局部檸檬酸鹽抗凝治療與全身肝素抗凝治療相比可顯著延長過濾器壽命
作者：
小柯機器人發布時間：2020/10/31 21:40:44
德國明斯特大學Melanie Meersch團隊比較了局部檸檬酸鹽抗凝治療與全身肝素抗凝治療對過濾器壽命和死亡率的影響。2020年10月23日，該研究發表在《美國醫學會雜誌》上。
儘管當前指南建議使用局部檸檬酸鹽抗凝治療（包括在體外透析循環過濾前在血液中添加檸檬酸鹽溶液）作為危重患者連續腎臟替代治療的一線治療，但該建議的證據僅基於少數臨床試驗和薈萃分析。
為了確定局部檸檬酸鹽抗凝治療與全身肝素抗凝治療對過濾器壽命和死亡率的影響，2016年3月至2018年12月，研究組在德國的26個中心進行了一項平行組、隨機、多中心、臨床試驗。在招募了596名嚴重急性腎損傷或有腎臟替代治療臨床適應症的危重患者後，該試驗提前終止。
研究組將596例患者隨機分組，其中300例接受局部檸檬酸鹽抗凝治療，296例接受全身肝素抗凝治療，以進行連續腎臟替代治療。共同的主要結局是過濾器壽命和90天死亡率。次要終點包括出血併發症和新發感染。
596名（93.4%）患者的平均年齡為67.5歲，共有183名（30.7％）女性。局部檸檬酸鹽組的過濾器中位壽命為47小時，顯著長於全身肝素組（26小時）。局部檸檬酸鹽組中有150名患者在90天內全因死亡，全身肝素組中有156名，Kaplan-Meier估計全因死亡率分別為51.2％和53.6％。在38個預先指定的次要終點中，有34個沒有顯著差異。與全身肝素組相比，局部檸檬酸鹽組的出血併發症明顯減少，但新發感染明顯增多。
總之，在接受連續腎臟替代治療的重症急性腎損傷患者中，局部檸檬酸鹽抗凝治療與全身肝素抗凝治療相比，過濾器使用壽命顯著延長。
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