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INTRODUCTION

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General anesthetics depress the CNS to a sufficient degree to permit the performance of surgery and unpleasant procedures. General anesthetics have low therapeutic indices and thus require great care in administration. The selection of specific drugs and routes of administration to produce general anesthesia is based on the pharmacokinetic properties and on the secondary effects of the various drugs. The practitioner should consider the context of the proposed diagnostic or surgical procedure and the individual patient’s characteristics and associated medical conditions when choosing appropriate anesthetic agents.

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ABBREVIATIONS

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Abbreviations

ACh: acetylcholine

AChE: acetylcholinesterase

ADME: absorption, distribution, metabolism, excretion

CBF: cerebral blood flow

CL: clearance

CMR: cerebral metabolic rate

CMRO2: cerebral metabolic rate of O2 consumption

CNS: central nervous system

CO: cardiac output

DA: dopamine

ED50: median effective dose

EEG: electroencephalogram

FDA: Food and Drug Administration

FIO2: inspired O2 fraction

GABA: γ-aminobutyric acid

GFR: glomerular filtration rate

GPCR: G protein–coupled receptor

Hb: hemoglobin

HR: heart rate

5HT: 5-hydroxytryptamine: serotonin

ICP: intracranial pressure

IV: intravenous

LD50: median lethal dose

MAC: minimum alveolar concentration

MAP: mean arterial pressure

MI: myocardial infarction

NE: norepinephrine

NK1: neurokinin 1

NMDA: N-methyl-D-aspartate

NSAID: nonsteroidal anti-inflammatory drug

PaCO2: arterial CO2 tension

PO2: partial pressure of O2

PRIS: propofol infusion syndrome

RBF: renal blood flow

RR: respiratory rate

RT: room temperature

t1/2β: β-phase (tissue elimination) half-life

TREK channel: mechanosensitive K+ channel

E: minute ventilation

VLPO: ventrolateral preoptic

Vss: volume of distribution at steady state

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GENERAL PRINCIPLES OF SURGICAL ANESTHESIA

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The administration of general anesthesia is driven by three general objectives:

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  1. Minimizing the potentially deleterious direct and indirect effects of anesthetic agents and techniques.

  2. Sustaining physiologic homeostasis during surgical procedures that may involve major blood loss, tissue ischemia, reperfusion of ischemic tissue, fluid shifts, exposure to a cold environment, and impaired coagulation.

  3. Improving postoperative outcomes by choosing techniques that block or treat components of the surgical stress response that may lead to short- or long-term sequelae.

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Hemodynamic Effects of General Anesthesia

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The most prominent physiological effect of anesthesia induction is a decrease in systemic arterial blood pressure. The causes include direct vasodilation, myocardial depression, or both; a blunting of baroreceptor control; and a generalized decrease in central sympathetic tone. Agents vary in the magnitude of their specific effects, but in all cases the hypotensive response is enhanced by underlying volume depletion or preexisting myocardial dysfunction.

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Respiratory Effects of General Anesthesia

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Nearly all general anesthetics reduce or eliminate both ventilatory drive and the reflexes that maintain airway patency. Therefore, ventilation generally must be assisted or controlled for at least some period during surgery. The gag reflex is lost, and the stimulus ...

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