Inhalational anesthetics

Inhalational anesthetics are used for the induction and maintenance of general anesthesia as well as sedation. The exact mechanisms by which they act are still unknown. The most common inhalational anesthetics are sevoflurane, desflurane, and nitrous oxide. Of these, sevoflurane is the most common because of its rapid onset of action and the fact that patients recover quickly from it. Inhalational anesthetics cause respiratory depression, a decrease in arterial blood pressure and cerebral metabolic demand, and an increase in cerebral blood flow. While side effects differ based on the substance (e.g., halothane can cause hepatotoxicity), the most common side effect is nausea.

Pharmacokinetic principles

• Uptake into the blood: inhalational anesthetics are taken up passively via diffusion, which depends on:
  • Blood solubility of the anesthetic
    • Blood-gas partition coefficient: the ratio of anesthetic concentrations in the blood and alveolar space when partial pressures in the two compartments are equal
    • The higher the blood-gas partition coefficient of an inhalational anesthetic, the higher the solubility of that substance in the blood.
  • Lung ventilation, volumes, and perfusion
• Distribution and uptake into the brain: Transport to and uptake into the brain depend on cerebral perfusion and the fat solubility of the inhalational anesthetic.
  • Brain-blood partition coefficient: the ratio of anesthetic concentrations between brain tissue and blood when partial pressures are equal. The higher the brain-blood partition coefficient, the higher the solubility of the anesthetic in brain tissue
• Onset of effect: : The lower the blood-gas partition coefficient of an inhalational anesthetic, the faster the substance takes effect (less induction time)
• Elimination
  • Inhalational anesthetics are eliminated by the lungs
    • The lower the blood-gas partition coefficient of an inhalational anesthetic, the faster the effect ceases (less recovery time)
  • Inhalational anesthetics are metabolized only to a small degree
    • Exception: halothane is metabolized in the liver
  • With prolonged duration of anesthesia in obese patients, inhalational anesthetics with a high fat solubility can accumulate in adipose tissue and slow down recovery from anesthesia (increased context-sensitive half-life).

Pharmacodynamic principles

• Measure of potency of inhalational anesthetics: minimum alveolar concentration (MAC)
  • MAC is the fraction of volume of the anesthetic present in the inspired air that provides sufficient analgesia in 50% of patients, meaning that patients will not respond to an extremely painful stimulus such as surgical skin incision.
  • MAC is inversely related to anesthetic potency (potency = 1/MAC) and represents the ED₅₀ value.
  • The lower the MAC value, the more fat soluble the anesthetic. For example:
    • Halothane has a slow induction and high potency because of its high lipid and blood solubility.
    • Nitrous oxide (N₂O), in contrast, has a fast induction and low potency due to low lipid and blood solubility.

Pharmacokinetics and pharmacodynamics of common inhalational anesthetics

References:^[3][4][5][6]

General effects

• Anesthesia
• Sedation/narcosis
• ↓ Respiration
• ↓ Arterial blood pressure
• Myocardial depression
• ↓ Cerebral metabolic demand
• ↑ Cerebral blood flow
• ↑ ICP
• Postoperative: nausea and vomiting

Specific characteristics of common inhalational anesthetics

References:^[4]

General side effects

• Postoperative nausea and vomiting ^[7]
• Risk of malignant hyperthermia (except nitrous oxide)
• Postoperative shivering

Side effects of specific substances

• Nitrous oxide
  • Can diffuse into gas-filled body compartments and cause expansion of the gas present there → potential damage to organs/tissues
  • Causes mild myocardial depression and increases pulmonary vessel resistance
• Desflurane ^[8]
  • ↓ Systemic vascular resistance → hypotension
  • Cardiac output is well-preserved.
  • High concentrations → transient stimulation of the sympathetic nervous system → possible tachycardia, hypertension, and dysrhythmias
• Sevoflurane
  • Interacts with soda lime → nephrotoxic breakdown products (known as compounds A–E)
  • ↓ Minute ventilation ^[8]
• Isoflurane
  • ↑ Intracranial pressure
  • Nausea and vomiting (postoperatively)
  • Malignant hyperthermia
• Methoxyflurane: nephrotoxic
• Enflurane: proconvulsive
• Halothane: hepatotoxic → halothane hepatitis ^[9]
  • Pathophysiology: underlying mechanism not fully understood
  • Clinical features
    • Occurs 2 days to 3 weeks after halothane exposure
    • Signs of acute hepatitis (e.g., jaundice, fever, vomiting, hepatomegaly)
    • Rash, arthralgias
  • Diagnostics: diagnosis of exclusion
    • Possible laboratory findings: ↑ eosinophils, ↑ serum transaminases ; , ↑ bilirubin, ↑ alkaline phosphatase
    • Biopsy shows massive centrilobular hepatic necrosis
  • Treatment: depending on the severity of liver damage, ranges from supportive treatment to liver transplantation ^[10]

References:^{[4][7][9][11]}

We list the most important adverse effects. The selection is not exhaustive.