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

Intek Hong, Kevin D. Bigam, Brie M. McConnell, Timur J. P. Özelsel, Rakesh V. Sondekoppam

¹Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada²Davis Centre Library, University of Waterloo, Waterloo, Ontario, Canada³Department of Anesthesia and Pain Medicine, University of Alberta, Edmonton, Alberta, Canada⁴Department of Anesthesia, Pain and Perioperative Medicine, Stanford University, Stanford, CA, USA

Abstract

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.

摘要：研究七氟醚或化合物A对肾功能的影响的动物模型是七氟醚麻醉后肾脏损伤的初步基础，并提出了最小新鲜气体流量的建议，但这一证据基础尚未得到严格评价。在MEDLINE OVID、PubMed、EMBASE、Cochrane Library、Cochrane Central Register of Controlled Trials、International HTA Database、CINAHL和Web of Science中进行初步文献检索，以确定在动物中使用七氟醚或化合物a的随机对照试验和准实验研究。主要结局包括肾功能，由血尿素氮、血清肌酐、肌酐清除率和尿量测定。次要结果包括血清氟化物浓度和组织病理学结果。共筛选2537份记录，筛选出21项随机对照试验和9项准实验动物研究。七氟醚暴露与随后的肾功能变化（血尿素氮、血清肌酐或尿量变化）之间没有关联。化合物A暴露后对肾功能有类似影响，但尿量升高。此外，化合物A暴露后的组织病理学损伤仅在临床实践中无法达到的浓度下观察到。我们对动物模型证据的回顾显示，七氟醚的使用与肾功能测试或尿量的变化无关。七氟醚暴露后的组织病理学改变要么不存在，要么很小。对化合物A的研究没有发现肾功能的改变，尽管组织病理学证据表明，当化合物A以非常高的非生理性浓度施用时，存在损伤。根据现有证据，基于动物研究的七氟醚相关肾毒性最初的担忧导致最小新鲜气体流量建议受到质疑。