Background & AimsA simultaneous decline in pro‐ and anticoagulant drivers in patients with liver diseases results in a “rebalanced” haemostatic system, even in acutely ill patients. Nevertheless, both bleeding and thrombotic events are common. Here, we explored efficacy of pro‐ and antihaemostatic strategies in compensated and acutely ill cirrhotics which may be unpredictable given the profound haemostatic changes.MethodsWe tested the effects in vitro of the addition of clinically relevant doses of commonly used pro‐ and antihaemostatic strategies in plasma from healthy individuals (n = 30) and patients with compensated (n = 18) and acutely decompensated cirrhosis (n = 18), and acute‐on‐chronic liver failure (n = 10). We used thrombin generation tests and fibrin clot permeability assays to assess potency of various approaches.ResultsFresh frozen plasma and recombinant factor VIIa modestly increased thrombin generation (10%‐20%). Prothrombin complex concentrate increased thrombin generation two‐fold in controls and 2‐4‐fold in patients. Clot permeability decreased after addition of fibrinogen concentrate by 51% in controls and by 50%‐60% in patients. Low molecular weight heparin decreased thrombin generation by 18% in controls and by 23%‐54% in patients. Similarly, dabigatran decreased thrombin generation by 33% in controls and by 47%‐100% in patients. In contrast, rivaroxaban decreased thrombin generation by 55% in controls, but only by 11%‐38% in patients.ConclusionsThese in vitro data suggest little prohaemostatic effect of fresh frozen plasma and recombinant factor VIIa in acutely ill cirrhotics, whereas prothrombin complex concentrate and fibrinogen concentrate clearly improved haemostasis. Furthermore, our data suggest the requirement for dose adjustments of commonly used anticoagulants in these patients.
Objectives: Hyperammonemia is a key contributing factor for cerebral edema in acute liver failure. Continuous renal replacement therapy may help reduce ammonia levels. However, the optimal timing, mode, intensity, and duration of continuous renal replacement therapy in this setting are unknown. We aimed to study continuous renal replacement therapy use in acute liver failure patients and to assess its impact on hyperammonemia. Design: Retrospective observational study. Setting: ICU within a specialized liver transplant hospital. Patients: Fifty-four patients with acute liver failure. Interventions: Data were obtained from medical records and analyzed for patient characteristics, continuous renal replacement therapy use, ammonia dynamics, and outcomes. Main Results: Forty-five patients (83%) had high grade encephalopathy. Median time to continuous renal replacement therapy commencement was 4 hours (interquartile range, 2–4.5) with 35 (78%) treated with continuous venovenous hemodiafiltration and 10 (22%) with continuous venovenous hemofiltration. Median hourly effluent flow rate was 43 mL/kg (interquartile range, 37–62). The median ammonia concentration decreased every day during treatment from 151 µmol/L (interquartile range, 110–204) to 107 µmol/L (interquartile range, 84–133) on day 2, 75 µmol/L (interquartile range, 63–95) on day 3, and 52 µmol/L (interquartile range, 42–70) (p < 0.0001) on day 5. The number of patients with an ammonia level greater than 150 µmol/L decreased on the same days from 26, to nine, then two, and finally none. Reductions in ammonia levels correlated best with the cumulative duration of therapy hours (p = 0.03), rather than hourly treatment intensity. Conclusions: Continuous renal replacement therapy is associated with reduced ammonia concentrations in acute liver failure patients. This effect is related to greater cumulative dose. These findings suggest that continuous renal replacement therapy initiated early and continued or longer may represent a useful approach to hyperammonemia control in acute liver failure patients.
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 mol/L (interquartile range [IQR], 91–172), median creatinine was 165 mol/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 mol/L [IQR, 102–198] v 91 mol/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 mol/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.
<b><i>Introduction:</i></b> Continuous renal replacement therapy (CRRT) can be used to treat hyperammonaemia. However, no study has assessed the effect of different CRRT techniques on ammonia clearance. <b><i>Methods:</i></b> We compared 3 different CRRT techniques in adult patients with hyperammonaemia, liver failure, and acute kidney injury. We protocolized CRRT to progressively deliver continuous veno-venous haemofiltration (CVVH), haemodialysis (CVVHD) or haemodiafiltration (CVVHDF). Ammonia was simultaneously sampled from the patient’s arterial blood and effluent fluid for each technique. We applied accepted equations to calculate clearance. <b><i>Results:</i></b> We studied 12 patients with a median age of 47 years (interquartile range [IQR] 25–79). Acute liver failure was present in 4 (25%) and acute-on-chronic liver failure in 8 (75%). There was no significant difference in median ammonia clearance between CRRT technique; CVVH: 27 (IQR 23–32) mL/min versus CVVHD: 21 (IQR 17–28) mL/min versus CVVHDF: 20 (IQR 14–28) mL/min, <i>p</i> = 0.32. Moreover, for all techniques, ammonia clearance was significantly less than urea and creatinine clearance; urea 50 (47–54) mL/min versus creatinine 42 (IQR 38–46) mL/min versus ammonia 25 (IQR 18–29) mL/min, <i>p</i> = 0.0001. <b><i>Conclusion:</i></b> We found no significant difference in ammonia clearance according to CRRT technique and demonstrated that ammonia clearance is significantly less than urea or creatinine clearance.
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) × 10 9 /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.
Objective: To examine the extent to which medical students in Australia are acting as interpreters in medical settings, and their perceptions of this activity.
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