat, give clonidine or a direct acting vasodilator such as hydralazine or
SNP
 Transdermal clonidine is effective for 7 days
Protamine:

 Derived from salmon sperm

 Polycationic substance that is strongly basic and combines ionically with heparin (acidic)
and neutralizes it to a stable salt complex
 Must be given slowly over at least 5 minutes (if not 10-15); rapid administration
associated with histamine release causing flushing, tachycardia and hypotension
 1 mg for every 100 units of heparin given in the last 90 min (t1/2 of Heparin)
o Activated Clotting Time (ACT)
o monitors heparin anticoagulation in the OR (cardiac and vascular surgeries)
o normal values: 90 - 120 seconds
o Heparin requires Factor III to be effective, may also be require to reverse Heparin
when ACT is unchanged after Protamine injection

795
  Problems: hypotension, pulmonary HTN (from 25/10 up to 45/25), and allergic reactions
 Allergic reactions most common in those patients taking protamine-containing insulin or
those allergic to fish. Can pre-treat with antihistamines, avoid protamine, or use an
alternative medicine
Rocuronium and NMB review:
Receptor is blocked by a competitive inhibitor and the endplate potential is not formed.
Nondepolarizing NMBs bind with cholinergic receptors but do not activate them.

 Muscle relaxants have in common a quaternary ammonium group (at least

one=monoquaternary).
 N binds with α subunit of postsynaptic cholinergic receptors
 Nondepolarizers - Benzylisoquinolinium or amino steroid compounds
o All contain 1+ (+) charged quaternary NH3
o Most have bisquaternary NH3 structure, therefore electrostatic association
between 2 ionized cationic centers of drugs & anionic groups on cholinergic
receptors
 Due to their quaternary ammonium groups, NMBs highly ionized, water-soluble
compounds
 Vd limited (~200 ml/kg)
 Don’t easily cross lipid membranes, e.g., BBB, placenta
o NMBs don’t produce CNS effects
 Age, volatile anesthetics, hepatic/renal disease all affect
o Plasma clearance
o Vd
o t1/2β
 Renal/hepatic elimination
o Access to large fraction of drug 2o high degree of ionization
 Maintains high plasma concentrations, prevents renal reabsorption
 NMBs not highly bound to plasma proteins
o Changes in protein binding won’t have effect on renal excretion of NMB
 Pharmacodynamics
o Affect small, rapidly moving skeletal muscles (eyes, digits) before diaphragm
o Nondepolarizers onset more rapid but less intense at laryngeal muscles than
peripheral muscles
 Thyroarytenoids (close glottis) have fast contraction times when compared
to adductor pollicis
o Intermediate/short nondepolarizers:
 laryngeal paralysis brief, may dissipate before max effect at adductor
pollicis

796
 Train of four (TOF)
o 4 separate stimuli, 500 msec apart, at 2Hz
o TOF ratio=height of the 4th twitch to that of the 1st twitch (T4/T1)
o Twitches in TOF↓ with ↑ NMB
 4th twitch disappears 1st (75% receptors blocked); then 3rd & 2nd (75-
90% block present); when 0 twitches present block >90%
 TOF ratio 0.25= <75% blocked and reversal likely successful
 TOF ratio 0.5= 50% blocked---ratio 0.75= 25% blocked
 TOF ratio 0.9-1.0—0 % block=full recovery
o Paralysis onset begins with eye muscles, followed by extremities, trunk (neck
muscles down through intercostal), abdominal muscles diaphragm
o Recovery returns in opposite manner
o Protective reflex muscles of pharynx & upper esophagus recover LATER than the
diaphragm, larynx, hands or face
 Rocuronium – 0.3 mg/kg ED95 dose, onset 1-2 min, duration 20-35 min, intubating
dose=0.6 mg/kg or RSI 1.2 mg/kg
o Vd = 0.27 L/kg; Clearance = 5.2 mL/kg/min; Renal excretion unchanged = 20-
25%; Biliary excretion unchanged = 50-70%
o Chemically similar to Vecuronium, but shorter duration of action.
o Onset 60-90 seconds, duration about 30 minutes
o Eliminated via biliary excretion
o At higher doses (1.2 mg/kg), an alternative in patients who cannot receive Suxx
for RSI—due to faster peak effect time
o With an intubating dose of 0.6 mg/kg, 40% of patients will have residual NMB at
2hrs and 10% will have at 4 hrs
 Factors potentiating neuromuscular blockade
o Volatile anesthetics
o Local anesthetics (procaine)
o Anticholinesterases such as echothiopate
o Antibiotics: Tetracycline, aminoglycosides (gentamicin, tobramycin, amikacin,
kanamycin), Clindamycin, Polymyxins
o Erythromycin, penicillin, and cephalosporins do not potentiate neuromuscular
blockade
o Cardiovascular drugs: Lidocaine, Quinidine, Verapamil
o Electrolytes:
 Mg++ decreases the release of Ach from the nerve terminal and decreases
the sensitivity of the end-plate to the effects of Ach—potentiating the
effects of both suxx and nondepolarizers
 Increased Li, Na
 Decreased Ca, K (potentiated by alkalosis)
o Physiologic states
 Hepatic dysfunction, hypothermia, acidosis, alkalosis

797
Vasopressin (ADH, Pitressin):
Per pharmacology & physiology book:

 Treatment for SIADH,

 evaluation of urine-concentrating ability of kidneys after fluorinated VA’s,
 management of uncontrolled hemorrhage from esophageal varices (20 u over 5 min),
 hemodynamic stabilization of hemorrhagic or septic shock and management of refractory
cardiac arrest (40 u IV which lasts 10-20 min rather than epi 1 mg every 3-5 min)
Causes:

 vasoconstriction and increased systemic BP with larger doses;

 due to effect on vascular smooth muscles that is not antagonized by denervation or
adrenergic blocking drugs;
 increases PA pressures; vasoconstriction in coronary arteries=angina, myocardial
ischemia, MI
 stimulates GI smooth muscle to increase peristalsis = abdominal pain, N & V; decrease
in platelet count due to arginine vasopressin mediated platelet aggregation via V1
receptors
Per Clinical Anesthesia Procedures of Mass. General Hospital:
Indications: 1. Diabetes insipidus 2. Upper GI Hemorrhage 3. Pulseless ventricular
tachycardia or Vfib 4. Shock refractory to fluid and vasopressor therapy
Dosage: 1. 5-10 units IM/SC q 8-12 hrs 2. 0.1-0.4 u/min IV infusion. 3. 40 u IV single
dose bolus 4. 0.04 u/min IV infusion
Effect: Increases urine osmolality and decreases urine volume; smooth muscle
constriction; vasoconstriction of splanchnic, coronary, muscular and cutaneous
vasculature
Clearance: Hepatic and renal metabolism; renal elimination
Comments: May cause oliguria, water intoxication, pulmonary edema; HTN, arrhythmias, MI;
abdominal cramps; anaphylaxis; contraction of gallbladder, urinary bladder or
uterus; vertigo or nausea. Patients with CAD are often treated with concurrent
nitroglycerin. Useful in shock states as effect of drug is not pH dependent.

798
Anti-diuretic hormone (per renal patho notes)
In the distal tubule and collecting duct, ADH controls water reabsorption, while aldosterone
controls sodium reabsorption and potassium secretion.
ADH increases the permeability of the DT & CD to water.
Consequently, when ADH is present, H2O is reabsorbed and a high, small volume (as low as 0.5
ml/kg/hr) concentrated urine is formed (1200-1500 mOsm)
Rate of release from posterior pituitary is proportionate to the osmolality of the ECF

 ↓ vascular volume (↑ osmolality )→ ADH release

 Thirst mechanism activated→↑ water ingestion
 Other triggers: hypotension, pain, trauma, CPAP, PEEP, volatile agents
Urine Osmolality Urine Volume
+ ADH 1200-1500 mOsm 0.5 ml/kg/hr
- ADH 50-100 mOsm 2-25 ml/kg/hr
SIADH

 Inappropriate ADH secretion

 Causes: surgery, intracranial tumors, hypothyroidism, porphyria, small cell lung CA
 Findings: inappropriately increased urine sodium concentration, and increased urine
osmolality, decreased plasma osmolality

Volume of distribution
Volume of distribution is calculated as the dose of drug administered IV divided by the resulting
plasma concentration of drug before elimination begins or when steady state conditions have
been achieved. As such, VD is influenced by physicochemical characteristics of the drug,
including: a) lipid solubility, b) binding to plasma proteins, and c) molecular size. Binding to
plasma proteins and poor lipid solubility limit passage of drug to tissues, thus maintaining a high
concentration in the plasma and a small calculated VD. Examples of poorly lipid soluble drugs
with a VD similar to extracellular fluid volume are the nondepolarizing neuromuscular blocking
drugs. A lipid soluble drug (diazepam) that is highly concentrated in tissues with a resulting low
plasma concentration will have a calculated VD that exceeds total body water. – Stoelting’s
Pharmacology and Physiology in Anesthetic Practice

799
  Volume of distribution (VD) is the ratio between the amount of drug in body (dose given)
and the concentration of the drug (C) measured in blood or plasma.
o Factors influencing the volume of distribution:
 drug pKa
 extent of drug-plasma protein binding
 partition coefficient of the drug in fat (lipid solubility)
 Vd may be affected by:
 patient's gender
 patient's age
 patient's disease
 patient's body composition
 Example of a poorly lipid soluble agent with a Vd about equal to
extracellular fluid volume: nondepolarizing neuromuscular blocking drugs
 Volume of distribution assesses the extent of compartmental distribution. Drugs with
large volumes of distribution indicate extensive tissue distribution.
 Volume of distribution of the central compartment is the volume the drug occupies after
an IV bolus dose before any tissue distribution or elimination. This volume is close to the
plasma volume
 Volume of distribution at steady state estimates the volume at which the amount of drug
input equals the amount of drug lost, and all compartments have equal free drug
concentrations
 Important – steady state can be achieved after a long-term IV infusion or after repeated
doses
o Acidic drugs are more likely to be bound to plasma albumin, particularly if they
are lipophilic
o Basic drugs are more likely to bind to alpha-1-acid glycoprotein
o Chronic renal and liver failure can reduce the extent of plasma protein binding
and increase the fraction unbound in plasma by decreasing albumin levels or
displacing drugs from their binding sites.
o Alpha-1-acid glycoprotein concentrations can be elevated by acute trauma and
infections
Vena caval obstruction—related to OB and in general
OB patients
Preventable cause of fetal distress – systemic HoT due to decreased venous return and increased
uterine venous pressure and uterine arterial hypoperfusion severely compromise uterine and
placental blood flows causing fetal asphyxia
Chronic partial caval obstruction in third trimester predisposes to venous stasis, phlebitis and
edema in the LE; distend and increases blood flow through collateral venous drainage
(paravertebral venous plexus and to minor degree the abdominal wall)
Elevation of diaphragm = changed position of heart (appears larger on chest film) and left axis
deviation with T wave changes on the ECG

800
Creation of Pneumoperitoneum

 The pneumoperitoneum is essential for surgical exposure and room for instruments
(trocars)
 The initial establishment of the pneumoperitoneum is the point at which most
complications/hemodynamic consequences ensue – pay attention to when this is
happening – surgeon may say “gas on”, etc. This is not the time to be charting, on the
phone, playing Sudoku, looking at your stock portfolio, etc.
 A small periumbilical incision is usually made and then the abdomen is insufflated with
gas
 Ideal insufflation gas:
o Limited systemic absorption across the peritoneum
o Limited systemic effects when absorbed
o Rapid excretion if absorbed
o Incapable of supporting combustion (surgeon uses cautery)
o Options:
 N20 used to be used, but, it supports combustion. Scattered case reports
exist about the abdomen igniting>>yikes. Advantages>limited physiologic
effects
 Air and Oxygen both support combustion
 Carbon Dioxide is the gas of choice, although there are consequences to
its use and absorption >> Cardiorespiratory implications
 We are creating a “restrictive” problem by blowing up the abdomen into a dome
 A patient classified as a ASA 3 or greater may not tolerate well the physiologic
consequences of this
 Increased Intraabdominal pressure (IAP) compresses venous capacitance vessels causing
an initial increase, then a sustained decrease in preload. Sources differ on agreement
related to this topic (Nagelhout says CVP increased or decreased for example)
 Compression of arterial vasculature > increased SVR
 Cardiac output may increase, decrease, or remain the same
o Depends on the insufflation pressure>ideally, this is less than 12 mmHg
o Depends on baseline cardiac status/ejection fraction
o Depends on volume status
o Impacted by position of the patient (Trendelenburg (gyne, for example) vs
Reverse Trendelenburg (lap chole, for example)
 Reverse Tburg > decreased preload
 Tburg > increased preload
 –But, still not straightforward>effects of anesthetic drugs
 Possible initial vasovagal response due to peritoneal “tugging” > bradycardia
 Tachycardia > minimal consequence in “healthy” patients, but what about the increased
demand/decreased supply caused by tachycardia in a pt with CAD?
 Regional circulatory changes > decreased splanchnic, renal, and hepatic blood flow> this
gets worse the longer this goes on
 Decreased pulmonary compliance>restrictive>greater difficulty ventilating>greater PIPs

801
 o In whom might this create a challenge?
 Morbidly obese
 Restrictive pulmonary disease
 Smokers/reactive airway disease
 Pregnant patient
 Increased IAP displaces the diaphragm upward, decreases FRC and total lung compliance
 Basilar atelectasis—may need to add PEEP
 Increased peak airway pressures
o Remember >what is the baseline peak airway pressure before a change in position
or insufflation?
o Check breath sounds again if patient position changes--why do we do this?
 Neurohumoral response=increased dopamine, vasopressin, epinephrine, norepinephrine,
renin, and cortisol
 Temperature may be decreased from cold gas/fluids
 And, we have to deal with increased CO2 load from insufflation > how will we ventilate
these patients?
o Need to increase minute ventilation to maintain normocarbia
o Acidosis and hypercapnia may occur if not (increase HR/BP)
o PIP will be the limiting factor. Trying to increase TV may increase PIP to an
undesirable level. So, you increase RR, but remember that this increases dead
space. You usually don’t have a choice >>It is common to increase RR into the
20s, for example. Employing muscle relaxants will help you achieve better
ventilation.
o LMA – Not for upper abdominal procedures; possibly/yes for lower abdominal
procedures provided it’s safe to do so (patient, size of patient, length of case,
position, etc.)

802
Pressure-volume loop
 Pressure-volume relationship depends on:
 Relaxation properties of ventricle
 Elastic recoil of ventricle
 Distensibility of ventricle
 Illustrate effects of different stresses on CO
 CO is product of HR & volume of blood pumped with each beat (stroke volume)
 Width of pressure-volume loop is difference between EDV & ESV (stroke
volume)
 Stroke volume depends on:
 Contractility, afterload & preload
 Changing contractility changes width of pressure-volume loop by
changing position of isovolumic systolic pressure curve
 Afterload: impedance against which heart must work
 Preload: amount of filling of ventricle at end-diastole

INCREASED PRELOAD;
Increased SV so the curve is wider

803
INCREASED AFTERLOAD;
Curve is thinner and taller

804
805
806
ECG rhythm—review the basics and the four phases and the ion
Transport
I didn’t reinvent the wheel with the rhythm stuff just referenced valley….

 Pacemaker cells
o No resting potential->spontaneous action potentials
o Slow inward Ca currents instead of fast Na channels for depolarization
o 3 Phases
 Phase 4- pacemaker potential
 Phase 0-depolarization
 Phase 3- repolarization


 Non Pacemaker cells
o Absolute refractory period comprises phases 0, 1, 2, and part of 3
o Ability of non-pacemaker cells to become pacemaker cells in hypoxic
conditions=>>>arrhythmias
o True resting potential, like other cells
 Phase 4 – resting; open K+ channels, closed and L-type slow Ca++
channels, closed Na
 Phase 0 – depolarization; fast Na+ channels open, K+ channels closing
 Phase 1 – partial repolarization; outward K+ channel open
 Phase 2- plateau; L-type Ca++ slow inward channels open
 Phase 3 – repolarization; K+ increases, Ca++ channels inactivated

807
EKG findings in A/L/I/S MIs
o Anterior (LAD) Elevation – V3, V4
o Lateral (Circumflex) Elevation – V5, V6, I, AvL
o Inferior (RCA) Elevation – II, III, AvF
o Septal (LAD) Elevation – V1, V2

You will be looking for

(1) Q waves,
(2) LVH with strain,
(3) LBBB, or
(4) down-sloping ST-segment depression greater than 0.5 mm to help discern LV function
and ischemia.
Of what significance is the LVH?
When you review an EKG with Q waves, remember that the extent and magnitude of the Q
waves correlate with LVEF, and that collectively these findings on a preoperative 12 Ld EKG
predict adverse peri-operative cardiac events

808
Heart blocks & other arrhythmias

 Blocked conduction
 1oAVB: abnormally long A-V conduction time (PR > 0.22 s)
 2oAVB: some but not all atrial impulses conducted to ventricles
 3oAVB: no association between atrial & ventricular activity
 A-V block can occur w/↑age, muscular dystrophy, SLE, sarcoidosis, gout, lyme dz

809
End stage liver and kidney disease
Renal anatomy & physiology
 Retroperitoneal
Center at L2 vertebral body
 Pain sensation → T10-L1
 Sympathetic innervation
Preganglionic T8-L1
 Parasympathetic
Vagus
 Ureters
Sympathetic innervation & nociceptive projection similar to kidneys
Innervation
 T-10-L1 pain sensation
Kidneys, ureters, lumbar area, flank, ilioinguinal area, scrotum/labia
 T-8-L1: sympathetic innervation
 Vagus: parasympathetic innervation
 Parasympathetic fibers from S2-S4 supply ureters
 Bladder:
Sympathetic innervation T11-T12 → conduct pain, touch, temperature sensation
Stretch: S2-S4 parasympathetic fibers
Innervation
 Prostate, penile urethra, penis:
Sympathetic fibers from T11-L2
Parasympathetic: S2-S4
 Glomerulus
Capillary network that serves as basic filtering unit of nephron
Outer cortex
Entry through afferent arteriole, exit via efferent arteriole
 Bowman’s capsule
Initial segment renal tubular system
Envelops glomerulus
 Glomerular filtrate from Bowman’s capsule → proximal tubule → descending loop →
medullary portion of kidney → ascending loop → cortex → distal tubule contacts
w/afferent & efferent arterioles → JTG apparatus.
 Distal tubule → cortex → cortical collecting ducts → renal pelvis → ureters

810
 Renal physiology

 Waste excretion
 Body fluid management
Filters large amounts of fluids/solutes from blood
Reabsorbs needed component of filtrate
Secreting waste products into tubular fluid
Filtration/reabsorption most susceptible to surgery or anesthesia-related changes
 Kidneys receive ~20% CO
180 L/d filtrate; >99% reabsorbed → 1-2L/d uo
 Renal blood flow & perfusion pressure determine GFR
 Tubular reabsorption of Na+ & H2O
 Neurohumoral regulation of Na+ reabsorption by kidney part of surgical stress response
Focus: maintain BP, circulating blood volume, organ blood flow
 Na+ reabsorption (energy-dependent) begins when filtrate enters prox tubule
ATP pump drives Na+ into tubular cells
Na+ pumps in distal tubule and collecting duct controlled by aldosterone
 H2O reabsorption is passive, osmotically driven
Tied to Na+ & other solute reabsorption
Depends on peritubular capillary pressure
Renin release by afferent arteriole due to:
Hypotension
SNS stimulation
Leads to angiotensin II production → renal efferent arteriolar vasoconstriction, aldosterone
release → reabsorb Na+ & H2O → ↑ intravascular volume
 Surgical stress response
↓ GFR, Na+ & H2O retention → oliguria, edema
Continues for several days 2o ongoing stress (pain, sepsis, hypovolemia)
Acute renal failure
 Prerenal azotemia
↑ BUN associated w/renal hypoperfusion/ischemia
Has not caused renal parenchymal damage
 Intrinsic acute renal failure
1o renal etiology of ARF
Includes ischemia, ATN, toxins (drugs, contrast media), parenchymal diseases
 Characteristics of ARF
Accumulation of creatinine & urea in blood
Reflects loss of ability to excrete waste products
U.O. < 0.5 ml/kg/hr useful sign of renal hypoperfusion when other signs of ↓ systemic blood
flow apparent

811
 Chronic renal failure
 Uremia associated w/electrolyte & acid-base abnormalities, multiple organ system
dysfunction
 Renal failure pts predisposed to develop ↑ K+
 Electrolyte/acid-base
Hyponatremia
Hyperkalemia
Hypercalcemia
Hypocalcemia
Hyperphosphatemia
Hypermagnesemia
Metabolic acidosis
 C-V
CHF
HTN
Pericarditis
Myocardial dysfunction
Arrhythmias
 Respiratory
Pulmonary edema
Central hyperventilation
 G-I
Delayed gastric emptying
N&V
Hemorrhage
Renal failure: Induction agents, sedatives
 Thiopental induction dose reqmt ↓ 2o ↓ protein binding
 Ketamine pharmacokinetics unchanged
 Etomidate has larger free fraction but clinical effects unchanged
 Propofol: extensive hepatic metabolism to inactive metabolites that are renally excreted.
Kinetics appear unchanged in renal failure
 Benzos: extensively protein bound; clinical effect may be prolonged. ↓ Initial dose.
ARF may slow plasma clearance of midazolam.
Drugs w/active metabolites may accumulate w/repeat doses
 Opioids and renal disease
 Morphine
Chronic administration results in accumulation of morphine-6-glucuronide, potent analgesic
 Meperidine
Normeperidine is neurotoxic and depends on renal excretion
 Codeine

812
 Potential for producing prolonged effects
 Opioids and renal disease
 Fentanyl
Absence of active metabolites
Sm doses tolerated by uremic pts
Lg doses (25 µg/kg) may result in prolonged effect
 Alfentanil
Extensively metabolized to inactive compounds
 Sufentanil
Active metabolite depends on renal excretion
 Remifentanil
Rapidly metabolized to weakly active metabolites that depend on renal clearance
 Muscle relaxants & renal disease
 Succinylcholine, Atracurium, mivacurium, Cisatracurium
Minimal renal excretion of unchanged parent compounds
Clearance & duration of Atracurium/Cisatracurium not changed by renal failure
Vecuronium duration of action prolonged 2o ↓ decreased clearance & accumulation of active
metabolite
 No dose change necessary w/anticholinergics & anticholinesterases

813
Digestive & Liver:

The bile duct, hepatic arteriole and portal venule is called the portal triad.

 Hepatitis A
Highly contagious, transmitted by feces-soiled hands of infected persons
May be sexually transmitted, or among IV drug abusers
Virus is shed in stool for 14 to 21 days before jaundice sets in
Patients are no longer infectious 21 days after onset
IgM antibodies detectable at onset and usually disappear within 60 to 120 days
IgG antibodies achieve high titers during convalescence and persist indefinitely, conferring
immunity

Hepatitis B
 Transmitted primarily through percutaneous inoculation of infected serum or blood
products
 Also sexually transmitted and can be transmitted to the fetus during pregnancy
 Chronic Hep B is a risk if person is immunosuppressed, but age at the time of infection is
a major determinant (90% of infected neonates are chronic carriers).
 Tx with interferon and lamivudine, liver transplantation if that fails

814
 Hepatitis C
Transmitted via parenteral routes (blood transfusions, occupational exposure to blood/blood
products, IVDA
Progression to chronic Hep C and cirrhosis is the most common indication for liver
transplant
With chronic Hep C, administration of interferon combined with ribavirin is the preferred
treatment
Chronic Hep C follows acute Hep C infection in 85% of patients
Chronic Hep C is treated as Chronic Hep B is, but relapse is common after interferon is
stopped.

 Hepatitis D
Occurs only in patients with Hepatitis B
Transmitted via the percutaneous route

HEPATITIS

 Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are sensitive

indicators of liver cell injury seen with viral hepatitis.
 AST and ALT increase 7 to 14 days before onset of jaundice and begin to decrease
shortly before jaundice develops
 Alkaline phosphatase is not increased unless cholestasis develops at a later phase
 Increased gamma globulins suggest chronic active hepatitis rather than active viral
hepatitis
Treatment is symptomatic with restriction of physical activity
May need fluids and electrolytes if severe

815
Liver transplantation is a consideration when patients develop encephalopathy and coagulation
abnormalities
Many drugs induce hepatitis (analgesics, volatile anesthetics, antibiotics, antihypertensives,
anticonvulsants, tranquilizers) that is indistinguishable from viral hepatitis
 Clinical signs usually occur 2-6 weeks after the initiation of drug therapy but can occur as
early as the first day or as late as 6 months afterward. The disease can progress despite drug
withdrawal.

HALOTHANE HEPATITIS

Halothane hepatitis: severe post op hepatitis

Symptoms ( usually 3-6 days post op): fever, N/V, chills, maculopapular rash, jaundice
Risks: prior exposure to halothane, obesity, Hispanic ethnicity
POST OP HEPATITIS

 minimize hepatotoxicity, MAXIMIZE hepatic O2 delivery

 Differential diagnosis of postoperative hepatic dysfunction
◦Review all drugs given, Sepsis, Exogenous bilirubin loads (transfused blood), Occult
hematomas, Hemolysis, Hypotension, arterial hypoxemia, hypoventilation, and hypovolemia can
cause such dysfunction leading to splanchnic ischemia, Extrahepatic abnormalities (CHF,
respiratory failure, pulmonary embolism, renal insufficiency)

CHRONIC HEPATITIS

◦ Long term elevation of liver enzymes and evidence of hepatocyte inflammation on liver
box
◦ Usually greater than 6 months of disease
◦ May be caused by virus, drugs, Wilson’s disease, alpha-1-antitrypsin deficiency, or early
primary biliary cirrhosis and primary sclerosing cholangitis
◦ S/S are fatigue, malaise, mild abdominal pain.
◦ Extrahepatic manifestations are common and include arthralgia’s, arthritis,
glomerulonephritis, skin rashes, amenorrhea, and thyroiditis

816
 SYMPTOMATOLOGY

 HEPATIC DISEASE -HIPATOBILIARY

o Icterus -Fatigue
o Palmar erythema -Anorexia
o Spider angiomas -N/V
o Gynecomastia -Biliary colic
o Ascites -Pruritus
o Peripheral edema -Fever
-Dark colored urine
-Light colored stools

LIVER CIRRHOSIS

 Is diagnosed with liver bx in which there is significant scarring and disruption of normal liver
architecture
Cirrhosis shares the same nondiagnostic signs as hepatitis, but other findings can include:
Palmar erythema, spider nevi, Gynecomastia, testicular atrophy, and evidence of portal
hypertension (splenomegaly, ascites).
Portal HTN reflects resistance to blood flow through a scarred, narrowed liver , hence
decreased hepatic blood flow
Cirrhotic liver is enlarged
Decreased serum albumin and prolonged Prothrombin time is characteristic of cirrhosis
Increased serum aminotransferases (GOT1) and alkaline phosphatase (ALP) concentrations
are common

There are different types of cirrhosis:

1. alcoholic
2. post-necrotic
3. primary biliary
4. hemochromatosis
5. Wilson’s disease
6. alpha-1—antitrypsin deficiency
7. nonalcoholic Steatohepatitis

817
 1. ALCOHOLIC CIRRHOSIS
Daily avg. consumption of 4 to 6 drinks for 10-15 years
Associated malnutrition is almost always present
Dx supported by an AST/ALT ratio of at least 2:1
Decrease albumin and prolonged Prothrombin times are common
ONLY effective therapy is cessation of alcohol ingestion
Manifestation of folate deficiency is macrocytic/ megaloblastic anemia
2. POSTNECROTIC
Characterized by a shrunken liver containing regenerating nodules
Commonly caused by chronic viral hepatitis
3. PRIMARY BILIARY
Most often in women 30 to 50 years of age
Autoimmune mechanism
Treatment is ursodiol to decrease bile acid toxicity
4. HEMOCHROMATOSIS
Large amounts of Iron deposited in hepatocytes, resulting in scarring and cirrhosis
Iron deposits in the pancreas and heart muscle are associated with CHF and DM
There is a bronze discoloration of the skin and hepatosplenomegaly is common
Tx is by removal of excess iron (phlebotomy) before cirrhosis develops

818
 5. WILSON’S DISEASE (hepatolenticular degeneration)
Autosomal recessive, a gene defect that codes for Copper binding, leading to a total body
copper increase
Neurologic dysfunction from copper toxicity manifests as tremors, gait disturbances, and
slurring of speech
Hepatic dysfunction (fatigue, jaundice, ascites, splenomegaly, gastroesophageal varices)
develop
Hemolytic anemia is an associated sign
Characteristic sign is the Kayser-Fleischer ring (thin brown crescent of pigmentation at the
periphery of the cornea) –Jay has this, caused by cholesterol
Lab: ↑ urinary copper excretion
Tx with chelating drugs that bind copper and urinary excretion
6. ALPHA-1-ANTITRYPSIN DEFICIENCY
Rare syndrome of progressive cirrhosis
Many patients have Hep B or Hep C
7. NONALCOHOLIC STEATOHEPATITIS
Fat accumulation associated with obesity, hyperlipidemia, and diabetes mellitus
Usually follows poor diabetic control or rapid weight loss
TX: controlled weight loss

819
CIRRHOTIC COMPLICATIONS
HEPATORENAL

 Renal failure associated with liver cirrhosis

 Most commonly fatal

MALNUTRITION

 Protein-calorie malnutrition which leads to salt and water retention

SYSTEMIC CIRCULATION

 Hyperdynamic circulation characterized by

 increased cardiac output (due to vasodilating substances such as glucagon; increased
intravascular volume, decreased viscosity of blood secondary to anemia)
 Cardiomyopathy seen as CHF occurs in alcoholic cirrhosis
 Megaloblastic anemia is frequent: due to antagonism of folate by alcohol rather than
dietary deficiencies
 Thrombocytopenia is likely
 Accumulation of fibrin degradation products may reflect the presence of DIC

ARTERIAL HYPOXEMIA

 PaO2 values of 60-70 mmHg are common in patients with cirrhosis due to impaired
diaphragmatic movement b/c of ascitic fluid accumulation.
 R  L intrapulmonary shunts may develop in the presence of portal vein hypertension
 May be associated with pneumonia

820
 HYPOGLYCEMIA

 Reflect glycogen depletion due to malnourishment plus alcohol-induced glycogenolysis and

interference with gluconeogenesis

1) Liver enzymes

LIVER FUNCTION TESTS

 Hepatocellular Injury:
o AST
o ALT
o LDH
o GST( Glutathione S-transferase)
 Cholestasis :
o Alkaline phosphatase
o GGT( Gamma glutamyl transferase)
 Liver Excretory Capacity :
o Bilirubin ( direct/indirect
 Synthesis :
o albumin, coagulation

Venous air embolism—types of surgical increase risks and signs and symptoms and treatments
 If sitting position, VAE precautions must be taken
 Occurrence depends on development of (-) pressure gradient between operative site and
R side of heart
As gradient between cerebral veins and RA increases, potential for air entry increases
Estimated incidence of VAE during neurosurgery is 5-50%
Clinical situations related to VAE

821
 Urologic surgery
Post spinal surgery
Epidural or caudal catheter insertion
Bone marrow harvesting
Laparoscopy
Radical pelvic surgery
Position
 Seated, prone, steep Trendelenburg
Transfusion rx
IV rx
Central venous catheterization
Liver surgery
Paradoxical air embolism
 Air entry into systemic circulation
 Existing connection between R & L heart
ASD, VSD, PFO especially at risk
PFO in 30-35% of population
If R sided pressures > L sided, systemic air may embolize & enter arterial circulation
 If preop murmur, pts who require seated position should have echo to r/o presence of
intracardiac defect
VAE detection
 Continued air entry can produce RV airlock
Pulm HTN, hypoxemia, CO2 retention, ↑ dead space ventilation, ↓ETCO2
Large alveolar air volume: sudden appearance of end-tidal N2
 Precordial Doppler can detect small entrainment rates
Placed over R heart along R sternal border between 3rd and 6th intercostal spaces
Placement confirmed w/change in Doppler signal when 10 ml saline bolus given through
CVP
Treatment of VAE
 Notify surgeon on detection (flood surgical field w/saline and wax bone edges)
 D/C N2O, give 100% O2
 Perform Valsalva maneuver or compress jugulars
 Aspirate air from atrial catheter
 Support BP w/volume, pressors
 Reposition in L lat deco w/15o head-down tilt if BP continues to fall
 Modify anesthetic to optimize hemodynamics

822
Pheochromocytoma-cover treatments both in OR and prior to OR
o Catecholamine secreting tumors that arise from chromaffin cells of the sympathoadrenal
system resulting in HTN, malignant HTN, CVA or MI
o 80% located in adrenal medulla, oragan of Zuckerkandl near the aortic bifurcation is most
common extra adrenal site
o Most secrete NE alone or in combo with Epi (85:15 which is reverse of normal secretion)
autonomously
o S&S – attacks vary (multiple daily to once monthly or less)
o The HALLMARK of pheos are HTN associated with diaphoresis, headache,
palpitations, tremulousness, and weight loss.
o The 3 SIGNS AND SYMPTOMS- TRIAD- Diaphoresis, headache, and
tachycardia.
o Most pheos secrete both epinephrine and norepinephrine with the percentage of
secreted norepinephrine being greater than that secreted by the normal gland.
 NE (α) predominates = elevated SBP and DBP with reflex bradycardia
 EPI (β) predominates = elevated SBP, decreased DBP, tachycardia
o Cardiomyopathy – excess Ca influx, toxicity from oxidized products of
catecholamines and myocardial damage by free radicals, high catecholamine
levels result in coronary vasoconstriction thru alpha adrenergic pathways = ↓ CBF
and ischemia
o Elevated blood sugar d/t catecholamine stimulation of glycogenolysis and
inhibited insulin release
o Diagnosis
o 24 hr urine collection or plasma measurement of metanephrines (catecholamines
are metabolized to free metanephrines within tumor cells)
o Clonidine Test – alpha agonist - lowers plasma catecholamine levels in patients
without pheo but has no effect on catecholamine levels in patients with pheo
o CT and MRI
o Anesthetic Management
o Preoperatively
 Alpha blockade to lower BP and increase intravascular volume
 Phenoxybenzamine – noncompetitive alpha 1 antagonist
 Pt. MUST be Alpha blocked before they are beta blocked to avoid
the possibility of unopposed alpha mediated vasoconstriction
putting them into heart failure
 BB to treat tachycardia after alpha blockade initiated
 Propranolol, atenolol, metoprolol and labetalol
 Calcium Channel blockers and ACE inhibitors
 Ca triggers catecholamine release from tumor

823
 o Intraoperatively
 HTN with pneumoperitoneum and tumor manipulation or HoT with
ligation of tumors venous drainage
 A-Line and CVP to monitor closely with no cardiac involvement
 Add TEE, PA cath for cardiac involvement
 Minimize catecholamine release – avoid histamine releasers (Morphine &
Atracurium)
 Treat HTN – nitroprusside, Mag inhibits release of catecholamines from
adrenal medulla and peripheral nerve terminals, reduces sensitivity of
alpha receptors to catecholamines, is a direct vasodilator and
antiarrhythmic
 Have Lidocaine, Esmolol, diltiazem and phentolamine handy
 Significant HoT with tumor vein ligation – volume resuscitation, decrease
anesthetic depth
o Postoperatively
 Continued HTN – d/t slow release of stored catecholamines from
peripheral nerves
 HoT – d/t poorly responsive vasculature to reduced levels of
catecholamines, may require steroid supplementation if hypoadrenalism is
present; dextrose fluid therapy with plasma glucose monitoring

Post-dural puncture headache

-I also attached the Power point but here it is with a little less fluff
- What is a PDPH & what causes it?
Also known as a spinal headache
Low CSF pressure resulting from CSF leakage through a hole in the dura which exceeds the
rate of CSF production.
PDPH arises when 10% of the estimated total CSF volume is lost.
PDPH is the 2nd most common complication of spinal anesthesia second to backaches
• Anatomy of the Dura
The spinal dura mater extends from the foramen magnum to the second segment of the
sacrum.

824
 The direction of the fibers that compose the dura are non-uniform.
• Cerebrospinal Fluid
Total adult CSF volume that is circulating at one time in the subarachnoid space is
approximately 150mL
• Produced in the choroid plexus and is reabsorbed in the arachnoid villi.
• Produced at a rate of 0.35mL/min, 21mL/hr, or 500mL daily.
• If the leaking of CSF exceeds the production, a low CSF pressure results and the
cushioning effect provided by the intracranial fluid is lost
Theory #1
• When CSF volume is low intracranial hypotension results which leads to traction on pain
sensitive intracranial structures such as the dura mater and dural venous sinuses.
• In the horizontal position, the lumbar, cisternae and intracranial pressures are equal. In
the upright position gravity causes a pressure gradient, moving CSF into the spinal dural
sac increasing the leak through the dural puncture and creating a negative intracranial
pressure.
• A loss of 10-15% of CSF can reduce intracranial pressure by more than 40% causing a
PDPH
• Symptoms of a PDPH can be related to the stimulation of cranial nerves causing pain in
specific locations.
C1, C2, C3; pain in the neck and shoulders
CN V; frontal headache
CN VI; visual symptoms
CN IX, X; pain in occipital region
Theory #2
• In accordance with the Monro-Kellie Doctrine, in an attempt to maintain
intracranial volume there is a reflex vasodilation of the meningeal vessels in
response to the lowered CSF pressure
• Pain receptors in the venous sinuses, dural arteries and cerebral arteries at the base
of the brain, as well as, portions of the dura in this area are all stimulated causing
pain.
• Symptoms of PDPH
• Headache with pain commonly in the frontal or occipital regions
• Pain is worse in the upright position and relieved in the horizontal position.
• Onset/Duration
Usually presents within 1-2 days after dural puncture
95% of headaches resolve within a week
Longest PDPH lasted 5 years!
• Pain can range from mild to incapacitating

825
 • Symptoms of PDPH
• Nausea 60%
• Vomiting 24%
• Neck stiffness 43%
• Ocular symptoms 13%(photophobia, Diplopia, difficulty with accommodation)
– Auditory12% (hearing loss, tinnitus)
– Symptoms may persist for months or even years
Non-modifiable Risk Factors
– Age;
– Risk greatest between 18-30 years
– Females 2x more likely than males
– Low BMI have greater risk
– History of previous PDPH
– Postpartum mothers are also at an increased risk for a multitude of factors including ….
Modifiable Risk Factors
– Equipment related factors
– Type of needle
– Size of needle
– Procedure related factors
– Direction of bevel
– Positioning
– Stylet replacement
– Experience of the anesthetist
Type of needle; cutting vs. pencil point
– Pencil point needles are designed to separate fibers instead of cut them
– The use of a pencil point needles has cut the incidence of PDPH in half (12.2% vs 24.4%)
– Pencil point needles are less susceptible then cutting needles to tip deformities after
boney contact
Size of Needle
– Incidence and severity of PDPH are directly related to the size of the needle.
– Smaller spinal needles can be associated with higher failure rates
Procedure Related Risk Factors
– Direction of the Bevel
– Returning the stylet before removal of the needle
– Positioning
– Provider Experience

826
Diagnosis of PDPH
– Diagnosed on the basis of clinical features;
– History of a procedure such as a diagnostic LP or spinal anesthesia is almost invariably
present.
– The hallmark sign of PDPH is a postural headache.
– Imaging can be used to confirm PDPH or r/o other possibilities
– Contrast enhanced MRI is the imaging method of choice
Oral and IV Caffeine; 300-500mg PO or IV BID
Epidural Blood Patch
– The spinal interspace chosen for the EBP should be as close as possible to the initial
puncture site
– A volume of 15-20mL is recommended
– Phlebotomy should be attempted after identifying the epidural space to avoid clotting.
– Inject slowly through the epidural needle until one of the following endpoints occurs
– Complaint of back pain, neck pain or radicular pain in the legs or worsening headache
during the performance of the injection
– When 20mL have been injected without complaint
– Patient should lay supine for 1-2 hours post EBP and avoid heavy lifting or straining for
48 hours
– Can provide instant relief of symptoms!!
– Prophylactic EBP is not recommended

Burns—remember fluid formulas and defining percentage burned and temp considerations
• I: Resuscitative Phase
– Attention to airway, breathing, and circulation
– Dry air at 300 Degrees C or steam at 100 Degrees C causes massive edema and
rapid airway obstruction
– Inhalation injury added to cutaneous burn more than doubles the mortality
– Get a history to determine if airway injury occurred
– Intubate early before swelling makes it impossible
• Upper airway injury
– inhaled fumes, toxic chemicals, hot air can injure upper airway and lower
respiratory tract
– common in victims of structural fires
– life-threatening airway edema in up to 30% of pts

827
• Lower respiratory tract injury
– rare
– steam or burning gas inhalation cause
• The depth of skin destruction is characterized and first, second or third degree, depending
on whether there is superficial, partial-thickness, or full-thickness destruction of
skin/appendages.
• Mortality related to area involved by deep 2nd or 3rd degree burns.
– other factors: age, presence of inhalational injury, presence of burns caused by
high-voltage (> 1000v) electrical shock

• Body is divided into 11 sections, each section accounts for approximately 9% of the
body’s skin coverage.
• Add up all the areas of the body that are burned deep enough to cause blisters.

828
Systemic Effects of Burn Injury
• Hyper metabolism, usually beginning by end of first week after burn injury
• Degree of increase in metabolic rate directly proportional to burn size
• Oxygen consumption 2.5X > baseline
• 4000 kcal daily needed to prevent catabolism
Burn Shock
• Circulatory instability and tissue hypoperfusion / hypovolemic shock
• Fluid loss due to direct transudation of plasma from the wound and diffuse capillary
leakage
• Loss of endothelial integrity
• Severe depletion of plasma volume
• Release of inflammatory mediators: histamine prostaglandins, leudotrienes, complement
cascade

829
Fluid replacement
• Many different formulas available
• Parkland formula: 4ml/kg/% burn during 1st 24 hrs
• half in 1st 8 hrs
• second half over next 16 hrs
• maintain urinary output 0.5-1 ml/kg/hr
• colloids are controversial in first 24 hours

Operative Management of the

Burned Patient
• Goal: rapidly restore skin integrity after burn injury
– early excision of eschar and grafting of burn wounds
– decreases mortality, improves functional & cosmetic outcomes
– excisions can start within 3 days of injury, so pt has just been resuscitated from
initial injury
– High risk for infection. Always use strict aseptic technique
• Burn debridement’s are extraordinarily bloody operations
• Prevent infection and promote healing
• Blood loss can be deceptively large
• Layers of eschar removed until brisk bleeding seen
• Eescharectomy can be so fast that it’s difficult to keep up with blood loss
• Can be lulled into false sense of security since surgical team uses epi-soaked sponges on
wound
• other implications of exogenous catecholamines
• May use tourniquet

• Large bore IVs mandatory

• Arterial line invaluable
• CVP useful
• May be difficult to get good mask fit due to edema (early), scars/contractures (late)
• Succinylcholine
• absolutely contraindicated 24 hrs - 2 years after major burns
• Nondepolarizing relaxants
• resistance, e.g., diminished response to conventional doses
• dose required may be 3-5X > than in non-burned pt
• No single preferred agent or combination
• Ketamine or etomidate useful if volume status uncertain (side effects?)

830
 • Greatly increased narcotic requirements
• tolerance
• increased volume of distribution
• Propofol has greater negative inotropic effect than etomidate or STP. May induce
profound hypotension
• Currently morphine is most commonly used
• Increased narcotic requirement
• IV route preferred over IM
• Demerol is a poor choice
• Accumulation of normeperidine (t1/2 24-36 hrs)
• Short duration (2.5-3.5 hrs)
• CAUTION with NSAIDS including Toradol
• Inhibit thromboxane A… failure of platelet aggregation
• Most comfortable body temp for burn pt is ~ 100oF (38oC)
• Burn units have warm, humid atmosphere
• Maintain normothermia during transport & surgery
• OR, IV fluids, blood products should be warmed
• Inspired gases should be heated/humidified
• Immune system suppressed for weeks to months after burn injury
• Wound is excellent medium for bacterial growth
• Use aseptic technique when handling pts, suctioning airways, or inserting intravascular
lines

Post-op shivering, reasons TX, definite TX etc

Where are the centers for heat loss and heat gain located?
Heat loss—anterior hypothalamus. Heat gain- posterior hypothalamus.
Why does one get post-op shivering? Hypothermia-why? From heat loss- evaporation,
humidification of dry gases, radiation and convection from skin and wound.
-Core temp decreases 1-2C during 1st hr of GA (phase 1).
-Gradual decline after this during 3-4hrs (phase II)
-Steady state after this (phase III)
Initial decrease in temp- reason- redistribution of heat from central compartments to cooler
periphery from anesthesia induced vasodilation.

831
Thermoregulation is compromised, decreased and less effective under anesthesia.
-Body cannot compensate- anesthetic induced inhibition in hypothalamic thermoregulatory
functions.
-The BEST solution is maintain normothermia!!
- What is effective in prevention of phase 1 hypothermia? Prewarming for ½ hr with
convective forced-air warming blankets
- In fact, convective forced air warming is MOST effective!
- Meperidine is the best pharmacologic method for rewarming usually 12.5-50mg IV. -
Why does it work? NOT mediated by mu, most likely by K-opioid receptors.
What does shivering do to body?
-Increases O2 consumption up to 5-fold
-Decreases arterial O2 saturation
-Increases CO2 production
-Increases risk of myocardial ischemia and angina, delayed wound healing, increased periop
mortality
+++++The BEST solution for postop shivering is maintaining normothermia++++

832
 Methyl methacrylate- bone Reimplantation sx and TX etc

-Exothermic reaction- mix polymerized methyl methacrylate powder with liquid monomer-
hardens cement and expands it against prosthesis.
-Expansion causes intramedullary hypotension- embolize fat, bone marrow, cement and air into
bone venous channels.
-DC N2O prior to Cementing!!!
-Residual volatile monomer of methyl methacrylate causes hypotension from decrease in SVR
and vasodilation. Also can be from release of histamine from degranulation. Of mast cells.
-Clinical manifestations of bone cement implantation syndrome-
1. Hypoxia (increased shunt)
2. Hypotension
3. Dysrhythmias, heart block, sinus arrest
4. Pulm HTN. 5. Decreased CO
-How can we minimize the chance of getting bone cement implantation sx? Increase FiO2,
maintain euvolemia prior to cement. Create a vent hole in distal femur. Perform high-pressure
lavage of femoral shaft to remove debris. Use no cement.

Cord transection

-Injury above C3-5 need vent support to stay alive

-Injury above T1- Quadriplegia. Injury above L4- Paraplegia.
-Most common sites of transection- C5-6 and T12-L1.

833
Acute transection- 1-3week of spinal shock immediately after.
-High dose methylprednisolone 30mg first hr, 5.4mg/kg/hr for 23hour immediately following
injury
-C-spine precautions, head inline stabilized with intubating. AWAKE FOB SAFEST
-High transections again- impaired airway reflexes, hypoxemia from decreased FRC.
-Hypotension and bradycardia present after induction. Art line monitoring indicated
-When to use SUX? ONLY during the first 24 hours!! After there is a risk of hyperkalemia- due
to proliferation of NaCH receptors outside neuromuscular cleft.

Chronic transection-
-Possibility of autonomic hyper-reflexia. Risk of hyperkalemia
-Overactivity of SNS- transection above T6 or above- Autonomic Hyper-reflexia
-REGIONAL and DEEP general anesthesia effective in prevention of hyperreflexia.
-Severe HTN TX aggressively- leads to pulm edema, MI or cerebral hemorrhage. Give direct
vasodilators, and a-blocking agents
-Use NMDAs vs. suxx.
-Correlate chronic transection with renal insufficiency- from recurrent calculi and amyloid
deposition- so AVOID drugs that are excreted renally.

Autonomic Hyperreflexia- usually transections above T5

-Interruption of normal descending inhibitory impulses- cutaneous or visceral stimulation below
level of injury- intense sympathetic discharge- HTN, vasoconstriction BELOW transection,
AND baroreceptor mediated Bradycardia and vasodilation ABOVE- Take away stimulus.

834
Trigeminal neuralgia define nerves and TX
-Affects middle aged and elderly, with 2:1 female to male ratio
-Usually Unilateral, - usually in V2 or V3 (maxillary, mandible) distribution of trigeminal nerve
- Electric shock quality lasting 2min. Provoked by contact
-Facial muscle spasm may occur.
- Drug of choice for tx- carbamazepine. May add Phenytoin or baclofen. Also can do glycerol
injection or radiofreq. Ablation of gasserian ganglion and microsurgical decompression of nerve.

835
 Negative pressure pulmonary edema- who what when and how

-Associated with airway obstruction. A generation of large negative intrapleural and alveolar
pressure against a closed glottis- such when occurs during laryngospasm etc? –NPPE is signaled
by appearance of frothy pink fluid in ETT with - decreased O2 sat, wheezing, dyspnea, increased
RR postop in previously extubated pt.
-Negative intrapleural pressure causes increase in venous return, enhances pulm blood volume.
This negative pressure leads to an increase in pulmonary vascular volume and pulmonary
capillary transmural pressure, creating a risk of disruption of the alveolar–capillary membrane.
The early detection of the signs of this syndrome is vital to the treatment and to patient outcome.
-A CXR showing diffuse bilat. Interstitial pulm infiltrates
-Tx is supportive. Maintain patent airway, O2 administration, and diuretic therapy. Severe cases
need ETT with vent and PEEP.

COPD, Pulmonary function tests

Normal FVC- 5L. Normal FEV1- 4L. Normal FEV1/FVC- 0.75-0.85

>0.7 in patients with restrictive diseases
<0.7 in patients with obstructive disease

FVC- Forced vital capacity- volume of air that can be forcibly and maximally exhaled after
taking the deepest possible breath. Useful in diagnosing obstructive and restrictive diseases

FEV1= Forced expiratory volume in one second. The volume that can be forcibly exhaled from
the lungs in the first second of a forced expiratory maneuver.

FEF25%-75%- Describes the amount of air expelled during middle half of the FVC test-
Indicator of obstructive disease.

836
MVV - Maximal Voluntary Ventilation - determined by having the patient breathe in and out as
rapidly and fully as possible for 12 -15 seconds - the total volume of air moved during the test
can be expressed as L/sec or L/min - this test parameter reflects the status of the respiratory
muscles, compliance of the thorax-lung complex, and airway resistance. Surgeons like this test
value because it is a quick and easy way to assess the strength of the patient's pulmonary
musculature prior to surgery - a poor performance on this test suggests that the patient may have
pulmonary problems postoperatively due to muscle weakness. MVV can therefore be viewed as
a measure of respiratory muscle strength. One major cautionary note is that this test is effort
dependant and therefore can be a POOR predictor of true pulmonary strength and compliance.

FRC, RV, and TLC CANNOT be measured directly by Spirometry

-Obstructive pulmonary diseases are asthma, chronic bronchitis and emphysema

-Restrictive pulmonary diseases are pulm. Fibrosis, pneumothorax, chest wall disease such as
scoliosis or neuromuscular diseases

- The FEV1/FVC ratio is normally >0.7.

-COPD is present if BOTH FEV1 and FVC are low AND the FEV1/FRC is <0.7
-Restrictive disease is present if BOTH FEV1 and FVC are low AND FEV1/FRC is >0.7.
-A MMEF (midmaximal expiratory flow) of <70% (FEF25-75%) is the early abnormality in the
course of COPD.
The MMEF (AKA FEF25-75%) BEST assesses early stages of COPD AND is MORE reliable
than FEV1/FVC. Normal MMEF is 4.7L/sec or 280L/min
FEF25-75% values are >2.0L/sec in males, and >1.6 females.
• Normal PFT Outcomes - > 85 % of predicted values
• Mild Disease - > 65 % but < 85 % of predicted values
• Moderate Disease - > 50 % but < 65 % of predicted values
• Severe Disease - < 50 % of predicted values

837
Pulmonary Function Tests - A Systematic Way to Interpretation
There is a systematic way to read the PFT and be able to evaluate it for the presence of
obstructive or restrictive disease. The following steps will be helpful.
1. Step 1. Look at the forced vital capacity (FVC) to see if it is within normal limits.
2. Step 2. Look at the forced expiratory volume in one second (FEV1) and determine if it is
within normal limits.
3. Step 3. If both FVC and FEV1 are normal, then you do not have to go any further - the
patient has a normal PFT test.
4. Step 4. If FVC and/or FEV1 are low, then the presence of disease is highly likely.
5. Step 5. If Step 4 indicates that there is disease then you need to go to the %predicted for
FEV1/FVC. If the %predicted for FEV1/FVC is 88%-90% or higher, then the patient has a
restricted lung disease. If the %predicted for FEV1/FVC is 69% or lower, then the patient has an
obstructed lung disease.

Case # 1.

Predicted Values Measured Values % Predicted

FVC 6.00 liters 4.00 liters 67 %

FEV1 5.00 liters 2.00 liters 40 %

FEV1/FVC 83 % 50 % 60 %

Decision: This person is obstructed

Case # 2.

Predicted Values Measured Values % Predicted

FVC 5.68 liters 4.43 liters 78 %

FEV1 4.90 liters 3.52 liters 72 %

FEV1/FVC 84 % 79 % 94 %

838
Decision: This person is restricted

Case # 3.

Predicted Values Measured Values % Predicted

FVC 5.04 liters 5.98 liters 119 %

FEV1 4.11 liters 4.58 liters 111 %

FEV1/FVC 82 % 77 % 94 %

Decision: This person is normal. This person is normal because the FVC and FEV1 are
normal. It is irrelevant that the %Predicted for FEV1/FVC is 94% when FVC & FEV1 are
normal. The % predicted values for FEV1/FVC are only relevant when the FVC and the
FEV1 are abnormal.

-COPD is the most common pulmonary disorder encountered by us. Associated w/smoking,
male predominance as well.

-TLC/FRC/RV is INCREASED in obstructive disorders.

Again- MMEF is MORE RELIABLE and sensitive than FEV1/FVC. I will shit a brick if this
isn’t addressed on boards.

839
 COPD/ASTHMA

-Antigen binding to IgE- mast cell degranulation- histamine release- reflex vagal activation
mediated by increase in CGMP- bronchoconstriction.

-Bronchoconstriction also results from these- bradykinin, leukotriene’s C D E, platelet-activating

factor, PGE2, PGF2a, PGD2, neutrophil/eosinophil chemotactic factors.

PaSNS plays a major role in maintaining normal bronchial tone. Vagal afferents to bronchi are
sensitive to histamine, and noxious stimuli

-An FEV1/FVC < 0.5, hypoxia, hypocapnia is indicative of moderate to severe asthma.
Hypercapnea is indicative of severe air trapping.

-Continue /bronchodilators up to the time of surgery.

-In order of effectiveness--- B-agonists, inhaled glucocorticoids, leukotriene blockers, mast-cell

stabilizers, theophylline’s, and anticholinergics

-If patient on long term glucocorticoids, give supplemental hydrocortisone 50-100mg preop and
100mg q8h for 1-3d.

-The most critical time for asthmatics for anesthesia is during instrumentation of the airway.

-Drugs that should be avoided/associated with histamine release- curare, Atracurium,

mivacurium, morphine, meperidine. SUX can induce histamine release but can be used safely
according to M and M.

840
-Halothane can sensitize heart to B-agonists and theophylline’s- so not a good choice at least on
asthmatics who most usually take these drugs.

Intraoperative Bronchospasm-- Wheezing, increased PIP, decreased tidal volume, obstructed

pattern on capnography.

-Ketamine has Bronchodilating properties and is a good choice for asthmatics when appropriate.

COPD- Chronic Bronchitis/Emphysema

-Most patients with COPD have an element of both chronic bronchitis and emphysema
- Strongly associated with cigarette smoking

Feature Chronic Bronchitis Emphysema

Cough Frequent With exertion

Sputum Copious Scant
Hematocrit Elevated Normal
PaCO2 Often elevated over 40mmHg Usually normal or <40
Chest XRAY Increased lung markings Hyperinflation
Elastic recoil Normal Decreased
Airway resistance Increased Normal to slightly increased
Cor pulmonale Early Late

-According to M&M- O2 therapy can dangerously elevate PaCO2 in patients with CO2
retention... elevating PaO2 >60 can precipitate respiratory failure- what is responsible is thought
to be abolition of a hypoxic vasoconstriction that results in greater blood flow to areas of low
V/Q. These patients have chronic respiratory acidosis and they rely on peripheral chemoreceptor
O2 drive for breathing.

-Pts with chronically elevated PaCO2 have increased HCO3 levels in the CSF- these ions reset
the central medullary chemoreceptors and decrease the central respiratory drive sensitivity to
CO2- so if PaO2> 60, PERIPHERAL chemoreceptor respiratory drive diminishes and the patient
will hypo ventilate.

841
-6 extubation criteria for COPD patient- PaCO2<50, PaO2>60 on 50% FiO2, maximal resp
effort over 20cmH20, normal pH, respiratory rate <30bpm and vital capacity>15ml/kg.

-Two diagnose chronic bronchitis patients, generally this includes having a chronic cough on
most days for 3 months a year for at least 2 years.

-In contrast to asthma, only limited improvement in resp function after a short period of intensive
preop preparation.

-Patients with greatest risk of complications are those with preop PFTs< 0.5 of predicted.
-Smoking should be stopped 6-8 weeks prior to operation

-COPD patients have an increased antero-posterior dimension.

-Know that in COPD, airway resistance increases, AND pulmonary compliance increases.
-Regional mismatching of ventilation and perfusion (V/Q) is the primary mechanism of
hypoxemia in COPD.

842
 Cocaine abuse

 Manifestations:
o Generally display euphoria, tachycardia, and hypertension
o More serious manifestations include seizure, coma, myocardial infarction,
pulmonary edema, or subarachnoid hemorrhage
 Anesthetic implications:
o Avoid pure ß-antagonist drugs because of the potential for worsening
hypertension related to unopposed å-receptor stimulation by cocaine
o General anesthesia may be associated with uncontrolled hypertension/tachycardia
and life-threatening dysrhythmias
o Cocaine is a local anesthetic, and systemic toxicity may be additive when using
amide local anesthetic for epidural anesthesia
o Chronic cocaine abuse may be associated with thrombocytopenia
Pericardial effusion

 Diastolic filling is impacted by pericardial restraint

o Diastolic filling is an active process and a major component of effective cardiac
performance
o Presence of diastolic dysfunction, whether resulting from loss in fluid volume, LV
disease, or pericardial restraint, is associated with potential deleterious surgical
outcomes
 Can be global, surrounding the entire heart, as seen mostly after cardiac surgery
 Because the intrapericardial volume is constant, cardiac chambers are compressed when
at their lowest pressure (atria in systole, ventricles in diastole)
 Dx. – Doppler echocardiography
Mediastinoscopy – complete via transverse incision just above the suprasternal notch or in the
second rib interspace

 Anesthesia implications:
o Arterial line in right radial artery to monitor for compression of innominate and
right brachiocephalic arteries
o Monitor BP in left arm
o Pulse ox on either hand – right would assess compression
o Large venous tear may mandate IV insertion in leg
o Endotracheal intubation
o Muscle paralysis
o Positive pressure ventilation – decreases risk of air embolism

843
  Complications:
o Hemorrhage
o Air embolus
o Nerve injury
o Pneumothorax
o Esophageal injury
o Thoracic duct injury
o Tracheal compression
Intra-aortic balloon pump

 Simplest and most readily available mechanical support device

 Device:
o 25-cm long, sausage shaped balloon composed of nonthrombogenic polyurethane
mounted on a 90-cm vascular catheter
 Placement:
o Generally inserted into the
femoral artery and
advanced so the distal tip is
below the left subclavian
artery (to prevent emboli to
the head vessels) and the
proximal above the renal
arteries
o Alternative placement –
insertion via the ascending
aorta
 Only method that decreases
myocardial oxygen demand and
increases oxygen supply to the myocardium
 Mechanics:
o Synchronized counter pulsation to assist a beating, ejecting heart: blood volume is
moved in a direction “counter” to normal flow
o Balloon is inflated during diastole and deflated during systole
o Balloon inflation elevates aortic diastolic blood pressure, thus increasing coronary
perfusion gradient proximally, and enhances forward flow distally
 During the subsequent systole, the LV will eject facing a lower systemic
diastolic pressure
o Proper timing of the balloon deflation is necessary to reduce end diastolic
pressure to maximally offload the ventricle
 Crucial to control heart rate and suppress atrial and ventricular dysrhythmias to ensure
proper balloon timing

844
  Indications:
o Complications of myocardial ischemia
o Acute cardiac instability
o Open heart surgery
 Contraindications:
o Severe aortic insufficiency
o Inability to insert
o Irreversible cardiac disease – not a transplant candidate
o Irreversible brain damage
 Complications:
o Ischemia distal to the site of balloon insertion
o Direct trauma to the vessel
o Thrombosis – most common
o Platelet destruction/thrombocytopenia
Heart murmurs

 Aortic regurgitation
o Diastolic murmur at left sternal border
o Produces eccentric left ventricular hypertrophy
o Goal:
 Rhythm – maintain sinus rhythm – avoid sudden decrease in heart rate
 Preload – maintain/increase
 Afterload – decrease – reduce with digitalis, diuretics, ACE inhibitors
 Mitral regurgitation
o Blowing, holosystolic murmur at apex, with radiation to the axilla
o Produces eccentric left ventricular hypertrophy
o Symptomatic progression
 Regurgitant factors < 30% = mild symptoms
 Regurgitant factors 30 – 60% = moderate symptoms
 Regurgitant factors > 60% = severe symptoms
o Goal:
 Rhythm – maintain sinus rhythm – bradycardia worsens regurgitant flow
 Preload – maintain/elevate preload
 Afterload – decrease to improve cardiac output
 Aortic stenosis
o Systolic murmur at the right second intercostal space with transmission into the
neck
o Produces concentric hypertrophy
o Goal:
 Rhythm – maintain sinus rhythm – maintain HR 60 – 90 bpm to control
oxygen utilization and prevent myocardial ischemia
 Preload – maintain
 Afterload – maintain to keep coronary perfusion pressure stable

845
  Mitral stenosis
o Goal:
 Rhythm – maintain sinus rhythm – maintain HR 60 – 90 bpm to allow for
diastolic filling
 Preload – maintain
 Afterload – should be maintained
Cardiac stretch receptors

 Baroreceptors:
o Sense changes in pressure within the vasculature
o Aortic bodies – innervated by Vagus nerve (CN X)
o Carotid sinus – innervated by
glossopharyngeal nerve (CN IX)
 Peripheral chemoreceptors:
o Respond to changes in PaO2 (also
PaO2 and H+)
o Aortic chemoreceptors – innervated
by Vagus nerve (CN X)
o Carotid bodies – innervated by
glossopharyngeal nerve (CN IX)
 Bainbridge (atrial) reflex:
o Elevation in CVP activates atrial
stretch receptors, causing a
compensatory increase in heart rate to
accommodate an increase in preload
Oculo-cardiac reflex – triggered by pressure on the
globe and by traction on the extraocular muscles, as
well as on the conjunctiva or the orbital structures.
May be elicited by retrobulbar block, ocular trauma,
direct pressure on tissue remaining in the orbital apex after nucleation

 Afferent pathway - TRIGEMINAL

 Efferent pathway – VAGAL
 Manifestations – SB, cardiac
dysrhythmias
o Reflex may appear
during local or general
anesthesia –
hypercarbia and
hypoxemia are believed to
augment the incidence and
severity of the problem
 Treatment:

846
 o Surgeon should be asked to cease operative manipulation
o Assess patient’s depth of anesthesia
o Administer atropine intravenously
Kellie-Monroe doctrine – there is a pressure-volume relationship between ICP, volume of CSF,
blood and brain tissue, and cerebral perfusion pressure (CPP)

 Hypothesis:
o The intracranial compartment is incompressible, and the volume inside the
cranium is a fixed volume
o The cranium and its constituents (blood, CSF, and brain tissue) create a state of
volume equilibrium, such that any increase in volume of one of the cranial
constituents must be compensated by a decrease in volume of another
 Cerebral blood flow (CBF):
o Increases – hyperventilation/reduction CO2, volatile agents, nitrous oxide,
ketamine
 CBF is a linear relationship with PaCO2 -
 CBF changes by ~ 3% of baseline for each 1 mm Hg change in PaCO2
 As CBF changes, so does cerebral blood volume (CBV) – hyperventilation
can be used for short periods of time to relax the brain/reduce ICP
o Decreases – isoflurane with hyperventilation, intravenous general anesthetics

Physiology- study of how an animal works

Anatomy- study of structure
Pathophysiology- study of changes in normal physiological and biochemical functions (diseases)
Level s of organization

 System, organ, tissue, cells *life is possible at cellular level

Cell theory

 cells are the basic units of life

 new cells are created by old cells dividing in two
Cell Membrane

 Fluid mosaic model: lipids, fats, CHO, proteins make sheath semi-permeable (ex: lung
cells thin, skin is thick)
 Membrane phospholipids form bilayers, micelles or liposomes
 Lipids/fats change configuration during digestion and create different structures
 Proteins (50% cell membrane): types=integral, peripheral, lipid-anchored. Do the work of
plasma membrane by bringing things thru/to /from the cell
 Cytoplasm compartments and their components:

847
 o Cytosol- intracellular fluid
o Membrane organelles- mitochondria, ER, Golgi complex, lysosomes,
peroxisomes
o Inclusions- lipid droplets, ribosomes, proteasomes, cytoskeleton, centrioles
(moves DNA), centrosome, cilia (move things inside/outside cell), flagella (sperm
cell)
o Cytoskeleton and cytoplasmic protein fibers: microvilli increase surface area,
microfilaments form network inside cell membrane, supports microvilli.
Microtubules are the largest cytoskeleton fiber. Intermediate filaments include
myosin and keratin
Mitochondria- food (sugar) is combined with oxygen to produce ATP - the primary energy
source for the cell.
Endoplasmic reticulum- ribosomes make proteins to do work inside cell
Golgi complex- proteins can by modified for specialized function
Cytoplasmic Vesicles

 Lysosomes and peroxisomes are places in the cell that have higher acid, lower pH and
degregate unwanted material
 Nucleus- selectively permeable, holds DNA “brain”
Tissues: collection of cells performing similar functions. Cells are bound together by cell-cell
junctions

 Cell types
o Muscle tissue
 Contractile- force and movement
 Signal conduction
 Types of muscles
 Cardiac-elongated divisions, intrinsic control
 Smooth- no striations, intestines, vessels (involuntary)
 Skeletal- multiple nuclei, does mechanical work
o Nervous tissue
 Neurons and signals- communicate and send impulses from one place to
another fast. Could cause a gland to secrete a hormone or sense pain, heat,
touch
 Excitable
 Electrical
 Chemical
 Glial cells- support the neurons and give them nutrients

848
 o Epithelial tissue- semi-permeable sheet of cells that separates environments. Lines
and covers body surfaces, forms membranes and glands, under a lot of wear and
tear and are therefore replaced often. Can be simple tissue (lung) or stratified
(skin)
 Exchange- leaky, allows movement through cell gaps
 Transporting- tight junctions prevent movement to adjacent cells. Must
pass thru apical and basolateral membrane to get across
 Secretory- exocrine directly secretes across gland and works locally and
endocrine tissue which secrete hormones into blood and ECF and carry to
remote receptor
o Connective tissue
 Dense connective: tendons and ligaments
 Loose connective ex: adipose- protective and insulates
 Supporting: ex: cartilage

Cell-cell junctions

 Tight junction- things cannot seep thru as well

 Adherents-serve as a bridge connecting the actin cytoskeleton of neighboring cells
 Desmosome- strong but not as tight (leaky) “anchoring junction”
 Gap junction- pores/channels that transmit chemical and electrical signals via direct
contact and local cell-cell communication Ex: myocardial cells pass one electrical signal
on to the next
Organs- anatomical and functional units made up of two or more primary tissues
 Lumens of hollow organs
o Heart
o Lungs
o Blood vessels
o Intestines
 Lumen
o Fluid-filled interior
o Not the internal environment
Organ Systems- group of organs working together to perform related functions
 Circulatory, digestive, endocrine, immune, integumentary, MS, nervous, reproductive,
respiratory, urinary

849
Body Cavities
1. Cranial- spinal cord
2. Thoracic- membranes around the heart and lungs
3. Abdominopelvic- renal, digestive, reproductive
Body Fluid Compartments
1. Extracellular fluid
a. Plasma- liquid portion of blood
b. Interstitial fluid- bathes cells
2. Intracellular fluid- inside of cell (aka cytosol)
Homeostasis- body can dictate environment within us
 “Environment” is the external world for an animal. Ex air around us is our environment.
ECF is environment for a cell

Membrane Transport/Diffusion
1. Passive diffusion – molecules move from higher concentration to lower concentration
(along its concentration gradient) without energy (O2, gases can move thru membranes
easily)
2. Ion-Selective channels- molecules will move across the membrane but only when a
“door/channel” is open. There are different size doors that semi-permeable and material
move from a high to low concentration.
3. Primary Active Transport via the Na/K ATPase pump (aka Sodium pump) ATP is
oxidized to ADP and the energy moves a molecule AGAINST t its electrochemical
gradient (uses up 10-25% energy in the body.) Consequently 3 Na are moved into the cell
and 2 K are moved out of the cell to maintain the cell potential
4. Secondary Active Transport- moves molecule AGAINST the concentration gradient.
Does not burn ATP directly but piggy-backs onto another cell while their moving in with
their concentration gradient (usually Na)
a. Antiport- Moves two or more molecules across membrane in opposite directions
b. Symport- Moves two or more molecules across membrane in same direction
Transport Proteins
Types
a. Open channels- water and ion channels that allow fluids/molecules from high to
low concentration
b. Carriers- never form an open channel between two sides of membrane. They
change shape to allow things to go thru then close

850
 Functions
o Structural proteins
o Enzymes
o Membrane receptor proteins
o Transporters (channel proteins and carrier proteins-used as receptors)
Diffusion and Properties
 Passive
 High to low concentration
 Net movement until concentration is equal
 Rapid over short distance
 Directly related to temp- high temp higher diffusion
 Inversely related to molecular size- bigger molecule takes longer to diffuse and size of
molecules thickness factors in to speed of diffusion
 In open system or across a partition (cell membrane)
Facilitated Diffusion- diffusion of glucose into cell via protein: needs protein to get molecule
across membrane when concentration is higher outside than inside. It stops when the
concentrations are equal. As glucose accumulates into the cell it is broken down into glycogen
via glycolysis so the amount of “free” glucose in the cell looks less to keep it coming in.
Bulk Transport- moves large molecules and particles across membranes (bacteria and viruses)
 Endocytosis- vesicle’s (ball of lipids) being brought into the cell
 Exocytosis- molecule floats to surface of membrane and goes out of cell
Osmosis
 Def: Net diffusion of H2O across a selectively permeable membrane. Needs a channel.
 H20 diffuses down its concentration gradient
 H20 is less concentrated where there are more solutes
 Cant burn energy to make h20 move across membrane but can “coax” it by adding
solutes where you want it to move
 Hypotonic- water-rich, salt poor. Cell swells
 Hypertonic-water-poor, salt rich. Cell shrinks
Oncotic pressure- amount of pressure needed to make sided equal.
Electrogenic transporters- Na, K, ATPase creates membrane potential by voltage difference
across membrane

851
Cell to cell communication
Methods:
a) Contact dependent signals- require interaction between membrane molecules on two
cells. Transfer signals in both directions
b) Autocrine signals- chemical signals that act on same cell that secreted them. Paracrine
signals are secreted by one cell and diffuse to adjacent cells
c) Hormones- long distance communication. Secreted by endocrine glands or cells into
blood and transported to target cells with accepting receptor.
d) Neurotransmitters- chemicals secreted by neurons that diffuse across a small gap to target
cell. Have a rapid effect
e) Neurohormones- chemicals released by neurons into the blood for action at distant targets
with that receptor
Signal pathways- target response depends on the target receptor
EX: Epinephrine with alpha receptor causes blood vessels to constrict but on the beta receptors
the vessels in the GIT dilate (shunting blood to crucial organs for “flight or fight” response)
Transducers- covert EC signals into IC messages which creates an amplified response
Homeostasis- constancy of the internal environment
Negative feedback: If a regulated variable is outside the desired range a sensor is activated which
goes to the integrating center (sets the “set point” and looks for error signals) that processes the
information and decides on response. Then sends information to effectors and goes back to
regulated variable. If the variable is then in the desired range the stimulus is stopped.
Factors under homeostatic control:
 nutrients
 gases
 waste products
 ph
 salt and other electrolytes
 temperature
 volume and pressure

852
 PATHOPHYSIOLOGY Remember When?

Cell Injury and Responses

Types of adaptation
1) Atrophy- decrease in workload/use, blood supply, nutrition, hormonal stimulation and
nervous stimulation
a. Mechanism:
i. decreased protein synthesis
ii. Increased protein catabolism
iii. Autophagy-cell eats themselves
b. Most commonly affects
i. Skeletal muscle
ii. Heart
iii. Secondary sex organs
iv. Brain
2) Reversible- loss of ATP, cellular swelling, detachment of ribosomes, autophagy of
lysosomes
a. May return but may not be to normal state
3) Irreversible- point of no return! Severe vacuolization occurs of the mitochondria and Ca
moves into cell including the mitochondria membrane damage
a. Lack of ATP generation due to mitochondrial dysfunction
b. Major disturbance and damage in membrane function
c. Chemical, hypoxic, free radical, unintentional, intentional, immunologic,
inflammatory
4) Chronic cell injury- persistent stimuli response may involve only specific organelles or
cytoskeleton
5) Necrosis- common type of cell death with severe cell swelling and breakdown of
organelles
a. Sum of cellular changes after local cell death and inflammatory response reaction
b. Leads to dense clumping and progressive disruption of genetic material
6) Apoptosis- cellular self-destruction for elimination of unwanted cell populations
a. Local deletion of cells during normal embryonic development, cells dying during
turnover.
7) Hypertrophy- increase in cell size
a. Due to increase work load
b. Most commonly affects heart and kidney
c. Mechanism
i. Increase accumulation of cellular protein
ii. Increase rate of protein synthesis
iii. Decrease rate of protein degradation
iv. Nucleus has increase in DNA synthesis

853
 8) Metaplasia- reversible replacement of one mature cell type by another less mature type
a. EX: Smokers lung- replacement of old normal epithelial and cilia with stratified
epithelium which do not have cilia and will case more secretions
9) Dysplasia- deranged cellular growth
a. Most common in epithelial cells of cervix and respiratory tract
b. Associated with neoplastic growth usually
c. Hyperplasia- increase in number of cell division due to increase number of cells
usually as a response to injury and cell death
i. Compensatory: normal or physiologic
ii. Hormonal hyperplasia- uterus and breast
iii. Pathologic hyperplasia- abnormal proliferation of normal cells, clumping
of chromatin, ex. Endometrial hyperplasia
Common forms of cell injury
 Hypoxic injury
o Decreased O2 availability d/t low Hgb or Hgb function
o Decreased RBCs
o Decreased blood supply ***ischemia most common
o Respiratory and CV disease
o Poisoning of ROS in cells
 Reactive oxygen species and free radical-induced injury
 Chemical injury
Causes of cell injury
 Lack of O2-deprivation of O2 and nutrients to cell
 ATP depletion-lack of protein synthesis
 Free radicals
 Intracellular calcium and loss of calcium steady state
 Defects in membrane permeability/transport- causes continued loss of proteins, essential
coenzymes and RNA
o Caused by chemicals
o Free radicals
o Ischemia
o Antibodies
o Genetics
Manifestations of cell injury
o Fever and increased heart rate
o Increased WBC d/t infection
o Pain r/t pressure, obstruction
o LDH- from RBC, liver, kidney, skeletal muscle
o CK- from skeletal muscle, brain, heart
o AST- from heart, liver, skeletal muscle, kidney, plasma

854
 o ALT- from liver, kidney, heart
o ALP- liver and bone
o Amylase-pancreas
o Aldolase-skeletal muscle, heart
Changes in hemoglobin will increase O2 capacity more than changing the O2 concentration due
to formula: CaO2= (SaO2*Hb81.31) + .003(PaO2)
o PaO2 is dissolved O2 of paO2
o CaO2 is carrying capacity of one O2 molecule
Suffocation- reduction in ambient O2 to 16%
Carbon monoxide poisoning- hypoxic injury causing high carboxyhemoglobin levels with
increased affinity of O2 to hgb due to CO high affinity (300 times) that of O2
ATP depletion
o Decrease in blood supply decreases O2
o Decreases mitochondrial phosphorylation decreasing ATP production
o Anaerobic metabolism temporarily raises ATP but then runs out
o ATP reduction leads to decreased plasma membranes NA/K pump (Na and water
move into cell and K out causing swelling) and Na/Ca exchange fails ( increase of
Ca in cytosol)
o Cell injury or death disrupting DNA replication
o Catabolites can produce free-radicals
Free Radicals
Def. electrically uncharged atom or group of atoms having an unpaired electron (unstable) it
gives up or steals an electron possibly injuring the chemical bond formation with proteins, lipids
and CHOs
Initiated within cell by:
a. Absorption of extreme energy source (UV, X-rays)
b. Endogenous, oxidative, reactions that occur normally
c. Enzymatic metabolism of endogenous chemicals or drugs
Reperfusion injury can happen during organ transplants, cardiac surgery, or strokes. Xanthine
dehydrogenase (free radical) f causes damage to membrane leading to calcium overload.
Treatment: low levels of nitric oxide

855
Hyperbilirubinemia-derived from structure of Hemoglobin.
Elevated when…
o Destruction in RBCs
o Diseases that affect metabolism and excretion of bilirubin in the liver
o Diseases that cause obstruction (gallstones, pancreatic mass)
o Certain drugs, hormones
Incidence- number of new cases of a disease in certain time frame /number of people in
population
Prevalence- proportion of population affected by disease at a specific time. Determined by
incidence rate and length of survival period. Certain types of cancer are higher depending on
location. Also takes into account genetic influence
Relative Risk- common measure of effect of a specific risk factor expressed as a ratio:
Incidence rate of the disease among individuals exposed to a risk factor/ incidence rate of the
disease among individuals NOT exposed to risk factor
Multifactorial Inheritance- many factors contributing to a disease (genetics plus environment) ex:
age, gender, diet, exercise, family hx
Polygenic- many genes cause a disease
Quantitative traits- wt BP can measure
Empirical risk- studies done making generalizations based on research (ex: women are more
prone to PONV than men)
Multifactorial inheritance
a. Recurrence risk is higher if more than one family members affects
b. If expression of disease is more severe
c. Proband is of less commonly affected sex
d. Decreases in more remote relatives
Body Mass Index
Wt (lbs) *703/ht (in) 2
Or wt (kg)/ ht (m) 2
Cancer cells

856
Xenobiotic- (a chemical compound (as a drug, pesticide, or carcinogen) that is foreign to a living
organism) is transported in blood by lipoproteins and penetrates the lipid membrane (injuring it.)
Then the chemicals react with proteins and DNA and cause cell damage.

857
 Cognitive Development:

 Person achieves competence through neural processes in Cognitive, Sensory, and Motor
systems
 Central nervous system is comprised of: Brain and spinal cord
 Peripheral nervous system is comprised of: cranial nerves (12 pairs) and cord nerves
(31 pairs)
Divisions of the Central Nervous System

 Spinal Cord
o Cranial nerves
 Olfactory
 Optic
 Oculomotor
 Trochlear
 Trigeminal
 Abducens
 Facial
 Acoustic
 Glossopharyngeal
 Vagus
 Spinal accessory
 Hypoglossal
 Cord Nerves
o Ventral= anterior (motor function) Dorsal=posterior (sensory function)
 8 cervical
 12 thoracic
 5 lumbar
 5 sacral
 1 coccygeal
 Forebrain –Located supratentorial. 2 cerebral hemispheres, conscious perception of
stimuli, thought and memory processes, and voluntary control of skeletal muscles.
o Cerebrum- largest portion of the brain
 Cerebral cortex- contains gray matter that receives, integrates, stores and
transmits information “powerhouse” of brain
 White matter- composed of myelinated nerve fibers
o **Diencephalon - deep portion of forebrain and processes incoming sensory data
 Thalamus (integrating center for afferent impulses to cerebral cortex),
hypothalamus (maintains constant internal environment, implementation
of behavioral patterns) epithalamus (has connections and functions closely
associated with those of limbic system), subthalamus (part of the basal
ganglia system))

858
 o **Frontal lobe- Risk taking behaviors, sex drive, and speech. Also center for
voluntary control of skeletal muscle movements.
o Parietal lobe-Sensory and verbal memory. center for somatic sensory input,
perception
o Occipital lobe- receives input from retinas, visual association
o **Temporal lobe- Language. Auditory center, reception and interpretation of
speech, and dysfunction may result in aphasia or dysphasia (Wernicke area.) Also
involved with long term memory, balance, taste and smell
o Brocas area- Left hemisphere. Responsible for motor aspects of speech (damage
causes expressive aphasia or dysphasia)
o Corpus callosum- connects the two hemispheres
 Midbrain- relay center for motor and sensory tracts and auditory and visual reflexes
 Hindbrain- Infratentorial. Allows sampling and comparison of sensory data from
periphery and motor impulses from cerebral hemispheres for the purpose of coordination
and refinement of skeletal muscle movement
o Cerebellum-proprioception. Composed of two cerebellar hemispheres.
Responsible for conscious and unconscious muscle synergy and for maintaining
balance and posture
o Pons- Important in control of respiration. Bulging appearance below midbrain
and above medulla oblongata. Transmits information from cerebellum to
brainstem.
o Medulla oblongata- lowest portion of brain stem. Reflex activities such as HR,
respiration, BP, coughing, sneezing, swallowing and vomiting
 Brainstem- Midbrain, medulla oblongata and pons
Reticular Activating System (RAS)
o Located in brain stem
o Controls consciousness/ LOC (arousal and attention)
 Composed of inhibitory and excitatory neurons in the reticular formation
o Detects sensory info and sends signals to higher centers of brain
o Regulate vital reflexes, CV function and respiration
 Two essential characteristics of central cognitive neural system
o Awakeness
o Awareness- meaningfully
 Cognition (part of RAS) is developed using distinct systems
o Attentional
o Memory
o Language
o Executive (reasoning)

859
Meninges

 Dura mater-Outermost layer. Forms rigid double thickness membranous plates that
support and separate various brain structures. Above this space is where epidurals are
placed.
 Subdural space- between dura and arachnoid. Contains small bridging veins.
 Arachnoid membrane- below dura. Filmy, web like structure that loosely follows the
contours of cerebral structures but goes over the sulci
 Subarachnoid space- contains CSF. This is where spinal anesthetics go.
 Pia mater- delicate and adheres to surface of brain and spinal cord, sulci and fissures.
Provides support for blood vessels serving brain tissue.
o Choroid plexus- arises from pia mater and produces CSF
Cognitive pathology processes

 Infection- meningitis
 Vascular- embolic, thrombotic, hemorrhagic, ischemic
 Neoplastic
 Traumatic- MVA, sports injury, altercations
 Psychogenic
 Genetic- early onset Alzheimer’s (#1 cause dementia) Parkinson’s (Lewy bodies)
 Metabolic- hypoxemia, hypoglycemia, uremia, ammonia, meds, epilepsy
1. Dementia- progressive cognitive decline without decline of LOC
a. Changes include: orientation, recent and remote memory, language, reasoning,
behavior
b. Irreversible causes:
i. Neurodegenerative: Alzheimer’s, Lewy bodies, frontotemporal,
Huntington and Parkinson’s disease
ii. Vascular: Vascular dementia, multi-infarct, amyloid angiopathy
iii. Infection: Mad cows, post encephalitic dementia, Dementia w HIV
2. Cerebral death- irreversible coma with permanent brain injury with maintenance of
cardiac, respiratory and other vital functions
3. Brain death: permanent brain damage without maintenance of cardiac, respiratory and
other vital functions

860
Assessing cognitive dysfunction
1. Stages of LOC:
 Confusion (dementia)
 Disorientation
 Lethargy
 Obtundation
 Stupor
 Coma – light (purposeful movement to stimuli) coma- (non purposeful movement to
stimuli) deep (nonresponsive to stimuli)
2. Respiratory patterns
 Hemispheric- Normal, post hypoerventilation apnea, Cheyne-Stokes
 Brainstem- Central reflex hyperapnea (hypertension- decreased CBF) apneusis,
cluster, ataxis, agonal
3. Pupillary Patterns
 Fixed and dilated:
o Epinephrine
o Amphetamines
o Atropine, Scopolamine
o Hypothermia
 Pinpoint
o Opioids
o High dose barbiturates
o Pontine damage
 + brisk oculocephalic and oculovestibular reflexes
o Cortical dysfunction with intact brain stem
 Abnormal eye movements, nystagmus, divergent gaze
o Brain stem dysfunction
 Fixed, unequal, moderately dilated
o Glutethimide
 Midposition and fixed
o Midbrain dysfunction
4. Abnormal motor response
 Purposeful movement- intact corticospinal tract
 Nonpurposeful movement- decerebrate, decorticate of both
 No movement present

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Cerebral blood volume and flow

 CBV: volume of blood inside cranial vault (CSF and blood)

o 10% brain content
o 70% venous (cerebral sat monitoring’s helpful)
o Influenced by changes in CBF
o Brain receives 15-20% of cardiac output
o Remains constant with change in pressure = Auto regulation
o Inhaled anesthetics decrease auto regulatory response
 CPP=MAP-ICP (or CVP)
o Normal is 60-100
 Cerebral blood flow
o For every 1mmHg reduction in CO2 there’s a 3% reduction in flow (d/t
vasoconstriction)
o Auto regulatory mechanism is sensitive to PaO2 <50
o Responsive to local factors (gray> white matter)
o #1 determinate of flow rate is the radius of the vessel (Poussels Law)
o Jugular bulb O2 is 55-70% (this is to the brain what sVo2 is to the body)
o Cerebral venous O2 sat is >50%
o Hyperglycemia can accelerate hypoxic brain injury (since the areas are already
injured)
o Hippocampus and cerebellum are most sensitive to hypoxic injury
o There is a direct proportion metabolism: temperature
 CBF changes 5-7% for every 1 degree Celsius
 At 20 degrees isoelectric EEG
o BBB- disrupted by several factors: Can attempt to TX with Mannitol if BBB
intact
 Severe HTN
 Tumor
 Stroke
 Infection
 Hypercapnia, hypoxia
 Sustained seizure activity
 Cerebral ischemia
o Increase in intracellular Na and Ca
o Decrease in intracellular K
o Due to influx of Ca
 lipases and proteases initiate structural damage to neurons
 Increase in free fatty acids which activate formation of prostaglandins and
leukotrienses which also mitigate cellular injury
 LOOK OVER CEREBRAL EXTRACTION OF OXYGEN

862
Circle of Willis

 Anterior and Central Circulation

o Internal carotid
o Middle cerebral artery (MCA)
o Anterior cerebral artery (ACA)
 Posterior Circulation
o Vertebral arteries
o Basilar arteries
o Posterior cerebral artery
ICP

 Normal is 0-10mmHg
CSF

 clear, colorless fluid similar to blood plasma and interstitial fluid

 prevents tugging on meninges, nerve roots and blood vessels
 600 ml of CSF is produced per day and 125-150 is circulating in the ventricles and
subarachnoid space at any given time
 CSF is produced by the choroid plexuses in the lateral, third and fourth ventricles
 Arachnoid villi reabsorbs CSF into venous circulation via a one way valve preventing
blood flow into the subarachnoid space
 CSF flow is the result of a pressure gradient between the arterial system and CSF filled
cavities
 Components of CSF are Na, K, Cl, HCO3, Glucose, PH 7.3, protein, albumin, gamma
globulins, WBCs and RBCs

Blood Brain Barrier

 Selectively inhibits certain substances in the blood from entering the interstitial spaces of
the brain or CSF
 It is impermeable to large and potentially harmful molecules
 Permeability can be affected by hormones and neurotransmitters,
 Maintains homeostasis

863
Head Trauma

 Compound fracture
o Coup and countercoup
o Bleeding from tears of small vessels causing brain edema then neural tissue
damage
o Increasing ICP if not resolved leads to necrosis and further bleeding and edema
 Contusion
o Severity r/t amount of energy transmitted from skull to brain
o Affects memory, motivation and planning
o Can be hemorrhagic
o s/S: LOC, loss of reflexes, momentary increase in ICP then return to
consciousness
 hematoma
o Epidural- arterial bleed 85% the time. With or without fracture, can shift brain if
significant
 S/S: LOC w/ periods of lucidity S/S accumulation: severe headaches,
vomiting, drowsiness, contusion, seizure,
 Surgical TX is burr holes or cranioplasty
o Subdural- acute or chronic
 Tearing of bridging veins
 Expanding mass that increases ICP and compresses bleeding vessels
leading to necrosis
 Bleeding is self-limiting but a displacement of brain causes temporal lobe
herniation
 Puts more pressure on the brain than in an epidural bleed
 S/S: chronic headaches and tenderness over area
 Tx: burr holes, clot evacuation may require craniotomy
 Diffuse brain injury (DAI)- cellular level
o Due to shaking affect, rotational acceleration and shearing (causes axonal
damage)
o Produces strain and distortions within the brain
o Affects cognition processing, responding and attention
o Secondary injury by oxygen-free radicals which leads to exotoxicity then cell
swelling and cell death
EX: concussions (mild to severe)
 Ischemic Cerebrovascular Accident (CVA)
o With or w/o infarct
o Global-insufficient blood flow (ex: heart surgery)
o Types:
 Thrombotic- arterial occlusions, increased coagulation, inadequate central
perfusion, hypotension
 Embolic- due to fragments of thrombi that causes occlusion

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  Hemorrhagic CVA
o Caused by: HTN
 Ruptured aneurysm
 AVM
 Amyloid angiopathy
 Angioma
 TBI
 Tumor
 Bleeding disorders, anticoagulation
 Tumors
o Primary or mets (breast and lung as primary)
o Compresses and decreases blood flow
o S/S: seizures, visual disturbances, unstable gait, increased ICP
Theory of Perfusion

 Cerebral Steal aka Reverse Robin Hood Syndrome

o Increased CO2 causes vasodilation to all areas. Ischemic areas are maximally
dilated so that flood is shunted to surrounding non-ischemic areas eventually
leading to their ischemia.
 Robin Hood Syndrome
o Decreased CO2 causes vasoconstriction which decreases blood flow to normal
areas of the brain and increase blood flow to ischemic areas
Spinal Cord Trauma

 Impingement/ischemia or severed spinal cord caused by vertebral injuries, fxs,

lacerations, concussion, contusion or hemorrhage
 Results in motor, sensory or both impediments at the level of the cord compression or
transection
o Clinical considerations: don’t have RA pts flex neck can cause trauma
 Level C3-C5 will leave pt at risk for respiratory failure (d/t innervation of phrenic nerve)
o Central cervical cord syndrome:
 UE motor deficits, especially hands.
 Varying degree of bladder function
o Anterior Cord Syndrome: (Anterior Spinal Artery)
 Loss of motor function below level of injury
 Loss of pain and temp sensation below level of injury
 Touch, pressure and position senses intact
o Posterior Cord Syndrome: (fx of Vertebral arch)
 Impaired light touch and proprioception
o Cauda Equina Syndrome (below L1 fracture, dislocation or disk herniation)
 LE motor deficits
 Variable sensorimotor dysfunction
 Variable reflex dysfunction
 Variable bladder, bowel and sexual dysfunction
 At risk for cauda equine syndrome with spinal anesthesia

865
 o Horner Syndrome
 preganglionic sympathetic truck or postganglionic sympathetic neurons of
cervical ganglion, or secondary to brachial plexus block (resolvable if
from block)
 ipsilateral pupil smaller than contralateral pupil
 sunken ipsilateral eyeball
 ptosis of affected eyeball
 lack of perspiration on ipsilateral side of face
Degenerative Joint Disease

 biochemical and biomechanical alterations of tissue of the intervertebral disk

 Types:
o Spondylosis- DDD soft tissue d/t wear and tear of cartilage
o Spinal stenosis- narrowing of spinal canal
o Low back pain
o Herniated intervertebral disk
 TX: surgery- microdisctectomy or fusion (to take the disc out)
Spinal Cord Tumors:

 Compresses spinal cord

 May be treated with surgery, long surgery, open back, bloody
Autonomic Hyperreflexia

 Transection/lesion of cord T6 or above

 Caused by stimulation of sensory receptors below level of cord lesion because PNS
remains intact but not functioning
 Occurs frequently with bladder or rectum distension, but can also be triggered with skin
or pain receptors
 Stimulation of sensory receptors below cord lesion causes reflexive response with
arteriolar spasm leading to increased BP. Baroreceptors stimulate PNS HR decreases.
 Massive sympathetic outflow:
o Uncompensated CV response
o Pounding headache
o Blurred vision
o Sweating above level of lesion with flushing of the skin
o Nasal congestion
o Nausea
o Piloerection
o Bradycardia

866
Hydrocephalus- compresses brain and destroys neural tissue d/t increased accumulation of CSF,
congenital
CSF leak from puncture:

 From spinal tap or spinal anesthesia

 Leak in dura that doesn’t close
 S/S: massive headache when person sits up but goes away when supine (decrease in CSF
when up)
 TX: IVF, IV caffeine, blood patch**
Neuropathies

 Dorsal root ganglion cells affected causing numbness

Radiculopathies

 Injury, damage, compression, infection, inflammation to spinal roots (of spinal nerves) as
they enter vertebral column
Plexus Injuries

 Nerve plexus distal to spinal roots but proximal to formation of peripheral nerves (C5-
T1)
 Caused by: trauma, compression, infiltration (anesthetic) positioning during surgery
 S/S: motor weakness, muscle atrophy, sensory loss in affected area, paralysis
o Root
o Trunk
o Division
o Cord
o Branches
Neuromuscular Junction Disorders

 Myasthenia Gravis
o Binding of auto bodies to Ach receptors (compete for Ach)
o Weakness results from interference with neuromuscular transmission
o Muscle relaxers make this worse DO NOT give NMB
 Amyotrophic Lateral sclerosis (ALS- Lou Gehrings)
o Motor system/neuron disease
o Involves lower and upper motor neuron degeneration secondary to demyelination
with glial proliferation causing sclerosis along corticospinal tract
o Involves CN III, IV, VI
o Results is progressive muscle weakness, respiratory failure and death

867
  Multiple Sclerosis
o Autoimmune disorder
o Degeneration of CNS myelin and loss of axons causing irreversible axonal
degeneration and scarring and sclerosis
o Affects gray and white matter
o Inflammatory changes in CNS increase progressive loss of brain tissue
o Can give NMB- weigh pros and cons
Pain

 Low back pain is most common disabling pain condition

 Pain is adaptive and protective
 Theories of Pain
o Specificity Theory:
 Intensity of pain is directly related to the amount of associated tissue
injury
 Does not allow for psychological contributions (attention to pain,
experience, emotion)
o Gate Control Theory:
 Pain transmission is modulated by balance of impulses transmitted to
spinal cord by large A delta and small C fibers. Fibers terminate in dorsal
horn of spinal cord
 Large A beta fibers=touch, vibration, thermal stimulation causes cells in
SG to close pain gate
o Neuromatrix Theory:
 Pain is multidimensional produced by neurosignature patterns of nerve
impulses generated by a widely distributed neural network in the brain
 Ex: Phantom limb pain
 Nociception=perception of pain
o Transmit chemical, mechanical and thermal stimuli
o Receptors are voltage gated Na, Ca, K channels and are located everywhere
 A delta=fast pain, myelinated, sharp pain
 C fibers=slow pain, unmyelinated, diffuse burning/aching sensations
 Pathway of Nociception: Rexed laminae (10 total)
o Connection in sub gelatinosa and other laminae which account for pain gate (gate
control theory of pain)
o Gate then to 2nd order neurons which may cross midline and ascent
o Synapse in the brainstem, thalamus , hypothalamus and limbic system
o Laminae I- marginal layer
o Laminae II- substantia gelatinosa (high synapse region)
o Laminae III-V- nucleus proprius

868
 Classes of 2nd order neurons:
o Projection cells- relay info to higher brain function, transmits cephalad
o Excitatory interneurons- relay transmission to projection cells, interneurons and
motor cells with local reflexes (ex knee jerk)
o Inhibitory interneurons-modulate nociceptive transmission and slow things down
 Thalamus is a major relay station!!
o Divided into VPM (ventral post medial- neck and up) and
o VPL- ventral posterior lateral (below neck)
o Facilitate localization of pain and integrate neuroendocrine response
o Then 3rd order neuron processes portion of path cortex, limbic and reticular
systems
o 3rd order neuron of VPM is Cerebral cortex which projects to parietal lobe. Also
where affective expression of pain comes from.
o Limbic and RAS- regulate complex emotional responses to pain
 Neuromodulator of Pain
o Gate control- activity in large fibers at dermatome level by innocuous mechanical
stimuli. Alpha beta stimuli synapses in dorsal column with C-fiber and A delta
and closes pain gate thru inhibitory interneuron
o Diffuse noxious inhibitory controls- noxious peripheral stimulation remote from
pain site relieves pain ex: acupuncture or deep massage
 Neurotransmitter of Neuromodulator
o Inflammatory
o Pain excitatory or
o Pain inhibitory
 Direct Excitation- nociceptors responds with threshold depolarization ex: heat, radiation,
tissue trauma
 Indirect Excitation- occurs after release of inflammatory mediators after tissue injury ex:
TNF, prostaglandins histamine
 Most common excitatory NT in brain and spinal cord= Glutamate (medicate spinal and
central pain responses to painful stimuli. Activates AMPA fast and NMDA receptors.)
And Asparate.
 Central sensitization- Mg present on dorsal horn of SC inhibits NMDA. Pain causes
glutamate to accumulate in dorsal horn displacing Mg causing a “wind-up” or
sensitization in CNS. This excitability will decrease the firing threshold. Normal
innocuous stimuli leads to severe pain= allodynia. Try injecting local anesthetic or
pushing Propofol. These pts are wired differently.
 Inhibitory neurotransmitters- GABA, Descending pain modulators, NE, serotonin,
opioids
o GABA and Glycine- major Inhibitory effects.
o Inhibitory agents in medulla and pons are NE and Serotonin
 Endogenous Opioids- morphine like neuropeptides that inhibit pain transmission by
binding to G-protein coupled opioid receptors (Mu, Kappa, and Delta) Inhibit release of
Substance P in dorsal horn.

869
 o Enkephalins- Met and Leu concentrated in hypothalamus and PAG
o Endorphins- synthesized in hypothalamus and pituitary “high” feeling, natural
pain relief
o Dynorphins- bind strongly to K receptors in dorsal horn impede pain signals by
activating Bradykinin
o Endomorphins- potent analgesic and GI effects (EM1- found in brain, EM2-
spinal cords) highest affinity to mu opioid receptor
 Pain threshold- stimulus is perceived as pain
 Pain tolerance- duration of time/intensity of pain that a pt will endure before initiating
pain responses
 Perceptual dominance- individual with multiple pain sites will report worst pain site
 Nociceptive pain- pain from normal tissue injury- MI, crushing finger
o Somatic-body injury , peripheral pain (A fibers)
o Visceral-, deeper structures, internal organ ( C fibers)
 Non-nociceptive pain- neuropathic or psychogenic (50% have psych disorder)
o Neuropathic- central pain (lesion in brain or spinal cord) MS. Peripheral pain
(lesion in PNS)
 Neurogenic pain- Neuralgia (pain in distribution of nerve)
o Constant- sympathetically independent or sympathetically depended
 Temporal Pain-time related. Acute vs chronic
o Acute somatic- arises from connective tissue, muscle, bone and skin. IS sharp and
well localized (A) and/or dull/aching (C)
o Acute visceral- transmitted by sympathetic fibers, often radiates. Poorly localized,
worse pain with distention of organs. Associated with hypotension, N/V and
shock
o Referred- Shoulder, arm pain from MI, back pain from pancreas/renal disease
 Regional- abd pain, chest pain, headache, LBP, orofacial and pelvis pain
 Etiologic pain- cancer, dental, inflammatory, ischemic, vascular
 Chronic Pain- greater than 3 months and associated with emotional changes
o Pain out of proportion to any observable tissue injury, depression, complete
recovery difficult
o Intermittent chronic pain- response c/w acute pain: tachycardia, diaphoresis, high
BP
o Persistent chronic pain- normal VS, allows for physiologic adaptation. Obsessed
with their pain. Imbalance of neuromodulation control with decreased levels of
endorphin and c-neuron stimulation. Threshold and tolerance lowers. Alterations
in DRG and up-regulation of receptors which means they need more meds to fill
increase in receptors
 Myofascial pain syndrome- injury to muscle, fascia, tendons. Result of low-threshold
mechanosensitive afferents projecting to dorsal horn neurons. May have trigger points!!
Compression of trigger point

870
 Chronic Post-Operative Pain- phantom limb, post-thora, post-mastect, chronic donor site
pain.
-Due to peripheral and central changes and need multi-modal treatment
 Cancer pain- associated with neuropathy. Most common cause of chronic pain with
identifiable cause
o Tx: assess, mgt breakthrough, anesthetic, neurosurgical, psychologic, rehab
 Neuropathic pain- result of trauma or disease of nerve:
o Changes along somatosensory pathways from periphery to cortex and abnormal
processing by PNS and CNS. Shooting pains, burning, stabbing by spontaneously
firing nerves (at rest) Activity helps desensitize.
 Central- brain or cord trauma, tumor, vascular lesion, MS, phantom limb
pain
 Peripheral- trauma, diabetic, alcoholic, carcinoma, HIV
 CRPS- Complex Regional Pain Syndrome: Develops 1-2 weeks after injury
o Combination of injury and presence of inflammatory cytokines and neuropeptides
which leads to peripheral nociceptive sensitization, pain transmission and
autonomic changes
o Discoloration, changes in skin texture, vasodilatation, cool, cyanotic, difficult to
treat
o Type I- fracture of radius, without nerve injury, starting IV
o Type II- causalgia- injury to nerves, brachial plexus, sciatic or peripheral
 Pain is functional in fetus by week 20-24 weeks
o Cocaine baby-spinal cord is permanently changed

871
 PHYSIOLOGY REVIEW

 Depolarization- Happens if ONLY sodium channels open (cell is more positive/less

negative)
 Hyperpolarization- Happens if ONLY potassium channels opens (cell is more negative)
 Cell always has a negative charge d/t Na/K ATPase with moving 3 Na’s out and 2K’s in.
This establishes a membrane potential (voltage difference across the membrane)
 Normal resting membrane potential is -70mV
 Equilibrium potential- membrane potential (change difference) at which there is no net
movement of an ion across a membrane that is permeable to that ion
o Electrical difference that equals chemical gradient
o Results from a balance of forces (diffusive-from chemical gradient and electrical-
from voltage difference across membrane)
o Nernst equation calculates equilibrium potential for any ion
o Goldman equation is predictive for determining resting membrane potential from
different factors: concentration gradient, permeability of membrane to ions and
charge of ions (electrical gradient)
 Importance of membrane potential
o Influences transport of substances into and out of cells
o Driving force in movement of salt and water across membrane
o Acts as important signal in many cells i.e. cardiac
o Critical for function of neurons and myocytes (muscle cells)
Nervous System

 Efferent neurons are grouped into

o Somatic: voluntary
o Autonomic: involuntary and further broken down into
 Sympathetic
 Parasympathetic
 Neuron- vary in size and shape but all have: cell body, dendrites, and axons
o Dendrites: receive signals
o Axon: conducts impulses to target cell body. The region closes to cell body is the
axon hillock and this is where AP’s are generated. They are covered in myelin
with nodes of Ranvier (gaps between myelin)
o Neurons are excitable cells
 Nerves- bundles of axons outside the CNS
o Have sensory and motor neurons (mixed)
o Some of the cranial nerves have sensory fibers only
o A bundle of axons in the CNS is a tract

 Cells of Nervous system

872
 o Slow- move by cytoplasmic flow
o Fast- move organelles fast, forward transport from cell body to axon terminal or
backward from axon terminal to cell body
 Glial cells provide physical and biochemical support for neurons in CNS
 Satellite cells provide physical and biochemical support for neurons in PNS
 Schwann cells form myelin sheaths in PNS
 Nodes of Ranvier unmyelinated parts of axon between Schwann cells for AP conduction
Central Nervous System Supporting cells:

 Microglia- migrate around tissue and phagocytize foreign and degenerated material (virus,
bacteria)
 Oligodendrocytes make myelin sheaths, gives tissue white color (white matter)
 Astrocytes- regulate external environment of neuron.
o Most abundant glial cell.
o Takes up K from extracellular environment to maintain ionic environment for
neurons
o Take up extra NT released from axon terminal
o Takes up glucose from blood for use by neurons to make ATP
 Ependymal cells- line ventricles of brain and secrete CSF

1. Signals and Graded Potential
o Signals (NT) arrive at the dendrite and binds with ligand gated Na channel
o Na enters cell thru open channels and causes graded potential
o Graded potentials depend on strength of stimulus- how much NT determines rate
of receptor binding
 If larger stimulus more ion channels open and greater change in membrane
permeability
 Graded potentials decrease as they travel
o Chemical signal is transformed into electrical signal and spread thru cytoplasm causing
change in membrane potential across cell
o Once signal gets to axon hillock there are voltage gated channels and if it is at or greater
than -55mV an AP will generate
o d/t voltage change and membrane permeability (Na channels open the K)
o larger axons and myelinated axons are faster
 Na rushed into cell (by diffusion) d/t the depolarization and domino effect
opens more Na channels (along Nodes of Ranvier)
 Deactivated at +30mV or after certain time limit is reached. Only closes
because deactivation gates close channels- Example of positive feedback.
 Na/K ATPase ensures K leaves the cell (repolarization) and the gates reset
to original positions (K equilibrium potential is -70mV)

873
 o Once the channels have closed they cannot be reopened for a certain time period
 Refractory period- channels reset and it is possible for next AP but unlikely
due to depressed rest potential (ex: stimulus would need to be -75 to
generate potential)
 Absolute period- cannot accept AP at that site for a certain time period

2. Signal gets to axon terminus and then…

o If in CNS second cell with be another neuron and in PNS will be a muscle or gland
o Electrical synapse has gap junctions such as smooth, cardiac, brain and muscle cells.
Electrical signals turn into chemical signals to cross the synapse.
o Chemical synapses have synaptic vesicles which are balls of lipids holding NT and are
released into ECS.
o AP depolarizes axon terminal which causes voltage gated Ca channels to open and Ca to
rush in
o Calcium triggers exocytosis of synaptic vesicle contents
o NT diffuse across synaptic cleft and binds with receptors on postsynaptic cell (maybe)
o NT binding initiates a response in postsynaptic cell
o Response could cause another AP, muscle contraction or hormones to be released
o NT can then be returned to axon for reuse or transported into glial cells
o Enzymes inactivates NT
o NT can diffuse out of synaptic cleft via interstitial fluid
Integration:
o Spatial- 3 excitatory neurons fire and their graded potentials separately all below threshold
but together sum to create supra-threshold signal
o Temporal- different signals initiated at separate times if too far apart will not generate AP
o Post synaptic inhibition- an inhibitory neuron fires blocking NT release at one synapse an
there is no response in any target cell
o Long-term Potentiation- Glutamate is key element.
o NT(Glutamate) is released in synapse and binds to AMPA and NMDA channels
o Na enters thru AMPA channels depolarizing cell
o Depolarization causes Mg to be ejected from NMDA receptor channel and opens
channel allowing Ca to enter cytoplasm (thru NMDA)
o Ca activates second messenger pathways which increases the likelihood the process
will continue
o Paracrine from postsynaptic cell enhances glutamate release (back to pre-synaptic
axon)

874
Recycling of Ach at synapse:

 In the synaptic cleft Ach is broken down by acetylcholinesterase and choline is transported
back into the axon terminal and is used to make more Ach
Receptors:

 Cholinergic: Nicotinic (on skeletal muscle, in PNS and CNS) and Muscarinic in CNS and
PNS (linked to G proteins)
 Adrenergic: alpha and beta, linked to G proteins

Efferent Division: Autonomic and Somatic Motor Control

 Autonomic Division
a. Autonomic reflexes
b. Antagonistic controls
c. Control of cardiac and smooth muscles, and glands in homeostasis
d. Agonist and antagonists in research and medicine
e. Targets are lymphoid, adipose, exocrine and endocrine, smooth muscle,
cardiac muscle
f. Initiate response:
i. Hypothalamus- Water, temperature and hunger
ii. Pons – respiration
iii. Medulla- respiration, cardiac, vomiting, swallowing
g. There are two neurons that synapse in autonomic ganglion
 Parasympathetic- rest and digest, restores body function
a. Major tract is Vagus nerve
b. Uses Acetylcholine as NT
c. Muscarinic receptors
d. Constricts pupils, slows heart; stimulates digestion, insulin release,
urination
 Sympathetic-fight or flight- energetic action- reaction without consciousness
a. Ex: if activated GI stops digesting, increase in glycogen release, increased
HR and RR
b. Enzymes: MAO
c. Pupil dilatation, salivation, increased HR and volume, blood vessel and
bronchiole dilation, fat breakdown
d. Inhibits: digestion, pancreas secretion, urination
 Somatic Division
a. CNS control of skeletal muscles thru NM junctions
b. Single neuron from CNS that’s myelinated
c. Terminus branches

875
 Muscles:

Three types are

 Skeletal- attached to bones by tendons, origin is closest to trunk, and insertion is more
distal. Has antagonistic muscle groups
 Cardiac
 Smooth- lungs, blood vessels, intestines, involuntary control usually
Ultrastructure of Muscle

 Myosin- thick filaments

 Actin- light filament
 I bands- only thin filaments
 H bands- center with only thick filaments
 A bands- contain thick and thin filaments
 Z discs- center of I bands
 M lines- center of A band, helps hole down thick filaments
 T-tubules- bring AP into interior of muscle fiber
 Sarcoplasmic reticulum- stores Ca
 Troponin- binds with Ca to move Tropomyosin out of the way to allow for contraction
 Tropomyosin- blocks binding site on actin, needs to be moved to make contraction
Mechanism of Contraction

 Ca levels increase in cytosol

 Bind to troponin
 Moves tropomyosin away from actin binding site
 Myosin binds to actin and completes power stroke
 Actin filament moves
 Duration of twitch depends on type of muscle fibers
 ATP binds to myosin and myosin releases actin
 ADP and Pi bind to myosin head in relaxed state during power stroke are released
Muscle relaxation
o Requires Ca re-uptake by SR Ca-ATPase
o So ATP is needed in re-uptake of Ca and to move myosin head
-Purpose of Phosphocreatine shuttle is to keep ATP constant
-Muscle at rest combines ATP and creatine to phosphocreatine and ADP with help of CK enzyme
-when at work converts phosphocreatine and ADP to create creatine and ATP

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Muscle fatigue

 Slow fibers- slower to contract and relax, rich capillary supply, more mitochondria,
myoglobin “red fibers”
 Fast fibers- fast to contract, speed, fatigue fastest, respiratory enzymes and less myoglobin
“white fibers”
 Extended submaximal exercise- deplete glycogen store decreasing ATP
 Short duration maximal exertion- decrease Ca release, slow Pi release from myosin and
increased levels of Pi
 Maximal exercise- K leaves muscle fiber causing decrease in Ca
 Genetic and training determine amount of red vs white muscle fibers
 Limiting factors of us doing endurance sports is VO2 max
o Ability to get O2 out of air into muscles

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Blood

 Composed of:
o Plasma: Water, ions, vitamins, gases and organic molecules such as:
 Amino acids
 proteins (albumin, globulin, fibrinogen)
 Albumin- Exerts colloid osmotic pressure and transports materials
 Globulin- clotting factors, enzymes
 Fibrinogen- forms fibrin threads essential to blood clotting
 Transferrin- iron transport, Glucose, lipids, nitrogenous waste
o Cellular elements
 RBC aka erythrocytes
 Live for 120 days
 Hgb components are recycled into new proteins, bilirubin, iron is
used in new heme groups
 WBC aka leukocytes
 Lymphocytes aka immunocytes
 Monocytes develop into macrophages
 Neutrophils along with monocytes and macrophages are
phagocytes
 Eosinophil’s along with neutrophils and basophils are granulocytes
 Basophils aka mast cells
 Platelets
 Form megakaryocytes-giant cells with multiple copies of DNA
which break off to form cell fragments which become platelets
 Platelet plug: exposure of collagen activates and binds platelets
which then release platelet factors that attract more platelets
causing platelet aggregation and platelet plug
 Hematocrit- ratio of RBCs to plasma
Endocrine

 Hormones
o use cell to cell communication
o Molecules are made in glands or cells and transported via blood to distant targets
which activate a physiological response
o Control of rates of enzymatic reactions, transport of ions or molecules across a
membrane, and gene expression and protein synthesis
o Exert effects at low concentrations and half=life indicates length of activity

o Classification:
 peptide or protein hormones
878
 Surface receptor, hormone binds and enzymes activated opening
channels, second messenger systems are used and cellular response
occurs
 steroid hormones
 cholesterol derived, cytoplasmic or nuclear, activate DNA for
protein synthesis
 slower acting with longer half life
 Ex: cortisol, estrogen, testosterone
 amine hormones
 thyroid hormones, catecholamine’s (epi, norepi, dopamine)
o hormone interactions
 synergism- multiple stimuli
 permissiveness- need second hormone to get full expression
 antagonism- glucagon opposing insulin
 Pheromones: organism to organism communication
Immune System

 Immunity- body’s ability to protect itself against infectious disease and recognize
molecules as foreign and attack them (ex: bacteria, viruses, parasites, toxins)
 Lymph- fluid that has been filtered out of the vessels is carried in a secondary circulation
 Three components:
o Lymphoid tissues
o Various immune cells
o Chemical signals that coordinate responses
 Pathologies of immune system:
o Incorrect immune responses- autoimmune ex: type I DM
o Overactive immune response- allergies
o Lack of immune response- immunodeficiency ex: HIV, SCID
 Body’s two lines of Defense
o Physical and chemical barriers: skin, epithelial lining, cilia, acids, mucous,
lysozymes
o Immune defenses:
 Innate- non-specific: responds to a range of signals, immediate
 Acquired- specific, attacks specific Ag or pathogen

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Inflammation

 Granulocytes are main cellular component to inflammation

 Release of histamine and prostaglandin causes local vessel dilation causing the tissue to
be warm, red and swollen increasing capillary permeability
 WBCs leak into tissues and phagocytes engulf and destroy bacteria
 Phagocytes move out of the vessel into the ICF
Type I Hypersensitivity

 Immediate or anaphylactic reaction usually associated with an allergy

 Reaction may involve the skin, eyes and nasopharynx
 Symptoms can range from mild discomfort to death
 Mediated by IgE released from mast cells and basophils
o IgE binds to mast cells and basophils causing them to degranulate and release
mediators
o Histamine: dilates and increases permeability of blood vessels, increases mucus
secretion, and smooth muscle contraction
o Prostaglandins: contraction of smooth muscle of respiratory system and increased
mucus secretion
o Leukotriene: bronchial spasms
Type II Hypersensitivity

 Occurs when antibodies bind to the antigens on the cell surface on the patient’s own cells
marking them for destruction- “Anti-body dependent”
 Mediated by IgG, IgM or IgA
 Involves activation of complement by IgG or IgM binding it to an antigenic cell the cell
is lysed
 Examples: hemolytic anemia, thrombocytopenia, graves, MG, transfusion reaction
o Graves: Abs’ attach to receptors on thyroid gland and stimulate production of
thyroid hormone. Symptoms: Goiter and bulging eyes
o Myasthenia Gravis: progressive muscle weakness. Abs’ block Ach receptors at
NM synapse. Treatment: immunosuppressant

Autoimmune: Immune Complex

 Systemic Lupus Erythematous (SLE)-

880
 o Autoantibodies react against DNA, blood cells, neurons, and other tissues
o Women make up 90% of affected
o Red skin rash on face in butterfly shape
o When cells die, immune complexes form and deposit under skin, joints, kidneys,
blood vessels and CNS and causes inflammation
o Most patients die from kidney damage and there is no cure
o Treatment: anti-inflammatory and immunosuppressive drugs
AIDS associated Diseases

 Gastrointestinal: cause most of illness and death of late AIDS

o Diarrhea, wasting, abdominal pain, infections of mouth or esophagus
o Pathogens: candida albicans, CMV, microsporidia, cryptosporidium
 Respiratory: 70% of AIDS patients develop serious Respiratory problems
o Bronchitis, PCP, TB, lung CA, sinusitis, pneumonitis
 Skin Disorders: 90% will develop skin or mucous membrane disorders
o Kaposi’s sarcoma-most common type of CA in AIDS pts.-usually men
o Herpes zoster, thrush, invasive cervical carcinoma
 Eye infections: 50-75% patients develop eye conditions
o CMV retinitis, conjunctivitis, dry eye syndrome
Lymphatic System
o Vascular system that collects tissue fluid and returns it to blood
o Lymphatic fluid is monitored for pathogens by immune system
o Primary lymphoid tissues: thymus and bone marrow
o Edema is caused by inadequate drainage of lymph or filtration far greater than
absorption
 Antibodies
o IgG-most abundant
o IgA-secretory form, saliva, tears, breast milk
o IgE-involved in allergic responses
o IgM- antibodies involved in primary response
o IgD- found on surface B cells role is unclear
Alterations in Platelet function and Coagulation

 Platelets:
o 150-400K is normal
o Life span is 5-9 days
o Removed by liver and spleen
o Secretes chemical-containing granules that promote blood clotting

 Acquired disorder of platelet function

o Systemic infections-CRF, liver disease, Fe++ or folate deficiency
o Hematologic conditions-leukemia, multiple myeloma, myeloproliferative disorder

881
 o Drugs the inhibit platelet membrane receptors and inhibit prostaglandin pathways
 Hemostasis
o Endothelium provides a physical barrier and secretes platelet inhibitory products
to prevent hemostasis under normal physiological conditions
o With endothelial injury platelets adhere to vWF in collagen layer of sub
endothelium then fibrin is incorporated into the growing platelet plug to form a
stable thrombus

o Clotting cascade is initiated by extrinsic (damaged tissues leaking tissue factor

thromboplastin into blood stream) or intrinsic pathway (epithelial damage) and
involves a cascade of reactions divided into three stages
 Calcium and clotting factor X combines with factor V to form
prothrombinase which turns PROTHROMBIN into THROMBIN
(happens in seconds)
 Then factor XIII causes SOLUBLE FIBRINOGEN to becomes FIBRIN
threads
 Activates fibrin stabilizing factor XIII, accelerates formation of
prothrombinase and activates platelets to release phospholipids
 Fibrin is then broken down into FDP (fibrin degradation products)
o Plasminogen turns into Plasmin (fibrinolysis)then dissolves clots by digesting
fibrin threads and inactivating fibrinogen, Prothrombin, factors V, VIII and XII
 Plasmin inhibitors: Amicar and Aprotinin
o Normal coagulation involves Vitamin K, clot retraction (tightening of clot) and
fibrinolysis (dissolution of the clot)
 Vitamin K dependent factors:
 II- Prothrombin made in liver
 VIII:C- AHF made in liver
 X- Stuart-Prower factor made in liver
 Disorders of Coagulation
o Defects in clotting factors
o Liver disease- cirrhosis ( can’t generate factors)
o Vitamin K deficiency
 Vit K is a fat soluble vitamin and is required for normal clotting and for
synthesis of 4 clotting factors by hepatocytes (II, VII, IX, X)
 Produced by bacteria in large intestine
 Coumadin is antagonist to Vit K receptor in liver – depressing production
of factors in the liver

o Consumptive thrombohemorrhagic disorders

 Disseminated Intravascular Coagulation (DIC)

882
 
blood clotting and bleeding at the same time throughout body

life threatening due to clotting factors removed by widespread
clotting that too few remain to permit normal clotting
 associated with infections, sepsis, shock, hypotension, severe
trauma, intravascular hemolysis, obstetric emergency,
malignancies, liver disease
 clots cause ischemia and necrosis leading to multisystem organ
failure
 Labs: decreased platelets and fibrinogen and increased FDP
o Thrombocytopenia
 Platelets less than 150K
 <50K-Hemorrhage from minor trauma
 <10-15K- spontaneous bleed with petechial, ecchymosis, purpura
 <10- spontaneous severe bleeding, GI Resp system or CNS, can be fatal
 Decreased production or increased consumption
 Can be congenital or acquired, primary or secondary
Acquired: decreased production due to:

 Viral infection- EBV,rubella, CMV, HIV

 Drugs-thiazides, estrogen, quinine, ethanol, chemo
 Vit B12 or folic acid deficiency
 CRF
 Bone marrow hypoplasia- aplastic anemia
 Radiation therapy
 Bone marrow infiltration by cancer
 HIT- Heparin Induced Thrombocytopenia:
o Diagnosed: dropping platelets post Heparin TX. Ab titer against heparin-platelet
factor IV not seen until subsequent exposures.
o Treatment: withdraw Heparin and use alternative such as Argatroban or
Lepirudin. If untreated will lead to arterial and venous thrombosis ; anaphylactic
shock
 ITP- Idiopathic thrombolytic Purpura
o Most common cause of thrombocytopenia secondary to platelet destruction
o Can be triggered by drugs, pregnancy, immune disorders (SLE), viral infections,
allergens
o Resolves after infection resolved
o Chronic- associated with platelet-specific antigens, true platelet antibodies
present, remissions and exacerbations
o Mostly IgG but IgA and IgM are also identified
o S/S: petechiae, Purpura, epistaxis, hematuria, bleeding gums, rare intracranial

 Hemophilia
o Inherited deficiency of clotting factors with spontaneous bleeding after minor
trauma

883
 o Subcutaneous or IM hemorrhaging
o Hemophilia A-lacks factor VIII:C and is most common (males only)
o Hemophilia B- lacks factor IX (males only)
o Hemophilia C- lacks factor XI, women can get as well and is less severe because
alternate clotting activators exist
o Treatment: FFP, cryo, factor VIII concentrate

 Hemolytic Disease of the Newborn

o Rh negative mom and Rh positive fetus have mixing of blood at birth
o Mom creates antibodies against fetus’s blood unless Rhogam given after birth
o Rhogam works by binding to loose fetal blood and removes it from the body
before antibodies can be formed
o In second child, hemolytic disease of the newborn may develop causing
hemolysis of fetal RBC’s
 Most common reason for coagulopathy in pts. receiving massive blood transfusion is lack
of platelets
 All Procoagulant are present in FFP except platelets
 PRBCs lack platelets, factors V and VIII
 Massive transfusion of one complete blood volume within 24 hours can change blood
type
 Anemia
o Iron-deficiency
o Pernicious- last of intrinsic factor from B12 absorption
o Hemorrhagic
o Hemolytic- defects in cell membrane causing rupture
o Thalassemia- hereditary deficiency of hemoglobin
o Aplastic- destruction of bone marrow- radiation/toxins
o Sickle cell
 Genetic defect in hemoglobin molecule (HgS)
 Sickles with low O2 levels and can rupture easily causing anemia, clots
and PAIN
 Increased resistance to Malaria because RBC leaks K and lower K kills the
parasite infecting the RBC
Cardiovascular Function

 Function: transport O2, CO2, nutrients, waste products, immune cells, and signaling
molecules throughout the body
 Humans move blood thru their bodies by bulk flow- movement of molecules as a group,
requires energy, transport can occur over great distance. Moves according to pressure
difference.

 Need system of tubes (arteries, veins, capillaries) Need fluid (blood) and pump (heart)
 Pumps from: Arteries => arterioles=> capillaries=>venules=>veins=>back to heart

884
 In closed system blood is distinct from interstitial fluid
 Advantages of closed system: 1- more control of where blood is distributed and 2- blood
moves faster (increased pressure and flow)
 External pumps: skeletal muscles of the legs and thorax- help to push blood back to the
heart
 The pressure that blood exerts on the walls of blood vessels generates blood pressure. As
the radius of a tube decreases the resistance to flow increases (blood flows faster thru
narrowed tubes)
 Pericardium- sac of connective tissue that surrounds the heart. Parietal and visceral layers
filled with lubricating fluid
 Epicardium- outer layer of the heart, continuous with visceral pericardium *contains
coronary arteries (heart’s own blood supply)
 Myocardium- layer of heart muscle cells (cardiomyocytes) *comprises most of heart
 Endocardium- innermost layer of connective tissue covered by epithelial cells
(endothelium)
 Ventricles are separated by intraventricular septum
 Heart valves ensure one-way flow
o Atrioventricular valves are the TRICUSPID on right and BICUSPID on left
o Semilunar valves are the AORTIC on left and PULMONIC on right
 Systole- contraction, blood forced into circulation
 Diastole- relaxation, blood enters the heart (decreased pressure in chamber)
 Resistance in the pulmonary circuit is low due to high capillary density and large SA,
closer proximity to RV and it protects delicate blood vessels of the lung
 Pacemaker cells- cells with fastest intrinsic rhythm located in RA SA node
o Derived from cardiomyocytes
o No refractory period
o Small with few myofibrils, do not contract, have unstable resting membrane
potentials
o P wave- depolarization of pacemaker cells and initiates cardiac cycle
o PR interval- atria contract-atrial systole
o QRS- ventricles contract-systole
 Isovolumetric contraction- pushes AV valves closed and increases
pressure inside ventricle
 Ventricular ejection- increased pressure forces semilunar valves open
o T wave- relaxation of ventricles-pressure in arteries exceeds ventricular pressure
closing semilunar valves. Then pressure in atria exceeds ventricular pressure and
the AV valves open and the ventricles fill passively.

o Control of pacemaker potentials to increase heart rate

885
  NE released from SNS and epi released from adrenal medulla
 AP caused by Ca entry
 Threshold potential is when Na and Ca enters
 Rate of depolarization and frequency of AP’s increase
o Control with decreased heart rate
 Ach released from PNS
 More K channels open and pacemaker cells hyperpolarize
 Time for depolarization takes longer, frequency of AP’s decrease
 Myocardial cells-gap junctions which communicate via electrical connection
o Has plateau phase which is extended depolarization that corresponds to refractory
period and lasts as long as the contraction- can’t start another AP until last ones
relaxed
o AP Caused by Na entry
 Modified cardiomyocytes- aka intermodal pathway
o Cells have elongated appearance and do not contract
o Undergo rhythmic depolarization’s and spread AP rapidly thru myocardium
 Stroke volume is the amount of blood pumped by one ventricle during a contraction
 Cardiac output is the volume of blood pumped by one ventricle in a given period of time
o CO=HRxSV
o Average is 5L/min
 Frank-Starling effect:
o Increased EDV (stretch)results in more forceful contraction and increased SV
o Heart automatically compensates for increases in volume of blood returning to the
heart via auto regulation
o NE increases EDV and SV causing an amplified Frank Starling effect
Alterations of Cardiovascular System

 Varicose vein- pooled blood forms in veins or LE’s due to incompetent valves.
o Can progress to chronic venous insufficiency
 Venous HTN
 Edema-plasma seeps into third space
 Stasis and hyperpigmentation
 Tissue hypoxia and venous stasis ulcers
o Causes are prolonged standing, pregnancy, increased estrogen use
o Risk factors: female and genetics

886
 Deep Vein Thrombosis (DVT)
o Thrombus is a clot that remains attached to vessel wall
o Thromboembolism is a detached thrombus
o Triad of Virchow
 Venous stasis
 Venous endothelial damage
 Hypercoagulable states
 Malignancy
 Pregnancy
 HRT
 Pregnancy
 Surgery
 Genetic abnormalities
 Superior Vena Syndrome (SVC syndrome)
o Progressive occlusion of the SVC leading to:
 Venous distension of UE’s and head
 Visual disturbances and tight collar, necklaces
 Increased ICP
o Caused by:
 Bronchogenic CA in 75% cases
 Lymphoma
 Invasive catheters
 Histoplasmosis
 TB
o Treatment:
 Balloon angioplasty
 SVC stent
 Thrombolysis
 Bypass graft
 Radiation
 Diuretics and steroids
 Disease of the Arteries:
o Aneurysm: localized out-pouching of a vessel wall or chamber
o Caused by:
 Ascending aorta- shear forces
 AAA- plaque erosion of vessel wall
 Trauma
 Collagen disorder
o True: weakening of all 3 layers
o False: break in only one layer
 Type 1- originates in ascending aorta and extends at least to aortic arch
 Type 2- confined to ascending aorta
 Type 3- originates in the descending aorta and extends distally

887
 Pathologic effects of
chronic, primary
Hypertension
SITE OF INURY MECHANISM OF INJURY PATHOLOGIC EFFECT
Heart Increased work load, LVH, ischemia, LHF (Do
afterload, resistance and Echo)
decreased O2 supply,
hypertrophy
Coronary arteries Accelerated atherosclerosis Angina, MI, sudden death
(EKG may show LVH)
Aorta weakened vessel wall Aneurysms and dissections
Kidneys Increased renin/aldosterone Retention of Na/H2O leading
a/w decreased RBF further increased BP (check
BUN, Creat, GFR)
Brain Accelerated atherosclerosis TIA, CVA, aneurysm
Eyes Reduced blood flow Retinal vascular sclerosis
Arteries of lower Accelerated atherosclerosis Intermittent claudication,
extremities thrombosis, gangrene
 Le Place’s Law- wall tension related to: thickness of septum(TEE), pressure during peak
systole, and radius inside vessel
 WT=P x R/2h ( h=thickness)
Hypertension

 Caused by genetics and the environment

 Leads to dysfunction of SNS, RAA, adducing and natriuretic hormones which causes:
o Vasoconstriction- causes increased PR and sustained HTN
o Renal salt and water retention causing increased blood volume contributing to
HTN
o Insulin resistance-causing endothelial damage (decreased NO) and narrowing of
vessels
o Inflammation causing renal and salt retention
o Increased SNS activity causes:
 Increased HR and PR
 Vascular remodeling- smooth muscle proliferation
 Procoagulant effects causing narrowing of vessels and vasospasm
 Normal= <120/80
 Prehypertension= 120-139/80-90
 Stage I= 140-159/90-99 TX: thiazide diuretics, ACE or ARB, Bblocker, CCB
 Stage II=160-179/100-109- 2 drug combo; thiazide and ACE or ARB or Bblocker or
CCB
 Stage III=180-209/110-119
 Stage IV aka Malignant HTN=>210/120

888
Unstable Angina

 Rest- usually greater than 20 minutes

 New-onset angina- pain with mild exertion
 Increasing angina- previously diagnosed with more frequent, longer episodes
Tissue Changes after MI

 4-10 days: greatest chance of SVD rupture

 10-14 days: start of revascularization, vulnerable to stress
 6 weeks: scarring complete replacing necrotic myocardium
MI leads to decreased Contractility which leads to:

 Decreased EF and increased LVEDV causing increased preload

 Decreased renal perfusion and increased renin and angiotensin causing increased
afterload
Coronary System

 PDA feeds inferior wall of LV if right dominant coronary system (majority) If Inferior
wall MI may also have infarcted their RV (15 lead EKG to assess)
 AV valves are the tricuspid and bicuspid valves
 Semilunar valves are the aortic and pulmonic valves
Infective Endocarditis:
1. Endothelial damage occurs
2. Bacteremia develops
3. Vegetation forms
 Perioperative Abx’s should be used for patients pre-disposed to developing Infective
endocarditis
Acute Pericarditis

 Causes:
o Idiopathic, metabolic,
o Infectious- TB, HIV, hepatitis, measles, mumps and varicella
o MI
o Trauma, surgery-post CABG
o Radiation
o Connective tissue disorder
 Diagnosis:
o Friction rub at cardiac apex and left sternal border
o Diffuse ST elevation in all leads, can persist for several weeks
o May have pericardial effusion

889
Restrictive Pericarditis

 Causes:
o Radiation
o Post CABG
o RA, uremia
o Idiopathic
Pericardial effusion

 Acute= tamponade
o Trauma, HD catheter, PICC, MVA, GSW, stabbing
 Chronic= neoplasm
Vascular Resistance
1. Peripheral Vascular Resistance- normal is 20-120
a. PVR= MPAP-LAP/CO x 80
2. Systemic Vascular Resistance
a. SVR=MAP-RAP/CO x 80
MAP= (DPx2) + SP/3

 Diastolic Cardiomyopathy
 Hypertrophic Cardiomyopathy- due to chronic increased afterload
o Hypertensive
o Valvular
o IHSS- most commonly inherited cardiac disorder
 Thickened septum
 LV outflow track obstruction
 Decreased LV compliance
 Decreased relaxation
 Worsens with increased inotropy and decreased preload
 At risk for sudden death due to Vfib
 Restrictive Cardiomyopathy
o Restricted filling
o Decreased compliance and EDV
o Mimics constrictive pericarditis (RHF and venous congestion)
o Dysrhythmias
o Etiologies: sarcoidosis, scleroderma, lymphoma

890
Right Heart Failure

 Aka Cor pulmonale

 Enlargement of RV due to high BP in the lungs caused by chronic lung disease
 Blue face and neck
 Caused by acute or chronic increase in afterload
o Hypoxic pulm vasoconstriction, sleep apnea
o COPD, cystic fibrosis, ARDS
o Left heart disease
o Saddle pulmonary embolus
Nitroglycerin

 decreased preload (decreased LVEDV)

 Decreased lumen of coronary arteries
 Increased perfusion to myocardium
 Decreased volume and pressure
Aortic stenosis Aortic Aortic Regurgitation
ischemia
LV Increased increased Increased and increased RV afterload
afterload (RVF)
LVEDV Decreased Increased
LVEDP Increased increased Increased
Myocardial Decreased decreased
O2 supply
Myocardial Increased increased
O2 demand
SV (CO) decreased increased
Cardiac diastolic systolic
failure
Caused by Atherosclerosis, AS Congenital, infective endocarditis, RA,
RA, congenital trauma, atherosclerosis, annular dilation,
connective tissue disorders
Other S/S PHTN, Muscle Dilated LV, wide PP, hypertrophied LV,
dyspnea, outgrown JVD, hepatic congestion, edema
angina, LVH, blood supply
can hear
murmur R2ICS,
remodeling

891
 Mitral regurgitation Mitral stenosis
LAV Increased during systole Increased
LVEDV Increased
LAP Increased increased
RV afterload Increased Increased
Cardiac failure RV RV
Other S/S A fib, stroke, LV dilatation A fib, stroke, PHTN that
and hypertrophy, gradual doesn’t resolve, Increased
increase r/t annular dilation, CVP, JVD, hepatic
PHTN, JVD, hepatic congestion, edema
congestion, edema
Caused by Infective endocarditis, RA, Seen in countries with RHD,
dilated cardiomyopathy, problem with heart muscle
atherosclerosis

Blood Flow and the control of blood pressure

 Blood vessel wall have three layers:

o Tunica intima-inner layer comprised of smooth sheet of epithelial cells
o Tunica media-middle layer comprised of smooth muscle and elastic connective
tissue
o Tunica externa- outermost layer comprised of collagen
 Blood Flow and Blood Pressure
o Resistance depends on: radius of vessel, viscosity of blood and length of system
o Blood pressure is highest in the arteries and decreases continuously as it flows
through the circulatory system
o Pulse pressure= SP-DP
o Mean arterial pressure is a function of CO and resistance in arterioles (TPR)
o Blood pressure control includes rapid responses from the CV system and slower
responses by the kidneys
o Baroreceptors- stretch sensitive mechanoreceptors in walls of carotid arteries and
aorta
 Sends nerve signals to medulla oblongata (CV control center)
 Baroreceptor reflex regulates MAP
o Gravity effects on Blood Pressure
 Hydrostatic pressure is the pressure of a column of fluid due to gravity
 Involves density of fluid, acceleration due to gravity and height of
column

892
  Blood flow may be with or against force of gravity
 Body position-changes in position can alter BP and flow
 Standing up causes pooling of blood in lower body decreasing
venous return, SV and MAP
 Baroreceptor senses change and brings MAP back to normal
increasing HR, SV and MAP
 Orthostatic hypotension
 Low BP upon standing when reflex is too slow
o Arterioles control blood distribution because arterioles are arranged in parallel
they can alter blood flow to various organs by:
 vasoconstricting or vasodilating based on changes in resistance (ex radius
change)
 Auto regulation is a direct response of the arteriole smooth muscle
stretch
o Acts as negative feedback loop
o Prevents excessive flow of blood into tissue
 Intrinsic factors- metabolic state of the tissues the bloods going to
o Sensitive to conditions of ECF
o Levels of metabolites/nutrients alter
vasoconstriction/dilation
o Blood flow is matched to metabolic requirements (ex:
increased metabolic rate increased O2 consumption leads to
decreased O2 supply and increased CO2, increased waste
then smooth muscles dilate reducing resistance in blood
vessel so more flow replenishes O2 and gets rid of CO2
and waste)
 Extrinsic factors-nervous and endocrine system
o Tonic control of arteriolar diameter determined by NE
o Capillaries
 Plasma and cells that surround capillaries exchange material across a thin
capillary wall by paracellular pathway or endothelial transport
 The capillary density is related to metabolic activity of cells
 Larger solutes and proteins move by vesicular transport
 Usually transported by transcytosis
 Starling Principle: Net filtration pressure
 Based on hydrostatic pressure of blood vs interstitial fluid and osmotic
pressure in capillary vs in interstitial fluid

893
 Bulk flow results from hydrostatic or osmotic pressure gradients
 Absorption- fluid movement into capillaries (venous end)
 Filtration-fluid movement out of capillaries (arterial end)
 Disruption of balance can occur if increased hydrostatic pressure,
decreased plasma protein concentration or increase in interstitial
proteins
 Sinusoids replace capillaries in bone marrow, liver and spleen (needs to be
more leaky) they have few tight junctions and are most porous for
exchange of large proteins, blood cells etc.
 Types:
 Sinusoids-most porous
 Continuous- cells held together by tight junctions (skin & muscle)
 Fenestrated- cells with pores specialized for exchange (kidneys,
endocrine organs and intestines)

894
Mechanisms of Breathing
Respiration= exchange of O2 and CO2 between the external environment and the mitochondria

 Mitochondrial respiration- production of ATP by oxidation of CHO, amino acids, fatty

acids. O2 is consumed and CO2 is produced
 External respiration- gas exchange at the respiratory surface (lungs)
 Internal respiration- gas exchange at the tissue

 Bulk flow and diffusion drive gas exchange

o Bulk flow- uses ventilation to move air over lung and circulation to transport
gases in circulatory system
 Altitude changes barometric pressure, temperature and humidity
o The higher the altitude the lower the PO2 is as well as lower temp and humidity
 Diffusion of gases is figured with Fick’s equation
o To maximize diffusion surfaces are thin with large surface area
o Formula takes into account a diffusion coefficient (constant), area of membrane
and pressure gradient
 Dalton’s Law of Partial Pressure- pressure exerted by a gas is related to the number of
moles (molecules) of the gas and the volume of the chamber.
o In a gas mixture each gas exerts its own partial pressure and the sum of all the
partial pressures is equal to the total pressure of the mixture
 Ideal Gas Law
o Pressure and volume have inverse relationship
o Number of moles of gas molecules
o Gas constant
o Temperature (in Kelvin)
 Henry’s Law
o Gas molecules in the air must first dissolve in liquid in order to diffuse into a cell.
The concentration of gas in a liquid is proportional to its partial pressure
 Variables are: concentration of the gas, partial pressure of the gas and its’
solubility
 Graham’s Law
o Diffusion rate is proportional to solubility/ molecular weight squared
o If volume is increased the pressure will decrease (inverse relationship)
o Rate of flow is determined by the difference in pressure and resistance to flow
 Boyle’s Law- gases move from areas of high pressure to areas of low pressure.
Temperature is constant and volume and pressure are inversely related.
 Negative intra-pleural space helps recoil the lungs (inward pull) whereas the elastic recoil
of the chest wall tries to pull the chest wall outward
 Low compliance lungs require more force to stretch. Pts that have restrictive lung disease
have low compliance. EX: fibrotic lung diseases, inadequate surfactant production
o Surfactant helps lung stretch/re-inflate
 Elastance- returning to its resting volume when stretching force is released. If elastance is
decreased then exhaling is more difficult.

895
  Pts. with constrictive airway disease have a higher resistance due to decreased diameter
of airways therefore the require a large trans pulmonary pressure gradient
o The parasympathetic nerve stimulates bronchoconstriction
o The Sympathetic nerve stimulates Bronchodilation
o Resistance is determined by the length, viscosity and RADIUS
 Tidal volume is the amount of air moved in during one ventilatory cycle
 Dead space is air that does not participate in gas exchange
o Anatomical dead space- volume of trachea and bronchi
o Alveolar dead space- volume of alveoli that are not perfused
 Alveolar ventilation=ventilation rate x (tidal volume- dead space volume)
 As alveolar ventilation increases alveolar PO2 increases and PCO2
decreases
 Ventilation-Perfusion matching
o Arterioles dilate or constrict to distribute blood to well-ventilated alveoli so if
there is low PO2 in alveolus arteriole will constrict to redirect blood to better
ventilated alveoli

Gas Exchange and Transport

 The surface area, membrane thickness and diffusion distance are constant
o Concentration gradient is the most important factor is diffusion and solubility
 Movement of gases are influenced by partial pressure gradient, solubility and temperature
 Normal blood values:

Arterial venous
PO2 95 (85-100) 40mmHg
PCO2 40mmHg (35-45) 46mmHg
pH 7.4 (7.38-7.42) 7.37
 Metalloproteins are respiratory pigments that contain metal ions which reversibly bind to
O2 to increase O2 carrying capacity. Ex: hemoglobin
o Hemoglobin contains iron (heme=iron + globin=protein)
o In RBCs and appears red when oxygenated
o Myoglobin is a type of hemoglobin found in muscles
 Oxygen transport from alveoli to tissue cell:
o O2 diffuses across alveoli membrane into plasma
o O2 (based on partial pressure gradient) diffuses into RBC and binds with Hb
(partial pressure of O2 decreases) Hemoglobin increases O2 transport by blood
o Oxyhemoglobin is formed and is diffused out of the RBC into plasma
o Hb releases the bound O2 (deoxyhemoglobin) increasing the partial pressure of
O2
o O2 diffuses into the tissue cell plasma and O2 is used in cellular respiration
o The total O2 content of arterial blood depends of the amount of O2 dissolved in
plasma and bound to Hemoglobin

896
  Carbon dioxide transport in the blood:
o CO2+H20 forms H2CO3 which dissociates into HCO3 and H
o Reaction is catalyzed by carbonic anhydrase, high concentration in RBC and very
low in plasma
o CO2 in transported primarily as HCO3 but also as carbamino complexes and
dissolved in plasma
o CO2 transport starts out with CO2 diffusing out of peripheral tissue into the
plasma (7%)
o CO2 diffuses into RBC and binds to Hgb (carboxyhemoglobin aka carbamino
complexes)
o Most CO2 binds with H2O (via CA enzyme) and forms HCO3 and H+Hgb
o HCO3 is exchanged with Cl- into the plasma (out of RBC)
o HbCO2 (carboxyhemoglobin) is then broken down to Hb and CO2
o CO2 then is dissolved into plasma and then passively diffuses into alveoli
o The HCO3 that got pumped out into the plasma exchanges with the intracellular
Cl to re-enter the RBC breaking down to H2O and CO2
o Then that CO2 product is also diffused out of RBC into alveoli to be blown off

 Bohr Effect:
o Facilitates O2 transport to active tissues and facilitates O2 binding at the
respiratory surfaces
o Altered by pH and PCO2- decreased pH or increased PCO2 reduces oxygen
affinity “right shift” on ODC
 Medulla controls inspiration and expiration
 Pons modulate ventilation by chemoreceptor-linked reflexes (monitor CO2 in CSF and
respond to changes in plasma CO2)
 Peripheral chemoreceptors located in carotid and aortic arteries sense changes in PO2,
PH and PCO2
o Senses pCO2 changes the fastest
Alterations in Pulmonary

 Volume flow loops- capnography that an identify obstructive vs. restrictive lung diseases
o Flow loop with long expiratory phase and more flattened out is obstructive
o Flow loop that looks like mini normal loop is restrictive- difficulty inspiring
 Minute volume is tidal volume x respiratory rate
 Causes of hypoxemia- reduced oxygenation in arterial blood due to inadequate:
o O2 to alveoli
o O2 content of inspired air (FiO2)
o Ventilation of alveoli
o Diffusion of O2 from alveoli into blood
o **V/Q mismatch= most common cause
o Diffusion of O2 across alveocapillary barrier
o Perfusion of pulmonary capillaries

897
 V/Q mismatch is due to right to left shunting leading to decreased PaO2 depends on
amount of air getting into alveoli and amount of blood perfusing the capillaries around
the alveoli
o Normal V/Q ratio: 0.8-0.9
o Caused by: low Hgb
o Barriers to exchange
o Destruction of alveoli
o Slowed perfusion
 Cyanosis- increased amounts of de-saturated Hb or reduced Hb
o Develops with 5gms Hb are de-saturated
o Decreased PaO2
o Enlargement of end of digits- clubbing
o Associated with diseases that interfere with oxygenation such as bronchiectasis,
cystic fibrosis, pulmonary fibrosis, lung abscess and congenital heart disease (late
stages)

 Most important test to differentiate between obstructive vs. restrictive diseases is

FEV1/FVC (PFT)
o >90% is restrictive
o Normal= 75-80%
o Restrictive diseases
 Aspiration
 Normal swallowing and cough reflex impaired, decreased LOC,
leads to PNA
 More serious is >30cc or ph< 2.5
 Aspirates can obstruct bronchi, cause inflammation, loss of cilliary
function, bronchospasm, damage to alveocapillary membrane,
movement of acidic fluid to plasma and blood cells from
capillaries into alveoli causes hemorrhagic pneumonitis
 Treatment= supplement O2 with mechanical ventilation and PEEP,
restrict fluids (decrease pulmonary edema) steroids 72 hours,
Abx’s (avoid bacterial pneumonitis)
 Pulmonary edema
 Surfactant helps to repel H2O normally
 PAWP >20mmHg
 Causes: fluid flows out of capillaries exceeding lymphatic systems
ability to remove it (CAD,CHF) injury to capillary permeability
(ARDS, inhalation of toxic gases) or obstruction of lymphatic
system (left sided heart failure)
 S/S: dyspnea, orthopnea, hypoxemia, increased WOB, inspiratory
crackles, S3 gallop and cardiomegaly
 Treatment: treat cause, remove offending agent, supportive therapy
 Negative Pressure Pulmonary Edema
 Occurs when patient bites down on tube and inhales at same time

898
  Fluids and plasma are pushed into capillaries
 Happens usually in muscular men or larger chested people (can
generate more pressure)
 Treatment: mechanical ventilation and restrict fluids/supportive
 ARDS
 Massive pulmonary inflammation with injury to alveocapillary
membrane that produces severe pulmonary edema.
 Less compliance leading to increased WOB, decreased minute
ventilation and Hypercapnia
 Treatment: supportive, mechanical ventilation with PEEP and high
FiO2, low tidal volumes high RR, prone positioning
 Cancer
 Want to know where tumor is…above or below carina?
o Obstructive diseases
 Emphysema
 Abnormal permanent enlargement of gas-exchange airways
accomplished by destruction of alveolar walls without obvious
fibrosis, loss of elastic recoil
 S/S: dyspnea on exertion, little coughing, tachypnea w/ prolonged
expiration, use of accessory muscles, AP diameter increased, hyper
resonant sounds with percussion, increased lung capacity, pursed
lip breathing
 Chronic bronchitis
 Hyper secretion of mucus causing bacteria to adhere
 Diagnosed if productive cough for 3 months of the year at least 2
consecutive years
 Impairs cilliary function, compromises lung defenses,
inflammation to bronchial walls and persistence leads to
bronchospasm and narrowing of airway
 Asthma
 Bronchial hyper responsiveness and underlying inflammatory
response causing airways to constrict leading to obstruction and
increased resistance to airflow causes air trapping and
hyperinflation distal to obstructions. Increased WOB leads to
hypoxemia
 S/S: coughing, wheezing, breathlessness, chest tightness, decreased
FEV1/FVC but increased FRC and TLC
 Increased level of Ach
 Treatment: bronchodilators, oral steroids, O2, mast cell mediators
(Singulair, Chromalin Sulfate)
 COPD
 Pathologic lung changes consistent with emphysema or chronic
bronchitis
 Airflow limitation is progressive and not reversible

899
Infectious Lung Diseases:

 Pneumonia
o Bacterial
 lower respiratory tract due to aspiration of oropharyngeal secretions to
lower respiratory tract or inhalation of microorganisms
 Most common bacteria is S Pneumoniae
 Inflammation damages bronchial mucus membranes causing infectious
debris and exudate to collect which leads to dyspnea and V/Q mismatch
and hypoxemia
o Viral
 Upper respiratory tract infection
 Influenza, H1N1, SARS, epiglottitis
 Destroys ciliated epithelial cells, goblet cells and mucus glands leading to
sloughing of destroyed epithelium preventing mucociliary clearance
 Tuberculosis (TB)
o M Tuberculosis lodges in lung periphery (ULs) causing inflammation and in
lymphatic system
o Immune response develops 10 days into disease and may remain dormant until
immunocompromised occurs again
Ventilation vs. Perfusion

 Ventilation
o Respiratory failure
 During surgery acute respiratory failure can occur due to our actions. Pt. is
paralyzed with no accessory muscle use, decreased FRC , prolonged
immobilization, blood loss decreases O2 carrying capacity and reserve,
changing positioning changes lung zones…potential problems;
 Atelectasis
 Pneumonia
 Pulmonary edema
 Pulmonary emboli
o Use SCD’s, PEEP, Lovenox, Abs, know EF before surgery
o Occlusion of portion of pulmonary vascular bed most
commonly from DVT, increased risk with disorders that
promote blood clotting
o Effects of embolus depend on extent of pulmonary blood
flow obstruction, size of affected vessel, nature of embolus
and secondary effects

900
 o S/s: increased PAP, decreased CO, right heart failure. If
absent blood flow can also lead to dead space ventilation
causing hypoxemia. Pt may have calf pain, sudden onset of
pleuritic chest pain, dyspnea, tachycardia, anxiety. If
massive hypotension, shock, severe PHTN
 Spirometry test that predicts respiratory failure post-operatively or post-intubation is
FVC<15mm/kg
o Avoid intubation with these patients if possible
 Pleural effusion
o Fluid in pleural space that accumulates in the lungs secondary to migration of
fluids and other components through the walls of intact capillaries
 Pulmonary artery hypertension
o Mean PAP >25 at rest >30mmHg with exercise
o Normal PAP is 15-18mmHg
o Usually familial link with connective tissue disorders
o Increased risk with AIDS, diet drugs, amphetamine and cocaine use and exposure
to high altitudes chronically
o Overproduction of vasoconstrictors and decreased vasodilators causing fibrosis
and thickening of vessel wall increasing resistance to pulmonary blood flow
which increases pressure in pulmonary arteries increasing workload to right
ventricle causing failure (cor pulmonale)
o S/s: EKG= RVH, abnormality on CXR, fatigue, chest discomfort, peripheral
edema, JVD, tachypnea. Definitive diagnosis is with right heart catheterization
o Treatment: O2, diuretics, anticoagulants, avoidance of air travel, decongestants,
NSAIDS, pregnancy, smokers,
 Cor Pulmonale
o Secondary to PAH. RV enlargement causing acute hypoxemia
o S/S: obscured by primary respiratory disease and appear only during exercise
testing. Normal heart at rest but with exercise CO falls, EKG= RVH, chest pain,
pulmonic or tricuspid valve murmur, pulmonary edema, hepatic congestion and
JVD
o Treatment is the same as for PAH

901
The Kidneys
 Functions
o Regulates EC fluid volumes, osmolality and BP
o Maintains ion balance
o Homeostatic regulation of pH
o Excretion of wastes- major waste product is urea (nitrogenous waste product)
broken down form ammonia
o Productions of hormones
 Kidneys are located retroperitoneal at the level of the lower ribs
 The afferent arteriole brings blood to the nephron (20% is filtered 80% exits via efferent
arteriole)
 Circulation starts at afferent arteriole and continues to the efferent arteriole to peritubular
capillaries then exiting via the renal vein. The circulation of blood is closely intertwined
with the lumen of the nephron to allow for absorption, filtration, secretion and excretion
o Filtration- blood to lumen
o Reabsorption- lumen to blood
o Secretion- blood to lumen
o Excretion- lumen to external environment
 The urinary excretion of substances depends on its filtration, reabsorption and secretion
and is <1%
 Podocytes- epithelium around glomerular capillaries that can expand/contract changing
the surface area (filtration slits)
 Hydrostatic pressure (aka BP) opposes colloid osmotic pressure (proteins) within
Bowman’s capsule and net forces influence filtration
o Auto-regulation of glomerular filtration rate (GFR) takes place over a wide range
of BP’s
o Resistance changes in renal arterioles alters renal blood flow and GFR
 Resistance is affected by length, viscosity and most importantly radius
 If there is an increase in resistance in the afferent arteriole, renal blood flow with be
decreased therefore decreasing GFR which increases flood flow to other organs
 If there is an increase in resistance in the efferent arteriole, renal blood flow will back up
due to restricted exit and GFR will increase. Incoming blood flow with be decreased due
to back pressure increasing flow to other organs
 GFR is also regulated by
o Myogenic response- similar to auto regulation in other systemic arterioles
o Tubuloglomerular feedback- paracrine control (hormones)
 GFR increases increasing flow through tubule and flow past macula densa.
Paracrine from macula densa to afferent arteriole causing constriction and
increased resistance. Hydrostatic pressure in glomerulus is decreased and
the GFR decreases

902
 o Hormones and autonomic neurons (endocrine)- changes resistance in arterioles
(BP) and by altering the filtration coefficient (measures how much space is
between gaps/pores/podocytes)
 Reabsorption:
o Na is reabsorbed by active transport in the proximal tubule
 Enters the cell through membrane proteins moving down its
electrochemical gradient. It is then pumped out the basolateral side of cell
by Na/K ATPase
o Na linked reabsorption in the proximal tubule (glucose, asparate etc.)
 Na moves down its electrochemical gradient using the SGLT protein to
pull into the cell ex. Glucose against its concentration gradient. Glucose
diffuses out the basolateral side the cell using the GLUT protein. Na is
pumped out by Na/K ATP-ase
o Anions (Cl-, HCO3- etc) use secondary active transport or facilitated diffusion
o H20 moves out by osmosis following solute reabsorption
o K, Ca, Urea, other solutes concentrations increase as fluid volume decreases and
permeable solutes are reabsorbed by diffusion
o Urea is passively reabsorbed
o Plasma proteins are reabsorbed by transcytosis and exocytosis out
o Trans epithelial transport is when substances cross both apical and basolateral
membranes to get into ECF
 Renal threshold is the plasma concentration at which saturation occurs and substance
cannot go back into blood it remains in nephron
 Filtration of glucose (from blood to kidney) has a linear relationship with plasma glucose
levels. If plasma glucose increases the filtration rate of glucose into the kidney increases
 Reabsorption of glucose is linear to the plasma glucose to a point. There is a Tm
(transport maximum) which is when the capacity is reached for moving glucose back into
the blood.
 Secretion- transfer of molecules from ECF into lumen of nephron (active process)
o Important in homeostatic regulation (K and H)
o Increasing secretion enhances nephron excretion
 Excretion= filtration-reabsorption+ secretion
 Micturition- as bladder fills stretch receptors fire causing parasympathetic neurons to fire
and motor neurons to STOP firing. Smooth muscle contracts and internal sphincter
passively is pulled open and external sphincter relaxes.
 Urine concentration
o Osmolality changes as filtrate flows through the nephron
 Isosmotic fluids leaves proximal tubule and becomes more concentrated in
descending limb. Solute is removed into eh ascending limb creating
hyposmotic fluid. Hormones control distal nephron permeability to water
and solutes. Urine osmolality depends on reabsorption in the collecting
duct.

903
  Vasopressin makes the collecting duct more permeable to water by leaving
the blood (from post pituitary) and binding to the cell membrane
activating cAMP second messenger which then inserts Aquaporin pores
into apical membrane so water can be absorbed by osmosis into the blood
 Factors increasing vasopressin are osmolality greater than 280mOsm,
decreased atrial stretch due to low blood volume and decreased blood
pressure
 Countercurrent exchange in the medulla of the kidney
o In ascending limb Na, K and Cl- are pumped out of tubule increasing
concentration in blood and creating a dilute filtrate in the lumen
o Salt is reabsorbed in the ascending limb and water is reabsorbed in the descending
limb
 Sodium Balance- homeostatic response to salt ingestion
o Aldosterone combines with a cytoplasmic receptor which initiates transcription in
the nucleus. New protein channels and pumps are made and aldosterone-induced
proteins modify existing proteins resulting in increased Na reabsorption and K
secretion
o With ingestion of salt there will be no change in volume but an increase in
osmolality
 Vasopressin is secreted (kidneys conserve H2O) and thirst is initiated to
increase H2O intake, increasing ECF and increasing BP causing kidneys
to excrete salt and H2O returning osmolality, BP and volume back to
normal
 Low sodium stimulates salt appetite
o Renin-Angiotensin-Aldosterone system (RAAS)
 ANG II is the signal controlling aldosterone release from adrenal cortex
 Renin converts angiotensinogen to angiotensin I and is then converted by
angiotensinogen converting enzyme to angiotensin II
 ANG II increases blood pressure by vasoconstriction, stimulating thirst
(increasing ECF), vasopressin secretion (conserving blood volume) and
increase sympathetic output to the heart and blood vessels
o Natriuretic peptides promote salt and water excretion
 Potassium balance
o Aldosterone plays critical role
o Hypokalemia- muscle weakness and failure of respiratory muscles and the heart
o Hyperkalemia- cardiac arrhythmias
o Causes can be kidney disease, diarrhea and diuretics

904
  Acid-Base Balance
o Normal pH of plasma is 7.38-7.42
o Abnormal pH affects nervous system
 Acidosis- neurons are less excitable and CNS depression
 Alkalosis- hyper-excitable
 pH disturbances can be associated with K disturbances
 pH homeostasis
o buffers-moderate changes in pH, combines with or releases H+, Hgb, HCO3, PO4
o ventilation- rapid response
o renal regulation- slowest response
o proximal tubule secretes H+ and reabsorbs HCO3-
 Na/H Antiport secretes H+
 H+ in filtrate combines with filtered HCO3- to form CO2
 CO2 diffuses into cell and combines with H2O to form H+ and HCO3-
(uses CA)
 H+ is secreted again and excreted
 HCO3- is reabsorbed
 Glutamine is metabolized to ammonium ion and HCO3-
 NH4+ is secreted and excreted
 HCO3- is reabsorbed
o Type A intercalated cells function in acidosis to excrete acid
o Type B intercalated cells function in alkalosis to excrete base
Pathophysiology of the Renal-Excretory System
 Common indications for renal and urologic surgeries: neoplasm, stone, obstruction
 Nephrology- involved with making urine (renal parenchymal disease and disorders of
renal function)
 Urology- involved with eliminating urine (collecting system disease, diseases of
elimination, sexual dysfunction and neoplasm) LOWER tract
 Glomerular disease
o Post-streptococcal glomerulonephritis- child with dark red urine following strep
infection
 AB’s made to basement membrane. Complement is triggered causing
injury
o Hypertensive glomerulosclerosis
o Diabetic glomerular disease- Kimmestiel-Wilson disease
 Polycystic renal disease- 1:20 nephrons don’t form normal tubules, cysts are formed and
inhinge on normal functioning nephrons

905
 Hydronephrosis- long term/uncorrected damages renal parenchyma and impairs function
of the involved kidney
o Back pressure of obstruction impairs filtration and overall renal function- lose
urine to lymphatic blood system
 Bladder emptying/micturition is dependent on: sympathetic sphincter, parasympathetic
contraction of bladder, cerebral cortex, spinal cord intact. SCI level of T8 or below may
prevent continence. Peripheral neuropathies from DM, Guillain Barre can also effect
elimination
 Stress incontinence (anatomic incontinence)
o Weakened pelvic muscles, weakening in the wall between bladder and vagina
o Change in the position of the bladder
o Most commonly in post-partum women
 Cystocele- herniation of urinary bladder and often urethra beneath vaginal mucosa. Due
to weakening of pelvic floor during vaginal delivery. Often associated with stress
incontinence
o Surgery: urethral sling- kinks off urethra
 Overflow incontinence- bladder fails to empty completely, leading to frequent urination
or dribbling
o Weakened bladder as a result of nerve damage from DM or other neuropathy or
o Urethral obstruction due to kidney or urinary stone, tumor, BPH
 Urge incontinence/overactive bladder- frequent, sudden urge to urinate with little control
of the bladder
o May be symptom of cystitis, stroke, diseases of nervous system, tumor, cancer of
uterus, bladder or prostate, prostatitis, C-section, hysterectomy, lower intestine or
rectal surgery
 Mechanisms of Acute Kidney Injury
o Infection
o Nephrolithiasis- stones, obstruction
o Vascular obstruction- renal vein thrombosis, embolism from a fib, LA thrombus
or appendage
o Bilateral renal obstruction
o Acute glomerular disease
o ATN- ingestion of toxins, nephrotoxic drugs, septic shock with GN or GP
o Hypoperfusion- pre-renal (decreased CO and BP)

906
 Types of AKI
o Pre-renal- secondary to hypovolemia (anesthetics, HF, ACS, valve problems,
sepsis) reversible but if not corrected will lead to ATN
 subjective signs of perfusion- CRT, cool skin, mottled
 Objective- urine output (best indicator of CO), Swan, Echo
o Intrinsic aka renal- ATN- sudden onset of renal injury due to toxicity, sepsis,
systemic disease (malignant HTN)
o Post-renal- obstruction, stone, tumor or trauma.
o Sudden loss of renal function can lead to: fluid retention, high K, Mg, PO4,
metabolic acidosis
 Abnormalities of renal function manifestations:
o Dysuria, incontinence, polyuria, hematuria, and renal colic
o Symptoms: fatigue, anorexia, muscle cramps, chest pain of pericarditic, pruritis,
N/V, dyspnea, lethargy, coma, pericardial rub (hold breath to distinguish from
cardiac etiology)
o Las: Plasma BUN and Creatinine approximate renal function
o Significant loss of GFR is necessary to demonstrate a change in BUN/Creat
 Chronic Renal Failure
o Indicators: EKG has peaked T waves, bradycardia, CHB,
o Should obtain: EKG, pulse-ox, ABGs, daily weights, CXR
o Treatment: correct electrolytes, HD, transplant
 #1 indication for renal transplant is diabetes (also HTN and glomerular
disease)
 Problems that can lead to deterioration of preexisting renal disease
o Hypotension- hypovolemia from diuretics, hemorrhage
o Low CO, sepsis- poor perfusion of kidneys
o Drugs- aminoglycosides, contrast dye, NSAIDs, statins, methotrexate,
cyclosporine
o Renal infection
o ACE/ARBs are given to DM patients to protect glomeruli by opening efferent
arteriole. As GFR drops in the later stages however, they may promote a more
rapid decline of renal function.
o Smoking
o Uncontrolled diabetes

907
 End Stage Renal Disease (ESRD): ex: transplant pts, AV fistula
o Coagulopathy- platelets are sequestered by vasculopathy in glomeruli, urea
impairs platelet aggregation, DDAVP treatment, HD can reverse
o Sepsis- neutrophil functions impaired decreasing the total lymphocyte count, poor
nutrition, need flu and pneuovax vaccines
o Accelerated cardiovascular disease- increase volume adds stress to ventricle
dilating it, chronic HTN, endothelial dysfunction, accelerates atherosclerosis,
CHF, CVA, PAD
o Anemia- decreased Erythropoietin, RAAS, aldosterone
o Secondary hyperparathyroidism- decreased Vit D so Ca is not absorbed from gut.
PO4 and Mg rely on Vit D also. PTH is stimulated chronically leading to
hyperparathyroidism. Bone matrix is broken down by osteocytes causing bone
disease, osteoporosis etc.
o Chronic serositis- pericardial disease, pleural effusion (decreasing respiratory
reserve), ascites. Can lead to tamponade
o Dialysis related morbidity- infection, sepsis, thrombosis, bleeding from graft/site.
Hypotension, arrhythmias, increased risk of HBV. PD catheters can lead to
peritonitis
o Acid-Base Electrolyte Disorders- low Ca, High PO4, K Mg, acidosis, increased
volume (normal Na)
 Renal transplantation is superior to RRT in the management of ESRD because:
o Better long term survival rate
o Quality of life is better with transplant
o Health care expenditures are less with transplant
 Intra-op problems that may arise with ESRD patients:
o Arrhythmias, electrolyte imbalance, acidosis, accumulation of drugs (benzos,
Demerol are bad)

908
The Digestive System
 Animals get basic organic molecules to make ATP from food which is then broken down
thru digestion by breaking polymers (CHO, fats, proteins) into monomers. Absorption
then takes these monomers into the bloodstream to be allocated.
o Some materials such as cellulose cannot be digested so it never actually “enters”
the body
 GI tract is 30 feet long (increased surface area for more absorption)
o Basic processes are digestion, motility, secretion, storage and elimination,
immune barrier and absorption
 Motility- ingestion, mastication, deglutination (swallowing), peristalsis,
segmentation (churning/mixing)
 Secretion- exocrine-digestive enzymes, acid, mucus and endocrine-
hormones to regulate digestion
 Digestion- breaks food down into smaller units chemically and
mechanically
 Absorption- passing broken down food into blood or lymph
 Storage and elimination- temporary storage of undigested foods
 Immune barrier- simple columnar epithelium with tight junctions prevent
swallowed pathogens from entering the body
o Accessory organs are teeth, tongue, salivary glands, liver, gallbladder, pancreas
 Four layers of Digestive Tract
o Mucosa- innermost- secretory and absorptive layer, contains thin layer of smooth
muscle, and goblet cells which secrete mucus
o Submucosa- very vascular, has some glands, nerve supply
o Muscularis externa- smooth muscle responsible for peristalsis, also major nerve
supply
o Serosa- outer protective layer of connective tissue
 Saliva contains antimicrobial agent and SALIVARY AMYLASE to start digesting
starches (CHOs)
 Pharyngeal muscles of upper esophagus under autonomic control by the swallowing
center of brain
 Protein digestion begins in stomach, kills bacteria in the food and forms chime
 Stomach
o Parietal cells- secrete HCl acid into the lumen of the stomach dropping pH to 2
and denaturing proteins (and intrinsic factor (Vit B12)
o Chief cells- secrete pepsinogen which is converted to active pepsin
o HCl acid does not eat stomach lining because there is a thin layer of mucus with
bicarbonate, tight junctions between epithelial cells and the whole digestive tract
cell system is regenerated every few days
o Peptic ulcer- erosions of mucosa of stomach/duodenum
 Helicobacter pylori- reduces mucosal barriers to acid
 Treatment: H/K ATPase inhibitor- Prilosec to reduce HCL acid and Abx’s
o Prostaglandins- stimulate mucus and HCO3 production
 NSAIDS inhibit prostaglandin activity, can cause bleeding
o Inflammation causes histamine release which causes more acid secretion into
stomach (positive feedback that is not helpful) TX: Zantac, Tagamet

909
 Small Intestine
o Duodenum, Jejunum and Ileum
 Mucosa and Submucosa are folded into plicae cirulares then into villi then
microvilli
 Rapid absorption due to high surface area
 Have goblet cells which secrete mucus
 Lacteals absorb fatty acids
 Paneth cells secrete antibacterial molecules
 Microvilli aka brush border contain digestive enzymes that
hydrolyze disaccharides
 Peristalsis and segmentation cause chime to move along small
intestines
o Carbohydrate absorption is driven by Na ATPase
 Large Intestine
o Chyme passes from ileum thru ileocecal valve down ascending, transverse,
descending, sigmoid colon
o Little to no digestive function
 Absorption of water, electrolytes, Vit K and some B vitamins
 Aldosterone stimulates greater salt and water absorption
o Large numbers of microorganisms referred to as intestinal microflora live here
 Some are commensal-bacterial benefit we aren’t harmed
 Mutualistic- we benefit too
 They take up room so bad bacteria can’t get in
 Liver
o Largest abdominal organ
o Blood from intestine is delivered to liver first via HEPATIC PORTAL VEIN then
circulates thru liver capillaries before leaving thru the hepatic vein (central vein)
o Hepatic artery and portal vein blood come together to form HEPATIC
SINUSOIDS
o Hepatocytes form hepatic plates separated by capillary spaces called hepatic
sinusoids. They have large fenestrated pores that allow proteins, fats and
cholesterol to pass thru.
o HEPATIC PLATES are arranged as liver lobules with hepatic arteries , hepatic
portal vein and a central vein and regulate composition of blood and bile
o Bile is secreted by hepatocytes and drained into bile ducts
o Kupffer cells line sinusoids and phagocytize bile
o Glycogenesis- removes glucose and stores it as glycogen
o Lipogenesis- removes and stores triglycerides
o Gluconeogenesis- liver makes glucose from amino acids (proteins)
o Ketogenesis- converts fatty acids into ketones

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 Pancreas
o Endocrine- Islets of Langerhans cells make insulin and glucagon
o Exocrine- acini cells make pancreatic juice (zymogens) which is delivered to
duodenum via pancreatic duct
o Bicarbonate secretion in pancreas and duodenum prevents stomach acid from
damaging the wall of small intestine
o Zymogens are inactive until they reach the small intestine where they are
activated
o Enterokinase on brush border activates TRYPSINOGEN which turns it into
TRYPSIN
o Trypsin- digests proteins in chime and activates other enzymes
 Digestion of Proteins
o Begins in stomach with pepsin and finishes in duodenum and jejunum with
pancreatic enzymes
 Digestion of fats
o Begins in duodenum when bile emulsifies fat and break them into small fat pieces
and they are exocytosed across basolateral membrane and go into lymph (lacteal)
then transported back to vena cava
 Little brain senses food/stretch and ENS is activated causing reactions to aid in digestion
( smooth muscle, secretions, HCO3)
 Brain can work with little brain or over-ride to enhance ability to digest food

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BRAIN PART FUNCTION

Cerebrum Involved w/ voluntary motor activity, sensory perception from body, special sensory functions, learning and language.

Frontal Lobe The primary motor cortex is located in the pre-central gyrus and on the medial side of the frontal lobe in an area called the paracentral gyrus. Large
nerves are located in the gray matter of this gyrus and are responsible for voluntary control of precise movements/volitional movements. All motor
areas are in frontal lobe. (*Sensory areas are located in the parietal, temporal, and occipital lobe*). The frontal lobe is involved w/ complex learning
skills, judgment, reasoning, and personality.

Pre-central gyrus Motor areas are located in the formal lobe. Involved w/ motor skills (contains pyramidal cells which are active in motor activity).
(motor cortex)

Broca’s Area Located anterior and inferior to pre-central gyrus. Broca’s area is the motor and speech area. It directs muscles of the tongue, lips, and throat which
are involved in speech production. Also involved in preparation of speech.

Pre-motor cortex Located anterior to motor cortex. Important in learned motor skills, repetitious movements, and planning movements.

Post-central gyrus The primary somatosensory area (body sense area: general sensory, touch, pain, temperature, and proprioception) is located in the post-central gyrus
of the parietal lobe and along the medial aspect in the paracentral gyrus.

Somatosensory Posterior to post-central gyrus in the parietal lobe. Integrates sensory information. Integration and understanding occurs in the somatosensory
association area association area. [If you have a key in your pocket and you put your hand in your pocket, you feel the key. The key is felt in your primary motor
cortex. But the fact that you know it’s a key is realized in your association cortex].

Occipital lobe The primary visual area is located on the medial aspect of the occipital lobe. It is located immediately superior and inferior to the calcarine sulcus. So
(primary visual area) the primary visual area is located immediately on either side of the calcarine sulcus, and as you move farther and farther away from the calcarine
sulcus, you get into the visual association area.

Visual association area Located on either side of the primary visual area/cortex. The visual association area interprets vision.

Primary auditory area Located at the superior and posterior portion of the temporal lobe and inside the lateral sulcus. Hearing is bilateral, meaning is located on both sides of
the brain (Unlike the speech area w/Broca’s area).

Auditory association Located posterior to the primary auditory area. (Wernicke’s area is an association area (it is primarily located on the left side of the cortex because is it
area associated w/ the speech area of Broca)).

Olfactory area (smell) The Olfactory area, are receiving info about smell which is located on the inferior part of the frontal lobe in a special area called the uncus. (The
olfactory area is located kinda “under” the frontal lobe.

Gustatory area (taste) Located in the inferior portion of the parietal lobe. It is part of the post central gyrus. (Gustatory area is located in the parietal lobe, at the inferior part
of the post-central gyrus, just above the temporal lobe)

Pre-frontal cortex An association area. Location on the anterior portion of the frontal lobe (anterior to the motor area). [Fineas Gage, a railroad worker, a large rod went
through the anterior part of his brain, specifically his prefrontal cortex, his personality, judgment, and reasoning, changed dramatically].

General interpretation Located in the temporal, parietal, and occipital lobes. They all integrate information.
areas

Language area Involved Wernicke’s and Broca’s area; Parietal and occipital area also.

Visceral association Inside lateral sulcus; insula. Important for visceral (organ) association area.
area

Left hemisphere Dominant for language. Left is involved with language, math, and logic.

Right hemisphere Spatial perception, intuition, emotion, artistic and musical skills.

Superior Calliculi Associated with the visual system.

(midbrain)

Inferior Calliculi Associated with the auditory system.

(midbrain)

Cerebellum Involved w/ equilibrium, muscle tone, and coordination and balance of somatic motor activities. The function of the cerebrum is to coordinate motor
activity and to control equilibrium. This is accomplished by connections of motor areas in the cerebral cortex and communications w/ basal ganglia.

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Thalamus The only sensory info that is not processed in thalamus is olfaction. Thalamus has a very important function in integrating all of our sensory info.
Very important relay for sensory info.

Hypothalamus Controls Autonomic Nervous System (ANS). Involved w/: emotion (connects w/ limbic system which is responsible for emotion), temp. Regulation
(hypothalamus is our central thermostat for heating and cooling), food intake (controls our desire to eat/not eat), water balance (it will increase or
decrease our retention of fluids, it has nuclei which are sensitive to osmolality), sleep-wake cycle (involved w/ circadian rhythm), endocrine system
(hypothalamus acts as our Chief organizer for our endocrine system. It secretes releasing factors which will then act on the pituitary gland which is
located immediately below the hypothalamus. The pituitary gland will then control the release of hormones from endocrine glands throughout the
body. The hypothalamus is also important in synthesizing Oxytocin and vasopressin/ADH.

Epithalamus Contains the pineal gland. Regulates sleep-wake cycle. Important for the onset of puberty.

Subthalamus Part of basal ganglia so it will influence motor function. Most importantly, it influences motor function.

Midbrain Contain a superior and inferior Calliculi. Involved w/ basal ganglia and motor system.

Pons 4 cranial nerves exit from the pons (CN’s- 5, 6, 7, 8). A numotaxic center is located w/in the pons, which is responsible for the control of respiration.
Dorsal to the pons is the 4th ventricle which is covered by the cerebellum.

Medulla Oblongata CN’s 9, 10, 11, and 12 are associated w/ medulla. Contains pyramidal decussation, this is where the pyramidal tracts cross. Medulla contains
important centers which control heart rate, cardiac center, blood pressure, and basal motor center. There is also a respiratory center w/in the medulla
that interacts w/the numotaxic center in the pons. Other visceral centers which control vomiting, swallowing, coughing, and sneezing are also located
in the medulla.

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 Action Innervation Origin Insertion
Serratus Posterior Respiratory movement Intercostal nerves; Lies deep to rhomboids. Extends To the vertebral column
Superior AND from the ventral from scapular spine. (Superior) downwards to ribs 2-5.
Serratus Posterior rami of the spinal Lies deep to latissmus dorsi. (Superior) to lower 4 ribs.
Inferior Superior is ribs 2-5. nerves Lower thoracic and upper lumbar (Inferior)
Inferior is ribs 9-12. spines (Inferior).
Splenius Capitis Extend (pull head posteriorly when working Dorsal rami of Ligamentum nuchae, spinous Mastoid process of
AND Splenius together), laterally flex head (if only one side cervical spinal processes of vertebrae C7-T6, temporal and occipital
Cervices contracts). nerves and occipital bone. (Capitis) bone. (Capitis) Transverse
Spinous processes of vertebrae processes of C1-C4
T3-T6. (Cervicis) vertebrae. (Cervicis)
Iliocostalis (erector Extends vertebral column (when acting with Dorsal rami from Iliac crest (lumborum), inferior 6 Angles of ribs (lumborum
spinae muscle; Has longissimus and spinalis), and lateral flexion spinal nerves at all ribs (thoracic), and ribs 3-6 and thoracic) and transverse
a lumborum, (bends vertebral column to same side if only one levels (cervicis). processes of cervical
thoracic and side contracts) vertebrae C6-C4 (cervicis)
cervicis portion)
Longissimus Largest portion of erector spinae. Thoracic and Dorsal rami of Transverse processes of lumbar Transverse processes of
(erector spinae cervices together will extend vertebral column. spinal nerves at all through cervical vertebrae. thoracic through cervical
muscle; has a One side contracting will bend vertebral column to levels. vertebrae and to ribs
thoracic, cervicis same side (lateral flexion). Capitis extends head superior to origin. Capitis
and capitis portion) (when both sides are acting), and turns face to inserts into mastoid process
same side (if only one side is acting). of temporal bone.
Spinalis (erector The capitis portion is very small and often cannot Dorsal rami of Spines of lumbar and thoracic Spines of upper thoracic
spinae muscle; has be distinguished. The spinalis muscle extends the spinal nerves at all lower vertebrae. and cervical vertebrae.
a thoracic, cervicis vertebral column and head. levels.
and capitis portion)
Semispinalis Bilaterally, extends head and spine. Unilaterally, Dorsal rami of Transverse processes of C7-T12. Occipital bone (capitis),
(transvers spinal rotates head and neck to opposite side. Extend spinal nerves spinous processes of
group; most from transverse processes to spinous processes cervical (cervicis) and
superficial and and cross about 6 vertebrae. thoracic vertebrae T1-T4
longest fibers.) (thoracic)
Multifidus Bilaterally, extends spine. Unilaterally, rotates Dorsal rami of Posterior sacrum, L1-L5 Spinous processes
(transvers spinal spine to opposite side. Extend from transverse spinal nerves mammillary processes, T1-T12
group; very thick processes to spinous processes and cross about 4 transverse processes, C4-C7
in the lumbar vertebrae. articular processes.
region)
Rotators (transvers Bilaterally, extends spine. Unilaterally, rotates Dorsal rami of Transverse processes Spinous processes
spinal group) spine to opposite side. Extend from transverse spinal nerves
processes to spinous processes, or the lamina
immediately above and cross about 1-2 vertebrae.
Quadratus Bilaterally, extends spine and fix 12th rib. T12 and upper Iliac crest and iliolumbar fascia Transverse processes of
Lumborum (Not a Unilaterally, flexes trunk to same side (lateral lumbar spinal upper lumbar vertebrae and
back muscle but flexion). Fills in space from the 12th rib and the nerves (ventral lower margin of 12th rib.
forms part of iliac crest. Can also participate in very forceful rami)
posterior respiration by holding 12th rib in place and by
abdominal wall) helping to expand the thoracic cavity.
Rectus Abdominis Flexes lumbar region of vertebral column (flexes Intercostal nerves Pubic crest and symphysis Xiphoid process of sternum
trunk), and compresses abdomen (increases intra- and costal cartilages of ribs
abdominal pressure). 5-7
External Oblique Aids rectus abdominis in flexing and rotating Intercostal nerves Lower 8 ribs (it interdigitates Linea alba (by way of its
spine/trunk (rotates trunk to opposite side so if with the serratus anterior) apaneurosis)
you contract the right side, then you would move
your right shoulder to the left side). Also
compresses the abdomen.
Internal Oblique Flexes and rotates spine/trunk (to same side). Also Intercostal nerves Lumbodorsal fascia Linea alba, pubic crest, last
compresses the abdomen. (thoracodorsal fascia), iliac crest, 3 ribs.
and the lateral inguinal ligament
Transverse Compresses abdomen and compresses the Intercostal nerves Inguinal ligament, Lumbodorsal Linea alba and pubic crest
Abdominis abdominal contents. fascia, cartilages of last 6 ribs and
iliac crest.
Iliacus (part of Hip/thigh flexion, and trunk flexion (also helps to Femoral nerve Iliac fossa of os coxa Lesser trochanter of femur
illiopsoas) stabilize the hip joint) (arises from lumbar via illiopsoas tendon along
segments 2,3, and 4) with the psoas major.
Illiopsoas is called the “chief flexor of the thigh
and trunk”

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Psoas Major (part Flexes the thigh and flexes the trunk. Ventral rami L1-L3 Transverse processes and bodies Lesser trochanter of femur
of illiopsoas) and discs of lumbar vertebrae and via illiopsoas tendon along
Illiopsoas is called the “chief flexor of the thigh T12-L5 with the iliacus.
and trunk”
Sartorius Flexes and abducts and laterally rotates the thigh. Femoral nerve Anterior superior iliac spine Inserts as part of the “Pes
Flexes leg (flexes hip and knee). (All of its actions Anserinus” which is on the
will help you sit w/a crossed leg; crossed leg upper medial tibia
sitting position).
Rectus Femoris Extends knee and flexes thigh at hip. (Not primary Femoral nerve Anterior inferior iliac spine and Patella and tibial tuberosity
(Part of quadriceps hip flexor because the illiopsoas takes care of that) rim of acetabulum via patellar ligament.
femoris) The only muscle in the quadriceps femoris to act
of hip/thigh.
Vastus Lateralis Extends knee (It crosses only the knee joint so it Femoral nerve Greater trochanter and Patella and tibial tuberosity
(Part of quadriceps extends only the knee; it has no action on the hip; intertrochanteric line and the via patellar ligament.
femoris) only Rectus Femoris acts on the hip/thigh) lateral lip of the linea aspera
Vastus medialis Extends knee (it does not cross the hip joint so it Femoral nerve Medial lip of the linea aspera and Patella and tibial tuberosity
(Part of quadriceps only extends the knee; only Rectus Femoris intertrochanteric line via patellar ligament.
femoris) crosses the hip and acts on it)
Vastus intermedius Extends knee (it does not cross the hip joint so it Femoral nerve Anterior and lateral surfaces of Patella and tibial tuberosity
(Part of quadriceps only extends the knee; only Rectus Femoris proximal femur and shaft. via patellar ligament.
femoris) crosses the hip and acts on it)
Tensor Fascia Flexes and abducts thigh, rotates thigh medially; Superior gluteal Anterior aspect of iliac crest and Iliotibial tract/band into the
Latae steadies trunk by inserting to iliotibial tract/band. nerve anterior superior iliac spine. lateral aspect of the tibia.
It also stabilizes the femur on the tibia and keeps
them in alignment when standing.
Adductor Magnus Adduction and medial rotation of thigh and active Obturator nerve Ischial ramus and inferior pubic Linea aspera (oblique/
(largest Adductor) in gait (flexion and extension of thigh) and posture (oblique/ triangular rami (oblique/ triangular portion). triangular portion).
(oblique/ triangular portion). portion). Tibial Ischial tuberosity (most vertical/ Adductor tubercle of femur
Extension of the thigh (most vertical/ medial nerve (most medial fibers). (most vertical/ medial
fibers). vertical/ medial fibers).
fibers).
Adductor Longus Adducts, medially rotates and flexes thigh. Also Obturator nerve Pubis near pubic symphysis Linea aspera
stabilizes thigh during gait.
Adductor Brevis Adducts, medially rotates and flexes thigh. Obturator nerve Body and inferior ramus of pubis Linea aspera above the
(Separates anterior and posterior Obturator nerve) insertion of adductor longus
Pectineus Adducts and flexes thigh. Also assists in medial Femoral nerve Pectineal line of pubis (and Inferior on the lesser
rotation of thigh. (most of the time) superior ramus) trochanter (in an area called
Obturator nerve the pectineal line of the
(may sometimes femur)
receive)
Gracilis Adducts thigh, flexes leg/knee, medially rotates Obturator nerve Inferior ramus and body of pubis Upper medial surface of
the leg tibia via Pes Anserinus
Gluteus Maximus Major extender of the thigh, assists in lateral Inferior Gluteal Dorsal ilium, sacrum, coccyx, Fibers run downward
rotation of the thigh. (Primarily acts under force: nerve and sacrotuberous ligament /lateral, insert into gluteal
going up stairs, rising from sitting position, tuberosity of femur (most
running, jumping. Used little during casual fibers) and iliotibial band
walking and standing). (some fibers).
Gluteus Medius Anterior fibers abduct and medially rotate thigh, Superior gluteal Between anterior and posterior Lateral aspect of greater
posterior fibers extend and laterally rotate thigh nerve gluteal lines (posterior side of trochanter of femur.
(most important in the walking mechanism ilium)
w/minimus)
Gluteus Minimus Anterior fibers abduct and medially rotate thigh, Superior gluteal Between anterior and inferior Anterior border of greater
posterior fibers extend and laterally rotate thigh nerve gluteal lines (posterior side of trochanter of femur.
(most important in the walking mechanism ilium)
w/medius).
Piriformis Primary action is lateral rotation. Helps abduct Ventral Rami of S1, Anterior surface of sacrum Superior border of greater
thigh when thigh is flexed. S2, and L5 trochanter of femur
Obturator Internus Primary action is lateral rotation of thigh. Ventral Rami of L5, Inner surface of Obturator Greater trochanter of femur
S1 membrane and margins of
Obturator foramen
Gamellus superior Rotates thigh laterally Ventral Rami L5, Ischial spine (superior gemellus), Common attachment with
AND inferior S1 Ischial tuberosity (inferior Obturator internus into the
gemellus) greater trochanter of femur.
Quadratus Femoris Primary action is lateral rotation of thigh. Ventral rami of L5, Ischial tuberosity (along with Greater trochanter of femur
S1 inferior gemellus) (a little off the trochanteric
crest)
Obturator externus Primary action is lateral rotation of thigh. Obturator nerve Outer surface of obturator Trochanteric fossa of the
membrane and margins of femur.
obturator foramen

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Biceps Femoris (2 Extends thigh and flexes knee (long head), Sciatic nerve; tibial Ischial tuberosity (long head), Common tendon; inserts
heads: long and laterally rotates leg when knee is flexed (short nerve (long head), linea aspera of femur and distal into head of fibula and
short) head) common fibular femur (short head) lateral condyle of tibia.
nerve (short head)
Semitendinosus Extends thigh at hip, flexes knee, and medially Sciatic nerve (tibial Ischial tuberosity in common Medial aspect of upper
rotates leg when flexed. branch) with the long head of biceps tibial shaft via the pes
femoris anserinus.
Semimembranosus Extends thigh and flexes knee, medially rotates Sciatic nerve (tibial Ischial tuberosity (along with Medial condyle of tibia
leg when knee is flexed. branch) semitendonosis and long head (forms oblique popliteal
biceps) ligament)
Tibialis Anterior Dorsiflexes and inverts the foot Deep fibular nerve Lateral condyle and upper 2/3rd of Medial cuneiform and 1st
(comes from tibia. Also partially off the metatarsal on medial side of
common fibular interosseous membrane. foot.
nerve which is a
branch of sciatic
nerve)
Extensor digitorum Extends toes, dorsiflexes foot, and everts foot. Deep fibular nerve Lateral condyle of tibia, proximal Phalanges of toes 2-5 via
longus ¾ of fibula, interosseous extension expansion hood
membrane
Fibularis/ Peroneus Dorsiflexes and everts foot Deep fibular/ Distal fibula and interosseous Dorsum of the 5th
Tertius peroneal nerve membrane metatarsal
Extensor hallucis Extends great toe and dorsiflexes foot Deep fibular/ Anterior fibula and interosseous Distal phalanx of great toe
longus peroneal nerve membrane via expansion hood
Fibularis/peroneus Plantar flexes, everts foot, supports arches of the Superficial fibular Head and upper portion of fibula 1st metatarsal and medial 1st
longus foot (peroneal) nerve cuneiform
Fibularis/peroneus Plantar flexes and everts foot Superficial fibular Distal fibula shaft (distal to origin Tuberosity of 5th metatarsal
brevis (peroneal) nerve of longus)
Gastrocnemius Flexes leg at knee joint and plantar flexes foot at Tibial nerve 2 heads: medial and lateral Calcaneus via calcaneal
ankle joint condyles of femur tendon (arkilles tendon)
Soleus Plantar flexes foot (does not cross knee) Tibial nerve Head of fibula and soleal line Calcaneus via calcaneal
(oblique line on posterior tibia) of tendon (arkilles tendon)
tibia
Plantaris Assists gastrocnemius in knee flexion and plantar Tibial nerve Posterior aspect of lateral condyle Long thin tendon into
flexion of ankle of femur (just medial to lateral calcaneus or medial aspect
head of gastrocnemius) of calcaneal tendon
Popliteus Flexes and medially rotates leg. Unlocks knee Tibial nerve Lateral condyle of femur Proximal tibia
from a fully extended position.
Flexor digitorum Plantar flexes and inverts foot and flexes toes Tibial nerve Posterior tibia Distal phalanges of toes 2-5
longus
Flexor Hallucis Plantar flexes and inverts foot, flexes big toe, Tibial nerve Lower shaft of fibula, & Distal phalanx of great toe
longus strong push off for walking (toe off) interosseous membrane
Tibialis posterior Inversion of foot, plantar flexes foot, supports arch Tibial nerve Superior aspect of tibia, fibula, & Several tarsal bones and
of foot interosseous membrane metatarsals 2-4
Extensor digitorum Extends medial 4 toes (toes 1-4) Deep fibular nerve Upper and lateral sides of Base of proximal phalanx
brevis calcaneus of great toe (as the
“extensor hallucis brevis”)
& tendons to the lateral
sides of the extensor
digitorum
Abductor hallucis Abducts and flexes great toe Medial plantar Medial process of tuberosity of Joins with tendon of flexor
calcaneus hallucis brevis, attaches to
base of proximal phalanx of
great toe
Flexor digitorum Flexes toes Medial plantar Medial process of tuberosity of 4 tendons divide to attach
brevis calcaneus on the lateral sides of
middle phalanges of toes 2-
5.
Abductor digit Abducts and flexes little toes Lateral plantar Tuberosity of calcaneus Lateral side of proximal
minimi nerve phalanx of small toe
Quadratus plantae Aids flexor digitorum longus in flexing toes Lateral plantar 2 heads attached to calcaneus on Lateral border of the tendon
(flexor accessories) nerve either side of the long plantar of flexor digitorum longus
ligament
Lumbricals (4) Flex proximal IPJ and extend 2 distal phalanges of 1st-medial plantar Medial side of tendons of flexor Medial side of base of
toes 2-5 2nd,3rd,4th- lateral digitorum longus proximal phalanges and
plantar extensor tendons of toes 2-5
Flexor hallucis Flexes proximal phalanx of great toe Medial plantar Cuboid & 3rd cuneiform (lateral Medial tendon joins
brevis (contains nerve cuneiform) abductor hallucis tendon,
sesmoid bone lateral tendon joins
adductor hallucis; base of

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 within each the proximal phalanx of big
tendon) toe
Adductor hallucis Adducts and flexes great toe Lateral plantar Base of metatarsals 2-4, & the Lateral side of proximal
(oblique head) tendon of fibularis longus as it phalanx of great toe with
passes along the plantar surface tendon of flexor hallucis
of the foot brevis
Adductor hallucis Adducts great toe Lateral plantar Metatarsophalangeal joint of toes Joins oblique head tendon
(transverse head) nerve 3-5 at lateral side of proximal
phalanx of great toe
Flexor digit minimi Flexes pinky toe Lateral plantar Base of 5th metatarsal and Lateral side of proximal
brevis nerve fibularis longus tendon phalanx of pinky toe
Plantar interossei Adduct toes 3-5 toward 2nd toe, flexes proximal Lateral plantar Bases and medial sides of Medial side of base of the
and extend middle &distal phalanges of toes 3-5 nerve metatarsals 3-5 proximal phalanges of toes
3-5
Dorsal interossei Abducts toes away from axis of 2nd toe, flexes Lateral plantar Bipennate muscles attaching to Proximal phalanx of both
proximal phalanx and extends middle and distal nerve adjacent shafts of metatarsals 1-5 sides of 2nd toe, & the
phalanges of toes 2-4 lateral side of 3rd and 4th
toes

action innervation origin insertion

Stabilizes scapula, pulls clavicle towards medial pectoral nerve

ribs 3, 4, and 5. Draws scapular down and (coming from brachial Anterior surface of ribs 3-
Pectoralis Minor forward, elevates ribs. plexus) 5 coracoid process

Serratus Anterior (Boxers

muscle; most powerful of Holds scapula against chest, protracts
pectoral girdle) scapula, elevates arm above 90 degrees, Long thoracic nerve Anterior surface of
used when forcefully punching, rotates (originates from Anterior/ lateral aspect of Vertebral/ medial border of
scapula laterally. brachial plexus) ribs 1-8 or 9 scapula

Holds clavicle in sternoclavicular joint nerve to Subclavius

(stabilized clavicle), depresses the (branch of brachial Inferior surface of lateral
Subclavius shoulder. plexus) Costal cartilage of rib #1. 1/3rd of clavicle.

Flexes head forward (nodding “yes”), Mastoid process of temporal

flexes head to the side, turns face to It has 2 heads: Clavice and bone (at lateral ½ of superior
Sternocleidomastoid opposite sides Spinal accessory nerve menubrium of sternum nuchal line)

Spine of scapula, acromion,

Trapezius Elevates, retracts, and depresses scapula Spinal accessory nerve Occipital bone lateral 1/3 of clavicle

Elevates scapula, extends neck posteriorly, Transverse process of C1- Superior vertebral border of
Levator Scapulae also flexes neck to same side Dorsal scapular nerve C4 vertebrae scapula

Minor- spine of scapula.

Rhomboid Major AND Rotates scapula downward, draws scapula Minor- spinous process of Major- medial border of
Minor medially, and retracts scapula downwards. Dorsal scapular nerve C7-T1. Major- T2-T5 scapula

{Has 2 heads: clavicular

and sternal} Clavicle,
Flex’s, adducts, and rotates arm medially. Lateral and medial sternum, and ribs 1-6 Intertubercular sulcus of
Pectoralis Major Forms anterior wall of armpit (axilla). pectoral nerves (cartilage) humerus

Powerful adductor, medial rotator or arm, Spinous process of T7-

depresses shoulder. {Used in climbing and T12, inferior angle of Intertubercular groove of
Latissmus Dorsi swimming} Thoracodorsal nerve scapula and iliac crest humerus

Anterior part: Flexion and medial rotation Lateral 1/3rd of clavicle,

of forearm. Posterior Part: extension and acromion and spine of Deltoid tuberosity of
Deltoid lateral rotation of arm Axillary nerve scapula humerus

Upper and lower Subscapular fossa of

Subscapularis Medial rotation of humerus subscapular nerves scapula Lesser tubercle of humerus

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 Initiates first 15 degrees of abduction,
helps to prevent downward dislocation of Supraspinous fossa of Superior part of greater
Supraspinatus humerus Suprascapular nerve scapula tubercle of humerus

Greater tubercle of humerus

Powerful lateral rotator of humerus, Infraspinatus fossa of the just posterior of
Infraspinatus stabilizes head in glenoid cavity. Suprascapular nerve scapula supraspinatus insertion

Greater tubercle of humerus,

Same as infraspinatus, also aids in Lateral border of dorsal inferior to infraspinatus
Teres Minor adduction of arm Axillary nerve scapular surface insertion.

Teres Major (aka- Same actions as Latissimus dorsi (adducts, Posterior surface of
Latissimus dorsi’s little extends, and medially rotates the arm) {its Lower Subscapular scapula along inferior Intertubercular sulcus of
helper) tendons fuse with latissmus dorsi} nerve angle humerus

Medial surface of humerus

Flexes and adducts arm, synergist with Musculocutaneous Coracoid process of shaft, opposite deltoid
Coracobrachialis pectoralis major nerve scapula tubercle

Short- coracoid process of

Flexes forearm. Primary Supinator of Musculocutaneous scapula. Long- Radial tuberosity and
Biceps Brachi forearm. nerve supraglenoid tubercle bicipital aponeurosis

Major forearm flexor in both supinated and

pronated positions (ex. picking up coffee Musculocutaneous
Brachialis cup) nerve Lower half of the humerus Coronoid process of ulna

Brachioradialis On lateral supracondylar

(considered as part of the Flexor of the forearm; used for quick ridge, at distal end of the
anterior forearm) flexion Radial nerve humerus Styloid process of radius.

Long- infraglenoid
tubercle of scapula.
Lateral- posterior humerus
above radial groove.
Primary extensor of forearm. (the long Medial- posterior humerus All 3 heads insert into
Triceps Brachii head also adducts arm) Radial nerve distal to radial groove. Olecranon process.

Anconeus (aka- sometime

called “the 4th tricept”. It
is on the posterior side of Lateral epicondyle of Lateral aspect of Olecranon
elbow) Assists in elbow extension Radial nerve humerus process of ulna

Medial epicondyle of
humerus and a little off of
Pronates the forearm and hand. Assists in the coronoid process of Lateral side of radius at
Pronator Teres flexion of elbow joint. Median nerve ulna. about the midshaft.

Powerful flexor of the wrist (when acting

with other flexors), abducts hand (acting
alone or with other extensors), assists with Medial epicondyle of Base of 2nd and 3rd
Flexor Carpi Radialis elbow flexion. Median nerve humerus metacarpals

Flexes the wrist (connects with palmar Medial epicondyle of Palmar aponeurosis (Fasha
Palmaris Longus aponeurosis) Median nerve humerus covering palm of hand)

Powerful flexor of the wrist, adducts hand, Medial epicondyle of

stabilizes wrist during finger extension, and humerus, olecranon
has some ability to flex elbow also (it process, and posterior Pisiform bone and base of 5th
Flexor Carpi Ulnaris crosses the elbow joint) Ulnar nerve surface of ulna. metacarpal

Flexes wrist, 1st and middle phalanges of Medial epicondyle of

fingers 2-5 (flexes at proximal humerus, coronoid process
Flexor Digitorum interphalangel joint and metacarpal of ulna, and shaft of 4 tendons into middle
Superficialis phalangel joint) Median nerve radius. phalanges of fingers 2-5

918
 Anterior surface of radius
and interosseous
Flexor Pollicis Longus Flexes distal phalanx of thumb Median nerve membrane Distal phalanx of thumb

Coronoid process,
Medial half by ulnar anteromedial surface of
Flexor Digitorum Flexes distal phalanx of fingers 2-5, assists nerve. Lateral half by ulna and interosseous 4 tendons into distal
Profundus in wrist flexion median nerve. membrane phalanges of fingers 2-5.

Primary pronator or forearm and hand

(assisted by pronator teres for more speed Distal portion of anterior Distal surface of anterior
Pronator Quadratus and power only when it is needed) Median nerve ulnar shaft radius

Extends and abducts hand/wrist

Extensor Carpi Radialis (synergistic with extensor carpi radialis Lateral supracondylar
Longus brevis) Radial nerve ridge of humerus Base of 2nd metacarpal

Extends and abducts hand/wrist

Extensor Carpi Radialis (synergistic with extensor carpi radialis Lateral supracondylar
Brevis longus) Radial nerve ridge of humerus Base of 3rd metacarpal

Lateral epicondyle of Four tendons insert into

Radial nerve (Posterior humerus at common extensor expansion hood and
Extensor Digitorum Extends fingers and hand interosseous nerve) extensor tendon distal phalanges

Radial nerve (Posterior Extensor expansion hood of

Extensor Digiti Minimi Extends the pinky and hand at wrist interosseous nerve) Common extensor tendon pinky.

Extends and adducts hand/wrist

Lateral epicondyle of
(when acting with extensor carpi radialis it humerus at common
will extend the hand and with flexor carpi Radial nerve (Posterior extensor tendon and
Extensor Carpi Ulnaris ulnaris it will adduct the hand) interosseous nerve) posterior border of ulna Base of 5th metacarpal

Supinates forearm and hand when slow

supination is needed (it joins the biceps Lateral epicondyle of Lateral surface of proximal
brachii when forceful and quick supination Radial nerve (Posterior humerus and proximal end of radius (reaches
Supinator is needed) interosseous nerve) portion of ulna attachment of pronator teres)

Posterior (proximal)
Radial nerve (Posterior surface of radius and ulna;
Abductor Pollicis Longus Abducts and extends thumb interosseous nerve) interosseous membrane Base of 1st metacarpal

Base proximal phalanx

Extensor Pollicis Brevis Radial nerve (Posterior Dorsal shaft of radius (brevis) and distal phalanx
AND Longus Extends thumb and abducts hand interosseous nerve) (brevis) and ulna (longus) (longus) of thumb

Posterior surface of distal Extensor expansion hood of

Radial nerve (Posterior ulna and interosseous index finger (joins tendon of
Extensor Indicis Extends index finger interosseous nerve) membrane extensor digitorum)

Tubercle of scaphoid and

adjacent trapezium, flexor Radial side of 1st phalanx of
Abductor Pollicis Brevis Abducts thumb Median Nerve retinaculum thumb

Flexor retinaculum and Base of radial side of

Flexor Pollicis Brevis Flexes thumb Median Nerve trapezium proximal phalanx of thumb

Opposition-moves thumb across palm to Flexor retinaculum and

Opponens Pollicis touch tip of pinky. Median Nerve trapezium Radial side of 1st metacarpal

2 heads: 1. oblique-
capitate and bases of 2nd
Adducts thumb (fills web between thumb and 3rd metacarpals. 2. Ulnar side of proximal
Adductor Pollicis and index finger) Ulnar nerve transverse- 3rd metacarpal. phalanx of thumb.

919
 Builds up hypothenar eminence, helps to Palmar aponeurosis and
Palmaris Brevis deepen the palm and helps with gripping. Ulnar Nerve flexor retinaculum. Skin of ulnar border of hand

Pisiform carpal and

Abducts little finger and flexes proximal tendon of flexor carpi Ulnar side of base of
Abductor Digiti Minimi phalanx Ulnar Nerve ulnaris proximal phalanx of 5th digit.

Flexor Digiti Minimi

Brevis (This does not have Hamulus of hamate and Ulnar side of base of
a longus) Flexes pinky finger Ulnar Nerve flexor retinaculum proximal phalanx of 5th digit.

Hamulus of hamate carpal

Opponens Digiti Minimi Opposes pinky finger to meet the thumb Ulnar nerve and flexor retinaculum. Ulnar side of 5th metacarpal

1, 2 (index and middle)

- median nerve. 3,4 Radial side of each tendon
Flex metatarsophalangeal joints, and (ring and pinky)- ulnar of flexor digitorum Radial side of extensor
Lumbricals extends at the interphalangeal joints. nerve profundus expansion hood of digits 1-4

All 3 insert into the proximal

phalanx on the same side of
their origin: 1. ulnar side of
3 interossei: 1. ulnar side proximal phalanx od index
of 2nd metacarpal. 2. finger. 2. Radial side of
Adducts fingers toward midline axis of Radial side of 4th proximal phalanx of ring
middle finger, flexes metacarpal phalangel metacarpal. 3. Radial side finger. 3. Radial side of
Palmar interossei (3) joint, extends interphalangel joint. Ulnar nerve of 5th metacarpal. proximal phalanx of pinky.

4 interossei: 1. adjacent
sides of 1st and 2nd
metacarpals. 2. Adjacent Proximal phalanges and
sides of 2nd and 3rd extension expansion hood. 1.
metacarpals. 3. Adjacent Radial side of index finger.
sides of 3rd and 4th 2. Radial side of middle
Abduct fingers away from midline axis of metacarpals. 4. Adjacent finger. 3. Ulnar side of
middle finger, flexes metacarpal phalangel sides of 4th and 5th middle finger. 4. Ulnar side
Dorsal interossei (4) joint, extends interphalangel joint. Ulnar nerve metacarpals. of ring finger.

920
 Case Studies:

Anaphylaxis Case Study:

E.S is a 5’ 0” 219 lb. 76 y/o female who was scheduled to have a right total knee arthroplasty vs
rigid spacer after a failed right total knee arthroplasty

Allergiessulfa-hives; ACEi-swelling; PCN’s-hives

PMHasthma, hypertension, DM 2, GERD, hyperlipidemia, breast cancer, depression, obesity

& MRSA

Surgical hxarthroplasty R knee 7/2/13 with GETA; closed tibia reduction 1/27/14; breast
biopsy. Pt denies any complications with anesthesia for her or her family.

Pre-op lab work was all WNL; BP 148/72, HR 68, RR 20, and O2 sat 96 on RA, T 97.9

Surgery was started on time with induction drugs including fentanyl 25 mcg, lidocaine 50 mg,
propofol 130 mg, rocuronium 50 mg. ETT was placed. Zofran 4 mg was given shortly after
induction. Maintenance with 1-1.2 mac desflurane, intermittent boluses of fentanyl 50 mcg, &
rocuronium 10 mg. The patients pre-op antibiotics were held d/t her current spacer being
infected. Per surgical request, the antibiotics (1500mg Vancomycin) were not to be given until
after aerobic/anaerobic cultures were obtained from the operative site. 15 min prior to the
antibiotics being given, tranexamic acid (TXA) 1000 mg was given slow IV push. The vanco
was started on a pump and running at the pre-programmed set rate of 167 mL/hr 25 minutes into
the case.
Eight minutes after the vanco was started and about 25 minutes after the TXA was given the pts
SBP’s dropped to the 60’s and HR to 130’s. Assessment of the pt revealed that she was bright
red. The vanco was immediately stopped, 100% Fi02 given along with 50 mg Benadryl. Help
was called. The patient then received 100mg hydrocortisone, albuterol inhaler delivered into
breathing circuit (pt was very wheezy). Pts O2 sats did remain 88-91% for about five minutes.
Through the 14 minutes of hypotension, surgery was stopped, “Epi lite” was given 10 mcg/mL
with a total dose of 180 mcg, 3 units vasopressin and a phenylephrine drip. The patient did have
ST elevation as well. An arterial line was placed along with two additional PIV’s. Fifteen
minutes after the initial reaction, an emergent TEE was done showing strong contractility with
decreased preload. More volume was given. ST elevation disappeared. Initial IVF was 0.9 NS
921
then LR and finally normosol d/t the patients ABG’s being acidotic. Total volume given 4500
mL crystalloid, 750 colloid. Other labs sent included CBC, TEG, tryptase & histamine (both
markers for anaphylaxis). Once the patient was stabilized the surgery was finished. TEE at the
end of the case revealed normal cardiac wall motion with adequate preload. The pt was
transferred, intubated to the PACU to await an ICU bed. In the ICU she did receive 3 units
PRBC’s for an Hct of 27. She was then extubated on POD 1 and transferred to the floor on POD
2 with plans for d/c on POD 5. I was able to see her on POD 4. She was neurologically intact and
her earliest recollection was being in the ICU intubated overnight. Due to the fact that both the
TXA and vanco were given relatively close together the decision was made to have them both
listed as allergies on the pts chart and she was encouraged to see an allergist for f/u testing.

Some things that we could have done were giving a different antibiotic, maybe a cephalosporin.
She had received vanco previously without any problems. We didn’t give and H2 blocker, which
helps to attenuate the reaction via competitive inhibition of histamine binding with H2 receptors.

Review of Anaphylaxis
IgE mediated reaction causing a massive degranulation of mast cells and basophils releasing
histamine, heparin and other cytokines. This massive release causes urticaria, pruritus,
vasodilation, and increased capillary membrane permeability which causes fluid to shift into the
extracellular compartment leading to cardiovascular collapse. Histamine also increases HR and
contractility, causes laryngeal edema and bronchospasm which can lead to hypoxemia.
First line treatment is several liters of crystalloid and epinephrine in 10-100 mcg doses IV. The
epi helps to restore capillary membrane permeability and decrease bronchoconstriction. A
combination of H1 and H2 agents to competitively inhibit histamines binding sites and attenuate
reaction. Corticosteroids do not immediately affect anaphylaxis but are used to decrease
inflammation and prevent biphasic anaphylaxis (second episode of anaphylaxis in response to
first triggering agent).

922
 Pre-Case Plan Development: CEA

Brief Description of The carotid artery is approached through an oblique neck incision along the anterior
Diagnostic/ Surgical border of the sternocleidomastoid muscle. Carotid sheath is opened and carotid
Procedure: artery is exposed. Heparin is administered, and the internal, external, and common
carotid arteries are clamped sequentially. An indwelling shunt may be utilized to
maintain carotid a. perfusion. The plaque is separated from the artery wall and is
removed. The arteriotomy is closed, with or without a patch, and the artery is
flushed and flow is restored. The incision is closed after hemostasis.

Positioning: Supine, neck is extended and turned to contralateral side.

Surgical Time: Total operating time: 90min

Carotid cross-clamp: 30min
EBL: 100-200mL

IV: 2 peripheral IVs at least one 16 gauge (or larger) and another for to run drips if
necessary.

Pain: 3-5/10

Other Considerations: Surgeon may or may not use shunt (shunt can increase risk of air embolism).
Maintain a stable, high-normal blood pressure blood vessels in hypoperfused
areas may have lost areas of autoregulation. Temporary cross-clamp of the carotid
artery acutely disrupts blood flow. Blood supply to the contralateral clamp side will
depend on adequate collateral blood flow through the circle of Willis if no shunt is
used. Pt will need post-operative ICU care 12-24hrs.

PATHOPHYSIOLOGY FOR SURGERY: Carotid endarterectomy (CEA) is frequently

used to treat severe atherosclerotic occlusive disease involving internal carotid arteries at the
common carotid artery bifurcation. Atherosclerotic carotid artery disease commonly causes
thromboembolic or hemodynamic stroke and transient ischemic attacks (TIAs). Carotid
endarterectomy (CEA) continues to be one of the commonly performed open vascular surgery
procedures in the United States, even as carotid stenting is being more frequently employed as an
alternative approach.

923
 Because of presumed microemboli from stenotic/ulcerated plaques at the carotid bifurcation,
CEA has been championed as an effective procedure to reduce the risk of subsequent stroke.
CEA is more effective than medical therapy for symptomatic patients with internal carotid artery
narrowing between 60% and 90%. Symptoms are usually hemispheric (contralateral, upper or
lower extremity paresis or numbness) or retinal (unilateral monocular blindness). Symptoms may
be transient (TIA or reversible ischemic neurological deficit [RIND]) or permanent (CVA).
Although some surgeons routinely prefer local anesthesia, most prefer GA with careful
hemodynamic monitoring because of the frequent concomitant CAD.
OTHER CONCERNS
Neuromonitoring: sensory evoked potentials are electrical potentials generated within the
neuraxis in response to stimulation of a peripheral or cranial nerve. As they travel from the
periphery to the brain, these potentials can be recorded by electrodes placed over the scalp and
along the transmission pathway. Evoked potentials have lower voltage than background EEG
activity, but summation of hundreds of signals using computerized devices makes it possible to
extract them by averaging out the random background EEG. A normal response implies that the
conduction pathway is intact. Damage to the pathway generally decrease amplitude or
prolongs latency (i.e. the time from peripheral stimulus to arrival of potentials at the recording
site) of the waveform peaks. EPs are classified according to the nerve tract being evaluated
Somatosensory evoked potentials (SSEPs) are obtained by stimulating a peripheral nerve and
recording the elicited signals over the spinal cord or cerebral cortex. SSEPs are used most
commonly to monitor spinal cord function during spinal cord or vertebral cord surgery. Because
SSEPs are conducted primarily by the dorsal column in the spinal cord, there are concerns about
the reliability of SSEP monitoring for detecting threatened motor function (anterior cord
ischemia). For this reason, the “wake-up test” is used in some centers as well as motor evoked
potential monitoring.
MEPs monitoring the integrity of the motor tracts within the spinal cord may be more reliable
than SSEP monitoring during spinal surgery. The ventral motor columns of the spinal cord may
be more susceptible to ischemia that the posterior proprioceptive fibers. Motor impulses can be
generated by transcranial electrical stimulation. The evoked responses are measured as a
potential over the spinal cord below the surgical field and in the muscle of interest, anesthetics
substantially modify transcranial induced potentials but less so if the stimulus is measured in the
spinal cord below the surgical field.
Anesthetic considerations: volatile anesthetics can depress SSEPs by reducing the amplitude or
prolonging the latency of the SSEPs and can abolish the far more sensitive MEPs. IV anesthetics
have less of an effect (propofol, fentanyl or Remifentanyl are compatible with effective
monitoring. All volatile agents depress evoked potentials. Nitrous oxide added to other volatile
agents profoundly depresses the amplitude of both SSEPs and VEPs.

924
Barash recommends using TIVA or at least above average IV opiates because they produce
minimal changes in SEP waveforms. Dexmedetomidine can be added to the anesthetic regimen
and will reduce MAC requirements while having essentially no effect on SSEP amplitude.
Sevoflurane and desflurane have less effect on SEPs than earlier anesthetic agents.
1. Isoflurane, desflurane, sevoflurane: 0.5-1.0 MAC*
2. N2O up to 50% can be used if baseline SSEP waves are not severely compromised. If the
baseline SSEP is poor, the addition of N2O may make the SSEP uninterpretable
3. Fentanyl infusion of 0.5-3 mcg/kg/hr
4. Morphine loading dose 0.1-0.3 mg/kg
5. Propofol (50-300 mcg/kg/min)*
•Titrate to EEG state desired
Anesthetic technique (regional): Historically, regional anesthesia--in the form of superficial
and deep cervical plexus blocks, supplemented as needed by a local field block--was used for
most CEAs. It provided the opportunity to evaluate cerebral function during a trial occlusion of
2-3 min. If the patient showed no adverse effects, the operation was completed under regional
anesthesia. If the patient developed neurological changes, a shunt was inserted or GA was
induced and ET intubation performed, following which the operation was completed. Regional
anesthesia, however, has several disadvantages: absence of cerebral protection, patients may
tolerate carotid occlusion for 10 min or more before suddenly losing consciousness or
developing a Sz; and conversion to GETA may be technically difficult. Nevertheless, the
technique still has some advocates among anesthesiologists and surgeons. It is claimed that: (1) it
decreases the need for a surgical shunt and, thereby, avoids the complications of shunt insertion;
(2) it decreases the length of stay in the ICU; and, (3) as an anesthetic technique, it is well-
accepted by some patients.
Anesthetic technique (GETA): GETA offers both direct and indirect advantages for patients
undergoing CEA: cerebral protection by decreasing CMRO2 and redistributing flow toward the
potentially ischemic area; greater patient comfort; and the ability to regulate PO2, PCO2, and
MAP. Despite these arguments favoring GA, recent studies comparing regional and GA suggest
that there is no clear outcome advantage of one technique over the other.
Circle of Willis: The common carotid arteries originate in the thorax. The right common carotid
artery originates at the bifurcation of the brachiocephalic trunk, and the left originates from the
aortic arch. In the neck, the common carotid arteries travel within the carotid sheath. At the level
of the thyroid cartilage each common carotid artery bifurcates into internal and external carotid
arteries.

925
Branches of the external carotid artery include the superior thyroid, lingual, facial, ascending
pharyngeal, occipital, and posterior auricular arteries.
The internal carotid artery passes through the neck without branching to enter the middle cranial
fossa through the carotid canal of the temporal bone, adjacent to the sphenoid bone. It supplies
the hypophysis cerebri, the orbit, and the major portion of the supratentorial region of the brain.
Cerebral arteries are derived from the internal carotid and vertebral arteries. The anastomosis
they form at the base of the brain is known as the Circle of Willis. The two anterior cerebral
arteries form the circle anteriorly. They are connected through the anterior communicating
artery. The two posterior cerebral arteries form the circle posteriorly, which then ends at the
junction of the basilar artery. The posterior cerebral arteries are connected to the internal carotid
arteries by the two posterior communicating arteries (Fig. 23.1). The middle cerebral artery
primarily supplies the lateral surface of each cerebral hemisphere. The anterior cerebral and
posterior cerebral arteries supply the medial and inferior surfaces of the cerebral hemisphere.

926
Co-morbidity Pathophysiology Anesthetic implications
Supine Position with neck -B/P remains relatively constant. Pre-op- Lay patient in supine position and insure
flexed -↑ CO by as much as 20% tolerance
-↑ SV (venous blood returns from lower extremities to central Induction Performed with head in neutral position.
circulation) Maintenance Arms placed on arm boards and padded,
-Abdominal expansion during inspiration decreases and rib keeping them extended less than 90°
cage expansion increases - With adducted arm, securely tuck arm to side with palm
-↓ FRC facing in and free of contact with hard surfaces.
- Pad dependent side of head/face/neck (ear is in natural
position)
EmergenceNo additional intervention needed.
Post-op Assess nerve damage in all extremities (motor
and sensory)
TIA -Brief episode of neurologic dysfunction caused by a focal Pre-op-Establish usual range of b/p: provides guide for
disturbance of brain or retinal ischemia with symptoms lasting acceptable perfusion pressures to brain.
less than 1hr and without evidence of infarction. -Assess for any neurological deficits.
-TIAs usually result due to intermittent blockage of circulation -Imaging or testing generally not required.
or spasm Induction-Maintain b/p within 20% of baseline.
-HTN is highly associated with TIAin HTN cerebral
autoregulation curve is shifted to the right.
-May need a higher MAP to maintain adequate cerebral
perfusion (70-80mmHg).
Maintenance-Maintain HR, b/p, pain, and decrease
stress related responses.
-Most anesthetic agents decrease CMRO2, protecting
against ischemia. (except ketamine)
Emergence-Smooth and emergence to limit sympathetic
response.
-Use short acting beta antagonists (10mg esmolol) for
HTN.
Post-op-Observe for neurological complications that
signal a new stroke or acute thrombosis.
-Continue to treat HTN with B-antagonists, nitroprusside,
angiotensin-converting enzyme inhibitors (enalapril),
alpha-2 agonists (clonidine), calcium-channel blockers
(nifedipine).
VAE -Air enters the venous circulation through open wound and Pre-op N/A
travels through right side of the heart or pulmonary InductionN/A
vasculature. Maintenance-Monitor for s/s: tachycardia, ↓ CO2, ↓
-↓ end-tidal CO2 and arterial saturation. SpO2, hypotension, and arrhythmias
-EKG might show signs and symptoms of ischemia. -avoid N2O
-Tachycardia If s/sx noted:
-Place patient in slight Trendelenburg
-100% FiO2
-flood surgical filed with wet sponges
-volume resuscitate with isotonic crystalloids or colloids
-Support CV collapse with vasopressors (50-100mcg
phenylephrine, 0.5-1 unit vasopressin, or 5-25mg
ephedrine) and inotropes (dopamine 3-10mcg/kg/min) as
needed.
-Surgeon may occlude gas entrainment point with electro
cautery
Emergence-Continue to monitor vital signs for s/s of air
embolism.
-confirmed VAEcontinue mechanical ventilation
Post-op assess for any neurological deficits

927
 Crash Section:

Positioning – identify nerve(s) at risk for injury

1. Supine with left lateral tilt: Supinate on arm boards (< 90º abduction) to prevent stretch on
ulnar nerves. Hips and knees slightly flexed, legs uncrossed, heels padded, and lumbar support
to protect lordotic curvature of back.
2. Ulnar nerves and brachial plexus at risk in supine position.

Anesthetic considerations:
Pre-op: Pregnant pts will present with a 50% increase in minute ventilation, and a 20% decrease
in FRC. Increased oxygen demand plus decreased FRC results in rapid onset of hypoxemia if
ventilation is not well controlled. Pregnant patient has compensated respiratory alkalosis (PCO2
=32-34 mmHg). Increased oxygen demand and decreased FRC also enhances uptake of
inhalational anesthetic agents.
Pregnant pts typically have a decrease in SVR, DBP, and MAP with an increase in HR and CO.
Immediately post-partum, 600-800 ml of blood will enter the mother’s central circulation due to
placental transfusion with a further result in CO. Also, these pts have an increase in PRBCs,
plasma volume, and overall blood volume.

Typical blood loss is 500-800 ml and is usually well tolerated.

Gastric motility will be decreased; pts will have GERD; raised intra-gastric pressures; and gastric
hyperacidity. Therefore it is important to treat these pts as full stomachs and pre-treat with
bicitra. Also, administer metoclopramide and famotidine before emergence. Sedatives are not
routinely administered, but if the pt is extremely anxious 0.5 mg-1.0 mg midazolam can be
administered without apparent effect on maternal memory/alertness or neonatal condition.

Intra-op: Primary concerns are which type of anesthetic should be delivered. The majority of
cesarean deliveries are performed under regional anesthesia, but sometimes the severity of the
fetal condition or contraindications for regional anesthesia necessitates the use of general
anesthesia.

928
Spinal: Preferred method for elective C-sections. With the use of pencil point needles (Sprotte,
Whitacre) the risk of headache is 1-2%. A decrease in BP is common with spinal anesthesia, but
can be easily treated with fluid loading, compression stockings, or vasopressors [ephedrine (5-10
mg)/phenylephrine (50-100 mcg)]. May consider epinephrine (50-100 mcg) if ephedrine and
phenylephrine are ineffective.

-Apply monitors, fluid load, and place the pt in the sitting or lateral decubitus position. Insert a
24/25 ga pencil-point needle and verify free flow of CSF. Inject hyperbaric 0.75% spinal
bupivacaine 12- 15 mg ± fentanyl 10-15 mcg and position the pt with left uterine displacement.
Monitor and treat decreases in BP as previously explained. Adjust OR table position to insure a
T4 level of anesthesia.

General: Severe maternal hemorrhage, prolapsed umbilical cord, severe fetal bradycardia, or the
need for intrauterine manipulation are all indications for GA over spinal anesthesia. It is very
important for constant communication between the anesthesia provider and the obstetrician
regarding maternal and fetal conditions.

-Pre-oxygenate for 3-min, administer 500-750 ml fluid load of crystalloid before induction.

Perform a RSI with 2-3 mg/kg of propofol (or 1-1.5 mg/kg of Ketamine if pt is hypovolemic) and
succinylcholine 1-1.5 mg/kg to induce GA and facilitate GA. Maintenance of GA should be
performed with 50 % N2O/O2 with sevoflurane with a MAC of ≤ 1 to prevent uterine atony.
Potential for difficult airway due to pharyngolaryngeal edema, weight gain, increased breast size,
combined with decreased FRC leading to rapid desaturation and decreased CO from aortocaval
compression.
Ventilation should be controlled to prevent hypocarbia (PCO2 < 30 mmHg), which decreases
umbilical blood flow. After delivery, substitute opioids for volatile agents and increase N2O to
70%. Midazolam (1-2 mg), given after delivery helps avoid maternal awareness.
Post-op: Typical fluid replacement is 1-3 L NS/LR. Position pt in left uterine displacement to
minimize aortocaval compression. Monitor for amniotic fluid embolism which can cause severe
hemodynamic instability, hypoxemia, DIC, and is often fatal. Provide supportive treatment with
100% O2, PEEP, and vasopressors.

929
Intraoperative Drugs

Drug Dose Duration Considerations

Trade name
(generic name)
Marcaine 1.5 ml of 0.75% Duration: 90- May cause HOTN, bradycardia,
(Bupivicaine) via epidural 120 min palpitations, heart block, ventricular
arrhythmias, cardiac arrest,
restlessness, anxiety, dizziness,
seizures, and N/V.
Sublimaze 25 mcg via Duration: 60- May cause bradycardia, HOTN,
(fentanyl) epidural 120 min N/V, constipation, and respiratory
depression.
Duramorph 0.25 mg via Duration: 12-24 May cause heart palpitations,
(morphine epidural hr HOTN, bradycardia, urinary
sulfate) retention, histamine release,
pruritus, respiratory depression, and
dyspnea.
Ephedrine 5-20 mg Half-life: 2.5-3.6 May cause HTN, tachycardia,
hr palpitations, chest pain,
arrhythmias, nervousness, anxiety,
N/V tremors and dyspnea. Repeated
doses will be less effective d/t
decreased endogenous
catecholamine stores.
Zofran 4-8 mg Onset: 30 Give at least 30 minutes prior to
(Ondansetron) minutes emergence. Reserved for pts with
Half-life: 3-6 known PONV due to cost. Common
hours SE: HA
Pitocin 10-40 units in Duration: < 30 May produce ADH effect (water
(oxytocin) 1000 ml of IV min intoxication), uterine hypertonicity,
fluid at a rate to spasm, titanic contraction, or
control uttering rupture of the uterus; severe water
atony intoxication and convulsions, coma,
and death are associated with a slow
oxytocin infusion over 24 hrs.

930
 Obesity Case Study:
1.68m 117kg BMI 42 → obesity is a concern
Preop Vital Signs:

BP 155/90
HR 72
RR 12
Preop O2 Sat % 99
LABS:

Na: 137 Cl: 103 BUN: 17 Glucose: 101

K: 4.4 Bicarb: 30 Creat: 0.96

Hg 13.1 Hct 40.1 WBC 7.1 PLT 230

AllergiesNKDA

PMH Chronic Ischemic Heart Disease, BPH, ETOH Abuse, Obesity

Surgical hx 6/2013 Drug eluding Stent Placement

Pt is aspiration risk due to obesity → Metoclopramide (Reglan) 10mg IV 30 min before

induction

OBSTRUCTIVE SLEEP APNEA: High Risk= > 3 Yes answers

Snore loudly no BMI > 35 yes

Tired often no Age > 50 yes
Observed stop breathing no Neck Circ >40 cm yes
Blood pressure tx no Gender Male yes

931
Obesity ↑ body fat → ↑Vd → ↑ storage of Preop: start the pt on medications for
lipid soluble drugs (inhalers, aspiration prophylaxis (bicitra PO 30ml,
barbs, benzos, sufentanil) → will cimetidine 200-400mg PO). Administer
maintain the drug concentration preop antibiotic as obese pts are prone to
No LMA!
for longer → delayed recovery infections. Perform thorough pre-op
airway exam. Can the pt tolerate supine
↑Blood volume, ↑RAA, position? Baseline sats. Ensure proper
↑catecholamines →↑ systemic cuff size available.
BP Induction: pt may be difficult to mask
↑ risk of sleep apnea due to ↑ ventilate or intubate, consider awake
adipose tissue in the pharyngeal fiberoptic intubation. Preoxygenate for
walls obstructing the airway → at least 3 min with 100% O2. Ensure the
hypoxemia pt is positioned with blankets under the
head and shoulders to create a Line
Insulin sensitivity is dependent between external auditory meatus to
on fat tissue amount → ↑ sternal notch for easier intubation. Be
difficulty of blood sugar control prepared for rapid desaturation and
paralyze only if can mask ventilate.
Already an ↑ work load on the Ensure pt is secured well on the bed.
heart
Intraop: monitor blood sugar levels,
↑O2 consumption (due to the start on insulin drip is sugars above 180.
need to supply the fat tissue) → ↑ Ensure good oxygenation. The pt should
SOB have been carefully positioned as the ↑
weight predisposes the pt to nerve
Fat surrounding the thoracic cage
damage.
and diaphragm → Inhibited Lung
inflation  ↓ FRC Emergence: pt may have delayed
recovery therefore ensure pt is
↑ risk of GERD and aspiration
hemodynamically stable and responds
appropriately prior to extubation. Make
sure pt meets the extubation criteria and
extubate only in upright position.
Consider reversal of muscle relaxants to
provide optimal pt respiratory effort.

Postop: CPAP can ↓the risk of

reintubation keeping the upper and small
airways open. Continue frequent BS
monitoring. Try to keep the pt sitting up
to assist ventilation. Monitor sats and
provide O2 as needed.

932
Anesthesia plan

Bezold-Jarisch reflex Case Study

Pt Info:
Patient is a 66y/o (5’6”, 104 lbs) female with a history of hypothyroidism, IBS, GERD,
“syncope” and essential tremor being seen for implantation of left thalamic deep brain stimulator
electrode for resolution of her tremor. Patient has allergies to codeine, lyrica, PCN, oxycodone,
and reglan. Anesthesia plan was to use minimal sedation for local administration to skull then
have the patient be completely conscious for testing of the stimulator. Per surgeon, goal sBP is
less than 130. To accomplish this, the plan was to minimize IV fluids and give small doses of
hydralazine. Beta blocker were to be avoided because of the effect they can have on decreasing
tremor.
Anesthesia:
The procedure started at 0830. The patient had a “cage” placed on her head before the surgery.
30 mg of propofol was given for local injections on the skull. Narcotics were avoided. Pt’s
baseline sBP was 130. The surgeon stated if her pressure was not less than 130 he could not
continue with the surgery. Therefore, we minimized the IV fluids and gave small dose (2mg) of
Hydralazine every 20-30 min as needed. The patient’s pressure was responsive to this. SBP
throughout the procedure was in the 120’s. Toward the end of the procedure (approx. 2 hours
into the procedure) the patient complained that she was nauseous, which is a normal side effect
of this type of surgery. As I turned around to grab the Zofran I saw that her HR was 30, as I
reached for the glycopyrrolate she became asystolic. The patient’s head was lowered and chest
compressions were started. 0.1 mg epinephrine was given. Approximately 30 seconds into chest
compressions the patient’s rhythm returned and she regained consciousness. The patient was
taken to CT to evaluate if there was any damage caused when the electrode had to be emergently
removed from her brain. The CT evaluation was cleared and the patient went back to surgery and
the electrode was placed. Later, we concluded that her history of syncope, and now cardiac
arrest, was really attributed to something called the Bezold-Jarisch Reflex.
Bezold-Jarisch Reflex:
The BJR includes a triad of bradycardia, hypotension, and peripheral vasodilation in response to
hypovolemia. The BJR is an inhibitory reflex usually denoted as a cardio inhibitory reflex
initiated by vagal C-fibers. The cardiac receptors mediating the BJR have very low basal firing
rates in the absence of any stimulation and output from these cardiac receptors contributes tonic
inhibition to the vasomotor centers. These receptors, when stimulated by electrical excitation,

933
show increased firing frequency with subsequent inhibition of the vasomotor centers, promoting
vasodilation. Prolonged upright posture results in some degree of pooling of blood in the lower
extremities that can lead to diminished intracardiac volume. This phenomenon is exacerbated if
the individual is dehydrated. The resultant arterial hypotension is sensed in the carotid sinus
baroreceptors, and efferent fibers from these receptors trigger autonomic signals that increase
cardiac rate and contractility. However, pressure receptors in the wall and trabeculae of the under
filled left ventricle may then sense stimuli, activating high-pressure C-fiber afferent nerves from
these receptors. They may respond by sending signals that trigger paradoxical bradycardia and
decreased contractility, resulting in additional and relatively sudden arterial hypotension. In
summary, normally during hypovolemia the body responds with increase HR and cardiac output
to compensate for the insult. The BJR does the opposite, causing parasympathetic activation and
sympathetic inhibition. During hypovolemia and decreased volume in the left ventricle causes a
paradoxical reaction the causes bradycardia, hypotension, and peripheral vasodilation. The BJR
is also theorized as a possible cause of cardiac arrest after placement of spinal and regional
anesthesia. Prevention includes restoration of intravascular volume and administration of
vasolytic medications (atropine and glycopyrrolate) before the event occurs. Treatment also
includes administration of epinephrine.

After Epinephrine is given:

After a dose of epinephrine is given, the patient’s HR and BP usually elevates to a significant
level. One question is how to treat this exaggerated response. One way is to give esmolol for
increased HR. However, administering a beta-blocker while a patient’s vessels are fully alpha
stimulated (constricted) can lead to cardiac collapse d/t the heart failing to pump effectively
against increased resistance. Therefore, the patient should first have decreased SVR using an
alpha antagonist (Phentolamine 30-70 mcg/kg IV), vasodilators such as nitroglycerin or sodium
nitroprusside (SNP), or calcium channel blocker such as nicardipine.

Because BJR this confusing and hard to explain reflex I have attached a couple articles I received
from the anesthesiologist to help understand this condition.

934
 Zenker’s Diverticulum

84 y/o female presents for scheduled CO2 laser assisted removal of Zenker’s diverticulum.
4’11” 69.4 kg BMI 30.9 Allergiesiodine and shellfish=pruritus/rash
NPO x 14 hours

Medical hxhyperlipidemia (not taking any meds and unsure of last cholesterol level);
generalized osteoarthritis; benign neoplasm of the colon; hemorrhoids; Zenker’s diverticulum;
macular degeneration of retina; glaucoma

Surgical hxtonsils/adenoids as a child; abdominal hysterectomy and bladder repair-1979;

balloon dilation of esophagus 11/15/13; bilateral cataract extraction with lens implant 8/2005
Pt has received both general and MAC anesthesia without any complications in the past.

Current medscholcalciferol, omeprazole, MVI

ROS
Airway examMallampatti 2, full set of pts own teeth, none chipped or broken, thyromental
distance > 3 FB, able to fit 3 fingers into open mouth, negative underbite test, good neck ROM
without pain
Respiratoryclear to auscultation bilaterally, no recent URI/fever. Pt does report cough that has
been bothering her since the esophageal pouch has gotten worse. Non productive
CVrate regular, no murmur, clicks or rubs. Normal S1/S2
Nervous/Muscular: pt denies any hx of CVA/TIA no numbness or tingling. Equal hand
strength. Hx of osteoarthritis no current complaints of any pain
Hepatic/GIdenies any hepatic issues. GI positive for dysphagia d/t Zenker’s diverticulum. Pt
taking Prilosec, denies any problems with acid reflux or ulcers

935
Endocrinedenies thyroid problems or DM
Rena denies any renal or urinary symptoms
Otherpt reports being a “hard stick” for IV starts. No other complaints offered

Plan
20 g PIV. Pre medicate with famotidine 20 mg IV 30-45 min prior to induction. RSI with cricoid
pressure (fentanyl, lidocaine, defasciculating dose of roc (1/10th of intubating dose), cricoid
pressure, propofol, and succinylcholine). “Laser resistant” 6.5 mm ETT with methylene blue dye
in the cuff, FiO2 < 30%. Assessment of mouth/teeth/lips after intubation and document if
atraumatic or any damage. A large modified laryngoscope is used to view the surgical area and
can cause soft tissue or teeth damage. Pt is in a supine position for surgery which lasts
approximately 1-2 hours. Laser goggles for everyone in the room including the patient. Use of
hydromorphone 0.6 mg about 45-60 min before end of case to help with pain and blunt coughing
reflex d/t surgical site stimulation. Also 50 mg lidocaine near the end of the case to help blunt
coughing as well. Perform leak test around ETT (deflate cuff and listen for air to pass around
ETT to help assess that there is not severe swelling around the ETT) suction the oropharynx to
make sure their isn’t significant secretions/bleeding and make sure that pt is awake enough to
protect airway prior to extubation.

What is Zenker’s Diverticulum?

A hypo pharyngeal (upper esophagus) diverticulum of the mucosa of the pharynx, just above the
Cricopharyngeus muscle. It is a false diverticulum, not involving all layers of the esophageal
wall. With excessive pressure within the lower pharynx, the weakest portion of the pharyngeal
wall balloons out forming a diverticulum. Can be asymptomatic or cause dysphagia, sense of a
lump in the neck, cause regurgitation, halitosis, and potential for infection of the pharyngeal area
d/t food getting stuck. These patient s are at a greater risk of pulmonary aspiration.

Review of RSI give fentanyl/lidocaine as normal, before giving propofol apply cricoid
pressure (Sellick’s maneuver) give succinylcholine or high dose rocuronium (1.2 mg/kg) then
immediately intubate without any bag/mask ventilation. Cricoid pressure is not released until
ETT placement is confirmed.

936
Cricoid pressurethis procedure occludes the esophagus, thereby preventing aspiration of
gastric contents and insufflation of the stomach with PPV. Cricoid pressure is properly applied
with the thumb and first finger placed on either side of the cricoid cartilage. Use the BURP
method Backward, Upward, Rightward Pressure until the fingers blanch. The upper and lower
esophageal sphincters serve as barriers to aspiration when the pt is awake. On loss of
consciousness (LOC) the upper esophageal sphincter relaxes and allows for passive flow of
gastric contents into the hypopharynx, which is why cricoid pressure must be applied before
LOC. Recommended pressure exerted before LOC is 20 N (approximately 2 kg of pressure).
After LOC pressure must be increased to 44 N (approximately 4 kg of pressure). Required
pressures are independent of age and sex. If cricoid pressure is done incorrectly, it can worsen
the laryngoscopic view by as much as 30%. Cricoid pressure itself can increase the incidence of
hypertension and tachycardia during induction.

Review of airway firesFire triangle=heat/ignition source, fuel, and oxidizer

Oxidizers used in the ORoxygen and nitrous oxide
Ignition sourceelectrosurgical/electro cautery, lasers, heated probes, drills and burrs, argon
beam coagulators, fiberoptic light cables and defib paddles/pads
FuelETT, sponges, drapes, gauze, alcohol containing prepping solutions, ether, acetone,
oxygen masks, nasal cannula, patients hair, dressing, ointments, gowns, blankets, suction
catheters, gloves

Prevent fires by mixing oxygen with air to deliver O2 content of <30%, vent; if using N2O wait
1-3 minutes after stopping before using an ignition source

937
ASA OR fire algorithm (airway fire portion)
Airway fire, immediately without waiting
1. remove tracheal tube
2. stop the flow of all airway gasses
3. remove sponges and any other flammable material from airway
4. pour saline into airway
5. if fire is not extinguished, use a CO2 fire extinguisher (may be used on the pt if
necessary)
6. re-establish ventilation
7. avoid oxidizer-enriched atmosphere if clinically appropriate
8. examine ETT to see if fragments may be left behind in airway
9. consider bronchoscopy

Laser ETTreinforced ETT that reflects laser light. Has methylene blue crystals in a small area
just after the cuff inflation port that when mixed with saline turn dark blue. This allows surgeon
to be aware if they rupture ETT cuff and also creates a splash of water that could potentially
extinguish a spark/fire.

938
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943
Advances in Anesthesia Book, November 2012, by McLoughlin

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944
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945
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946
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Essentials of Pain Medicine Book, November 2004, by Raja

Essentials of Pain Medicine Book, July 2011, by Benzon

Ethics in Anaesthesia and Intensive Care Book, July 2003, by Draper

Evidence-Based Management of Low Back Pain Book, January 2011, by Dagenais

Evidence-Based Practice of Anesthesiology Book, February 2013, by Fleisher

Evidence-Based Practice of Critical Care Book, June 2010, by Deutschman Examination

Anaesthesia Book, December 2010, by Thomas

Examination Intensive Care & Anaesthesia Book, May 2007, by Blackwell

Faust's Anesthesiology Review Book, March 2014, by Murray

Foundations of Anesthesia Book, October 2005, by Hemmings

FRCA Book, December 1998, by Bailey

947
Gray's Atlas of Anatomy Book, December 2009, by Drake

Handbook for Stoelting's Anesthesia and Co-Existing Disease Book, September 2012, by Hines

Handbook of Nitrous Oxide and Oxygen Sedation Book, October 2007, by Clark

Handbook of Pain Management Book, August 2003, by Melzack

Handbook of Pain Medicine Book, November 2013

Hemoglobin-based Oxygen Carriers (HBOCs): The Future in Resuscitation? An Issue of Critical

Care Clinics Book, April 2009, by Napolitano

Historical Aspects of Critical Illness and Critical Care Medicine, an Issue of Critical Care Clinics
Book, April 2009, by Kumar

Imaging of Pain Book, August 2010, by Waldman

Information Technology Applied to Anesthesiology, an Issue of Anesthesiology Clinics Book,

September 2011, by Tremper

Intensive Care Book, August 2008, by Hinds

Intensive Care Aftercare Book, December 2001, by Griffiths

Intensive Care of the Cancer Patient, an Issue of Critical Care Clinics Book, December 2009, by
Pastores

Interventional Spine Book, October 2007, by Slipman

Intrathecal Drug Delivery for Pain and Spasticity Book, September 2011, by Buvanendran

Johns Hopkins Anesthesiology Handbook Book, September 2009, by Heitmiller

Local and Regional Anaesthesia in the Emergency Department Made Easy Book, June 2010, by
Wells

Management of Acute and Chronic Neck Pain Book, July 2006, by Bogduk

Manual of Pediatric Anesthesia Book, December 2009, by Lerman

MCQ's in Anaesthesia Book, May 1998, by Ganado

Meyler's Side Effects of Drugs Used in Anesthesia Book, September 2008, by Aronson

Miller's Anesthesia Book, May 2009, by Miller

948
Miller's Anesthesia 2 volume set Book, May 2009, by Miller

Miller's Anesthesia Review Book, May 2012, by Sdrales

More Case Presentations in Paediatric Anaesthesia and Intensive Care Book, October 2000, by
Morton

Musculoskeletal Ultrasound Book, January 2001, by van Holsbeeck

Neuroanesthesia Book, January 2002, by Dinsmore

Neurosurgical Anesthesia, an Issue of Anesthesiology Clinics Book, August 2012, by Kirsch

Neurosurgical Pain Management Book, June 2004, by Follett

Non-Operating Room Anesthesia Book, August 2014

Nunn's Applied Respiratory Physiology Book, September 2012, by Lumb

Obstetric and Gynecologic Anesthesia Book, May 2006, by Braveman

Obstetric and Gynecologic Anesthesia, an Issue of Anesthesiology Clinics Book, September

2013, by Gaiser

Obstetric Anesthesia, an Issue of Anesthesiology Clinics Book, March 2008, by Vasdev

Obstetric, Thoracic and Cardiac Anesthesia Book, June 2009, by Gaiser

Oh's Intensive Care Manual Book, December 2013, by Bersten

Optimizing Hemodynamic Support in Severe Sepsis and Septic Shock, an Issue of Critical Care
Clinics Book, May 2010, by Nichols

Outcomes in Critical Care Book, January 2002, by Ridley

Paediatric & Neonatal Anaesthesia Book, August 2004, by Black

Pain in Neonates and Infants Book, May 2007, by Anand

Pain Management Book, March 2008, by Hughes

Pain Management Book, June 2011, by Waldman

Pain Management, 2-Volume Set Book, December 2006, by Waldman

Pain Management and Procedural Sedation Handbook Book, March 2008, by Phillips

949
Pain Medicine Book, April 2006, by Abram

Pain Medicine Manual Book, November 2003, by Dolin

Pain Modulation Book, November 1988, by Fields

Pain Review Book, January 2009, by Waldman

Pediatric Anesthesia and Critical Care in the Hospital Book, April 2003, by Morton

Pediatric Anesthesiology, an Issue of Anesthesiology Clinics Book, March 2014, by Schwartz

Perioperative Diagnostic and Interventional Ultrasound with DVD Book, December 2007, by
Harmon

Perioperative Drug Manual - Downloadable PDA Software Book, December 2004, by White

Perioperative Medicine Book, October 2007, by Newman

Perioperative Pharmacotherapy, an Issue of Anesthesiology Clinics Book, December 2010, by

Kaye

Perioperative Transesophageal Echocardiography Book, September 2013, by Reich

Peripheral Nerve Blocks and Peri-Operative Pain Relief Book, October 2010, by Harmon

Pharmacology and Physiology for Anesthesia Book, January 2013, by Hemmings

Physical Diagnosis of Pain with DVD Book, August 2009, by Waldman

Post Anesthesia Care Unit, an Issue of Anesthesiology Clinics Book, September 2012, by Falk

Postoperative Pain Management Book, July 2006, by Shorten

Practical Management of Pain Book, September 2013, by Benzon

Practical Perioperative Transesophageal Echocardiography Book, March 2011, by Sidebotham

Preoperative Medical Consultation: A Multidisciplinary Approach, an Issue of Anesthesiology

Clinics Book, December 2009, by Fleisher

Problems in Obstetric Anaesthesia Book, May 1993, by Rubin

Problems with Geriatric Anesthesia Patients, an Issue of Anesthesiology Clinics Book,

November 2009, by Silverstein

950
Quality of Anesthesia Care, an Issue of Anesthesiology Clinics Book, March 2011, by Neuman

Raj's Practical Management of Pain Book, March 2008, by Nuyianes

Reducing Risks and Complications of Interventional Pain Procedures Book, March 2012, by
Ranson

Regional Analgesia and Acute Pain Management, an Issue of Anesthesiology Clinics Book, June
2011, by Ganapathy

Regional Anesthesia and Pain Management Book, March 2009, by Burkey

Sedation and Analgesia in the ICU: Pharmacology, Protocolization, and Clinical Consequences,
an Issue of Anesthesiology Clinics Book, December 2011, by Pandharipande

Sedation and Analgesia in the ICU: Pharmacology, Protocolization, and Clinical Consequences,
an Issue of Critical Care Clinics Book, July 2009, by Pandharipande

Sepsis, an Issue of Critical Care Clinics Book, December 2009, by Dellinger

Serie Secretos: Anestesia Book, November 2006, by Duke

Simulation in Anesthesia Book, October 2006, by Gallagher

Sleep and Anesthesia, an Issue of Sleep Medicine Clinics Book, April 2013, by Chung

Smith and Aitkenhead's Textbook of Anaesthesia Book, September 2013, by Aitkenhead

Smith's Anesthesia for Infants and Children Book, March 2011, by Davis

Smith's Anesthesia for Infants and Children Book, December 2005, by Moto Yama

Spinal Injections & Peripheral Nerve Blocks Book, September 2011, by Huntoon

Statistical Methods for Anaesthesia and Intensive Care Book, September 2000, by Myles

Surgical Palliative Care and Pain Management, an Issue of Anesthesiology Clinics Book, March
2012, by Dunn

TEE Pocket Manual Book, July 2011, by Groban

Textbook of Critical Care Book, June 2011, by Vincent

The Intensive Care Unit Manual Book, September 2013, by Lanken

The MGH Textbook of Anesthetic Equipment Book, October 2010, by Sandberg

951
The MGH Textbook of Anesthetic Equipment E-Book Book, October 2010, by Sandberg

Thoracic Anesthesia, an Issue of Anesthesiology Clinics Book, October 2012, by Slinger

Total Burn Care Book, June 2012, by Herndon

Transplantation, an Issue of Anesthesiology Clinics Book, December 2013, by Niemann

Trauma, an Issue of Anesthesiology Clinics Book, February 2013, by Weiss

Understanding Anaesthesia Book, August 2001, by Simpson

Understanding Pain for Better Clinical Practice Book, May 2005, by Linton

Veterinary Anesthesia Book, November 2000, by Cornick-Seahorn

Wall & Melzack's Textbook of Pain Book, May 2013, by McMahon

WALL Y MELZACK. Tratado del dolor + e-dition Book, by McMahon

Ward's Anaesthetic Equipment Book, December 2011, by Davey

Year Book of Anesthesiology and Pain Management 2010 Book, June 2010, by Chestnut

Year Book of Anesthesiology and Pain Management 2011 Book, May 2011, by Chestnut

Year Book of Anesthesiology and Pain Management 2012 Book, June 2012, by Chestnut

Year Book of Critical Care Medicine 2010 Book, May 2010, by Dellinger

952