A Randomized Controlled Trial of Regional Citrate Versus Regional Heparin Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Adults
A Randomized Controlled Trial of Regional Citrate Versus Regional Heparin Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Adults
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DOI：
10.1097/ccm.0000000000001004
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发表时间：
2015-08-01
影响因子：
8.8
通讯作者：
Bellomo, Rinaldo
中科院分区：
文献类型：
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作者：
Gattas, David J.;Rajbhandari, Dorrilyn;Bellomo, Rinaldo
目的：确定与使用肝素和鱼精蛋白进行局部抗凝相比，使用枸橼酸盐和钙对连续性肾脏替代治疗（CRRT）回路进行局部抗凝是否能延长回路寿命和/或影响循环细胞因子水平。
设计：多中心、平行组随机对照试验。
地点：澳大利亚和新西兰的7个重症监护病房（ICU）。
患者：需要连续性肾脏替代治疗的重症成人患者。
干预措施：患者被随机分配接受两种局部回路抗凝方法中的一种：枸橼酸盐和钙或肝素和鱼精蛋白。
测量和主要结果：主要结局是按小时测量的功能性回路寿命，使用重复事件生存分析进行评估。此外，我们测量了白细胞介素 - 6、白细胞介素 - 8和白细胞介素 - 10血液水平的变化。我们将212名受试者随机分组，他们接受了857次连续性肾脏替代治疗回路治疗（每位患者中位数为2次回路[四分位间距，1 - 6]，枸橼酸盐组390次，肝素组467次）。两组在基线特征方面匹配良好。接受肝素和鱼精蛋白进行局部连续性肾脏替代治疗抗凝的患者比接受枸橼酸盐和钙的患者更易出现回路凝血（风险比，2.03[1.36 - 3.03]；p < 0.0005；857次回路）。每位患者第一个研究回路的中位寿命在枸橼酸盐和钙组为39.2小时（95%置信区间，32.1 - 48.0小时），而在肝素和鱼精蛋白组为22.8小时（95%置信区间，13.3 - 34.0小时）（对数秩检验p = 0.0037，204次回路）。与肝素和鱼精蛋白抗凝相比，枸橼酸盐和钙进行回路抗凝对细胞因子水平的影响相似。被分配到肝素和鱼精蛋白抗凝组的不良事件更多（11例对2例；p = 0.011）。
结论：与局部肝素和鱼精蛋白抗凝相比，局部枸橼酸盐和钙抗凝可延长连续性肾脏替代治疗回路寿命，不影响细胞因子水平，且不良事件更少。
Objective: To determine whether regional anticoagulation of continuous renal replacement therapy circuits using citrate and calcium prolongs circuit life and/or affects circulating cytokine levels compared with regional anticoagulation using heparin and protamine.Design: Multicenter, parallel group randomized controlled trial.Setting: Seven ICUs in Australia and New Zealand.Patients: Critically ill adults requiring continuous renal replacement therapy.Interventions: Patients were randomized to receive one of two methods of regional circuit anticoagulation: citrate and calcium or heparin and protamine.Measurements and Main Results: The primary outcome was functional circuit life measured in hours, assessed using repeated events survival analysis. In addition, we measured changes in interleukin-6, interleukin-8, and interleukin-10 blood levels. We randomized 212 subjects who were treated with 857 continuous renal replacement therapy circuits (median 2 circuits per patient [interquartile range, 1-6], 390 in citrate group vs 467 in heparin group). The groups were well matched for baseline characteristics. Patients receiving regional continuous renal replacement therapy anticoagulation with heparin and protamine were more likely to experience circuit clotting than those receiving citrate and calcium (hazard ratio, 2.03 [1.36-3.03]; p < 0.0005; 857 circuits). The median lifespan of the first study circuit in each patient was 39.2 hours (95% CI, 32.1-48.0 hr) in the citrate and calcium group versus 22.8 hours (95% CI, 13.3-34.0 hr) in the heparin and protamine group (log rank p = 0.0037, 204 circuits). Circuit anticoagulation with citrate and calcium had similar effects on cytokine levels compared with heparin and protamine anticoagulation. There were more adverse events in the group assigned to heparin and protamine anticoagulation (11 vs 2; p = 0.011).Conclusions: Regional citrate and calcium anticoagulation prolongs continuous renal replacement therapy circuit life compared with regional heparin and protamine anticoagulation, does not affect cytokine levels, and is associated with fewer adverse events.