Halothane Biotransformation in Man

Rehder, Kai; Forbes, Joseph; Med, Cand; Alter, Helmuth; O, Hessler; Stier, A.

doi:10.1097/00000542-196707000-00018

Cited by 156 publications

(32 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This postulates the presence of either more metabolic sites, becoming available through enzyme induction, or metabolism and excretion beginning earlier with repeated exposures. The variability between metabolite formation and urinary excretion shown by Rehder, et al, 12 Cascorbi, et al, la and Cohen, et al TM tends to oppose the latter theory. Time-constant determinations in our study not only suggest enzyme induction but favour this theory.…”

Section: Methodsmentioning

confidence: 92%

The effects of repeated14C halothane exposure in mice

Stoyka

Havasi

1977

Canad. Anaesth. Soc. J.

View full text Add to dashboard Cite

THE ANAESTHETIC ADMINISTRATION Of 14C labelled halothane has been shown to cause non-volatile halothane metabolites to accumulate in the liver of mice) These labelled halothane metabolites are bound to liver microsomes in proportion to liver blood flow, hepatic arterial oxygen tension and enzyme induction? Cohen 3 showed that repeated weekly injections of labelled halothane caused non-volatile metabofires to accumulate and increase in the liver suggesting stimulation of enzyme induction. In contrast, Topham and Longshaw 4 showed that repeated daily inhalations of labelled halothane produced no accumulation of non-volatile metabolites using whole body auto-radiography techniques. Stevens and co-workers 5 reported that constant subanaesthetic inhalations of halothane for 35 days caused reproducible dose dependent liver toxicity. This could be related to Sawyer's 6 work which showed optimum halothane metabolism at 1/100 MAC. It was hypothesized that increasing halothane concentrations depressed the necessary enzyme systems for halothane metabolism and that optimum metabolism may only be present in the post-anaesthetic period.In an attempt to clarify the divergent results of other workers, our study measured metabolism of halothane with chronic repeated exposures, determined the specific site of metabolism and assessed possible hepatotoxicity by light and electron microscopy. METHODS

show abstract

Section: Methodsmentioning

confidence: 92%

The effects of repeated14C halothane exposure in mice

Stoyka

Havasi

1977

Canad. Anaesth. Soc. J.

View full text Add to dashboard Cite

show abstract

“…The problem is that these metabolites can be stored by the body so that chronic exposure, even to low pollution concentrations of inhalational agent, might lead to accumulation. For example, studies by Stier, Alter, & Hessler (1964) and Rehder, Forbes & Alter (1967) demonstrated that metabolites of halothane could be recovered from the urine of patients as long as 20 days after anaesthesia. Similarly, Holaday, Rudofsky & Treuhaft (1970) found that metabolites of methoxyflurane were still being excreted 10 days after surgical anaesthesia.…”

Section: Hepatic and Renal Dysfunctionmentioning

confidence: 99%

Anaesthetic gases and health risks to laboratory personnel: a review

Green

1981

Lab Anim

View full text Add to dashboard Cite

The evidence that chronic exposure to inhalational anaesthetic agents may be associated with psychomotor, hepatic and renal dysfunction, to increased susceptibility to infections and neoplastic disease, and to an increased incidence of miscarriages and foetal abnormalities, is discussed. The risk to pregnant women seems greatest after exposure to rather high concentrations of nitrous oxide. Although it is not suggested that all laboratory premises will be equally at risk, such levels as 400 ppm halothane and 8000 ppm nitrous oxide can build up in small poorly-ventilated rooms when these agents are used for several hours at a time. A strong plea is entered for all to be aware of the hazard and to ensure that good ventilation and preferably, purpose-built scavenging equipment are installed wherever inhalational agents are used.

show abstract

“…It was Van Dyke's and Stier's groups working independently that determined that halothane was extensively biotransformed by man and animals, both in vivo and in vitro (10,11). The primary metabolic products formed were trifluoroacetic acid and bromide.…”

Section: Introductionmentioning

confidence: 99%

Halothane hepatotoxicity and the reduced derivative, 1,1,1-trifluoro-2-chloroethane.

Brown¹,

Sipes²,

Baker³

1977

Environ Health Perspect

View full text Add to dashboard Cite

-trifluoro-2-bromo-2-chloroethane) is a safe, clinically useful inhalation anesthetic. Rare, unpredictable cases of liver necrosis have been reported following its use. Although the mechanism of this reaction in man is unknown the most plausible is biotransformation to reactive intermediates compounds. The oxidative metabolism of halothane appears to be benign. There is early evidence that reductive (nonoxygen dependent) may be harmful. Since the bromine atom of halothane appears to possess weak bond energy, the reduced, debrominated derivative of halothane, 1,1,1-trifluoro-2-chloroethane, was synthesized and tested for hepatotoxicity in the rat. The derivative is unstable and thus was prepared anaerobically and trapped in propylene glycol solvent. Injection of small amounts of this compound into the portal vein of rats produces extensive liver necrosis. It is postulated that biotransformation of halothane via a reductive pathway could produce this reactive intermediate metabolite.

show abstract

Halothane Biotransformation in Man

Cited by 156 publications

References 0 publications

The effects of repeated14C halothane exposure in mice

The effects of repeated14C halothane exposure in mice

Anaesthetic gases and health risks to laboratory personnel: a review

Halothane hepatotoxicity and the reduced derivative, 1,1,1-trifluoro-2-chloroethane.

Contact Info

Product

Resources

About