Severely Hyperammonemic Acute Liver Failure due to Paracetamol Overdose: The Impact of High-Intensity Continuous Renal Replacement Therapy

Introduction: Paracetamol (acetaminophen)-induced acute liver failure (ALF)with severe hyperammonemia (ammonia <100 μmol L-1) is a life-threatening condition. A strategy based on high-intensity continuous renal replacement therapy (CRRT) without early (up to day seven) transplantation may enable clinicians to safely identify which patients can recover and survive and which patients require transplantation. Methods:We conducted a single-center, retrospective cohort study of patients with severely hyperammonemic paracetamol-induced ALF. The primary outcome was early transplant-free survival. Results: We studied 84 patients (median age: 38; female sex: 79 [85%]) over a 12-year period (median ammonia level at ICU admission: 153 μmol L-1; median peak aspartate aminotransferase (AST): 10,029 U L-1;median lactate: 5.0mmol L-1; and median INR: 4.4) and 55 (65%) with King's College criteria for transplantation. Overall, 87% received high-intensity CRRT (92% in 2020-2023). Median CRRT intensity was 54 mL kg-1 hr-1 within the first 48 h and increased by 1.8 mL kg-1 hr-1 per year during the study period (p = 0.002). Transplant-free survival to day 7 was 86% in 2011-2023 and 96% in 2020-2023. Overall, only 4 patients were transplanted and only 1 (4%) in 2020-2023. On multivariable Cox analysis, factors independently associated with failure to achieve day seven transplant-free survival were higher APACHE III score (HR = 1.05, 95% CI: 1.02-1.08), higher lactate (HR = 1.27, 95% CI: 1.12-1.44), and lower platelet count at ICU admission (HR = 0.85, 95% CI: 0.78-0.93) and the median effluent dose applied within the first 48 h of ICU admission (HR = 0.67, 95% CI: 0.46-0.98). Conclusions: Early transplant-free survival is achievable in most patients with paracetamol-induced ALF and severe hyperammonemia with a treatment based on highintensity CRRT. Such transplant-free survival increased over time together with increased CRRT dose.