Endocrinology DNB Q & A

Dr. Azam’s....
Notes in Anesthesiology
Postgraduates appearing
Updated up to December 2013, 3rd Edition for MD, DNB & DA Exams
Endocrinology
Edited by:
Dr. Azam
Consultant Anesthesiologist
& Critical Care Specialist
www.drazam.com
Dr Azam’s Notes in Anesthesiology 2013
Dedication
To Mohammed Shafiulla, my father, my oxygen, companion, and best friend; for

being my major pillar of support and making this vision a reality. Thank you for your
continual sacrifices with boundless love and limitless gratitude, for the sake of your
children. I owe you a debt I can never repay.
I also would like to thank my mom (Naaz Shafi), my wife (Roohi Azam), my two lovely
kids (Falaq Zohaa & Mohammed Izaan), for their support, ideas, patience, and
encouragement during the many hours of writing this book.
Finally, I would like to thank my teachers (Dr.Manjunath Jajoor & team) & Dr T. A. Patil . The
dream begins with a teacher who believes in you, who tugs and pushes and leads you to the next
plateau, sometimes poking you with a sharp stick called "truth."

A NOTE TO THE READER
Anesthesiology is an ever-changing field. Standard safety precautions must be followed, but as new research and clinical experience
broaden our knowledge, changes in treatment and drug therapy may become necessary or appropriate. Readers are advised to check the
most current product information provided by the manufacturer of each drug to be administered to verify the recommended dose, the
method and duration of administration, and contraindications.
However, in view of the possibility of human error or changes in medical sciences, neither the author nor the publisher nor any other party
who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect
accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information
contained in this work. Readers are encouraged to confirm the information contained herein with other sources. It is the responsibility of the
licensed prescriber, relying on experience and knowledge of the patient, to determine dosages and the best treatment for each individual
patient. Neither the publisher nor the editor assumes any liability for any injury and/or damage to persons or property arising from this
publication.
Dr. Azam

Contents Dr Azam’s Notes in Anesthesiology 2013
1. Glycoslylated Hemoglobin.HbA1C - 4 23. Acromegaly. (Transphenoidal Hypophysectomy) - 143

2. Anatomy & Physiology of Thyroid - 6 24. Carcinoid Syndrome - 147
3. Goiter - 12 25. Flow chart & Diagram - 148
4. Hyperthyroidism - 15
5. Thyroid Storm - 23 & 137
6. Myxoedema & Anesthetic Implications - 25
7. Parathyroid Gland - 28
8. Adrenal Gland - 31
9. Anesthetic Problems in Adrenocortical Insufficiency - 34
10. Hyperaldosteronism.(Mineralocorticoid Excess) 40
11. Anesthetic Management of Diabetic patient for elective &
Emergency surgery - 42
12. Hyperthyroidism - 58
13. Diabetes - Pathogenesis & Anesthesia - 72
14. Pheochromocytoma - 93
15. Case Discussion on Diabetes Mellitus - 107
16. Describe clinical manifestation of diabetic autonomic
neuropathy. what are its implication? A 50 year old man with
known diabetic is scheduled for upper abdominal surgery. How
will you evaluate the autonomic nervous system? - 117
17. .Discuss the pre-anesthetic preparation, anesthetic goals &
operative management of a 30 years old female patient with
diagnosis of Pheochromocytoma scheduled for excision of
adrenal tumor - 125
18. Describe the Manifestation & management of Thyroid Storm
intraoperatively - 129
19. A 30 years old women is scheduled for removal of carcinoid
tumor. write the anesthetic management - 131
20. Diabetic Ketoacidosis - 133
21. Porphyria - 139 & 145
22. Cushingʼs Syndrome - 141

1. Glycoslylated Hemoglobin.HbA1C Dr Azam’s Notes in Anesthesiology 2013
• It is also called glycohemoglobin, (or) diabetic control index (DCI) Blood:

measured by high performance chromatography (liquid) (HPLC). 3ml venous blood sample with EDTA anticoagulant.
Normal values: Results are expressed as percentage of total Hb. Clinical implications:
1. Values are frequently increased in poorly controlled and with
• Normal (non-diabetic): 5.5% to 8.5%. diagnosed DM, Hb AIC levels may constitute greater than 15% of
• Diabetes:" Good control"7.5% to 11.4% the total Hb.
" " Moderate control " 11.5 to 15% 2. With optimal control, the Hb AIC moves towards normal.
" " Bad control " " > 15% 3. Valves are increased in iron-deficiency anemia, splenectomy,
alcohol and lead toxicity.
Mechanism of HbAlc formation: (Glycosylated Hb) 4. Decrease in HbAlc is seen in hemolytic anemia, chronic blood loss,
It is non-enzymatic glycosylation of Hb. pregnancy, CRF.
B chain of Hb 5. The concentration of glycosylated haemoglobin (HbA1c) reflects
+ mean blood glucose concentration over approximately 60 days.
Glucose Increased amounts of glucose exposed to a target proteins, such
↓ as haemoglobin, leads to increased covalent binding of the target
Aldenine (Pre HbAlc) protein to glucose (glycosylation). As such measurement of HbA1c
provides the most accurate.
↓
6. Glycosylated haemoglobin or glycated haemoglobin refers to the
Ketoamine (HbAlc)
glucose derived products of normal adult Hb glycation is a post
• Glycosylated hemoglobin reflects blood sugar levels for 2 to 3
translational, non enzymatic addition of sugar residue to amino
months period before the test.
acids of protein.
• It provides and tracks control of blood glucose.
7. Among the glycated hemoglobin, most abundant form is HbA1c.
• A blood sample can be drawn at any time.
HbA1c is produced by the condensation of glucose with N-terminal
• Glycohemoglobin is a normal type of hemoglobin.
valine of each β chain of HbA.
• Hemoglobin A1 undergoes changes (or) glycosylation to H1a,
HbA1c and HbA1c, by a slow, non enzymatic process with in the
red blood cell, during their 120 days of circulating life span.
• Glycohemoglobin is blood glucose bond to Hb.
• The amount of glycosylated Hb bound to the erythrocyte is
directly proportional to the amount of glucose available to it over
120 days.
• In hyperglycemia, an increase in glycohemoglobin is usually
seen as an increase in Hb AIC.
• Alternate to Hb AIC is fructose amine assay .It will show glucose
control over 2-4 weeks. 6

Glycoslylated Hemoglobin.HbA1C.Continuations: Dr Azam’s Notes in Anesthesiology 2013
Diagnostic importance:" • The degree of glycation of other proteins such as albumin has been
• Measurement of HbA1c is the standard method of assessing long used an alternative indicator of glycemic control when HbA1c is
term glycemic control. The rate of synthesis of HbA1c is directly inaccurate (hemolytic anemia and haemoglobinopathies).
related to the exposure of RBC of glucose. When the plasma • The fructosamine assay (using albumin) is an example of alternative
glucose level increases there is an increase in the non enzymatic measurement of glycemic controls reflects the glycemic control over
glycation of haemoglobin, this alteration reflect the glycemic prior 2-4 wks.
history over the previous 2-3 months since erythrocytes have an
average life span of 120 days.
• The non diabetic range of HbA1c is < 6.05% and the goal of
intensive therapy in patient with IDDM is to maintain HbA1c at
less than 7.5%.
• There are various methods for assessing long term glycemic
control. Where are numerous methods laboratory methods for
measuring the various forms of glycated Hb and these have
significant inter assay variations. Because of its superior
specificity and reliability HbA1c assay performed by the high
performance liquid chromatography (HPLC) has become the
standard method for most glycated Hb measurements.
• Depending on the assay methodology for HbA1c
haemoglobinopathies, hemolytic anemia and uremia may
interface with HbA1c result.
• Glycated Hb (HbA1c) should be measured in all individuals with
DM during their initial evaluation and as a part of their
comprehensive diabetic care. As a primary predictor of long term
complication of DM the HbA1c should mirror to a certain extent
the short term measurement of SMBG (self monitoring blood
glucose). These 1400 measurements are complementary in that
recent inter current illnesses may impact the SMBG
measurement but not HbA1c likewise PP and nocturnal
hyperglycemia may not be detected by SMBG of fasting and pre
prandial capillary plasma glucose but will be reflected in the
HbA1c. When measured by HPLC, the HbA1c approximates the
following mean plasma glucose values.
• HbA1c of 6% is 6.6 mmol/L, 7% 8.3 mmol/L and 8% 10 mmol/L
[A1% rise in the HbA1c translates into a 1.7 mmol/L (30mg/dl)
increase in mean glucose level. 7

2. Anatomy & Physiology of Thyroid. Dr Azam’s Notes in Anesthesiology 2013
Embryology: • Lateral surface is covered by (superficial), sternothyroid, sternohyoid,

• Thyroid gland is developed from the median bud of the pharynx superior belly of omohyoid and anterior border of sternomastoid.
(the thyroglossal duct-median endodermal thyroid diverticulum) • Medial surface: is related to trachea and oesophagus, muscles –
which passes from foramen caecum at the base of the tongue to inferior constrictor and cricothyroid.
the isthmus of thyroid. The lower end of the diverticulum remains • Nerves – external laryngeal and recurrent laryngeal.
narrow and is known as the thyroglossal duct, most of the duct • Posterior surface: is related to carotid sheath and overlaps
soon disappears. common carotid artery.
• Remnants of thyroglossal duct may form thyroglossal cyst or • Anterior border: related to anterior branch of superior thyroid artery.
thyroglossal fistula. Sometimes thyroid tissue may develop along • Posterior border: is related to inferior thyroid artery and
the course of the duct resulting in lingual or retrosternal thyroid. anastomosis between inferior and superior thyroid arteries,
parathyroid gland, and thoracic duct on left side.
Anatomy: Extends from C5 to T1 • Apex- is directed upwards and laterally.
• Thyroid gland is highly vascular, ductless gland, along the upper • Base- is at the level of 4-5th tracheal ring.
part of trachea, situated in lower part of front and sides of the • Isthmus- this median band extends between 2nd and 3rd tracheal
neck. rings.
• It is enclosed in a sheath of pretracheal fascia attached to the • The third pyramidal lobe extends from upper border of isthmus. It
line and arch of cricoid cartilage. This ensures that the thyroid may be attached to the hyoid bone by a narrow slip of muscle,
gland moves with larynx during swallowing and speaking. This levator glandular thyroidae or fibrous strand. This strand is remnant
helps to differentiate the swelling in the gland from those of of thyroglossal duct.
adjacent structures. Gland lies against C5 C6 C7 and T1, vertebra 2 surfaces: anterior and posterior.
up to the oblique line on thyroid cartilage. 2 borders: superior and inferior.
• Lobes: Gland consists of right and left lobes that are joined • Anterior surface is covered by right and left sternothyroid,
together by isthmus. sternohyoid muscles, anterior jugular veins, fascia and skin.
• Each lobe extends from middle of thyroid cartilage to 4-5th • Posterior surface – related to 2nd and 3rd tracheal rings.
tracheal ring. • Superior / upper border: related to anastomosis between (R) and (L)
superior thyroid arteries.
Relations: • Inferior / Lower border: Inferior thyroid veins leave the gland at this
Lobes are conical in shape, consisting of border.
1. Apex
2. Base
3. 3 surfaces – lateral, medial and postero lateral.
4. 2 borders – anterior and posterior

Anatomy & Physiology of Thyroid.Continuation: Dr Azam’s Notes in Anesthesiology 2013
Capsule of thyroid. Venous drainage:

• True capsule – is peripheral condensation of the connective • Thyroid gland is drained by superior, inferior and middle thyroid
tissue of gland. veins. Superior thyroid vein emerges at the upper pole and
• False capsule – derived from pretracheal layer of deep cervical accompanies superior thyroid artery. It ends either in internal jugular
fascia. vein or common facial vein.
• Dense capillary plexus is present deep to true capsule. • Middle thyroid vein emerges at middle of the lobe and enters internal
• Therefore to avoid hemorrhage thyroid is removed along with the jugular vein.
true capsule. • Inferior thyroid vein emerges at lower border of isthmus drains into
left brachiocephalic vein.
! ()*+,!-).+/*,! • Fourth thyroid vein of Kocher emerges between middle and inferior
veins and drains into internal jugular vein.
0*)1,!"2!-*,)3)4,!! Lymphatic drainage:
• Upper lower deep cervical L.N.
! "!!"!!!"!!"!!"!!!"!"!! ! 56/,!-).+/*,!! • Pre tracheal L.N.
• Para tracheal L.N.
Nerve supply:
7,1"/+!.*,8/+!! • Cervical ganglion of sympathetic trunk
#$%&'!! • Cardiac and laryngeal branch of vagus.
Physiology of thyroid gland:
BLOOD SUPPLY: • Thyroid secretes 3 hormones (T3, T4 & thyrocalcitonine) and consists
Arterial supply: of 2 types of secretary cells.
I. Superior thyroid artery: is a branch of external carotid artery, • Follicular cells: Secretes triiodothyronin (T3) and tetraiodothyronin
runs in relation to external laryngeal nerve. It divides into (T4 ) which stimulates B.M.R, somatic and psychic growth of the
anterior and posterior branch at upper pole of the lobe. individuals.
II. Inferior thyroid artery: is a branch of thyrocervical trunk which • Parafollicular cells – secretes thyrocalcitonine which promotes
arises from subclavian artery. deposition of calcium salts in skeletal and other tissues. Tends to
III. In 3% of individuals thyroid is also supplied by lowest thyroid procedure hypocalcaemia.
artery i.e. arteria thyroidae ima which arises from
brachiocervical trunk or directly from arch of aorta.
IV. Accessory thyroid arteries arise from tracheal and
oesophageal arteries to supply thyroid.

Formation and secretion of thyroid hormone:

• Thyroid gland contains 5-7 mg of iodide mostly in the form of
• 4 steps are involved in synthesis of hormones: iodinated AA. (Iodothyroxin and iodothyronine)
! !"#$ !%&'()*+*,-.$/-0(%1'0*,-$ !
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• Thyroxine formation requires 100-125 μg/day of iodine (50mg/yr:
50',-'1)<&<$*+3$0-1-*<-$';$!?$*+3$!@$ 1 mg/wk; 150 μg/day).
!"#$ • Inorganic iodides are transported from ECF into the thyroid glandular
cells and follicles, brought by iodine pump which depends on the
1) Iodide trapping: activity of Na – K dependent ATPase system. Energy is provided by
• Essential raw material – iodine. aerobic metabolism of acinar cells.
• Source – sea fish, bread, milk, vegetables and drinking water. • Both iodine pumps and ATPase system à stimulated by TSH.
• Iodine in gut is transformed to iodide à absorbed from upper Depressed by hypophysectomy.
G.I.T à blood and ECF.
• Thiocyanate and perchlorate depress iodide transport by competitive
Normal dietary intake of I2 is 100-200 μg/day. inhibition.
< 50 μg/day for long period à leads to I2 deficiency. If hormone • Carbimazole does not affect the trapping process. Plasma iodide
production is decreased, then TSH is increased à thus restoring concentration 0.5-1.5 μg/lt.
normal hormone output.
Definition: The ability of the thyroid gland epithelial cells to
concentrate iodide above the concentrations present in plasma is
referred to as iodide trapping.
Thyroid gland stores enough thyroid hormone to maintain
euthyroid state for 3 months (100 days) without hormone
synthesis.
Plasma I2: thyroid I2 = 1:20.
10

2) Oxidation of Iodide ion: 4) Proteolysis and release:

• Conversion of iodide ions into an oxidised from of iodine by • Release is initiated by the action of TSH à promotes formation of
enzyme peroxidase. pseudopodia on follicular cells. The pseudopodia engulfs colloid
• Iodination of tyrosine and formation of thyroid hormone. droplets, enter the cells by endocytosis. Lysozymes fuse with colloid
• Iodine binds with 1/6th of tyrosine A.A. within thyroglobulin droplets to form phagolysosomes on which proteases are released.
molecule assisted by an enzyme tyrosine iodinase to form These enzymes liberate iodothyronine and iodothyroxine from
monoiodotyrosine (MIT) and dioiodotyrosine (DIT), neither of thyroglobulin which enters the blood stream.
which has hormonal activity. The binding of I2 with thyroglobulin • 90% - T4
is called organification of thyroglobulin. • 10% - T3
• T4 is deiodinised to form T3 when it comes in contact with target
Coupling reaction, Decreased by oxidative condition. tissue. Hence the hormone finally delivered and used by tissue is T3
• Combination of 2 DIT molecules à T4 which is physiologically important hormone.
• One MIT and one DIT à T3!
Transport of thyroid hormones:
3) Storage of thyroglobulin: • Thyroid hormones on entering the blood stream become firmly bound
• Thyroglobulin is synthesized by follicular cells of thyroid. It is a to plasma protein.
glycoprotein with M.W. 670,000 stored as colloid in the follicles. • T4 – 99-95% bound – 0.05% free.
Thyroid hormones are formed within thyroglobulin molecules and • TBG – 75% (Thyroxin binding globulin)
are stored in colloid. • TBPA – 15-20% (Thyroxin binding prealbumin)
• Each thyroglobulin molecule contains 1-3 thyroxin molecules and • Albumin – 5-10%
an average of 1 T3 molecule for every 10 molecules of T4 • T3 – 99.5% bound to TBG
(thyroxin). o 0.5% unbound free T3 → Contributes to biological activity
• Potency " " " à T3: T4" " 3-5: 1 of T3.
• Secretory ratio " " à T4: T3" 10-20: 1 • None to TBPA " " " " "
• Plasma concentration " à T4: T5" " 2: 1 • Very little to albumin " " " "
T3: • T3 is quick acting within few hours,
• 20% secreted • T4 acts more slowly 4-14 days.
• 80% by peripheral conversion of T4à T3 • t½ of T4 – 7 days (4 + 3)
• Daily around 80-100 µg of iodine is secreted. • t ½ of T3 – 1 day (4-3)
o Vd à T3: 35 – 45 lt, T4: 10-12 lt.
• Total serum T4 – 50-150 nmol/lit or 8 µg/dl.
o T3 – 1.5 – 3.5 nmol/lit or 0.5 µg/dl.
• T4 – long latent period, activity begins by 2-3 days peaks by
10-12 days.
• T3 – activity begins within 6-12 hours, peaks by 2-3 days.
11

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• It is circulating fee T4 and T3 that regulate TSH release by negative
Metabolism of thyroid hormones: 56-7+/8#981,1+/# feedback effect at anterior pituitary and probably at hypothalamus.
# • T4à T3 peripherally (extra thyroid conversion accounts for (increased levels of free T3 and T4 inhibit TSH secretion).
• >80%).
? #@#&7,1A1,4#B-31/)#<1,01/#C5;:#0+D")E#F-&G)#B4#:5?#8&4)=#
%&'()*+,-.$*/$'012*,3$0*2.*4&-5$ • Pituitary gland:
• Liver, kidney and all tissues can de-iodinate T4à T3 • T4à T3 by monoiodinase enzyme and intra-pituitary T3 plays a role in
# >H!#>?#F-"1F0-"&224#I-J,"&#,04"+18#7+/A-")1+/#&77+D/,)#K+"#LMNO=#
Metabolized by:
# P1A-"E#G18/-4#&/8#&22#,1))D-)#7&/#8-1+81/&,-#>H!#>?# negative feedback in pituitary.
• De-iodination
%&'()*+,6&3$)15$
• Deamination and
!-1+81/&,1+/# Increase TSH secretion –
• Conjugation with glucuronic acid à secreted via bile duct
!-&'1/&,1+/#&/8##
" " " " ↓ • Oestrogen
Q+/RD3&,1+/#<1,0#32D7D"+/17#&718#!#)-7"-,-8#A1&#B12-#8D7,#
!# Intestine
• Large doses of iodide

./,-),1/-## • (Because it inhibits T4 and T3 release and thereby ↓↓ T4 and T3).
• T4 and T3 excreted mainly in faces, small amount in urine.
>H#&/8#>?#-J7"-,-8#'&1/24#1/#K&7-)E#)'&22#&'+D/,#1/#D"1/-=## Somatostatin
Decrease TSH secretion –
7*4'2*+$*/$'012*,3$/849',*45$
Control of thyroid function:
!!!!!!!!"#$!
• DOPA
0$'1)7&-2-4<35! • Dopamine
!! • Bromocriptine
!!!!!!!!!!!!!!!!!!!!!"%$!
!!!!!!!!!!!!!!!!!!!!!!!!!! 0-.79(*)(!1*7<*7-('5! Thyroid auto-regulation:
*-3&,1A-# K--8B&7G# • Also regulated by intrinsic control system.
!!!!!!"&'()*+! '-70&/1)'# +
!!
0.9:-7*>95! • High concentration of intra-thyroid inorganic iodide ! !" thyroid
hormone release.
!!!!!!",!-.+!"/! • High concentration and organic iodide à decreases iodide uptake.
012-34-5!
# Goitrogens: are substances that suppress the function of the
"#$!6!7&'()7()1&*8!(929-3*.:!&)(4).9!03'.7&93*;9+!*.!&'1)7&-2-4<35! thyroid gland by interfering with iodine uptake which can result
!! in enlargement of thyroid gland i,e, A GOITRE
TRH - thyrotrophic releasing hormone (synthesized in
"(-.31)(79+!7)!49+*-.!94*.9.89!037)(9+5!!
hypothalamus) I. Iodine deficiency
!! 7&()<:&!&'1)1&'39-2!1)(7-2!3'3794!!
=.79(*)(!1*7<*7-('!! ↓ II. Brassica family of vegetables à turnips, cabbage, soya bean
>ST# !!"+
Transported to median eminence (stored)
#U&)+F012)#,+#)-7"-,-#>6T=# III. Drugs à PAS, antithyroid drugs.
>6T# ! !"+
↓ through hypophyseal portal system
#;O#>04"+18#K+22172-)#,+#)-7"-,-#,04"+18#0+"'+/-)=## IV. Genetic factors – with deficiency of enzymes concerned with
# :O#6-"A-)#+K#70-'17&2#"-&7,1+/)#,0&,#2-&8)#,+#)4/,0-)1)#+K#>H#&/8#>?#
Anterior pituitary production.
.,# 1)# 71"7D2&,1/3# K--# >H# &/8# >?# ,0&,# "-3D2&,-# >6T# "-2-&)-# B4# /-3&,1A-# K--8B&7G# -KK-7,# &,#
+
&/,-"1+"#• TRH !&/8#
F1,D1,&"4# !"F"+B&B24#
Basophils to secrete
&,# 04F+,0&2&'D)=# TSH.2-A-2)# +K# K"--# >?# &/8# >H#
I1/7"-&)-8#
1/01B1,#>6T#)-7"-,1+/O=##
+
• TSH ! !
V1,D1,&"4#32&/8W#
" 1) Thyroid follicles to secrete thyroid hormones.
2) Serves of chemical reactions that leads:;#to
" " synthesis of T4 and T3 Endocrinology #
<<<=!"$%&'=7+'############################################################################### 12
#
Effects if thyroid hormone – (Yao P 573)

• Cellular effects
• Organ effects
• Systemic effects
THYROID FUNCTIONS:
1. Increases BMR
2. Except brain, thymus, lungs, spleen, gonads, skin, accessory
and sex organs.
3. Activates Na+/K+ ATPase.
4. Thermogenic effect
5. Essential for bone growth.
6. Neurological tissue maturation – myelination (brain)
7. Normal lactation
Metabolic effects.
8. CHO metabolism
• Physiological dose – potentiates insulin (Glucogenesis)
• Pharmacological dose – glycogenolysis
10. Protein
" Physiological dose – anabolic
" Large doses – catabolic
11. Fat
" Lipolytic effect more than lipogenic effect
12. Vitamin
" Required for sequestration vitamin A.
Thyroid hormones alter the:
• speed of reactions.
• Total O2 consumption
• Heat production
13

3. Goiter Dr Azam’s Notes in Anesthesiology 2013
It is a non inflammatory, non-neoplastic enlargement of the thyroid Causes:

gland. • Iodine deficiency - daily requirement 100-125 μg/day (1 mg/wk).
Classification: • Defect in thyroid hormone synthesis like peroxidase, iodinase,
I. Simple goiter – Diffuse hyperplastic goiter (Parenchymatous) deiodinase.
• Nodular goitre • Deficiency due to – goitrogens in diet – turnips, cabbage, soya bean.
• Multinodular (usually endemic) Drugs – PAS
• Solitary (usually sporadic) • Antithyroid drugs
• Colloid goitre. • Excess iodide
II. Toxic goitre – Diffuse toxic goitre (Primary – gravesʼ disease) Grading of goiter:
• Toxic nodular goitre (secondary) Grades:
• Toxic nodule. • 0 à Not palpable
Other enlargements of thyroid. • 1 à Palpable, visible only with head raised
III. Neoplastic – • 2 à Easily visible with head in normal position
• Benign – Adenoma. • 3 à Visible at a distance.
" " - Malignant Stages of formation of goiter.
• Primary-papillary, follicular and medullary, malignant I. Persistent TSH stimulation à diffuse hyperplasia (All follicles
lymphoma active and behave uniformly).
• secondary II. Reversible when TSH stimulation is withdrawn.
IV. Thyroiditis: III. Due to fluctuating levels of TSH. There develops a mixed pattern
• Granulomatous (De Quervain's ) of areas of active lobules and inactive lobules.
• Autoimmune "(Hashimoto's)
IV. Active lobules à
• Riedelʼs thyroiditis
" " " Become more vascular
V. Rare types:" " " " " " ↓ Leading to
• Acute bacterial
" " " " Hyperplasia
• Chronic bacterial (Syphilis ,TB)
• Amyloid " " " " " ↓ Continue till
" " " " Hemorrhage occurs
Simple goiter:
↓
Low circulatory levels of thyroid hormones.
↓ Central necrosis and a ring of active follicles surrounding it.
Increases TSH stimulation. I. Necrotic lobules à coalesce to form nodules
• May be filled with iodine free colloid.
↓
• Contain inactive follicles à newly formed.
Formation of Goiter.
II. Continuous repetition of this process à nodular goiter.
III.In nodular goitre, the nodules are inactive with active follicles only in
the internodular tissue.
14

Goiter.Continuation: Dr Azam’s Notes in Anesthesiology 2013
Simple goiter: Complications

• Diffuse hyperplasia • Tracheal obstruction
• Colloid • Secondary thyrotoxicosis
• Nodular • Carcinoma
Diffuse hyperplasia: • Haemorrhage -suddenly leading to dyspnoea – tracheostomy may be
• Appears with increase in metabolic demand Ex: Puberty, necessary
pregnancy etc. • Calcification
• Regresses when TSH secretion ceases.
• Contains active follicles with uniform iodine uptake. Treatment
• Soft and diffuse 1. Prevention: by iodized salt (potassium iodide 1 part in 10,000)
Causes: 2. Early stages of hyperplastic goiter.
• I2 deficiency 2.1. Reversible with L-thyroxine
• Goitrogenic substances 2.2. 0.3 mg/day for several months
• Defect in thyroid hormone synthesis. 2.3. mg/day maintenance for several years.
Colloid goitre: 3. If regression does not occur (if pressure sym occur, resort to
• Correlates with later stages of diffuse hyperplasia. thyroidectomy leaving 8 gms normal thyroid in each remnant)
• When TSH stimulation ceases follicles become inactive, active 4. Post operatively: 0.1 mg of α-thyroxine until / after menopause.
follicles are pushed to periphery.
• Inactive follicles are filled with iodine free colloid. Solitary nodule: 3 types (treatment lobectomy / excision.)
Nodular goitre: • Hyperthyroid with hot nodule: treatment excision / radioiodine.
• Results due to formation of nodules caused by persistent • Euthyroid with warm nodule: treatment excision.
fluctuating TSH stimulation. • Euthyroid with cold nodule: treatment with lobectomy.
• Nodules may be cellular / colloid, cystic degeneration or Retrosternal goitre
hemorrhagic are common. 3 types : Symptoms:
• Patient is usually euthyroid.
• Nodules are visible, palpable, smooth, firm, painless moves on ! "#$%&'()*+!
swallowing. If hard and irregular, that is due to calcification,
which simulates carcinoma. ,+#)-.)-!!!/)&(*&01(*2.2!$#&!31(2'4!1#&!13!)'25!60.+'!
/)&(*&01(*2.2!! 21#-0.)-!!
15

Goiter.Continuation: Dr Azam’s Notes in Anesthesiology 2013
• Dyspnoea particularly at night

• Cough and stridor
• Engorgement of neck veins and superficial veins on chest
wall.
• Dysphagia occurs rarely.
• Recurrent laryngeal palsy rarely.
• Distinguished from mediastinal tumor by I 123 uptake.
• Lower border not palpable
Ask patient to raise both arms over head until they touch the
ear. This position is maintained for a while, congestion of face
and distress à evident due to obstruction of great veins in
thoracic inlet.( Pembertonʼs sign.)
• C X R – soft tissue shadow in superior mediastinum /
calcification
• compression / deviation of trachea
• I131 scan – locates the gland.
• Arteriography
16

4. Hyperthyroidism. Dr Azam’s Notes in Anesthesiology 2013
• Hyperthyroidism is a clinical state which results from exposure of CLINICAL FEATURE OF HYPERTHYROIDISM:
body tissues to excess circulating levels of free thyroid • General: Weight loss, tremor, and heat intolerance, Sweating, goiter,
hormones. Hyperthyroidism is estimated to affect approximately Fatigue, apathy
2% of women and 0.2% of men. • CVS: Tachycardia, Cardiac arrhythmias, Wide pulse pressure, heart
CAUSES OF HYPERTHYROIDISM: failure
Primary: • Respiratory: Dyspnea
• Graveʼs disease • GIT: Diarrhea nausea vomiting
• Toxic multi nodular goiter • CNS: Anxiety, irritability insomnia, Depression and anxiety in elderly
• Single toxic nodule • Neuromuscular: Proximal myopathy (diff in climbing stairs or getting
• Thyroiditis up From sitting) muscular weakness
• Thyroid Carcinoma • Ophthalmic: Lid lag. Lid retraction reduced blinking,
Secondary: exophthalmoses (in Gravesʼ disease) corneal ulceration, loss of
• Excess TSH – Pituitary tumor visual acuity
Iatrogenic: • Reproductive: Amenorrhea, Oligomenorrhea infertility, impotence
• Drugs Thyroxine • Thyroid hormones cause uncoupling of oxidative phosphorylation
• Iodides such that energy cannot be stored and increase heat production.
• Amiodarone They also have impact on rate and speed at biochemical reactions,
Thyroid Hormone Excess: total body O2 consumption and energy production.
• An increase circulating levels of thyroid hormones may be • A hyper dynamic circulation characterized by tachycardia,
present without an increase the free, active hormone due to tachydysarrhythmias, and increase CO suggests excessive activity of
increased binding of thyroid hormones to TBG. The patient is the sympathetic N. system and a compensatory attempt to eliminate
clinically euthyroid. heat. The sensitivity of β receptors is increased in hyperthyroid
Causes of increase levels of Serum TBG: patients.
• Pregnancy • The pulse pressure is increase due to an increase in systolic B.P
• Oral contraceptive pills and reduction in diastolic pressure due to peripheral vasodilatation.
• Estrogen secreting tumors Circulating plasma catecholamine levels are normal in
• Liver disease Thyrotoxicosis. But, thyroid hormones increase the sensitivity to
• Acute intermittent porphyria catecholamines.
Among many possible causes of hyperthyroidism, Gravesʼ disease
is the most common, occurring typically in women 20-40 years of
age. An autoimmune pathogenesis for Gravesʼ disease is
suggested by the presence of TSH –receptor antibodies (IgG auto
antibodies) such as long, acting thyroid stimulator LATS (12 hrs
compared with 1 hr for normal TSH)
17

Hyperthyroidism.Continuation: Dr Azam’s Notes in Anesthesiology 2013
• Lid lag and lid retraction, widened palpebral fissures and WAYNEʼS CLINICAL DIAGNOSTIC INDEX
decrease frequency of blinking are due to potentiation of the Symptoms Present Absent
effects of catecholamine. Exophthalmos is due to an infiltrative
Palpitations → +2
process that involves retro bulbar fat. If retro bulbar edema is so
severe, the optic nerve may get compressed which result in Excessive sweating → +3
blindness. Increased Appetite → +3
• RR is increased. Ventilator response to hypoxia and hypercapnia Decreased Appetite → - -3
is potentiated. VC, lung compliance decreased. RV increased,
TLV is normal. Gastrointestinal transit time is shortened, so Weight increased → - -3
diarrhea is a common symptom. Weight decreased → +3
DIFFERENCE BETWEEN PRIMARY AND SECONDARY Preference for cold → +5
THYROTOXICOSIS
Preference for heat → - -5
Primary Secondary
• Goitre appears along with toxic • Goiter appears first and Signs
symptoms toxic symptom appear Palpable thyroid → +3 -3
• Goitre is diffuse, vascular bruit may later.
Exophthalmos → +2
be present. • Goiter is nodular.
Lid retraction → +2
• Symptoms appear suddenly and are • Symptoms appear
Finger tremor → +1
severe gradually and are mild.
• CNS manifestation dominate • CVS manifestations Bruit over thyroid → +2 -2
(Tremors, Hyperkinetic movements dominate Atrial fibrillation → +4
increased tendon reflexes) • Exophthalmos and eye Pulse rate 90/mt → +3
• Exophthalmos and eye signs are signs are rare. 80/mt → - -3
common
Index
• >19 indicates Toxic goiter
• < 11 indicates non-toxic goiter
Treatment:
The treatment of choice includes
• Anti thyroid drugs
• β- adrenergic blockers (non – specific Rx)
• Radioactive iodine
• Surgery
18

Anti thyroid drugs: • Given for 10 days prior to the surgery. If given longer periods (>2
• Ion inhibitions: Perchlorate, Thiocyanate wks) causes Hyper secretion of thyroid hormones and
• Thiourea derivatives: Propylthiouracil hypervascularization of the gland. Iodine Escape.
• Imidazole derivatives: Carbimazole, Methimazole • Indicated in patient preparing for surgery and thyrotoxic crisis.
• Iodides: Lugolʼs iodine • KI /NaI → 60 mg 8th hourly
• KI • Lugolʼs iodine → 30 drops 6th hourly
• NaI. • (5% iodine in 100ml of 10% KI sol)
Propylthiouracil: Disadvantages of Anti thyroid drugs:
• Prevents synthesis of thyroid hormones by • Anemia, thrombocytopenia, agranulocytosis → which needs regular
• Inhibiting oxidative iodination of thyroid blood checkup.
• Coupling of iodothyronine. • Thrombocytopenia → which causes excess bleeding during surgery.
• Prevents peripheral conversion of T4→T3 • Pruritis, skin rashes, fever, nausea, arthralgia etc.
• Inhibits general metabolic response to T4. • Hypothyroidism -so patient may need supplemented T3/T4.
Dosage:100 – 150 mg PO 6 – 8th hourly (t1/2 – 1-2 hrs) • T3 – 5µgm/ day (6hrs to have its effect t1/2 – 1day)
• In parturient PTU is preformed, as it crosses the placenta in the • T4- 100µgm/ day (10 days to have its effect t ½ - 7 days)
least amount. β - Blockers:
Carbimazole and Methimazole:
• Mode of action: attenuates symptoms Nervous system activity
• Acts by preventing the oxidative iodination of tyrosine and • Inhibits deiodination of T4 – T3 in peripheral circulation and tissues.
coupling at iodothyronine.
• Its efficacy is increase when given with K1.
Dosage:
• Propranolol 40 - 80mg 6th hourly (up to 1 gm /day)
• Methimazole 10-15 mg 8th hourly (t ½ 4 -6 hrs) • Nadolol 160 mg OD
• Carbimazole 1st wk → 1.5 ms 8th hourly • (Longer acting)
• Next 3 wks → 10mg 8th hourly. Radioactive iodine:
• Maintenance → 5-20 mg daily (t1/2 4-8 hours) • The objective of radioiodine therapy is to destroy sufficient thyroid
• Subjective improvement occurs in 2 wks and euthyroid by 4 wks. tissue to cure hyperthyroidism.
Iodides: • Indicated in recurrence of hyperthyroidism following Anti thyroid drug
• Act by preventing the oxidative iodination at tyrosine and release therapy or surgery.
of thyroxin. • Severe systemic disorders that contraindicates thyroidectomy
• Reduces the vascularity of the gland. • Contraindicated in pregnancy women and lactating mother.
• Should be used along with Anti thyroid drugs, when given alone
it may increase the hormone synthesis by promoting the iodide
trapping by the gland.
19

• ATD should be stopped 24-48 hrs before I131 therapy (induce Examination for Toxic Manifestations
enzyme block →↓ in effect of radiation). • Exophthalmos
• Given on an empty stomach /light breakfast. • Enlarged thyroid gland
• 5 -1 0 micro-curie of I131 orally. • Tachycardia
• Onset action 3-4 wks • Tremors, most skin, thyroid bruit
• Max effect 3-6months. Exophthalmos – is protrusion of one or both eye balls. Clinically
Surgery: detected by observing the white sclera both above and below the iris.
• Indicated in young adults who failed to respond to oral ATD. Signs observed in this condition are:
• Relapse after course of drug therapy, large goiter von Graefe's sign upper eye lid lags behind the eye ball as the
• When malignancy cannot of be ruled out patient is asked to look downwards
• Subtotal thyroidectomy, total thyroidectomy. Hemi thyroidectomy Stellwagʼs sign Infrequent and incomplete blinking, staring look
(1 lobe + isthmus)+lobectomy Dalrympleʼs sign upper sclera is visible due to retraction of upper
Pre-operative Evaluation:
eye lid.
History: in history elicit
Joffroyʼs sign Absence of creases on the forehead on
• H/o pressure symptoms – Dysphasia (esophagus)
superior gaze.
• Stridor / dyspnoea (trachea) Mobiuʼs sign Difficulty to converge the eyeballs.
• Hoarseness of voice (RLN involved)
Gifford`s sign Difficulty in eversion to the upper lid.
• H/o Symptoms of primary and secondary toxicity
• H/o pain of the goiter
• Personal history / past history / Family history • Tachycardia – sleeping Pulse Rate.
• Drug History • <80 -90- mild
Physical Examination: • 90 – 110 – moderate
Look for – • 110 – Severe.
• Built, nourishment (with reference to increase or decrease • Tremors: when the patients asked to hold his hand straight in front of
appetite ) him with fingers spread out – Fine tremors are seen in the fingers.
• Anemia, Jaundice, edema,cyanosis clubbing ,ascites Systemic Examination:
• Involvement of bone, spleen, liver for secondaries. C VS – More common in Sec. Thyrotoxicosis
• Temperature, resting / sleeping PR,BP • s/s of CCF, AF
• Skin cold / warm moist / dry • Enlarged heart
• Tremors • Systolic murmurs may be due to hyper dynamic circulation.
• Mental status (anxiety, nervousness)
20

• CNS: tremors, myopathy Thyroid Function Tests:

• Assessment of Airway.\ • In –vitro tests
• In – vivo tests
Investigations • Miscellaneous tests.
• Hb% In – vitro tests
• TC, DC, ESR - (Patients on ATD therapy may have Anemia, • Estimation of Serum Protein Bound Iodine (PBI)
thrombocytopenia, Agranulocytosis.) • N 4-8 µg/dl
• BT, CT, platelet count • This tests lack specificity, as it measures
• urine - albumin, Sugar, Microscopy. • Non –hormonal forms of iodine in blood.
• RBS \ Bu\ SC (Blood sugar may increased in hyperthyroidism) • False +ve result s in patients with increase TBG
• Recording sleeping PR • False –ve results in patients with decreased TBG
• ECG – may be seen • Estimation of total Serum T3 and T4:
• Serum Electrolytes. • Measured by radio immune assay
• Indirect laryngoscopy by ENT surgeon - To assess vocal cord • N T4 – 5-10 µg/dl
movements, • T3 - 80 – 220 ng/dl
• Medico legal importance – To know the pre-op and post op • Influenced by TBG levels.
difference • T3, T4 levels are increase in Hyperthyroidism
• Decreased in Hypothyroidism
X-ray • T3 – resin uptake (RT3U):
• N – 0.9 – 1.2 taking 100% as the mean normal value
• AP – view – position of trachea – deviation, compression
• 89% or < suggests – hyperthyroidism
• Mediastinal extension in cases of retro
• 121% or > suggests - hypothyroidism
• Sternal goiter.
• PA view - Cardiomegaly in CCF • Free thyroxin index:
• Pulmonary congestion in patients with CCF • F.T.I = sérum T4 (or PBI) x T3 up take %
• Lateral view Barium swallow – To detect pressure effect on • N-3.7 – 8.6 %
trachea and esophagus. • (Indirectly mesures free T4)
• Flow volume loops: Best indicators of airway obstruction. • Serum TSH:
• By RIA method
• N -1-5 μU/ ml
• Increase in Hyperthyroidism up to 40 μU/ml
• Decreased in Hyperthyroidism (undetectable)
21

• TRH test (for Hypothalamic – pituitary axis) • Measurement of LATS and Antibodies in serum Presence of LATS
• (IV 200 μg TRH) → Graveʼs disease
• Normal- Increase TSH upto 10μU/ml with in 20 min Anti-thyroglobulin,
• In hypothyroidism → TSH levels further increase Anti-microsomal In auto immune thyroiditis
• In Hyperthyroidism → no response. Antibodies
In –Vivo Tests
• FNAC
• Uptake Tests:
• Tracer dose of 5 μ curie of I131 will be given • Serum Creatine (N 0.8 – 1.6 ng/ml) ↑
• Thyroid uptake N 30% in 24 hrs • Creatinine (N 50 – 150 μ mol /lit) ↓ in thyrotoxicosis
• In hyperthyroidism increase > 55% Pre – operative Preparation of the Patient:
• In Hypothyroidism decreased • Before elective surgeries patient must be made euthyroid; by
administering ADT, β blockers, iodides, steroids like dexamethasone
• T3 suppression Test: (WERNER) (8-12mg/day)
• Helps to differentiate thyrotoxicosis from other causes of raised
• Euthyroid state is clinically assessed by
uptake (ex I2 deficiency) • Sleeping PR < 80 bpm
• Initial uptake is measured • Normal TFT
• 40μg of T3 8th hourly for 5 days (orally) • Disappearance of Toxic symptoms likes nervousness, anxiety,
• N suppression of thyroid uptake by 50-80% Tremors, etc.
• In thyrotoxicosis – suppression is only by 10-20% During emergency surgery
TSH stimulation test:
• Measures should be taken to prevent thyroid storm and to attenuate
Helps in distinguishing between primary and secondary
S.N. system over activity.
hypothyroidism • ATD should start immediately (To increase further thyroid hormone
• Initial thyroid uptake is measured synthesis)
• Injection of 10: u of bovine TSH • Esmolol 100-300 μg/kg/min I v until HR comes < 100/hr
• Increase in uptake in → Hypopitutarism • Dexamethasone 2mg 6th hourly I.V
• No increase in uptake → primary thyroid failure • Hydrocortisone 40mg 6th hourly I.V
• Thyroid scan: • (To decrease thyroid hormone release and peripheral conversion of
• Used are I131 and 99m Tc T4 –T3 )
• It distinguish between functioning (hot) and non-function (cold) • KI 5 drops (60 mg) PO every 6 hourly
• Thyroid nodules • Or Lugolʼs solution 30 drops 6-8 hourly
Miscellaneous tests • Antithyroid drugs and β blockers should be continued till the morning
• BMR increased in hyperthyroidism of the surgery.
• Serum cholesterol → increase in hypothyroidism
22

Premedication: • If air way problem is anticipated

• To prevent sympathetic activity • (dyspnea, dysphagia hoarseness of voice etc.
• To relieve anxiety • Induction with O2 + N2O + halothane
• T. Diazepam 5-10 mg P.O or • 4% lidocaine spray
• Inj. promethazine 50 mg im or ½ hr – 1 hr before surgery • Intubation with cuffed armoured tube
• Inj. morphine 10mg im Position: Fowlerʼs position
• Extension of head and neck (hyperextension causes stretch on
No premedication carotids)
• If airway problem is anticipated anticholinergic drugs are not • Eye care is important, eyes are lubricated and shielded
recommended. • 250 head up tilt to aid venous drainage
Intra-op Monitoring • Foot rest → to prevent patient from sliding down
• HR • Arms should be placed by the side
• B.P • IV line preferably put on leg.
• O2 saturation Maintenance of Anesthesia:
• ECG Goals:
• Body Temperature • Avoid drugs which stimulate SNS
• ET CO2. • Provide sufficient anesthetic depth to prevent exaggerated response
• CVP to surgical stimulation
• Doppler ,echocardiography • Isoflurane is the volatile Anesthetic of choice
• To detect air embolism. • Suppresses sympathetic activity to surgical stimuli
General Anesthesia: • Doesnʼt sensitize the myocardium to catecholamines
Pre-oxygenation with 100% O2 is a must • Halothane, enflurane may cause Hepatotoxicity"
• Increased BMR • Enflurane, Sevoflurane may cause Nephrotoxicity
• Hypoxia may stimulate Sympathetic.N.S. • Alternative to nitrous plus isoflurane anesthesia is nitrous plus short
Induction: acting opioid (Fentanyl 1-2 μg/kg)
• Before induction all the emergency drugs and equipment
required during difficult intubations should be kept ready (LMA,
intubating fibroscope, different size of ETT tube, and size and
types blades etc.)
• If no airway problem is anticipated
• Induction with inj. thiopentone 3-5 mg iv
• Inj. lidocaine 2 %( 1- 1.5 mg/kg iv) (To attenuate pressure
response during laryngoscopy)
• Relaxation with inj. Scoline 1-2 mg iv
• Intubation with cuffed armoured tube
23

Muscle relaxants: COMPLICATIONS:

• In Vecuronium 0.03- 0.05 mg/kg iv Intraoperative Immediate Post Op Late Post Op
• In Atracurium 0.3 – 0.5 mg/kg iv Haemorrhage Thyroid crisis Hypothyroidism
• Pancuronium and Gallamine are not better choice as they Thyroid crisis Hematoma Hypoparathyroidism
increase HR Air embolism Tracheomalacia
• The existing skeletal muscle weakness and incidence of RLN damage
myasthenia gravis in hyperthyroid patients emphasizes the need Laryngeal edema
to reduce initial dose of muscle relaxant Hypoparathyroidism
• Controlled ventilation with BAINʼs circuit is preferred
REVERSAL:
inj. Neostigmine 0.05 mg/kg
" +
Inj. Glycopyrrolate 8-10 μg/kg
Glycopyrrolate is preferred than atropine (less chromotropic effect
than atropine)
EXTUBATION:
• Deep extubation ↓ laryngoscopic vision is preferred to assess
the vocal cord function.
• Administration of lidocaine IV 60-90 mg prior to extubation.
24

5. Thyroid Storm. Dr Azam’s Notes in Anesthesiology 2013
Thyroid storm is an abrupt exacerbation of hyperthyroidism caused • Shock: Cardiogenic / hypovolemic.

by sudden excessive release of thyroid gland hormones into the • Electrolyte imbalance.
circulation. • Marked agitation, anxiety and psychosis.
Pre-disposing factors:
• Medical factors Clinical features under anesthesia:
• Surgical factors 1. Hyperthermia
2. Tachycardia
1) Medical factors: 3. Hypertension
a) Infection, fever, uncontrolled toxicity. 4. High output failure and then to low output failure
b) Improper treatment 5. Arrhythmia (Atrial fibrillation common)
" 1) Irregular drug intake 6. Flushing or sweating
" 2) Improper / inadequate investigation 7. Increase ETCO2
" 3) Stopping drug well in advance to surgery 8. Hypo / hyperglycemia
c) Pregnancy Differential diagnosis:
d) Anxious and nervous patient before surgery A. Malignant hyperthermia
B. Pheochromocytoma
2) Surgical factors: Treatment:
" a) Too much handling of gland before surgery I) General Measures:
" b) Rough handling of gland during surgery. I. Increase the percentage of inspired O2 concentration.
• This complication can occur both intra-operatively or in the II. Cooling measures
immediate post-op periods. A. Surface cooling à Sponging, Icepack, decreasing OT
• It is common in post-operative period. It occurs between 6-18 temperature
hours post operatively. B. Administration of cold IV fluid.
III. Drugs à? Largactil (by action on medullary center)
Clinical features: IV.Avoid aspirin: as it competes for thyroxine binding globulin and
(Increased temperature, tachypnea, tachycardia, extreme anxiety, hence releases more T3-T4 into circulation, aggravating the
CVS instability). condition.
Hyperthermia: Rise of 20C/hr over normal temperature. It may be II) Suppression of hormone activity:
difficult to notice during operation because the surgery may not 1. Propylthiouracil à 200-400 mg IV/orally through Ryleʼs tube 8th
last for more than 1-1 ½ hour. hrly
Tachycardia: Arrhythmias of any kind may occur, atrial fibrillation 2. Carbimazole à 50-100 mg orally (RT) followed by 20 mg 6th hrly.
is the commonest. 3. Na iodide à 500-1000 mg IV 8th hrly.
Initially there is flushing and sweating, later leading to dehydration.
CCF à initially high output failure, later may go for low output
failure.
25

Thyroid Storm.Continuation: Dr Azam’s Notes in Anesthesiology 2013
III) Suppression of sympathetic activity: Tracheomalacia

I. Propranolol 1-2 mg IV à Sufficient to decrease HR < 90/mt. • It occurs after removal of long standing goiter, especially within the
II. Esmolol 50-300 μg/kg/min. thoracic inlet, that has compressed and weakened cartilaginous rings
III. Treatment of shock and CCF supporting the tracheal wall.
IV. CCF due to increase in ventricular rate, it will respond to • Immediate intubation or tracheostomy should be performed.
esmolol – by decreasing HR. • Later options include stenting, extrinsic tracheal support,
V. Digoxin à High output failure may not respond to digoxin. Tracheoplasty
VI. IV fluids should be given with reference to CVP. • Hematoma: haemorrhage into tracheal bed following surgery results
VII. Otherwise over infusion may further worsen CCF in tracheal compression and respiratory distress.
VIII. IV fluid preferably the crystalloid containing glucose to supply • The wound should be reopened immediately at the bedside to relieve
enough energy for increased metabolism. the compression and pt should be shifted to OT secure homeostasis.
IX. Supplementation of corticosteroid • Hypoparathyroidism: Results from accidental removal of
X. Hydrocortisone 100-200 mg IV 8th or sometimes as high as parathyroid gland.
500 mg initial dose may be given. • Hypocalcaemia develops typically 24-72 hours post operatively, but
Dexamethasone à prevents conversion of T4 à T3 ,prevents may manifest as early as 1-3 hrs after surgery.
release of T4. • Laryngeal muscles are sensitive to hypocalcaemia and inspiratory
• If it is during intraoperative à handling of gland should be stridor progressing to laryngospasm, may be the first indication.
stopped and should stabilize the patient. • Treatment: I v calcium until laryngeal stridor ceases.
• RLN Damage Regional anesthesia
• If it is unilateral, it is characterized by hoarseness of voice. If the • Regional anesthesia is a potentially useful choice for hyperthyroid
injury is permanent Polytef (Teflon) injection into the paralyzed patient. Epidural anesthesia is preferred over spinal because of
cord may lead to voice improvement. (Usually it is transient) slower onset of sympathetic system blockade. If hypotension occurs
• B/L RLN palsy- It is evident immediately after extubation as decreased doses of phenylephrine is recommended. (Ephedrine
unopposed action of adductors close the vocal cords causing increases cathocholamine release and increases sympathetic
complete airway obstruction. nervous system activity, so better avoided.)
• Immediate reintubation is necessary
• If damage is transient, a trial of extubation can be performed in
next few days.
• If this fails àTracheostomy.
26

6. Myxoedema & Anesthetic Implications. Dr Azam’s Notes in Anesthesiology 2013
Introduction: Signs and symptoms:

Sir William Withey Gull in 1873 was one of the first to understand Depend on the age of onset of thyroid gland dysfunction.
that the cause of myxoedema is atrophy of the thyroid gland. The • In neonatal period, can result in cretinism which is characterized by
word Myxedema was introduced by Four years later, William Miller decreased physical development and mental retardation.
Ord (1834–1902. It is the generic term for exposure of the body to • In adult, development of hypothyroidism is insidious and may go
subnormal amounts of physiologically active thyroid gland unrecognized for several years.
hormone. Physical examination:
Etiology of hypothyroidism: • Delayed ankle jerks
Decreased function of thyroid gland may be due to secondary or • Husky voice
primary causes. • Presence of dry skin
Secondary Etiology • Generalized reduction in metabolic activity
hypothyroidism • Lethargy is prominent and intolerance to cold.
1. Hypothalamic Deficiency of thyroid releasing Cardiovascular system:
dysfunction hormone. • Bradycardia and decreased stroke volume.
2. Anterior pituitary Deficiency of thyroid stimulating • Decreased cardiac output, increased systemic vascular resistance
and decreased blood volume, result in prolongation of circulation
dysfunction hormone.
time.
Primary hypothyroidism
• Narrowed pulse pressure.
1. Thyroid gland Previous subtotal thyroidectomy, • Peripheral vasoconstriction leads to cool and dry skin.
destruction previous I131 therapy, irradiation of the • Many manifestations mimic cardiac failure, Cardiomegaly, pleural
neck effusion, peripheral edema and ascetics.
2. Thyroid gland hormone Chronic inflammation Endocrine system:
deficiency Dietary iodine deficiency • Associated atrophy of adrenal cortex.
• Associated atrophy of pituitary.
Excess iodides (inhibits release)
• Unrecognized hypoadrenocorticism could lead to cardiovascular
Antithyroid drugs. collapse during anesthesia and surgery.
Subclinical hypothyroidism, present in about 5% of population, is

manifested solely by elevated plasma concentration of thyroid
stimulation hormones. Chronic thyroiditis – Hashimotoʼs thyroiditis
is assumed to be the cause of dysfunction.
Diagnosis:
1. Clinical signs and symptoms.
2. Decreased thyroid gland function demonstrated by appropriate
tests.
27

Myxoedema & Anesthetic Implications.Continuation: Dr Azam’s Notes in Anesthesiology 2013
Treatment: Premedication:
1. Exogenous replacement of the hormones. 1. Cortisol support
2. Thyroid hormone concentration in circulation must be restored 2. Reduced dose of sedatives or anticholinergic drugs can be
slowly because of the danger of precipitating angina pectoris, administered intravenously on arrival in the operating room if
cardiac dysrrhythmias and congestive cardiac failure. essential.
3. Thyroxine takes 10 days to exert a physiological effect and Pre induction monitoring:
hence not useful. 1. Pulse oximetry
4. Triiodothyronin acts within six hours and reaches peak with in 2. Invasive blood pressure monitoring
forty eight to seventy two hrs. 3. Central venous pressure monitoring for guiding the rate of I/V fluids
5. Exogenous administration of cortisol. infusion.
6. Digitalis for congestive cardiac failure may adversely affect the 4. Core temperature recording for early detection of the onset of
hypothyroid heart which cannot perform increased myocardial hypothermia.
contractility. 5. Continuous electrocardiogram monitoring
• Adequacy of thyroid replacement confirmed by normalization of 6. Pulmonary artery catheterization and transoesophageal
serum TSH. echocardiography for left ventricular function monitoring.
Management of anesthesia: Induction of anesthesia:

Elective: Postponed until the patient is euthyroid. • This is accomplished with slow intravenous ketamine. Short acting
Emergency: In emergency situation, the following items that affect muscle relaxants like Scoline are used to facilitate intubation.
Anesthetic management should be noted and corrected.
1. Hypothyroid patientʼs exhibit marked sensitivity to depressant Maintenance of anesthesia:
drugs. This is achieved with inhalation of Nitrous Oxide and oxygen.
2. Cardiovascular system is characterized by a low cardiac Supplementation if necessary with minimal opioids (Alfentanyl),
output, high systemic vascular resistance and low heart rate. benzodiazepine, (midazolam) or ketamine.
3. Drug metabolism reduced.
4. Baroreceptors tend to be unresponsive and beta receptors Precautions:
down regulated. 1. Volatile Anesthetic agents if used, the sensitivity to myocardial
5. Intravascular volume is decreased depression should be borne in mind. Temperature below 370C and
6. Ventilating response to hypoxemia and hypercarbia are slow hepatic metabolism and renal elimination would reduce the
blunted. Anesthetic requirements of these drugs.
7. Free water clearance is impaired resulting in hyponatremia. 2. Non depolarizing muscle relaxants like Pancuronium with mild
8. Gastric emptying is delayed. sympathomimetic effect is beneficial.
9. Baseline hypothermia is common.
10. Normocytic anemia is common.
11. Primary adrenal insufficiency and consequent hypoglycemia.
28

Myxoedema & Anesthetic Implications.Continuation: Dr Azam’s Notes in Anesthesiology 2013
3. Controlled ventilation is necessary as these patients have

tendency to hypoventilate – avoid hyperventilation.
4. Reversal of non depolarizing neuromuscular blockade with
anticholinesterase drugs combined with anticholinergics poses
no known hazard.
5. Recovery from sedative effects of Anesthetic drugs may be
delayed, resulting in prolonged post operative sedation.
6. Extubation should be done only after patient responds and body
temperature is near 370 Celsius.
7. Post operative analgesia, only with non-opioids.
8. Post operative hypotension treated with hydrocortisone.
Regional anesthesia:
Doses of local Anesthetic necessary might be reduced. The
metabolism of amide local Anesthetics seem to be slowed. This
could predispose to development of systemic toxicity.
Myxoedema coma: rare complication, severe hypothyroidism
Loss of tendon reflexes, spontaneous hypothermia,
hypoventilation, cardiovascular collapse, coma and death.
Precipitating events; sepsis in elderly, exposure to cold, surgery,
trauma.
Treatment
1. I.V T3 (exerts physiological effects within 6hrs)+cortisol, if
adrenal insufficiency is suspected +fluid replacement (keeping
in mind they are vulnerable to water intoxication and
hyponatremia )
2. Slow warming (wrapping)
3. High flow oxygen, broad spectrum antibiotics
4. Hypoxia, hypercarbia and respiratory acidosis are corrected
with ventilation
5. T3 i.v bolus 20µgm, 8th hrly till clinical improvement.
6. After 24-48 hrs oral thyroxine 50µgm /day
29

7. Parathyroid Gland Dr Azam’s Notes in Anesthesiology 2013
• 4 parathyroid glands are located behind the upper and lower Sign and symptoms -
poles of the thyroid gland and secrete polypeptide hormone, 1. Earliest s/s –sedation and vomiting.
parathormone 2. Neuromuscular → Skeletal muscle weakness - Fréquent complains
• Parathormone is released into systemic circulation by a negative neuropathy – proximal muscle of LL Réversible.
feedback mechanism that depends on the plasma calcium 3. Cardiac " → systemic HTN
concentration. " " Prolonged PR interval
• Hypocalcaemia stimulates release of parathormone " " Short QT interval – ser.Ca >8 mEq/L
• Hypercalcemia suppresses both the synthesis and release of Cardiac conduction abnormalities.
hormone 4. Renal → polyuria and polydypsia Decreased GFR, kidney stones
• Parathormone maintains normal plasma calcium concentrations 5. GIT → vomiting, abdominal pain, Peptic ulcers, pancreatitis,
(4.5 to 5.5 mEq/ L) by promoting the movement of calcium 6. Hemopoietic → Anemia
across three interfaces represented by the GIT, Renal tubules 7. Skeletal → skeletal demineralization, osteitis Fibrosa cystica (bone
and bone.
cysts). Collapse of vertebral bodies, pathological fractures.
HYPERPARATHYROIDISM
8. Nervous → somnolence
Primary - increased PTH, increase Ca +2
Secondary – increase PTH, decrease Ca+2 9. Ocular → calcifications, Conjunctivitis
Ectopic – increase PTH
Treatment:
• Increased secretion of parathormone
Initially medical means followed by definitive surgical removal of gland
• Serum calcium concentration may be increased, decreased or Medical management→
unchanged.
• Saline infusion (150ml /hr) to produce a daily urine output of 0.5ml/
• Classified as primary, secondary or ectopic. kg/hr (3-5 ltr) – guided by CVP
PRIMARY HYPERPARATHYROIDISM
• Furosemide (40-80mg IV every 2 hrs) after intravascular fluid
• Results from excessive secretion of parathormone owing to
volume is reestablished as reflected by CVP
benign parathyroid adenomas (responsible for 90% of patients),
Carcinoma of parathyroid gland or hyperplasia of parathyroid • Pamidronate 60-90mg IV/ Calcitonin (2-80u/Kg SC)
• Biphosphonates (disodium Etidronate) administered IV for life
glands
Diagnosis threatening hypercalcemia (>15mg/dl)
• Hemodialysis – calcitonin (transient effect) - Mithramycin
• Serum calcium cone. >5.5 mEq/L
Surgical management
• Ionized calcium cone >2.5 mEq/L
• Removal of diseased or abnormal portions of the parathyroid glands
• Patients in surgical ICU for prolonged periods of time may
(serum calcium concentration. normalize within 3- 4 days)
develop Hypercalcemia, which reflect increase secretion of
parathormone in response to repeated episodes of
hypocalcaemia due to sepsis, shock and blood transfusions.
• Marked hypocalcaemia (> 7.5 mEq/L) is more likely due to
cancer.
30

Parathyroid Gland.Continuation: Dr Azam’s Notes in Anesthesiology 2013
Management of Anesthesia: Etiology:-

1. There is no evidence that specific anesthetic drugs or I. Deceased or absent Parathormone
techniques are indicated. A. Accidental removal of parathyroid glands during thyroidectomy
2. Maintenance of hydration and urine output is important during B. Parathyroidectomy to treat hyperplasia
postoperative management of hypercalcemia. C. Idiopathic (digeorge syndrome)
3. Somnolence and skeletal muscle weakness suggest possible II. Resistance of peripheral tissues to effects of parathormone
decreased requirements for anesthetic drugs and muscle A. Congenital -pseudohypoparathyroidism
relaxants. B. Acquired -Hypomagnesaemia , Chronic renal failure ,
4. Hyperventilation of the lungs in undesirable, as respiratory C. Malabsorption Anticonvulsive therapy (phenytoin)
alkalosis lowers serum potassium concentration and leaves the o Unknown
actions of calcium unopposed. o Osteoblastic metastasis
5. Careful positioning is necessary. Because of likely presence of o Acute pancreatitis
osteoporosis and associated vulnerability to pathological Diagnosis
fractures. • serum calcium conc <4.5 mEq /L
6. Acidosis avoided –so as to not raise plasma (Ca+2) any • Ionized calcium conc. < 2.0 mEq/L
further.
SECONDARY HYPERPARATHYROIDISM: Signs and symptoms
• Reflects appropriate compensatory responses of the parathyroid Acute hypocalcaemia (accidental surgical removal)
glands to secrete more parathormone to counteract a disease • Perioral paraesthesias
process (chronic renal failure or intestinal malabsorbtion • Restlessness
syndrome) that produces hypocalcaemia. • Neuromuscular irritability (positive Chovstek sign (also Weiss sign) or
• Ectopic hyperparathyroidism: Trousseau sign, inspiratory stridor)
• Is due to secretion of Parathormone (or a substance with similar Chronic hypocalcaemia:
endocrine effects) by tissues other than the parathyroid glands. • Fatigue
• Ca of lung, breast, pancreas, or kidney and lympho-proliferative • Skeletal muscle weakness
diseases are most likely ectopic sites for Parathormone • Prolonged QT interval
secretion. • Cataract
HYPOPARATHYROIDISM • Neurologic changes → lethargy, cerebration deficits and personality
• Hypoparathyroidism is present when secretion of Parathormone changes
is absent on deficient or peripheral tissues are resistant to the Treatment:
effects of the hormone. • Infusion of calcium (10 ml 10% calcium gluconate IV) until signs of
neuromuscular irritability disappear.
• Correction of any co-existing respiratory or metabolic alkalosis.
• Thiazide diuretics may be useful, as these drugs cause sodium
depletion without proportional potassium excretion, tending to
increase serum calcium concentration. 31

Parathyroid Gland.Continuation: Dr Azam’s Notes in Anesthesiology 2013
Anesthetic management:
• Management of anesthesia in the presence of
hypocalcaemia is designed to prevent any further
decrease in the serum calcium concentrations and to treat
the adverse effects of hypocalcaemia, particularly those on
the heart.
32

8. Adrenal Gland. Dr Azam’s Notes in Anesthesiology 2013
Physiology: Adrenal androgens: Insignificant

Adrenal gland is divided into 2 parts. Catecholamines:
• Adrenal cortex • Adrenal medulla is specialized part of sympathetic nervous system
• Gluco corticoids (e.g. cortisol) • Synthesis Nor-epinephrine and epinephrine – 80% adrenal
• Mineralo corticoids (e.g. aldoste rone) catecholamines is epinephrine.
• Androgens • Regulated mainly by cholinergic preganglionic fibers of sympathetic
• Adrenal medulla Nervous System that innervates adrenal medulla.
• Catecholamines (e.g. Epinephrine, nor-epinephrine, • Stimuli: Hypotension, hypothermia, hypoglycemia, hypercapnia,
dopamine). hypoxemia, pain.
Glucocorticoids – cortisol essential for life GLUCOCORTICOID EXCESS – HYPERCORTISOLISM

Regulation: Cushing syndrome:
• ACTH or corticotrophin is secreted by anterior pituitary in • Corticotrophin dependent – inappropriately high plasma
response to corticotrophin-releasing hormone (CRH) secreted by corticotrophin (ACTH) concentration à (+) adrenal cortex à
hypothalamus and carried to anterior pituitary in the portal blood. Cortisol
Corticotrophin stimulates adrenal cortex to release cortisol. • Cushingʼs disease (70%) – Cushing syndrome caused by excess
Metabolic actions: secretion of corticotrophin. E.g. Pituitary corticotrophic tumors
• Anti insulin effectsà increase gluconeogenesis and inhibition of (microadenomas).
peripheral glucose utilization à↑ glucose levels. • Acute ectopic corticotrophin syndrome associated with small cell lung
• Promote Na+ retention and K+ excretion (mineralocorticoid carcinoma.
effects) Corticotrophin – Independent:
• Anti-inflammatory effects • Excessive production of cortisol by abnormal adrenocortical tissues.
• Required for vascular bronchial smooth muscle to be responsive • Suppresses secretion of CRH and corticotrophin.
to Catecholamines (facilitates conversion of Nor-Epinephrine to • Benign and malignant adrenocortical tumours – most common.
Epinephrine in adrenal medulla) Exogenous administration of steroid hormones:
Diurnal rhythm:
(+) stress
(–) circulating glucocorticoids
* Endogenous cortisol production average 20 mg/day
Mineralocorticoids:
• Aldosterone – involved in fluid and electrolyte balance.
• Na+ reabsorption in distal renal tubule in exchange for K+ and H
+ ions. (ECF expansion, decrease Pl. K+ and Met. Alkalosis).
• Regulated by rennin-angiotensin system, ser K+ concentration
and ACTH.
33

Adrenal Gland.Continuation: Dr Azam’s Notes in Anesthesiology 2013
Clinical features: GLUCOCORTICOID DEFICIENCY- HYPOCORTISOLISM

• Relatively sudden onset of weight gain- central obesity. Primary adrenal insufficiency Secondary adrenal insufficiency
• Thickening of facial fat (moon facies) – florid complexion
• Addisonʼs disease • Panhypopituitarism
(telengectasias)
• Systemic HTN, Glucose intolerance. • Destruction of adrenal gland by • inadequate corticotrophin (HTH)
hemorrhage, sepsis, secretion
• Frequent ecchymosis , Oligomenorrhea / Amenorrhea
• Muscle weakness and – decreased libido (men), wasting grammlomatous disease, cancer • Mineralocorticoid secretion
(difficulty in climbing stairs). • Combined mineralocorticoid + Normal
• Depression and insomnia, Osteoporosis, mental status change. glucocorticoid def. • Addisonian crisis (Acute adrenal
• 24 hour urinary secretion of cortisol - ↑ • Mineralocorticoid def insufficiency) à trigged in steroid
• Measurement of plasma corticotrophin – immunoradiometric (hyponatremia, hypovol, dependent patients who do not
assays.
hypotension, hyperkalemia, met. receive increased doses during
• High dose dexamethasone suppression test – distinguishes
Cushingʼs disease from ectopic corticotrophin syndrome Acidosis) stress.
(complete resistance present). • Glucocorticoid def (weakness, • CFà circulatory collapse, fever,
• Imaging procedures – location of tumor. fatigue, hypoglycemia, weight hypoglycemia, decrease
loss) abdominal/back pain. mentation
Treatment Cushingʼs disease:
• Etomidate suppresses adrenal • Medical emergency.
• Transpenoidal microadenomectomy.
function
• 85-90% resection of anterior pituitary.
• Pituitary radiation – between total adrenalectomy (Adrenal • Hyperpigmentation – palmer
adenoma). surface and pressure points
Anesthetic considerations:
• Preoperative evaluation of systemic HTN, electrolyte balance
and blood glucose measurements
• Volume overload and hypokalemic met alkalosis corrected with
spironolactone, Supplemental K+.
• Osteoporosis – risk of fracture during positioning
• Muscle weakness – decrease dose of NDMR (Hypokalemia).
• Cortisol replacement – IV hydrocortisone succinate 100 mg 8
hourly – in cases of B/L adrenalectomy and Cushingʼs syndrome
due to exogenous glucocorticoids.
• Significant blood loss, pneumothorax, transient diabetes
insipidus, meningitis (after microadenomectomy).
34

Adrenal Gland.Continuation: Dr Azam’s Notes in Anesthesiology 2013
S/S: Anesthetic considerations:

1. Weight loss, 1. Ensure adequate steroid replacement therapy during the
2. Skeletal muscle weakness perioperative period.
3. Hypotension 2. High index of suspicion for 10 adrenal failures – in presence of
4. Hyponatremia unexplained intraoperative hypotension.
5. Hyperkalemia 3. All patients who receive potentially suppressive doses of steroids
6. Hypoglycemia. (e.g. the daily equivalent of 5 mg of prednisolone) by any route of
7. Pain caused by hemorrhage into the adrenal cortex, as in anti- administration (topical, inhalational, or oral) for a period of more
coagulated patient, may be the only clue to the onset of than 2 weeks any time in the previous 12 months –are considered
adrenal insufficiency. unable to respond appropriately to surgical stress.
8. Hyperpigmentation are seen principally over the palmar surface 4. Adequate steroid coverage – normal adults secrete 20 mg/day of
and pressure points. cortisol this may increase to 300 mg under conditions of maximal
stress.
Treatment: 5. 100 mg of hydrocortisone every 8 hourly, beginning the evening
1. I.V administration of cortisol 100mg IV, followed by continuous before or on the morning of surgery.
infusion at the rate of 10 mg/hr I.V. 6. Low dose regimen 25 mg hydrocortisone at induction followed by
2. I.V. fluids to restore the intravascular fluid volume. an infusion of 100 mg during subsequent 24 hours
3. Replacement therapy for chronic hypocortisolism is with Appropriate for diabetic patients in whom glucocorticoid administration
administration of cortisone, 20 to 25 mg PO in the morning and often interferes with control of blood glucose.
10mg to 15 mg PO in the afternoon. Monitors:
4. Mineralocorticoid effect is provided with fludrocortisone 0.05 to • NIBP, pulse oximetry, IABP to monitor cardiac filling pressure is
0.10 mg PO daily. indicated.
• Plasma glucose and electrolytes.
Diagnosis: • Neuro muscular monitoring
• The definitive diagnosis of hypocortisolism requires • Emergency surgery – supplemental corticosteroids – I.V infusion of
measurement of plasma cortisol concentration before and 1 hr Na+ containing fluids.
after administration of corticotrophin • Minimal doses of anesthetic drugs sensitive to drug induced
myocardial depression.
• Skeletal muscle weakness à initial dose of relaxants decrease and
response monitored.
• Plasma concentration of glucose and electrolytes monitored
frequently.
• Invasive monitoring systemic BP and cardiac filling pressures.
35

9. Anesthetic Problems in Adrenocortical Insufficiency. Dr Azam’s Notes in Anesthesiology 2013
• The need for patients with adrenocortical hormone deficiency to • Total serum cortisol levels may be altered under various conditions
increase their dose of glucocorticoids when under stress is a (transcortin is decreased in hypothyroidism, cirrhosis, multiple
principle that rests in one of the most tranquil corners of medical myeloma, obesity, nephrotic syndrome and increase in pregnancy,
dogma. estrogen therapy, thyrotoxicosis, chronic active hepatitis and during
Levy A 1996 (Lancet). treatment with anticonvulsant drugs) that alter the amount of bond
• Two case reports published in the early 1950s described cortisol, yet the unbound active form is present in normal amounts.
cardiovascular collapse and death in young patients under-going The endogenous cortisol production is between 25 and 30 mg/ day,
routine orthopedic surgery. First case was of a 34-year-old man circulating concentrations vary in a circadian pattern and the half-life
who died after the withdrawal of steroids (25 mg cortisone bid) of cortisol in the circulation is between 60 and 90 min. Since cortisol
48h pre-operatively and the second patient was a 20-year-old acts through intracellular receptors, its pharmacokinetics is based on
woman who had taken 62.5-100 mg cortisone daily for 4 months; well-documented prolonged end organ effects and not on serum
she became hyperpyrexia and died less than 6hr after surgery. levels, which are not good indicator of activity. Cortisol is inactivated
Autopsy findings in both the cases revealed gross bilateral primarily in the liver and excreted as 17 hydroxycorticosteriod in
adrenal hemorrhage and histological changes of complete, urine. Some amount is also filtered and excreted unchanged in urine.
adrenal cortical atrophy. • Secretion of glucocorticoids (cortisol and cortisone) from adrenal
• These reports are considered the initial clinical recognition of gland is regulated by pituitary adrenocorticotrophic hormone (ACTH
iatrogenic adrenal insufficiency and its implication during serum half life 10 min).Which is synthesized from
perioperative period. Subsequently many other case reports and preopiomelanocortin that breaks into b-lipotropin (endorphin) and
animal studies supported the contention that patients with ACTH. ACTH is secreted by corticotrophic cells in the anterior lobe of
adrenocortical insufficiency or with suppression of the the pituitary gland under the stimulus of corticotrophin-releasing
hypothalamo-pituitary-adrenal (HAP) axis, required significant hormone (CRH) from hypothalamus. ACTH release from pituitary has
glucocorticoid supplementation during physiological stress. a diurnal rhythm normally greatest during the early morning hours in
men, later in women, and is regulated at least in part by light dark
PHYSIOLOGIC PROPERTIES OF ADRENOCORTICAL HORMONES: cycles. High cortisol levels in blood inhibit release of CRH and ACTH
• Three major classes of hormones -glucocorticoids, thus constituting a feedback loop mechanism.
mineralocorticoids and androgens are secreted by the adrenal • The synthetic glucocorticoids vary in their binding specificity in a
cortex. The principal glucocorticoid, cortisol, is an essential dose-related manner. When given in supraphysiologic doses (more
regulator of carbohydrate, protein, lipid and nucleic acid than 30mg/day), cortisol and cortisone bind to mineralocorticoid
metabolism. It exerts its effects through specific intracellular receptor sites and cause salt and water retention and loss of
cytoplasmic receptors. Most of cortisol (90-97%) is in protein potassium and hydrogen ions. When these steroids are administered
bond form. 90% is bond to Corticosterone binding globulin (CBG- in maintenance does of 30 mg/day or less, patients require a specific
transcortin half life in plasma is 5 days), and rest to albumin. mineralocorticoid for electrolyte and volume homeostasis. Relative
potencies of synthetic steroids are as follow: Cortisol 1, cortisone 0.8,
prednisolone 7, dexamethasone 30 times as potent as cortisol.
36

Anesthetic Problems in Adrenocortical Insufficiency.Continuation: Dr Azam’s Notes in Anesthesiology 2013
GLUCOCORTICOID RESPONSE TO SURGICAL STRESS CAUSES OF ADRENOCORTICAL HORMONE DEFICIENCY:

• Plasma cortisol concentration increases rapidly in response to • Primary adrenal insufficiency (Addison's disease) is associated with
surgical stimulation and remain elevated for a variable time local destruction of all zones of the adrenal cortex and causes both
following surgery. Peak values are achieved within 4-6h after glucocorticoid and mineralocorticoid deficiency, if the insufficiency is
surgery or injury and return towards baseline after 24h; this bilateral. Various causes of Addisonʼs disease are destruction of
increase in plasma cortisol may however, be sustained up to adrenal gland by cancer, tuberculosis, hemorrhage, autoimmune
48-72h following major surgery such as cardiac surgery. The diseases like association with Hashimoto's thyroiditis, administration
magnitude and duration of cortisol response reflect the severity of cytotoxic drugs and enzymatic defects in cortisol synthesis such
of surgical trauma. In stress conditions also the increased as in congenital adrenal hyperplasia. Because adrenal insufficiency
cortisol production is secondary to ACTH secretion, but the usually develops slowly, such patients developed marked
plasma ACTH concentration is far greater than that required to pigmentation from excess ACTH trying to stimulate an unproductive
produce a maximal adrenocortical response, and the normal adrenal gland and cardiopenia apparently secondary to chronic
pituitary adrenocortical feedback mechanism is no longer hypotension.
effective, as both hormones remain increased simultaneously. • Secondary adrenal insufficiency occurs when ACTH secretion is
Furthermore, arginine vasopressin (AVP) plays an important role deficient, often because of pituitary or hypothalamic tumour. Among
in the control of ACTH secretion during stress, by directly all of these causes for adrenocortical hormone deficiency, withdrawal
stimulating the release of ACTH and acting synergistically with of steroids or suppression of synthesis by steroid therapy is the
CRH, as well as regulating pituitary CRH receptor expression. leading cause of underproduction of corticosteroids.
• Under perioperative conditions, the adrenal gland secretes 100 ASSESSMENT OF HPA AXIS:
to 200 mg of cortisol daily. Under maximum stress they may • Therapy with glucocorticoids results in suppression of pituitary-
secrete up to 200-500 mg/day. In animal studies deficiency of adrenal function. Failure of cortisol secretion in such cases is due
glucocorticoids during stressful conditions lead to severe primarily to inhibition of synthesis of ACTH as a result of inhibited
hypotension associated with a significant decrease in systemic transcription of the corticotrophin gene. Stimulation tests are usually
vascular resistance (SVR) and a reduced left ventricular stroke required to identify patients with suppressed, endogenous adrenal
work index (LVSWI) ultimately leading to death. The filling function. Biochemical evaluation is based on three important
pressures of the heart were unchanged suggesting no evidence principles of HPA physiology:
of hypovolemia or severe congestive heart failure. Despite the 1. Cortisol exerts feedback inhibition at the pituitary and hypothalamic
low SVR, the animals did not become tachycardiac. All these levels;
responses are compatible with interaction of glucocorticoids and 2. The adrenal glands depend upon ACTH as a tropic hormone so
catecholamines, suggesting that glucocorticoids mediate that ACTH deficiency results in a reversible inability to secrete
catecholamine-induced increases in cardiac contractility and cortisol;
maintenance of vascular tone and this effect of steroids is 3. The HPA axis can be activated by pharmacological and
immediate on supplementation. physiological stimuli that override the normal diurnal pattern of
cortisol production.
37

a) The insulin tolerance test (ITT) ANESTHETIC DRUGS AND ADRENAL FUNCTIONS:
• The insulin stress test is accepted by many as the gold standard • Within the perioperative period, various anesthetic agents and
for overall assessment of the entire HPA axis, but is unpleasant techniques are used which can ablate, or obtund the cortisol
and not without risk. Loss of consciousness, seizures, resistant response to surgery.
hypoglycemia, myocardial infarction and even death are a) Intravenous induction agents
recognized complications. • Etomidate an imidazole derivative is a potent inhibitor of adrenal
b) The short synacthen test (SSI) steroidogenesis and acts on the mitochondrial 11β hydroxylase step
• Uses synthetic corticotrophin (ACTH) 250µg intravenously and and cholesterol cleavage part of the biosynthetic pathway. Single
the plasma cortisol response at 0, 30 and 60 min. are measured induction dose of etomidate can inhibit cortisol and aldosterone
by fluorometric assay. Peak cortisol concentration is achieved at production for up to 8 hour. The etomidate is often used in sick
30min to reflect the maximal response and after 60min cortisol patients with limited cardiovascular reserve without adverse effect,
level are decreased and will reach baseline value after 4h. Peak thereby raising the question of how much circulating cortisol is
cortisol concentration more than 400 nmol/lt at 30min are taken required in routine surgery for cardiovascular stability. Midazolam,
as criteria for establishing adequate adrenal function. However which has an imidazole ring in addition to its benzodiazepine
SST may be less reliable in assessing the HPA axis in patients structure was also found to decrease the cortisol response to
withdrawing from steroids, those with pituitary disease and in the peripheral surgery and major upper abdominal surgery and may also
first 14 days following pituitary surgery. have a direct effect on ACTH secretion.
c) Stimulation CRH testing
• This is useful in both diagnosis and localization of adrenal b) Volatile anesthetic agents
insufficiency. Human or ovine CRH is given in a dose of 1µ/kg • Volatile anesthetic agents probably have little effect on the HPA axis
(100 µg bolus), which provide near maximal stimulation with when used at low concentration up to1.5 MAC.
minimum side effects. Following injection of CRH, ACTH and c) High dose opioid anesthesia
cortisol concentrations are evaluated over the succeeding 2 • The ability of morphine to inhibit the HPA axis has been known for
hours. In secondary adrenal insufficiency, baseline ACTH values many years. Fentanyl in doses 50 µg/kg abolished the cortisol
are low and do not respond to CRH. response to pelvic surgery. In general, the majority of studies have
• Despite intensive investigation during the past 30 years there is shown that cortisol secretion is attenuated by opioids only until the
little consensus over what constitute the best overall test of start of cardiopulmonary bypass in cardiac surgery.
adrenal function and reserve. No single test appears to satisfy all
the criteria of efficacy, safety, simplicity and cost, although most
of the work assessing the HPA axis in patients undergoing
surgery has used the SST. Patients who satisfy clearly defined
end-points at each stage, for example random serum cortisol
>500 nmol/1, increase in plasma cortisol concentration during
stress testing more than 7-25 µg/dl usually indicate normal
pituitary adrenal responsiveness and need not proceed to further
testing. 38

d) Regional anesthesia • Primary adrenal insufficiency is associated with skeletal muscle

• It is well recognized that complete afferent blockade, both weakness, weight loss, anorexia, hypotension, hyperpigmentation
somatic and autonomic, is necessary to prevent stimulation of (from excess secretion of melanocyte-stimulating hormone from the
the HPA axis. Thus an extensive T4-S5 block for pelvic surgery anterior pituitary), and circulatory collapse during stress. Adrenal
completely abolishes stress response but it is very difficult in insufficiency is particularly difficult to diagnose in the postoperative
upper abdominal surgery to prevent cortisol secretion completely patient. Abdominal pain, hypotension, fever, tachycardia, volume
with regional anesthesia. depletion, nausea and vomiting and delirium are all signs and
• However when steroid supplementation is planned in indicated symptoms of adrenal insufficiency; however, in the early
patients, choice of anesthetic technique is not important. In such postoperative period, they are often ascribed to other more frequent
situations preparation of a patient with adrenal insufficiency for causes. Postoperative insufficiency may occur in patients with
anesthesia and surgery should require more attention towards Addison's disease who are on inadequate corticosteroid doses
the treatment for hypovolemia, hyperkalemia, and hyponatremia. considering the stress of surgery or it may occur de novo due to
ANESTHETIC CONSIDERATIONS IN ADRENAL INSUFFICIENCY: adrenal hemorrhage as a complication of surgery or sepsis. Although
• The syndrome of adrenal insufficiency is characterized by spontaneous adrenal hemorrhage may occur in any patients, it is
disturbances in a number of organ systems. Failure to produce more likely to occur in those patients subjected to the greatest
the mineralocorticoid aldosterone leads to sodium wasting, as stresses. The etiology of adrenal hemorrhage is unknown, but it may
the ability of the distal nephron to retain sodium chloride is be produced experimentally with large doses of endotoxin or
greatly diminished. Potassium excretion likewise fails, and corticotrophin. Laboratory findings include hypernatremia,
hyperkalemia results; however, total body stores of potassium hyperkalemia, hypoglycemia, hemoconcentration, leukocytosis and
are generally decreased in this disease due to vomiting and increased blood urea nitrogen. The diagnosis of adrenal insufficiency
diarrhea. So while the initial therapy may be directed at reversing is, confirmed the short synacthen test.
hyperkalemia, total body stores of potassium may eventually
need to be repleted. The inability to retain sodium leads to a Anesthetic management:
state of intravascular volume depletion and hypotension. The • Intravenous volume replacement with glucose containing salt
hyponatremia is worsened by the release of vasopressin by the solutions and the monitoring of intravascular volume are important.
pituitary in response to hypotension, causing further free water Circulatory collapse from suspected adrenal insufficiency requires
retention. Renal blood flow is compromised reducing distal emergency steroid replacement with 100mg of Intravenous cortisol
delivery of filtrate and further impairing the diluting ability of the followed by 50mg every 4 to 6 hours for the first 48 hours of the crisis
kidney. or 10mg/hour infusion.
• The diagnosis of adrenal insufficiency is very often a difficult one to
establish under anesthesia, especially in absence of such cardinal
features as hyperpigmentation. Unfortunately, the proper diagnosis is
often made at autopsy. Treatment of the patients in Addisonian crisis
has four principal objectives; depletion of glucocorticoids, repletion of
sodium and water deficits, correction of hypoglycemia and
hypothermia. 39

• Addisonian crisis is a life-threatening syndrome, and treatment Perioperative steroids supplementation:

with high-dose intravenous glucocorticoids must be instituted as Many experimental studies and reports concerning the adrenal
soon as the diagnosis is suspected. Whenever, this crisis is responses during perioperative period in patients taking steroids for
suspected, a sample should be taken for cortisol assay, and if other diseases indicate the following:
possible, a short corticotrophin-stimulation test should be 1. Perioperative stress relates to the degree of trauma and the depth
performed if there is doubt regarding the proper diagnosis. of anesthesia. Deep general anesthesia or regional anesthesia
However, treatment should not be withheld until the results are causes the usual intraoperative glucocorticoid surge to be
available. Volume replacement should begin immediately in the postponed to the postoperative period.
form of isotonic normal saline. Fluid is replaced until the patient 2. Few patients who have suppressed adrenal function have
becomes euvolemic-central venous monitoring may be a useful perioperative cardiovascular problems if they do not receive
guide. Vasopressors may be required to sustain adequate blood supplemental steroid preoperatively.
pressure in the initial stages of therapy. Agents such as nor- 3. Occasionally, a patient who chronically takes steroids becomes
epinephrine should be avoided, as tissue perfusion is already hypotensive preioperatively, but this event has only rarely been
compromised. Hydrocortisone, 50 to 100 mg every 6 hours, documented sufficiently to implicate glucocorticoid or mineralo-
should be administered intravenously for the first 24 hours of corticoid deficiency as the cause.
treatment. Glucocorticoid therapy may be switched to oral 4. Although it occurs rarely, acute adrenal in sufficiency (Addisonian
supplementation on day 2 if the patient is well stabilized. crisis) can be a life threatening event if steroid supplementation is
Glucocorticoid doses should be tapered daily until maintenance withheld.
dosage (20 to 30_mg/day) is reached. Doses in this range have 5. There is little risk in giving these patients low-dose steroid coverage
enough mineralocorticoid activity to obviate the need for perioperatively.
supplementation. Fludrocortisone acetate, 0.1 to 0.2 mg orally, Steroid treatment regimens:
may be required in primary adrenal failure when more Usually laboratory data defining pituitary adrenal adequacy are not
mineralocorticoid activity is necessary. available before surgery. However, rather than delay or postpone
• Hyperkalemia is rarely in excess of 7mmol/L and usually surgery or test most patients, it is wise to assume that any patient who
responds to glucocorticoid replacement, glucose administration, has taken steroids (even topical application without use of occlusive
and rehydration. dressing) at any time during the preceding one year has suppressed
• In addition to these measures, a careful history and physical pituitary adrenal functioning and will require perioperative
examination along with blood urine, and sputum cultures and a supplementation. The precise amount required has not been
chest x-ray are necessary. It is wise to institute empirical broad- established but following guidelines can be followed:
spectrum antibiotic coverage after all appropriate cultures are 1. Administer intravenously the maximum amount of glucocorticoid
performed, that the body manufactures in response to a maximal stress (i.e.
approx. 200 mg/day of hydrocortisone phosphate/70 kg body
weight) in case of major surgery.
2. No patient should receive less than his or her routine glucocorticoid
therapy preoperatively.
40

3. Physiological (low dose) supplementation regimen: Patients on MINERALOCORTICOID DEFICIENCY:

chronic steroid therapy should receive their usual dose on the • Hypoaldosteronism, a less common condition can be congenital or
day of surgery plus 25 mg hydrocortisone intravenously at can occur after unilateral adrenalectomy or prolonged administration
induction and an infusion of 100 mg/day hydro-cortisone for the of heparin_ or as a consequence of long standing diabetes and renal
first 48-72 hours. failure. Nonsteroidal inhibitors of prostaglandin synthesis (NSAIDS)
4. Supraphysiological (high dose) supplementation regimen: It is may also inhibit renin release and exacerbate this condition in
based on the result of studies implicating that short term high patients who have renal insufficiency. Most symptoms are caused by
dose steroid supplementation involve little risk. These patients hyperkalemic acidosis rather than hypovolemia, in fact, some
should be given 100mg hydrocortisone at the time of induction patients are hypertensive. These patients can have severe
in addition to their usual dose plus 250 mg hydrocortisone hyperkalemia, hyponatremia and myocardial conduction defects.
infusion over 24 hour during perioperative period. Afterwards Before taking these patients for surgery foresaid defects can be
infusion should be decreased by 25% per day until oral intake treated successfully by administering mineralocorticoids (9a-
dose is reached and patient can take orally. At this point, the fluorocortisol, 0.05 to 0.1 mg/day) preoperatively. Doses must be
usual maintenance dose of glucocorticoids can be employed carefully treated and monitored to avoid an increase in
orally. hypertension.
Risk of steroid supplementation: CONCLUSION
A rare potential risk of perioperative supplementation with steroids • In the management of a patient with adrenocortical hormone
includes aggravation of hypertension, fluid retention, inducement deficiency, the etiology of this deficiency is important consideration.
of stress ulcers and psychiatric disturbances. Although data are Whereas patients with HPA suppression due to steroid therapy
not available to assess the incidences of these risks with short simply require steroid supplementation, patients with long standing
term supplementation, two common complications of short term Addison disease require treatment for hypovolemia, hyperkalemia,
perioperative supplementation with steroids are described in the and hyponatremia before anesthesia along with steroid
literature are abnormal wound healing and increased rate of supplementation since the threat of acute adrenal crisis is real in
infections. Hence current literature recommends only physiological these patients. Most of the studies now indicate towards
supplementation of steroids during perioperative period. Vitamin A physiological perioperative steroid supplementation.
topical application has been found to be somewhat protective
against delayed healing, presumably because of its effect on
stabilizing lysosomes.
41

10. Hyperaldosteronism.(Mineralocorticoid Excess). Dr Azam’s Notes in Anesthesiology 2013
Primary aldosteronism Secondary aldosteronism Anesthetic considerations:

Conn syndrome Some disease stimulate Preoperative hypokalemia correction, treatment of HTN.
aldosterone secretion by • NDMR – modified response in presence of hypokalemia.
• Sevoflurane – use with caution in presence of hypokalemic
affecting renin – angiotensin nephropathy and polyuria
system • Measurement of cardiac filling pressures.
Excess secretion of aldosterone CHF, cirrhosis with ascetic, • Preoperative evaluation- orthostatic hypotension.
from a functional tumor nephrotic syndrome, HTN (Renal • Acid-base status and plasma electrolytes monitored frequently.
(aldosteronoma) independent of art stenosis) • Supplementation of exogenous cortisol–B/L mobilization of adrenal
physical stimuli. gland.
HYPOALDOSTERONISM
Unilateral adenoma, bilateral Increase aldosterone levels ,
• Isolated hypoaldosteronism à unilateral adrenalectomy, diabetes or
hyperplasia, carcinoma of increased rennin levels heparin treatment.
adrenal gland • Combined mineral corticoid and glucocorticoid def – atrophy/
Women associated with PCC, 10 desaturation of both adrenals.
hyperparathyroidism / • Hyperkalemia in the absence of renal insufficiency suggest the
Acromegaly presence of hypoaldosteronism.
Clinical feature:
Clinical features: • Hypotension, hyperkalemia, Hyperchloremic metabolic acidosis.
Systemic HTN, hypervolemia, hypokalemia, muscle weakness, • Treatment with exogenously administered mineralocorticoid (e.g.
metabolic alkalosis (decrease K+ - polyuria, nocturia, muscle Fludrocortisone).
cramps). GLUCAGON
Diagnosis: • Glucagon is a catabolic hormone (polypeptide ) unlike insulin which
1. Increased urinary excretion of K+
(< 30 mEq/day) in presence is anabolic "" " " "
of hypokalemia. • It is produced from the alpha cells of pancreas
2. PRA (Plasma rennin activity) suppressed in untreated 10& ESS • It has its major effect on the liver where it causes hepatic adenylate
HTN - 20 high. cyclic stimulation leading to glycogen breakdown to glucose, also it
Treatment: brings about gluconeogenesis from amino acids and brings about
• Supplemental potassium breakdown of fats to it Stimulate secretion of G.H, Insulin &
• Spironolactone (competitive Aldosterone antagonist). Somatostatin.
• Antihypertensives – HTN – K+ sparing diuretics – triamterene • CVS has inotropic and chronotrophic action an heart. It enhances
• Surgical excision automaticity in the SA and AV node without increase in automaticity
of the ventricle.
• Renal effects similar to Dopamine but less effective potent.
• Half life is less than 10 min.
42

10. Hyperaldosteronism.(Mineralocorticoid Excess). Dr Azam’s Notes in Anesthesiology 2013
Dosage:
1. Hypoglycaemia -- 0.5 to 1mg IV/IM
2. β-receptor antagonist overdose --50-150/µg/kg IV
Uses:
1. Emergency hypoglycemia
2. β-adrenergic antagonist poisoning
3. Used as a provocative test in differential diagnosis of
Pheochromocytoma (1-2 mg IV). 1-3 min after IV
administration. 3/more >increase in plasma catecholamine –
increase in systolic BP by 15-20 mm Hg
Side effects:
1. Nausea, vomiting.
2. Hyperglycemia.
3. Paradoxical hypoglycemia (in patients who do not have
sufficient glycogen storage in liver to offset the increased
insulin release by glucagon.
4. Stimulates the release of catecholamines so may evoke HTN in
patients with Pheochromocytoma.
5. Hypokalemia reflects increase in secretion of insulin and
subsequent intracellular transfer of glucose and K.
43

11. Anesthetic Management of Diabetic patient for elective & Emergency surgery. Dr Azam’s Notes in Anesthesiology 2013
INTRODUCTION: CLASSIFICATION:
• Diabetes mellitus is an Iceberg disease. The incidence of ETIOLOGIC CLASSIFICATION OF DIABETES MELLITUS
Diabetes mellitus (DM) continues to increase alarmingly, 171 TYPE I DIABETES
million people being affected worldwide, India having the highest I. Type I A: Immune mediated" "
incidence i.e. 12.1%. Every 5th diabetic in the world is an Indian. II. Type I B: Idiopathic
Prevalence in India is 3-8% and it is estimated that by 2025, TYPE II DIABETES
Indian would have 55 million diabetics, making India the • Insulin resistance with relative insulin deficiency
diabetes capital of the world. Thus more diabetic patients will Type III - Other Specific types:
present for both elective and emergency surgery. A. Genetic defects of insulin secretion
Anesthesiologists are therefore likely to encounter diabetic " Maturity onset diabetes (MODY 1, 2, 3, 4, 5, 6)
patients on a day-to-day basis; hence we have made an attempt B. Genetically-related insulin resistance
to discuss the perioperative management of diabetic patients. " Type A insulin resistance, Lipodystrophy syndrome
C. Disease of exocrine pancreas
DEFINITION: " Pancreatitis, Cystic fibrosis, Neoplasia
DM is a metabolic syndrome due to relative or absolute deficiency D. Endocrinopathies
of insulin. Characterized by hyperglycemia, glycosuria, " Cushingʼs syndrome, Acromegaly, Glucagonoma
hyperlipemia, negative nitrogen balance and sometimes E. Drug / Chemical induced
ketonemia. " Thyroid hormones, Glucocorticoids,
F. Infection induced
DIAGNOSIS: " CMV, rubella, coxsackie
WHO / ADA Criteria G. Uncommon forms of immune mediated diabetes
Normal Pre –Diabetes " Stiff person syndrome, anti insulin receptor antibody
Diabetes
glucose Impaired glucose
mellitus H. Uncommon syndrome association
tolerance tolerance
FBS or " Downʼs syndrome, , Turnerʼs syndrome
(mg/dl) Type IV- Gestational Diabetes mellitus (GDM)
< 100 100 – 125 > 126
(mmol/L) < 5.6 5.6 – 6.9 >7
Or
PPBS or
(mg/dl) < 140 140 – 199 > 200
(mmol/L) < 7.8 7.8 – 11.1 > 11.1
Or
Symptoms of diabetes with casual glucose of > 200 mg/dl
In two occasions, on different days.
44

Anesthetic Management of Diabetic patient for elective & Emergency surgery. Dr Azam’s Notes in Anesthesiology 2013
Pathophysiology: EFFECTS OF DIABETES ON SURGERY AND

ANAESTHESIA:
Acute
Hyperglycemia
• Endothelial dysfunction
• Affects Oxygen transport
• Autonomic dysfunction: Altered regulation of HR, BP
• Osmotic diuresis à dehydration à ischemic events
(cerebral ischemia, MI , ARF)
• Electrolyte disturbances (K+, Na+, Mg++) à
Arrhythmogenic risk
• Hypothermia
• Postoperative sepsis, Impaired wound healing
• End organ effects - Late complications
Hypoglycemia: if uncorrected, irreversible brain
damage may occur.
Chronic
I. Macro-vascular
CVS
• Coronary artery disease - risk of silent Myocardial
Ischemia/Infarction
• Peripheral Vascular Disease - Claudication, ischemia
• Cerebrovascular disease – Transient Ischemic Attack ,
stroke
II. Microvascular
• Retinopathy, Cataract
• Nephropathy - ESRD
Others
• GI – gastroparesis - increased risk of aspiration
• Genitourinary – bladder and bowel incontinence
• Infections
• Foot disease – non healing ulceration, arthropathy
45

#
%&&%'()$*&$)+,-%,.$*/$0123%(%)4$
Induction agents may affect glucose homeostasis perioperatively:
2/(1$1/)+51/$%&&%'()$
EFFECTS OF SURGERY ON DIABETES:
ANTI INSULIN EFFECTS: • Ketamine is shown to increase blood glucose level marginally
#
• Etomidate blocks adrenal steroidogenesis and cortisol synthesis,
#####*9>?@9*!@A?.*9#6B?966#?96C@*69#6789:;<$=>$7?89:;$<8;@A;8=BC#
thereby decreasing hyperglycemic response to surgery
# Benzodiazepines
# • Decrease secretion of ACTH, cortisol, ( in high doses during surgery)
./7"-&)-8#)4'D&,0-,17#&7,1E1,4#################./7"-&)-8#7+F/,-"#"-3F2&,+"4# • Decrease sympathetic stimulation
0+"'+/-)=# • Stimulate growth hormone secretion thereby decreasing in the
# # # #A&,-70+2&'1/-)G#A+",1)+2# glycemic response to surgery.
# # # ###H2F7&3+/G#H"+<,0#I+"'+/-# • These effects are minimal when midazolam is given in usual sedative
# doses, but may be relevant when given by continuous i.v infusions.
# Volatile anesthetics: Halothane, enflurane, isoflurane, in-vitro, inhibit
./01J1,1+/#+K#1/)F21/#)-7"-,1+/################################./)F21/#"-)1),&/7-# the insulin response to glucose in a reversible and dose dependent
# manner.
Propofol: The effect of Propofol on insulin secretion is not known.
#
Diabetic patients show a reduced ability to clear lipids from circulation,
H2F7+/-+3-/-)1)#
although this is unlikely to be relevant during short anesthetics, it may
# # # H247+3-/+24)1)#####
have implications for patients receiving propofol for prolonged sedation
# # # #####L1D+24)1)G#
in ICU.
C"+,-+24)1)####
Other induction agents, muscle relaxants and premedicant drugs in
#
common use do not have much effect on the blood glucose level.
DEFG>HA;AI=?8<J#
$ SYNDROME X or Reavenʼs Syndrome or cardiometabolic syndrome or
D.K%,-5.'%L12# Metabolic Syndrome
%&&%'($*&$2/2%)(D%)12$*/$0123%(%)$$
EFFECT OF ANAESTHESIA ON DIABETES 1. Hyperinsulineamia
-GBG>A?$2BG<;:G<8A4$*-F"+-/8+7"1/-#),"-))#"-)D+/)-#!#?-2-&)-#+K#A+F/,-"5"-3F2&,+"4#
• General Anesthesia: Neuroendocrine stress response à Release 2. Type 2 DM / impaired OGT
0+"'+/-)#!#I4D-"3247-'1&#
of Counter-regulatory hormones à Hyperglycemia 3. Hypertension
,G98=BA?$2BG<;:G<8A4#2-))#'-,&J+217#"-)D+/)-#
• Regional Anesthesia: less metabolic response 4. Low HDL
1BM@H;8=B#&3-/,)#'&4#&KK-7,#32F7+)-#0+'-+),&)1)#D-"1+D-"&,1E-24#
5. Increased TGʼs
• M-,&'1/-#1)#)0+</#,+#1/7"-&)-#J2++8#32F7+)-#2-E-2#'&"31/&224#
6. Central Obesity
• 9,+'18&,-# J2+7N)# &8"-/&2# ),-"+18+3-/-)1)# &/8# 7+",1)+2# )4/,0-)1)G# ,0-"-J4#
7. Microalbuminuria
8-7"-&)1/3#04D-"3247-'17#"-)D+/)-#,+#)F"3-"4#O-/%+81&%-D1/-)##
8. Increased Fibrinogen
• !-7"-&)-#)-7"-,1+/#+K#$ABIG#7+",1)+2G#P#1/#0130#8+)-)#8F"1/3#)F"3-"4Q#
9. Increased Plasminogen activator inhibitor
• !-7"-&)-#)4'D&,0-,17#),1'F2&,1+/##
10. Increased plasma uric acid
• 6,1'F2&,-# 3"+<,0# 0+"'+/-# )-7"-,1+/# ,0-"-J4# 8-7"-&)1/3# 1/# ,0-# 3247-'17#
11. Increased sympathetic activity
"-)D+/)-#,+#)F"3-"4=##
:;# 46
<<<=!"$%&'=7+'###############################################################################Endocrinology #
#
PERIOPERATIVE PROBLEMS Anticipated Surgery

• Surgery induced stress response with catabolic hormone • Type of surgical procedure
secretion • Inpatient or Outpatient
• Interruption of food intake • Type of Anesthesia
• Altered consciousness • Start time
• Circulatory disturbances • Duration of the procedure
PRE ANESTHETIC EVALUATION CLINICAL EXAMINATION:
TYPE AND SEVERITY OF DIABETES Airway Assessment:
HISTORY Look for “STIFF JOINT SYNDROME” due to diffuse glycosylation of
H/O polyuria, polydypsia, Polyphagia, loss of weight, fatigue, collagen tissues of cervical spine, atlanto-axial, temporomandibular,
recurrent burning micturition, non healing ulcers, intermittent metacarpophalangeal and interphalangeal joints with limited mobility
claudication. leading on to DIFFICULT LARYNGOSCOPY AND INTUBATION
CNS – headache, blurring of vision, numbness, tingling sensations
in limbs, documentation of sensory and motor neuropathy (glove “Prayer sign”.
and stocking parasthesia).
CVS – palpitations, angina, silent MI, associated hypertension.
RS – recurrent pulmonary infections
Renals – puffiness of face, generalized edema
Autonomic neuropathy – orthostatic hypotension, resting
tachycardia, bowel & bladder incontinence. Delayed gastric
emptying.
Detailed assessment of END ORGAN DAMAGE
DIABETIC THERAPEUTIC REGIMEN
• Medication type, Dosage, Timing, Duration.
METABOLIC STATUS OF THE PATIENT

HYPOGLYCEMIA
• Frequency / Awareness / Severity
EPISODES OF DKA
• Meal plan, Activity level
Routine risk factors
• Cardiac
• Renal
• Pulmonary
• Hematologic
47

Palm print sign – TESTS TO ASSESS AUTONOMIC NEUROPATHY

1. Resting tachycardia:
• Eliminating anxiety, if HR > 100 at basal conditions, it suggests
resting tachycardia.
2. Heart rate response during deep breathing:
• Patient sits quietly and breathes deeply at about 6 breaths per min
for one minute. An ECG is recorded throughout. The maximum and
minimum R-R interval during each breath cycle is measured with a
ruler and converted into beats/min. the result is expressed as the
# Palm print grade 0 Palm print grade 1 mean of the difference between maximum and minimum HR for 6
• Neuropathy of vagus and the recurrent laryngeal nerves resulting measured cycles in beats/min. If difference of ≥15 beats/min -
in bilateral vocal fold immobility – insidious onset of dysphonia Normal, 11 – 15 - Borderline, < 10 – Abnormal.
and stridor. 3. Immediate heart rate response to change in posture:
• The patient lies quietly on the couch while the ECG is recorded
DIABETIC AUTONOMIC NEUROPATHY: leading to difficulty in continuously. The patient is asked to standup unaided and the point
anesthetic management resulting in increased morbidity & at which the patient standup is marked on the ECG. The shortest R-
mortality in diabetic patients R interval at or around 15th beat and the longest R-R interval at or
• Hypertension around 30th beat after standing is measured.
• Silent myocardial ischemia • If 30: 15 ratio of R-R interval is
• Orthostatic hypotension" " " • ≥ 1.04 – Normal, 1.01 – 1.03 – Borderline, ≤ 1.10 – Abnormal
• Resting tachycardia" " " " 4. Valsalva maneuver:
• Absence of sinus arrhythmia" " • The Valsalva maneuver consists of forced expiration against a
• Abnormal Valsalva maneuver standardized resistance for a specified period of time. The patient
• Gastroperesis" " blows forcefully into the mouth piece attached to a mercury
• Early satiety manometer to maintain 40 mmHg positive pressure for 15 seconds.
• Neurogenic bladder Then he releases the pressure rapidly and breathes quietly for one
• Loss of sweating minute. A continuous ECG is recorded throughout the procedure.
• Impotence • Valsalva ratio is expressed as the ratio of largest R-R interval after
the maneuver (reflecting bradycardia following release) to the
shortest R-R interval during the maneuver (reflecting tachycardia
during the maneuver).
• Valsalva ratio ≥ 1.20 - Normal, 1.11 – 1.19 – Borderline, ≤ 1.10 –
Abnormal
48

56-7+/8#981,1+/#
Anesthetic Management of Diabetic patient for elective & Emergency
# surgery. Dr Azam’s Notes in Anesthesiology 2013
%&'%(&()*+,$+-$.*(/')*0$%()*',)$-+&$'1'0)*2'$34&5'&6$
5. Blood pressure response to standing: PREPARATION OF DIABETIC PATIENT FOR ELECTIVE SURGERY:
#
BP is measured while patient is lying down quietly and while he
(77$89:;<=:>$
stands up, the postural fall of BP is taken as the difference
# # # # # # ################=#>2&/#8&,-#+?#)@"3-"4#
between SBP lying and in standing.
# # # # # # #####################=#A-&'#;+"B#
• If the fall is ≥ 30 mmHg – Abnormal, 11 – 29 mmHg – borderline, # # # # # # #########################=#+C,1'1%-#3247-'17#7+/,"+2#
< 10 mmHg – Normal.
# # # # # # #############################=#>"-+C-"&,1D-#1/D-),13&,1+/)#
6. Blood pressure response to sustained hand grip:
#
• Handgrip is maintained at 30% of the maximum voluntary
>&,1-/,)#/+,#,"-&,-8#;1,0#1/)@21/# # ####>&,1-/,)#,"-&,-8#;1,0#1/)@21/#
contraction which is determined by dynameter, for as long as 5
minutes. BP is measured 3 times before and at one minute #
intervals during the hand grip. The result is expressed as the #
difference between the highest DBP during the handgrip and the #####E1/+"#)@"3-"4#F# # # # # #####E&G+"#)@"3-"4#F#
mean of the 3 DBP readings taken before handgrip. H++8#3247-'17#7+/,"+2# # # ###############>++"#3247-'17#7+/,"+2#
• A rise of ≥ 16 mmHg – Normal, 11 – 15mmHg – borderline, #
< 10 mmHg – Abnormal. #
All the five tests can be performed simply and quickly at the #
bedside, providing an objective guide to whether or not autonomic #I-C2&7-#2+/3#&7,1/3# # # # # $8'1,#J#=#K#8#L-?+"-#)@"3-"4#
damage is present and also to quantify the extent of damage. #####6@2C0+/42@"-&# # # # ################6,&",#.M#1/)@21/#F#),&L121%-#
Peripheral neuropathy: ###$8'1,#8&4#L-?+"-#)@"3-"4#
• Sensory neuropathy may be manifested as nocturnal sensory #
discomfort of the lower extremities. #
• Increased incidence of carpal tunnel syndrome. Median and N1"),#1/#,0-#21),O#NP6# # # # ##################N1"),#1/#,0-#21),O#NP6#
ulnar nerves of forearm are often involved. Q'1,#L"-&B#?&),#F#QR$# # # # #6,&",#.M#./)@21/#F#H2@7+)-#
• Segmental demyelination and vascular occlusion of nutrient $D+18#H2@7+)-#7+/,&1/1/3#1/?@)1+/# # # #M&"1+@)#"-31'-/)#
arteries especially to the cranial nerves occur. E+/1,+"#P2++8#32@7+)-<#J/8#0+@"24<########################### #E+/1,+"#P2++8#H2@7+)-#0+@"24#
#
#
#
I-),&",#QR$#;1,0#?1"),#'-&2######### # # # S+/,1/@-#.M#1/)@21/O###########
# # ###################################################################################E+/1,+"#P2++8#H2@7+)-#
49
Dr Azam’s Notes in Anesthesiology 2013 ::#

;;;<!"$%&'<7+'###############################################################################Endocrinology #
PREOPERATIVE INVESTIGATIONS ORAL HYPOGLYCEMIC AGENTS (OHA)

• Blood: CBC, Drugs that increase insulin secretion
• Blood glucose: FBS, PPBS, HbA1C Sulfonylureaʼs:
• Sr. Electrolytes – K+, Na+ • I generation - Tolbutamined, Chlorpropamide
• Urine: albumin, sugar, microscopy, ketone bodies, urine output • II generation - Glibenclamide, Glipizide, Gliclazide, Glimepiride
• CVS assessment – ECG – for established previous ischemia, • Megliturnides analogues (non Sulphonylurea) – Repaglinide,
• TMT – for subclinical ischemia Nateglinide
• ECHO – for ejection fraction, wall motion abnormalities, chamber Drugs that increase the sensitivity to insulin
enlargements • Biguanides – Metformin
• X ray - Chest • Thiazolidinediones – Rosiglitazone, Pioglitazone
• Fundoscopic examination • Drugs that decrease glucose / fat absorption
• PFT, ABG • α glucosidase inhibitors - Acarbose
• LFT • Intestinal lipase inhibitors.
• RFT – B.Urea, S.Creatinine ORAL HYPOGLYCEMIC AGENTS
Oral agent Mechanism of Duration Adverse Contraindicatio
GLYCATED HEMOGLOBIN (HbA1C): action of action effects ns
Measurement of glycated hemoglobin is the standard method of Sulphonylurea Increased Hypoglycemia Renal / Liver
assessing long term glycemic control. When plasma glucose is s insulin 12 – 18 h Weight gain disease.
consistently elevated; there is an increase in non-enzymatic Glipizide secretion Drug
glycation of hemoglobin; reflecting the glycemic history over the Glimepiride > 48 h interactions
previous 2-3 months. Chlorpropamide
HbA1C of Mean plasma glucose Biguanides Potentiates 6 – 8 h Lactic acidosis SCr > 1.5 mg/dl
• 6%" - 135 mg/dl (7.5 mmol/l) (< 6 % - good control) Metformin insulin Diarrhea, CHF, acidosis
• 7% " - 170 mg/dl (9.5 mmol/l) Thiazolidinediones Peripheral 12 – 24 h Edema, CHF, CHF, liver
Rosiglitazone insulin action disease
• 8% " - 205 mg/dl (11.5 mmol/l) (> 10 % - poor control)
• A 1% rise in A1C translates into 35 mg/dl (2 mmol/l) increase in Megliturnides Releases 3–5h Dyspepsia,
the mean glucose. Repaglinide insulin arthralgia,
weight gain
Glucosidase Decreases GI flatulence Renal / liver
inhibitors intestinal disease
Acarbose glucose
absorption
50

INSULIN PREPARATIONS METABOLIC ACTIONS OF INSULIN:

Type Onset (hr) Peak (hr) Duration (hr) Increase (ANABOLIC) Decrease (CATABOLIC)
Rapid acting CARBOHYDRATE METABOLISM Gluconeogenesis
• Insulin Lispro 0.2 – 0.4 1–2 3–5 Glucose transport (muscle, Glycogenolysis
• Insulin Aspart 0.2 – 0.4 1 – 1.5 3–5 adipose tissue)
• Insulin Glulisine 0.3 – 0.5 1–2 2-4 Glucose phosphorylation
Short acting Glycogenesis
• Regular (soluble) insulin 0.5 – 1 2–4 6-8 Glycolysis
Intermediate acting Pyruvate dehydrogenase activity
• Insulin Zinc (Lente) 1–2 8 – 10 20 – 24 Pentose phosphate shunt
• NPH / Isophane 1–2 8 – 10 20 - 24 LIPID METABOLISM Lipolysis
Long acting TG synthesis Lipoprotein lipase (muscle)
• PZI (ultra lente) 4–6 14 – 20 24 – 36 FA synthesis (liver) Ketogenesis
• Insulin Glargine 2–4 5 – 12 24 Lipoprotein lipase activity (adipose FA oxidation (liver)
Premixed insulin tissue)
PROTEIN METABOLISM Protein degradation
• 70/30, 50/50, 75/25 < 0.25 1.5 10 - 16
AA transport
• NPH / Regular Protein synthesis
• In a 70 kg patient, 1 unit of regular insulin lowers the glucose by
25-30mg/dL. (1.5 mmol/L). Short acting regular insulin should always
be used for immediate control of hyperglycemia.
INHALED INSULIN:
• A novel method for delivering a pre-prandial powdered form of insulin
by inhalation.
• Rapid onset of action with peak insulin level in the blood at 30-60
mins (Average – 49 mins).
• Duration of action longer
• Bioavailability is 10%, 300 – 400 U insulin inhaled per day.
• Administered 10 mins prior to meals
• 1 mg of inhaled insulin = 3 U of s/c insulin
• Side Effects – cough, sore throat, shortness of breath, dry mouth.
51

SOMOGYI PHENOMENON: INTRAOPERATIVE GLYCEMIC CONTROL

• Rebound hyperglycemia in response to nocturnal hypoglycemia Measure random sugar preoperatively
manifesting as fasting hyperglycemia • 4 hourly for TYPE 1 DM
• Rx: Reducing the night dose of insulin • 8 hourly for TYPE 2 DM
DAWN PHENOMENON: • Test urine for ketones and sugar whenever necessary
• Fasting hyperglycemia due to nocturnal surge of GH release or • Place first on operating list
increased clearance of insulin in the morning. • Aim for blood glucose of 100 – 180 mg/dl (6-10mmol/l
• Rx: Increasing the night dose of insulin MINOR SURGERY:
PERIOPERATIVE ANESTHETIC GOALS: • Shift from long acting OHA or insulin to short acting OHA or insulin.
• The main concern for the anesthesiologist in the perioperative • NPO for 8 hours preoperatively.
management has been avoidance of harmful hypoglycemia, • On the morning of the surgery – place first on the list
although mild hyperglycemia is acceptable. • Skip OHA
AVOID • If FBS < 80 mg/dl – infuse D5W.
• Hypoglycemia • 120 mg/dl – infuse NS.
• Hyperglycemia CONDUCT ANESTHESIA
• Ketoacidosis • Resume OHA or insulin with first meal.
• Fluid and Electrolyte disturbances. MAJOR SURGERY:
AIM is to mimic normal metabolism as closely as possible. All Type 1 DM & Type 2 DM who are poorly controlled.
INTRAOPERATIVE THREATS • Admitted 2-3days before surgery
• Hemodynamic instability • Thorough preoperative evaluation
• Hypoglycemia • Switch over to IV insulin bolus / infusion
• DKA • Correction of metabolic and electrolyte abnormalities
• Lactic acidosis • Close perioperative monitoring
• Silent MI • Blood Glucose and potassium 1 hour preoperatively and the 2 hourly
• CVA from the start of infusion, at least once during surgery, at least once
• ARF in the recovery area, 2 hourly postoperatively
INTRAOPERATIVE MONITORING: Change patientʼs treatment from OHA to soluble insulin in case of;
Minimizes morbidity and mortality • Uncontrolled type 2 diabetes mellitus
• Pulse oximetry • During major surgeries – ex. bowel anastomosis, Thoracotomy
• During CPB/CABG
• ECG
• Gestational DM
• ETCO2 • Critically ill patients
• Temperature • Ketoacidosis
• Non invasive / Invasive BP • Uncontrolled infections
• Blood glucose – hourly
• Electrolytes – 4th hourly
• Urine output. 52

Management regimens: ! "#!$!%!"&!'()*+'(!!

• There is no consensus about the optimal way to manage
perioperative metabolic changes in diabetic patients; many
options are available. Factors to consider in selecting a plan
include the type of DM, how aggressively euglycemia will be
sought, whether the patient takes insulin, whether the surgery is ,--.+!/!01!!
minor and in an ambulatory unit, whether the surgery is elective
or an emergency, and the ability of hospital resources to safely
administer a complex plan. The goal of any regimen should be to
minimize metabolic derangements and, most obviously, to avoid
hypoglycemia.
I. The VELLORE REGIMEN for Glucose – Insulin infusion (Rule of
1-2-3-4) II. CONTINUOUS INSULIN INFUSION (CII) protocol
Blood glucose Regimen Initiating CII
(mg/dl) • Prepare solution – 1 U / 1ml of 0.9% NS
< 70 Stop insulin, administer 100 ml D5W rapidly. • Start CII when blood glucose > 140mg/dl
Measure blood glucose after 15 minutes. • Initial rate – blood glucose(mg/dl) / 100, then round to nearest 0.5 U
71 – 100 Stop insulin, infuse D5W @ 100 ml/h Insulin infusion rate change
Blood glucose(mg/dl) Instructions
101 – 150 1 U insulin + D5W 100 ml/h
> 200 ↑ rate by 2U/h
151 – 200 2 U insulin + D5W 100 ml/h
> 160 - 200 ↑ rate by 1U/h
201 – 250 3 U insulin + D5W 100 ml/h > 120 - 160 ↑ rate by 0.5U/h
251 – 300 4 U insulin + D5W 100ml/h 80 - 120 No change in rate
> 300 1 U insulin for every 1 – 50 mg > 100 mg/dl + 60 – 80 If < 10% lower blood glucose,↓ rate by 1U/h
100 ml/h of NS. If > 10% lower blood glucose, ↓ rate by 50%,
Check BG within 30 mins
• K+ is not added to keep the regimen simple. Routine K+ < 60 Stop infusion
supplementation is not required for short surgery as dose of Give IV Dextrose 12.5g (25ml of 50%D)
insulin is not large. Check BG within 30 mins
Advantages: Restart infusion at 50% of previous rate
• Simple
• Safe
• Inexpensive
• User friendly
53

Patient monitoring Disadvantages:

• Check capillary Blood Glucose every hour until it is within goal • Throws more heat than light
range for 2 hours, and then reduce it to every 2 hours. • Hypertonic 10% glucose has to be infused through a central line
• Treatment of Hypoglycemia • Strict ECG monitoring during K+ infusion
III. GLUCOSE–INSULIN–POTASSIUM (GLIK) or ALBERTI Regimen • High dose of insulin is administered
(Rule of 5-10-15-20) TIGHT GLYCAEMIC CONTROL:
• Suitable for patient who are likely to be remain NBM for < 48h. • Maintenance of blood sugar level between 78-110 mg/dl is
• Single combined infusion of soluble insulin & glucose. associated with a better outcome. Hence it is desirable to maintain
• Safe and easy to administer the blood glucose levels between 120 – 180 mg/dl during the
• Main drawback – new bag is needed every time the Blood perioperative period.
Glucose, potassium falls outside the desired range INDICATIONS:
! "#$!%!! • Type 1 DM
*! Type 2 DM – major surgery, bowel anastomosis
"#&&'(!) •
"#+,-./0(1.! • During CPB / CABG
• Gestational DM
• Critically ill
ADVANTAGES
"##&(!2!34!! • Maintenance of normal leucocyte and macrophage function
• Fewer blood stream infections
• Improved wound healing
• Insulin induced beneficial trophic changes in skin and mucosal
barriers.
• Enhanced erythropoeisis or reduced hemolysis.
• Reduced cholestasis.
Soluble • Direct anabolic effect of insulin on respiratory. Muscles function there
Blood Glucose mg/ by facilitating weaning.
insulin (U/ Sr.K (mmol/l) KCl (mmol / bag)
dl / (mmol/l) • Less hyperglycemic injury of neuronal axons.
bag)
< 70 (< 4.0) 0 • Less axonal dysfunction and degeneration associated with
71 – 110 (4 – 6) 5 <3 20 hyperglycemia and insulin deficiency.
111 – 180(6 – 10) 10 3-5 10
181-360(10 – 20) 15 >5 0
>360 (> 20) 20
54

• K-),&,1+/&2#!@#
• G"1,17&224#122##
)'.)&*)/0,$$
• @&1/,-/&/7-#+L#/+"'&2#2-D7+74,-#&/8#'&7"+>0&3-#LD/7,1+/#
DISADVANTAGES: ANESTHETIC PLAN:
•• M-;-"#F2++8#),"-&'#1/L-7,1+/)#
Increased risk of Hypoglycemia OPTIONS
• .'>"+N-8#;+D/8#0-&21/3##
Glycemic targets should be appropriate to age and physical • Regional Anesthesia: Spinal / Epidural
condition of patient.
• ./)D21/#1/8D7-8#F-/-L171&2#,"+>017#70&/3-)#1/#)O1/#&/8#'D7+)&2#F&""1-")<#• Peripheral nerve blocks
Strict glycemic control is inappropriate in: • General Anesthesia
• 9/0&/7-8#-"4,0"+>+-1)1)#+"#"-8D7-8#0-'+24)1)<#
• Those with impaired awareness of hypoglycemia • TIVA
•• P-8D7-8#70+2-),&)1)<#
Very young and very elderly ANESTHETIC TECHNIQUE OF CHOICE:
•• !1"-7,#
Severe&/&F+217# -LL-7,# +L#
macrovascular 1/)D21/# +/# "-)>1"&,+"4<# @D)72-)# LD/7,1+/# •,0-"-#
complications F4# techniques are to be preferred whenever the situation
Regional
L&7121,&,1/3#;-&/1/3<#####################
Initiation of tight control: permits.
• NBM after midnight
• Q-))#04>-"3247-'17#1/CD"4#+L#/-D"+/&2#&R+/)<# ADVANTAGES:
6AM-FBS
• • Q-))# &R+/&2# 84)LD/7,1+/# &/8# 8-3-/-"&,1+/# &))+71&,-8# ;1,0# 04>-"3247-'1&# • Epidural
&/8# and spinal anesthesia blocks the stress response to surgery
• First on list (T4 – S5 level)
1/)D21/#8-L171-/74<#
• Omit morning insulin • Avoidance of difficult intubation & pulmonary aspiration
'%,)'.)&*)/0,-$
• 2 lines - Piggyback insulin (50u/250ml NS) • Awake patient to warn of impending hypoglycemia
5% dextrose
• • ./7"-&)-8#"1)O#+L#S4>+3247-'1&# • Early return to normal eating, less nausea & vomiting
• Infusion of 5% dextrose with insulin according to formula • Excellent analgesia
/1234563$789:47;$;<=>1?$@4$8AA9=A96874$7=$8:4$8B?$A<2;6381$3=B?676=B$=C$A8764B7D$
DISADVANTAGES:
6,"17,#3247-'17#7+/,"+2#1)#1/&>>"+>"1&,-#1/T# • Episodes of sudden bradycardia and hypotension à Unresponsive to
• =0+)-#;1,0#1'>&1"-8#&;&"-/-))#+L#04>+3247-'1&# atropine and ephedrine.
• U-"4#4+D/3#&/8#N-"4#-28-"24# • Exacerbation of peripheral neuropathy
• 6-N-"-#'&7"+N&)7D2&"#7+'>217&,1+/)# • Infection – epidural abscesses
• Vascular damage
%B676876=B$=C$76:<7$3=B79=1-$ GENERAL ANAESTHESIA:
• *I@#&L,-"#'18/130,## 1. Risk of aspiration - acid aspiration prophylaxis. Premeditation –
• V$@5MI6# metoclopramide, pantoprazole.
• M1"),#+/#21),## 2. Rapid Sequence Induction with thiopentone and Scoline
• W'1,#'+"/1/3#1/)D21/# 3. Maintenance of Sellickʼs maneuver
Hemodynamic instability during induction
• A#21/-)##5#H1334F&7O#1/)D21/#XYZDJAYZ'2#*6[##
• Tachycardia, hypertension – Attenuated by IV xylocard.
• Y\#8-R,"+)-##
• • Hypotension, Sudden bradycardia.
• ./LD)1+/#+L#Y\#8-R,"+)-#;1,0#1/)D21/#&77+"81/3#,+#L+"'D2&## • Difficult laryngoscopy and intubation: tools for difficult intubation to be
• M+"'D2&#5# # kept ready.
$
::# 55
;;;<!"$%&'<7+'###############################################################################Endocrinology #
#
High dose opiate anesthetic techniques produce not only CAUSES FOR FAILURE TO REGAIN CONSCIOUSNESS:
hemodynamic, but also hormonal and metabolic stability. These • Hypoglycemia
techniques effectively block the entire sympathetic nervous system • Diabetic Ketoacidosis in late stages
and the hypothalamic-pituitary axis, probably by a direct effect on • Hyperglycemic, hyperosmolar nonketotic coma
the hypothalamus and higher centers. Abolition of the catabolic • Lactic acidosis (late stages)
hormonal response to surgery, will therefore, abolish the • Cerebrovascular accidents
hyperglycemia seen in normal patients and may be of benefit in • Silent MI with pulmonary edema
the diabetic patient.
Fluid and volume Replacement: DIABETIC patient in Ketoacidosis coming for emergency surgery, (ex.
• Ringer Lactate (RL) is an inappropriate solution for diabetics as it Diabetic foot)
contains 28 mEq/L of lactate which is a gluconeogenic substrate, Symptoms Signs
and may aggravate the stress induced hyperglycemia. Nausea/vomiting Tachycardia, hypotension
• Saline or other non lactate containing crystalloids are preferred Thirst, polyuria Dehydration
for 3rd space replacement. Banked blood contains variable
Abdominal pain Tachypnea / Kussumalʼs
amounts of lactate derived from anaerobic metabolism during
storage. Insulin requirements may increase significantly after Shortness of breath Abdominal tenderness
large transfusions. Lethargy/ obtundation/ coma
INTRA-OPERATIVE HYPOGLYCEMIA: Precipitating events Diagnostic criteria
Detection and management Inadequate insulin administration pH < 7.3
Hypoglycemia is defined as blood glucose < 4 mmol/L (50mg/dl), < Infections HCO3 < 15 mmol/L
30 mg in children. Infarctions Blood Glucose > 250 mg/dl (>14
• Under Spinal Anesthesia – sweating, restlessness, thirst,
Drugs mmol/L)
confusion, anxiety, tremor, tachycardia, hypotension, convulsions
and coma. Pregnancy Serum ketones positive
• Under General Anesthesia – unexplained tachycardia,
hypertension, pupillary dilatation, sweating, RBS by glucometer.
Treatment –
• 50 ml of 25% D / 25 ml of 50% D
• (Each ml of 50 % D will raise the blood glucose by approximately
2 mg/dl)
• Additional boluses or infusions (5-10%D) may be administered in
severe or recurrent hypoglycemia. Glucagon 1 mg IM or IV is an
alternative to IV glucose and produces a response in 15-30 mins.
56

DKA HHS Denominator 100 if on steroids, obesity, infection, etc.

Glucose (mg/dl) 250 – 600 600 – 1200 Preparation – 50 units insulin added to 500 ml NS.
IV. Potassium:" "
Sodium ( mEq/L) 125 – 135 135 - 145
• > 5.5 = No K+
Potassium (mEq/L) Normal / increase Normal
• 3.5 – 5.5 = K+ 20 mmol
Phosphate Decrease Normal • < 3.5 = K+ 40 mmol
Creatinine ( mg/dl) Slightly increased Moderately increased V. Sodium bicarbonate:
• Most often not required. Acidosis gets corrected after starting insulin
Osmolality (mOsm/L) 300 - 320 330 - 380
infusion.
Plasma Ketones ++++ +/- • When " pH < 7.1
Sr. HCO3 < 15 mEq/L Normal to slightly –
• HCO3 < 10 MEq/L. 1 ml/kg of 8.4% NaHCO3
decreased NaHCO3 administration and rapid reversal of acidosis:
Arterial pH 6.8 – 7.3 > 7.3 It worsens intracellular acidosis, paradoxical CSF acidosis,
Arterial pCO2 20 - 30 Normal hypokalemia,
Reduced tissue oxygenation
(mmHg)
Impair cardiac function
Anion gap Increased Normal to slightly
• Increase hyperosmolarity and systemic alkalosis
increased • IF pH < 7.0, 50 mmol/l of sodium bicarbonate in 200 ml of sterile
water over 1 hr.
Protocol for the management of diabetic Ketoacidosis: • Mortality rate from DKA 5 – 10%, usually secondary to late
I. Volume of fluids: complications such as MI, infection or cerebral oedema (children),
!"#$%&'()#*+,-)#./#$/-),0-)1+2+34######
• 1st 30 min – 1 ltr venous !"##$
thrombosis, ARDS.
• Next 1hr – 1 ltr ANESTHETIC OPTIONS FOR DIABETIC FOOT:
• Next 2 hrs – 1 ltr
56-7+/8#981,1+/
II. Nature of fluid: if Na+ •
#
• TIVA
TIVA
– ketamine in the absence of hypertension, IHD.
– propofol
• # > 155 MEq/dl, infuse 0.45% NS. • Low unilateral spinal in the absence of autonomic neuropathy
< 140 MEq/dl infuse 0.9% NS.
• .?#@2++8#32A7+)-#B#CD;#'3E#1/?A)-#DE#!># • GA – N2O / O2 / Halothane – spontaneous ventilation
If blood glucose < 250 mg% infuse 5% D.
• ...>#./)A21/F# • Balanced Anesthesia technique
III. Insulin:
# G+2A)F#:;#A/1,)#.H#I;>:D#A/1,)JK3L#
• Bolus: 10 units IV (0.15 units/kg)
• # Infusion:
./?A)1+/F#;>:#A/1,JK3J0"#
0.1 unit/kg/hr.
M&,-#+?#1/?A)1+/#I?+"'A2&L#N# #
!-/+'1/&,+"#:;;#1?#+/#),-"+18)O#+@-)1,4O#1/?-7,1+/O#-,7>#
P"-Q&"&,1+/#N#D;#A/1,)#1/)A21/#&88-8#,+#D;;#'2#*6># 57
.H>#P+,&))1A'F# # R#D>D#S#*+#TU#
Dr# Azam’s
# Notes# in Anesthesiology
# <>D#N#D>D#S#T
2013U#C;#''+2#
# # # # B#<>D#S#TU#V;#''+2##
GESTATIONAL DIABETES: ANESTHETIC CONSIDERATIONS:

• Defined as hyperglycemia diagnosed for the first time in • Altered utero-placental blood flow
pregnancy • Altered buffering capacity in newborns
Screening for gestational diabetes • Decreased epinephrine responses to hypoglycemia during sleep, GA
Gestation Fasting venous plasma glucose • DKA
concentration • Hypertension – PE
Up to 20 wks > 105 mg/dl • Stiff joint syndrome
20 – 40 wks > 120mg/dl • Requires relatively high doses of insulin
• Insulin requirement falls dramatically after the delivery of placentaà
Class Fasting plasma 2 h postprandial therapy appropriate adjustments
glucose(mg/dl) glucose(mg/dl) ANESTHETIC MANAGEMENT:
A1 < 105 < 120 diet Obstetrical analgesia - Lumbar epidural block
• Excellent pain relief
A2 > 105 > 120 insulin • ↓ maternal endogenous catecholamines during labour – benefit
placental circulation
INTRAPARTUM MATERNAL GLYCEMIC CONTROL
• A Valsalva maneuver during 2nd stage is contraindicated –
Plasma capillary Infusion rate Fluids predispose to virtual hemorrhage.
glucose (mg/dl) 25 U in 250 ml NS
• Awake state
< 80 Insulin off 5% D @ 125 ml/h (6.5 • Less fetal acidosis
Anesthesia for LSCS:
g glucose/h)
• Well controlled spinal or Graded epidural with particular attention to
80 – 100 0.5 5%D /RL
avoiding hypotension, hypoxia
101 – 140 1.0 5% D / RL • Volume preloading by dextrose free solution before induction of
141 – 180 1.5 NS anesthesia
181 – 220 2.0 NS • Hypotension treated promptly with IV ephedrine
> 220 2.5 NS • Prompt left uterine displacement
General anesthesia:
• Acid aspiration prophylaxis
• Preliminary denitrogenation with 100% oxygen for 5 minutes
• Rapid sequence induction with 3-5mg/kg of thiopentone, Scoline
50-100 mg.
• Maintenance with nitrous oxide/oxygen/muscle relaxant
• Reversal: neostigmine + atropine / glycopyrrolate
58

NEWER CONCEPTS: Kindly Note:

• Pancreas transplantation • Each 50% of 1 ml of dextrose will increase blood glucose to 2 mg/dl
• Islet cell transplantation • One unit of regular insulin will decrease blood glucose by 25 to 30 mg/dl
• Insulin subcutaneous pumps.
• Battery driven, pumps implanted subcutaneously in the abdomen
or the chest to deliver insulin by IV route continuously.
Complications:
• Ketosis due to pump failure
• Abscess formation
Artificial pancreas (Closed loop controller)
• Systems have been devised that can infuse glucose and insulin,
as determined by an on-line glucose analyzer. Such systems are
capable of very tight control to any stated blood glucose
concentration. In most cases, such complexity is unnecessary
and probably introduces more hazards than benefits. However,
in cardiac surgery involving extracorporeal circulation, when
insulin requirements may be very large, they may have a place.
They are, however, complex, expensive, demanding of technical
supervision, and not yet a practicable proposition outside the
research environment.
CONCLUSION:
• Perioperative management of diabetes is generally more art than
clinical science. Circumstances governing glucose homeostasis
during this period are highly variable and unpredictable. Better
glycemic control in diabetic patients undergoing major surgery
has been shown to improve perioperative mortality and morbidity.
Though there are myriad protocols, none with any clear
superiority, clinical judgment, intensive monitoring remains the
key component in the perioperative treatment of diabetic
patients.
59

12. Hyperthyroidism. Dr Azam’s Notes in Anesthesiology 2013
DEFINITION OF HYPERTHYROIDISM Iodide trapping:

• Hyperthyroidism is a clinical state resulting from excess of • Essential raw material → iodine.
thyroid hormones (T3 & T4 / both) 5-15 times the normal. Source: Sea fish, bread, milk, vegetables and drinking water.
• Majority of the cases have an initial phase of excess of T3 GUT
production followed by an overproduction of both T3 and T4.
!"#$%&'()#*+,-)#./#$/-),0-)1+2+34######
• Iodine → iodide → absorbed from upper GIT → blood. !"##$
PHYSIOLOGY OF THYROID
• Normal dietary intake is 100-200 µg/day.
Thyroid secretes 3 hormones and consists of 2 types of Secretory
cells.
56-7+/8#981,1+/
• If it is < 50 µg/day for long periods → leads to I2 deficiency.#
1. Follicular cells: Secretes tri-iodothyronine (T3) and # • The ability of thyroid gland epithelial cells to concentrate iodide
tetraiodothyronin (T4) which stimulates BMR. Psychic growth of • above concentrations
?0-# &@121,4# present
+A# ,04"+18# 32&/8# in plasma
-B1,0-21&2# 7-22)#is,+#
referred to as 1+818-#
7+/7-/,"&,-# iodide&@+C-#
trapping.
7+/7-/,"&,1+/)#B"-)-/,#1/#B2&)'&#1)#"-A-""-8#,+#&)#1+818-#,"&BB1/3>##
the individuals.
2. Parafollicular cells: Secretes thyrocalcitonine which promotes •• ?04"+18# gland
Thyroid 32&/8# contains
7+/,&1/)# 5-7
D5E# mg
'3#mostly
'+),24#in1/#the,0-#form of iodinated
A+"'# AA $$#
+A# 1+81/&,-8#
(Iodothyronine and Iodothyroxin)
F.+8+,04"+/1/-#&/8#.+8+,04"+G1/H#
deposition of calcium salts in skeletal and other tissues, tends to
of 5-7 mg of iodide
•• +A#D5E#'3#+A#1+818-##
produce hypocalcaemia.
FORMATION AND SECRETION OF THYROID HORMONE:
#
Steps involved in synthesis of hormones:
Iodide trapping in thyroid gland by Na+/I- pump # # DI# # ###<DI#
↓
Oxidation and iodination of tyrosine # ./,"&7-22J2&"#)B&7-#+A## # ################9G,"&7-22J2&"#)B&7-#
↓ by peroxidase enzyme # K+2217J2&"#-B1,0-21J'#
Binding of Iodine with tyrosine to from iodotyrosines
# # # # # # # #
↓ by tyrosine iodinase
Coupling of monoiodotyrosine and dioiodotyrosine to from T3& T4
↓ ###################################################################################LMN####################:MN#
Hormone storage as part of thyroglobulin
# # #
↓
Proteolysis and release of T3& T4 # # # # # # #####./&7,1C-######################F$7,1C-H#
# # # # # # F.+8+,4"+)1/-)H# F.+8+,04"+G1/-H#
90%"→T4
•
5# <;I# !?O#
10%"→
• T3
5# T4
• is de-iodinised
:;I# !#?N# to form T3 when it comes in contact with target
tissue, hence the hormone finally delivered and used by tissue is T3
• which is physiologically important hormone.
?O#1)#8-1+81/1)-8#,+#A+"'#?N#=0-/#1,#7+'-)#1/#7+/,&7,#=1,0#,&"3-,#,1))J-P#0-/7-#
,0-#0+"'+/-#A1/&224#8-21C-"-8#&/8#J)-8#@4#,1))J-#1)#?N##=0170#1)#B04)1+2+317&224#
1'B+",&/,#0+"'+/-##
60
!%$ &'()*+(,-$ ,.$ (,)()/$ (,-0#Q+/C-")1+/#+A#1+818-#1+/)#1/,+#&/#+G181%-8#A+"'#+A#1+81/-#
@4#-/%4'-#B-"+G18&)-#
1%$ 2,)(-*+(,-$ ,.$ +34,5(-/$ *-)$ .,46*+(,-$ ,.$ +734,()$ 7,46,-/0$ .+81/-# @1/8)# =1,0#
• Oxidation of iodide ion: Conversion of iodide ions into an • STORAGE OF THYROGLOBULIN:

oxidized form of iodine by enzyme peroxidase • Each thyroglobulin molecule contains 1-3 tyrosine molecule and
• Iodination of tyrosine and formation of thyroid hormone: an average of 1T3 molecule for every 10 molecules of T4.
Iodine binds with 1/6th of thyrosine A.A within thyroglobulin • Potency → T3: T4 → 3-5: 1
molecule assisted by an enzyme thyrosine iodinase to form MIT Secretory ratio → T4: T3 → 10-20: 1
and DIT, neither of which has hormonal activity. The binding of I2 Plasma concentration → T4: T3 → 2:1
with thyroglobulin is called organification of thyroglobulin. T3-20% secreted
Combination of 2 DIT molecule → T4 -80% by peripheral conversion of T4 → T3.
One MIT and one DIT → T3 I" - coupling reaction. • PROTEOLYSIS AND RELEASE:
• Release is initiated by the action of TSH → promotes formation of
TRANSPORT OF THYROID HORMONES: pseudopodia on follicular cells.
• Thyroid hormones on entering the blood stream become firmly • The pseudopodia engulfs colloid droplets, enter the cells by
bound to plasma protein. endocytosis, lysosomes fuse with colloid droplets to form
• T4 → 99.95% bound → 0.05% is free, of which phagolysosomes on which proteases are released.
TBG → 75% (thyroxine binding globulin) • These enzymes liberate iodothyronine and iodothyroxin from
TBPA → 15-20% (thyroxine binding pre-albumin) thyroglobulin which enters blood stream.
Albumin → 5-10%.
• T3 → 99.5% bound to TBG CONTROL OF THYROID FUNCTION:
0.5% unbound free T3 → contribute to biological activity of T3. TRH (hypothalamus)
• None to TBPA ↓
Very little to albumin TSH (anti-pituitary)
T3 is quick acting within few hours ↓(-ve feed back mechanism)
T4 acts more slowly 4-14 days Thyroid
T ½ of T4 → 7 days Vd" → T3 → 35-45 Lts ↓
T ½ of T3 → 1 day" → T4 → 10-12 Lts T3 &T4
• Total serum concentration
• T4 →
T3 →
TSH →
T4 → long latent period, activity begins by 2-3 days peaks by 10-12
days
T3 → activity begins within 6-12 hrs, peaks by 2-3 days.
61

THYROID FUNCTIONS: Goitrogens:

1. ↑BMR - except-brain, thymus lungs, • Iodine deficiency"
2. Activates Na+/K+ ATPase Vegetables - cabbage, soya bean
3. Thermogenic effect Drugs – PAS, anti-thyroid drugs
4. Essential for bone growth Genetic factors – with deficiency of enzymes, concerned with
5. Neurological tissue maturation → myelination production.
6. Metabolic effects. Causes of thyrotoxicosis:
CHO metabolism: 1. Primary hyperthyroidism
• Physiological dose → potentiates insulin (Glucogenesis) • Graves disease (primary thyrotoxicosis)
• Pharmacological dose → glycogenolysis, gluconeogenesis → • Toxic nodular goiter
utilization of glucose. • Multi-nodular (Plummer disease)
o Single toxic adenoma
• Fat:" Lipolytic effect more than lipogenic effect ↓ LDL.
o Functioning thyroid carcinoma metastasis
o Drugs: iodine excess (JOD – based-dow phenomenon)
Vitamin:
o Stroma ovaries."
• Required for sequestration of Vit. A.
2. Thyrotoxicosis without hyperthyroidism
• CVS:Hyperdynamic state ↑ HR, contractility and CO, fast
• Sub-acute thyroiditis
bounding pulse
• Ingestion of excess thyroid hormone.
• CNS:Anxiety nervousness, tremors, hyper-reflex seen in 3. Secondary hyperthyroidism
hyperthyroidism. • TSH - secreting pituitary adenoma
Mental retardation, cretinism seen in hypothyroidism. • Gestational thyrotoxicosis
• GIT:Constipation seen in hypothyroidism , • Chorionic - gonadotropin - secreting tumours.
Diarrhea seen in hyperthyroidism.
Other regulations of TSH: • Clinical features of hyperthyroidism:
↑ TSH secretion due to • Thyroid hormones cause uncoupling of oxidative phosphorylation so
• Oestrogen that energy cannot be stored and heat production increases.
• Large doses of iodide (because it inhibits T4 and T3 release and 1. Goiter
thereby U ↓↓T4 and T3). • Diffuse
• Somatostatin. • Nodular
↓TSH secretion due to 2. Neuromuscular
• DOPA • Nervousness, irritability, emotional liability tremors of hands/tongue.
Dopamine • Hyper-reflexes, ill sustained myopathy
Bromocriptine. • Associated with periodic paralysis
62

3. Ocular 8. Others
• Lid retraction, lid lag • Heat intolerance
• Grittiness, excessive lacrimation • Fatigue, apathy
• Chemosis • Gynaecomastia, lymphadenopathy
• Exophthalmos, corneal ulceration • Thirst
• Ophthalmoplegia, diplopia • Osteoporosis
• Papilloedema, loss of visual acuity. • In the elderly patients, features of thyrotoxicosis may be subtle or
4. Cardio-respiratory: masked
• Palpitations, sinus tachycardia (increased sleeping pulse rate) • Patients may present with heart failure due to papillary dysfunction
• Increased pulse pressure, systolic hypertension and AF without any other signs and symptoms.
• Ankle oedema in absence of cardiac failure Differences between primary and secondary thyrotoxicosis:
• Stages of development of arrhythmias are Primary Secondary
• Multiple extrasystoles
Goiter diffuse vascular Nodular
• Paroxysmal atrial tachycardia
Paroxysmal atrial fibrillation Onset – abrupt, swelling appears Insidious, nodular goiter present
•
• Persistent AF not responding to digitalis. with hyperthyroidism before hyperthyroidism
5. GIT Thyrotoxicosis – more severe Hyperthyroidism less severed
• Weight loss despite normal or increased appetite. CVS – rare involvement Present with CCF or AF
• Diarrhea and staetorrhoea Other signs – orbital proptosis Eye signs rare
• Anorexia, gastritis, vomiting. pretibial myxoedema
6. Dermatological
• Increased sweating, pruritis.
• Palmar erythema, spider naevi
• Separation of finger nail from nail bed (Plummerʼs nail)
• Alopecia, pigmentation, vitiligo, digital clubbing
• Pretibial myxoedema
7. Reproductive system
• Amenorrhea / Oligomenorrhea
• Infertility, spontaneous abortion
• Loss of libido, impotence
• Pregnancy is associated with increased low birth weight infants
and pre-eclampsia.
63

Diagnosis of thyrotoxicosis: Index:

Usually diagnosed by clinical signs Wayneʼs diagnostic index • < 11"" " :" Non toxic
Symptoms Present Absent • Between 11-19" :" Equivocal
Dysponoea on effort +1 • > 19"" " :" Toxic
TREATMENT OF THYROTOXICOSIS:
Palpitation +2 Includes:
Tiredness +2 1. Antithyroid drugs
Nervousness +2 2. β -adrenergic blockers and other antihypertensive drugs
3. Radioactive iodine
Excessive sweating +3
4. Surgery
Decreased appetite -3 Antithyroid drugs:
Increased weight -3 Indications:
• In children
Decreased weight +3
• In young adults with mild thyrotoxicosis
Preference to heart -5 • Conjugation with radioactive iodine to hasten recovery, while awaiting
Preference to cold +5 the effects of radiation.
Indifferent to temp 0 • In pregnant women
CLASSIFICATION:
Signs Present Absent a. Inhibit hormone synthesis (Antithyroid drugs)
Finger tremors +1 " Propylthiouracil, Methimazole, Carbimazole.
Lid lag +1 b. Inhibit iodide trapping (ionic inhibitors)
" Thiocyanate, perchlorate, nitrates.
Moist hands +1 c. Inhibit hormone release
Lid retraction +1 " Iodine, iodides of Na and K, organic iodide.
Exophthalmos +2 d. Destroy thyroid tissue
Radio-active iodine (131I, 125II, 123I )
Bruit over thyroid +2
Miscellaneous:
Palpable thyroid +3 a. Lithium → inhibits thyroid hormone release.
Hyperkinetic movements +4 b. Amiodarone → Inhibits peripheral conversion of T4 to T3 and interferes
with thyroid hormone action.
Atrial fibrillation Present Absent c. Sulfonamides, paraminosalicylic acid: Inhibit thyroglobulin iodination and
Heart rate 80/min +3 -3 coupling reaction.
80-90/min, d. Phenobarbitone, phenytoin, carbamazepine, rifampicin → induce
metabolic degradation of T4/T3.
> 90/min
64

#
Hyperthyroidism.Continuation:
$
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ANTITHYROID DURGS: Drugs Dose Frequency Adverse
23456789:$;<$%4=8;71$
Mechanism of Action: Effects
:=# >?;@AB=58;C?648B1# Propylthiouracil 100-150 mg 6-8th hrly
# # # # # >?18&,1+/#&/8#1+81/&,1+/#+@#,4"+)1/-# Methimazole 10-15 mg 8th hrly
# A"-B-/,)C# # # D+EA21/3#
Carbimazole 10-20 mg 8th hrly
# # # # # F-"1A0-"&2#7+/B-")1+/#+@#GH#,+#GI#
KI/Na I 60 mg 8th hrly
#
# Lugolʼs iodine (5% 0.3 ml (3 drops) 8th hrly
J=# 23=58:6D;B31# iodine in 100ml of 10%
KI solution)
# # # # # #
Propranolol 40-80 mg 6th hrly
#################################################################>?18&,1+/#&/8#1+81/&,1+/#+@#,4"+)1/-#
# # T3 5 µg/day 6th hrly to have its
##########F"-B-/,)C# effects. T ½ → 1 day
########### # T4 100 µg/day 10 days to have its
D+EA21/3# effect T ½ → 7 day
I=# E(F$&6F$(;G8G31#
Adverse Effect:
# # # # # >?18&,1+/#&/8#1+81/&,1+/#+@#,4"+)1/-#
• Starts to appear after 2-4 weeks of treatment
# A"-B-/,)C# Rashes -2%"
# # # # # K-2-&)-#+@#,04"+?1/# Agranulocytosis - 2%
# • Initially symptoms of sore throat or oral candidiasis may be noticed.
!"#$%$ !&%'$ ("')#'*+,$ -./'"%'0122'+3%$
Patient is advised to stop drug immediately.
!"#$%&'()#*"+,)&- .//0.1/-23- 405 -("&%-
'( -
67'()2+8#&7- ./0.1-23- 5 -("&%-
'( - Iodides: Prevents
9+":)2+8#&7- ./0;/-23- 5'(-("&%- - • Oxidative iodination of tyrosine (wolf-chaikoff effect – Thyroid
Constipation)
<=>?+-=- 4/-23- 5'(-("&%- -
• Release of thyroxin
@*3#&AB-)#C)D7-E1F-)#C)D7-)D- /IJ-2&-EJ-C"#$BH- 5'(-("&%- -
.//2&-#G-./F-<=-B#&*')#DH-
!"#$"+D#&#&- K/05/-23- 4'(-("&%- -
LJ- 1-M3>C+%- 4 - ("&%- '#- (+N7- -
'(
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LK- .//-M3>C+%- ./- C+%B- '#- (+N7- -
)'B- 7GG7,'- L- O- !- 65
P-C+%-
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High dose prevents effect of TSH on gland: Advantages of ATD:

• Reduces vascularity of glands makes the gland firmer-facilitates • Well tolerated
removal • Rapidly effective
• Always used along with antithyroid drams • Euthyroid state maintained as long as desired with maintenance
• Mainly used in impending thyrotoxic crisis and severe cardiac dose .
disease • Therapeutic test in doubtful diagnosis.
• Given for 10-14 days prior to surgery. Disadvantages:
• 2 weeks- hyper secretion hypervascular IODIDE escape • Prolonged treatment and follow up
• Lugol's iodine -3-5 drops PO 8th hourly (SSKI) • Remission in 50%
• Ipodate-0.5 to 1g/day PO • Serious toxicity like agranulocytosis and aplastic anemia
• Alternative is Nal-0.25g 6th hourly-ice Radioactive iodine:
• If patients allergic to iodine, lithium carbonate 300mg, 6th hourly • Acts by destroying functioning thyroid cells or by inhibiting their ability
PO or per NGT tube inhibits hormone synthesis. to replicate.
Beta adrenergic blockade: • Emits β and γ rays
Mode of Action: • Patients should be rendered euthyroid ATD stopped, 48 hours
• Attenuates sympathetic nervous system activity before.
• Interferes with deiodination of T4 to T3 in peripheral circulation • Dose(µ) = Estimated thyroid wt (q) X planed dose (µ/g)
and tissue. Fractional 24 hr radio iodine uptake X 100
• Combination of β blocker and KI reliable control even in severe • Planned dose - 80-200pci/g
thyrotoxicosis. Dose 5-10 µ of 1131 therapy po
• Propranolol- 40-60 mg 6th hourly PO 2 weeks pre operatively Onset of action -3-4 weeks
• Nadolol-160mg OD Maximum effect-3-6 months
• Atenolol-25-100mg/day After 2 months further dose of 1131 given in 25% of patients
• Esmolol-100-200 µg/kg/min infusion. Follow up every 3 months up to 10 years
Glucocorticoids: Indications:
Prevents • Not responding to ATD or not fit for surgery
• Glandular release of T4 • Patients aged > 45 years
• Peripheral conversion of T4-T3 • Recurrence of hyperthyroidism after surgery
• Immune suppression • When associated with severe systemic disease contraindicating
• Dexamethasone 2mg iv 6th hourly thyroidectomy
• Hydrocortisone 40mg iv 6th hourly • Women can conceive safely 6-12 months after RI therapy.
66

Contra Indication: Pregnancy Local examination:

Advantages Disadvantages Inspection: Whether diffuse nodular swelling
Definitive treatment of Delayed control of thyrotoxicosis Pizzillo's method: In obese and short necked patient hands are
placed behind head and patient is asked to push head backwards
thyrotoxicosis transient exacerbation of
against her clasped hand.
ophthalmopathy Ask the patient to swallow, thyroid slowly moves upwards on
Rare, mild side effect Lower efficacy in large goiters deglutition.
No surgical risks High incidence of hypothyroidism Kocher's Sign: Starting and frightened appearance of eye which is
Easy to perform, fast Care should be taken while marked on attentive fixation. In retrosternal goiter lower border of
voiding swelling cannot be made out during deglutination.
Pemberton's sign: Patient is asked to raise both the arm over his
Expensive
head until they touch the ears. This is maintained for a while,
Non – availability an all centers congestion of face and distress becomes evident because of
obstruction of great veins at thoracic inlet.
Preoperative evaluation for hyperthyroidism: Palpation: Patient should be sitting on a stool and neck slightly flexed.
History: Lahey's Method: Examined in front, to palpate the left lobe, gland is
• History of onset, duration, rate of growth pushed to left from the right side by the left hand of examiner. This
• History suggestive of primary or secondary toxicity makes the left lobe more prominent.
• History of pain From behind: Patient is asked to flex neck, the thumbs of both hands
• History of palpitation, precordial pain, exhaustion are placed behind the neck and other four fingers are placed on each
• History of pressure effects- like dyspnoea, dysphagia, lobe and isthmus.
hoarseness of voice. Grile's method: For impalpable nodule, patient is asked to deglutinate
• Past history/family history. and nodule is felt.
• Personal history-diet, menstrual, mental attitude, sleep. Kocher's test: If pressure on trachea is suspected, slight push on
Physical examination: lateral lobes will produce stridor. Positive indicates obstructed trachea
GPE: from both sides. Carotid pulsation is usually felt laterally and
• Built, nourishment backwards.
• Fullness of thyroid region, pallor, icterus, cyanosis, clubbing, Berry's Sign: Absence of carotid pulsation due to malignant swelling
oedema engulfing carotid sheaths.
• Temperature, sleeping, pulse rate, blood pressure Percussion: Clear manubrium sterni to exclude presence of a
• Skin- hot and moist palm retrosternal goiter.
• Tremors Auscultation: A systolic bruit may be heard over goiter due to
• Mental status-anxiety, nervousness. increased vascularity in primary toxic goiter.
Lymph nodes: All LNS are palpated.
67

Examination for toxic manifestation: Airway assessment:

1. Exophthalmos: In early stages, may be unilateral but later • Mallampatti score
may become bilateral." • Samson and young's modification of mallampatti
2. Von Graffes sign: Upper eye lid lags behind the eye ball as • Mentohyoid thyromental distance
the patient is asked to look downwards. • Tempero-mandibular joint function
3. Stellwag's sign: Infrequent blinking of eyes with widening of • Wilson's rule of predicting difficult intubation.
palpabral fissure. Investigation:
4. Dalrymphe's sign: Upper sclera is visible due to retraction of • Complete hemograms, BT CT to rule out anemia, thrombocytopenia
upper eye lid. and agranulocytosis.
5. Joeffroy's sign: Absence wrinkling in the forehead on looking • Urine" Albumin
upwards with the face inclined downwards. " " Sugar
6. Mobiu's sign: Inability or failure to converge the eye balls " " Microscopy
7. Gifford's ` sign: Difficulty in eversion of the upper lid. • RBS, B. Urea, Serum Creatinine
Tachycardia: TFT's
Resting pulse rate should be recorded at early morning 3 am. • ECG-Sinus tachycardia, ST elevation, QT shortening, pulse rate
" 80-90 pm -moderate thyrotoxicosis prolongation, atrial fibrillation/flutter, ventricular ectopic
" 90-110 pm-moderate thyrotoxicosis Indirect laryngoscopy:
" > 110 pm- severe thyrotoxicosis • To assess normal cord movement preoperatively and for Post-op
Tremors: ventilation requirement.
• Tremors in stretched hands protruded tongue and fingers are • Medico-legal importance → To know the preoperative and
seen in primary thyrotoxicosis. postoperative difference(surgical trauma).
Systemic examination:
CVS: Chest X-ray:
• Enlarged heart • PA view- position of trachea, deviation, retrosternal goiter,
• Atrial fibrillation calcification.
• Sings of CCF. • Lateral view and barium swallow- pressure effects on trachea and
• Systolic murmurs oesophagus
CNS:# • Flow volume loop- best indications of airway obstruction.
• Myopathy and tremors • CT scan and MRI scan-for airway evaluation and extension of
Reflexes- hyper-reflex thyroid.
68

Pre operative preparation Monitoring:

For Elective Surgery • Pulse oximetry
Patient must be made euthyroid or near euthyroid at operation. • NIBP
Euthyroid is clinically assessed by. • ECG
• Sleeping pulse rate < 90/bpm • Temperature monitoring
• Progressive weight gain • ETCO2
• Disappearance of toxic symptoms like tremors, nervousness, • Neuro muscular monitoring
anxiety etc. • CVP line
• No requirement of sedation for sleep. • Doppler echocardiography
• Normal pulse pressure, sinus rhythm, disappearance of cardiac • Urine out put
murmurs
• The last dose of ATD may be given on the evening before General anesthesia:
surgery. • IV line is secured preferably in lower limb
For emergency surgery: • Before induction all the emergency drugs should be kept ready
• ATD should be started immediately PTU 600-1000 mg PO • LMA, intubating fiber optic bronchoscopy different sizes of ETT and
followed by 200-250mg of 4th hourly. laryngoscope blades should be ready.
• β blockers • Care of eyes is important -lubricated, lids secured and shielded.
• Propranolol 40mg PO 6"' hourly or 1mg iv bolus or When airway problem is not anticipated:
Nadolol 160mg OD or Esmolol infusion 100-200µg/kg/min 1. Pre-oxygenation: With 100% 02 for 3-5 minutes.
• Glucocorticoids. 2. Induction.
• Inj. Dexamethasone" " Inj. Thiopentone sodium 5-7mg/kg is the drug of choice.
• Inj. Hydrocortisone 40mg 6th hourly iv. " Inj. Glycopyrrolate - 0.01mg/kg.
Premedication: " Attenuation of sympathetic response to intubation by Inj.
Aim is to suppress sympathetic activity. " Xylocard 1.52mg/kg or Opioid/Esmolol can be used.
Psychological: Reassurance to the patient. 3. Relaxation: Inj. Succinylscoline 1-1.5mg/kg
Pharmacological: When airway problem is anticipated.
• T diazepam 10mg PO HS and 5mg PO in the morning or • Pre-oxygenation
• T Lorazepam 2-3mg oral • Inhalation induction with N20.02 and halothane, isoflurane
• Iv inj. Morphine 0.1 to 0.15mg/kg IM 30 mins before 4%xylocaine spray.
• Inj. Promethazien 25-50mg/iv or IM and " " • If patient has stridor/signs of inadequate ventilation-anesthesia is
• Premedication is avoided if airway problem is anticipated. lightened.
Anticholinergic drugs are not recommended. • Awake intubation can be done with local anesthesia.
69

Intubation. Reversal and extubation:

• Gentle laryngoscopy • With"Inj. Neostigmine 0.05 mg/kg
• Intubation is done with cuffed armored tube or cuffed ETT or Inj. Glycopyrrolate 0.01 mg/kg
north polar oral tracheal tube or intubating LMA with fiber optic Inj. Xylocaine 1-1.5 mg/kg IV 60-90 sec. Before extubation.
bronchoscopy guidance. • A fiber optic endoscope may be used to view the vocal cord. When
Position (Fowler's position). adequate spontaneous respiration and laryngeal reflexes have
• The patient is positioned with a sand bag between the shoulder returned the patient is extubated.
blades and the head resting on a padded horse shoe or with lock Regional anesthesia:
head rest. Under bilateral superficial and deep cervical plexus block.
" Avoid hyperextension. Indication:
" 20°-25° head up tilt to aid venous drainage • Cooperative patients
" Arms should be secured by the side • Cases not fit for GA
Maintenance of Anesthesia: • For small nodules
• Controlled ventilation is used with N20 + 02 + NDMR + Inj. Contraindication:
Fentanyl inhalation agents • Huge non toxic goiter
Advantage of controlled ventilation are – • Malignant thyroid disease.
• Less movement of ET tube Complications:
• Less sympathetic stimulation if normocarbia is maintained. • CNS toxicity due to vertebral artery puncture or epidural/
• Less occurrence of post operative tracheatis. subarachnoid injection.
NDMR: • Bilateral or unilateral phrenic nerve palsy
• Inj. Vecuronium 0.05 mg/kg or • Complications of thyroid surgery
Inj. Atracurium 0.3 - 0.4 mg/kg or 1.# Intraoperative:#
Inj. Rocuronium 0.3 - 0.4 mg/kg. • Carotid sinus stimulation - bradycardia + hypotension
• Already existing myopathy may prolong N-M blockade. • Thyroid crisis
• Associated myasthenia gravis emphasize the need to reduce • Haemorrhage
initial dose of muscle relaxation. • Air embolism
• Use of a peripheral nerve stimulator to monitor N-M blockade. • Tracheal injuries, pneumothorax, pneumomediastinum
• Isoflurane is preferred to halothane. • Damage to nerves.
Intraoperative monitoring:
• Better avoid adrenaline, if must Infiltration of 1: 2,00,000, not to
exceed 30 ml.
• Avoid halothane.
• Normocarbia should be maintained.
• Blood loss replacement if it exceeds 10% of blood volume.
• Watch for crisis.
70

2. Post operative Surgical factors:

Immediate • Anxious and nervous patient before surgery, too much handling of
• Thyroid crisis gland just before surgery. This can occur both intraoperative or in
• Hematoma the immediate post operative period, but the latter is more common
• Trachemalacia between 6-18 hours post operatively.
• Damage to nerves Clinical features:
• Laryngeal oedema • Hyperthermia ; rise of 20C/ hour over normal temperature
• Hypoparathyroidism • Tachycardia ; arrhythmias commonly atrial fibrillation
• Initially flushing and sweating later leading to dehydration
Late postoperative • CCF- initially high output failure, later may go for low output failure.
• Hypoparathyroidism • Shock – cardiogenic / hypovolemia
• Hypothyroidism • Electrolyte imbalance
Thyroid storm: • Hypo/hyperglycemia may also be present.
• Is an emergency characterized by sudden appearance of clinical • Marked anxiety, agitation and psychosis.
signs of hyperthyroidism due to the abrupt release of T4 and T3 Treatment:
into circulation. General measures:
• Mortality is as high as 25% to 30%. • Stop manipulation
• Commonly associated with Grave's disease. • Surgery is stopped
• Increase the FiO2
Etiopathogenesis: • Cooling measures: surface cooling - sponging, ice packs, decrease
• Increased T3 and T4 levels and increased saturation of thyroid OT temperatures, Cold IV fluids.
binding proteins. • Drugs – Largactil
• Presence of thyroid hormone binding inhibitors. • Establishment of an indwelling arterial line to follow metabolic
• Increased β adrenergic receptors. derangements and also to aid in diagnosis.
Pre disposing factors: • Treat the precipitating cause.
Medical factors: Suppression of hormonal activity:
• Infection • Propylthiouracil - 600mg loading dose and 200-300mg every 6"' hour
• Fever given orally or through NGT." OR
• Uncontrolled toxicity • Carbimazole → 50-100 mg Orally (Ryleʼs tube) followed by 20 mg 6th
• Irregular drug intake hrly
• Pregnancy, toxemia of pregnancy • Na I → X500-1000mg IV 8th hrly
• Radio iodine therapy
• DKA
71

Suppression of sympathetic activity: Hematoma:

• Propranolol → 1-2 mg IV • May cause obstruction to respiration by pressing over trachea.
Esmolol -+ 100-300 mg/kg/min." • Relieved by opening 1-2 sutures, requires re-intubation or
tracheotomy in acute emergencies.
Treatment of shock and CCF: Tracheomalacia:
• Digoxin → High out failure may not respond to digoxin • Due to pressure necrosis by a very large thyroid swelling or due to
• IV fluids should be given with reference to CVP line, otherwise malignant invasion of carcinoma.
over infusion may further worsen CCF. • Requires permanent tracheostomy.
• IV fluids preferably to crystalloids containing glucose to supply Laryngeal oedema:
enough energy for increased metabolism. • Diagnosed by inspiratory stridor, in severe cases - complete
Supplementation of corticosteroids: obstruction and cyanosis.
• Hydrocortisone -> 100- 200mg IV 8th hrly. Treatment:
Air embolism • Relieved by inhalation of warm humidified O2, nebulized spray of
• Occurrence of air embolism is influenced by volume of air (≥ adrenaline 0.5ml of 1:1000 solution in 1.5ml of distilled water.
0.5ml/kg/min). • Steroids
• Speed of injection • Intubation /tracheostomy may be preferred in emergencies.
Pressure in veins Hypoparathyroidism:
Posture and general conditions. • Due to inadvertent removal of parathyroid gland
Features: • Hypocalcaemia typically develops in 24-72 hrs post-op. But may
• Unexplained hypotension, tachycardia, cyanosis, mil wheel manifest as early as 1-3 hrs after surgery.
murmur, engorged neck veins, hyperapnoea and arrest. • Initially produces inspiratory stridor.
• Diagnosis by oesophageal stethoscope, Doppler, ultrasonic flow • Stridor progressing to spasm is first indication of tetany.
detector, ETCO2, ECG RV strain pattern. Treatment:
Treatment: • Inj. Calcium gluconate 10% 10ml for 10 minutes.
• Flood the wound the saline
• Left lateral position so that bubbles are carried away from the Damage to nerves:
mouth of pulmonary artery. 1. Superior - laryngeal nerve: Loss of sensation above vocal cords,
• Prevent further entry by venous compression. increased chance of aspiration.
• 100% oxygen 2. Recurrent laryngeal nerve.
• IPPV • Unilateral - usually transient, characterized by hoarseness of vice.
• Insertion of catheter into right atrium for aspiration. If permanent - Polytef (Teflon) Inj. into paralyzed cord may improve
voice
72

Bilateral: Differential diagnosis;

• Immediate re-intubation necessary Neuroleptic malignant
If damage is transient - a trial of extubation done in next few Thyroid storm Malignant hyperthermia
syndrome
days. Characterized sudden Acute in onset, rapid if Onset ranges from
If it fails - tracheostomy. appearance of clinical anesthesia includes hours to days after
Anesthesia for non thyroid surgery:
signs of potent volatile drug treatment
Regional anesthesia:
• Is preferred as it is associated with sympathetic nervous hyperthyroidism due Anesthetic or Scoline (Haloperidol,
blockade to abrupt release of T4 Metoclopramide,
• Avoided in high output failure and T3 carbamazepine)
• Adding epinephrine to local anesthesia is avoided. postoperatively.
• Anxiety - decreased by benzodiazepines. Temperature Temp. > 430 C Hyperthermia
• Hypotension is treatment with phenylephrine. increases not beyond
General anesthesia:
400 C
• Pre-cautions are similar to that taken for thyroid surgeries.
No muscle rigidity is Malignant hyperthermia Impairment of motor
seen results in metabolic function → rigidity,
acidosis profound akinesia extra-
hypercarbia (↑ ETCO2), pyramidal
muscle rigidity seen disturbances.
Deterioration of
mental status →
coma, stupor, delirium
Creatinine Creatinine -
phosphokinase level is phosphokinase levels re
decreased to about increased
half normal
Treatment includes → Treatment includes → Symptomatic control of
antithyroid drugs, iodides discontinue the Anesthetic temperature, acid base
and β - blockers agent and hyperventilate with balance, muscle tone
100% oxygen. In refractory cases and in
Dantrolene 2mg/kg/5 min. catatonic features ECT is
Sodabicarbonate 2-4 mEq/kg used
IV
73

13. Diabetes - Pathogenesis & Anesthesia. Dr Azam’s Notes in Anesthesiology 2013
• It is an endocrine disorder due to pathology in B-cells of 5." Mitochondrial DNA

Langerhans of pancreas-causing absolute or relative lack of 6." Other
insulin – leading to hyperglycemic and glycosuria. B." Genetic defect in insulin action
• It does not represent a single disease entity but rather a set of 1." Type A insulin resistance
disease status sharing certain characteristics. Foremost 2." Leprechaunism
presence of hyperglycemia in a patient is used both to diagnose 3." Rabson mendenhall syndrome
diabetes and to guide management decisions which are largely 4." Lipoatrophic diabetes
directed in avoiding hyperglycemia. It results from the C." disease of exocrine pancrease
combination of defects in insulin action, insulin secretion or both. " Pancreatitis
Any definition of diabetes that refers only to carbohydrate " Trauma
metabolism is incomplete disordered fat and protein metabolism " Neoplasia
must be included in a complete definition of the disease. " Cystic fibrosis
History: D.# Endocrinopathies
• Paul Langerhans: 1869 discovered that pancreas contain two 1." Crushing syndrome
distinct groups of cells. 2." Pheochromocytoma
• Oskar Minkowski & Joseph Von Mering: 1889 3." Pheochromocytoma
• Showed that pancreatetomized dogs exhibit a syndrome similar 4." Somatostatinoma
to DM in human beings. 5." Aldosteronoma
• Frederick G. Banting & Charles H. Best: 1921, discovered 6." Hyperthyroidism
insulin. 7." Other
• Leonard Thompson age 14 was first patient to receive active E." Drugs or chemical induced
extracts prepared by Banting & Best: 1960. 1." Nicotinic acid
• Sanger: 1960, established amino acid sequences of Insulin. 2." Glucocorticoids
3." Thyroid hormone
CLASSIFICATION:# 4." Diazoxide, Thiazide
Classification of diabetes mellitus 5." β adrenergic agonists
1.# Type I diabetes 6." Protease inhibits
A." Immune mediated
" a. Idiopathic
II# Type 2 diabetes
III# other specific types
A." Genetic defects of β cell function
1." HNF – 4 α (MODYI)
2." Glucokionase (MODY2)
3." HNF – 4 α (MODY3)
4." IPF – 1 (MODY3) 74

Diabetes - Pathogenesis & Anesthesia.Continuation: Dr Azam’s Notes in Anesthesiology 2013
F.# Infection Etiopathogenesis:

" Congenital rubella • Type I DM develops as a result of the synergistic effects of genetic,
" Cytomegalovirus environmental immunologic factors that ultimately destroy the
" others pancreatic (3 cells. Individuals with genetic susceptibility have normal
G.# Uncommon form of immune mediated disease (3 cell mass at birth but begin to lose R cells secondary to
" Stiff man syndrome autoimmune destruction over months to years. But before diabetes
" Anti insulin receptor antibodies. becomes clinically overt. β cell mass decreases and insulin secretion
H.# Other genetic syndromes associated with diabetes becomes progressively impaired although normal glucose tolerance
" Downʼs syndrome is maintained." Features of diabetes do not become evident until
" Klinefleterʼs syndrome a majority of β-cell are destroyed >80% . The events that trigger the
" Turners syndrome transition from glucose intolerance to frank diabetes are often
" Frederickʼs ataxia associated with increased glucose requirements as might occur with
" Huntingtonʼs chorea puberty or during infections.
" Lawrence - Moon-Beidl syndrome • After the initial clinical presentation of Type I DM a `honey moon'
" Myotonic dystrophy phase may ensure during which glycemic control is achieved with
" Porphayria modest doses of insulin or rarely insulin is not needed. However, this
IV Gestational diabetes mellitus fleeting phase of endogenous insulin production from residual β-cells
disappears as the autoimmune process destroys the remaining β-
Type I Diabetes cells and individual becomes completely insulin deficient.
• It is characterized by the development of complete insulin Genetic consideration:
deficiency. In fully developed forms patients will, if deprived of • Genetic susceptibility involves multiple genes. The major
insulin, develop ketoacidosis, coma & death. Peak incidence susceptibility gene is located in the HLA region on chromosome 6.
occurs in childhood and adolescence may occur at any age. Polymorphism in the HLA complex accounts to 40-50% of genetic
Peak incidence in girls occurs earlier in boys. The prevalence risk of developing type I DM. HLA haplotype DR3 and/or DR4
does not usually exceed to 0.3. predispose to type I diabetes. Account for t/3 of the susceptibility to
type 1 DM.
• The risk of developing Type I DM is increased 10 folds in relatives of
individuals with the disease. Nevertheless, most individuals with
predisposing haplotype do not develop diabetes. In addition most
individuals with type I A DM do not have first degree relative with
disorder.
75

Environmental Factors: Type II DM

• Coxsackie β -virus has been isolated, propagated in in-vitro • The pathogenesis of type II DM remains unclear. Insulin resistance
cultures of endocrine pancreatic cells and thus shown to have and abnormal insulin secretions are central to the development of
diabetic activity. type II DM.
• These viruses induces β -cell neoantigens which initiates an • Principally disease of middle aged and elderly.
autoimmune reaction. • Type II DM has strong genetic component. Major genes that
• The neoantigen may have destructive reaction if the structure predispose to this disorder is yet to be identified but it is clear that the
mimics a self protein or disease is polygenic and multifactorial. The occurrences of type II
• Virus replication in β -cells results in β -cell necrosis and DM in identical twins between 70 to 90%. Individuals with parent with
formation of antibodies against β-cell constituents or hidden type II DM have increased risk of diabetes. If both parent have risk
antigens not normally surveyed by the immune system. approximately 40%.
• The offspring with congenital rubella have found to develop type Risk factors for Type II DM:
I diabetes at very high frequency." Reo virus mumps are • Family history of DM
also capable of inducing diabetes thought to be due to R cell • Habitual physical inactivity
destruction. • Race/ethnicity
• Bovine serum albumin, a major constituent of cow's milk has • Previously identified IFG and IGT.
been implicated in triggering type I DM. • History of gestational DM or delivery of baby > 4 Kg.
• Various nitrosamines (found in smoked and cured meats) and • Hypertension (BP ≥ 140/90 mmHg)
coffee are proposed as potentially diabetogenic. • HDL cholesterol level ≤ 35mg/dl & or Triglyceride level ≥ 250mg/dl.
Pathology: • Polycystic Ovary syndrome.
• Gland size is diminished. • History of vascular disease.
• An atrophic pancreas with little or negligible residual insulin is
typical with long standing type I DM. Three major metabolic abnormalities co-exist in type II DM each
• Primarily affects tail of pancreas. contributing to hyperglycemic states.
• Pancreatic atrophy lower serum levels of pancreatic trypsin and 1. The role of liver in the pathogenesis of type II DM diabetes is over
isoamylase. production of glucose. Increased basal hepatic glucose production
• Characteristic of the pancreas in children with newly diagnosed is the characteristic feature of essentially all type II DM patients
type I DM is presence of inflammatory cells insulitis. T. with fasting hyperglycemia.
lymphocytes, β-lymphocytes macrophages and occasional 2. Skeletal muscles in insulin stimulated state take-up 70-80% of all
natural killer cells may be seen. glucose.
3. Abnormal islet cell function plays a central role in development of
hyperglycemia- decreased β - cell function an increased glucagon
secretion are frequent concomitant of diabetic state.
76

Causes of Insulin Resistance:

1) Abnormal β -cell secretory product
! Abnormal insulin molecule
" Incomplete conversion of pro-insulin to insulin
2) Circulating insulin antagonists
! Elevated levels of counter regulation hormones
" E.g.: Growth hormones; cortisol, glucagon, catecholamines
• Cytokines
• Free fatty acid
• Anti insulin antibodies
• Anti insulin receptor antibodies.
3) Target tissue defects.
• Insulin receptor defects
• Post receptor defects.
• Free fatty acid
DIAGNOSTIC CRITERIA FOR DM

Diabetes:
• Fasting plasma glucose greater than 126 mg/dl or greater
confirmed by a repeat test or symptoms of diabetes plus casual
plasma glucose greater than 200mg/dl or greater. Or
• Plasma glucose greater than 200mg/dl or greater 2 hours after
75g oral glucose tolerance test confirmed by a repeat test.
• Normal fasting glucose: Less than 110 mg/dl (6.1mmol/Itr.)
• Impaired fasting glucose: Fasting plasma glucose levels greater
than or equal to I 10mg/dl but less than 126mg/dl.
• Impaired glucose tolerance: Two hour plasma glucose level
greater than or equal to 140mg/dl or less than 200mg/dl.
Pathogenesis of the Complications of Diabetes:
• The morbidity associated with long-standing diabetes of either
type results from complications such as micro-angiopathy,
retinopathy, nephropathy, and neuropathy.
• Many mechanisms inking hyperglycemia to the complications of
longstanding diabetes have been explored. Currently, two such
mechanisms are considered important.
77

• Non-enzymatic glycosylation is the process by which glucose • Intracellular hyperglycemia with disturbances in polyol pathways is
chemically attaches to free amino groups of proteins without the the second major mechanism proposed for complications related to
aid of enzymes. The degree of non-enzymatic glycosylation is hyperglycemia. In some tissues that do not require insulin for glucose
directly related to the level of blood glucose. Indeed, the transport (e.g., nerves, lens, kidney, blood vessels), hyperglycemia
measurement of glycosylated hemoglobin (HbA1c) levels in leads to an increase intracellular glucose, which is then metabolized
blood is a useful adjunct in the management of diabetes mellitus, by aldose reductase to sorbitol, a polyol, and eventually to fructose.
because it provides an index of the average blood glucose levels These changes have several untoward effects. The accumulated
over the 120-day life span of erythrocytes. The early sorbitol and fructose lead to increased intracellular osmolarity and
glycosylation products on collagen and other long-lived proteins influx of water, and, eventually, to osmotic cell injury. In the lens,
in interstitial tissues and blood vessel wall undergo a slow series osmotically imbibed water causes welling and opacity. Sorbitol
of chemical rearrangements to form irreversible advanced accumulation also impairs ion pumps and is believed to promote
glycosylation end products (AGEs), which accumulate over the injury of Schwann cells and pericytes of retinal capillaries, with
life time of the vessel wall. AGES have a number of chemical resultant peripheral neuropathy and retinal micro aneurysms. In
and biologic properties that are potentially pathogenic. keeping with this hypothesis, experimental inhibition of aldose
• AGE formation on proteins such as collagen causes cross-links reductase is capable of ameliorating the development of cataracts
between polypeptides; this in turn may trap non-glycosylated and neuropathy.
plasma and interstitial proteins. Trapping of circulating low-
density lipoprotein (LDL), for example, retards its efflux from the !
!"#$%&#'()'*'$%+(,'-'+$.( /0'.%$1(
vessel wall and pro accelerating atherogenesis. AGEs may also
affect the structure and function of capillaries, including those of
the renal glomeruli, which develop thickened basement
membranes and become leaky.
• AGES bind to receptors on many cell types - endothelium,
monocytes, macrophages, lymphocytes, and mesangial cells. 2'34*)',(%*."#%*( 6*4,'7"4$'()#"+5.'(
Binding induces a variety of biologic activities, including .'+3'$%5*( ( "$%#%84$%5*(
monocytes emigration, release of cytokines and growth factors
from macrophages, increased endothelial permeability, and
enhanced proliferation of fibroblasts and smooth muscle cells 91&'3)#1+':%4(
and synthesis of extracellular matrix. All these effects can
potentially contribute to diabetic complications.
;'$4<(+'##('=>4".$%5*(
?1&'(66(,%40'$'.(
78

GENETIC PREDISPOSITION 3) Delays carbohydrate absorption

! • α glucosidase inhibitors
!"#$%$&'()*+$,*(*-$.(+$
/01*2$,*(*0'3$&/3'$ Oral hypoglycemic drugs :
Classified as
1) SULFONYLUREAS
First generation# # Second generation
Tolbutamide" " " Glibenclamide
4556(*$2*-7/(-*$.,.'(-0$ >'2.&$'(?*30'/(@$
Chlorpropamide" " Glipizide
(/25.&$8*0.$3*&&-$ A/&*36&.2$5'5'32B$
#9:;<=$
" " " " Gliclazide
#9:;<=$
4556(*$2*-7/(-*$.,.'(-0$ :.5.,*$0/$8*0.$3*&&-$
" " " " Glimepramide
.&0*2*+$8*0.$3*&&-$ 2) BIGUANIDES
" Phenformin
" Metformin
C*0.$%$3*&&$+*-02630'/($ 3) MEGLITINIDE ANALOGUES

" Repaglinide
" Netaglimide
DB7*$4$:'.8*0*-$ 4) THIAZOLIDINEDIONES
" Rosiglitazone
Management and Anti-hyperglycemic drugs and insulin therapy: " Pioglitazone
Anti-hyperglycemic drugs:
Classification 5) α – GLUCOSIDASE INHIBITORS
1) Improve insulin availability • Acarbose
• Exogenous insulin • Miglitol
• Sulfonylureaʼs
• Megliturnides analogues
2) Overcome insulin resistance
• Biguanides
• Thiazolideidiones
79

SULFONYLUREA Type to enter text

Most commonly used
• They enhance insulin secretion by binding to specific SU
receptors on the β cell which lead to closing of Potassium
Adenosine Triphosphate channel on β cell membrane enhances
Ca2+ influx – degranulation.
• The released insulin both reduces hepatic glucose production
and enhances muscle glucose uptake. A minor action reducing
glucagonʼs increasing Somatostatin release has been
demonstrated. Hepatic degradation may be slowed. They
sensitize the target tissue to the action of insulin. They increase
the number of insulin receptors and/or a post receptor action. It
may inhibit gluconeogenesis in the liver.
Pharmacokinetics: Well absorbed orally 90% bound or more to
plasma proteins. Fasting glucose is reduced by 60-70 mg/dl and
HbAIC by 1.5% to 2.0%.
Adverse Effects:
• Hypoglycemia
Nausea, vomiting, flatulence, diarrhea or constipation
Headache, paraesthesia, and weight gain.
80

Duration No. of
Plasma Clearance
Drug Preparations of action Daily dose doses remarks
T ½ (hr) route
(hr) per day
SULFONYLUREAS
1. Tolbutamide Rastinon, 6-8 6-8 L 0.5-3 g 2-3 Weaker, shorter acting, flexible dosage, safer in those prone to
0.5 g tab hypoglycaemia.
2. Chlorpropamide Diabinese, 30-36 36-48 K.L 0.1-0.5 g 1 Lonest action, can cause prolonged hypoglycaemia, potentiates ADH
0.1, 0.25g tab action more cholestatic jaundice, alcohol flush
3. Glibenclamide Daonil, Euglucon, 4-6 18-24 L 5-15 mg 1-2 Potent but low acting, marked initial insulinemic action, may work
(Glyburide) Betanase when other fail, metabolite excreted in urine as well as bile single
2.5, 5mg tab daily dose possible despite short T ½ weight gain less likely
4. Glipizide Glynase, Glide 3-5 12-18 L 5-20 mg 1-2 Fast acting, insulinemic action persists even after prolonged use, can
Minidiab 5 mg tab be given once daily despite short T ½, weight gain less likely.
5. Gliclazide Diamicron 80mg tab 8-20 12-24 L 40-240 mg 1-2 Has antiplatelet action, reduces free radicals, may delay diabetic
diazide 20, 80mg tab retinopathy, less weight gain
Glizid 30, 40 80mg tab
6. Glimepiride Amaryl, glypride 5-7 24 L 1-6 mg 1 Stronger extrapancreatic action; less hyperinsulinemia. Divided in
Glimer 1,2 mg tab two if daily dose ≥ 4 mg
BIGUANIDES
1. Phenformin DBI 25 mg tab 3-10 8-12 L.K 25-150 mg 1-3 Lactic acidosis more common, withdrawn in many countries
DBI – TD 50mg tab
2. Metformin Glyciphage 1.5-3 6-8 K 0.5-2 mg 2-4 Not metabolized at all, lactic acidosis less common
Glycomet
0.5, 0.85 g tab
MEGLILTINIDE
ANALOGUES
1. Repaglinide Eurepa, Raplin 0.5, 1, ≤1 2-3 L 1.5-8 mg 3-4 Give ½ hr before each meal for limiting P.P hyperglycaemia
2mg tab
2. Nateglinide Glinate 60, 120mg tab 1.5 2-3 L 180-480 mg 3-4 Stimulates 1st phase insulin secretion, less likely to cause delayed
hypoglycaemia
THIAZOLINDINEDIONES
1. Rosiglitazone Reglit, rosinorm 4 12-24 L 4-8 mg 1-2 Reverses insulin resistance. No hypoglycaemia, C/I in liver and
ross, 2,4,8 mg tab heart disease
2. Pioglitazone Pionorm, Piorest, 3-5 24 L 15-45 mg 1 Reverses insulin resistance. No hypoglycaemia, C/I in liver and
Piozone 15, 30 gm tab heart disease may improve lipid profile
81

Metformin: • It induces rapid onset and short lasting insulin release. It is

• Metformin is a Biguanide that has been used worldwide for administered before each major meal to control postprandial
decades. hyperglycemia; the dose may be omitted if a meal is missed.
• It enhances insulin sensitivity primarily in the liver but also in the • Side effects are mild headache, dyspepsia, arthralgia and weight
peripheral tissues (muscle more than fat). The receptor gain. Indicated only in type 2 DM. Avoided in liver disease.
mechanism by which this enhanced sensitivity occurs is not Nateglinide
known. Fasting glucose is reduced in direct correlation to the • Principally stimulates the first phase insulin secretion
suppression of hepatic glucose output. Rapid onset and short duration of action.
• Metformin reduces fasting glucose readings by 60-70mg/dl and Ingested 10-30 min before meal.
HbAIC value by 1.5% to 2.0%. The most common approach to It limits post prandial hyperglycemia in type II diabetes.
dosing is to start 500mg at supper and then add 500mg every • Side effects: Dizziness, nausea, flu like symptoms and joint pain.
1-2 weeks until the patient has achieved SNMG goals or has Thiazolidinediones
reaches: 1000mg with breakfast and supper. • Rosiglitazone
• In addition to lowering glucose, metformin reduces triglycerides, • Pioglitazone
low density lipoprotein, plasma free fatty acids and Plasminogen • These novel class of drug enhance insulin sensitivity mainly at the
activator inhibitor 1 levels. There is modest weight loss or no level of muscle and adipose tissue with some effect in the liver.
weight gain. These drugs are selective agonists for nuclear peroxisome
• Side effects are predominantly gastrointestinal upset and proliferators activated receptor γ (PPARr) which enhances the
diarrhea but these are transient and only 5% of patient cannot transcription of several insulin responsive genes, which modulate
tolerate the drug. glucose and to some degree, lipid metabolism, activation of genes
• When used alone doesn't cause hyperglycemia. Contraindicated regulating fatty acid metabolism and lipogenesis in adipose tissue
in hepatic disease, respiratory insufficiency, severe infection and may contribute to insulin levels in type 2DM patients.
alcohol abuse and congestive cardiac failure. • They are approved for use as both monotherapy and combination
Megliturnides Analogues: therapy. As a monotherapy all TZD's reduce HbAIC fraction 1.0% to
These are recently developed quick and short acting insulin 1.5%.
releases. • They reduce free fatty acid levels. Pioglitazone lowers serum triglyceride
Repaglinide: level and raises HDL level without much change in LDL level.
• It is the first member of a new class of oral hypoglycemic drug • Both Pioglitazone and Rosiglitazone are well tolerated. Adverse effects are
designed to normalize meal time glucose excursions though not plasma volume expansion, edema, weight gain, headache, myalgia and
a sulfonylurea, it acts in an analogous manner by binding to mild anemia. Not associated with hypoglycemia when used alone. May
sulfonylurea receptors as well as other distinct receptors. cause hepatic dysfunction and some cardiovascular events have been
reported. Contraindicated in liver disease and CHF.
• It acts in an analogous manner by binding to sulfonylurea
receptors as well as other distinct receptors.
82

&))+71&,-8# =1,0# 04@+3247-'1&# =0-/# A)-8# &2+/-># Q&4# 7&A)-# 0-@&,17# 84)BA/7,1+/# &/8#
1/)>21/#K"+'#J#7-22)#1)#"-3>2&,-8#B4#70-'17&2P#0+"'+/&2#&/8#/->"&2#'-70&/1)'
Diabetes - Pathogenesis & Anesthesia.Continuation:
)+'-# 7&"81+K&)7A2&"# -K-/,)# 0&K-# E--/# "-@+",-8># T+/,"&1/817&,-8# 1/# 21K-"# 81)-&)-# &/8# Dr Azam’s Notes in Anesthesiology 2013
78+91:/.6$
TSX>#
# # # # # # $7&"E+)-# Chemical:
3$4$)*5612+-&2($+,/+7+'182# • L0-#!#7-22)#0&?-#32>7+)-#)-/)1/3#'-70&/1)'#8-D-/8-/,#+/#-/,"4#+K#32>7+)-#1/,
The β cells have glucose sensing mechanism dependent on entry of
# # # # # # # # glucose into β cells.
Q1321,+2# X2>7+)-#
J0-)-# &3-/,)# 8-2&4# 813-),1+/# +B# 7+'@2-L# 7&"E+048"&,-# E4# &7,1/3# &)## 7+'@-,1,1K-24#
# # # # # # # $'1/+#&718)##
• These agents delay digestion of complex carbohydrate by acting
1/01E1,+")#+B#,0-#1/,-),1/&2#Y#32A7+)18&)-#-/%4'-)#,0&,#048"+24)-#+213+)&770&"18-)#1/,+# # # # # # # # # V&,,4#&718)#
as competitively inhibitors of the intestinal α glucosidase
'+/+)&770&"18-)# ,0-"-E4#oligosaccharides
enzymes that hydrolyse @+),@"&/81&2# 04@-"3247-'1&#into monosaccharides 1)# "-8A7-8# =1,0+A,# # #
1/7"-&)1/3## # # # # # W-,+/-#B+81-)#
thereby postprandial hyperglycemia is reduced without
#
1/)A21/#2-K-2)>#
increasing+B#insulin # # # # # $7,1?&,1+/#+K#X2>7+"-7-D,+"#NXYSL5RO#
C-8A7,1+/# SE$.T#levels.
1)# &@@"+L1'&,-24# <>;U# ,+# :><U># C-8A7-)# E+84# =-130,# &/8# )-"A'#
• Reduction of HbAIC is approximately 0.5% to 1.0%. Reduces
,"13247-"18->#Q&4#E-#A)-8#&)#&8I&7-/,#,+#81-,#1/#,0-)-#81&E-,-)>#
# #
body weight and serum triglyceride. May be used as adjacent to
Q&4# #
diet@"+8A7-#
in these B2&,A2-/7-#
diabetes. &/8# 2++)-# ),++2# 1)# &E+A,# ;<U# @&,1-/,)# 8A-# ,+# B-"'-/,&,1+/# +B#
./01B1,)#$LZ#
•A/&E)+"E-8#7&"E+048"&,->#
May produce flatulence and loose stool is about 50% patients
due to fermentation of unabsorbed carbohydrate. # 6-/)1,1?-#W#[# # # Z&",1&2#!-D+2&"1%&,1+/#+K#!#7-22)#
INSULIN # :;<#
M0&//-2)#
•===>!"$%&'>7+'
Insulin was discovered###############################################################################
in 1921 by Banting and best. Endocrinology
# # ## # # # #
•# Insulin is a two chain polypeptide have 51 amino acids and MW #./7"-&)-)#1/,"&7-22>2&"#M&#A[#
about 6000. A chain has 21 while B chain has 30 amino acids.
#
• Insulin is synthesized in the R cells of pancreatic islets a single
chain peptide preproinsulin. The C. peptide (35AA) is split off by # # # # # # #
proteolysis in golgi apparatus. Both insulin and peptide are 9\+74,+,17#"-2-&)-#+K#1/)>21/#
stored in granules within the cell. The peptide is secreted in
blood along with insulin. • Glucose and other nutrients are more effective in invoking insulin
Regulation of insulin: <<<=!"$%&'=7+'
release when given orally than i.v. They generate chemical signals
############################################################################### Endocrin
"incretins" from gut which act on p cells to cause anticipatory release
• Insulin production by a normal, thin healthy person is between #
1840U/day or about 0.2-0.5U per kilogram of body weight per of insulin.
day. About half of this is secreted in basal state and about half in • The incretins are, gut glucagon, secritin, gastrin, gastric inhibitory
response to meals. Thus basal secretion is about 0.5-1 U/hour. polypeptide, vaso-active intestinal peptide, pancreozymin
After an oral glucose load insulin secretion may increase to 6U cholecystokinnen etc.,
per hour. Secretion of insulin from R cells is regulated by
chemical, hormonal and neural mechanisms.
83

Hormonal Effect of insulin on promoting liver uptake storage, and use of glucose:
• growth hormone The mechanism by which insulin causes glucose uptake and storage
• corticosteroids with in liver includes several almost simultaneous steps.
• Thyroxine 1. Insulin inhibits liver phosphorylase - inhibits glycogen to split into
• Modify insulin release in response to glucose. More important is glucose.
intra islet of pancrease interaction between hormones produced 2. Enhances uptake of glucose by the liver cells by increasing the
by different types of islet cells. activity of the enzyme glucokinase which is the enzyme which
• Somatostatin inhibits release of both insulin and glycagon. causes the initial phosphorylation of glucose that diffuses in to
Glucagonʼs evokes release of insulin as well as Somatostatin. cells.
Insulin inhibits glucagonʼs secretion. These three hormone 3. Increase the activities of phosphofructokinase and glycogen
influence each otherʼs secretion and appear to provide fine- synthetase which is responsible for polymerization of
tuning of their output in response to metabolic needs. monosaccharide units to form glycogen molecules. The net effect is
• Neural: the islets are richly supplied by sympathetic and vagal to increase the amount of glycogen in the liver.
nerves. Adrenergic α2 receptor activation decreases insulin 4. When the quantity of glucose entering the liver cells is more than
release by inhibiting β cell adenylyl cyclase. Adrenergic β2 can be stored insulin promotes conversion of all of this excess
stimulation increases insulin release by stimulating β cell glucose into fatty acids - which are packaged as triglycerides in
adenylyl cyclase. VLDL and transported to adipose tissue and deposited as fat.
• Cholinergic – muscarinic activation by ach or vagal stimulation 5. Inhibits gluconeogenesis.
causes increased insulin secretion. Effects of insulin on protein metabolism:
• These neural influences appear to govern both basal as well as 1. Insulin causes active transport of amino acids into the cells.
evoked insulin secretion. The primary central site of regulation of 2. Has a direct effect on ribosomes in increasing the translation of
insulin secretion is in the hypothalamus; stimulation of messenger RNA thus forming new proteins.
ventrolateral nuclei evokes insulin release, whereas stimulation 3. Over longer period of time insulin increases the rate of transcription
of ventro medial nuclei has opposite effect. of selected DNA genetic sequences in cell nuclei thus forming
Actions of insulin: increased quantities of RNA and still more protein synthesis.
The overall effects of: insulin are to favors storage of fuel. 4. Inhibits catabolism of proteins.
Effects of insulin on glucose metabolism in muscle: 5. Depresses the rate of gluconeogenesis.
• Insulin has direct effect on the muscle cell membrane to facilitate Adipose tissue:
glucose transport. Insulin can increase the rate of transport of • Increased glucose entry
glucose into the resting cell by at least 10-20 folds. • Increased fatty acid synthesis
• Increased glycerol phosphate synthesis
• Increased triglyceride depositions
• Activation of lipoprotein lipase
• Increased K+ up-take
84

Fate of insulin: Insulin is distributed only extracellularly. It is a peptide - 2. Highly purified insulin preparation
degraded in G.I.T. if given orally. Injected insulin or released from pancrease is a. Single peak insulin: Purified by gel filtration and
metabolized primarily in liver and to smaller extent in kidney and muscles. The repeated crystallization, they contain 50-200 ppm
plasma tV2 is 5-9 mins proinsulin.
b. Monocompetent Insulinʼs: After gel filtration it is
Insulin Preparation: further purified by ion exchange chromatography,
1. Conventional preparations of insulin content of proinsulin is reduced to < 20 ppm.
Appear Onset Peak Duration
A. Type Can be mixed with
ance (hr) (hr) (hr) Human Insulinʼs:
Short Acting Clear 0.5-1 2-4 6-8 All preparations • Human insulinʼs were produced by recombinant
Regular (soluble) Insulin Cloudy 1 3-6 12-16 regular, lente DNA technology in e-coli ʻproinsulin recombined
Prompt insulin zinc preparations bacterialʼ and in yeast ʻPrecursor yeast
suspension (amorphous) recombinantʼ or by enzymatic modification of
or semilente porcine insulin.
Intermediate acting Cloudy 1-2 8-10 20-24 Regular, semilente

Insulin zinc suspension or
lente (ultra: semi: 7:3)
Neutral protamine Cloudy 1-2 8-10 20-24 Regular
hagedom (NPH) or
isophane insulin
Long acting
Extended insulin zinc Cloudy 4-6 14-18 24-36 Regular, semilente
suspension (Crystalline)
or ultralente)
Protamine zinc insulin Cloudy 4-6 14-20 24-36 Regular
(PZI)
85

Natural History of Diabetic Retinopathy:

• The earliest clinically apparent changes of diabetic retinopathy are
retinal micro aneurysms these lesions usually appear as round red
dots in size from 20 to 2001m and present as out pouching of retinal
capillaries. They often appear first in macular area in areas of
capillaries.
• It is usual to detect retinal micro aneurysms within 3 years of the
diagnosis of type I diabetes. After 10 years of diabetes 69% of
people with type I and 55% of people with type II.
• By themselves micro aneurysms are not threat to vision. As the
disease progress hard exudates decreases and retinal blot
hemorrhage appears. The later are round with blurred edges and
result from extravasation of blood from capillaries of micro-
aneurysms into inner nuclear layer of the retina. They usually
disappear within 3-4 months.
• Retinal hard exudates are sharply defined yellow and variable in
size; they may be aggregated scattered or ring-like in their
distribution. It results from leakage of lipoprotein material from retinal
micro aneurysms or capillaries into outer retinal layer and may
Diabetes Mellitus: Oculopathy persist for months to years - posterior layer of the retina. With closure
• Retinal anatomy in brief, the inner part of the eye is lined by this, of retinal capillaries and arterioles whitish or grayish swelling appear
transparent neural tissue the retina. The retina consists of 10 in the nerve fiber layer of retina termed cotton wool spots or soft
well-defined layers (The nuclei of three sequential neurons, their exudates are micro infarcts of nerve fiber layer. Dilated capillaries are
axons and synaptic connections of glial supporting cells. The another manifestation of focal retinal ischemia.
inner one third is fed by central retinal artery, which branches into
arterioles at optic nerve head. The internal third is supplied by
the choriocapillaris of the choroid. A blood retinal barrier
composed of light junction of endothelial cells of retinal blood
vessels and tight junctions of retinal pigment epithelial cells in
outer portion of retina permits only a few important metabolic
products.
• The macular area is approximately 4mm in diameter and
centered about 4mm temporal to the optic dick the fovea is
15mm in diameter and its is usual devoid of retinal pigments.
86

Proliferative Retinopathy: !
• Proliferative retinopathy is characterized by the growth of
abnormal new blood vessels and fibrous tissue from the inner
retinal surface or from the optic nerve head and consists of fine !"#$%&'#()* +#(%',&$()*
tufts "naked" vessels that grow on the back surface of the "#$%&%'!(#))'!*#)+!,-'! 89&,#!3%##!#)662!%-')$5%#1,#!
vitreous. They are prone to hemorrhage into vitreous especially if )./0%-,$1)-2!!%#%3$&)45/61)#)013,#! 4&)#1*%&,$1)-2!3,41##,&/!3#)69&%2!
the vitreous in the process of contracting. In addition, the new '%*%3$62!1-3&%,6%!3,41##,&/! 713&)!,-%9&/676!*)&7,$1)-2!
vessels are often associated with fibrous tissue. If this fibro- 4%&7%,(#/! -%):,639#,&1;,$1)-!
vascular tissue contracts, traction detachment of the retina may
result. Other risk factors:
• Increased permeability of retinal capillaries and micro aneurysms 1)" Blood pressure
may result in accumulation of extracellular fluid and thickening of 2)" Serum lipids
normally compact macular tissue. The edema is most often 3)" Proteinuria & renal disease
associated with deposition of hard exudative material in rings, 4)" Cigarette smoking & alcohol consumption.
clumps or large deposits. Accumulation of exudate is often 5)" Pregnancy
gradual and spontaneous resolution may occur in time. Severe Other ocular disease associated with diabetes
long standing leakage may result in the appearance of cystoid 1)" Cataract
spaces in the outer position of the retina in foveal area. This 2)" Glaucoma
abnormality is often associated with profound drop in visual Diabetes Mellitus: Neuropathy
acuity. The pathogenesis of diabetic retinopathy is not known. • It is defined as "the presence of symptoms and/or signs of peripheral
However many mechanisms have been suggested and are nerve dysfunction in people with diabetes after the exclusion of other
summarized as follows. causes".
HYPERGLYCEMIA
Clinical features
Biochemical
Focal and multifocal neuropathies:
• ↑ Protein kinase actively
• A number of characteristics focal and multifocal neuropathies occur
↑ Non enzymatic glycosylation in diabetes. They account for more than 10% of all neuropathies.
↑ Aldose reductase activity Most of this tend to occur in older type II patients and prognosis is
↑ Vaso-active substances (endothelin prostanoids) generally for recovery of the deficits (either partial or complete) and
↑ Histamine, nitrous oxide, pain which may be frequently be present.
↑ Free radical damage, growth factor release.
87

a) Cranial Mono-neuropathies: Cardiovascular:

• The nerves supplying the extraocular muscles - III cranial nerve • Cardiac autonomic neuropathy manifests initially as an increased
are most commonly affected. Diabetes Ophthalmoplegia may be rate due to vagal denervation. The parasympathetic arm of ANS is
of relatively rapid onset, presenting with pain in the orbit diplopia affected earlier and more profoundly than the sympathetic one.
and ptosis; thus exclusion of other causes (especially rupture of Therefore a resting tachycardia is usually earlier symptom. Exercise
PCA aneurysms) intolerance may occur when sympathetic nervous system is affected.
b) Isolated and Multiple Mononeuropathies: This is followed by decrease in heart rate due to sympathetic
• A number of nerves are prone to pressure damage in diabetes denervation and finally fixed heart rate supervenes which responds
most common is median nerve as it passes under flexor minimally to physiologic stimulus. Autonomic neuropathy may cause
retinaculum. Other entrapments neuropathies are less frequently postural hypotension which has been defined in two ways; either
seen among involve ulnar nerve, lateral cutaneous nerve of thigh 30mm Hg fall in Autonomic Neuro pathysystolic BP or l mm Hg fall in
(myalgia paresthetica) radial nerve -wrist drop and peroneal n- diastolic B.P. 2 minutes after standing. Patient complains of
foot drop occurring in isolation. Most of the above (except foot dizziness, weakness, nausea and occasionally vomiting and syncope
drop) carry good prognosis although surgical decompression after standing quickly.
may be required. Gastrointestinal:
c) Truncal Neuropathies: • Autonomic neuropathy of the gastrointestinal system manifests as
• Truncal neuropathies are typically characterized by pain abnormality in motility, secretion and absorption through
occurring in a band distribution around the chest or abdomen in derangement of both extrinsic parasympathetic and sympathetic as
dermatomal distribution. The pain may be severe and have well as intrinsic innervations provided by Auerbach's plexus.
characteristic of both nerve trunk pain & dysesthesias patient Clinically present with two major problems: diabetic gastroperesis
may experience dull aching, loosing pain together with burning manifests by nausea, postprandial vomiting and alternating diarrhea
discomfort or allodynia. and constipation.
d) Proximal motor neuropathy: • Bladder dysfunction and in males retrograde ejaculation and
• Typically affecting older, male, type 2 diabetes patients, proximal impotence are the result of autonomic neuropathy involving
motor neuropathy (Amyotrophy) presents with pain, wasting and genitourinary tract.
weakness in proximal muscles of lower limbs either unilaterally Sweating Abnormalities:
or with asymmetrical bilateral involvement. • Abnormalities of sweating are common but often neglected
Symmetric Neuropathies: symptoms of autonomic dysfunction reduced sweating in extremities.
• Cardiovascular Drenching truncal sweating
• Gastrointestinal • Gustatory sweating (profuse sweating in head and neck region on
Autonomic Neuropathy" " eating certain foods is a highly characteristic of diabetic AN)
• Erectile dysfunction Autonomic dysfunction finally leads to hypoglycemia unawareness.
Bladder dysfunction
Sweating abnormalities
88

TREATMENT Stage 2: Early glomerular lesion

Current Treatment: • Expansion of the glomerular mesangial matrix and thickening of the
• Glycemic control glomerular basement membrane are subtle morphologic changes
• Tricyclic antidepressants Amitriptyline & imipramin for painful noted 18 to 36 months after the onset of diabetes may become
neuropathy. pronounced after 3'h to 5 years. Normal excretion of albumin is less
• Anticonvulsants like carbamazepine is widely used in than 20 µg/min or 30mg/24 hours.
management of neuropathic pain. Stage 3: Incipient diabetic nephropathy.
Potential Future Therapies: • Characterized by microalbuminnuria at rest. This is defined as
• Aldose reductase inhibitors elevated excretion rates of albumin between 20-200 µg/min
• α lipoic acid (30-300mg/24 hours).
• ϒ linolenic acid • At this stage GFR begins to decline.
• nerve growth factor • B.P. are higher than in non-diabetic subjects may increase to
Nephropathy: A major diabetic complication abnormally high levels during exercise. (B.P. increases 3-4 mm Hg/
• Diabetes mellitus is universally recognized as the leading cause year)
of irreversible renal failure - unfortunately termed end stage renal Stage 4: Clinical Nephropathy.
disease. Diabetic nephropathy is the inclusive term applied to • Is characterized by clinical proteinuria - that is a level of urinary
myriad renal complications of type I and type Il diabetes. proteins detectable by simple tests. The overt DN is defined by
• Nephropathy due to nodular and diffuse intercapillary glomerular urinary protein excretion exceeding 0.5g/h (500-3000mg/dl) may
sclerosis develops in about one third of those type I diabetes surpasses the liver's maximum ability to synthesis albumin resulting
although equivalent proportion of those with type 2 diabetes. in proteinemia. A full nephrotic syndrome is noted when proteinurea
Renal involvement has been divided into 5 stages. rises to 4-40g/day.
• Early in the clinical course GFR may be normal but usually declines
Stage 1: Glomerular hyperfiltration and Renomegaly slowly and steadily. There is a linear relationship between the GFR
• occurs at the onset of the disease and serum creatinine once the serum creatinine level reaches 2.3mg/
• Characterized by 30% to 40% increase in GFR above normal. dl. The average GFR declines approximately l ml/min/month. During
• Does not reverse acutely with insulin therapy this stage BP increases approximately 7mm Hg/year and thus
• Return to normal within several weeks to few months. hypertension eventually occurs in all patients. Aggressive treatment
• Associated with enlarged kidney and increased intra glomerular of hypertension slows the rate of decline of GFR whereas treatment
pressure. of hyperglycemia has little impact.
• This may increase transient increase in albumin excretion. Stage 5: End stage renal disease.
• It is similar to kidney failure due to any other causes, signs and
symptoms include progressive weakness, anorexia, nausea vomiting
diarrhoea hiccups, pruritis, difficulty in controlling hypertension
anemia and electrolyte imbalance.
89

Clinical Management: DIABETIC KETOACIDOSIS (DKA)

1) Antihypertensive drugs • Is caused by profound lack of effective insulin
2) Dietary protein restriction • Acute complication of type IDM
3) Glycemic control
4) Control of urinary infection. The clinical hallmark of DKA is
5) Hemodialysis • Acidosis
6) Peritoneal dialysis • Dehydration
7) Kidney transplantation • Electrolyte imbalance
Reaction to Insulin: • Precipitating causes of DKA

1) Hypoglycemia Infection
2) Local reactions: Swelling, edema, and struggling sometimes • Cessation of insulin
occur. Lipodystrophy occurs at injection sites after long use. • new onset diabetes
3) Allergy. • MI
4) Edema • Pancreatitis
• shock and hypovolemia
• Stroke
Symptoms# # Sign
Polyuria" " Hypothermia
Polydypsia" " Hypercapnia
Weakness" " Acetone breath"
Lethargy " " Dehydration
Myalgia" " Hyporeflexia
headache" " Acute abdomen
anorexia" " Stupor
nausea" " Hypotonia
vomiting" " Uncoordinated eye movements
Abdominal pain" Fixed, dilated pupils
Dyspnea
Initial laboratory values
90

Treatment: • Hypertriglyceridemia
• Fluids • Low LDL
• Insulin • Increased apolipoprotien B
• K + replacement • Hypertension
• Phosphate replacement • Hyperinsulinemia/insulin resistance
• Bicarbonate therapy • Central obesity
• Family History of atherosclerosis
Complications: • Cigarette smoking
• Cerebral oedema" • Abnormalities in platelet aggregation coagulation /fibrinolysis in
• DIC diabetics increase the risk of myocardial infarction.
• Serious infection" • Diabetics have greater risk of congestive cardiac failure, recurrent
• ARDS infarction, arrhythmias and cardiogenic shock post MI than non
• Unrelenting shock"Aspiration diabetics.
• Cardiac arrest" • Present with acute pulmonary odema more commonly than non
• Pulmonary embolism diabetics despite similar infarcts size and LVEFs.
• Respiratory arrest" • Diabetic cardiomyopathy
• Rhabdomyolysis
• Arterial thrombosis"
• Pneumomediastinum
• Subcutaneous Emphysema
• Non ketotic hypermolar coma
Heart disease in diabetes mellitus
Major cause of mortality and morbidity among diabetics
The risk of cardiovascular death is 3 times higher in diabetics than
in non diabetics. Coronary artery disease is more extensive among
diabetic patients
Diabetes increases the risk and accelerates atherosclerosis.
Cardiovascular risk factor in DM
91

Insulin (Use only

Time Fluid
short – acting Potassium (i.v) Other
(Hrs) (I.v.)
(Soluble) Insufin)
0 Start i.v insulin Start i.v. 0.9% saline Check capillary blood glucose. If ≥ 17 mmol/I,
infusion 5 u/hr infusion, 1 litre in 30 obtain venous blood for urgent laboratory
(attematively, mins measurement of glucose, Na K, CI, CO2, urea and
10-20u i.m followed pH or (H+) test urine for ketones
by 5 U/hr i.e.
therafter)
0.5 Continue insulin 5 0.5 litre of 0.9% saline If plasma K+ > 5.5 mmol/I, If plasma Na +> 155 mmol/l, give Na + falls to 140
U/hr i.v. in 30 mins give no KCI: 3.5-5.5 mml/I, if pH < 7.0 (H+) > 100 nmol/l) give 300 ml
mmol/I, give 20 mmol KCI/ 1.26% sodium bicarbonate over 30 mins into large
I of infused fluid; vein
< 3.5 mmol/I, give 40
mmol KCI/I of infused fluid
1. Continue insulin 5 0.5 litre of 0.9% saline As above Recheck biochemistry
U/hr i.v. in 2 hrs
2. Continue insulin 5 0.5 litre of 0.9% saline As above Recheck biochemistry
U/hr i.v. (higher rate in 2 hrs
if fall in blood
glucose < 3 mmol/
hr)
When blood glucose Change to 5% glucose Continue i.v. K Continue to check biochemistry every 2-4 hrs.
< 15 mmol/l reduce infusion 0.5% glucose supplements
rate of insulin infusion 0.5 litre/ 2hrs
infusion to 1-4 U/hr
Continue with regimen until fluid deficit replaced, ketonuria abolished and adequate oral intake of carbohydrate feasible.
N.B. these guidelines of a typical ʻ averageʼ case should be modified appropriately in the individual patient after considering the
blood biochemistry and clinical features e.g. see page 668 for information on treatment of non-ketotic hyperosmolar diabetic
coma
92

Fluid replacement: Fluid replacement

• 6 Liters deficit • Intravenous fluid replacement is required since, even when the
• 3 liters from intracellular compartment: replaced by saline patient is able to swallow, fluids given by mouth may be poorly
• 3 Liters from intracellular compartment: replaced by dextrose. absorbed. The extracellular fluid deficit should be replenished by
infusing isotonic saline (0.9% NaCl) early and rapid rehydration is
Capillary blood glucose measurement essential, otherwise the administered insulin will not reach the poorly
• An accurate laboratory measurement of blood glucose should be perfused tissues. If the plasma sodium is greater than 155 mmol/l,
taken at an early stage. 0.45% saline may be given initially instead of 0.9%.
• A capillary blood glucose measurement ≥ 17mmol/l using visually • The intracellular water deficit must be replaced by using 5% or 10%
read glucose strips can be very misleading since the actual dextrose and not by more saline it is best given when the blood
blood glucose concentration is often considerably higher when glucose concentration approaches normal. An accurate record of
measured accurately in the laboratory; therefore an accurate fluid balance must be maintained.
measurement should be taken at an early stage. Potassium
Additional procedures • As the plasma potassium is often high at presentation, treatment with
• Catheterization if no urine passed after 3 hrs. intravenous potassium chloride should be started cautiously (see box
• Nasogastric tube to keep stomach empty in unconscious or 15.28) and carefully monitored sufficient should be given to maintain
semiconscious patients a normal plasma concentration and large amounts may be required
• Central venous line if cardiovascular system compromised so (100-300 mmol in the first 24 hours). Cardiac rhythm should be
that fluid replacement can be adjusted accurately. monitored in severe cases because of the risk of electrolyte induced
• Plasma expander if BP does not rise with i.v. saline. cardiac arrhythmia.
• Antibiotic if infection demonstrated or suspected. Bicarbonate
Monitoring • In patients who are severely acidotic (pH < 7.0 H > 100 nmol/l the
• Blood glucose and electrolytes hourly for 3 hrs and every 2-4 hrs infusion of sodium bicarbonate 300ml 1.26%.
thereafter
• Temperature, pulse, respiration, BP hourly
• Urinary output and ketones
• ECG plasma osmolality, arterial pH in some cases
93

Pathophysiology of diabetic ketoacidosis The mechanisms by which, insulin and fluids reverse ketoacidosis.
94

14.Pheochromocytoma. Dr Azam’s Notes in Anesthesiology 2013
INTRODUCTION Adrenal Glands

• Phaeochromocytoma is a rare catecholamine producing tumour • The Adrenal Gland is a flattened yellowish structure that weighs less
arising from chromaffin cells in the adrenal medulla and the than 10gm in an adult and is situated in retroperitoneum adjacent to
paraganglionic system. 90% of the tumours arise from the the upper pole of kidneys enclosed within the renal fascia. The
adrenal medulla and 10% extra adrenal. The extra adrenal normal adrenal measures approximates 5×3×1 cm.
tumors can arise anywhere along the sympathetic adrenal axis • It is supplied by branch from aorta, Inferiorphrenic and Renal
between the neck and pelvis. The most common extra adrenal arteries. A short adrenal vein on right drains in the IVC and on the left
site is organ of zucker kandl at the aortic bifurcation and other a longer adrenal vein drains in to renal vein.
sites are carotid body, aortic chemoreceptors, sympathetic • It consists of Adrenal cortex and adrenal medulla. The Adrenal cortex
ganglia etc., and they are called as paragangliomas, glomus is again divided into 3 zones outer zona glomerulosa, middle Zona
tumours depending on the anatomic location. fasiculata & inner Zona reticularis which secretes
• Itʼs also called as 10% tumour • Glucocorticoids- Which has effect on protein & carbohydrate
• 90% originate in adrenal medulla metabolism.
• 10% bilateral • Mineralocorticoids- Essential for maintenance of Sodium balance
• 10% malignant & ECF volume.
• 10% outside adrenal gland • Sex hormones
• 10% in children So adrenal cortex is essential for life.
• 10% metastasis Adrenal Medulla:
• 10% recurrence rate • It constitutes about 28% of mass of adrenal gland. It secretes Nor-
HISTORY epinephrine, Epinephrine & Dopamine. In normal individuals 90% of
• 1886 - First diagnosis by Frankel at autopsy. the cells are epinephrine secreting type & only 10% are nor-
• 1912 - Name proposed by pick, comes from Greek words phaios epinephrine secreting type. The type of cell that secretes dopamine
→ dusky and chroma → color, which refers to the staining that is unknown.
occurs when the tumours are treated with chromium salts. • These hormones are not essential for life but they help to prepare
First surgical removed by ROUX in Europe & C.H. Mayo in individual to deal with emergencies.
USA." • The adrenal medulla is a sympathetic ganglion in which its post
• 1926 ganglion neurons have lost their axons and become secretory cells.
• 1927-" The cells secrete when stimulated by the preganglionic nerve fibers
• 1936"Epinephrine was isolated from phaeochromocytoma from that reach the gland via splanchnic nerves.
by Kelly et al. Development:
• 1949"Holton demonstrated presence of nor-epinephrine in • The adrenal medulla develops from the cells of neural crest that
phaeochromocytoma. migrate to and penetrate the primitive adrenal cortex to take central
position of the gland.
95

Pheochromocytoma.Continuation: Dr Azam’s Notes in Anesthesiology 2013
Catecholamine: Actions of these Catecholamines:

• Post ganglionic sympathetic neurons produce nor-adrenaline, • These act on nearly every tissue and organ in the body through
while adrenal medulla and part of brain secrete both nor- adrenergic receptors. Their release by the sympathetic nervous
adrenaline and adrenaline. system has an important regulatory function in helping the body
adjust from moment to moment during both rest and stress.
• The normal plasma level of free nor-epinephrine is 300 pg/ml or
(1.8 mmol/l) and free epinephrine level is 30pg/ml (0.16n mol/l). Receptor Tissue Response
The plasma free dopamine level is about 35pg/ml (0.23n mol/l), α1 Vascular smooth muscle Contraction
half of it comes from the adrenal medulla and remaining from the Genitourinary smooth muscle Contraction
sympathetic ganglia.
Liver Glycogenolysis
Gluconeogenesis
Synthesis and Metabolism:
Intestinal smooth muscle Hyperpolarization and relaxation
• The Principal catecholamines are formed by hydroxylation and
decorboxytation of the amino acid tyrosine. The synthesis begins Heart Increased contractile force,
with active transport of amino acid tyrosine from circulation in to Arrhythmias
postganglionic sympathetic nerve endings. α2 Pancreatic Islets Decreased insulin secretion
• The catecholamine are then transported into the granulated Platelets Aggregation
vesicles and released from autonomic nervous system and Nerve terminals Decreased release as NE
adrenal medullary cells by exocytosis.
Vascular smooth muscles Contraction
• The catecholamines have a half life of about 2 min in circulation.
Reuptake / Elimination: β1 Heart Increased force and rate of
• These catecholamines are removed from the synaptic cleft by contraction and AV nodal conduction
• Binding to presynaptic or postsynaptic receptors velocity
• Reuptake in the presynaptic neuron, which is the major J.G. cells Increased renin secretion
mechanisms by which NE is eliminated β2 Smooth muscle Relaxation
• Catabolism (vascular ,bronchial, GI, and
• Epinephrine and nor-epinephrine are metabolized to biologically genitourinary)
inactive products by oxidation (MAO) and methyl (COMT= Skeletal muscle Glycogenolysis, uptake of K+
catechol-O-methytransferase). Liver Glycogenolysis, Gluconengenesis
• About 50% of secreted catecholamine appears in the urine as
β3 Adipose tissue Lipolysis
free or conjugated metanephrine and norometanephrine and
35% as VMA. Only small amount of nor epinephrine & DA1 Renal and mesenteric vascular Vasodilatation
epinephrine are excreted unchanged in urine. smooth muscle
DA2 Presynaptic-adrenergic nerve Inhibits Nor-epinephrine release
endings
96

To summarize:# # # # Associated syndromes:

• CVS: Increase HR, Blood pressure, myocardial contractility and 1. MEN 2A [Sippleʼs syndromes]. It is Autosomal dominant
conduction velocity in the heart. The clinical features include:
• RS: Relaxation of tracheal & bronchial muscles. • Medullary thyroid carcinoma (95%)
• GIT: Decreases the intestinal motility & tone and also inhibit • Phaeochromocytoma (40%)
secretion. • Hyperparathyroidism (25%)
• Relaxes the gall bladder. • Cutaneous lichens amyloidosis.
• Genitourinary: Stimulates renin secretion in the kidney, relaxes 2. MEN 2B
detrussor muscles of urinary bladder. The clinical features includes
• Blood: Aggregation of platelets. • Medullary thyroid carcinoma (100%)
• Metabolic: Hyperglycemia, Hyperlipidaemia thermogensis, • Phaeochromocytoma (50%)
Increased O2 Consumption, Hypokalemia. • Multiple mucosal ganglioneuroma
• Skin: Sweating of palms and hands referred as adrenergic • Rarely hyperparathyroidism
sweating. 3. Von Hippel-Lindauʼs disease
Pheochromocytoma: " " " " • It is also autosomal dominant.
It is a catecholamine producing tumours from chromaffin cells of • Phaeochromocytoma occurs in approximately 10-20% of these
adrenal medulla. patients.
Incidence: Other features are:
• It is a rare tumour, found in 0.1% of autopsies & 0.1-1% of • Renal cell carcinoma (70%)
hypertensive patients. The annual incidence is 1-2 per 1, 00, • CNS & retinal Hemangioblastoma
000, population. • Pancreatic islet cell tumours
• This tumour was previously called as 10%tumour because • Endolymphatic tumours
frequency of bilateral, multiple, extra adrenal, familial & • Renal, pancreatic, Epididymal cysts.
malignant variants were all 10%. But the incidence of familial and 4. Neurofibromatosis type I [Von Recklinghausenʼs disease]
possibly malignant disease is now greater than • It is also a Autosomal dominant
• 2% of these patients have Pheochromocytoma.
• Previously reported.
• Other manifestations are café au lait spots, optic nerve glioma &
iris hamartomas.
97

Pathophysiology: • Hypertension is hallmark of disease and found in > 90% of them. It

• Pheochromocytomas are highly vascular tumours, usually Dusky is either sustained in 50%, intermittent in 33% and remaining with
colored with necrotic or hemorrhagic areas. It usually weighs normal blood pressure.
less than 100g and less than 10cm in diameter. • Classically it is labile and occurs in paroxysm. A typical paroxysm is
• Extra adrenal Pheochromocytoma usually weight 20-40gms and characterized by sudden major increase in blood pressure, severe
are <5cm diameter. headache (pounding/throbbing, bilateral), profuse sweating all over
• Pheochromocytomas synthesize and store catecholamine by especially over trunk, palpitation with or without tachycardia, anxiety
processes resembling those of normal adrenal medulla. The or a sense of doom, skin pallor, nausea with/without emesis, pain in
tumour is not innervated and catecholamine release does not chest or abdomen. It may occur daily or as frequently as every few
result from neural stimulation. Pheochromocytoma also store & month.
release variety of peptides like endogenous opioids, Lability of BP is due to
adrenomedullin, endothelin, erythropoietin, parathyroid hormone- • Episodic catecholamine release
related protein, neuropeptide & chromagranin. • Impaired sympathetic reflexes
• Most phaeochromocytoma contain and secretes both nor- • Unrecognized chronic volume depletion.
epinephrine and epinephrine and the percentage of nor- • The paroxysm may occur spontaneously or it may precipitated by
epinephrine is usually greater than in the normal adrenal. Most of physical stress such as increase in intra-abdominal pressure from
extra adrenal Pheochromocytoma produce NE exclusively & palpation, defecation, a fall, an automobile accident, or by the act of
rarely Pheochromocytoma produce epinephrine alone. voiding in case of phaeochromocytoma of urinary bladder.
Clinical Features: • These paroxysms may also be precipitated by opiates,
• It can have a wide range of presentations from no symptoms to a metachloperamide, droperidol (dopaminergic antagonist), intra-
sudden heart attack, cerebral hemorrhage or malignancy arterial injection of radiographic contrast, Indirect acting amines like
hypertension. amphetamine, Drugs that block catecholamine reuptake e.g.-
• The classic triad of symptoms associated with cocaine, TCA, Guanithidine, MAO inhibitors.
Pheochromocytoma are: • Some patients may be normotensive even with sustained elevation in
! Headache plasma catecholamines. It is due to hypovolemia and receptor down
regulation.
• The major factor maintaining the hypertension is increased
peripheral resistance.
In association with hypertension • An important clue in the diagnosis of phaeochromocytoma in
hypertension that is poorly responsive to standard antihypertensive
drugs. It responds to α-blocking drugs but made worse by β-blocking
Palpitation Sweating drugs.
98

Other prominent symptoms: Indications for Screening: Hypertension with episodic features
• Postural hypotension – it is due to decrease in circulating blood suggesting Pheochromocytoma (triad)
volume in patients with high catecholamines and sustained • Refractory hypertension
hypertension. • Prominent lability of blood pressure
• Hyperglycemia usually mild due to α-adrenergic inhibition of • Severe pressure response during anesthesia / surgery
insulin release and does not need any treatment. • Unexplained hypotension during anesthesia
• Tremors, seizures, hypermetabolism, weight loss, fever and even • Family history
mental changes may be present. • Incidentally discovered adrenal masses
• Some patients may also present with features of acute • Idiopathic dilated cardiomyopathy
myocardial infarction with ST segment elevation/depression or Diagnosis:
inversion of T waves. Other features like LV hypertrophy, sinus Ross is 1972 described it as “Think of it, confirm it, find it & remove it”
tachycardia, and rhythm disturbances may also be present. It involves two categories
Differential diagnosis: • To confirm the diagnosis
Hyperadrenergic essential Paroxysmal tachycardia • To localize & define the extent of tumour to plan for surgery.
hypertension
Anxiety, panic attacks Angina pectoris/Myocardial Biochemical Tests:
infarction • Diagnosis can be established by demonstration of increased
excretion of catecholamine or catecholamine metabolites.
Thyrotoxicosis Brain tumor or SAH 1. Urine tests:
Migraine or cluster head ache Abdominal catastrophe/aortic Prerequisite for urine collection
dissection • Full 24hr urine is preferable. It should be collected in a strong acid
Abrupt clonidine withdrawal Cardiovascular reconditioning that is either 20ml of 6N HCl or 25 ml of 50% acetic acid. The
container should be easily sealed and leak proof & need not be
Amphetamine Menopausal syndrome
refrigerated.
Cocaine Neuroblastoma in child • The collection should be made
Alcoholism Diencephalic or temporal lobe • When the patient is at rest
seizures • Should not be on anti hypertensive medication and other
Hypoglycemia Toxemia of pregnancy medications which interfere with assay
• Should not have exposed to radiographic contrast in the recent
past.
• The urine should not be collected during clinical situation which
increase the catecholamine level which include Hypoglycemia,
strenuous exertion, raised ICP, Hypoxia.
• The urine is better collected when patient is hypertensive or during
crisis.
• Creatinine should be measured for adequacy of its solution. 99

Pharmacologic tests:
Free catecholamine:
• These tests have become almost obsolete, because they are non-
The upper limit of normal for total urinary catecholamine is specific and entail considerable risk.
between 100-150µg/24 hrs.
• NE is < 75µg/24 hr
• E is < 25 µg/24hr Suppression test:
• In phaeochromocytoma values in excess of 250µg/day is usually • Administration of phentolamine (short acting α-blocker, nonselective
alpha-adrenergic antagonist) 1-5mg IV bolus, it reduces BP 35/25,
obtained.
which peaks at 2 minutes and if persists for 10-15 minutes then it is
• In MEN increased epinephrine may be the only abnormality and
suggestive. It is never diagnostic and a biochemical confirmation is
so it should be measured, a value more than 50µg/24hr is
essential.
suggestive.
Metanephrine and VMA: • Clonidine is used more often now-a-days. 0.3 mg PO suppress
patients concentration of catecholeamines in HTN patients, but not in
• The upper limit is 1.3pg/24 hours of total metanephrine and
7.0mg of VMA/24 hours. patients with Pheochromocytoma.
• In phaeochromocytoma it usually increases more than 3 times
the normal range. Provocative tests:
Plasma catecholamines: • Glucagon is the drug usually used, in patients with paroxysmal
• The measurement of plasma catecholamine is unnecessary as hypertension and non diagnostic basal catecholamine levels. It is
the urinary test results are satisfactory. Plasma catecholamines given in a dose of 1mg iv bolus. Blood for plasma catecholamine is
are worthwhile when, clinical features are suggestive of taken 2 minutes before and after the drug is injected. In normal
phaeochromocytoma and urinary assay results are border line or patients and hypertensive patients, it has no effect on blood pressure
equivocal. or plasma catecholamines. In patients with Pheochromocytoma
• The blood should be collected when the patient is fasting, supine increases the blood pressure, and the serum catecholamines is
and needle is place in the vein for at least 20 minutes before the raised by three fold. During the test life threatening pressure crisis
sample is drawn. may occur, so phentolamine should be at hand.
• Normal values are less than 500pg/ml for NE and < 100pg/ml for
E. values greater than 1500pg/ml and 300pg/ml respectively are Localization technique:
suggestive. • It is done only after the biochemical studies have established the
• Intermediate values may be due to exaggerated sympathetic presence of Pheochromocytoma.
response. • CT scan and MRI are the two modalities of choice to localize. CT
• The best confirmatory test: Free catecholamines in a 24 hour detects tumors 1cm and larger. MRI can detect still smaller tumours,
urine collection Extra adrenal tumours and offer little advantage over CT scan. MRI
• Most sensitive 99% test: Plasma free metanephrine, which is avoids X-ray exposure, so can be used in pregnancy.
independent of posture
• Most specific 95% test: Urinary VMA estimation, which is useful
for screening and follow up.
100

I131, MIBG scan is the most useful procedure for locating a hard 2. The non competive covalent binding causes an irreversible block.
to find phaeochromocytoma. This is most useful in localizing extra The pharmacologic half life of Phenoxybenzamine is 24 hours, but
adrenal tumours not seen with conventional imaging and in the prolongation of receptor blockade depends on re-synthesis of
following patients with malignant pheochromocytomas, as it the receptors. As a result there will be marked prolongation of α -
selectively accumulates in chromaffin tissues. blockade in the post operative period even if the drug in stopped 24
Treatment: hours before surgery.
• Surgical excision is the only definitive treatment for 3. As the systemic arterioles are insensitive to α -agonists, so
Pheochromocytoma. intravascular volume is expanded in excess of predicted or
measured fluid loss, which results in interstitial fluid retention and
Preoperative preparation: widespread peripheral oedema.
It includes: 4. Other side effects – somnolence, headache, stiffness, postural
• Pharmacological measures to control hypertension and hypotension, reflex tachycardia, gastric irritation.
arrhythmias • Phenoxybenzamine is started in small doses 10-20mg twice daily
• Assessment of end organ damage and increased gradually until either all signs of pressor activity have
• Cardiomyopathy suppressed or until patient complains of side effects. Many patients
• Renal function require a dose between 40-80mg per day.
Pharmacological control:
• Doxazosin a competitive and selective α1-blocker has a long
Main objectives:
duration of action and allows once daily dosage. It is started orally
• Control arterial pressure, heart rate, arrhythmia 1mg/day and can be gradually increased up-to 16mg/day. The
• To restore blood volume to normal advantages of this drug is, it avoids the rise in nor-adrenaline
Alpha blockade:
secretion associated with α 2 blockade and limit the tachycardia that
• Preparation should start at least 2 weeks prior to surgery to allow
is due to cardiac β receptor stimulation, so it may be unnecessary to
full alpha blockade with gradual restoration of circulating blood
administer β -adrenoceptor antagonist unless it is a epinephrine
volume.
secreting tumour.
• Phenoxybenzamine (is a non-specific, irreversible alpha
antagonist.) a non selective alpha blocker in the most commonly
used drug. Its advantages are it has a long duration of action,
allowing twice daily oral ingestion and produces a non
competitive blockade. Its disadvantages are:
1. As it is non-selective it blocks the α2-adrenoreceptors on the
presynaptic membrane of adrenergic nervous terminals which
are part of negative feedback regulating release of nor-
epinephrine consequently the release of nor-epinephrine is
uninhibited.
101

β -adrenoceptor antagonist: Magnesium Sulphate:

There are two reasons for the use of these drugs in the It can be used as an alternative therapeutic strategy to adrenergic
preoperative treatment. block during anesthesia and surgery for Pheochromocytoma.
• To limit the symptoms and signs referable to increased
circulating epinephrine, which manifest as tachycardia with or Mechanism of action:
without cardiac arrhythmias. • inhibition of release of catecholamines from the adrenal medulla
• So selective β, antagonists such as atenolol 100mg/day or • inhibition of release of catecholamines from peripheral adrenergic
bisoprolol 10-20mg/day can be used. nerve endings
• Labetalol (is a mixed alpha/beta adrenergic antagonist) • direct blockade of catecholamine receptors
100-400mg/day antagonizes both α and β adrenoceptor. The β:α • vasodilatation by direct effect on vessel
antagonism of Labetalol is approximately 3:1. α block is • Myocardial protection by preservation of adenosine triphosphate and
competitive & weak. These patients are more prone for glycogen stores.
hypotension postoperatively as its β mediated anti renin effect Dose: 40-60mg/kg of MgSO4 as loading dose followed by an infusion
may prevent adequate preoperative plasma volume expansion. of 1-2g/hr to achieve serum concentration between 2-4mmol/lt,
• Other non selective β antagonist can also be used like continuing until tumor devascularization.
Propranolol 40-240mg/day, metaprolol 50-200mg/day in patients In a study conducted by James, in most of the patients only MgSO4
who do not have history of airway or peripheral vascular disease. was sufficient even during tumor handling and few (5 out of 23)
• Celiprolol 200-400mg/day (It has a unique pharmacodynamics: it required SNP to control the response to tumor manipulation.
is a selective β1 antagonist, but a β2 partial agonist. It is also a
weak α2 antagonist.) is the drug of choice in patients with airway Other drugs:
and peripheral vascular disease as it is a β1 antagonist and β2 • Alpha methyl-p-tyrosine (AMPT) was used in 1960 to inhibit rate
agonist. limiting conversion tyrosine to DOPA by suppressing tyrosine
• To block cardiac sympathetic drive secondary to suppression of hydroxylase, this decreasing synthesis of catecholamines by
presynaptic α 2 receptors, by drugs like Phenoxybenzamine. It is 40-80%.
unnecessary to use β antagonist with Doxazosin, except in • It is not used due to high incidence of side effects like anxiety,
patients known to be epinephrine secretors. lethargy, diarrhea, extra pyramidal symptoms.
Why α blockade first: • Calcium channel blockers, ACE inhibit were also used in few studies
• β-blockade should not be instituted in the absence of α-blockade and are of doubtful value.
because the heart depressed by β-blockade might not be able to
maintain the cardiac output, as uninterrupted α-mediated
vasoconstriction from release of catecholamines result in abrupt
increase in SVR.
102

For rapid intravenous α-blockade:

• Echocardiography may reveal global myocardial dysfunction or
• On day 1: Phenoxybenzamine HCL 1mg/kg in 500ml of 5% regional wall motion abnormalities with decreased ejection fraction.
dextrose over 2 hours and Propranolol orally if pulse rate > 120
• The condition is partially reversible after treatment with β blocker or
bts/min.
resection of tumour
• On day 2: Phenoxybenzamine HCL 1-1.5mg/kg over 2 hours and
• Intravenous amiodarone can be used instead of β-blocker to treat
Propranolol to keep pulse rate < 100.
dysryhtmias in such patients.
• On day 3: Phenoxybenzamine HCL 1-2mg/kg over 2 hours and
• β-blockade is better avoided in patients increased catecholeamines
Propranolol as necessary.
as it may precipitate pulmonary oedema (CCF).
• On day of surgery: Phenoxybenzamine HCL 50mg and
• Monitoring with pulmonary artery catheter is helpful in patients with
Propranolol as necessary.
cardiomyopathy.
• Blood pressure should be around 110/70 and pulse rate < 90/ Glucose intolerance:
min.
• Raised plasma catecholamine by (Epinephrine) β2 mediator
mechanism inhibit insulin release and antagonize its action. This
Roizenʼs criteria for evaluation of efficacy of preparation:
together with increased glycogenolysis and FFA mobilization result in
• BP record for at least 48 hours prior to surgery should be <
hyperglycemia and glycosuria in 60% of patients. This rarely requires
160/95 all times.
treatment with insulin and resolves following tumour resection. A
• Mild orthostatic hypotension indicates optimal α-blockade. BP
period of hypoglycemia may occur postoperatively and delay
should not be < 80/45 in standing position. Less than that
recovery.
indicates inadequate hydration.
• ECG free of ST-T changes at least for 2 weeks Surgery:
• Ventricular ectopic < 1 every 5 minutes. • Conventional approach is anterior transperitoneal approach and
• Serial monitoring of hematocrit is a useful method for evaluating small tumours can be removed by posterior approach
the adequacy of intravascular fluid volume expansion and a
• Laparoscopic adrenalectomy is also done; it offers advantage of
satisfactory α-blockade is implied if hematocrit decreases by rapid recovery and easy discharge from the hospital.
about 5% from 45 to 40%.
Catecholamine cardiomyopathy:
• Cardiomyopathy is seen in approximately 25-50% of
Pheochromocytoma as a result of sustained exposure of
myocardium to high levels of catecholamines
• Patients may present with symptoms and signs of CCF,
Dysrhythmia, acute pulmonary edema, non-specific ECG
changes like left ventricular hypertrophy, conduction defects, ST-
T wave changes consistent with ischemia/infection.
103

Management of Anesthesia: Premedication:

It is based on • An anxiolytic – sedative, benzodiazepine are administered to prevent
• Administration of drugs that do not stimulate the sympathetic the anxiety induced sympathetic release of catecholamine
nervous system • Anticholinergics are better avoided as it may cause tachycardia and
• Use of invasive monitoring techniques to facilitate early and hypertension.
appropriate intervention when catecholamine induced changes in • Morphine based premedication are also avoided as it has the
cardiovascular function occur. potential to release histamine and induce catecholamine release
• The α and β antagonist therapy should be continued till the day • If bilateral adrenalectomy is planned, then supplemental cortisol
of surgery. If Phenoxybenzamine is used, it can be stopped should be instituted at the time of preoperative medication.
24-48 hours prior to surgery.
• The times of intraoperative hazards are Monitoring:
• During tracheal intubation • Large bore venous access for rapid fluid administration
• During manipulation of tumour • Indwelling radial artery cannulation is done under local anesthesia
• After ligation of tumours venous drainage and sedation for beat to beat assessment of blood pressure and
blood gas measurement.
Anesthesia technique: • Pulse oximetry
• A combined general and regional anesthesia technique, using a • ECG
segmental mid to low thoracic epidural combined with adequate • Urinary catheter
general anesthesia and selective adrenergic antagonists to • Temperature probe
control hemodynamic status, is the preferred technique of • Capnography
choice. • CVP – to assess volume status
Pre Anesthetic Examination: • Pulmonary artery catheter – useful for monitoring the status of
• Routine hematological and biochemical investigation like – intravascular fluid volume in patients with cardiomyopathy or
• Hb%"" " impaired LVF. It also measures cardiac output, helpful in evaluating
• Serum electrolytes cardiac function and the need for intervention with inotropic and
• Hematocrit" " vasodilator drugs.
• Serum calcium • Transoesophageal echocardiography: It almost gives the same
• Blood sugar" " information that is available from pulmonary artery catheter. It is less
• ECG – To detect arrhythmia, LVH, ischemia, infarction invasive. In presence of decreased left ventricular compliance,
• X-ray – Cardiomegaly, pulmonary edema PAOP may not provide an accurate assessment of left ventricular
• Echocardiography – LV function assessment, cardiomyopathy. preload. In such patients end diastolic left ventricular area can be
used to assess filling and fluids can be given to maintain baseline
levels.
104

Induction of anesthesia: • Inj. lignocaine 1-2mg/kg iv about 90 seconds before laryngoscopy

Midazolam 0.05mg/kg given in pre-anesthetic room calms down and Fentanyl 2-3 µg/kg just before laryngoscopy attenuates the
the patient. Another 0.05mg/kg of midazolam given prior to hypertensive response as well provides adequate analgesia.
induction helps in smooth induction." • Inj. sodium nitropruside 1-2µg/kg as a rapid injection is effective for
• Induction can be most often accomplished with IV administration treating acute and persistent increases systemic blood pressure and
of thiopentone or propofol or etomidate. should be readily available.
• Etomidate is thought to release catecholamines due to pain and • Inj. Phentolamine 1-5mg iv as intermittent and injections is an
involuntary movement alternative.
• Propofol 1-1.5mg/kg seems to be logical choice.
• Induction agents are given slowly along with close monitoring of Maintenance:
heart rate and blood pressure. • Anesthesia is maintained with oxygen, nitrous oxide, isoflurane/
Sevoflurane/ Desflurane, with intermittent doses of Vecuronium and
Neuromuscular blockade: IPPV with a rate of 10-12 breath/min tidal volumes of 10ml/kg.
• A non depolarizing muscle relaxant inj. Vecuronium 0.1mg/kg is • Concentration of volatile agent is adjusted in response to change in
of choice blood pressure.
• Rocuronium, cisatracurin can also be used. • Careful monitoring with watchful expectancy should be maintained
• Other NDMR which release histamine are avoided. throughout with easy access to drugs for control of hypertension,
• Scoline is also avoided, because the fasciculation and rise in hypotension, arrhythmias, pulmonary oedema, CCF, hypoglycemia.
intra-abdominal pressure associated with Scoline can squeeze • Intravascular fluid volume status is maintained via CVP or PA
the tumour mechanically resulting is rise in blood pressure, and it catheter and fluids are given generously maintain CVP around 10-12
also release histamine. mm of H2O
Inhalation agents: Epidural anesthesia:
• The choice of volatile agent is based on the ability to decrease • After intubation the patient can be turned to their side for careful
sympathetic nervous system activity and the low likelihood of sterile placement of epidural catheter in mid to low thoracic inter-
sensitizing the heart to dysryhtmias. space. Inj. Bupivacaine 0.25-0.5% 6-8ml is injected and repeated at
• Isoflurane is preferred agent appropriate time intervals.
• Desflurane and Sevoflurane are also used successfully • It suppresses the release of catecholamines from adrenal gland
• Halothane, enflurane are avoided because of their except for tumour handling.
arrhythmogenic potential. • Extensive epidural sympathetic blockade may complicate already
difficult hemodynamic control after removal of the gland.
Laryngoscopy and intubation: • It also gives advantage of adequate post operative analgesia, which
contributes to early tracheal extubation.
• Direct laryngoscopy and intubation is initiated only after
establishing a surgical depth with volatile Anesthetics to minimize
increase in systemic blood pressure.
105

Hypotension:
Perioperative problems:
It is may occur due to
Hypertensive crisis and dysryhtmias:
Precipitating factors: • Rapid decrease in circulatory catecholamines following ligation of
venous drainage of tumour.
Mainly – intubation and tumour manipulation
Others –" preoperative anxiety • In association of hypovolemia
" " Induction • Due to residual long acting α and β blockade
Management:
" " Hypercarbia
• Adequate fluid replacement guided by invasive monitoring to
" " Hypoxemia
maintain a CVP of around 10-12cm of H2O is all that required. It is
" " Hypoglycemia
frequently large 0.5-1.5 times the patients total blood volume during
Drugs used in the management:
the first 24-48 hours after removal of tumour
1. Phentolamine: A non selective α blocker given in 30-70µg/kg iv
intermittent bolus produces a prompt, transient decrease in • Rarely infusion of dopamine (3-10µg/kg/min) or phenylephrine
(20-50µg/min in adults) may be required.
systemic blood pressure. Onset of active is within 2 minutes
duration is 10-15 minutes. Post operative management:
2. Sodium nitroprusside: A 0.01% solution in a dose of 0.2-3µg/
• The neuromuscular blockade can be reversed and extubated post
kg/min iv infusion titrated as required. It has immediate onset of operatively or kept electively on artificial ventilation depending on the
action and very short duration (2-3 minutes) of action. hemodynamic stability.
3. Nitroglycerin: It can be given in doses up to 2µg/kg/min iv
• All patients should be managed in the ICU, with close invasive
infusion. It is also fast acting with short duration. It has an monitoring.
advantage of coronary vasodilatation.
• Adequate postoperative analgesia through the epidural catheter is
4. Esmolol: A short acting selective β, antagonist in a dose of provided.
100-300 mg/kg/min infusion. Its onset of action is 2 minutes
• Persistent hypotension refractory to fluid replacement, reflects
with a short half life of 9 minutes. It controls intraoperative preoperative down regulation of adrenergic receptors is presence of
hypertension and tachyarrhythmia without precipitating cardiac excessive catecholamine secretion.
failure.
• About 50% of patients remain hypertensive for up-to 3 days following
5. Propranolol: 1-2mg iv is also used to control tachycardia, its tumour resection. Catecholamine levels should return to normal by
duration of action lasts for 30-45 minutes, so its action persists 72 hours. After 3-10 days, 75% of the patients will be normotensive
following tumour removal, contributing hypotension. and if hypertension persists beyond 2 weeks post surgery, than
6. Other drugs like Labetalol, calcium channel blockers (diltiazem, plasma and urinary catecholamines should be measured to eliminate
nicaridipine): Are also used to treat hypertension. residual or metastatic disease.
7. The use of β blockers should be limited in patients with
• Hypoglycemia may develop as the α-adrenergic induced suppression
catecholamine induced cardiomyopathy. Amiodarone, to treat of insulin waves after removal of tumour so glucose must be
supraventricular tachycardia and lidocaine for ventricular supplemented at the end of surgery.
arrhythmias are also used.
106

Pheochromocytoma in pregnancy:
• It is a rare but dangerous condition • The use of β-blocker during pregnancy is associated with fetal
• It may be confused with preeclampsia bradycardia, hypotension, uterine irritability and decreased fetal
• Localization of the tumour is done by MRI/ultrasonography response to acidosis and hypoxia. Labetalol is safe for both mother
• The management of pregnant patient with Pheochromocytoma and fetus even if it crosses placenta.
and constricted blood volume is compounded by normal • β-blocker with a higher specificity for β, receptors and lower lipid
physiological changes of pregnancy including increase in blood solubility are more appropriate as lesser amount crosses the
volume, aortocaval compression and hemodynamic changes placenta. E.g. metaprolol, atenolol.
during delivery. Clinical Features
• If the patient is in first two trimesters than the tumour should be • Hypertension is the most common manifestation, 60% of then have
removed as soon as α blockade is achieved. In third trimester sustained elevated blood pressure & 40% have only during attacks
patient is treated with α-blockers and carefully monitored till the or paroxysms.
fetus reaches sufficient maturity to be viable. At this point Paroxysm or Crisis:
caesarean section is performed, as vaginal delivery is • The symptoms are usually similar with each attack. It may occur
hazardous. frequently or at intervals as long as week to months.
• Epidural analgesia for vaginal delivery may obtain the • It is usually sudden in onset, lasts for minutes to hours. Headache,
sympathetic response to painful labor but will have no effect on profuse sweating, palpitation and apprehension with a sense of
systemic response to catecholamines, liberated directly from the impending doom are common features.
tumour. • Pain in chest or abdomen associated with nausea and vomiting
• MgSO4 can be used as sole agent for preparation and control of • Paroxysm may also be precipitated,
Drugs like,
hypertensive emergencies during surgery, provided therapeutic
• MAO inhibitors
serum level of 2-4 mmol/lt is achieved, in view of preexisting
• Tricyclic Antidepressants
hypomagnesaemia. It can be considered as a ideal agent of
• Phenothiazines
choice in pregnant patient with Pheochromocytoma as it is safe
• Metachloperamide
in pregnancy and because of potential adverse effects of other
• Naloxone
drugs on fetus.
• Eating,
• Most of the adrenergic blockers cross the placenta, but are safe
• Exercise,
when used long term.
• Smoking,
• The α-blocker of choice is Phenoxybenzamine its use has been
• Change of body posture,
reported to be without any adverse effects in many patients.
• Valsalva maneuver,
• carotid body massage and
• Pain.
107

Cardiovascular manifestations:
• Sinus tachycardia or bradycardia
• Supra ventricular arrhythmias
• Ventricular premature contractions
• Angina or MI in the absence of CAD
• Catecholamine induced cardiomyopathy
• CCF with myocarditis, Myocardial fibrosis,
• Concentric hypertrophy / asymmetrical hypertrophy.
• Rarely multiple organ failure and non cardiogenic pulmonary
oedema.
Other features:
" - Fatigue" " " - Stroke
" - Anxiety" " " - Acute renal failure
" - Weight loss"" " - Elevated temperature
" - Glucose Intolerance
• The clinical signs and symptoms may not correlate well with
catecholamine levels, and a normal blood pressure may be seen
with high plasma levels & may reflect decreases in α receptor
concentration [Down Regulation], secondary to chronic exposure
to high levels of catecholamine.
108

15. Case Discussion on Diabetes Mellitus. Dr Azam’s Notes in Anesthesiology 2013
Diabetes mellitus: Clinical Feature:

Definition: Feature (1DDM) type I Type II NIDDM
• It is an endocrine disorder due to pathology in B-cells of Genetic locus Chromosome 6 Chromosome 1
Langerhans of pancreas – causing absolute or relative lack of Age of onset < 16 yrs > 16 yrs
insulin – leading to hyperglycemic and glycosuria. Onset of symptoms
Etiology: Abrupt Always gradual
Duration of symptoms Days or weeks Months to years
• Hereditary Diagnosis c/o polyuria, polydypsia, No complaints,
• Viral infection – Coxsackie B, Reo virus type I, Rubella,
polyphagia detected on routine
Classifications/Types: examination
Body habitus
Type I: Plain insulin weight loss Obese
• Juvenile / 1DDM / < 16 yrs / immune mediated / ketoacidosis Plain glucagon Normal – Low to absent Normal – high
prone Highly – susceptible High – resistant
Type II:# Acute complications
• MODM / NIDDM / > 16 yrs / non-immune mediated / ketoacidosis Ketoacidosis Hyperosmolar coma.
resistant Insulin therapy
Type III:" Responsive Responsive to
" A – pancreatic pathology Sulphonylurea urea resistant
• Pancreatitis treatment Un-responsive Responsive
• Haemochromotosis Auto-antibodies
Other auto immune Yes No
• Pancreatectomy, Neoplasm
diseases
" B – Hormonal abnormalities Yes
Family H/o DM
• Acromegaly Yes
Rapid diet control
• Cushingʼs syndrome without treatment with No No
• Pregnancy (HPL) insulin Yes
" C – Liver disorder
• Hepatitis
• Cirrhosis
# D# – Genetic syndrome "
• DIDMOAD
• Downʼs syndrome
• Klinefilterʼs syndrome
" E - Cancer
• Pancreatic carcinoma
Type IV:#
• Gestation DM
109

Case Discussion on Diabetes Mellitus.Continuation: Dr Azam’s Notes in Anesthesiology 2013
Diagnostic criteria: Indications

ADA and who recommendation in 1997 • Not done in all patients
• Indicated in patients with Impaired Glucose Tolerance to confirm
Impending DM diagnosis
Normal
tolerance confirmed • Border line diabetes
• Glycosuria in pregnancy
FBS < 6 mmol/L 6.1 – 7 >7 Impaired Glucose tolerance (IGT):
(< 110 mg %) (110-126) ( > 126) • If the 2 hours blood glucose value 15 between 140mg 200 mg % and
one other value during test is ≥ 200 mg / dl – is diagnosis as IGT.
PPBS <7 7 – 11.1 > 11.1 Insulin:
(> 200 mg %) • Discovered by Banting and Bert, 1922, Jan 11 – first admistered to a
student of 11+yr age at Toronto – Canada
RBS • Secreted by B cells or longer lens of pancreas
- - > 200mg in patient with
symptoms of diabetes • 40 – 60u/ day secretion(1.5 u/kg)
• it is protein, poly peptide with 51 amino-acids and two chains A & B
Patient with symptoms and RBS > 200 mg % are diabetic linked by disulphide bonds
Difference between Bovine and Human insulin:
• Risk of allergy is more with bovine than porcine
Oral Glucose Tolerance Tests (GTT): • Potency is less WITH bovine
• The patient is fasts overnight, next day morning before test; • t ½ or IV insulin – 5-6 minutes
patient should rest for 30 minutes. A sample of blood taken for • Molecular weight – 6000
estimating blood glucose level. A glucose load or (1.75 gm/kg ) • PH or plain insulin 3.2 and all others insulin 7.2
over 75 gm for adult dissolved in 300ml water given orally. Blood • Human insulin is free of allergy
samples drawn at half hour intervals for 2 hours and glucose
levels estimated.
Diagnostic criteria:
Fasting:
• Venous plasma glucose concentration ≥ 120 mg % on at least 2
separate occasions
• Following ingestion or 75 gm or glucose, venous plasma glucose
concentration ≥ 200 mg % at 2 hours and at least one other
occasion during 2 hours test.
110

Actions of insulin: Classification of insulin drugs:

It is an anabolic hormone promotes peripheral uptake of glucose Type Onset (hrs) Peak (hrs) Duration (hrs)
and K+ Short acting: 15 min 30 – 90 min 3 – 4 hrs
↑ Increases (Anabolic) ↓ Decrease (Anti catabolic) Insulin lispro (hemalog) 0.5 – 1 2–4 6–8
Carbohydrate metabolism Gluconeogenesis Regular/crystalline/plain / 1 – 3 5 – 10 12 – 16
Glucose transport Glycogenolysis soluble
Glucose phosphorylation Semilente
Glycogenesis Intermediate acting: 2–4 6 – 12 18 – 26
Lente 2–4 6 – 12 18 – 26
Glycolysis
NPH+ or isophane insulin
Lipid metabolism: Lipolysis
Triglyceride synthesis Lipoprotein lipase Long acting 4–8 14 – 24 24 – 36
Ultralente 4-8 14 – 24 24 – 36
FA synthesis (liver) Ketogenesis
Protamin zinc insulin
Lipoprotein lipase (adipose FA oxidation (liner)
tissue activity)
Protein metabolism Protein degradation
Amino acid transport
Protein synthesis
Electrolytes
Cellular K+ uptake
Human insulin:
• Actrapid ( Rapid ) – highly purified regular insulin duration – 8 hrs
• Manotard MC – monocomponent late insulin DOA 2 hrs
• Mixtard 30:70 – semi-lente: ultralente
Newer insulinʼs (insulin Analogs):

• Insulin lispro
• Glougine
• once daily
• maintain slow glucose throughout the day
111

Oral hypoglycemic drugs (OHA): 1. Thiazolideidiones:

Approved name Dosage Duration Metabolism Remarks • Onset of action 6 weeks
• Rosiglitazone
Sulphonylurea
• Pioglitazone
ureas: 100-750m 736m (up- Kidney Disflurine like
First • Trogliazme – associated with hepatic failure, so banned
g to 60hrs) Liver reactions,
generations: 2. Megliturnides: (non Sulphonylurea)
500-3000 6-12 Liver/ cholestasis •
Chlorpropamide E.g.: Repaglinide, Nateglinide
mg 12-18 kidney jaundice •
Tolbutamide Has shot duration of action
250-1500 12-24 Liver exflovative •
Acetahexamide Treat post prandial hyperglycemia
mg dermatitis 3. α-glucosidase inhibitor:
Second 100-1000 • Acarbose
generation: mg 18-24 Liver/ • Miglitol
# 12-18 kidney Hypoglycemia Evaluation of patient:
Glibenclamide Liver/ prolongs Clinical examination for general anesthetic:
# Glypizide 2.5-20mg kidney Stiff Joint syndrome:
5-40mg 24hrs • Diffuse glycosylation of proteins in long standing diabetes.
Third generation: • Shows evidence of limited joint movements, initially manifesting in
# Liver/ small joints of digit and hands.
Glimepramide 1-8mg 3-10 kidney • Appearance or tight, waxy skin short stature, joint rigidly
2-4hrs GI symptoms • Inability to approximate the palmar surface of interphalangeal joints –
Biguanides: lactic acidosis prayerʼs sign
20-15 Liver/ deficiency of • The atlanto-occipital joint may be involved, causing difficulty in
Phenformin
500-2000 Kidney vitamin B12 laryngoscopy of inhibition of trachea
# Metformin
mg Kidney Gastroperesis:
• Resulting in delayed gastric emptying, occurs in 20-30% all diabetic
patients
• Manifests as Nausea, vomiting, abdominal distension.
• Treatment – metoclopramide treat as full stomach and adopt rapid
sequence intubation.
112

For spinal Anesthetic: Immediate HR response to change in posture:

• Autonomic neuropathy reflects dysfunction of ANS. The The patient lies quietly and asked to standup throughout, the ECG is
manifestations of diabetic neuropathy include recorded.
CVS manifestations The shortest R-R interval at or around 15th beat and largest R-R
• Postural hypotension interval at or around 30th beat after standing is measured.
• Resting tachycardia If 30:15 ratio a R-R interval is ≥1.04" -" normal
• Absence of sinus arrhythmia " " " " 1.01-1.03" -" borderline
• Abnormal valsalva maneuver " " " " ≤ 1.0" " -" abnormal
• Painless Myocardial infarction Blood pressure response to standing:
Various tests to assess CVS involvements: BP measured while patient lying down quietly and while he stands up,
Heart Rate response during deep breathing: the postural fall blood pressure taken as difference between the SBP
• Patient sits quietly and breathe deeply at about 6 breaths per lying and in standing.
minute for one minute. An ECG is recorded throughout. The " If fall ≥ 30mmHg" -" abnormal
maximum and minimum R-R internal during each breathing cycle " " 11-29" " -" borderline
measured with a ruler and converted into beats per min (HR) " " < 10" " -" normal
• Result is expressed as the mean of the difference between Blood pressure response to sustained hand grip:
maximum and minimum HR for 6 measured cycles in bts/min, • Handgrip is maintained to 30% of maximum voluntary contraction
if difference is ≥ 15 beats/min" -" normal which determined by dynameter, for as long as up-to 5 min BP
" " " 11-15 "" -" borderline measured 3 times before and at one minute interval during handgrip.
" " " <10" " -" abnormal The result and difference between highest DBP during handgrip and
mean or three DBP before. A rise of Diastolic Blood Pressure
Valsalva maneuver: VM
• ≥ 16mmHg"" normal
• V.M. consists of forced expiration against a standardized
• " " " borderline
resistance for a specific period of time.
• < 10"" abnormal
• The patient blows forcefully into mouth piece attached to the
mercury to maintain 40 mmHg positions pressure for 15
seconds. Then he releases and breaths quietly for 1 min.
• Valsalva ratio is expressed as ratio of largest R-R interval after
the maneuver (reflecting bradycardia) to shorted R-R interval
during maneuver. (Reflecting tachycardia)
If ratio ≥ 1.20"" -" normal
" 1.11-1.19 " " -" borderline
" ≤" 1.10" " -" abnormal.
113

Investigations: Anesthesia for major surgery:

Blood: Aim: To prevent hyperglycemia/hypoglycemia
• Haemoglobin • Hypoglycemia is more dangerous à it causes irreversible cerebral
• TC. DC ischemia
• ESR • Patient is admitted at-least 3 days prior to surgery because of long
Urine: half life of OHA
• Albumin • DM is confirmed and controlled
• Glucose • Switch over OHA to plain insulin
• Benedicts test (reducing sugar) • NPO orders for 8hrs
• Glucose - oxidase test (specific for glucose) • First case on the day or surgery list, to avoid stress and
• Microscopy – albuminuria – 30 – 300 mg/day – early hypoglycemia
nephropathy • Skip morning dose of insulin
• Ketone bodies • Ask for morning FBS and serum potassium
• Rotheraʼs Test • Start 500ml 10% dextrose + 10 U insulin + 10mmol of k+ at 100ml/hr
• Gerhardʼs test • Flush 40ml of this infusion through drip set, to overcome insulin
• Blood glucose – FBS/RBS/GTT absorption
• Hb – HbsAg • Alternatively human albumin can be added to bottle
• Blood urea/serum creatinine • Another i-v line secured for isotonic fluid for maintenance
• Fundus examination • Ringer Lactate should not be used (because lactate gets converted
• ECG to glucose)
• Chest X-ray • RBS is checked every hourly till the end of surgery
• ECHO • Sugar levels maintained according to sliding scale
• < 110mg – 5U
Syndrome ʻXʼ: • 110-180-10U
• It is a constellation of various system involvement – • 180-300-15U
hypertension; obesity; Diabetes Mellitus, hyperlipedemic. • >300mg-20U
Anesthesia: for minor surgery: Tight control:

• Usually a day care surgery, patient not admitted • Maintenance or blood sugar level between 100-200 mg%
• Diabetes confirmed and controlled • Indication: Major surgery (like bowel anastomosis)
• It is not necessary to switch from OHA to insulin • Gestation DM
• Change over from long activity OHA to short acting OHA • CABG (more insulin required)
• Anesthesia is usually with ketamine/propofol gas-O2-Halothane/
blocks
• Patients can resume oral feeds and OHA 3-4hrs after surgery
114

Permissive hyperglycemia: Treatment of volume depletion:

• Can permit glucose up-to 250mg% • 0.9% NS 1 lit – 30 min
• 0.9% NS 0.5 lit –30min
Intraoperative hypoglycemia: • 0.9% NS 0.5 lit – 1 hr
• Detection and management • 0.9% NS 0.5 lit – 2 hr
• RBS < 50mg% • 0.45% NS – if blood sugar level ≤ 250mg% change over to 5%
• Under Spinal Anesthesia – sweating, restlessness, thirst, dextrose with insulin: 10-20units IV followed by infusion 0.1ml/kg/hr
confusion, anxiety, tremor, tachycardia, hypotension, seizure and • How dose continuous infusion provides steady glucose control
coma (< 40mg%) prevents insulin resistance
• Under General Anesthesia – Unexplained tachycardia, sweating, • K+: if K+≥ 5.5 – No K+ added
RBS by glucometer • 3.5-5.5 – 20mmol/kcl/lit
• Treatment – 50 ml of 25% glucose • < 3.5 – 40mmol/kcl/lit
• NaHCO3 added if pH < 7.2, if pH >7.2, K+ not necessary
Anesthesia for B/K amputation with DKA emergency: Choice of anesthesia:
Diabetic ketoacidosis:
• Low and unilateral spinal
Clinical: Laboratory investigations: • No sedation to be given
Nausea, vomiting, dehydration, Hyperglycemia > 250mg% • Fresh blood to be arranged
hypotension, tachycardia, Acidosis pH - 73 • Tourniquet should not be applied (because of – thromboembolism)
abdominal pain, ileus and coma HCO3< 15 mEq
Ketones in blood and urine
Hyperosmolarity Anesthesia for slough excision in foot:
Hypokalemia • Nerve blocks – ankle block knee block – if no neuropathy
Increased BUN, Serum- • If neuropathy present – refrigeration anesthesia by packing ice packs
creatinine over the caused nerve.
Diagnostic essential:
• Hyperglycemia > 250mg%
• Acidosis pH < 7.3
• HCO3< 15 mEq
• Urine for ketone
• Ketone bodies: aceto-acetic acid: B (OH) butyric acid and
acetone
115

Diabetic ketoacidosis pathogenesis: Complications Can be divided into:

Acute complications
! Insulin deficiency Hyperglycemia Glucagon excess • Diabetic ketoacidosis
• Hyperosmolar nonketotic diabetic coma
• Hypoglycemia
Activation of
Lypolysis (Adipose Hyperosmolar Activation of • Lactic Acidosis
state carnitive acyl Late complications
tissue)
transferase • Macroangiopathy
• Microangiopathy (IDDM)
Increases plasma
free fatty acid Osmatic diuresis • Retinopathy
concentration Act on
• Nephropathy
• Disorders of nervous system
Volume depletion • ANS neuropathy
and dehydration • Peripheral neuropathy
Somagyi phenomenon:
Increases " Fasting hyperglycemia
hepatic FFA " Night hypoglycemia
concentration Treatment: Decrease the evening dose of insulin
Dawn phenomenon:
" Lasting hyperglycemia
Increases " No night hypoglycemia
ketone bodies Treatment: increasing the dose of insulin
Management of diabetes mellitus:
1. Diet alone (70%)
Ketoacidosis 2. Diet and oral hypoglycemic agents (20-30%)
Complications of diabetes mellitus (NIDDM) 3. Diet and insulin (20-30%)
• Coronary - A disease
Uses of insulin:
• Cerebrovascular diseases
• Diabetic ketoacidosis
• Peripheral vascular diseases
• Hyper osmolar non ketotic diabetic coma
• Glucose insulin drip (treat hyperkalemia)
• GLK drip to treat arrhythmia due to hypokalemia
• To treat completeness and vagotomy
• Insulin in tolerance test
116

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• Plan C2&/#8&,-#&/8#)B"3-"4##
date and surgery )*6%6+/26/7%8(69%(),-:()%
B++"#3247-'17#7+/,"+2## =1,0#1/)@21/###
• Evaluate Anesthetic sugar diabetic treatment K-L+"-#&8'1))1+/#
9A&2B&,-#$/-),0-,17#)B3&"#81&D-,17#,"-&,'-/,## #
E@,1'1%-#3247-'17#7+/,"+2## &/8#@"-+@-"&,1A-#
• Optimize glycemic control #
./A-),13&,1+/)#9FGH#FIJH#92-7,"+24,-)# +"8-")# ?1/+"# )@"3-"1-)# &/8# $8'1,#:5C#8&4)#D-E+"-## $8'1,# :5C# 8&4)# D-E+"-#
• Investigations ECG, CXR, Electrolytes #
# 3++8#3247-'17#7+/,"+2## 6,&D121%-# =1,0# )0+",# )@"3-"4##
# &7,1/3#1/)@21/### 6,&D121%-# &/8# 7+/,"+2# 1E#
Mechanism for Long term Complications Diabetes Mellitus: /-7-))&"4####
Polyol !"#$%&'()*+,-*.,&/*0"-)*1,)23'#%0',&(*4'%5"0"(*!"33'06(7*
! Replace any long
Pathway: # acting OHA to short
# OHA ! FBS, serum
G2B7+)-# ! Admit day before potassium
# surgery ! Operate as 1st case
! Start iv, insulin/
$28+)-#J-8B7,&)-# # glucose (GIK
! FBS
regimen)
# ! Operative care
6+"D1,+2# ! Omit insulin morning
./7"-&)-)# E)'+2&21,4# NO&P-)# ! Omit breakfast and
dose
,0-#7-22#6=-22#B@Q## #
Intraoperative OHA
! Monitor blood glucose
surgery ! Avoid glucose
# hourly
containing fluids
! NPO 8 hrs
C+24+2# ! Monitor blood
# glucose 2nd hourly
./L2BR#+L#S:E#1/,+#,0-#7-22# #
! Monitor daily ! Monitor blood
! Monitor blood
# glucose glucose
M"B7,+)-# ./TB"4#,+# glucose ! Transfer to ! Restart
670=&//#F-22)# # ! Restart oral agents subcutaneous subcutaneous
with first post insulin if unstable insulin
6=-221/3#+L#,0-#F-22# # operative meal ! Return to oral ! Discontinue iv
Postoperative hypoglycemic agent insulin 2-3hrs later
surgery #
E,0-"# O-70&/1)'# when stable
1)# 1,# 1/01D1,)# .+/# #
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117

Complications:
Intraoperative due to diabetes:
• hypoglycemia,
• hyperglycemia,
• hypokalemia,
• ketoacidosis,
• electrolyte imbalance,
• Acedemia and
• volume depletion
Others
• Angina,
• CHF,
• MI,
• Arrhythmia,
• CVA,
• ARF,
• Pulmonary edema,
• Embolism
Postoperative
All complications of intraoperative,
• Delayed recovery,
• Compressive neuropathy/palsy and infection
118

16. Describe clinical manifestation of diabetic autonomic neuropathy. what are its Dr Azam’s Notes in Anesthesiology 2013
implication? A 50 year old man with known diabetic is scheduled for upper abdominal
surgery. How will you evaluate the autonomic nervous system?
Cardiovascular:
Clinical Manifestation : Possible symptoms of autonomic
• Orthostatic hypotension (often associated with or exacerbated by
neuropathy
eating, exercise and raised temperature)
Sweating:
• Other orthostatic symptoms ( for example, nausea, palpitations, light-
• There may be no sweating or reduced sweating (anhidrosis headedness, tinnitus, shortness of breath)
and hypohidrosis), but excessive sweating (or
• Syncope (may occur with micturition, defaecation)
hyperhidrosis) can occur as a compensatory mechanism
Temperature regulation: • Inability to stand without syncope (severe cases)
• Arrhythmias
• Hypothermia and hyperpyrexia can result from disruption of
the various temperature regulatory mechanisms. Sweating, • Supine hypertension
shivering and vasoactive reflexes can be affected • Loss of diurnal variation in blood pressure (BP)
Respiratory:
Face:
• In diabetics, reduced bronchoconstrictor reflexes have been detected
• Pallor
(contributing to reduced responses to hypoxia)
• Reduced or absent sweating Gastrointestinal:
Vision:
• Constipation
• Blurring of vision
• Diarrhea
• Tunnel vision
• Incontinence
• Light sensitivity
• Dry mouth
• Difficulty focusing
• Disturbance of taste
• Reduced lacrimation
Feet:
• Gradual reduction of pupillary size
• Burning sensation
Sexual: • Hair loss
• Impotence • Pruritus
• Ejaculatory failure • Dry skin
• Female sexual dysfunction • Pale, cold feet
• Worsening of symptoms at night • Worsening of symptoms at night
119

Describe clinical manifestation of diabetic autonomic neuropathy. what are its implication? Dr Azam’s Notes in Anesthesiology 2013
A 50 year old man with known diabetic is scheduled for upper abdominal surgery. How will you
evaluate the autonomic nervous system? Continuation:
Bed side autonomic tests:

In patients with a positive history or disease processes associated with autonomic dysfunction, a
number of simple tests can be performed by anesthesiologist during bedside visit. These can be divided into:
Test of cardiac vagal function: Test for sympathetic function:
• Respiratory Sinus Arrhythmia (RSA) Cardiac

• Valsalva ratio (phase IV/II) • Tachycardia during standing or head up tilt
• Bradycardia during phenylephrine challenge. • Tachycardia during valsalva strain (phase II)
Absence of tachycardia with atropine. Peripheral
•
• Blood pressure overshoot after valsalva release (phase IV)
• Blood pressure increase with cold pressor test
• Diastolic blood pressure increase with isometric hand grip exercise
• Systolic and diastolic blood during response to upright posture.
Postural Stress: Supine to Standing (Sympathetic Function)

• The easiest and most commonly performed bed side test to evaluate autonomic function is to record blood pressure and heart rate response to
assumption of the upright posture.
Procedure:
• Heart rate and blood pressure should be recorded in the patient in supine position after a resting period of 10 min. Then the patient is asked to stand
up unaided and after 50 seconds pulse rate and blood pressure are to be measured. When taking blood pressure in a standing subject the cuff
should be approximately at the phlebostasis axis to eliminate the error due to gravity.
Result:
• A decline in systolic blood pressure of greater than 20 mmHg is generally used as a critical value suggestive of autonomic dysfunction. Similarly
diastolic blood pressure should not decrease by more than 10mm Hg during 1 min standing .Heart rate should increase at least by 10beats/min in
the upright position. The absence of tachycardia during standing has also been interpreted as an impairment of sympathetic drive to the heart.
• Ratio of RR interval in ECG corresponding to 30th and 15th beats (30:15 ratios) is a measure of integrity of vagal inhibition. A ratio in young adults of
less than 1.04 is abnormal.
120

A 50 year old man with known diabetic is scheduled for upper abdominal surgery. How will
you evaluate the autonomic nervous system? Continuation:
Cold Pressor Test: (Sympathetic Function)

• This is used to evaluate the peripheral sympathetic vasoconstrictor mechanism.
Procedure:
• Record blood pressure response to a 1 min immersion of the hand in ice cold water.
Result:
• Both systolic and diastolic blood pressures at the end of 1 min of immersion should increase at least by 10mm Hg.
Isometric Hand Grip Exercise (Sympathetic Function)
Procedure:
• Record the blood pressure response to a sustained isometric contraction at 30% of the patientʼs maximum strength.
Result:
• Diastolic blood pressure should increase at least by 10-15 mmHg at the end of contraction. The failure to record a raise in diastolic blood pressure
more than 10 mmHg is suggestive of deficient efferent sympathetic mechanisms.
Respiratory Sinus Arrhythmia: (RSA) (Parasympathetic Function)

• Perhaps the most sensitive test of cardiac vagal function is to determine the maximum to minimum
heart rate variation that occurs during forceful breathing.
Procedure:
• Seated or lying subjects should breathe in at 6 breaths/min (5 sec. inspiration and 5 sec.
expiration). Maximum and minimum heart rate and RR interval variation are recorded.
Result:
• The average maximum to minimum heart rate variation during 3 consecutive breaths should be
greater than10 beats/min. The ratio of longest during inspiration constitutes expiration and
inspiration ratio. E:I less than 1.2 is abnormal in patientsʼ up-to 40 years of age.
121

Describe clinical manifestation of diabetic autonomic neuropathy. what are its implication?
Valsalvaʼs Maneuver: (Sympathetic and parasympathetic Function)

Instruments Required:
1. Pressure manometer connected to mouth piece.
2. Continuous recording of ECG or Intra arterial blood pressure.
Procedure:
• The subject sits quietly or lies supine and blows into a mouth piece with an open glottis and holds an airway pressure of
40mmHg for 15 seconds (Phase II) and is asked to release the strain (Phase IV).
Result:
• Heart rate normally increases during phase II of the maneuver i.e., 10 to 15 seconds after initiating the blowing but prior to
release of the strain. This tachycardia is due to baroreflex stimulation to the fall in blood pressure seen as result of raised
intrathoracic pressure (decreased venous return). On release of strain (Phase IV) preload and cardiac output are restored
and there is a blood pressure over shoot. This hypertension stimulates baroreceptors initiating rapid reflex bradycardia.
• The ratio of longest RR interval during phase IV to the shortest RR interval during phase II has been used as an index of
cardiac vagal function known as “Valsalva Ratio”. A ratio of less than 1.2 is abnormal. Failure of heart rate increase during
positive intrathoracic pressure phase points to sympathetic dysfunction and failure of the heart rate to slow during the period
of BP overshoot points to a parasympathetic dysfunction.
• Failure to observe BP overshoot flowing release of strain suggests that peripheral sympathetic vasoconstriction has not
occurred.
122

CLINICAL TESTS OF AUTONOMIC FUNCTION:

Non-Invasive Bedside Tests:
Test Normal response Part of reflex ARC –tested
BP response to Standing / Vertical tilt Fall in BP <30/15 mmHg- Afferent and efferent limbs
HR response to Standing Increase 11-29 beat/min 30:15 ratio Afferent and Efferent limbs
>1.04
Isometric Exercise Diastolic BP increase by 15mmHg Sympathetic Efferent limb
HR variation with respiration Max. Min. HR >15 beats/min Vagal Afferent and Efferent limbs
Valsalva Ratio >1.4 Vagal Afferent and Efferent
Sweat Tests Sweating all over body and limbs Sympathetic efferent limbs
Valsalva Maneuvers Phase I-Raise in BP Afferent and Efferent limbs
Phase II -Gradual reduction of BP to
plateau-Tachycardia. Phase III-Fall in
blood pressure
Phase IV-Overshoot of BP and
Bradycardia
123

A 50 year old man with known diabetic is scheduled for upper abdominal surgery. How will
you evaluate the autonomic nervous system? Continuation:
ANESTHETIC IMPLICATIONS IN AUTONOMIC DYSFUNCTION

A. Pharmacological Alteration:
• Drugs may alter the autonomic transmission and thus interfere with the maintenance of blood pressure, cardiac output under anesthesia. These drugs
may form part of a regular therapeutic regimen or might be administered by anesthesia. These drugs may form part of a regular therapeutic regimen or
might be administered by anesthesiologist. Due attention must be paid to the various modes of action which include.
1. Ganglion blockade –e.g. Trimethaphan
2. Interference with noradrenaline synthesis E.g. Alpha Methyldopa, Carbidopa
3. Prevention of noradrenaline release e.g. Reserpine
4. Interference with noradrenaline uptake E.g. Guanithidine
5. Interference with not adrenaline breakdown E.g. MAO inhibitors
6. Agonists and Antagonists of autonomic receptors.
B. Effect of anesthetic agents on autonomic activity:
Opioids:
• Morphine causes a biphasic response of circulation. The initial reduction in BP is secondary to release of histamine and is followed by increase in BP
which is due to sympathetic stimulation. Plasma adrenaline increases up to 4 fold and Nor adrenaline 2 fold.
Agonists and antagonists:
• Atropine – Muscarinic antagonist
• Metoclopramide – Dopaminergic antagonist
• Metoprolol – Beta 1 antagonist
• Clonidine – Alpha 2 agonist
Some of these drugs may be used for premedication purpose.
IV Induction agents:
• Intravenous Induction agents cause a reduction in arterial pressure associated with baroreceptor-mediated tachycardia except Ketamine. Plasma
catecholamines are usually reduced suggesting that central sympathetic activity is reduced Inspite of baroreceptor stimulation.
• Etomidate, an Imidazole derivative is a potent inhibitor of adrenal steroidogenesis regulating in inhibition of cortisol and aldosterone synthesis.
• Ketamine produces sympathetic stimulation.
124

17.Discuss the pre-anesthetic preparation, anesthetic goals & operative management of a 30 years Dr Azam’s Notes in Anesthesiology 2013
old female patient with diagnosis of Pheochromocytoma scheduled for excision of adrenal tumor.
Pharmacological measures to control hypertension and arrhythmias

Preoperative preparation:
It includes: Main objectives:
1. Pharmacological measures to control • Control arterial pressure, heart rate, arrhythmia
hypertension and arrhythmias •To restore blood volume to normal
2. Assessment of end organ damage
" Cardiomyopathy
" Renal function
Other Drugs:
β -‐adrenoceptor antagonist: • Alpha methyl-‐p-‐tyrosine (AMPT) was used in 1960
to inhibit rate limiting conversion tyrosine to DOPA
• There are two reasons: by suppressing tyrosine hydroxylase, this decreasing
Alpha blockade: • To limit the symptoms and signs referable to synthesis of catecholamines by 40-‐80%.
• Preparation should start at least 2 weeks increased circulating epinephrine, which • MgSO4:
prior to surgery to allow full alpha manifest as tachycardia with or without • It can be used as an alternative therapeutic strategy
blockade with gradual restoration of cardiac arrhythmias. to adrenergic block during anesthesia and surgery
circulating blood volume. • To block cardiac sympathetic drive secondary for Pheochromocytoma.
to suppression of presynaptic α2 receptors, by
• Phenoxybenzamine (is a non-‐speciCic,
drugs like Phenoxybenzamine Mechanism of action:
irreversible alpha antagonist.) a non • β, antagonists such as atenolol 100mg/day
selective alpha blocker in the most or Propranolol 40-‐240mg/day, metaprolol • Inhibition of release of catecholamines from the
commonly used drug. 50-‐200mg/day in patients who do not have adrenal medulla
• Dose: history of airway or peripheral vascular • Inhibition of release of catecholamines from
• Initially at 5 -‐ 10 mg oral BD disease. peripheral adrenergic nerve endings
Why α blockade first:
• increased gradually until either all • Direct blockade of catecholamine receptors
signs of pressor activity have • β-blockade should not be instituted in the
absence of α-blockade because the heart • Vasodilatation by direct effect on vessel
suppressed or until patient complains • Myocardial protection by preservation of adenosine
depressed by β-blockade might not be able
of side effects (somnolence, headache, triphosphate and glycogen stores.
to maintain the cardiac output, as
nasal stufCiness, postural hypotension, uninterrupted α-mediated vasoconstriction Dose:
reClex tachycardia, gastric irritation) from release of catecholamines result in • 40-60mg/kg of MgSO4 as loading dose followed by
• Many patients require a dose between abrupt increase in SVR. an infusion of 1-2g/hr to achieve serum
40-‐80mg per day. concentration between 2-4mmol/lt, continuing until
• Alternate drugs: Doxazosin a competitive tumor devascularization.
and selective α1-‐blocker & Prazocin.
125

Discuss the pre-anesthetic preparation, anesthetic goals & operative management of a 30 years old Dr Azam’s Notes in Anesthesiology 2013
female patient with diagnosis of Pheochromocytoma scheduled for excision of adrenal
tumor.Continuation:
Assessment of end organ damage Anesthetic Goals:
It is based on
Catecholamine cardiomyopathy: • Administration of drugs that do not stimulate the sympathetic nervous system
Cardiomyopathy is seen in approximately 25-‐50% of • Use of invasive monitoring techniques to facilitate early and appropriate
intervention when catecholamine induced changes in cardiovascular function
Pheochromocytoma as a result of sustained exposure
occur.
of myocardium to high levels of catecholamines. • The α and β antagonist therapy should be continued till the day of surgery. If
Phenoxybenzamine is used, it can be stopped 24-48 hours prior to surgery.
S/S: CCF, Dysrhythmia, acute pulmonary edema, non-‐ • The times of intraoperative hazards are
speciCic ECG changes like left ventricular • During tracheal intubation
hypertrophy, conduction defects, ST-‐T wave changes • During manipulation of tumour
consistent with ischemia/infection. • After ligation of tumour venous drainage
• The condition is partially reversible after treatment

with β blocker or resection of tumour Roizenʼs criteria for evaluation of efficacy of preparation:
1. BP record for at least 48 hours prior to surgery should be < 160/95 all
• Intravenous amiodarone can be used instead of β-‐ times.
blocker to treat dysrrhythmias in such patients. 2. Mild orthostatic hypotension indicates optimal α-blockade. BP should not
be < 80/45 in standing position. Less than that indicates inadequate
• β-blockade is better avoided in patients increased hydration.
catecholamines as it may precipitate pulmonary 3. ECG free of ST-T changes at least for 2 weeks
edema (CCF). 4. Ventricular ectopic < 1 every 5 minutes.
• Serial monitoring of hematocrit is a useful method

for evaluating the adequacy of intravascular Cluid
volume expansion and a satisfactory α-‐blockade is
implied if hematocrit decreases by about 5% from
45 to 40%.
126

tumor.Continuation:
Pre Anesthetic Examination: Monitoring:

• Routine hematological and biochemical investigation like – • Large bore venous access for rapid fluid administration
• Indwelling radial artery cannulation is done under local anesthesia and sedation
– Hb% for beat to beat assessment of blood pressure and blood gas measurement.
– Hematocrit • Pulse oximetry
– Serum calcium • ECG
– Serum electrolytes • Urinary catheter
– Blood sugar • Temperature probe
– Urine -‐ Metanephrine and VMA • Capnography
• CVP – to assess volume status
• ECG – To detect arrhythmia, LVH, ischemia, infarction
• Pulmonary artery catheter
• X-‐ray – Cardiomegaly, pulmonary edema • Transesophageal echocardiography
• Echocardiography – LV function assessment, cardiomyopathy
Anesthesia technique:
A combined general and regional anesthesia technique, using a segmental mid to low thoracic epidural combined with adequate general anesthesia
and selective adrenergic antagonists to control hemodynamic status, is the preferred technique of choice.
Premedication:
• An anxiolytic – sedative, benzodiazepine are administered to prevent the anxiety induced sympathetic release of catecholamine
Induction of anesthesia:
• Midazolam 0.05mg/kg given in pre-‐anesthetic room calms down the patient. Another 0.05mg/kg of midazolam given prior to induction helps in smooth
induction.
• Propofol 1-1.5mg/kg seems to be logical choice.
• Induction agents are given slowly along with close monitoring of heart rate and blood pressure."
Neuromuscular blockade:
• A non depolarizing muscle relaxant inj. Vecuronium 0.1mg/kg is of choice Rocuronium, cisatracurin can also be used.
• Other NDMR which release histamine are avoided.
• Scoline is also avoided, because the fasciculation and rise in intra-‐abdominal pressure associated with Scoline can squeeze the tumour mechanically
resulting is rise in blood pressure, and it also release histamine.
127

tumor.Continuation:
Inhalation agents:
• The choice of volatile agent is based on the ability to decrease sympathetic nervous system activity and the low likelihood of sensitizing the heart to
dysrhythmia.
• Isoflurane, Desflurane and Sevoflurane is preferred agent
• Halothane, enflurane are avoided because of their arrhythmogenic potential.
Laryngoscopy and intubation:
Direct laryngoscopy and intubation is initiated only after establishing a surgical depth with volatile Anesthetics, Inj. lignocaine 1-‐2mg/kg iv about 90 seconds
before laryngoscopy and Fentanyl 2-‐3 µg/kg just before laryngoscopy attenuates the hypertensive response.
Maintenance:
• Anesthesia is maintained with oxygen, nitrous oxide, isoClurane/SevoClurane/ DesClurane, with intermittent doses of Vecuronium and IPPV with a rate of
10-‐12 breath/min tidal volumes of 8 ml/kg.
• Careful monitoring of HTN, Hypotension, Hypercarbia, arrhythmias, pulmonary edema, CCF, Hypoglycemia & monitoring intravascular Cluid volume status is
maintained via CVP.
Perioperative problems:
Hypertensive crisis and dysryhtmias:
Precipitating factors:
Mainly – intubation and tumour manipulation
Others – preoperative anxiety
Induction
Hypercarbia
Hypoxemia
Hypoglycemia
Post operative management:
• The neuromuscular blockade can be reversed and extubated post operatively or kept electively on artiCicial ventilation depending on the hemodynamic
stability.
128

18. Describe the Manifestation & management of Thyroid Storm intraoperatively. Dr Azam’s Notes in Anesthesiology 2013
Thyroid storm is an abrupt exacerbation of hyperthyroidism caused by

sudden excessive release of thyroid gland hormones into the circulation.
Pre-‐disposing factors:
• Medical factors Clinical features under anesthesia:
• Surgical factors a) Hyperthermia -‐ 20C/hr
1) Medical factors:
b) Tachycardia -‐
a) Infection, fever, uncontrolled toxicity. c) Shock: Cardiogenic / Hypovolemic
b) Improper treatment d) Hypertension
" 1) Irregular drug intake
" 2) Improper / inadequate investigation e) High output failure and then to low output failure
" 3) Stopping drug well in advance to surgery f) Arrhythmia (Atrial Cibrillation common)
c) Pregnancy g) Flushing or sweating
d) Anxious and nervous patient before surgery h) Increase ETCO2
i) Hypo / hyperglycemia
2) Surgical factors: j) Electrolyte imbalance
a) Too much handling of gland before surgery
b) Rough handling of gland during surgery.
• This complication can occur both intra-operatively or in the
immediate post-op periods.
• It is common in post-operative period. It occurs between 6-18 hours
post operatively.
129

Describe the Manifestation & management of Thyroid Storm intraoperatively. Dr Azam’s Notes in Anesthesiology 2013
Treatment:
I) General Measures:
I. Increase the percentage of inspired O2 concentration.
II. Cooling measures
a) Surface cooling à Sponging, Icepack, decreasing OT temperature
b) Administration of cold IV Cluid.
III. Drugs à? Largactil (by action on medullary center)
IV. Handling of gland should be stopped and should stabilize the patient.
Avoid aspirin: as it competes for thyroxine binding globulin and hence releases more
T3-‐T4 into circulation, aggravating the condition.
II) Suppression of hormone activity:
1. Propylthiouracil à 200-‐400 mg IV/orally through Ryle’s tube 8th hrly
2. Carbimazole à 50-‐100 mg orally (RT) followed by 20 mg 6th hrly.
3. Na iodide à 500-‐1000 mg IV 8th hrly.
III) Suppression of sympathetic activity:
1. Propranolol 1-‐2 mg IV à SufCicient to decrease HR < 90/mt.
2. Esmolol 50-‐300 µg/kg/min.
3. Treatment of shock and CCF
4. CCF due to increase in ventricular rate, it will respond to esmolol – by
decreasing HR.
5. Digoxin à High output failure may not respond to digoxin.
6. IV Cluids should be given with reference to CVP.
Otherwise over infusion may further worsen CCF
7. IV Cluid preferably the crystalloid containing glucose to supply enough energy
for increased metabolism.
8. Supplementation of corticosteroid
9. Hydrocortisone 100-‐200 mg IV 8th or sometimes as high as 500 mg initial dose
may be given.
10. Dexamethasone à prevents conversion of T4 à T3 ,prevents release of T4.

130

19. A 30 years old women is scheduled for removal of carcinoid tumor. write the anesthetic Dr Azam’s Notes in Anesthesiology 2013
management.
Carcinoid tumors are the most common of the neuroendocrine Preoperative drug therapy:
tumors, derived from enterochromaffin or Kulchitsky cells and Its given to prevent the release of peptides
arise from the different embryonic divisions of the gut. • Serotonin Antagonist:
May occur in several locations like GI tract, bronchus, pancreas. • Cyproheptadine & Methysergide
• Ketanserin blocks effect of serotonin mediated by 5HT2 receptor & it also has
Carcinoid cells secrete: adrenergic antagonist activity & reduces central sympathetic outflow
Amine and neuropeptide hormones • Bradykinin Antagonist:
• Serotonin • Aprotinin - inhibits kallikrein cascade
• Histamine • Steroids (methylprednisolone) - reduces synthesis of prostaglandins which
• Prostaglandin mediate action on bradykinin
• Corticotropin • Histamine Antagonist:
• Kallikrein • H2 Blockers
• Bradykinin • Inhibitors of mediator release by tumor:
• Vasoactive peptide • Somatostatin - inhibits release of mediators from carcinoid tumor, it has short
• Substance P half life, hence infusion should be given.
• Octreotide - long acting synthetic somatostatin analogue, it also inhibits release
Preoperative evaluation & management: of mediators.
Patients presents with symptoms like: Anesthetic Consideration:
• Intestinal obstruction • Preoperative considerations
• Haemoptysis • Continue Octreotide
• Right heart valve lesion • Anxiolysis with benzodiazepines
• systemic effect of peptides released by tumour. • Consider additional Octreotide does 50-150ucg subcutaneous ; intraoperative
infusion 100ucg/hr
Serotonin: • Avoid all histamine producing drugs
• watery diarrhea - leads to cramps, dehydration, • Give an antihistamine
hyponatremia, Hypokalemia & decreased Cl • May have delayed gastric emptying-take appropriate precautions
• Hypertension - stimulates release & inhibits • Electrolyte abnormalities pre‐operatively are to be expected and treated
uptake of noradrenaline • Anesthetics known to trigger 5‐HT release should be avoided (e.g., morphine)
• Tachycardia - 5HT positive chromotrope • Both hypotension and hypertension can occur from the release of vasoactive
• Right heart failure - due to pulmonary stenosis peptides from the tumor and therefore mandate that all patients have invasive BP
& TR resulting in sub endocardial fibrosis. monitoring
• Catecholamines generally should be avoided as first line treatments for
Bradykinin & Histamine: hypotension and instead agents such as vasopressin and alpha‐adrenergic agents
• Tachycardia, flushing & bronchospasm used first
131

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A 30 years old women is scheduled for removal of carcinoid tumor. write the anesthetic management. Dr Azam’s Notes in Anesthesiology 2013
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GOALS: *3$%&*5*:! Intraoperative & Post operative problems:
• ECG
• -,*7)%235&%:10!
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• EtCO2 - end tidal carbon dioxide
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warm (&$.'5$'"/* !"#$%"&$#'(! B3(%-(.-! 8SQJ0! • Octreotide 100 microgram/hr infusion during surgery.
• Invasive Arterial line before induction
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•5%?(*5?$!
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• <%$-:$%('"9$2! >$-6$! '.$**).$: • REMEMBER that epinephrine, norepinephrine, dopamine will
• urine out put monitoring
• '.$'(.(35&%!4,"! trigger a crisis
• TEE in Heart failure
• B&/(3&*3(35%! (%(+&6)$! • Monitor blood glucose levels closely may require insulin infusion
CDEµ6FG1! *:2:! 8&23$.$&35-$9!3H! • Elevated serotonin levels may cause need for less anesthetic
drugs and may delay awakening
!
• Postoperative ICU close monitoring for continuing effects of
Q1&52$!&.!(%$*31$*5(! catecholamines
@$65&%(+! ! J$%$.(+! • Octreotide or Somatostatin infusion during the post operative
V&3!'.$7$..$-! ! L%-)235&%"!7$%3(%,+!N!?$2).&%5)/! period & weaning will take one week.
→!2(.25%&5-!2.5*5*!57!/(%-(3&.,! V&! '.&'&7&+! &.! 315&'$%3&%$→! • Epidural for post operative pain relief.
>531!6&&-!*$-(35&%:! 1,'&3$%*5&%!
TO! F! VOT! N! 7$%3(%,+! N! #@! >531!
2&%3.&++$-!?$%35+(35&%!
;?&5-"!L:R:!(6$%3*!→!1,'&3$%*5&%! Q(.25%&5-! 2.5*5*"! *$?$.$! 7&./! &7!
L%1(+(35&%(+! →!1,'&3$%*5&%! 1,'&3$%*5&%! (%-F&.!
T'5&5-*! 8/&.'15%$9→! 15*3(/5%$! 1,'$.3$%*5&%0! 4.&%21&*'(*/:!B&0!
.$+$(*$! (?&5-! 7(23&.*! 31(3! '.$25'53(3$!
#:@! 8(3.(2).5)/9→! 15*3(/5%$! 2.5*5*"!
.$+$(*$! = K,'&3$%*5&%"! 8(?&5-! .$65&%(+!
>&'%(-:$%('"9$* (%$*31$*5(0! LR:! (%$*31$352*0!
/-1:)"/('"-&.2! -$$'!(%$*31$*5(0!1,'&?&+$/5(9:!
24 !
132

20. Diabetic Ketoacidosis Dr Azam’s Notes in Anesthesiology 2013
• Diabetic ketoacidosis is a problem that occurs in

patients with Type I diabetes. Problems in DKA:
• It occurs when the body cannot use sugar (glucose) as • Dehydration
a fuel source because there is no insulin or not enough • Lack of Insulin & raised blood sugars
insulin. • Acidosis
• Fat is used for fuel instead. Byproducts of fat • Ketonuria
breakdown, called ketones, build up in the body. • Infection
Essentials for Diagnosis:
• Hyperglycemia > 250 mg/dl Goals of therapy
• Acidosis pH < 7.3 ¤ Correct dehydration
• Serum HCO < 15 meq/L ¤ Correct acidosis and reverse ketosis
• Serum positive for ketones (Ketonemia & Ketonuria) ¤ Restore blood glucose to near normal
• Increased Leucocytosis > 25,000 ¤ Avoid complications of therapy
• Glycosuria 4+ ¤ Identify and treat any precipitating event
•
• Increased serum potassium
Clinical manifestations of DKA Protocol for the management of adult patients with DKA
• Dehydration
• Rapid, deep, sighing (Kussmaul respiration) Complete initial evaluation. Check capillary glucose & serum/urine
• Nausea, vomiting, and abdominal pain mimicking an acute ketones to confirm hyperglycemia & ketonemia/Ketonuria. Start IV
abdomen fluids: 1.0 L of 0.9% NaCl per hour.
• Progressive obtundation and loss of consciousness
• Increased leukocyte count with left shift Follow the )low chart for treatment/management:
• Non-specific elevation of serum amylase
• Fever only when infection is present
133

Diabetic Ketoacidosis: Continuation Dr Azam’s Notes in Anesthesiology 2013
Consensus Guidelines
I. Dehydration: Fluids
Pathophysiology of Diabetic Ketoacidosis
(DKA) Management:
Absolute insulin deficiency
or
Determine dehydration status
Stress, infection or insufficient insulin intake
Counter-regulatory hormones
Glucagon Cortisol
Catecholamines Growth Hormone
Lipolysis Glucose utilization Proteolysis Glycogenolysis Severe Mild Cardiogenic

Protein synthesis Hypovolemia dehydration Shock
Gluconeogenic substrates
++
FFA to liver Gluconeogenesis
Ketogenesis Hyperglycemia
Administer 0.9%
Alkali reserve Glucosuria (osmotic diuresis) NaCl (1.0L/hr) Hemodynamic
monitoring &
Acidosis Loss of water and electrolytes
Decreased fluid intake pressors
Lactate Dehydration Hyperosmolarity
Evaluate corrected serum sodium
Impaired renal function
of diabetic ketoacidosis. Copyright # 2006 American Diabetes Association. From Diabetes Care, Vol. 29, 2006;
ith permission from The American Diabetes Association.
Check electrolytes, BUN, venous pH, Serum Serum
Serum Na Normal
ar creatinine
filtration.& glucose
At presentation, the
every 2 - 4 hrly ¤ Increased leukocyte count with left
Nashift
high Na Low
until stable.After resolution of
ic deficits in an individual patient DKA & ¤ Non-specific elevation of serum amylase
ponwhen thepatient is ableand
duration to eat, Initiate SC
severity of ¤ Fever only when infection is present
multi-dose insulin regimen. continue IV
to infusion
which for the1-2
patient
hrs afterwas able to
SC insulin to When Serum glucose reaches
f fluid
ensureand electrolytes,
adequate and levels.
plasma insulin the 200 mg/dl, change to 5 % 0.45% NaCl (250-500 ml/hr) 0.9% NaCl (250-500 ml/hr)
Lookconsumed
fluids for precipitating cause.
before coming to Definition of DKA
Dextrose with 0.45% NaCl at depending on hydration state depending on hydration state
150 - 250 ml/hr
Consumption of fluids with a high- The biochemical criteria for the diagnosis of DKA
nt (juices or sugar containing soft are (4): 134
the hyperglycemia (3).
¤ Hyperglycemia (blood glucose . 11 mmol/L [!200
II.Lack of Insulin - Insulin III. Electrolytes - Potassium
Establish adequate renal function

& urine output ( at least 50ml/hr)
Uncomplicated
IV Route
DKA - SC route
If serum K+ is < 3.3 mEq/L, hold insulin

Insulin: Regular Rapid-acting Insulin: & give 40 mEq, K+ per hour (2/3 KCL &
0.1 U/Kg B.wt as 0.3 U/Kg then 0.2 U/Kg 1/3 KPO4) until K > 3.3 mEq/L
IV bolus one hr later
0.1U/kg/hr Rapid-acting If serum K+ > 5.5 mEq/L, but check K+

continuous Insulin: 0.2 U/kg every 2 hour.
insulin infusion every 2 hours
If serum K+ > 3.3 but < 5.5 mEq/L,

give 20 - 30 mEq/L in each liter of IV
If serum glucose does not fall by fluid (2/3 KCL & 1/3 KPO4) to keep
50 - 70 mg/dl in first hour, double serum K+ at 4-5 mEq/L
IV or SC insulin bolus
When serum glucose reaches Check electrolytes, BUN, venous pH,

200mg/dl, reduce regular insulin creatinine & glucose every 2 - 4 hrly until
infusion to 0.05 - 0.1 u/kg/hr IV, or stable.After resolution of DKA & when patient
give rapid-acting insulin at 0.1U/kg When Serum glucose reaches 200 is able to eat, Initiate SC multi-dose insulin
SC every two hrs. Keep serum mg/dl, change to 5 % Dextrose with regimen. continue IV infusion for 1-2 hrs after
glucose between 150-200 mg/dl until 0.45% NaCl at 150 - 250 ml/hr SC insulin to ensure adequate plasma insulin
resolution of DKA levels. Look for precipitating cause.
135

IV. Acidosis - Assess the need of Bicarbonate
pH > 7.0
pH < 6.9 pH 6.9 to 7.0
Dilute NaHCO3 Dilute NaHCO3 No HCO3

(100 mmol) in 200 (50 mmol) in 200
ml NS. Infuse at ml NS. Infuse at
200ml/hr 200ml/hr
136

21. Thyroid Storm Dr Azam’s Notes in Anesthesiology 2013
• Shock: Cardiogenic / hypovolemic.

Thyroid storm is an abrupt exacerbation of hyperthyroidism caused by • Electrolyte imbalance.
sudden excessive release of thyroid gland hormones into the circulation.
Pre-disposing factors: • Marked agitation, anxiety and psychosis.
• Medical factors
• Clinical features under anesthesia:
Surgical factors
1) Medical factors: a) Hyperthermia
a) Infection, fever, uncontrolled toxicity. b) Tachycardia
b) Improper treatment c) Hypertension
" 1) Irregular drug intake d) High output failure and then to low output failure
" 2) Improper / inadequate investigation e) Arrhythmia (Atrial fibrillation common)
" 3) Stopping drug well in advance to surgery f) Flushing or sweating
c) Pregnancy g) Increase ETCO2
d) Anxious and nervous patient before surgery h) Hypo / hyperglycemia
2) Surgical factors:
Differential diagnosis:
a) Too much handling of gland before surgery
I. Malignant hyperthermia
b) Rough handling of gland during surgery.
II. Pheochromocytoma
This complication can occur both intra-operatively or in the immediate post-

op periods. Treatment:
It is common in post-operative period. It occurs between 6-18 hours post I) General Measures:
operatively. I. Increase the percentage of inspired O2 concentration.
Clinical features: II. Cooling measures
(Increased temperature, tachypnea, tachycardia, extreme anxiety, CVS a) Surface cooling à Sponging, Icepack, decreasing OT
instability). temperature
Hyperthermia: Rise of 20C/hr over normal temperature. It may be difCicult to b) Administration of cold IV Cluid.
notice during operation because the surgery may not last for more than 1-‐1 ½ III. Drugs à? Largactil (by action on medullary center)
hour. Avoid aspirin: as it competes for thyroxine binding globulin and
Tachycardia: Arrhythmias of any kind may occur, atrial Cibrillation is the hence releases more T3-‐T4 into circulation, aggravating the
commonest. condition.
Initially there is Clushing and sweating, later leading to dehydration.
CCF à initially high output failure, later may go for low output failure.
137

Thyroid Storm. Continuation: Dr Azam’s Notes in Anesthesiology 2013
II) Suppression of hormone activity:

1. Propylthiouracil à 200-400 mg IV/orally through Ryleʼs tube 8th hrly
2. Carbimazole à 50-100 mg orally (RT) followed by 20 mg 6th hrly.
3. Na iodide à 500-1000 mg IV 8th hrly.
III) Suppression of sympathetic activity:

1. Propranolol 1-2 mg IV à Sufficient to decrease HR < 90/mt.
2. Esmolol 50-300 μg/kg/min.
3. Treatment of shock and CCF
4. CCF due to increase in ventricular rate, it will respond to esmolol – by decreasing HR.
5. Digoxin à High output failure may not respond to digoxin.
6. IV fluids should be given with reference to CVP.
7. Otherwise over infusion may further worsen CCF
8. IV fluid preferably the crystalloid containing glucose to supply enough energy for increased
metabolism.
9. Supplementation of corticosteroid
10. Hydrocortisone 100-200 mg IV 8th or sometimes as high as 500 mg initial dose may be given.
• Dexamethasone à prevents conversion of T4 à T3 ,prevents release of T4.
• If it is during intra-operative à handling of gland should be stopped and should stabilize the
patient.
138

22. Porphyria. Dr Azam’s Notes in Anesthesiology 2013
• Inborn errors of Haem synthesis characterized by overproduction of Diagnostic

porphyrins compounds and their precursors. • Increase urinary excretion of porphyrins and their precursors.
• The porphyrins synthesis is required for haeme synthesis and • Urine turns Red or Dark brown on standing.
Precipitating factors:
cytochrome P 450.
•Starvation
• The rate limiting enzyme of haeme synthesis is the δ Aminolevulinic •Dehydration
acid (ALA) synthetase – normally inhibited by haeme. •Sepsis
• When subsequent enzymes in the pathway are deficient this inhibition •Pregnancy
fails and abnormal precursors (porphyrias) are formed in excess. •Drug- like
• All porphyrias have high ALA synthetase activity. • Barbiturates
• Sulphonamides
Classification: • Anticonvulsants (phenytoin)
Hepatic porphyrias Erythropoietic porphyrias • Alcohol
• Pentazocine
Acute intermittent porphyria Erythropoietic uroporphyria • Corticosteroids
Variegate porphyria (AD) Erythropoietic proto porphyria • Tolbutamide
Hereditary coproporphyria • Imipramine
Prevention – Avoidance and precipitating factors and drugs
Porphyria cutania tarda(AD)
Acute intermittent porphyria – most serious form of Hepatic

porphyrias
• Autosomal dominant
• Increase ALA synthetase and decrease uroporphyrinogen synthetase
• -S/S Acute abdominal pain + Neurotoxicity in females (during
menstruation)
• Neurotoxicity: Psychosis (cerebral cortex dysfunction), SIADH,
Hyponatremia (Hypothalamus dysfunction), " Bulbar paralysis
(Swallowing difficulty and Aspiration – (cranial N), Tachycardia,
orthostatic hypotension, HTN (ANS) pain and paresis (Peripheral
nerves),
• Cutaneous photosensitivity.
139

Porphyria. Continuation: Dr Azam’s Notes in Anesthesiology 2013
Treatment – Acute attack.

• Haematin – repressor of ALA synthetase – 3 to 4 mg/kg + glucose 20 g/hr.
• Decreasing urinary excretion of porphyrinogen to normal within 24 hrs.
• Halts progression of peripheral neuropathy.
• Prolongation of PT, PTT, Cibrinolysis
• Opioids – Pain controls
• Blocker – For control of sympathetic over activity.
• Tracheal intubation and mechanical ventilation – Respiratory paralysis.
• NG suction – Bulbar involvement.
Anesthetic Management: Avoid precipitating drugs – Induction à Ketamine,
propofol, NO, Barbiturates.
-‐ All other drugs for sedation, Analgesia, Relaxation and reversal can be used
safety.
-‐ Regional Anesthesia. Neurological deCicits may be falsely attributed to SA
-‐ ANS involvement -‐ labile BP.
140

23.Cushingʼs Syndrome. Dr Azam’s Notes in Anesthesiology 2013
• It is a clinical state of increased free circulating glucocorticoid • Careful history to be reviewed

• Frequently as a result of exogenous corticosteroid administration • Diabetes mellitus, hypertension, obesity, hirguitism, nom face, buffalo
hemp, fracture, growth arrest, proximal myopathy, depression
Causes: psychosis edema.
1. ACTH dependent disease
• Pituitary dependent (Cushingʼs disease) producing bilateral Investigations
adrenal hyperplasia • Full blood count
• Ectopic ACTH producing tumors (bronchia, pancreas tumor) • Urea, electrodytes, blood glucose levels
• ACHT administration • ECG (decreased K+, ischemia)
• Chest X-ray
2. Non ACTH Dependent • PFT
• Adrenal carcinoma / adenoma Premedication
• Glucocorticoid administration • Supplemental steroid may require
3. Other • Other medications for diabetes Mellitus, Hypertension to be
• Alcohol induced pseudo-Cushings syndrome continued
• Continue diuretics, insulin antibiotics, inhibitors of cortisol synthesis
Main actions of glucocorticoid • Antiaspiration prophylaxis given
• Suppresses pituitary ACTH secretion • DVT prophylaxis given
• Glycogen deposition, increased gluconeogenosis, fat deposition
• Increased protein catabolism and decreased synthesis Monitoring:
• K+ loss, Na retention, increased free water clearance and uric Arterial BP, CVP and palm artery pressure measurement
•
acid production Blood sampling for ABG blood glucose Hct level
•
• Immunosuppression and increased circulating of neutrophils • ECG (lead II and V)
• Capnography, SaO2
Preoperative Assessment:
• Peripheral nerve stimulator, urine output
• Optimal treatment of Diabetes Mellitus, Hypertension or cardiac
failure and restrictive lung disease Intra operative management
• Fluid and electrolyte abnormalities corrected • Anesthetic agents given slowly and carefully as those patients are
• Supplemental steroids to be given sensitive to any cardiac depressant effects.
• Airway assessed in obese patient
• Careful positioning (because osteoporosis and pathological
fracture)
• Assessment of fragile veins and arteries
• Assessment of ease of local anesthesia techniques.
141

Cushingʼs Syndrome.Continuation: Dr Azam’s Notes in Anesthesiology 2013
General Anesthesia:
• Rapid sequence induction for obese patients (O2 + N2O +
Thiopentone + Scoline Opioid + Volatile agents + titrated doses)
• Prepare equipment for difficult intubation
• IPPV with high FIO2 may required with careful position of patient
to be done (opioid + NDmR + volatile for maintenance)
Local Anesthesia:
• It will lesser the stress response to surgery (epidural anesthesia)
technically difficult but provides good analgesia and enables less
administration of opioids and rapid mobilization also reduces
thromboembolism.
Post operative management

• Continuous humidified O2 given
• Avoid excessive administration of Na containing iv fluids because
mineralocorticoid effect of excess cortisol
• Adequate analgesia à opioid infusion, PCA, epidural opioid /
local anesthesia
• Steroids for maintenance therapy after operation
• Insulin infusion for sugar control
• Physiotherapy and early mobilization
• DVT prophylaxis
• Vitamin D
142

24. Acromegaly. (Transphenoidal Hypophysectomy) Dr Azam’s Notes in Anesthesiology 2013
• Acromegaly results from pituitary adenosis / ectopic GH Preoperative Assessment:

secretion • Assess upper airway for stridor,s noring, sleep apea
• Assess Cardiovascular System, respiratory system and endocrine
Diagnosis: system for associated conditions
• Random GH level > 5mg/ml • Prepare for difficult airway management
• Failure of GH to fall in response to 75gm oral glucose tolerance • Respiratory excercises can be taught pre operative.
test
• IGE-1 indicator of GH activity
Premedication:
Pathophysiology: • Avoid respiratory depressants
CVS: • Anticholinergic (glycopyrrolate) for drying of secretism if difficult
• Hypertension airways
• Cardiomegaly • If glucose intolerance à glucose and insulin infusion started
• Cardiomyopathy • Somatostatin analogues used sometimes
• Complications of drug
Investigations:
Neuromuscular:
• Blood tests à urea, electrolytes, glucose, Ca++, thyroid function
• Proximal neuropathy
tests
• Nerve entrapment syndrome
• Neck radiography (glottis involvement, pharyngeal tissue over
• Kyphoscoliosis
growth)
• Indirect laryngoscopy à to see the vocal cords
Respiratory: • CVS + ECG, Echo, X-ray, ABG (Baseline)
• Somnolence, sleep apnoea
• Partial URT obstruction due to hypertrophy of soft tissue
Voice changes (glottis stnenosis) Monitor:
•
• Mouth opening less because of thondrocul sinosis • ECG, SPO2, NIBP, EtCO2, Temperature urine output
• Macroglossia pragnathism
Perioperative Management:
• Invasive arterial blood pressure, CVP à for fluid may be a difficult
Endocrine: airway, prepared for difficult airway management preoxygenate with
• Over growth of head, tongue, jaw, hands 100% O2, mask ventilation may be difficult.
• Impaired glucose tolerance
• Hpypercalemia and hypercalciurias
• Hypopituitarism
• Diabetes insipidus
• Nodular goiter which may compress trachea 143

Acromegaly. (Transphenoidal Hypophysectomy).Continuation: Dr Azam’s Notes in Anesthesiology 2013
Induction:
• A wake fibre optic intubation done using flexometallic tube, oral
route is preferred because nasal glucose may be thickened
• iv sedation drugs used à midazolam (1-2mg) fentanyl (1µg/kg)
• airway should be anesthetized with local anesthesia nebulisation
(4% lignocaine)
• Intratracheal local anesthesia (lignocaine 2% 2-4 ml) injected
and tell the patient to cough.
• Superior laryngeal nerve block with 2% lignocaine
• Lignocaine 2% spray when the scope is inserting into airway.
Maintenance:
• O2 + N2O + Opioid + NDMR + Volatile agent
• Decrease the pressure response to intubation with allentanil
10µg/kg or fentanyl 1-2µg/kg
• If difficult airway and fibre optic intubation not possible
• Or history of sleep apnea present
• Or vocal cords are involved
• Lumbar drain may be we have to put if surgeon ask
Extubation:
• Patient should be awake and meet all extubation criteria
• Reversed with neostigmine and atropine
• Ask the patient to breath by mouth
Postoperative Management:
• Monitor airway response to opioids, so respiratory depression to
be avoided
• Humidefiedand given
• Insulin requirement will become less, so monitor glucose level
• Some may develop diabetes insipidus à treat with DDAVP /
ACTH and TSH
• Treat hypertension with antihypertensive drugs.
144

25. Porphyria. Dr Azam’s Notes in Anesthesiology 2013
• Porphyria are a group of diseases in which there is an enzymes Anesthetic Management:

defect in synthesize of haem moiety leading to accumulation of • Premedication à important to minimize stress givetemazepam /
precursors that are oxidized into porphyrins. midazolam
There are hepatic and erythropoietic varieties • Minimize preoperative fasting à use dextrose saline iv avoid
• Only the three hepatic forms inherited in AD manner affect the dextrose alone because frequency of hyponatremia
administration of anesthesia. • Regional anesthesia à bupivacaine considered safe for epidural
1. Acute intermittent porphyria (AIP) à (Sweden) à increased • In acute crises avoid regional anesthesia as neuropathy may be
urinary porphabilinogen and D-ALA rapid in onset and progressive
2. Variegate porphyria (VP) à (Africa) à increased copro and General Anesthesia
protoporph in stool leading to dermal photosensitivity • Proponal as induction agent
3. Hereditary copro porphyria (HCP) à rare, increased urine • N2O / propofol infusion for maintenance
porphyrins dermal photo sensitivity. • Scoline / vecuronium for muscle relaxation
• Fentanyl / morphine / pethadine for analgesia
Porphyric Crises: Monitoring
• Common in women, in 3rd to 4th decade • Invasive blood pressure monitoring during acute crisis
• Precipitated by drugs, stress, infection, alcohol, menstruation, • As hypovolemia is common and automic neuropathy may cause
pregnancy, starvation or dehydration labile blood pressure
• Perform CVP if clinically indicated
Clinical Features:
• Acute abdominal pain, vomiting, motor and sensory peripheral Problems during anesthesia:
neuropathy autonomic dysfunction, cranial nerve palsies, mental • Hypertension and tachycardia à treatment with β-blockers (Atenolol)
disturbance coma, convulsions and pyrexia. • Convusions à Treatment with diazepam, propofol or MgSO4 (avoid
barbiturates and phenytoin)
General Principles:
• Positive family history should be taken seriously Postoperative management:
• Biochemical tests have normal in between attacks • Crisis may be delayed for upto 5 days, so we have to be careful
• It present with unrelated pathology mimic surgical pathologies Treatment of acute porphyric crisis:
• Withdraw crisis precipitating drugs
• Reverse factors which increase ALA synthetase
• Give haem arginate 3mg/kg iv OD for 4 days
• Treat infection, dehydration, electrolyte imbalance, give glucose
20mg/hr
• Treat symptoms with safe drugs
• Monitor patient appropriately
145

Porphyria.Continuation: Dr Azam’s Notes in Anesthesiology 2013
Probable safe Definitely unsafe Controversial

Induction agent Propofol Barbiturates Ketamine
Etomidate
Inhalational agents N2O, ether cyclopropane Enflurane Halothane Sevo/isoflurane
NMB agents Suxamethonium tubocurarine Alcurronium Pancuronium
gallaminevecuronium Atracurium
Rocuronium
Mivacuronium
Analgesics Allfentanil, fentanyl, morphine, Pentazocine Diclofenac
pethidine, aspirin, codeine, Ketorolac
buyprenorphine, Naloxane Sufentanil
Local anesthetics Procaine, prilocaine, Mepivacaine Cocaine
bupivacaine, pracainamide Ropivacaine Lignocaine
Sedatives Midazolam Chlordiazoxide Diazepam
Temazepam Nitrazepam
Lorazepam
Chlorpromazine
Chloral hydrate
Antiemetics Droperidol Simitidine Andansteron
H2 antagonists Phenothiazines Metoclopramide Ranitidine
CVS drugs Adrenaline Hydralazine Diltiazem
α and β agonists Nifedipine SNP
β blockers Phenoxybenzamine Verapamil
Magnesium
Phentalamine
Procainamide
Others - Aminophylline Steroids
OcP, phenytoin
Sulphonamides
146

26. Carcinoid Syndrome. Dr Azam’s Notes in Anesthesiology 2013
• Carcinoid tumours are derived from enterochromaffin or b. Bradykinin antagonists:

Kulchitsky cells and arise from the different embryonic divisions • Aprotinin à inhibits kallikrein ascade steroids (methylprednisolone)
of the gut. May occur in several location like bronchus, reduce synthesis of prostaglandins which mediate action of
pancreas, GI tract and in appendix bradykinin.
• The amines and peptides responsible for symptoms of carcinoid c. Histamine antegonists à mainly H2 blockers
syndrome are produced by malignant tumors. These are d. Inhibitors of medicator release by tumours
serotonin, bradykinin, histamine, somatostatin, prostaglandins, • Somatostatin à inhibits release of mediators from carcinoid tumor it
vasoactive peptide and substance P. has short t ½ so infusion is used.
• Octeotide à long acting synthetic somatostatin analogue it also
Preoperative Evaluation: release of mediators.
• CT and MRI will determine the site of tumour and possible Anesthetic consideration:
existence of metastases • Prevent release of mediators à _____ somatostatin and its
• Patients will presents with symptoms like analgesics
• Intestinal obstruction • Correct hypovolemia and electrolyte disturbances
• Haemoptysis • Avoid factors that trigger carcinoid crisis
• Right heart valve lesions • Anxiety, hypocapnia, hypothermia, low Blood Pressure
• Systemic effects of peptides released by tumour • Drugs that release histamines (morphine scoline atracurium)
• Serotoninà watery diarrhea pallor à cramps, dehydration, • Hypertemion which causes and release of bradykinin
decrease Na, decrease K, decrease Cl- • Prepare for carcinoid crisis (resistant bronchospasm and sudden
• Hypertension à stimulates release and inhibits uptake of variation in arterial blood pressure at induction of anesthesia nd
noradrenaline during handling of tumor)
Preoperative management:
• Tachycardia à 5HT is positive chromopop hyperglycemia
• Correct fluid and electrolyte imbalance, nutritional support
• Right heart failure à due to pulmonary stenosis and tricuspid
• Echocardiography to rule out right heart failure and tricuspid valve
regurgitation resulting from subendocardial fibrosis. function
• Bradykinin and histamine à flushing, hypotension, • Octreotide 100µg s.c. 2-3 times/day for 2 weeks prior surgery
bronchospasm followed by 10µgm iv at induction of anesthesia and a slow
postoperative wean over a few days, reduces mediator release
Preoperative Drug Therapy:
• Continue antagonists of histamine, serotonin, bradykine and maintain
It is given to prevent the release of peptides hemodynamic stability.
a. Serotonin:
• All emergency drugs (ketanserjn, cyprohepatadine, somatostatin)
• Cyproheptadine and methysergide should be available for immediate administration.
• Ketanserin block effects of serotonin mediatedby 5HT2
receptorand it also has adrenergic antagonist and activity and
reduces central sympathetic outflow.
147

Carcinoid Syndrome.Continuation: Dr Azam’s Notes in Anesthesiology 2013
• Premedication Post operative management:

• Anxiolytic à BZn • Recovery from anaesthesia in this group of patients may be delayed
• Antihistamine à promethazine so, close monitoring is required in HOU (because serotonin cannel
sedation)
• If octreotide was used before operation, it should be reduced slowly
Perioperative management: over the first post operative week.
• Preinduction monitoring • Post operative pain relief à epidural anesthesia is preferred.
• ECG, CVP, IABP, ABG, Blood Sugar, Airway pressure in patients
with right heart lesions pulmonary artery catheterization.
• Regional anesthesia is (relatively C/I because hypotension may
occur) but it reduces perioperative stress and release of
vasoactive agents
• General anesthesia is preferred
Induction:
• Propofol etomidate + Rocuronium (0.6mg/kg) + opioids
(pentanyl) 1-2 µg/kg O2 + N2O + volatile agent (titrated)
• Laryngoscopic response treated with iv lignocaine (1-1.5mg/kg)
Maintain:
• O2 + N2O + high dose opioids + NDMR + titrated volatile agents
+ IPPV (flow generating ventilator to over come /bronchospasm)
• Hypotension treated with iv fluids guided by CVP or with infusion
of aprotinin
• Avoid sooline and ketamine
• Somatostatin analogue may be helpful during crisis should be
continued intra operative (100µg/hr infusion during surgery)
• Hypertension is controlled with iv ketaserine and cyprohepadine
Extubation:
• Patient should meet criteria give adequate reversal
148

Flow chart & Diagram Dr Azam’s Notes in Anesthesiology 2013
Formation & Synthesis of Thyroid Hormone: WAYNEʼS CLINICAL DIAGNOSTIC INDEX

! !"#$ Symptoms - SWAPT Present Absent
!%&'()*+*,-.$/-0(%1'0*,-$
Palpitations → +2
2'3&3-$,0*//&+4$&+$,%)0'&3$41*+3$$ Excessive sweating → +3
50'/)1,%&'60*(&1.$7-,%&7*8'1-$$ Increased Appetite → +3
!"#$
Decreased Appetite → - -3
9:&3*,&'+$*+3$&'3&+*,&'+$';$,)0'<&+-$$
Weight increased → - -3
!"#$ 50'/)1,%&'60*(&1.$7-,%&7*8'1-$$ Weight decreased → +3
Preference for cold → +5
#'07'+-$<,'0*4-$*<$/*0,$';$,%)0'41'=61&+$$
Preference for heat → - -5
!"#$ 2'3&3-.$>&,%&67$$ Signs - BEAP - FLP
Palpable thyroid → +3 -3
50',-'1)<&<$*+3$0-1-*<-$';$!?$*+3$!@$
Exophthalmos → +2
!"#$
Lid retraction → +2
DIFFERENCE BETWEEN PRIMARY AND SECONDARY THYROTOXICOSIS
Finger tremor → +1
Primary Secondary
Bruit over thyroid → +2 -2
• Goitre appears along with toxic • Goiter appears first and
Atrial fibrillation → +4
symptoms toxic symptom appear
• Goitre is diffuse, vascular bruit may later. Pulse rate 90/mt → +3
be present. • Goiter is nodular. 80/mt → - -3
• Symptoms appear suddenly and are • Symptoms appear Index
severe gradually and are mild. • >19 indicates Toxic goiter
• CNS manifestation dominate • CVS manifestations • 11 - 19 _ Equivocal
• < 11 indicates non-toxic goiter
(Tremors, Hyperkinetic movements dominate
increased tendon reflexes) • Exophthalmos and eye
• Exophthalmos and eye signs are signs are rare.
common
149

Eye Signs observed in this condition are: Hypothyroidism:

von Graefe's sign upper eye lid lags behind the eye ball as the Secondary Etiology
patient is asked to look downwards hypothyroidism
Stellwagʼs sign Infrequent and incomplete blinking, staring 1. Hypothalamic Deficiency of thyroid releasing
look dysfunction hormone.
Dalrympleʼs sign upper sclera is visible due to retraction of 2. Anterior pituitary Deficiency of thyroid stimulating
upper eye lid.
dysfunction hormone.
Joffroyʼs sign Absence of creases on the forehead on
Primary hypothyroidism
superior gaze.
Mobiuʼs sign Difficulty to converge the eyeballs. 1. Thyroid gland Previous subtotal thyroidectomy,
Gifford`s sign Difficulty in eversion to the upper lid. destruction previous I131 therapy, irradiation of the
Tachycardia – sleeping Pulse Rate. neck
• <80 -90- mild 2. Thyroid gland hormone Chronic inflammation
• 90 – 110 – moderate deficiency Dietary iodine deficiency
• 110 – Severe. Excess iodides (inhibits release)
COMPLICATIONS of Hyperthyroidism: Antithyroid drugs.
Intraoperative Immediate Post Op Late Post Op
GLUCOCORTICOID DEFICIENCY- HYPOCORTISOLISM
Haemorrhage Thyroid crisis Hypothyroidism Primary adrenal insufficiency Secondary adrenal insufficiency
Thyroid crisis Hematoma Hypoparathyroidism
• Addisonʼs disease • Panhypopituitarism
Air embolism Tracheomalacia
• Destruction of adrenal gland by • inadequate corticotrophin (HTH)
RLN damage
hemorrhage, sepsis, grammlomatous secretion
Laryngeal edema Mineralocorticoid secretion Normal
disease, cancer •
Hypoparathyroidism Addisonian crisis (Acute adrenal
• Combined mineralocorticoid + •
glucocorticoid def. insufficiency) à trigged in steroid
• Mineralocorticoid def (hyponatremia, dependent patients who do not receive
hypovol, hypotension, hyperkalemia, increased doses during stress.
met. Acidosis) • CFà circulatory collapse, fever,
• Glucocorticoid def (weakness, fatigue, hypoglycemia, decrease mentation
hypoglycemia, weight loss) abdominal/ • Medical emergency.
back pain.
• Etomidate suppresses adrenal function
• Hyperpigmentation – palmer surface
and pressure points
150

Hyperaldosteronism: Pathophysiology:
Primary aldosteronism Secondary aldosteronism
Conn syndrome Some disease stimulate
aldosterone secretion by
affecting renin – angiotensin
system
Excess secretion of aldosterone CHF, cirrhosis with ascetic,
from a functional tumor nephrotic syndrome, HTN (Renal
(aldosteronoma) independent of art stenosis)
physical stimuli.
Unilateral adenoma, bilateral Increase aldosterone levels ,
hyperplasia, carcinoma of increased rennin levels
adrenal gland
Women associated with PCC, 10
hyperparathyroidism /
Acromegaly
“Prayer sign”.
Palm print sign –
151

#
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Flow chart & Diagram
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EFFECTS OF SURGERY ON DIABETES: PREPARATION OF DIABETIC PATIENT FOR ELECTIVE SURGERY:
# EFFECTS:
ANTI INSULIN #
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<<<=!"$%&'=7+'###############################################################################Endocrinology #
# Dr Azam’s Notes in Anesthesiology 2013 ::#
;;;<!"$%&'<7+'###############################################################################Endocrinology #
ORAL HYPOGLYCEMIC AGENTS METABOLIC ACTIONS OF INSULIN:

Oral agent Mechanism Duration Adverse Contraindicati Increase (ANABOLIC) Decrease (CATABOLIC)
of action of action effects ons
CARBOHYDRATE METABOLISM Gluconeogenesis
Sulphonylureas Increased Hypoglycemia Renal / Liver Glucose transport (muscle, Glycogenolysis
Glipizide insulin 12 – 18 h Weight gain disease. adipose tissue)
Glimepiride secretion Drug
Glucose phosphorylation
Chlorpropamide > 48 h interactions
Glycogenesis
Biguanides Potentiates 6 – 8 h Lactic acidosis SCr > 1.5 mg/dl Glycolysis
Metformin insulin Diarrhea, CHF, acidosis
Pyruvate dehydrogenase activity
Thiazolidinediones Peripheral 12 – 24 h Edema, CHF, CHF, liver
Rosiglitazone insulin action disease Pentose phosphate shunt
LIPID METABOLISM Lipolysis
Megliturnides Releases 3–5h Dyspepsia,
Repaglinide insulin arthralgia,
TG synthesis Lipoprotein lipase (muscle)
weight gain FA synthesis (liver) Ketogenesis
Lipoprotein lipase activity (adipose FA oxidation (liver)
Glucosidase Decreases GI flatulence Renal / liver tissue)
inhibitors intestinal disease PROTEIN METABOLISM Protein degradation
Acarbose glucose AA transport
absorption Protein synthesis
INSULIN PREPARATIONS
Type Onset (hr) Peak (hr) Duration (hr)
Rapid acting
• Insulin Lispro 0.2 – 0.4 1–2 3–5
• Insulin Aspart 0.2 – 0.4 1 – 1.5 3–5
• Insulin Glulisine 0.3 – 0.5 1–2 2-4
Short acting
• Regular (soluble) insulin 0.5 – 1 2–4 6-8
Intermediate acting
• Insulin Zinc (Lente) 1–2 8 – 10 20 – 24
• NPH / Isophane 1–2 8 – 10 20 - 24
Long acting
• PZI (ultra lente) 4–6 14 – 20 24 – 36
• Insulin Glargine 2–4 5 – 12 24
Premixed insulin
• 70/30, 50/50, 75/25 < 0.25 1.5 10 - 16
• NPH / Regular 153

I. The VELLORE REGIMEN for Glucose – Insulin infusion (Rule of ! "#!$!%!"&!'()*+'(!!

1-2-3-4)
Blood glucose Regimen
(mg/dl)
< 70 Stop insulin, administer 100 ml D5W rapidly.
Measure blood glucose after 15 minutes. ,--.+!/!01!!
71 – 100 Stop insulin, infuse D5W @ 100 ml/h
101 – 150 1 U insulin + D5W 100 ml/h
151 – 200 2 U insulin + D5W 100 ml/h
201 – 250 3 U insulin + D5W 100 ml/h
251 – 300 4 U insulin + D5W 100ml/h II. CONTINUOUS INSULIN INFUSION (CII) protocol
> 300 1 U insulin for every 1 – 50 mg > 100 mg/dl + Initiating CII
100 ml/h of NS. • Prepare solution – 1 U / 1ml of 0.9% NS
DIABETIC patient in Ketoacidosis coming for emergency surgery, • Start CII when blood glucose > 140mg/dl
• Initial rate – blood glucose(mg/dl) / 100, then round to nearest 0.5 U
(ex. Diabetic foot)
Insulin infusion rate change
Symptoms Signs Blood glucose(mg/dl) Instructions
Nausea/vomiting Tachycardia, hypotension > 200 ↑ rate by 2U/h
Thirst, polyuria Dehydration > 160 - 200 ↑ rate by 1U/h
Abdominal pain Tachypnea / Kussumalʼs > 120 - 160 ↑ rate by 0.5U/h
Shortness of breath Abdominal tenderness 80 - 120 No change in rate
Lethargy/ obtundation/ coma 60 – 80 If < 10% lower blood glucose,↓ rate by 1U/h
Precipitating events Diagnostic criteria If > 10% lower blood glucose, ↓ rate by 50%,
Inadequate insulin administration pH < 7.3 Check BG within 30 mins
Infections HCO3 < 15 mmol/L < 60 Stop infusion
Give IV Dextrose 12.5g (25ml of 50%D)
Infarctions Blood Glucose > 250 mg/dl (>14
Check BG within 30 mins
Drugs mmol/L) Restart infusion at 50% of previous rate
Pregnancy Serum ketones positive
154

• 9/0&/7-8#-"4,0"+>+-1)1)#+"#"-8D7-8#0-'+24)1)<#
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III. GLUCOSE–INSULIN–POTASSIUM (GLIK) or ALBERTI Regimen L&7121,&,1/3#;-&/1/3<#####################
Initiation of tight control:
(Rule of 5-10-15-20) NBM after midnight
• • Q-))#04>-"3247-'17#1/CD"4#+L#/-D"+/&2#&R+/)<#
• Suitable for patient who are likely to be remain NBM for < 48h. 6AM-FBS
Single combined infusion of soluble insulin & glucose. • • Q-))# &R+/&2# 84)LD/7,1+/# &/8# 8-3-/-"&,1+/# &))+71&,-8# ;1,0# 04>-"3247-'1&#
• • First on list
• Safe and easy to administer 1/)D21/#8-L171-/74<#
• Omit morning insulin
• Main drawback – new bag is needed every time the Blood '%,)'.)&*)/0,-$
• 2 lines - Piggyback insulin (50u/250ml NS)
Glucose, potassium falls outside the desired range 5% dextrose
• • ./7"-&)-8#"1)O#+L#S4>+3247-'1&#
! "#$!%!! • Infusion of 5% dextrose with insulin according to formula
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Blood Glucose mg/ •
insulin (U/ Sr.K (mmol/l) KCl (mmol / bag)
dl / (mmol/l)
bag)
• ./LD)1+/#+L#Y\#8-R,"+)-#;1,0#1/)D21/#&77+"81/3#,+#L+"'D2&##
< 70 (< 4.0) 0 • M+"'D2&#5# #
71 – 110 (4 – 6) 5 <3 20
111 – 180(6 – 10) 10 3-5 10 $
181-360(10 – 20) 15 >5 0
>360 (> 20) 20
;;;<!"$%&'<7+'###############################################################################Endocrinology
#
155

DKA HHS Screening for gestational diabetes

Glucose (mg/dl) 250 – 600 600 – 1200 Gestation Fasting venous plasma glucose
concentration
Sodium ( mEq/L) 125 – 135 135 - 145
Up to 20 wks > 105 mg/dl
Potassium (mEq/L) Normal / increase Normal
20 – 40 wks > 120mg/dl
Phosphate Decrease Normal
Creatinine ( mg/dl) Slightly increased Moderately increased Class Fasting plasma 2 h postprandial therapy
Osmolality (mOsm/L) 300 - 320 330 - 380 glucose(mg/dl) glucose(mg/dl)
A1 < 105 < 120 diet
Plasma Ketones ++++ +/-
Sr. HCO3 < 15 mEq/L Normal to slightly A2 > 105 > 120 insulin
decreased
INTRAPARTUM MATERNAL GLYCEMIC CONTROL
Arterial pH 6.8 – 7.3 > 7.3
Plasma capillary Infusion rate Fluids
Arterial pCO2 20 - 30 Normal glucose (mg/dl) 25 U in 250 ml NS
(mmHg)
Anion gap Increased Normal to slightly < 80 Insulin off 5% D @ 125 ml/h (6.5
increased g glucose/h)
80 – 100 0.5 5%D /RL
Drugs Dose Frequency Adverse
Effects 101 – 140 1.0 5% D / RL
Propylthiouracil 100-150 mg 6-8th hrly 141 – 180 1.5 NS
Methimazole 10-15 mg 8th hrly 181 – 220 2.0 NS
> 220 2.5 NS
Carbimazole 10-20 mg 8th hrly
KI/Na I 60 mg 8th hrly
Lugolʼs iodine (5% 0.3 ml (3 8th hrly
iodine in 100ml of drops)
10% KI solution)
Propranolol 40-80 mg 6th hrly
T3 5 µg/day 6th hrly to have its
effects. T ½ → 1
day
T4 100 µg/day 10 days to have its
effect T ½ → 7 day
156

#
Flow chart & Diagram
$
%&'(')*+,(-$-.+/01$
ANTITHYROID DURGS: Pizzillo's method: In obese and short necked patient hands are
23456789:$;<$%4=8;71$
Mechanism of Action: placed behind head and patient is asked to push head backwards
:=# >?;@AB=58;C?648B1# against her clasped hand.
# # # # # >?18&,1+/#&/8#1+81/&,1+/#+@#,4"+)1/-# Ask the patient to swallow, thyroid slowly moves upwards on
# A"-B-/,)C# # # D+EA21/3# deglutition.
# # # # # F-"1A0-"&2#7+/B-")1+/#+@#GH#,+#GI# Kocher's Sign: Starting and frightened appearance of eye which is
#
marked on attentive fixation. In retrosternal goiter lower border of
# swelling cannot be made out during deglutination.
J=# 23=58:6D;B31#
Pemberton's sign: Patient is asked to raise both the arm over his
head until they touch the ears. This is maintained for a while,
# # # # # #
congestion of face and distress becomes evident because of
#################################################################>?18&,1+/#&/8#1+81/&,1+/#+@#,4"+)1/-# obstruction of great veins at thoracic inlet.
# # Palpation: Patient should be sitting on a stool and neck slightly flexed.
##########F"-B-/,)C# Lahey's Method: Examined in front, to palpate the left lobe, gland is
########### # pushed to left from the right side by the left hand of examiner. This
D+EA21/3# makes the left lobe more prominent.
I=# E(F$&6F$(;G8G31# From behind: Patient is asked to flex neck, the thumbs of both hands
# # # # # >?18&,1+/#&/8#1+81/&,1+/#+@#,4"+)1/-# are placed behind the neck and other four fingers are placed on each
# A"-B-/,)C# lobe and isthmus.
# # # # # K-2-&)-#+@#,04"+?1/# Grile's method: For impalpable nodule, patient is asked to deglutinate
#
and nodule is felt.
Kocher's test: If pressure on trachea is suspected, slight push on
!"#$%$ !&%'$ ("')#'*+,$ -./'"%'0122'+3%$
lateral lobes will produce stridor. Positive indicates obstructed trachea
!"#$%&'()#*"+,)&- .//0.1/-23- 405'(-("&%- - from both sides. Carotid pulsation is usually felt laterally and
67'()2+8#&7- ./0.1-23- 5'(-("&%- - backwards.
9+":)2+8#&7- ./0;/-23- 5'(-("&%- - Berry's Sign: Absence of carotid pulsation due to malignant swelling
<=>?+-=- 4/-23- 5 -("&%-
'( - engulfing carotid sheaths.
@*3#&AB-)#C)D7-E1F-)#C)D7-)D- /IJ-2&-EJ-C"#$BH- 5'(-("&%- -
.//2&-#G-./F-<=-B#&*')#DH-
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Differential diagnosis; Type to enter text

Neuroleptic
Thyroid storm Malignant hyperthermia
malignant syndrome
Characterized Acute in onset, rapid if Onset ranges from
sudden appearance anesthesia includes hours to days after
of clinical signs of potent volatile drug treatment
hyperthyroidism due Anesthetic or Scoline (Haloperidol,
to abrupt release of Metoclopramide,
T4 and T3 carbamazepine)
postoperatively.
Temperature Temp. > 430 C Hyperthermia
increases not beyond
400 C
No muscle rigidity is Malignant Impairment of motor
seen hyperthermia results in function → rigidity,
metabolic acidosis akinesia extra-
profound hypercarbia pyramidal
(↑ ETCO2), muscle disturbances.
rigidity seen Deterioration of
mental status →
coma, stupor,
delirium
Creatinine Creatinine -
phosphokinase level phosphokinase levels
is decreased to re increased
about half normal
158

Duration No. of
Plasma Clearance
Drug Preparations of action Daily dose doses remarks
T ½ (hr) route
(hr) per day
SULFONYLUREAS
1. Tolbutamide Rastinon, 6-8 6-8 L 0.5-3 g 2-3 Weaker, shorter acting, flexible dosage, safer in those prone to
0.5 g tab hypoglycaemia.
2. Chlorpropamide Diabinese, 30-36 36-48 K.L 0.1-0.5 g 1 Lonest action, can cause prolonged hypoglycaemia, potentiates ADH
0.1, 0.25g tab action more cholestatic jaundice, alcohol flush
3. Glibenclamide Daonil, Euglucon, 4-6 18-24 L 5-15 mg 1-2 Potent but low acting, marked initial insulinemic action, may work
(Glyburide) Betanase when other fail, metabolite excreted in urine as well as bile single
2.5, 5mg tab daily dose possible despite short T ½ weight gain less likely
4. Glipizide Glynase, Glide 3-5 12-18 L 5-20 mg 1-2 Fast acting, insulinemic action persists even after prolonged use, can
Minidiab 5 mg tab be given once daily despite short T ½, weight gain less likely.
5. Gliclazide Diamicron 80mg tab 8-20 12-24 L 40-240 mg 1-2 Has antiplatelet action, reduces free radicals, may delay diabetic
diazide 20, 80mg tab retinopathy, less weight gain
Glizid 30, 40 80mg tab
6. Glimepiride Amaryl, glypride 5-7 24 L 1-6 mg 1 Stronger extrapancreatic action; less hyperinsulinemia. Divided in
Glimer 1,2 mg tab two if daily dose ≥ 4 mg
BIGUANIDES
1. Phenformin DBI 25 mg tab 3-10 8-12 L.K 25-150 mg 1-3 Lactic acidosis more common, withdrawn in many countries
DBI – TD 50mg tab
2. Metformin Glyciphage 1.5-3 6-8 K 0.5-2 mg 2-4 Not metabolized at all, lactic acidosis less common
Glycomet
0.5, 0.85 g tab
MEGLILTINIDE
ANALOGUES
1. Repaglinide Eurepa, Raplin 0.5, 1, ≤1 2-3 L 1.5-8 mg 3-4 Give ½ hr before each meal for limiting P.P hyperglycaemia
2mg tab
2. Nateglinide Glinate 60, 120mg tab 1.5 2-3 L 180-480 mg 3-4 Stimulates 1st phase insulin secretion, less likely to cause delayed
hypoglycaemia
THIAZOLINDINEDIONES
1. Rosiglitazone Reglit, rosinorm 4 12-24 L 4-8 mg 1-2 Reverses insulin resistance. No hypoglycaemia, C/I in liver and
ross, 2,4,8 mg tab heart disease
2. Pioglitazone Pionorm, Piorest, 3-5 24 L 15-45 mg 1 Reverses insulin resistance. No hypoglycaemia, C/I in liver and
Piozone 15, 30 gm tab heart disease may improve lipid profile
159

Pathophysiology of diabetic ketoacidosis The mechanisms by which, insulin and fluids reverse ketoacidosis.
160

Receptor Tissue Response Pheochromocytoma Triad:

α1 Vascular smooth muscle Contraction ! Headache
Genitourinary smooth muscle Contraction
Liver Glycogenolysis
Gluconeogenesis In association with hypertension
Intestinal smooth muscle Hyperpolarization and relaxation
Heart Increased contractile force,
Arrhythmias Palpitation Sweating
α2 Pancreatic Islets Decreased insulin secretion
Platelets Aggregation Differential diagnosis:
Nerve terminals Decreased release as NE Hyperadrenergic essential Paroxysmal tachycardia
Vascular smooth muscles Contraction hypertension
Anxiety, panic attacks Angina pectoris/Myocardial
β1 Heart Increased force and rate of
contraction and AV nodal
infarction
conduction velocity Thyrotoxicosis Brain tumor or SAH
J.G. cells Increased renin secretion Migraine or cluster head ache Abdominal catastrophe/aortic
β2 Smooth muscle Relaxation dissection
(vascular ,bronchial, GI, and Abrupt clonidine withdrawal Cardiovascular reconditioning
genitourinary)
Amphetamine Menopausal syndrome
Skeletal muscle Glycogenolysis, uptake of K+
Cocaine Neuroblastoma in child
Liver Glycogenolysis, Gluconengenesis
Alcoholism Diencephalic or temporal lobe
β3 Adipose tissue Lipolysis
seizures
DA1 Renal and mesenteric vascular Vasodilatation
Hypoglycemia Toxemia of pregnancy
smooth muscle
DA2 Presynaptic-adrenergic nerve Inhibits Nor-epinephrine release
endings
161

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&/8#@"-+@-"&,1A-#
Flow
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chart & Diagram
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Mechanism for Long term Complications Diabetes Mellitus: #
Polyol !"#$%&'()*+,-*.,&/*0"-)*1,)23'#%0',&(*4'%5"0"(*!"33'06(7*
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# OHA ! FBS, serum
! Admit day before potassium
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! Start iv, insulin/
./L2BR#+L#S:E#1/,+#,0-#7-22# # glucose (GIK
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! Omit breakfast and
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670=&//#F-22)# #
Intraoperative OHA
! Monitor blood glucose
surgery ! Avoid glucose
# hourly
6=-221/3#+L#,0-#F-22# containing fluids
! NPO 8 hrs
! Monitor blood
# glucose 2nd hourly
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! Monitor daily ! Monitor blood
@B'@# ! Monitor blood
# glucose glucose
glucose ! Transfer to ! Restart
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C-"174,-)#+L# with first post insulin if unstable insulin
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162

CLINICAL TESTS OF AUTONOMIC FUNCTION:Non-‐Invasive Bedside Tests: Classification porphyrias:

Part of re@lex ARC – Hepatic porphyrias Erythropoietic porphyrias
Test Normal response
tested Acute intermittent porphyria Erythropoietic uroporphyria
BP response to Fall in BP <30/15 Afferent and efferent
Variegate porphyria (AD) Erythropoietic proto porphyria
Standing / Vertical mmHg-‐ limbs
Hereditary coproporphyria
tilt
HR response to Increase 11-‐29 beat/ Afferent and Efferent Porphyria cutania tarda(AD)
Standing min 30:15 ratio >1.04 limbs
Isometric Exercise Diastolic BP increase Sympathetic Efferent
by 15mmHg limb
HR variation with Max. Min. HR >15 Vagal Afferent and

respiration beats/min Efferent limbs
Valsalva Ratio >1.4 Vagal Afferent and
Efferent
Sweat Tests Sweating all over body Sympathetic efferent
and limbs limbs
Valsalva Maneuvers Phase I-‐Raise in BP Afferent and Efferent
Phase II -‐Gradual limbs
reduction of BP to
plateau-‐Tachycardia.
Phase III-‐Fall in blood
pressure
Phase IV-‐Overshoot of
BP and Bradycardia
163

Consensus Guidelines
I. Dehydration: Fluids
Pathophysiology of Diabetic Ketoacidosis
(DKA) Management:
Absolute insulin deficiency
or
Determine dehydration status
Stress, infection or insufficient insulin intake
Counter-regulatory hormones
Glucagon Cortisol
Catecholamines Growth Hormone
Lipolysis Glucose utilization Proteolysis Glycogenolysis Severe Mild Cardiogenic

Protein synthesis Hypovolemia dehydration Shock
Gluconeogenic substrates
++
FFA to liver Gluconeogenesis
Ketogenesis Hyperglycemia
Administer 0.9%
Alkali reserve Glucosuria (osmotic diuresis) NaCl (1.0L/hr) Hemodynamic
monitoring &
Acidosis Loss of water and electrolytes
Decreased fluid intake pressors
Lactate Dehydration Hyperosmolarity
Evaluate corrected serum sodium
Impaired renal function
of diabetic ketoacidosis. Copyright # 2006 American Diabetes Association. From Diabetes Care, Vol. 29, 2006;
ith permission from The American Diabetes Association.
Check electrolytes, BUN, venous pH, Serum Serum
Serum Na Normal
ar creatinine
filtration.& glucose
At presentation, the
every 2 - 4 hrly ¤ Increased leukocyte count with left
Nashift
high Na Low
until stable.After resolution of
ic deficits in an individual patient DKA & ¤ Non-specific elevation of serum amylase
ponwhen thepatient is ableand
duration to eat, Initiate SC
severity of ¤ Fever only when infection is present
multi-dose insulin regimen. continue IV
to infusion
which for the1-2
patient
hrs afterwas able to
SC insulin to When Serum glucose reaches
f fluid
ensureand electrolytes,
adequate and levels.
plasma insulin the 200 mg/dl, change to 5 % 0.45% NaCl (250-500 ml/hr) 0.9% NaCl (250-500 ml/hr)
Lookconsumed
fluids for precipitating cause.
before coming to Definition of DKA
Dextrose with 0.45% NaCl at depending on hydration state depending on hydration state
150 - 250 ml/hr
Consumption of fluids with a high- The biochemical criteria for the diagnosis of DKA
nt (juices or sugar containing soft are (4): 164
the hyperglycemia (3).
¤ Hyperglycemia (blood glucose . 11 mmol/L [!200
II.Lack of Insulin - Insulin III. Electrolytes - Potassium
Establish adequate renal function

& urine output ( at least 50ml/hr)
Uncomplicated
IV Route
DKA - SC route
If serum K+ is < 3.3 mEq/L, hold insulin

Insulin: Regular Rapid-acting Insulin: & give 40 mEq, K+ per hour (2/3 KCL &
0.1 U/Kg B.wt as 0.3 U/Kg then 0.2 U/Kg 1/3 KPO4) until K > 3.3 mEq/L
IV bolus one hr later
0.1U/kg/hr Rapid-acting If serum K+ > 5.5 mEq/L, but check K+

continuous Insulin: 0.2 U/kg every 2 hour.
insulin infusion every 2 hours
If serum K+ > 3.3 but < 5.5 mEq/L,

give 20 - 30 mEq/L in each liter of IV
If serum glucose does not fall by fluid (2/3 KCL & 1/3 KPO4) to keep
50 - 70 mg/dl in first hour, double serum K+ at 4-5 mEq/L
IV or SC insulin bolus
When serum glucose reaches Check electrolytes, BUN, venous pH,

200mg/dl, reduce regular insulin creatinine & glucose every 2 - 4 hrly until
infusion to 0.05 - 0.1 u/kg/hr IV, or stable.After resolution of DKA & when patient
give rapid-acting insulin at 0.1U/kg When Serum glucose reaches 200 is able to eat, Initiate SC multi-dose insulin
SC every two hrs. Keep serum mg/dl, change to 5 % Dextrose with regimen. continue IV infusion for 1-2 hrs after
glucose between 150-200 mg/dl until 0.45% NaCl at 150 - 250 ml/hr SC insulin to ensure adequate plasma insulin
resolution of DKA levels. Look for precipitating cause.
165

IV. Acidosis - Assess the need of Bicarbonate
pH > 7.0
pH < 6.9 pH 6.9 to 7.0
Dilute NaHCO3 Dilute NaHCO3 No HCO3

(100 mmol) in 200 (50 mmol) in 200
ml NS. Infuse at ml NS. Infuse at
200ml/hr 200ml/hr
166

Probable safe Porphyria Definitely unsafe in Porphyria Controversial in Porphyria

Induction agent Propofol Barbiturates Ketamine
Etomidate
Inhalational agents N2O, ether cyclopropane Enflurane Halothane Sevo/isoflurane
NMB agents Suxamethonium tubocurarine Alcurronium Pancuronium
gallaminevecuronium Atracurium
Rocuronium
Mivacuronium
Analgesics Allfentanil, fentanyl, morphine, Pentazocine Diclofenac
pethidine, aspirin, codeine, Ketorolac
buyprenorphine, Naloxane Sufentanil
Local anesthetics Procaine, prilocaine, Mepivacaine Cocaine
bupivacaine, pracainamide Ropivacaine Lignocaine
Sedatives Midazolam Chlordiazoxide Diazepam
Temazepam Nitrazepam
Lorazepam
Chlorpromazine
Chloral hydrate
Antiemetics Droperidol Simitidine Andansteron
H2 antagonists Phenothiazines Metoclopramide Ranitidine
CVS drugs Adrenaline Hydralazine Diltiazem
α and β agonists Nifedipine SNP
β blockers Phenoxybenzamine Verapamil
Magnesium
Phentalamine
Procainamide
Others - Aminophylline Steroids
OcP, phenytoin
Sulphonamides
167

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Dr. Azam’s....

To Mohammed Shafiulla, my father, my oxygen, companion, and best friend; for

Dr Azam’s Notes in Anesthesiology 2013

A NOTE TO THE READER

Dr Azam’s Notes in Anesthesiology 2013

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Dr Azam’s Notes in Anesthesiology 2013

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Dr Azam’s Notes in Anesthesiology 2013

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Dr Azam’s Notes in Anesthesiology 2013

Dr Azam’s Notes in Anesthesiology 2013

Dr Azam’s Notes in Anesthesiology 2013

Dr Azam’s Notes in Anesthesiology 2013

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Dr Azam’s Notes in Anesthesiology 2013

Dr Azam’s Notes in Anesthesiology 2013

Premedication: • If air way problem is anticipated

Dr Azam’s Notes in Anesthesiology 2013

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Dr Azam’s Notes in Anesthesiology 2013

III) Suppression of sympathetic activity: Tracheomalacia

Dr Azam’s Notes in Anesthesiology 2013

Introduction: Signs and symptoms:

Subclinical hypothyroidism, present in about 5% of population, is

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Management of Anesthesia: Etiology:-

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Dr Azam’s Notes in Anesthesiology 2013

Physiology: Adrenal androgens: Insignificant

Glucocorticoids – cortisol essential for life GLUCOCORTICOID EXCESS – HYPERCORTISOLISM

Dr Azam’s Notes in Anesthesiology 2013

Clinical features: GLUCOCORTICOID DEFICIENCY- HYPOCORTISOLISM

Dr Azam’s Notes in Anesthesiology 2013

S/S: Anesthetic considerations:

Dr Azam’s Notes in Anesthesiology 2013

Dr Azam’s Notes in Anesthesiology 2013

GLUCOCORTICOID RESPONSE TO SURGICAL STRESS CAUSES OF ADRENOCORTICAL HORMONE DEFICIENCY:

Dr Azam’s Notes in Anesthesiology 2013

Dr Azam’s Notes in Anesthesiology 2013

d) Regional anesthesia • Primary adrenal insufficiency is associated with skeletal muscle

Endocrinology DNB Q & A

Endocrinology DNB Q & A

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