| Objective:Liver failure(LF)and increased bleeding risk are common co-morbiditiesofcritically ill patients underwent continuous renal replacement therapy(CRRT).Anticoagulation is often required for the maintaining of the patency of CRRT circuit.For LF patients with increased bleeding risk,there were controversial opinions on the choice of anticoagulation for CRRT.The KDIGO(Kidney Disease: Improving Global Outcomes)guideline listed severe LF as one of the major contraindications of regional citrate anticoagulation(RCA).Additionally,heparin should not be the choice for patients with increased bleeding risk as well.Therefore,for patients with LF and increased bleeding risk,KDIGO guideline recommended the performance of CRRT without the use of any anticoagulant.However,parts of LF patients underwent CRRT with no-anticoagulation resulted in very shorter filter lifespan(average filter lifespanwas only 7-8 hours)and affected treatment effect of CRRT.Several cohort studies have shown that the use of RCA in patients with liver failure did not aggravate liver injury and significantly improved the filter lifespan.However,all of the current evidences were limited in observational cohort study and limited to the low quality of research,so many centers and guidelines do not recommend RCA in patients with LF.At present,the advantages and disadvantages of anticoagulation and no-anticoagulation in patients with LF with high-risk bleeding for CRRT therapy are still unclear,and the choice of an appropriate anticoagulation method is important in clinical practice.Therefore,we conducted a retrospective case-control study and a prospective randomized controlled study to evaluate the efficacy and safety of RCA versus no-anticoagulation for CRRT in these patients.Methods:In the retrospective cohort study,liver failure patients with increased bleeding risk underwent CRRT between January 2013 and October 2016 in our hospital were screened.The included patients were divided into RCA and no-anticoagulation group according to the CRRT anticoagulation strategy.Filter lifespan,bleeding,citrate accumulation,catheter occlusion,and tot Ca/ion Ca > 2.5 were evaluated as outcomes.Univariate and multivariate Cox regression analysis was used to determine the risk factors of filter failure,and the safety and effectiveness of the two anticoagulant methods were evaluated.Addtionally,a prospective randomized controlled trialfrom August 2018 was started to compare the filters lifespan,complications related to citrate accumulation,metabolic alkalosis,metabolicacidosis,hypocalcemiaand bleeding in patients in the RCA group and no-anticoagulation group.Results:1.Retrospective cohort study: in the original cohort,the filter lifespan of the RCA group(41 patients,79 filters)was significantly longer than the no-anticoagulation group(62patients,162 filters)(> 72 hours vs 39.5 hours [IQR 31.2-47.8],P = 0.002).The 72 hours accumulated filter failure rate of RCA and no-anticoagulant group was 44.6% and 81.4%,respectively.In the multivariate Cox regression model,the adjusted results demonstrated that RCA could significantly reduce the risk of filter failure(HR = 0.459,95%CI0.26-0.82,P = 0.008).Four episodes of tot Ca/ion Ca > 2.5 were observed in the RCA group and continuously accepted RCA-CVVH after the reduction of citrate dose or increment of blood flow.No obvious citrate accumulation was observed in these patients.In the matched cohort,the filter lifespan of the RCA group was significantly longer than the no-anticoagulation group(> 72 hours vs.41 hours [IQR 10.2-71.7],P = 0.013)as well.No significant difference in the episodes of tot Ca/ion Ca > 2.5 was observed between the two matched groups(P = 0.074).Both in the original cohort and the matched cohort,the incidences of bleeding,acidosis,alkalosis,and catheter occlusion were not significantly different between the two groups.2.Up to now,a total of 45 patients were enrolled in the prospective randomized controlled study,and one patient was excluded from the analysis.Fourty-four patients were included in the safety and effectiveness analysis.Of the 44 patients underwent CRRT,22 patients received RCA,and the other 22 patients received no-anticoagulation.The filter median survival time of no-anticoagulation group was 25.5hours(IQR15.5-66),and the filter median survival time of the RCA group was > 72 hours.RCA group had a significantly higher filter lifespan than no-anticoagulant group(P = 0.001).The 24 hours accumulated filter failure rate of RCA and no-anticoagulant group was 36.3% and 50%,respectively.Univariate and multivariate Cox analysis showed that anticoagulation of RCA significantly reduced the risk of filter failure(HR =0.167,95%CI 0.047-0.591,P = 0.006).There was no significant difference in the incidence of bleeding,catheter dysfunction,metabolic acidosis,and metabolic alkalosis.Conclusions:Both retrospective cohort study and prospective randomized controlled study results showed that RCA for CRRT could significantly extend the filter lifespan in patients with LF and increased bleeding risk and may not significantly increase the risk of citrate accumulation,bleeding,catheter occlusion,metabolic acidosis,and metabolism alkalosis,compared with no-anticoagulation.In conclusion,in LF patients with increased bleeding risk who underwent CRRT,RCA could prolong the filter lifespan and be safely used with careful monitoring and citrate dose adjusting. |
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