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.