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Background: Anticoagulation of the extracorporeal circuit is required in continuous renal replacement therapy
(CRRT). Heparin is the classic choice for anticoagulation, although it may increase the risk of bleeding. Regional citrate anticoagulation reduces the risk of bleeding, but may cause hypocalcemia and metabolic disturbances.

Study Design: Systematic review and meta-analysis of randomized controlled trials (RCTs).

Setting & Population: Patients admitted to the intensive care unit with acute kidney injury that required CRRT.

Selection Criteria for Studies: RCTs regardless of publication status or language.

Intervention: Regional citrate versus heparin anticoagulation in CRRT.

Outcomes: The primary outcomes were circuit survival time, the occurrence of major bleeding defined as a site of
gross bleeding with a decrease in blood pressure or requiring transfusion of 2 or more units of red blood cells, metabolic alkalosis, hypocalcemia, and thrombocytopenia. The secondary outcome was cost.

Results: 6 RCTs with 488 patients were identified. Citrate anticoagulation was associated with a significant decrease
in bleeding (RR, 0.34; 95% CI, 0.17-0.65). Circuit survival time, the incidence of metabolic alkalosis, and thrombocytopenia showed no significant difference between groups. Hypocalcemia was more common in patients receiving citrate, although no clinical adverse event was reported in the included studies.

Limitations: Significant heterogeneity in the primary outcome.

Conclusion: The efficacy of citrate and heparin anticoagulation for CRRT was similar. However, citrate anticoagulation
decreased the risk of bleeding with no significant increase in the incidence of metabolic alkalosis. We recommend citrate as an anticoagulation agent in patients who require CRRT but are at high risk of bleeding.