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.
ADME: absorption, distribution, metabolism, excretion
CBF: cerebral blood flow
CMR: cerebral metabolic rate
CMRO2: cerebral metabolic rate of O2 consumption
CNS: central nervous system
CO: cardiac output
ED50: median effective dose
FDA: Food and Drug Administration
FIO2: inspired O2 fraction
GABA: γ-aminobutyric acid
GFR: glomerular filtration rate
GPCR: G protein–coupled receptor
HR: heart rate
5HT: 5-hydroxytryptamine: serotonin
ICP: intracranial pressure
LD50: median lethal dose
MAC: minimum alveolar concentration
MAP: mean arterial pressure
MI: myocardial infarction
NK1: neurokinin 1
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
V̇E: minute ventilation
VLPO: ventrolateral preoptic
Vss: volume of distribution at steady state
GENERAL PRINCIPLES OF SURGICAL ANESTHESIA
The administration of general anesthesia is driven by three general objectives:
Minimizing the potentially deleterious direct and indirect effects of anesthetic agents and techniques.
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.
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.
Hemodynamic Effects of General Anesthesia
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.
Respiratory Effects of General Anesthesia
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 ...