Effect of Continuous Renal Replacement Therapy on Outcome in Pediatric Acute Liver Failure

Objectives: To establish the effect of continuous renal replacement therapy on outcome in pediatric acute liver failure. Design: Retrospective cohort study. Setting: Sixteen-bed PICU in a university-affiliated tertiary care hospital and specialist liver centre. Patients: All children (0-18 yr) admitted to PICU with pediatric acute liver failure between January 2003 and December 2013. Interventions: Children with pediatric acute liver failure were managed according to a set protocol. The guidelines for continuous renal replacement therapy in pediatric acute liver failure were changed in 2011 following preliminary results to indicate the earlier use of continuous renal replacement therapy for both renal dysfunction and detoxification. Measurements and Main Results: Of 165 children admitted with pediatric acute liver failure, 136 met the inclusion criteria and 45 of these received continuous renal replacement therapy prior to transplantation or recovery. Of the children managed with continuous renal replacement therapy, 26 (58%) survived: 19 were successfully bridged to liver transplantation and 7 spontaneously recovered. Cox proportional hazards regression model clearly showed reducing hyperammonemia by 48 hours after initiating continuous renal replacement therapy significantly improved survival (HR, 1.04; 95% CI, 1.013-1.073; p = 0.004). On average, for every 10% decrease in ammonia from baseline at 48 hours, the likelihood of survival increased by 50%. Time to initiate continuous renal replacement therapy from PICU admission was lower in survivors compared to nonsurvivors (HR, 0.96; 95% CI, 0.916-1.007; p = 0.095). Change in practice to initiate early and high-dose continuous renal replacement therapy led to increased survival with maximum effect being visible in the first 14 days (HR, 3; 95% CI, 1.0-10.3; p = 0.063). Among children with pediatric acute liver failure who did not receive a liver transplant, use of continuous renal replacement therapy significantly improved survival (HR, 4; 95% CI, 1.5-11.6; p = 0.006). Conclusion: Continuous renal replacement therapy can be used successfully in critically ill children with pediatric acute liver failure to provide stability and bridge to transplantation. Inability to reduce ammonia by 48 hours confers poor prognosis. Continuous renal replacement therapy should be considered at an early stage to help prevent further deterioration and buy time for potential spontaneous recovery or bridge to liver transplantation.