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

BACKGROUND: Citrate has theoretical advantages over heparin for locking hemodialysis central venous catheters (CVCs), but the comparative effectiveness of these agents is not clear. OBJECTIVES: 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. DATA SOURCES: CENTRAL, MEDLINE, EMBASE, CINAHL, ISI Web of Science, and nephrology conference abstracts. STUDY ELIGIBILITY PARTICIPANTS AND INTERVENTIONS: 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. APPRAISAL AND SYNTHESIS METHODS: 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. RESULTS: 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. LIMITATIONS: Outcome definitions varied across studies. Imprecision due to small sample sizes and low event rates reduce our overall confidence in the pooled effect estimates. IMPLICATIONS: Benefits and harms of citrate vs. heparin locking solutions remain unclear; larger studies and standardization of outcome measurement and reporting are warranted. TRIAL REGISTRATION: Protocol Registration Number: CRD42013004781.