Halothane


  • Halothane is a halogenated hydrocarbon
  • It has a chiral carbon
  • As a volatile anaesthetic it has largely been superseded
Time constant graph
  • Is unstable when exposed to light
  • Corrodes certain metals
  • Dissolves into rubber and may leak into breathing circuits even after the vaporiser is turned off

  • Is therefore stored with 0.01% thymol to prevent decomposition by light and liberation of free bromine


MAC Blood:gas coefficient Oil:gas coefficient Molecular weight Boiling point SVP at 20ºC Safe ppm
0.8% 2.2 224 197 50.2ºC 32.3kPa 10
  • Non-irritant
  • Sweet odour

Metabolism

  • 20 - 25% oxidative metabolism by CYP2E1 enzyme, producing:
    • Trifluoroacetic acid
    • Bromide and chloride ions

  • There is also reductive metabolism to fluoride and other reductive metabolites when there is liver hypoxia
  • While these are toxic they are not thought to be involved in halothane hepatitis

Respiratory

  • Some reduction in VT but overall does not affect PaCO2
  • Significant bronchodilator properties and therefore useful in asthma

Cardiovascular

  • Net reduction in blood pressure owing to:
    • Direct myocardial depressant effect therefore significantly reduced contractility
    • Indirect effects increasing vagal tone, reducing heart rate
    • Reduces SVR

  • Reduces splanchnic blood flow
  • Significant sensitisation to endogenous and exogenous catecholamines
    • Doses of adrenaline should be limited to 10ml of 1:100,000 in 10mins to reduce risk of VT

Neurological

  • Massive increase in CBF causing raised ICP, but reduces CMRO2
  • Burst suppression on EEG
  • Some potentiation of muscle relaxation and some uterine relaxation
  • No analgesic properties

Reversible hepatic damage

  • Occurs in 25% of patients
  • Often subclinical
  • Associated with rise in transaminase levels
  • Can affect metabolism of drugs used in peri-operative period
  • Probably secondary to hepatic hypoxia as halothane reduces splanchnic blood flow

Halothane hepatitis

  • A severe centrilobular hepatic necrosis and consequent fulminant liver failure
  • Occurs in 1 in 80,000 - 200,000 children, and 1 in 2,500 - 35,000 adults

  • Oxidative metabolism of halothane generates trifluoroacetyl chloride
  • Trifluoroacetyl chloride acts as a hapten
    • Binds covalently to hepatic proteins
    • Induces antibody formation in a T-cell mediated process

  • Risk factors include:
    • Middle aged
    • Female
    • Liver disease
    • Hypoxia
    • Obesity
    • Repeated exposure (avoid halothane if administered within previous 3 months)
    • Previous reaction

  • Mortality 50 - 75%