Cancer and Other Outcomes After Surgery With Fluoridated Anesthesia —Reply

In Reply We thank Waugh for the interest he has shown in our article and the Editor for the opportunity to reply to his comments. It is true that serum fluoride levels are elevated during anesthesia with sevoflurane, which occurs as a result of its metabolism by hepatic cytochrome P450 enzymes to yield hexafluoroisopropanol and inorganic fluoride. Indeed, there were well-documented concerns about the potential toxicity of these metabolites when sevoflurane first came into clinical use in the 1990s, although it rapidly transpired that reported cases of nephrotoxicity in rats were actually caused by compound A (fluoromethyl 2,2-difluoro-1-[trifluoromethyl]vinyl ether), a degradation product formed by the interaction of sevoflurane with carbon dioxide absorbers under specific conditions within the anesthetic breathing circuit. Since then, studies of sevoflurane biotransformation and degradation toxicity in humans have yielded minimal evidence of harm, and it continues to be used routinely and safely in millions of patients each year. Notwithstanding this or the equivocal data connecting chronic fluoride exposure with tumorigenesis, to our knowledge, the specific contribution of inorganic fluoride to the observed signaling activities and phenotype of cancer cells has not yet been directly assessed. This may transpire to be a topic of interest for future research, particularly as extrahepatic expression of cytochrome p450 enzymes has been identified in numerous human cancers. Howe...
Source: JAMA Surgery - Category: Sports Medicine Source Type: research