General Anesthetics and Stages of Anesthesia

By: Naghman Zuberi

Naghman Zuberi

Anesthesia

Allow surgical, obstetrical and diagnostic procedures to be performed in a manner which is painless to the patient

Allow control of factors such as physiologic

functions and patient movement

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Anesthetic techniques

General anesthesia Regional anesthesia Local anesthesia Conscious Sedation (monitored anesthesia care)

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What is Anesthesia

No universally accepted definition Usually thought to consist of:

Oblivion Amnesia Analgesia Lack of Movement Hemodynamic Stability

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What is Anesthesia
Sensory -Absence of intraoperative pain

Cognitive: -Absence of intraoperative awareness -Absence of recall of intraoperative events Motor: -Absence of movement -Adequate muscular relaxation
Autonomic: -Absence of hemodynamic response -Absence of tearing, flushing, sweating
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Goals of General Anesthesia

Hypnosis (unconsciousness) Amnesia Analgesia Immobility/decreased muscle tone

(relaxation of skeletal muscle)

Inhibition of nociceptive reflexes Reduction of certain autonomic reflexes

(gag reflex, tachycardia, vasoconstriction)

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Desired Effects Of General Anesthesia (Balanced Anesthesia)

Rapid induction Sleep Analgesia Secretion control Muscle relaxation Rapid reversal

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Stages Of General Anesthesia Phases of General Anesthesia

Induction- initial entry to surgical anesthesia Maintenance- continuous monitoring and medication

Maintain depth of anesthesia, ventilation, fluid balance, hemodynamic control, hoemostasis

Emergence- resumption of normal CNS function

Extubation, resumption of normal respiration

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Stages Of General Anesthesia Phases of General Anesthesia

Stage I: Disorientation, altered consciousness Stage II: Excitatory stage, delirium, uncontrolled movement, irregular breathing. Goal is to move through this stage as rapidly as possible. Stage III: Surgical anesthesia; return of regular respiration. Plane 1: light anesthesia, reflexes, swallowing reflexes. Plane 2: Loss of blink reflex, regular respiration (diaphragmatic and chest). Surgical procedures can be performed at this stage. Plane 3: Deep anesthesia. Shallow breathing, assisted ventilation needed. Level of anesthesia for painful surgeries (e.g.; abdominal exploratory procedures).

Plane 4: Diaphragmatic respiration only, assisted ventilation is required. Cardiovascular impairment.

Stage IV: Too deep; essentially an overdose and represents anesthetic crisis. This is the stage between respiratory arrest and death due to circulatory Naghman Zuberi collapse.

Routes of Induction

Intravenous
Safe, pleasant and rapid

Mask
Common for children under 10 Most inhalational agents are pungent, evoke coughing and gagging

Avoids the need to start an intravenous catheter before induction of anesthesia

Patients may receive oral sedation for separation from parents/caregivers

Intramuscular
Used in uncooperative patients
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Anesthetic Techniques

Inhalation anesthesia

Anesthetics in gaseous state are taken up by inhalation

Total intravenous anesthesia Inhalation plus intravenous (Balanced Anesthesia)

Most common

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Anesthetic drugs have rapid onset and offset

Minute to minute control is the holy grail of general anesthesia

Allows rapid adjustment of the depth of anesthesia

Ability to awaken the patient promptly at the end of the surgical procedure Requires inhalation anesthetics and short-acting intravenous drugs

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Anesthetic Depth

During the maintenance phase, anesthetic doses are adjusted based upon signs of the depth of anesthesia Most important parameter for monitoring is blood pressure There is no proven monitor of consciousness

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Selection of anesthetic technique

Safest for the patient Appropriate duration

i.v. induction agents for short procedures

Facilitates surgical procedure Most acceptable to the patient

General vs. regional techniques

Associated costs

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MAC Minimal Alveolar Concentration

"The alveolar concentration of an inhaled anesthetic that prevents movement
in 50% of patients in response to a standardized stimulus (eg, surgical incision)."

A measure of relative potency and standard for experimental studies. MAC values remain constant regardless of stimuli, weight, sex, and even
across species

Steep DRC: 50% respond at 1 MAC but 99% at 1.3 MAC

MAC values for different agents are approximately additive. (0.7 MAC N2O +
0.6 MAC halothane = 1.3 MAC total)

"MAC awake," (when 50% of patients open their eyes on request) is

approximately 0.3.

Light anesthesia is 0.8 to 1.2 MAC, often supplemented with adjuvant i.v.
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drugs

Factors Affecting MAC

Circadian rhythm Body temperature Age Other drugs

Prior use Recent use

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How do Inhalational Anesthetics Work?

Membrane Stabilization Theory:
Site of action in lipid phase of cell membranes (membrane stabilizing effect) or

Hydrophobic regions of membrane-bound proteins

May induce transition from gel to liquid crystalline state of phospholipids Supported by NMR and electron-spin resonance studies Anesthesia can be reduced by high pressure

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Receptors Possibly Mediating CNS Effects Of Inhaled Anesthetics

Potentiation of inhibitory receptors

Inhibition of excitatory receptors

GABAA Glycine Potassium channels

NMDA (glutamate) AMPA (glutamate) Nicotinic acetylcholine Sodium channels

Inferred from demonstration of effect on receptor at clinically relevant concentrations and lack of effect in absence of receptor
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Inhaled Anesthetics

Gases
Nitrous oxide Present in the gaseous state at room temperature and pressure Supplied as compressed gas

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Inhaled Anesthetics

Volatile anesthetics

Present as liquids at room temperature and pressure Vaporized into gases for administration

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Inhaled Anesthetics

Volatile anesthetics

Present as liquids at room temperature and pressure BUT NOT ALWAYS! Vaporized into gases for administration

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Concentration of Inhaled Anesthetics Determines Dose

Partial pressure (mmHg)

Applies to gas phase or to dissolved gases

Percentage of total gas volume contributed by anesthetic Percentage of total gas molecules contributed by anesthetic Partial pressure/atmospheric pressure

Volumes %

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Solubility of Inhaled Anesthetics Determines Dose and Time-course

Ratio of concentration in one phase to that in a second phase at equilibrium Important solubility coefficients for inhaled anesthetics

Lower blood-gas partition coefficient leads to faster induction and emergence

Higher oil-gas partition coefficient leads to increased potency

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Inhaled Anesthetics - Historical

Ether Slow onset, recovery, explosive
Chloroform Slow onset, very toxic Cyclopropane Fast onset, but very explosive

Halothane (Fluothane) first halogenated ether (non-flammable)

50% metabolism by P450, induction of hepatic microsomal enzymes; TFA, chloride, bromide released Myocardial depressant (SA node), sensitization of myocardium to catecholamines Hepatotoxic Methoxyflurane (Penthrane) - 50 to 70% metabolized Diffuses into fatty tissue Releases fluoride, oxalic acid Renotoxic
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Inhaled Anesthetics Currently

Enflurane (Ethrane) Rapid, smooth induction and maintenance
2-10% metabolized in liver Introduced as replacement for halothane, canabilized to make

way for isoflurane

Isoflurane (Forane) smooth and rapid induction and emergence Very little metabolism (0.2%) Control of Cerebral blood flow and Intracranial pressure Potentiates muscle relaxants, Uterine relaxation CO maintained, arrhythmias uncommon, epinephrine can be used

with isoflurane; Preferential vasodilation of small coronary vessels

can lead to coronary steal No reports of hepatotoxicity or renotoxicity
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Most widely employed

Inhaled Anesthetics Currently

Nitrous Oxide is still widely used
Potent analgesic (NMDA antagonist) MAC ~ 120%

Used ad adjunct to supplement other inhalationals

Xenon Also a potent analgesia (NMDA antagonist) MAC is around 80% Just an atom what about mechanism of action?

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Malignant Hyperthermia
Malignant hyperthermia (MH) is a pharmacogenetic hypermetabolic state of skeletal muscle induced in susceptible individuals by inhalational anesthetics and/or succinylcholine (and maybe by stress or exercise).

Genetic susceptibility-Ca+ channel defect (CACNA1S) or RYR1 (ryanodine receptor) Excess calcium ion leads to excessive ATP breakdown/depletion, lactate production, increased CO2 production, increased VO2, and, eventually, to myonecrosis and rhabdomyolysis, arrhythmias, renal failure May be fatal if not treated with dantrolene increases reuptake of Ca++ in Sarcoplasmic Reticulum Signs: tachycardia + tachypnea + ETCO2 increasing + metabolic acidosis; also hyperthermia, muscle rigidity, sweating, arrhythmia Detection:

Caffeine-halothane contracture testing (CHCT) of biopsied muscle; Naghman Zuberi Genetic testing for 19 known mutations associated with MH

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