Chapter 14  ·  Module 1  ·  Visual Summary

Principles of General Anesthesia

Inhalational pharmacokinetics, anesthetic potency, intravenous agents, and preanesthetic medications

Inhalational Pharmacokinetics

Key Pharmacokinetic Property

Blood:Gas Partition Coefficients and Induction Speed

Agent Blood:Gas Coefficient Induction Speed Clinical Notes
Desflurane ~0.42 (lowest) Fastest Pungent — not used for inhalational induction; very rapid emergence
Nitrous oxide ~0.47 Very fast Minimum alveolar concentration 104% — cannot produce surgical anesthesia alone
Sevoflurane ~0.65 Fast Preferred agent for pediatric inhalational induction; pleasant odor
Isoflurane ~1.4 Moderate Standard volatile agent for maintenance; pungent odor limits inhalational induction
Halothane ~2.4 (highest) Slowest High hepatotoxicity risk — largely replaced by newer agents

Rule: Low blood:gas coefficient = low solubility in blood = fast rise in alveolar partial pressure = fast induction. High coefficient = slow induction, slow emergence.

Anesthetic Potency

Minimum Alveolar Concentration

Factors That Decrease MAC

  • Advanced age (most clinically significant)
  • Hypothermia
  • Opioids
  • Benzodiazepines
  • Alpha-2 agonists (dexmedetomidine, clonidine)
  • Acute alcohol intoxication
  • Pregnancy

Minimum Alveolar Concentration

Factors That Increase MAC

  • Hyperthermia
  • Chronic alcohol use
  • Hypernatremia
  • Pediatric age (children have higher minimum alveolar concentration than adults)

MAC additivity: 0.5 minimum alveolar concentration isoflurane + 0.5 minimum alveolar concentration nitrous oxide = 1.0 minimum alveolar concentration effect. MAC-awake (return of consciousness) = approximately 0.3–0.4 minimum alveolar concentration.

Intravenous Anesthetic Agents

IV Induction Agent

Propofol

  • Mechanism: gamma-aminobutyric acid type A potentiation
  • Most widely used induction agent; antiemetic properties
  • Propofol infusion syndrome: metabolic acidosis, rhabdomyolysis, cardiac failure — prolonged high-dose infusion; avoid in pediatric intensive care

IV Induction Agent

Etomidate

  • Mechanism: gamma-aminobutyric acid type A potentiation
  • Minimal cardiovascular effects — preferred in hemodynamic instability
  • Adrenocortical suppression: inhibits 11-beta-hydroxylase; blocks cortisol for 6–24 hours after single dose

IV Induction Agent

Ketamine

  • Mechanism: N-methyl-D-aspartate receptor antagonism → dissociative anesthesia
  • Sympathomimetic: increases heart rate, blood pressure, cardiac output
  • Potent bronchodilator
  • Increases intracranial pressure — caution in head injury
  • Emergence reactions: hallucinations, dysphoria — mitigated by benzodiazepine

IV Sedation Agent

Dexmedetomidine

  • Mechanism: alpha-2 adrenergic agonist (locus coeruleus)
  • Sedation without respiratory depression
  • Arousable, cooperative patients — ideal for procedural sedation and intensive care sedation
  • Adverse effects: bradycardia, hypotension

Preanesthetic Medications

Drug Classes and Mechanisms

Preanesthetic Medication Summary

Drug Mechanism Primary Use Key Point
Midazolam Gamma-aminobutyric acid type A potentiation Anxiolysis, anterograde amnesia, reduces minimum alveolar concentration Most widely used preanesthetic sedative
Fentanyl Opioid receptor agonist Baseline analgesia; blunts laryngoscopy hemodynamic response Rapid onset IV; risk of respiratory depression
Ondansetron 5-hydroxytryptamine type 3 antagonist Postoperative nausea and vomiting prophylaxis Given at end of surgery for early nausea and vomiting
Dexamethasone Glucocorticoid Postoperative nausea and vomiting prophylaxis Given at induction (delayed onset)
Droperidol Dopamine D2 antagonist Postoperative nausea and vomiting prophylaxis Black box warning: QT prolongation / torsades de pointes
Glycopyrrolate Muscarinic antagonist (quaternary amine) Antisialagogue; does not cross blood-brain barrier No central anticholinergic effects (compare atropine)
Metoclopramide Dopamine D2 antagonist + 5-hydroxytryptamine type 4 agonist Aspiration prophylaxis: empties stomach, increases lower esophageal sphincter tone Contraindicated in bowel obstruction
Sodium citrate Non-particulate antacid (direct buffer) Rapid neutralization of gastric acid before induction Safe if aspirated (non-particulate)