Regionale citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill patients with acute kidney injury (RICH-Trial)
Final Report Abstract
Although current guidelines suggest the use of regional citrate anticoagulation as first-line treatment for continuous renal replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses. In the RICH trial, we wanted to determine whether regional citrate anticoagulation is superior to systemic heparin anticoagulation in terms of filter lifetime and mortality. We performed a large multicenter, parallel-group, randomized-controlled trial between March 2016 and December 2018 and included 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of renal replacement therapy. Patients were randomized to receive either regional citrate or systemic heparin anticoagulation for continuous renal replacement therapy. The two co-primary outcomes were filter lifetime and 90-day all-cause mortality. Secondary endpoints included bleeding complications and new infections. Patients were analyzed according to the intention to treat principle. Of 596 included patients, 300 were randomized to the regional citrate group and 296 patients to the systemic heparin anticoagulation group. Filter lifetime was significantly longer in the regional citrate as compared to the systemic heparin group (47h [interquartile range: 19-70h] vs. 26h [interquartile range: 12-51h]; P<0.001). 90-day all-cause mortality was 51.2% (150/300) in the regional citrate and 53.6% (156/296) in the systemic heparin anticoagulation group (hazard ratio, 0.91 [95% confidence interval, 0.72 to 1.13]; P=0.38). In the regional citrate anticoagulation group, bleeding complications were significantly lower (15/300 (5.1%) vs. 49/296 (16.9%); odds ratio, 0.27 [95% confidence interval, 0.15 to 0.49; P<0.001) whereas the rate of infections was significantly higher as compared to systemic heparin anticoagulation (204/300 (68.0%) vs. 164/296 (55.4%); odds ratio, 1.71 [95% confidence interval, 1.23 to 2.39]; P=0.002). In conclusion, among critically ill patients receiving acute continuous renal replacement therapy, regional citrate anticoagulation was superior in terms of filter lifetime but not in terms of 90-day mortality. The results of our study demonstrate a significant higher rate of new onset of infections in those patients randomized to the regional citrate anticoagulation group. As catheter details as well as the number of catheters inserted are similar in both groups, catheter infections may not be the underlying cause. Two possible reasons for the higher infection rate in the regional citrate anticoagulation group can be suggested: 1) the drug by itself, and/or 2) the increased filter running time. However, it is not possible to finally clarify this with our results. In small observational studies, it has been shown that citrate modulates the activation of neutrophils and complement factors. However, these trials did not focus on the occurrence of infections.
Publications
- Regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill patients with acute kidney injury (RICH-Trial): study protocol for a multicenter, randomized controlled trial. BMJ Open. 2019 Jan 21;9(1): e024411
Meersch M, Küllmar M, Wempe C, SepNet Critical Care Trials Group, et al.
(See online at https://doi.org/10.1136/bmjopen-2018-024411)
