Lactate as a Predictor of Citrate Accumulation in Patients Undergoing Continuous Renal Replacement Therapy? A Systematic Review

Regional citrate anticoagulation (RCA) is the preferred strategy for continuous renal replacement therapy (CRRT). However, impaired citrate metabolism, observed in patients with liver failure, mitochondrial dysfunction, and/or shock, can result in potentially lethal citrate accumulation (CA). We aimed to evaluate the ability of elevated lactate levels to predict CA in critically ill patients undergoing RCA-CRRT. We performed a comprehensive search in PubMed and Embase databases for studies involving adult critically ill patients who underwent RCA-CRRT, where both CA and lactate levels were assessed. The primary outcome was lactate levels in relation to patients with and without CA. The certainty of the effect estimates for each outcome and the quality of the included studies were assessed. We included seven observational studies comprising 1573 critically ill patients undergoing RCA-CRRT. Five studies were deemed good quality evidence and two poor to answer the research question. We found a significant mean difference (MD) in baseline lactate levels (MD: 0.87, 95% CI [0.04; 1.70] p = 0.04, six studies, 1474 patients) between the CA and the non-CA group with low confidence in the estimate. This difference was persistent between the two groups when using peak lactate levels (MD: 6.05, 95% CI [0.06; 12.03], p = 0.05, three studies, 271 patients), and the CA group had an overall higher mortality risk (OR: 5.24, 95% CI [1.05; 26.25], p = 0.04, five studies, 1427 patients). The evidence is very uncertain, but elevated lactate may be associated with an increased risk of CA in critically ill patients undergoing RCA-CRRT.