Inhalational Anesthetic Agents

Halothane, CF₃-CHBrCl

Physical Properties

• halogenated ethrane
• vapor pressure = 243 mmHg at 20 deg C
• spontaneous oxidative decomposition retarded by
  • thymol preservative
  • amber-colored bottle
• least expensive volatile anesthetic agent

Organ System Effects

• direct myocardial depressant and coronary artery vasodilator
  • interfers with Na-Ca exchange and
  • intracellular Ca utilization
  • depresses cardiac output and lowers arterial BP
  • depresses myocardial O₂ demand so that
  • myocardial O₂ delivery is adequate
• depresses SA-node function
  • bradycardia
  • AV nodal rhythm
• depresses baroreflex
• enhances myocardial sensitivity to the dysrhythmogenic effects of epinephrine
  • limit epi to < 1.5 mcg/kg

• fast, shallow breathing, with
• increased p_aCO₂ (during spontaneous ventilation) that
• partly reverses cardiovascular depression
• severe depression of hypoxic ventilatory drive (even at 0.1 MAC)
• potent bronchodilator (inhibits intracellular Ca mobilization)
• depresses mucocilliary function

• general anesthesia, MAC = 0.75
• cerebral vasodilator
• increases CBF
• blunts cerebrovascular autoregulation
• hyperventilation prior to halothane may prevent the expected rise in ICP

Biotransformation and Toxicity

• oxidized in liver by cytochrome P-450 2EI to trifluroacetic acid
• absent O₂, hepatotoxic reduction products may arise
• halothane hepatitis
  • extremely rare (1:35,000 cases)
  • factors that increase risk:
    • multiple exposures to halothane over a short interval
    • middle-aged, obese women
    • familial predisposition
    • personal history of toxicity
  • centrilobular necrosis
  • antibody that binds to halothane-exposed hepatocytes may be isolated

Contraindications/Precautions

• malignant hyperthermia susceptibility
• unexplained liver dysfunction after previous halothane exposure
• intracranial mass lesion
• hypovolemia
• aortic stenosis
• pheochromocytoma
• with aminophylline has been associated with severe ventricular dysrhythmias

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