Continuous renal replacement therapy and its impact on hyperammonaemia in acute liver failure.

OBJECTIVE: Hyperammonaemia contributes to complications in acute liver failure (ALF) and may be treated with continuous renal replacement therapy (CRRT), but current practice is poorly understood. DESIGN: We retrospectively analysed data for baseline characteristics, ammonia concentration, CRRT use, and outcomes in a cohort of Australian and New Zealand patients with ALF. SETTING: All liver transplant ICUs across Australia and New Zealand. PARTICIPANTS: Sixty-two patients with ALF. MAIN OUTCOME MEASURES: Impact of CRRT on hyperammonaemia and patient outcomes. RESULTS: We studied 62 patients with ALF. The median initial (first 24 h) peak ammonia was 132 µmol/L (interquartile range [IQR], 91-172), median creatinine was 165 µmol/L (IQR, 92-263) and median urea was 6.9 mmol/L (IQR, 3.1-12.0). Most patients (43/62, 69%) received CRRT within a median of 6 hours (IQR, 2-12) of ICU admission. At CRRT commencement, three-quarters of such patients did not have Stage 3 acute kidney injury (AKI): ten patients (23%) had no KDIGO creatinine criteria for AKI, 12 (28%) only had Stage 1, and ten patients (23%) had Stage 2 AKI. Compared with non-CRRT patients, those treated with CRRT had higher ammonia concentrations (median, 141 µmol/L [IQR, 102-198] v 91 µmol/L [IQR, 54-115]; P = 0.02), but a nadir Day 1 pH of only 7.25 (standard deviation, 0.16). Prevention of extreme hyperammonaemia (> 140 µmol/L) after Day 1 was achieved in 36 of CRRT-treated patients (84%) and was associated with transplant-free survival (55% v 13%; P = 0.05). CONCLUSION: In Australian and New Zealand patients with ALF, CRRT is typically started early, before Stage 3 AKI or severe acidaemia, and in the presence hyperammonaemia. In these more severely ill patients, CRRT use was associated with prevention of extreme hyperammonaemia, which in turn, was associated with increased transplant-free survival.

Coagulation abnormalities, bleeding, thrombosis, and management of patients with acute liver failure in Australia and New Zealand.

BACKGROUND AND AIM: To study the management of coagulation and hematological derangements among severe acute liver failure (ALF) patients in Australia and New Zealand liver transplant intensive care units (ICUs). METHODS: Analysis of key baseline characteristics, etiology, coagulation and hematological tests, use of blood products, thrombotic complications, and clinical outcomes during the first ICU week. RESULTS: We studied 62 ALF patients. The first day median peak international normalized ratio was 5.5 (inter-quartile range [IQR] 3.8-8.7), median longest activated partial thromboplastin time was 62 s (IQR 44-87), and median lowest fibrinogen was 1.1 (IQR 0.8-1.6) g/L. Fibrinogen was only measured in 85% of patients, which was less than other tests (P < 0.0001). Median initial lowest platelet count was 83 (IQR 41-122) × 109 /L. Overall, 58% of patients received fresh frozen plasma, 40% cryoprecipitate, 35% platelets, and 15% prothrombin complex concentrate. Patients with bleeding complications (19%) had more severe overall hypofibrinogenemia and thrombocytopenia. Thrombotic complications were less common (10% of patients), were not associated with consistent patterns of abnormal hemostasis, and were not immediately preceded by clotting factor administration and half occurred only after liver transplantation surgery. CONCLUSION: In ALF patients admitted to dedicated Australia and New Zealand ICUs, fibrinogen was measured less frequently than other coagulation parameters but, together with platelets, appeared more relevant to bleeding risk. Blood products and procoagulant factors were administered to most patients at variable levels of hemostatic derangement, and bleeding complications were more common than thrombotic complications. This epidemiologic information and practice variability provide baseline data for the design and powering of interventional studies.

Characteristics, management and outcomes of patients with acute liver failure admitted to Australasian intensive care units.

OBJECTIVE: Acute liver failure (ALF) leads to severe illness and usually requires admission to the intensive care unit (ICU). Despite its importance, little is known about patients with ALF in Australia and New Zealand. DESIGN: Binational observational study to evaluate the aetiology, baseline characteristics, patterns of illness, management, and outcomes for patients with ALF admitted to Australian and New Zealand ICUs. SETTING: All six Australian and New Zealand ICUs in liver transplant centres submitted de-identified data for ten or more consecutive patients with ALF. Data were obtained from the clinical record and included baseline characteristics, aetiology, mode of presentation, illness severity, markers of liver failure, critical care interventions, utilisation of transplantation, and hospital outcome. RESULTS: We studied 62 patients with ALF. Paracetamol overdose (POD) was the underlying cause of ALF in 53% of patients (33/62), with staggered ingestion in 42% of patients (14/33). Among patients with POD, 70% (23/33) were young women, most had psychiatric diagnoses, and most presented relatively early with overt liver failure. This group were transplanted in only 6% of cases (2/33) and had an overall mortality of 24% (8/33). The remaining patients with ALF had less common conditions, such as hepatitis B and non-paracetamol drug-induced ALF. These patients presented later and exhibited less extreme evidence of acute hepatic necrosis. Transplantation was performed in 38% of patients (11/29) in this subgroup. The mortality of nontransplanted non-POD patients was 56% (10/18). Illness severity at ICU admission, initial requirement for organ support therapies and length of hospital stay were similar between patients with POD and non-POD ALF. CONCLUSION: POD is the major cause of ALF in Australian and New Zealand liver transplant centres and is a unique and separate form of ALF. It has a much lower associated mortality and treatment with liver transplantation than non-POD ALF. Non-POD patients have a poor prognosis in the absence of transplantation.