Goldberg M E, Cantillo J, Gratz I, Deal E, Vekeman D, McDougall R, Afshar M, Zafeiridis A, Larijani G
Department of Anesthesiology, The Cooper Health System, University of Medicine and Dentistry of New Jersey, The Robert Wood Johnson Medical School at Camden, 08103, USA.
Anesth Analg. 1999 Feb;88(2):437-45. doi: 10.1097/00000539-199902000-00040.
Administration of sevoflurane in a circle absorption system generates Compound A, a nephrotoxin in rats. Reports examining the potential of Compound A to produce renal injury in humans have provided conflicting results. We tested the possibility that there is a threshold to Compound A-induced renal injury in humans and that, above this threshold, renal injury increases with increasing doses of Compound A. Eleven volunteers received 3% sevoflurane for 8 h at 2 L/min, and three volunteers received 3% sevoflurane for 8 h at 4-6 L/min. We measured inspired and expired concentrations of Compound A and urinary excretion of albumin, alpha-glutathione-S-transferase (GST), and glucose. The median urinary excretion of albumin, glucose, and alpha-GST for the first 3 days after anesthesia increased significantly from preanesthetic values in the 2-L/min group. Compound A doses < 240 ppm-h resulted in normal urinary excretion of albumin, glucose, and alpha-GST. Five of seven subjects who received doses > 240 ppm-h had abnormal excretion of albumin, and six of seven had abnormal alpha-GST urinary excretion (P < 0.05). Urinary excretion of albumin, alpha-GST, and glucose was normal by 14 days after exposure. We conclude that sevoflurane administration for 8 h at 2 L/min results in albuminuria and enzymuria when the dose of Compound A exceeds 240 ppm-h. That is, a Compound A concentration of 30 ppm breathed for > or = 8 h may produce transient renal injury.
We examined the dose-response relationship of sevoflurane/Compound A and urinary excretion of albumin, glucose, and alpha-GST. Sevoflurane exposure for 8 h at a 2-L/min inflow rate produces transient albuminuria and enzymuria in healthy volunteers when the dose of Compound A exceeds 240 ppm-h (30 ppm for 8 h).
在循环吸收系统中使用七氟醚会生成化合物A，这是一种对大鼠具有肾毒性的物质。关于化合物A对人类造成肾损伤可能性的研究报告结果相互矛盾。我们测试了人类中化合物A诱导肾损伤是否存在阈值，并且在此阈值之上，肾损伤会随着化合物A剂量的增加而加重。11名志愿者以2升/分钟的流量接受3%七氟醚8小时，3名志愿者以4 - 6升/分钟的流量接受3%七氟醚8小时。我们测量了化合物A的吸入和呼出浓度以及白蛋白、α - 谷胱甘肽 - S - 转移酶（GST）和葡萄糖的尿排泄量。麻醉后前3天，2升/分钟组白蛋白、葡萄糖和α - GST的尿排泄中位数较麻醉前值显著增加。化合物A剂量<240 ppm - 小时时，白蛋白、葡萄糖和α - GST的尿排泄正常。接受剂量>240 ppm - 小时的7名受试者中有5名白蛋白排泄异常，7名中有6名α - GST尿排泄异常（P<0.05）。暴露后14天时，白蛋白、α - GST和葡萄糖的尿排泄正常。我们得出结论，当化合物A剂量超过240 ppm - 小时时，以2升/分钟的流量使用七氟醚8小时会导致蛋白尿和酶尿。也就是说，呼吸浓度为30 ppm≥8小时的化合物A可能会产生短暂性肾损伤。
我们研究了七氟醚/化合物A与白蛋白、葡萄糖和α - GST尿排泄之间的剂量反应关系。当化合物A剂量超过240 ppm - 小时（8小时为30 ppm）时，以2升/分钟的流入速率暴露于七氟醚8小时会在健康志愿者中产生短暂性蛋白尿和酶尿。
