Sevoflurane and its metabolic byproduct compound A induce nephrotoxicity: a systematic review and meta-analysis of animal studies.

Animal models investigating sevoflurane or compound A and renal function serve as the initial basis for concerns regarding renal injury following sevoflurane anesthesia and subsequent recommendations of minimum fresh gas flow, but this evidence basis has not been critically appraised. Primary literature searches were performed in MEDLINE OVID, PubMed, EMBASE, the Cochrane Library), the Cochrane Central Register of Controlled Trials, the International HTA Database, CINAHL, and Web of Science to identify randomized controlled trials and quasi-experimental studies in animals utilizing sevoflurane or compound A. The primary outcomes included renal function as determined by blood urea nitrogen, serum creatinine, creatinine clearance, and urine volume. The secondary outcomes included the serum fluoride concentration and histopathological findings. A total of 2537 records were screened, and 21 randomized controlled trials and 9 quasi-experimental animal studies were identified. No associations between sevoflurane exposure and subsequent changes in renal function (blood urea nitrogen, serum creatinine or changes in urine volume) were noted. A similar effect on renal function was observed following compound A exposure, but urine volume was elevated following compound A exposure. In addition, the histopathological damage following compound A exposure was observed only at concentrations that are unachievable in clinical practice. Our review of evidence from animal models revealed that sevoflurane usage was not associated with changes in renal function tests or urine volume. Histopathologic changes after sevoflurane exposure were either nonexistent or minor. Studies on compound A did not reveal an alteration in renal function, although histopathological evidence of injury was present when compound A was administered at very high, unphysiologic concentrations. In light of the existing evidence, the initial concerns of sevoflurane-related nephrotoxicity based on animal studies that leads to minimum fresh gas flow recommendations are called into question.