Effect of Regional Citrate Anticoagulation vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury A Randomized Clinical Trial
Effect of Regional Citrate Anticoagulation vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury A Randomized Clinical Trial
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DOI：
10.1001/jama.2020.18618
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发表时间：
2020-10-23
影响因子：
120.7
通讯作者：
Meersch, Melanie
中科院分区：
文献类型：
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作者：
Zarbock, Alexander;Kullmar, Mira;Meersch, Melanie
重要性尽管当前指南建议使用局部柠檬酸盐抗凝（包括在体外透析回路的过滤器之前向血液中加入柠檬酸盐溶液）作为危重患者连续性肾脏替代疗法的一线治疗，该建议的证据基于少数临床试验和荟萃分析。设计、设置和参与者：2016年3月至2018年12月期间，在德国的26个中心进行了一项平行组、随机多中心临床试验（随访的最终日期为2020年1月21日）。干预患者随机接受局部柠檬酸盐抗凝治疗（n = 300）或全身肝素抗凝治疗（n = 296），局部柠檬酸盐抗凝治疗包括目标离子钙水平为1.0至1.40 mg/dL，包括目标活化部分凝血活酶时间为45 - 60秒，用于连续肾脏替代治疗。主要结局和指标共同主要结局为滤器寿命和90天死亡率。次要终点包括出血并发症和新发感染。结果在638例随机分组的患者中，596例（93.4%）（平均年龄67.5岁; 183例[30.7%]女性）完成了试验。在局部柠檬酸盐组与全身肝素组中，中位滤器寿命分别为47小时（四分位距[IQR]，19 - 70小时）与26小时（IQR，12 - 51小时）（差异，15小时[95% CI，11 - 20小时]; P <.001）。90天全因死亡率分别为150/300和156/296（Kaplan-Meier估计百分比，51.2% vs 53.6%;未校正差异，-2.4%[95% CI，-10.5%至5.8%];未校正风险比，0.91 [95% CI，0.72至1.13];未校正P = 0.38;校正差异，-6.1%[95% CI，-12.6%至0.4%];主要校正风险比，0.79 [95% CI，0.63至1.004];主要校正P = 0.054）。在38个预先设定的次要终点中，34个没有显示出显著差异。与全身肝素组相比，局部柠檬酸盐组的出血并发症明显较少（15/300 [5.1%] vs 49/296 [16.9%];差异，-11.8%[95% CI，-16.8%至-6.8%]; P <0.001）和显著更多的新感染（204/300 [68.0%] vs 164/296 [55.4%];差异，12.6%[95% CI，4.9%至20.3%]; P =.002）。结论和相关性在接受连续性肾脏替代治疗的急性肾损伤危重患者中，与全身肝素抗凝相比，局部柠檬酸盐抗凝可显著延长滤器寿命。该试验提前终止，因此不足以得出抗凝策略对死亡率影响的结论。
IMPORTANCE Although current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses.OBJECTIVE To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality.DESIGN, SETTING, AND PARTICIPANTS A parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled.INTERVENTIONS Patients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy.MAIN OUTCOMES AND MEASURES Coprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections.RESULTS Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P < .001). Ninety-day all-cause mortality occurred in 150 of 300 patients vs 156 of 296 patients (Kaplan-Meier estimator percentages, 51.2% vs 53.6%; unadjusted difference, -2.4% [95% CI, -10.5% to 5.8%]; unadjusted hazard ratio, 0.91 [95% CI, 0.72 to 1.13]; unadjusted P = .38; adjusted difference, -6.1% [95% CI, -12.6% to 0.4%]; primary adjusted hazard ratio, 0.79 [95% CI, 0.63 to 1.004]; primary adjusted P = .054). Of 38 prespecified secondary end points, 34 showed no significant difference. Compared with the systemic heparin group, the regional citrate group had significantly fewer bleeding complications (15/300 [5.1%] vs 49/296 [16.9%]; difference, -11.8% [95% CI, -16.8% to -6.8%]; P < .001) and significantly more new infections (204/300 [68.0%] vs 164/296 [55.4%]; difference, 12.6% [95% CI, 4.9% to 20.3%]; P = .002).CONCLUSIONS AND RELEVANCE Among critically ill patients with acute kidney injury receiving continuous kidney replacement therapy, anticoagulation with regional citrate, compared with systemic heparin anticoagulation, resulted in significantly longer filter life span. The trial was terminated early and was therefore underpowered to reach conclusions about the effect of anticoagulation strategy on mortality.