Anestezie curs 1

Dr. Radu T Stoica

 21 - Alors lternel Dieu fit tomber un profond sommeil sur lhomme, qui sendormit ; il prit une de ses ctes, et referma la chair sa place.

Anestezia?

History

Original discoverer of general anesthetics

19th Century physician administering chloroform

Crawford Long: 1842, ether anesthesia James Simpson: 1847 Horace Wells

Chloroform introduced

Nitrous oxide

 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 < 36C 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 postsynaptic 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 Segment Intermediate Chain Hydrophilic Segment

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 Vasodilatation Mode of administration Presence of vasoconstrictor Lipid solubility Vasodilatation Tissue pH Concentration of drug

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 Anesthetics 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 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

Agent
Procaine Lidocaine Bupivacaine

(%)
0.5-1.0 0.5-1.0 0.25

Adult (mg)
500 (600) 300 (500) 175 (225)

Pediatric (mg/kg) 7.0 (9) 4.5 (7) 2.0 (3)

Onset (min) 2-5 2-5 2-5

Duration
15-45 min 1-2 hr 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