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Chapter: Modern Medical Toxicology: Neurotoxic Poisons: Anaesthetics and Muscle Relaxants

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Halothane - Inhalational Anaesthetics

Synonyms · Bromochlorotrifluoroethane. Physical Appearance · Halothane is a non-flammable, volatile liquid. It is colourless and has a sweetish odour. It is light-sensitive.

Halothane

Synonyms

·              Bromochlorotrifluoroethane.

Physical Appearance

·              Halothane is a non-flammable, volatile liquid. It is colourless and has a sweetish odour. It is light-sensitive.

Uses

·              Halothane can be used in combination with oxygen, or other gas mixtures such as nitrous oxide and oxygen for general anaes-thesia. During such use, the arterial blood levels of halothane usually range from 80 to 260 mg/L.

·              Halothane is known for its abuse potential among hospital personnel since inhalation of small amounts produces pleasur-able effects. A popular method of halothane abuse is to drip the liquid onto a pad held over the face.

Toxicokinetics

·              Approximately 60 to 80% of absorbed halothane is elimi- nated unchanged in the exhaled gas in the first 24 hours, and smaller amounts continue to be exhaled over the subsequent days or even weeks.

·              Of the non-exhaled fraction, 50% undergoes biotransfor- mation by the hepatic P450 system, while the remaining is eliminated unchanged by other routes, especially urine which contains organic fluorine-containing compounds such as trifluoroacetic acid.

·              Metabolites include apart from trifluoroacetie acid, bromide and chloride salts, chlorotrifluoroethane, and chlorodif- luoroethylene.

Adverse Effects

·              Hypotension, cardiac rhythm disturbances, malignant hyper-thermia. Malignant hyperthermia has been reported in patients given halothane with and without suxam-ethonium (succinylcholine).

Drug Interactions

·              Concomitant administration of adrenaline increases the risk of ventricular arrhythmias and acute pulmonary oedema. Halothane potentiates the effect of neuromuscular blocking agents.

·              Chlorpromazine and morphine enhance the respiratory depressant properties of halothane.

Clinical (Toxic) Features

·      The most important toxic effect is hepatitis. Two types of hepatitis have been observed.

o     The first is a mild dysfunction which develops in about 20% of exposed patients, is characterised by moderate elevation of serum aminotransferase level, and is associ-ated with complete recovery.

o     The second is a life-threatening hepatitis occurring in about 1 in 10,000 exposed patients which can terminate in massive hepatic necrosis in approximately 1 in 35,000 patients. Chills and fever are often associated with the hepatitis reaction seen with halothane. The histopathological findings in such a case are identical to those seen in viral hepatitis.

o     Predisposing factors to halothane hepatitis include multiple exposures, obesity, female sex, and old age. Genetic factors may also play a role as some races (e.g. Mexican-Indian or Mexican-Spanish) are more susceptible.

·      Pulmonary oedema and seizures occur if halothane is administered intravenously, while inhalation is not associ-ated with such effects.

·      On ingestion, there is vomiting, depression of conscious-ness, hypotension, shallow breathing, bradycardia with extrasystoles, and pulmonary oedema. Asystole has occurred with therapeutic use.

·      Sinus tachycardia occurs often in early phases of halothane overdose.

·      There is a characteristic fruity or sweet odour to the breath.

Treatment

·      Full recovery is usual with supportive care, endotracheal intubation, and gastric lavage. Ingestion of this inhalational anaesthetic is unlikely, but has occurred. Absorption is rapid and gastric lavage is not routinely recommended as it is unlikely to be useful unless performed very soon after ingestion. Consider administration of activated charcoal after a potentially toxic ingestion.

·      For bradycardia, give 0.5 mg to 1 mg of atropine intrave-nously; repeat every five minutes if bradycardia persists. 3 mg (0.04 mg/kg) intravenously is a fully vagolytic dose in most adults. Doses less than 0.5 mg may cause paradoxical bradycardia in adults.

·      Dantrolene may be used for malignant hyperthermia. The dose is 1 mg/kg by rapid intravenous infusion until symp-toms subside (maximum dose 10 mg/kg in a single dose).

·      N-acetylcysteine has been an effective pre-treatment in protecting against halothane-induced hepatotoxicity in animals. The importance of this finding is unknown in human overdoses, as hepatitis is not a commonly occurring effect with acute overdose.

 

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