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γ-羟基丁酸和己酮可可碱对冠状动脉手术干预中肾功能参数的影响

[Effect of gamma-hydroxybutyric acid and pentoxifylline on kidney function parameters in coronary surgery interventions].

作者信息

Kleinschmidt S, Bauer M, Grundmann U, Schneider A, Wagner B, Graeter T

机构信息

Klinik für Anaesthesiologie und Intensivmedizin, Universitäts-kliniken des Saarlandes, Homburg/Saar.

出版信息

Anaesthesiol Reanim. 1997;22(4):102-7.

PMID:9376042
Abstract

After cardiac surgery, transient renal dysfunction often occurs. The main reasons for impairment of renal function are intraoperative hypotension, ischemia/reperfusion injury and inflammatory response to cardiopulmonary bypass (CPB). Pentoxifylline is known to have anti-inflammatory properties. Gamma-hydroxybutyrate (GHB), an endogenous regulator of energy metabolism, showed beneficial effects on experimental intestinal ischemia/reperfusion injury and liver graft function. Both drugs may be of practical interest in diminishing renal damage during and after cardiac surgery. After approval by the ethics committee and informed consent, 45 patients for elective coronary artery bypass grafting with no clinical and laboratory impairment of renal function were randomized into 3 groups (15 patients each): group 1 received saline as control, group 2 received pentoxifylline intraoperatively (1 mg/kg/h after a priming dose of 1 mg/kg) and group 3 received GHB intraoperatively (25 mg/kg/h after a priming dose of 25 mg/kg) in a double-blinded fashion. During 3 periods (before CPB, from the beginning of CPB until the end of surgery, 24 hours postoperatively), glomerular (creatinine clearance, CCr) and tubular markers of renal function (beta-NAG, alpha 1-microglobulin) were detected in addition to clinical routine standards (creatinine, urea, fractional excretion of sodium). Changes in glomerular and in tubular function were comparable in all groups without characteristic effects of either GHB or pentoxifylline. With CPB, CCr decreased significantly until the end of operation, but showed a rise to preoperative levels on the first day after operation. Tubular function markers (beta-NAG, alpha 1-microglobulin, related to simultaneous excretion of creatinine) showed a remarkable rise after the beginning of CPB up to the postoperative period. The results of the present pilot study suggest the detection of tubular proteins and enzymes a useful addition to present routine clinical standards for recognizing early intraoperative changes in renal function. In the patients studied, there were no clinical signs of renal dysfunction. Neither GHB nor pentoxifylline--in the doses applied--was able to show a therapeutic benefit despite the theoretical advantages.

摘要

心脏手术后,常发生短暂性肾功能障碍。肾功能受损的主要原因是术中低血压、缺血/再灌注损伤以及对体外循环(CPB)的炎症反应。己酮可可碱已知具有抗炎特性。γ-羟基丁酸(GHB)是一种能量代谢的内源性调节剂,对实验性肠缺血/再灌注损伤和肝移植功能显示出有益作用。这两种药物在减少心脏手术期间及术后的肾损伤方面可能具有实际意义。经伦理委员会批准并获得知情同意后,45例择期冠状动脉搭桥术且肾功能无临床和实验室损害的患者被随机分为3组(每组15例):第1组接受生理盐水作为对照,第2组术中接受己酮可可碱(首剂1mg/kg后以1mg/kg/h输注),第3组术中接受GHB(首剂25mg/kg后以25mg/kg/h输注),采用双盲方式。在3个时间段(CPB前、从CPB开始至手术结束、术后24小时),除了临床常规指标(肌酐、尿素、钠分数排泄率)外,还检测了肾功能的肾小球指标(肌酐清除率,CCr)和肾小管指标(β-N-乙酰氨基葡萄糖苷酶、α1-微球蛋白)。所有组中肾小球和肾小管功能的变化具有可比性,GHB和己酮可可碱均无特征性影响。CPB期间,CCr在手术结束前显著下降,但术后第一天升至术前水平。肾小管功能指标(β-N-乙酰氨基葡萄糖苷酶、α1-微球蛋白,与肌酐同时排泄相关)在CPB开始后直至术后阶段均显著升高。本初步研究结果表明,检测肾小管蛋白和酶有助于在目前的常规临床标准基础上识别术中早期肾功能变化。在所研究的患者中,没有肾功能障碍的临床体征。尽管理论上有优势,但所应用剂量的GHB和己酮可可碱均未能显示出治疗益处。

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