Anestezie curs 1

Dr. Radu T Stoica

• 21 - Alors l’Éternel Dieu fit tomber un profond
sommeil sur l’homme, qui s’endormit ; il prit
une de ses côtes, et referma la chair à sa
place.
Anestezia?
 History

 19th Century physician administering

Original discoverer of chloroform
general anesthetics
 Crawford Long: 1842,
ether anesthesia
 Chloroform introduced
 James Simpson: 1847
 Nitrous oxide
 Horace Wells
• 1853
• Anesthesie “a la reine”
• Regina Victoria, usor cloroformizata, l-a nascut
pe al 8-lea fiu, Leopold
• Dr. John Snow
 History of Anesthesia
• Endotracheal tube discovered in 1878

• Local anesthesia with cocaine in 1885

• Thiopental first used in 1934

• Curare first used in 1942 –

opened the “Age of Anesthesia”
 Definition of general anesthesia

• Tripod on a platform
Analgesia
Muscular relaxetion
Hypnosis and amnesia

Maintaining homeostasis during surgical

procedure
 Principles of general anesthesia

 Minimizing the potentially harmful direct and

indirect effects of anesthetic agents and techniques

 Sustaining physiologic homeostasis during surgical

procedures

 Improving post-operative outcomes

 The Body and General Anesthesia

• Hemodynamic effects: decrease in systemic arterial

blood pressure
• Respiratory effects: reduce or eliminate both
ventilatory drive and reflexes maintaining the airway
unblocked
• Hypothermia: body temperature < 36˚C
• Nausea and Vomiting
– Chemoreceptor trigger zone
• Emergence
– Physiological changes
 Tipuri de anestezie

• Dupa mecanisme
• Anestezie generala
• Anestezie, locala, loco-regionala
• Tehnici combinate (generala si loco-regionala)

• Dupa durata interventiei chirurgicale

Anestezie de o zi (one-day anesthesia)
• Dupa locatie Anestezie in ambulator, in spital
 Mechanism
• Early Ideas
– Unitary theory of anesthesia
• Anesthesia is produced by disturbance of the physical
properties of cell membranes
• Problematic: theory fails to explain how the proposed
disturbance of the lipid bilayer would result in a
dysfunctional membrane protein

• Focus on identifying specific protein binding

sites for anesthetics
 Cellular Mechanism
• Intravenous Anesthetics
– Substantial effect on synaptic transmission
– Smaller effect on action-potential generation or
propagation
– Produce narrower range of physiological effects
• Actions occur at the synapse
– Effects the post-synaptic response to the released
neurotransmitter
• Enhances inhibitory neurotransmission
 Molecular Actions: GABAA Receptor

• Ligand-gated ion channels

– Chloride channels gated by the
inhibitory GABAA receptor
• GABAA receptor mediates the
effects of gamma-amino
butyric acid (GABA), the major
inhibitory neurotransmitter in
the brain
– GABAA receptor found
throughout the CNS
» Most abundant, fast
inhibitory, ligand-gated
ion channel in the
mammalian brain
» Located in the post-
synaptic membrane
Molecular Action: GABAA Receptor

• Receptor sits in the membrane of

its neuron at the synapse
• GABA, endogenous compound,
causes GABA to open
• Receptor capable of binding 2
GABA molecules, between an alpha
and beta subunit
– Binding of GABA causes a
conformational change in
receptor
• Opens central pore
• Chloride ions pass down
electrochemical gradient
– Net inhibitory effect, reducing
activity of the neuron
 Current News
• March 30, 2007
• The Wall Street Journal: “FDA Wants More
Research on Anesthesia Risk to Kids”
– Anesthesia can be harmful to the developing brain,
studies on animals suggest, raising concerns about
potential risks in putting young children under for
surgery
• Prolonged changes in behavior; memory and learning
impairments
– Relevance of the animal findings to pediatric
patients is unknown
 Inhalational Anesthetic Agents

• Inhalational anesthesia refers to the delivery

of gases or vapors from the respiratory system
to produce anesthesia

• Pharmacokinetics--uptake, distribution, and

elimination from the body

• Pharmacodyamics-- MAC value

 Nitrous Oxide

• Simple linear compound

• Not metabolized

• Only anesthetic agent

that is inorganic
 Nitrous Oxide
• Major difference is low potency

• MAC value is 105%

• Weak anesthetic, powerful analgesic

• Needs other agents for surgical anesthesia

• Low blood solubility (quick recovery)

 Nitrous Oxide Systemic Effects
• Minimal effects on heart rate and blood
pressure

• May cause myocardial depression in sick

patients

• Little effect on respiration

• Safe, efficacious agent

 Halothane

• Synthesized in 1956 by
Suckling

• Halogen substituted
ethane

• Volatile liquid easily

vaporized, stable, and
nonflammable
 Halothane
• Most potent inhalational anesthetic

• MAC of 0.75%

• Efficacious in depressing consciousness

• Very soluble in blood and adipose

• Prolonged emergence
 Halothane Systemic Effects

• Decreases respiratory drive-- central response

to CO2 and peripheral to O2
– Respirations shallow-- atelectasis
– Depresses protective airway reflexes
• Depresses myocardium-- lowers BP and slows
conduction
• Mild peripheral vasodilation
 Halothane Side Effects

• “Halothane Hepatitis” -- 1/10,000 cases

– fever, jaundice, hepatic necrosis, death
– metabolic breakdown products are hapten-protein
conjugates
– immunologically mediated assault
– exposure dependent
 Halothane Side Effects

• Malignant Hyperthermia-- 1/60,000 with

succinylcholine to 1/260,000 without
– halothane in 60%, succinylcholine in 77%
• Classic-- rapid rise in body temperature, muscle
rigidity, tachycardia, rhabdomyolysis, acidosis,
hyperkalemia, DIC
– most common masseter rigidity
– family history
 Sevoflurane and Desflurane

• Enflurane, Isoflurane…
• Low solubility in blood-- produces rapid
induction and emergence
• Minimal systemic effects-- mild respiratory
and cardiac suppression
• Few side effects
• Expensive
• Differences
 Intravenous Anesthetic Agents

• First attempt at intravenous anesthesia by

Wren in 1656-- opium into his dog
• Use in anesthesia in 1934 with thiopental
• Many ways to meet requirements-- muscle
relaxants, opoids, nonopoids
• Appealing, pleasant experience
Local anesthesia. Physiochemical
Properties
Aromatic Hydrophilic
Segment Intermediate Segment
Chain

Amino-ester Amino-amine

“Esters” “Amines”
 Physiochemical Properties

• Amino-esters (“Esters”)
– Older class of drugs
– Derivatives of PABA (p-aminobenzoic acid)
– Hydrolyzed by serum cholinesterase
• Examples
– Procaine (Novocaine)
– Cocaine
– Tetracaine
– Benzocaine
• Amino-amines (“Amines”)
– Newer class of drugs
– Derivatives of aniline
– Hepatic degradation
• Examples
– Lidocaine
– Bupivocaine (Marcaine, Sensoricaine, Polocaine)
– Mepivocaine (Carbocaine)
– Etidocaine
– Prilocaine
 Mechanism of action
Protein binding Lipid solubility
Vasodilatation Vasodilatation
Mode of administration Tissue pH

ion

Pot
Presence of vasoconstrictor Concentration of drug

ra t

enc
Du

y
Onset
Inherent pKa
Myelination
Interspersed tissue
Dosage of drug
 Ideal Anesthetic
• Immediate onset
• Reversible
• Appropriate duration
• No permanent damage
• No tissue irritation / pain
• Wide therapeutic range
• Effective regardless of application
 Topical anesthesia
• Epidermis
– Avascular layer measuring 0.12 to 0.7 mm
– Barrier to diffusion of topicals
• Dermis
– Support structure
– Contains blood vessels and nerve endings
– Anesthetic’s targeted site of action
 Uses
• Intact skin procedures
– Venopuncture
– Punch biopsies
– Lumbar puncture
 Lidocaine Cream
• 30% lidocaine cream
• Saturated on gauze pad adherent to an elastic
patch
• 45 minutes minimum application time
• ½ hour anesthetic duration = 2 hour
application
• Effective and safe, but not practical
 EMLA
(Eutectic Mixture of Local Anesthetics)
• 2.5% lidocaine and 2.5% prilocaine
• 1-hour application time
• Maximum dose at 2-3 hours
• Depth of anesthesia correlated to duration of
application
• Duration of 1-2 hours after removal
• Hypersensitivity and systemic toxicity rare
 Ethyl Chloride (C2H5CL)
• Not an anesthetic, but a vapocoolant
• Immediate anesthesia, but limited duration
• Spray for 3 to 7 seconds
• Used for injections and lancing small
abscesses or boils
• Not used for punch biopsies
 Mucous Membranes
• Nose, mouth, throat, tracheobronchial tree,
esophagus, and genitourinary tract
• Tetracaine
• Lidocaine
• Cocaine
• Benzocaine
 Infiltration Anesthesia
• Injection of anesthetic agent directly into
tissue
• Excision of skin lesions
• Incision of abscess
• Suturing of wounds
 Advantages & Disadvantages
• Advantages
– Quick and safe
– Provides hemostasis
• Disadvantages
– Large dose for small area
– Distorts wounds
 Choice of Agent

Maximum Dose
Concentration Pediatric Onset
Agent (%) Adult (mg) (mg/kg) (min) Duration
Procaine 0.5-1.0 500 (600) 7.0 (9) 2-5 15-45 min
Lidocaine 0.5-1.0 300 (500) 4.5 (7) 2-5 1-2 hr

Bupivacaine 0.25 175 (225) 2.0 (3) 2-5 4-8 hr

 Injection Technique
• Lowest concentration effective
• Prep wound first if possible
• Smallest needle available (27g)
• Use wound margin
• Subdermal injection
• Insert, then inject
 Injection
• Injection should be subdermal
• Bury the hub and inject as you withdraw
• Through wound edge
 Allergic Reactions
• Fisher,et al
• Anesthetic allergy clinic
• 208 patients with “allergy” to local anesthetic over
20 year period
• Intradermal testing
• 4 immed, 4 delayed
• 39 to “additives”

Fisher MM, Bowie CJ Alleged Allergy to Local Anesthetics Anaesth Intensive

care 1997 Dec;25(6):611-4
 Systemic Toxic Reaction
• Host Factors
– Hypoxia
– Acid-base status
– Protein binding
– Concomitant drugs