Toxicity of Inhalation Anaesthetic Agents

Abstract

Although hundreds of compounds on the chemist's shelf are known to produce anaesthesia, relatively few are used clinically. The requirements for a clinically useful anaesthetic agent are necessarily stringent and include: a wide margin of safety, total reversibility of anaesthetic effect and an absence of long-term toxicity. In addition, a successful inhalation anaesthetic agent must combine the capacity for depression of the central nervous system with low levels of interference with respiration and the circulation. The central nervous system effects must be quickly reversible. The acute depressant effects produced by the inhalation anaesthetics contrast with the slower development of long-term toxicity involving organs such as the liver, the kidneys or the reproductive system. Although such long-term toxicity associated with anaesthetics has been recognized for many years, in the past it has been considered to occur infrequently, to be of little importance and of undetermined aetiology. More recent findings suggest that not only are these long-term effects serious, but they occur more frequently than was previously recognized. In addition the aetiological factors are now beginning to be understood. RELATIONSHIP BETWEEN ANAESTHETIC METABOLISM AND TOXICITY Several reports now suggest there is a significant association between the metabolism of anaesthetic agents and the development of toxicity. Whilst the majority of drugs are metabolized in the body to less toxic derivatives, this is not always so. Occasionally, chemically inert compounds can be transformed into reactive metabolites which can combine with tissue macromolecules. These combinations may be toxic.

Anesthetic gases as an occupational hazard--a review.

“…Solvents, as well as anesthetic agents, are fat-soluble, which is also one of the conditions for the narcotic effects. Besides, anesthetic gases can form toxic metabolites (15) in the same manner as many solvents; these metabolites react on the cellular level and can induce cell damage there (58). The chronic damage caused by solvents has been studied to a great extent during the last 10 a, and many studies have shown effects on the central nervous system as a consequence of long-term exposure to solvents (38).…”

COVID-19, Anesthesia and Liver: Traditional Review

“…45 In addition to its toxic effects on the liver, halothane also impairs hepatic hemodynamics. 46 Severe halothane hepatitis is seen in 1/6,000-1/35,000 patients administered halothane. Although repetitive applications are generally blamed, it has been reported even in the case of first exposure to a volatile anesthetic (39%).…”

Identification and characterization of conservative organic tracers for use as hydrologic tracers for the Yucca Mountain site characterization study. Final report

“…This same research reports that the TFAA does not appear to block the Krebs cycle like the more toxic monofluoroacetic acid (Airaksinen, 1968). Research to date seem to confirm that TFAA is less harmful when taken orally than intravenously because, at physiological pH, it is ionized and therefore unlikely to penetrate the cellular membranes (Cohen, 1978;Cohen, 1975). Mice were not killed by intraperitoneal doses of 5,000 mg/kg of sodium fluoroacetate (Blake, et al, 1969) and no effects were seen after 100 mg/kg of trifluoroethanol ip daily for 18 days except for a failure to gain weight.…”