Citrate for continuous renal replacement therapy: safer,better and cheaper

In a previous issue of Critical Care, Schilder and colleagues report the results of their multicenter trial (Citrate Anticoagulation Versus Systemic Heparinization; CASH) comparing regional anticoagulation with citrate to heparin anticoagulation. They found that citrate was safer, more efficacious and cheaper than heparin. In contrast to the largest previous trial, however, a survival benefit was not found, which was the primary endpoint of the CASH trial. Different explanations are possible, including selection bias and a lower severity of disease. Selection bias was high: only 6% of the renal replacement therapy patients were included (versus 56% in the previous trial) and exclusion was 56% for increased risk of bleeding, 2.5 times as frequent as in the previous trial. Thus, the trial with survival benefit apparently included more patients with risk of bleeding and also more severely ill patients and these are the groups that potentially benefit the most from citrate. Nevertheless, the CASH trial is the third large randomized trial showing superiority of citrate over heparin, supporting the recommendation of citrate as first choice anticoagulant.Continuous renal replacement therapy (CRRT) is used for critically ill patients with acute kidney injury in the setting of multiple organ failure. To prevent clotting in the extracorporeal circuit, anticoagulation is required. The commonly used strategies are heparin, causing systemic anticoagulation, and citrate, providing regional anticoagulation of the circuit. As a result, citrate does not increase the patient’s risk of bleeding. On account of this, citrate should be the first choice in critically ill patients. However, many doctors doubt its safety. The time has come to drop this delusion. The recently published multicenter CASH trial (Citrate Anticoagulation versus Systemic Heparinisation) is the third large randomized controlled trial in a row showing superiority of citrate over heparin [1-3]. Citrate was safer, more efficacious and cheaper. In contrast to the OLVG (Onze Lieve Vrouwe Gasthuis) trial [2], however, a survival benefit, which was the primary endpoint of the CASH trial, was not found.