Citrate anticoagulation versus systemic heparinisation in continuous venovenous hemofiltration in critically ill patients with acute kidney injury: a multi-center randomized clinical trial

Abstract

IntroductionBecause of ongoing controversy, renal and vital outcomes are compared between systemically administered unfractionated heparin and regional anticoagulation with citrate-buffered replacement solution in predilution mode, during continuous venovenous hemofiltration (CVVH) in critically ill patients with acute kidney injury (AKI).MethodsIn this multi-center randomized controlled trial, patients admitted to the intensive care unit requiring CVVH and meeting inclusion criteria, were randomly assigned to citrate or heparin. Primary endpoints were mortality and renal outcome in intention-to-treat analysis. Secondary endpoints were safety and efficacy. Safety was defined as absence of any adverse event necessitating discontinuation of the assigned anticoagulant. For efficacy, among other parameters, survival times of the first hemofilter were studied.ResultsOf the 139 patients enrolled, 66 were randomized to citrate and 73 to heparin. Mortality rates at 28 and 90 days did not differ between groups: 22/66 (33%) of citrate-treated patients died versus 25/72 (35%) of heparin-treated patients at 28 days, and 27/65 (42%) of citrate-treated patients died versus 29/69 (42%) of heparin-treated patients at 90 days (P = 1.00 for both). Renal outcome, i.e. independency of renal replacement therapy 28 days after initiation of CVVH in surviving patients, did not differ between groups: 29/43 (67%) in the citrate-treated patients versus 33/47 (70%) in heparin-treated patients (P = 0.82). Heparin was discontinued in 24/73 (33%) of patients whereas citrate was discontinued in 5/66 (8%) of patients (P < 0.001). Filter survival times were superior for citrate (median 46 versus 32 hours, P = 0.02), as were the number of filters used (P = 0.002) and the off time within 72 hours (P = 0.002). The costs during the first 72 hours of prescribed CVVH were lower in citrate-based CVVH.ConclusionsRenal outcome and patient mortality were similar for citrate and heparin anticoagulation during CVVH in the critically ill patient with AKI. However, citrate was superior in terms of safety, efficacy and costs.Trial registrationClinicaltrials.gov NCT00209378. Registered 13th September 2005.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-014-0472-6) contains supplementary material, which is available to authorized users.

Implementation of a Simplified Regional Citrate Anticoagulation Protocol for Post-Dilution Continuous Hemofiltration Using a Bicarbonate Buffered, Calcium Containing Replacement Solution

“…There were no instances of clinical citrate accumulation. Filter lifespans were acceptable and similar to some previous reports of RCA-CRRT [15], but lower than median values (39-46 h) reported in recent randomized trails comparing citrate to heparin [5,6]. It should be noted that our patients were selected for having contraindications to heparin or prior poor filter lifespans and were thus likely to be predisposed to poorer filter lifespans; by comparison, historical data suggest typical filter lifespans using no anticoagulation in our unit were three-fold worse than those achieved with citrate in this pilot [16].…”

“…Recent evidence has confirmed the superiority of regional citrate compared with systemic heparin anticoagulation both to maintain patency of the extracorporeal circuit and to reduce bleeding complications [3,4,5,6]. Despite this weight of favorable evidence, the uptake of RCA has been limited in many countries, including in the UK [7].…”

The incidence of thrombocytopenia associated with continuous renal replacement therapy in critically ill patients

“…These researchers deemed this drop as clinically suspected HIT despite never being confirmed by further laboratory evaluation. 5 Literature assessing the use of citrate, a regional anticoagulant, versus the systemic anticoagulant heparin has eluded to thrombocytopenia in CRRT. In a comparison of citrate versus heparin circuit anticoagulation, there was a significantly lower rate (3% vs. 10%) of thrombocytopenia, defined in these studies as HIT.…”

Continuous Renal Replacement Therapy and Anticoagulation:

“…Schilder et al 37 Brain et al 44 Hertzel et al 33 Morgera et al 45 Nurmohamed et al 36 Betjes et al 43 Monchi et al 35 …”

“…36 Regardless of the protocol followed for the infusion of citrate, a replacement infusion of calcium is administered at the end of the extracorporeal circuit or via a separate venous access to correct for the calcium that is chelated and also to replace any calcium chelated in the blood or lost into the ultrafiltrate or dialysate. 31,34,37 The calcium infusion must be administered after the filter or into a central catheter to prevent tissue sloughing and necrosis, which can occur with infiltration. 31,38 Generally, because calcium interferes with the action of the citrate, calcium-free dialysate or replacement fluids are often used with citrate anticoagulation.…”