Citrate 4% versus Heparin and the Reduction of Thrombosis Study (CHARTS)

Background and objectives: Citrate 4% has antithrombotic and antibacterial properties, which makes it a potentially superior alternative to heparin as an indwelling intraluminal locking agent.Design, setting, participants, and measurements: Sixty-one prevalent hemodialysis (HD) patients dialyzing with a tunneled cuffed HD catheter were randomized in a pilot study to receive either heparin 5000 U/ml or citrate 4% as a locking agent after HD. The primary outcomes were the development of catheter dysfunction (defined as a blood pump speed <250 ml/min or the use of tissue plasminogen activator) and catheter-associated bacteremia. The secondary outcomes were the development of an exit-site infection or bleeding complications (either local or systemic).Results: Citrate had comparable catheter dysfunction episodes to heparin (13/32 [41%] cases versus 12/29 [41%] cases, respectively). There were no differences in the development of catheter-associated bacteremia (2.2/1000 catheter days citrate versus 3.3/1000 catheter days heparin group; P = 0.607) or exit-site infection (2.2/1000 catheter days for both groups).Conclusions: The preliminary findings from our pilot study demonstrate that 4% citrate is effective in maintaining catheter patency and does not appear to have any increased incidence of infections. Because citrate is significantly cheaper and has a more favorable side effect profile than heparin, it can be considered a potentially better locking agent in HD catheters.Catheter use among hemodialysis (HD) patients continues to be high; in fact, recent data indicates that up to 33% of patients in Canada are dialyzing with a catheter (1). Complications of catheters are well known and include catheter dysfunction (CD), infection, and central vein stenosis. The burden of catheter-associated infections contributes to morbidity and subsequent mortality in HD patients. Catheter-related infections may start with bacterial colonization of the catheter hub or exit site and lead to subsequent exit-site infection (ESI) with or without bacteremia.The use of a catheter and all of its associated complications significantly increases the cost of care in these patients as compared with a native arteriovenous fistula (2). There is a renewed interest in citrate as an alternate to heparin as a locking solution in HD catheters because of its antithrombotic and antibacterial properties and the reduced costs relative to heparin. Furthermore, complications of heparin include local and systemic bleeding events as well as the potential for thrombocytopenia (3). Citrate may be a useful alternative to heparin because it is not known to produce the complications of thrombocytopenia or bleeding.Despite the use of citrate 4% in many HD units there is only one published randomized trial that compares citrate 4% and heparin in the HD catheter population (4). This study allocated 30 patients with temporary catheters to citrate 4%, heparin 5000 U/ml or polygeline (4). Unfortunately this study was not designed to compare outcomes of infection or thrombosis and the main outcome (i.e., visible clot formation in the catheter) is of questionable clinical relevance. Two prospective observational trials (5,6) recently examined the rate of catheter exchange, tissue plasminogen activator (TPA) use, and bacteremias in a HD population who were converted from heparin to citrate 4%. These studies gave conflicting results, with Lok et al. demonstrating significant reductions in catheter exchange rates, TPA use, and bacteremias in the citrate group whereas Grudzinski et al. found no reduction in catheter exchanges or bacteremias.Weijmer et al. performed a randomized trial involving 210 patients (98 tunneled cuffed catheters and 193 uncuffed catheters) who received either heparin 5000 U/ml or citrate 43% (7). There was a significant reduction in catheter-associated bacteremia (CAB): 1.1/1000 catheter days for citrate and 4.1 catheter days in the heparin group (P < 0.01) but no difference in the CD episodes.Initial studies of citrate were halted because of cardiac toxicity of 43% solutions (8); recent advances have demonstrated that 4% solutions are safe and effective, but direct comparisons of citrate to heparin are limited and have been performed in variable populations with different outcomes (9,10). We conducted a pilot study using a randomized design to compare the effect of citrate 4% and 5000 U/ml heparin in terms of CAB, ESI, and thrombotic episodes in a Canadian cohort of prevalent dialysis patients with cuffed catheters. The purpose of this pilot study is to assess the feasibility of pursuing a large, multicenter, quasi-randomized trial by exploring the resources and recruitment methods required.