Carcoana Olivia V, Mathew Joseph P, Davis Elizabeth, Byrne Daniel W, Hayslett John P, Hines Roberta L, Garwood Susan
*Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut; †Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; ‡Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN; and §Department of Internal Medicine (Section of Nephrology), Yale University School of Medicine, New Haven, Connecticut.
Anesth Analg. 2003 Nov;97(5):1222-1229. doi: 10.1213/01.ANE.0000086727.42573.A8.
In this prospective, randomized, placebo-controlled, double-blinded study, we determined the effects of two commonly used adjuncts, mannitol and dopamine, on beta(2)-microglobulin (beta(2)M) excretion rates in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). beta(2)M excretion rate has been described as a sensitive marker of proximal renal tubular function. One-hundred patients with a preoperative serum creatinine level <or=1.5 mg/dL were prospectively randomized into 4 groups: 1). placebo, 2). mannitol 1 g/kg added to the CPB prime, 3). dopamine 2 microg kg(-1x. min(-1) from the induction of anesthesia to 1 h post-CPB, or 4). mannitol plus dopamine. The primary outcome measure was beta(2)M excretion rate at 1 h post-CPB. Secondary outcome measures included beta(2)M excretion rate at 6 and 24 h post-CPB; urinary flow rate and creatinine clearance at 1, 6, and 24 h post-CPB; and the highest postoperative serum creatinine level. Length of intensive care stay and hospitalization, as well as adverse events, were also considered secondary outcomes. Dopamine significantly increased beta(2)M excretion rate at 1 h post-CPB (2.48 +/- 3.61 microg/min) compared with placebo (0.59 +/- 1.04 microg/min; P = 0.001). This effect was not ameliorated by the addition of mannitol (beta(2)M excretion rate, 2.05 +/- 2.77 microg/min; P = 0.007 compared with placebo). beta(2)M excretion rate was similar in patients given placebo or mannitol alone (P = 0.831). Rather than being a protective drug in the setting of CPB, dopamine alone or in combination with mannitol increases beta(2)M excretion rate, which may be a measure of renal tubular dysfunction. The clinical implications of this increase and whether it is also seen in patients with established renal dysfunction undergoing CPB require additional investigation.
In many clinical settings, an increased beta-2-microglobulin (beta(2)M) excretion rate indicates renal tubular injury. In this cardiopulmonary bypass (CPB) study, a dopamine infusion (alone or with mannitol) resulted in an increased beta(2)M excretion rate. It is unclear whether this dopamine-related increase implies renal injury after CPB, and further investigations are required to examine the mechanism/clinical relevance of this observation.
在这项前瞻性、随机、安慰剂对照、双盲研究中，我们确定了两种常用辅助药物甘露醇和多巴胺对接受体外循环冠状动脉搭桥手术患者的β2-微球蛋白（β2M）排泄率的影响。β2M排泄率已被描述为近端肾小管功能的敏感标志物。100例术前血清肌酐水平≤1.5mg/dL的患者被前瞻性随机分为4组：1）安慰剂组；2）在体外循环预充液中加入1g/kg甘露醇组；3）从麻醉诱导至体外循环后1小时给予多巴胺2μg·kg-1·min-1组；4）甘露醇加多巴胺组。主要观察指标是体外循环后1小时的β2M排泄率。次要观察指标包括体外循环后6小时和24小时的β2M排泄率；体外循环后1小时、6小时和24小时的尿流率和肌酐清除率；以及术后最高血清肌酐水平。重症监护病房停留时间和住院时间以及不良事件也被视为次要观察指标。与安慰剂组（0.59±1.04μg/min；P = 0.001）相比，多巴胺显著增加了体外循环后1小时的β2M排泄率（2.48±3.61μg/min）。添加甘露醇并未改善这种效应（β2M排泄率为2.05±2.77μg/min；与安慰剂组相比P = 0.007）。单独给予安慰剂或甘露醇的患者β2M排泄率相似（P = 0.831）。多巴胺单独或与甘露醇联合使用时，并非体外循环情况下的保护性药物，反而会增加β2M排泄率，这可能是肾小管功能障碍的一种表现。这种增加的临床意义以及在接受体外循环的已确诊肾功能不全患者中是否也会出现，需要进一步研究。
在许多临床情况下，β2-微球蛋白（β2M）排泄率增加表明肾小管损伤。在这项体外循环（CPB）研究中，输注多巴胺（单独或与甘露醇联合）导致β2M排泄率增加。尚不清楚这种与多巴胺相关的增加是否意味着体外循环后肾损伤，需要进一步研究来探讨这一观察结果的机制/临床相关性。
