Halothane is a general anesthetic that is inhaled. Its IUPAC name is
2-bromo-2-chloro-1,1,1-trifluoroethane. It is the only inhalational anesthetic
containing bromine. It is colorless and pleasant-smelling, but unstable in
light. It is packaged in dark-colored bottles and contains 0.01% thymol as a
stabilizing agent. It is on the WHO Model List of Essential
Medicines, the most important medications needed in a basic health
system. Its use in developed countries has been mostly superseded by newer
agents such as sevoflurane, isoflurane, and desflurane. As of 2014 it cost about
22 to 52 USD for a 250 ml bottle. Medical uses
It is a potent anesthetic with a MAC of 0.74%. Its blood/gas partition
coefficient of 2.4 makes it an agent with moderate induction and recovery
time. It is not a good analgesic and its muscle relaxation effect is moderate.
Side effects In rare cases, repeated exposure to
halothane in adults was noted to result in severe liver injury. This occurred in
about one in 10,000 exposures. The resulting syndrome was referred to as
halothane hepatitis, and is thought to result from the metabolism of halothane
to trifluoroacetic acid via oxidative reactions in the liver. About 20% of
inhaled halothane is metabolized by the liver and these products are excreted in
the urine. The hepatitis syndrome had a mortality rate of 30% to 70%. Concern
for hepatitis resulted in a dramatic reduction in the use of halothane for
adults and it was replaced in the 1980s by enflurane and isoflurane. By 2005,
the most common volatile anesthetics used were isoflurane, sevoflurane, and
desflurane. Since the risk of halothane hepatitis in children was substantially
lower than in adults, halothane continued to be used in pediatrics in
the 1990s as it was especially useful for inhalation induction of anaesthesia
. However, by 2000, sevoflurane, excellent for inhalation induction, had
largely replaced the use of halothane in children.
Halothane sensitises the heart to catecholamines, so it is liable to cause
cardiac arrhythmias, occasionally fatal, particularly if hypercapnia has been
allowed to develop. This seems to be especially problematic in dental
anaesthesia. Like all the potent inhalational
anaesthetic agents, it is a potent trigger for malignant hyperthermia.
Similarly, in common with the other potent inhalational agents, it relaxes
uterine smooth muscle and this may increase blood loss during delivery or
termination of pregnancy. = Occupational safety =
People can be exposed to halothane in the workplace by breathing it in as
waste anaesthetic gas, skin contact, eye contact, or swallowing it. The National
Institute for Occupational Safety and Health has set a
Recommended_exposure_limit of 2 ppm over 60 minutes.
Pharmacology Halothane activates GABAA and glycine
receptors. It also acts as an NMDA receptor antagonist, inhibits nACh and
voltage-gated sodium channels, and activates 5-HT3 and twin-pore K+
channels. It does not affect the AMPA or kainate receptors.
Chemical and physical properties Chemically, halothane is an alkyl
halide. The structure has one stereocenter, so- and-optical isomers
occur. Synthesis
The commercial synthesis of halothane starts from trichloroethylene, which is
reacted with hydrogen fluoride in the presence of antimony trichloride at
130°C to form 2-chloro-1,1,1-trifluoroethane. This is
then reacted with bromine at 450°C to produce halothane.
Related substances Attempts to find anesthetics with less
metabolism led to halogenated ethers such as enflurane and isoflurane. The
incidence of hepatic reactions with these agents is lower. The exact degree
of hepatotoxic potential of enflurane is debated, although it is minimally
metabolized. Isoflurane is essentially not metabolized and reports of
associated liver injury are quite rare. Small amounts of trifluoroacetic acid
can be formed from both halothane and isoflurane metabolism and possibly
accounts for cross sensitization of patients between these agents.
The main advantage of the more modern agents is lower blood solubility,
resulting in faster induction of and recovery from anaesthesia.
History Halothane was first synthesized by C. W.
Suckling of Imperial Chemical Industries in 1951 in Widnes and was first used
clinically by M. Johnstone in Manchester in 1956. It became popular as a
nonflammable general anasthetic replacing other volatile anesthetics
such as trichloroethylene, diethyl ether and cyclopropane. In many parts of the
world it has been largely replaced by newer agents since the 1980s but is
still widely used in developing countries and in veterinary surgery
because of its lower cost. Halothane was given to many millions of
adult and pediatric patients worldwide from its introduction in 1956 through
the 1980s. Its properties include cardiac depression at high levels,
cardiac sensitization to catecholamines such as norepinephrine, and potent
bronchial relaxation. Its lack of airway irritation made it a common inhalation
induction agent in pediatric anesthesia. Due to its cardiac depressive effect, it
was contraindicated in patients with cardiac failure. Halothane was also
contraindicated in patients susceptible to cardiac arrhythmias, or in situations
related to high catecholamine levels such as pheochromocytoma.
Availability It is available as a volatile liquid, at
30, 50, 200, and 250 ml per container but in many first world nations is not
available having been displaced by newer agents.
References Further reading
Atkinson, Rushman, Lee. A Synopsis of Anaesthesia. 1987.
Eger, Eisenkraft, Weiskopf. The Pharmacology of Inhaled Anesthetics.
2003.