Molenaar I Q, Begliomini B, Grazi G L, Ringers J, Terpstra O T, Porte R J
Department of Surgery, Leiden University Medical Center, The Netherlands.
Transplantation. 2001 Jan 27;71(2):247-52. doi: 10.1097/00007890-200101270-00014.
In the European Multicenter Study on the Use of Aprotinin in Liver Transplantation (EMSALT), a randomized, double-blind, placebo-controlled, prospective study, we demonstrated that aprotinin significantly reduces intraoperative blood loss during orthotopic liver transplantation (OLT). Aprotinin is metabolized in the kidney and potentially nephrotoxic at high concentrations. Renal insufficiency is a common and serious complication after OLT. It is unknown whether aprotinin increases the risk of renal failure after OLT.
We analyzed intraoperative urine output, need for postoperative dialysis, perioperative serum creatinine levels, and creatinine clearance in 93 patients enrolled in EMSALT, receiving a high dose of aprotinin, a regular dose, or placebo.
Peak increase in serum creatinine exceeding 0.5 mg/dl during one of the postoperative days occurred in 11 (35%) patients in the placebo group, in 11 (34%) patients in the high-dose group, but only in 1 (3%) patient in the regular-dose group (P=0.007). Furthermore, a perioperative decrease in creatinine clearance was seen in the placebo group (-23.9+/-10.1 ml/min) but not in both high-dose (-1.6+/-13.3 ml/min) and regular-dose (9.7+/-10.3 ml/min) groups (P<0.02 comparing regular-dose and placebo group).
Despite its potential nephrotoxicity, the use of aprotinin for reducing blood loss during OLT does not lead to a higher incidence of postoperative renal insufficiency. In combination with the observed reduction in blood loss, these findings support the prophylactic use of regular-dose aprotinin during OLT.
在欧洲肝脏移植中抑肽酶应用多中心研究(EMSALT)这一随机、双盲、安慰剂对照的前瞻性研究中,我们证明了抑肽酶可显著减少原位肝移植(OLT)术中失血。抑肽酶在肾脏代谢,高浓度时可能具有肾毒性。肾功能不全是OLT术后常见且严重的并发症。目前尚不清楚抑肽酶是否会增加OLT术后肾衰竭的风险。
我们分析了EMSALT研究中93例接受高剂量抑肽酶、常规剂量抑肽酶或安慰剂的患者的术中尿量、术后透析需求、围手术期血清肌酐水平及肌酐清除率。
术后某一天血清肌酐峰值升高超过0.5mg/dl的情况在安慰剂组11例(35%)患者中出现,高剂量组11例(34%)患者中出现,而常规剂量组仅1例(3%)患者出现(P=0.007)。此外,安慰剂组出现围手术期肌酐清除率下降(-23.9±10.1ml/min),而高剂量组(-1.6±13.3ml/min)和常规剂量组(9.7±10.3ml/min)均未出现(常规剂量组与安慰剂组比较,P<0.02)。
尽管抑肽酶具有潜在肾毒性,但在OLT中使用抑肽酶减少失血并不会导致术后肾功能不全发生率升高。结合观察到的失血减少情况,这些发现支持在OLT中预防性使用常规剂量的抑肽酶。