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

Abstract

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; I2 = 0%). The rate ratio for bacteremic episodes was 0.54 (95% CI = 0.23–1.29; p = 0.16; I2 = 65%) while the rate ratio for bleeding was 0.48 (95% CI = 0.3–0.75; p = 0.001;I I2 = 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