Benefits and Harms of Citrate Locking Solutions for Hemodialysis Catheters: A Systematic Review and Meta-Analysis

Citrate has theoretical advantages over heparin for locking hemodialysis central venous catheters (CVCs), but the comparative effectiveness of these agents is not clear. 1) To compare the benefits and harms of citrate versus heparin locking solutions among patients undergoing hemodialysis through CVCs; 2) to appraise methodological quality of the supporting evidence. CENTRAL, MEDLINE, EMBASE, CINAHL, ISI Web of Science, and nephrology conference abstracts. We included randomized, parallel arm clinical trials that enrolled adult patients (>18 years) receiving chronic hemodialysis through CVCs using a citrate locking solution. We excluded studies in which citrate was combined with other agents, such as antibiotics. We used the GRADE approach to systematic reviews and quality appraisal. Two reviewers performed data extraction independently and in duplicate. We pooled count data using generic inverse variance with random-effects models, and used fixed-effect models when only two studies were available for pooling. Subgroups included low (≤5%) vs. higher (≥30%) citrate. We screened 600 citations. Forty-one proceeded to full-text screen; 5 met inclusion criteria. Studies included between 19 and 291 participants (Median N = 61) followed for a total of 174.6 catheter-years; 2 were multi-centred trials. Three studies assessed all-cause mortality; the pooled relative risk for death was 0.71 (95% CI = 0.42-1.24; p = 0.21; I(2) = 0%). The rate ratio for bacteremic episodes was 0.54 (95% CI = 0.23-1.29; p = 0.16; I(2) = 65%) while the rate ratio for bleeding was 0.48 (95% CI = 0.3-0.75; p = 0.001;I I(2) = 5%). Rates of catheter exchange/replacement, all-cause hospitalization and in-situ thrombolysis were not significantly different between groups in any of the pooled analyses. Risk of bias within pooled studies was low. Outcome definitions varied across studies. Imprecision due to small sample sizes and low event rates reduce our overall confidence in the pooled effect estimates. Benefits and harms of citrate vs. heparin locking solutions remain unclear; larger studies and standardization of outcome measurement and reporting are warranted. Protocol Registration Number: CRD42013004781.