Mahesh Balakrishnan, Yim Boyd, Robson Desiree, Pillai Ravi, Ratnatunga Chandana, Pigott David
Cardiothoracic Center, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.
Eur J Cardiothorac Surg. 2008 Mar;33(3):370-6. doi: 10.1016/j.ejcts.2007.12.030.
Renal dysfunction following cardiac surgery is more apparent in high-risk patients with pre-existing renal dysfunction, diabetes and impaired left-ventricular function, and following complicated procedures involving prolonged cardiopulmonary bypass (CPB). The aim of this prospectively randomised double-blinded placebo-controlled study was to evaluate reno-protective effect of low-dose furosemide infusion in this high-risk group.
Patients with preoperative serum creatinine >130 micromol/l (1.4 mg/dl), left-ventricular ejection fraction <50%, congestive heart failure, diabetes, or procedures involving prolonged CPB were randomised to receive either saline at 2 ml/h (n=21), or furosemide at 4 mg/h (n=21). Infusion was commenced after induction of anaesthesia and continued for 12h postoperatively. Renal dysfunction was defined as >50% increase in serum creatinine postoperatively, or >130 micromol/l (1.4 mg/dl), or requirement for haemodialysis, or all of these. In patients with preoperative serum creatinine >130 micromol/l, >50% increase over preoperative levels was used to define postoperative renal dysfunction.
Following cardiac surgery, patients receiving furosemide had a higher urine output (3.4+/-1.2 ml/kg/h in furosemide group and 1.2+/-0.5 ml/kg/h in placebo group; p<0.001), higher postoperative fluid requirement (4631+/-1359 ml in furosemide group and 3714+/-807 ml in placebo group, p=0.011), and lower urinary-creatinine (2+/-1.3 micromol/l in furosemide group and 5.9+/-2.5 micromol/l in placebo group p<0.001). Both groups had significant increase in retinol binding protein/creatinine ratio (7.2+/-6 to 3152+/-1411 in furosemide group; 4.9+/-2.1 to 2809+/-1125 in placebo group; p<0.001) and peak serum creatinine (98+/-33 to 177+/-123 micromol/l in furosemide group; 96+/-20 to 143+/-87 micromol/l in placebo group; p<0.001), and a significant decrease in peak creatinine-clearance (64.3+/-29.4 to 39.1+/-16.6 ml/min in furosemide group; 65.5+/-38.6 to 41.8+/-17.8 ml/min in placebo group; p<0.001) following cardiac surgery, implying significant renal injury following cardiac surgery. Peak creatinine levels (177+/-123 micromol/l in furosemide group and 143+/-87 micromol/l in placebo group; p=0.35) and peak creatinine-clearance (39.1+/-16.6 ml/min in furosemide group and 41.8+/-17.8 ml/min in placebo group; p=0.61) were similar in the two groups. Importantly, there was no difference in incidence of renal dysfunction between the furosemide group (9/21) and the control group (8/21) (relative risk 1.1, 95% confidence interval 0.6-2.2; p=0.99).
Our randomised trial did not demonstrate any benefit of furosemide-infusion postoperatively in high-risk cardiac surgical patients. Although urinary output increased with furosemide, there was no decrease in renal injury, and no decrease in incidence of renal dysfunction.
心脏手术后的肾功能障碍在已有肾功能障碍、糖尿病及左心室功能受损的高危患者中更为明显，且在涉及长时间体外循环（CPB）的复杂手术之后也更为常见。这项前瞻性随机双盲安慰剂对照研究的目的是评估低剂量呋塞米输注对该高危组患者的肾脏保护作用。
术前血清肌酐>130微摩尔/升（1.4毫克/分升）、左心室射血分数<50%、充血性心力衰竭、糖尿病或涉及长时间CPB的手术患者被随机分为两组，分别接受2毫升/小时的生理盐水输注（n = 21）或4毫克/小时的呋塞米输注（n = 21）。输注在麻醉诱导后开始，并在术后持续12小时。肾功能障碍的定义为术后血清肌酐升高>50%，或>130微摩尔/升（1.4毫克/分升），或需要进行血液透析，或具备以上所有情况。对于术前血清肌酐>130微摩尔/升的患者，以超过术前水平>50%来定义术后肾功能障碍。
心脏手术后，接受呋塞米治疗的患者尿量更高（呋塞米组为3.4±1.2毫升/千克/小时，安慰剂组为1.2±0.5毫升/千克/小时；p<0.001），术后液体需求量更高（呋塞米组为4631±1359毫升，安慰剂组为3714±807毫升，p = 0.011），尿肌酐水平更低（呋塞米组为2±1.3微摩尔/升，安慰剂组为5.9±2.5微摩尔/升，p<0.001）。两组患者的视黄醇结合蛋白/肌酐比值（呋塞米组从7.2±6升至3152±1411；安慰剂组从4.9±2.1升至2809±1125；p<0.001）和血清肌酐峰值（呋塞米组从98±33微摩尔/升升至177±123微摩尔/升；安慰剂组从96±20微摩尔/升升至143±87微摩尔/升；p<0.001）均显著升高，肌酐清除率峰值显著降低（呋塞米组从64.3±29.4毫升/分钟降至39.1±16.6毫升/分钟；安慰剂组从65.5±38.6毫升/分钟降至41.8±17.8毫升/分钟；p<0.001），这表明心脏手术后存在明显的肾损伤。两组的肌酐峰值水平（呋塞米组为177±123微摩尔/升，安慰剂组为143±87微摩尔/升；p = 0.35）和肌酐清除率峰值（呋塞米组为39.1±16.6毫升/分钟，安慰剂组为41.8±17.8毫升/分钟；p = 0.61）相似。重要的是，呋塞米组（9/21）和对照组（8/21）之间的肾功能障碍发生率没有差异（相对风险1.1，95%置信区间0.6 - 2.2；p = 0.99）。
我们的随机试验未证明术后给予呋塞米对高危心脏手术患者有任何益处。尽管呋塞米使尿量增加，但肾损伤并未减轻，肾功能障碍的发生率也未降低。
