Malan T P, Kadota Y, Mata H, Frink E J, Brown B R
Department of Anesthesiology, University of Arizona Health Sciences Center, Tucson 85721.
Anesth Analg. 1993 Oct;77(4):817-21. doi: 10.1213/00000539-199310000-00028.
Sevoflurane is metabolized to inorganic fluoride, a potential nephrotoxin. To evaluate the nephrotoxic potential of sevoflurane, 1-yr-old male Fischer 344 rats were anesthetized with 10 minimal alveolar anesthetic concentration (MAC) h sevoflurane or enflurane with or without pretreatment with biotransformation-enhancing agents. Peak serum fluoride levels reached 35 microM with sevoflurane anesthesia after pretreatment with phenobarbital and 40 microM after enflurane anesthesia after pretreatment with isoniazid. One day after anesthesia, sevoflurane-anesthetized rats concentrated urine normally in response to subcutaneous administration of 1-deamino-8-D-arginine vasopressin and exhibited no increase in urinary excretion of N-acetyl beta-glucosaminidase. Isoniazid-treated, enflurane anesthetized rats developed a 31% reduction in maximal urinary concentrating ability and a 3.5-fold increase in excretion of N-acetyl-beta-glucosaminidase. Sevoflurane produced no evidence of fluoride-induced nephrotoxicity in noninduced or enzyme-induced rats. Under similar conditions, enflurane produced laboratory evidence of nephrotoxicity.
七氟醚可代谢生成无机氟化物，这是一种潜在的肾毒素。为评估七氟醚的肾毒性潜力，对1岁雄性Fischer 344大鼠使用10倍最小肺泡浓度（MAC）的七氟醚或安氟醚进行麻醉，且使用或不使用生物转化增强剂进行预处理。在使用苯巴比妥预处理后，七氟醚麻醉的大鼠血清氟化物峰值水平达到35微摩尔/升，在使用异烟肼预处理后，安氟醚麻醉的大鼠血清氟化物峰值水平达到40微摩尔/升。麻醉一天后，七氟醚麻醉的大鼠在皮下注射1-去氨基-8-D-精氨酸加压素后能正常浓缩尿液，且N-乙酰-β-氨基葡萄糖苷酶的尿排泄量未增加。用异烟肼处理、接受安氟醚麻醉的大鼠最大尿浓缩能力降低了31%，N-乙酰-β-氨基葡萄糖苷酶的排泄量增加了3.5倍。七氟醚在未诱导或酶诱导的大鼠中未产生氟化物诱导的肾毒性证据。在类似条件下，安氟醚产生了肾毒性的实验室证据。
