德国明斯特大学Melanie Meersch团队比较了局部柠檬酸盐抗凝治疗与全身肝素抗凝治疗对过滤器寿命和死亡率的影响。2020年10月23日，该研究发表在《美国医学会杂志》上。

尽管当前指南建议使用局部柠檬酸盐抗凝治疗（包括在体外透析循环过滤前在血液中添加柠檬酸盐溶液）作为危重患者连续肾脏替代治疗的一线治疗，但该建议的证据仅基于少数临床试验和荟萃分析。

为了确定局部柠檬酸盐抗凝治疗与全身肝素抗凝治疗对过滤器寿命和死亡率的影响，2016年3月至2018年12月，研究组在德国的26个中心进行了一项平行组、随机、多中心、临床试验。在招募了596名严重急性肾损伤或有肾脏替代治疗临床适应症的危重患者后，该试验提前终止。

研究组将596例患者随机分组，其中300例接受局部柠檬酸盐抗凝治疗，296例接受全身肝素抗凝治疗，以进行连续肾脏替代治疗。共同的主要结局是过滤器寿命和90天死亡率。次要终点包括出血并发症和新发感染。

596名（93.4%）患者的平均年龄为67.5岁，共有183名（30.7％）女性。局部柠檬酸盐组的过滤器中位寿命为47小时，显著长于全身肝素组（26小时）。局部柠檬酸盐组中有150名患者在90天内全因死亡，全身肝素组中有156名，Kaplan-Meier估计全因死亡率分别为51.2％和53.6％。在38个预先指定的次要终点中，有34个没有显著差异。与全身肝素组相比，局部柠檬酸盐组的出血并发症明显减少，但新发感染明显增多。

总之，在接受连续肾脏替代治疗的重症急性肾损伤患者中，局部柠檬酸盐抗凝治疗与全身肝素抗凝治疗相比，过滤器使用寿命显著延长。

附：英文原文

Title: 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

Author: Alexander Zarbock, Mira Küllmar, Detlef Kindgen-Milles, Carola Wempe, Joachim Gerss, Timo Brandenburger, Thomas Dimski, Bartosz Tyczynski, Michael Jahn, Nils Mülling, Martin Mehrlnder, Peter Rosenberger, Gernot Marx, Tim Philipp Simon, Ulrich Jaschinski, Philipp Deetjen, Christian Putensen, Jens-Christian Schewe, Stefan Kluge, Dominik Jarczak, Torsten Slowinski, Marc Bodenstein, Patrick Meybohm, Stefan Wirtz, Onnen Moerer, Andreas Kortgen, Philipp Simon, Sean M. Bagshaw, John A. Kellum, Melanie Meersch, RICH Investigators and the Sepnet Trial Group

Issue&Volume: 2020/10/27

Abstract:

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.

DOI: 10.1001/jama.2020.18618

Source: https://jamanetwork.com/journals/jama/article-abstract/2771925