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Data on perioperative extracorporeal membrane oxygenation (ECMO) in liver transplantation (LT) are scarce. ECMO has been used preoperatively, intraoperatively, and postoperatively for a variety of indications at our center. This retrospective, single-center study of ECMO use peri-LT aimed to describe predictors for successful outcome in this highly select cohort of patients. Demographics, support method, and indication for LT were compared between survivors and nonsurvivors. Twenty-nine patients received venovenous (V-V; n = 20), venoarterial (V-A; n = 8), and venoarteriovenous (n = 1) ECMO. Twelve (41.4%) patients were bridged to emergency LT for acute liver failure, and emergency redo LT. Four (13.3%) patients required intraoperative V-A ECMO salvage, 2 necessitating extracorporeal cardiopulmonary resuscitation. Thirteen (43.3%) patients required ECMO support after LT: V-V ECMO (n = 9); V-A ECMO (n = 1); and extracorporeal cardiopulmonary resuscitation (n = 3) between postoperative days 2 to 30. Overall, 19 patients (65.5%) were successfully weaned off ECMO; 15 (51.7%) survived to intensive care unit discharge. All patients who underwent intraoperative salvage ECMO and all who were bridged to emergency redo LT died. Peri-LT ECMO is feasible. Post-LT ECMO outcomes are encouraging, in particular for V-V ECMO. Intraoperative ECMO salvage, uncontrolled sepsis, and graft failure are associated with poor outcomes., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Despite considerable advances in maternity care, maternal death rates remain unacceptably high. Even with optimal care, unexpected complications can result in catastrophic consequences. Hemorrhage, cardiovascular and coronary conditions, and cardiomyopathy make up the three most common causes of pregnancy-associated deaths, followed by sepsis and thromboembolic disease. Although a number of deaths may be deemed to be potentially avoidable with appropriate education and infrastructure, others such as refractory hypoxia and peripartum cardiomyopathy are not. All possible interventions should be explored, including the use of more novel and aggressive life support technologies, such as extracorporeal membrane oxygenation. We report the successful use of extracorporeal membrane oxygenation in three cases of severe peripartum morbidity. The first case describes spontaneous coronary artery dissection supported with veno-arterial extracorporeal membrane oxygenation for refractory cardiogenic shock after out-of-hospital cardiac arrest. The second is a case of severe pregnancy-related liver disease bridged to emergency liver transplantation with veno-venous extracorporeal membrane oxygenation. Finally, we report the use of extracorporeal cardiopulmonary resuscitation for refractory cardiac arrest in a postpartum patient. Peripartum extracorporeal membrane oxygenation is feasible in carefully selected patients, and should be considered early when conventional therapy is failing, or as a salvage rescue therapy when it has failed.

Background: Liver volume (LV) can be non-invasively determined from the analysis of computed tomography (CT) images, and in patients with acute liver injury (ALI) or failure (ALF), it can reflect the balance of structural collapse with hepatic regeneration. We examined its relation to cause of liver injury, measures of liver function and histopathological findings, and utility in prediction of complications and mortality., Methods: Two hundred and seventy-three patients with ALF/ALI admitted to a specialist intensive care unit were studied. One hundred and ninety-nine patients (73%) had non-acetaminophen (NA) aetiologies and 74 (27%) had acetaminophen-induced disease. LV and proportion of predicted LV (PLV%) were determined from admission CT imaging., Results: LV and PLV% showed marked variation when aetiologic groups were compared (P < .0001), including loss in cases with indeterminate cause (LV 939 cm 3 [IQR 680-1259], PLV% 56% [42-84]) and increase in Budd-Chiari syndrome (1891 cm 3 [1601-2094], 121% [111-131]). Progression to high-grade encephalopathy was more common with smaller LV and PLV. A < 1000 cm 3 threshold identified NA patients who later developed it with 93% (95%CI 83-98) specificity and odds ratio 10.6 (3.3-34.5) at median 5 days prior to onset, and risk of death in those with NA-drug-induced (DILI) or indeterminate disease with 91% (71-99) specificity and 63% (50-75) sensitivity., Conclusion: In patients with ALF/ALI, LV shows marked variation by the cause of disease, and in prognostic importance. In indeterminate and DILI cases, loss of volume to <1000 cm 3 may indicate irreversible liver injury and regenerative failure and serve as an early clinical predictor for the development of high-grade encephalopathy and death., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Patients with acutely decompensated (AD) cirrhosis are at risk for developing acute-on-chronic liver failure (ACLF) syndrome. This syndrome is associated with a high short-term mortality rate. The aim of our study was to identify reliable early predictors of developing ACLF in cirrhotic patients with AD., Patients and Methods: We assessed 84 cirrhotic patients admitted for AD without ACLF on admission. We performed routine blood testing and detailed ultrasound Doppler studies of systemic arteries and mayor abdominal veins and arteries. We also calculated liver-specific and intensive care unit predictive scores. The area under the ROC curve (AUROC) was calculated for all variables that were significantly different between patients who developed ACLF and those who did not. Sensitivity, specificity, positive and negative predictive values, as well as diagnostic accuracy predicting the short-term development of ACLF were determined., Results: of the 84 patients, 23 developed ACLF whereas 61 did not. In the univariate analysis, serum levels of creatinine and urea, prothrombin time ratio, MELD score, portal vein and femoral artery flow velocity as well as the renal and interlobar artery resistive indices (RI) were associated with the short-term development of ACLF. However, only interlobar artery RI had independent predictive value in the multivariate analysis. The AUROC value for RI of the interlobar arteries was 0.9971., Conclusion: On the first day of admission, ultrasound measurement of the RI of the interlobar arteries recognizes with high predictive accuracy those cirrhotic patients admitted with AD who will develop ACLF during hospital admission., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background & Aims: Patients with acute liver failure (ALF) have defects in innate immune responses to microbes (immune paresis) and are susceptible to sepsis. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4), which interacts with the membrane receptor B7 (also called CD80 and CD86), is a negative regulator of T-cell activation. We collected T cells from patients with ALF and investigated whether inhibitory signals down-regulate adaptive immune responses in patients with ALF., Methods: We collected peripheral blood mononuclear cells from patients with ALF and controls from September 2013 through September 2015 (45 patients with ALF, 20 patients with acute-on-chronic liver failure, 15 patients with cirrhosis with no evidence of acute decompensation, 20 patients with septic shock but no cirrhosis or liver disease, and 20 healthy individuals). Circulating CD4 + T cells were isolated and analyzed by flow cytometry. CD4 + T cells were incubated with antigen, or agonist to CD3 and dendritic cells, with or without antibody against CTLA4; T-cell proliferation and protein expression were quantified. We measured levels of soluble B7 molecules in supernatants of isolated primary hepatocytes, hepatic sinusoidal endothelial cells, and biliary epithelial cells from healthy or diseased liver tissues. We also measured levels of soluble B7 serum samples from patients and controls, and mice with acetaminophen-induced liver injury using enzyme-linked immunosorbent assays., Results: Peripheral blood samples from patients with ALF had a higher proportion of CD4 + CTLA4 + T cells than controls; patients with infections had the highest proportions. CD4 + T cells from patients with ALF had a reduced proliferative response to antigen or CD3 stimulation compared to cells from controls; incubation of CD4 + T cells from patients with ALF with an antibody against CTLA4 increased their proliferative response to antigen and to CD3 stimulation, to the same levels as cells from controls. CD4 + T cells from controls up-regulated expression of CTLA4 after 24-48 hours culture with sera from patients with ALF; these sera were found to have increased concentrations of soluble B7 compared to sera from controls. Necrotic human primary hepatocytes exposed to acetaminophen, but not hepatic sinusoidal endothelial cells and biliary epithelial cells from patients with ALF, secreted high levels of soluble B7. Sera from mice with acetaminophen-induced liver injury contained high levels of soluble B7 compared to sera from mice without liver injury. Plasma exchange reduced circulating levels of soluble B7 in patients with ALF and expression of CTLA4 on T cells., Conclusions: Peripheral CD4 + T cells from patients with ALF have increased expression of CTLA4 compared to individuals without ALF; these cells have a reduced response to antigen and CD3 stimulation. We found sera of patients with ALF and from mice with liver injury to have high concentrations of soluble B7, which up-regulates CTLA4 expression by T cells and reduces their response to antigen. Plasma exchange reduces levels of B7 in sera from patients with ALF and might be used to restore antimicrobial responses to patients., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The profound hemodynamic changes seen in acute liver failure (ALF) resemble the hyperdynamic state found in the later stages of septic shock. Vasopressor support frequently is required after initial volume therapy. Markers of preload dependency have not been studied in this patient group. Dynamic maneuvers such as passive leg raising or end-expiratory hold, which have shown good predictive accuracy in a general intensive care unit population, cannot be considered safe in this cohort because of the concerns of intracranial hypertension., Methods: Mechanically ventilated patients with ALF admitted to a tertiary specialist intensive care unit in shock and multiorgan failure were enrolled. Markers of fluid responsiveness derived from transpulmonary thermodilution, pulse contour analysis, and echocardiography were compared between responders (cardiac index ≥15%) and nonresponders to a colloid fluid challenge (5 mL/kg predicted body weight). The ability to predict fluid responsiveness of stroke volume variation, pulse pressure variation (PPV), and respiratory change in peak (delta V peak) left ventricular outflow tract velocity for preload dependency were analyzed., Results: Thirty-five patients (mean ± SD age, 38 [14] years, 13 male, 22 female]) were assessed after a single fluid challenge. Ten patients (29%) were fluid responders. Changes in cardiac index and stroke volume index in the cohort of 35 patients were correlated (R = 0.726 [99% confidence interval, 0.401-0.910]; P < .001). PPV predicted fluid responsiveness (area under the receiver operating characteristic curve [AUROC], 0.752 [95% confidence interval, 0.565-0.889]; P = .005; cutoff >9%). The AUROC for stroke volume variation was 0.678 ([95% confidence interval, 0.499-0.825]; P = .084; cutoff >11%). The AUROC for [delta] V peak before fluid bolus was 0.637 (95% confidence interval, 0.413-0.825; P = .322)., Conclusions: PPV based on pulse contour analysis predicted fluid responsiveness in ALF.

Background: Early, accurate prediction of survival is central to management of patients with paracetamol-induced acute liver failure to identify those needing emergency liver transplantation. Current prognostic tools are confounded by recent improvements in outcome independent of emergency liver transplantation, and constrained by static binary outcome prediction. We aimed to develop a simple prognostic tool to reflect current outcomes and generate a dynamic updated estimation of risk of death., Methods: Patients with paracetamol-induced acute liver failure managed at intensive care units in the UK (London, Birmingham, and Edinburgh) and Denmark (Copenhagen) were studied. We developed prognostic models, excluding patients who underwent transplantation, using Cox proportional hazards in a derivation dataset, and tested in initial and recent external validation datasets. Mortality was estimated in patients who had emergency liver transplantation. Model discrimination was assessed using area under receiver operating characteristic curve (AUROC) and calibration by root mean square error (RMSE). Admission (day 1) variables of age, Glasgow coma scale, arterial pH and lactate, creatinine, international normalised ratio (INR), and cardiovascular failure were used to derive an initial predictive model, with a second (day 2) model including additional changes in INR and lactate., Findings: We developed and validated new high-performance statistical models to support decision making in patients with paracetamol-induced acute liver failure. Applied to the derivation dataset (n=350), the AUROC for 30-day survival was 0·92 (95% CI 0·88-0·96) using the day 1 model and 0·93 (0·88-0·97) using the day 2 model. In the initial validation dataset (n=150), the AUROC for 30-day survival was 0·89 (0·84-0·95) using the day 1 model and 0·90 (0·85-0·95) using the day 2 model. Assessment of calibration using RMSE in prediction of 30-day survival gave values of 0·1642 for the day 1 model and 0·0626 for the day 2 model. In the external validation dataset (n=412), the AUROC for 30-day survival was 0·91 (0·87-0·94) using the day 1 model and 0·91 (0·88-0·95) using the day 2 model, and assessment of calibration using RMSE gave values of 0·079 for the day 1 model and 0·107 for the day 2 model. Applied to patients who underwent emergency liver transplantation (n=116), median predicted 30-day survival was 51% (95% CI 33-85)., Interpretation: The models developed here show very good discrimination and calibration, confirmed in independent datasets, and suggest that many patients undergoing transplantation based on existing criteria might have survived with medical management alone. The role and indications for emergency liver transplantation in paracetamol-induced acute liver failure require re-evaluation., Funding: Foundation for Liver Research., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: There is a marked propensity for patients with acetaminophen-induced acute liver failure to develop sepsis, which may culminate in multiple organ failure and death. Toll-like receptors sense pathogens and induce inflammatory responses, but whether this is protective or detrimental in acetaminophen-induced acute liver failure remains unknown., Design, Setting, and Patients: We assessed Toll-like receptor expression on circulating neutrophils and their function in 24 patients with acetaminophen-induced acute liver failure and compared with 10 healthy controls., Interventions: Neutrophil Toll-like receptor 2, -4, and -9 expression and cytokine production and function were studied ex vivo at baseline and following stimulation with lipopolysaccharide, oligodeoxynucleotides, ammonium chloride, and interleukin-8. To examine the influence of acetaminophen-induced acute liver failure plasma and endogenous DNA on Toll-like receptors-9 expression, healthy neutrophils were incubated with acetaminophen-induced acute liver failure plasma with and without deoxyribonuclease-I., Measurements and Main Results: Circulating neutrophil Toll-like receptor 9 expression was increased in acetaminophen-induced acute liver failure on day 1 compared with healthy controls (p = 0.0002), whereas Toll-like receptor 4 expression was decreased compared with healthy controls (p < 0.0001). Toll-like receptor 2 expression was unchanged. Neutrophil phagocytic activity was decreased, and spontaneous oxidative burst increased in all patients with acetaminophen-induced acute liver failure compared with healthy controls (p < 0.0001). Neutrophil Toll-like receptor 9 expression correlated with plasma interleukin-8 and peak ammonia concentration (r = 0.6; p < 0.05) and increased with severity of hepatic encephalopathy (grade 0-2 vs 3/4) and systemic inflammatory response syndrome score (0-1 vs 2-4) (p < 0.05). Those patients with advanced hepatic encephalopathy (grade 3/4) or high systemic inflammatory response syndrome score (2-4) on day 1 had higher neutrophil Toll-like receptor 9 expression, arterial ammonia concentration, and plasma interleukin-8 associated with neutrophil exhaustion. Healthy neutrophil Toll-like receptor 9 expression increased upon stimulation with acetaminophen-induced acute liver failure plasma, which was abrogated by preincubation with deoxyribonuclease-I. Intracellular Toll-like receptor 9 was induced by costimulation with interleukin-8 and ammonia., Conclusion: These data point to neutrophil Toll-like receptor 9 expression in acetaminophen-induced acute liver failure being mediated both by circulating endogenous DNA as well as ammonia and interleukin-8 in a synergistic manner inducing systemic inflammation, neutrophil exhaustion, and exacerbating hepatic encephalopathy.

Objective: Prognostic stratification of patients with cirrhosis is common clinical practice. This study compares the prognostic accuracy (28-day and 90-day transplant-free mortality) of the acute-on-chronic liver failure (ACLF) classification (no ACLF, ACLF grades 1, 2 and 3) with that of acute kidney injury (AKI) classification (no AKI, AKI stages 1, 2 and 3)., Design: The study was performed in 510 patients with an acute decompensation of cirrhosis previously included in the European Association for the Study of the Liver-Chronic Liver Failure consortium CANONIC study. ACLF was evaluated at enrollment and 48 h after enrollment, and AKI was evaluated at 48 h according to Acute Kidney Injury Network criteria., Results: 240 patients (47.1%) met the criteria of ACLF at enrollment, while 98 patients (19.2%) developed AKI. The presence of ACLF and AKI was strongly associated with mortality. 28-day transplant-free mortality and 90-day transplant-free mortality of patients with ACLF (32% and 49.8%, respectively) were significantly higher with respect to those of patients without ACLF (6.2% and 16.4%, respectively; both p<0.001). Corresponding values in patients with and without AKI were 46% and 59%, and 12% and 25.6%, respectively (p<0.0001 for both). ACLF classification was more accurate than AKI classification in predicting 90-day mortality (area under the receiving operating characteristic curve=0.72 vs 0.62; p<0.0001) in the whole series of patients. Moreover, assessment of ACLF classification at 48 h had significantly better prognostic accuracy compared with that of both AKI classification and ACLF classification at enrollment., Conclusions: ACLF stratification is more accurate than AKI stratification in the prediction of short-term mortality in patients with acute decompensation of cirrhosis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background & Aims: During the past decade, survival has increased among patients admitted to general intensive care units, but it is not clear if it has increased for patients admitted with cirrhosis and organ failure. The chronic liver failure-sequential organ failure assessment (CLIF-SOFA) recently was developed as an adaptation to the SOFA to predict outcomes of patients, but requires validation. We investigated changes in outcomes of patients with cirrhosis and organ failure since 2000, compared the abilities of SOFA and CLIF-SOFA to predict patient survival, and validated the CLIF-SOFA system., Methods: In a retrospective study, we collected data from 971 patients (median age, 52 y; age range, 16-90 y; 62% male) with cirrhosis (54% alcohol associated, 12% viral, and 34% other causes). The patients were admitted under emergency conditions from January 1, 2000, to December 31, 2010, to a liver intensive therapy unit in the United Kingdom. Patient survival while in the hospital was compared with measures of illness severity, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, model for end-stage liver disease (MELD) scores, SOFA scores, and CLIF-SOFA scores., Results: Patients had a median APACHE II score of 21 (range, 5-50) and a median MELD score of 23 (range, 6-40). The median APACHE II score at admission decreased from 23 to 22 over the study period (P < .001), whereas the median MELD score at admission decreased from 23 to 18 (P < .001). Overall survival until hospital discharge was 51%; this value increased from 40% in 2000 to 63% in 2010 (P < .001). The unadjusted odds ratio for change in mortality/year was 0.87 (95% confidence interval, 0.83-0.91; P < .001). The APACHE II score adjusted odds ratio for mortality was 0.89 (95% confidence interval, 0.84-0.93; P < .001). The etiology of cirrhosis was not associated with a significant difference in survival. CLIF-SOFA and SOFA scores at the time of admission predicted patient survival with area under the receiver operating curve (AUROC) values of 0.813 and 0.799, respectively; the scores at 48 hours after admission predicted survival with AUROC values of 0.853 and 0.840, and scores after 1 week predicted survival with AUROC values of 0.842 and 0.844, respectively. These AUROC values were higher than those obtained from APACHE II or MELD scores., Conclusions: The proportion of patients with cirrhosis who survived after admission to intensive care increased from 2000 to 2010. SOFA and CLIF-SOFA scores during the first week of critical care appear to have similar abilities to predict patient survival., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: To establish the relationship between CT signs of pulmonary hypertension and mean pulmonary artery pressure (mPAP) in patients with liver disease, and to determine the additive value of CT in the detection of portopulmonary hypertension in combination with transthoracic echocardiography., Methods: Forty-nine patients referred for liver transplantation were retrospectively reviewed. Measured CT signs included the main pulmonary artery/ascending aorta diameter ratio (PA/AAmeas) and the mean left and right main PA diameter (RLPAmeas). Enlargement of the pulmonary artery compared to the ascending aorta was also assessed visually (PA/AAvis). CT measurements were correlated with right-sided heart catheter-derived mPAP. The ability of PA/AAvis combined with echocardiogram-derived right ventricular systolic pressure (RVSP) to detect portopulmonary hypertension was tested with ROC analysis., Results: There were moderate correlations between mPAP and both PA/AAmeas and RLPAmeas (rs = 0.41 and rs = 0.42, respectively; p < 0.005). Compared to transthoracic echocardiography alone (AUC = 0.59, p = 0.23), a diagnostic algorithm incorporating PA/AAvis and transthoracic echocardiography-derived RVSP improved the detection of portopulmonary hypertension (AUC = 0.8, p < 0.0001)., Conclusions: CT contributes to the non-invasive detection of portopulmonary hypertension when used in a diagnostic algorithm with transthoracic echocardiography. CT may have a role in the pre-liver transplantation triage of patients with portopulmonary hypertension for right-sided heart catheterisation., Key Points: • CT signs correlate with right-sided heart catheter data in portopulmonary hypertension • CT adds to the transthoracic echocardiography detection of portopulmonary hypertension • CT may have a complementary role in pre-liver transplantation triage.

Purpose of Review: Acute liver failure (ALF) is associated with significant mortality. Although specific therapies may be available, the evidence base for these and for many aspects of supportive therapy has been slow to emerge. Liver transplantation continues to be a cornerstone of treatment, and the management of ALF, therefore, remains the domain of the specialist ICU. The purpose of this review is to identify and critically appraise the recent evidence and to inspire those who strive to provide excellent care for a difficult patient cohort., Recent Findings: Effective vaccination programmes have reduced the incidence of viral hepatitis in Europe and the USA. Spontaneous survival has improved in causes such as acetaminophen toxicity. Early recognition and proactive intensive management have reduced the incidence of early neurological death. The use of artificial liver assist devices and therapeutic plasma exchange is controversial, yet intriguing, with some early evidence of efficacy., Summary: Increasingly sophisticated prognostication tools are evolving, which have the potential to transform clinical decision-making. A review of the indications for transplantation in acetaminophen toxicity is overdue. The use of therapeutic plasma exchange and extracorporeal liver support in ALF requires further investigation.

Background & Aims: Acute-on-chronic liver failure (ACLF) has a rapidly progressive disease course associated with significant mortality. The prevalence of clinically significant cerebral oedema in ACLF is unknown., Methods: We aimed to describe the prevalence of cerebral oedema in a cohort of ACLF adult (>18 years). We identified patients admitted to a single, specialist intensive care unit between January 2005 and January 2011 with high-grade hepatic encephalopathy (≥3) and a clinical picture of either ACLF or chronic liver disease (CLD). Patients who had undergone cranial CT imaging were identified and their imaging reviewed. The ACLF and CLD groups were compared., Results: One thousand and eight patients with CLD were admitted. One hundred and seventy-three patients (110 male) underwent neuroimaging. Eighty-one (48 male) fulfilled criteria for ACLF. Variceal bleeding (30%) and sepsis (31%) were the most frequent precipitants of ACLF. Of those with neuroimaging from the total cohort, 30% of CT scans were normal, 30% demonstrated increased cerebral atrophy for age, 17% small vessel disease and 16% intracranial haemorrhage (ICH). Cerebral oedema was seen in three patients with ACLF only. An increased prevalence of ICH was observed in the ACLF group (23% vs. 9%, P = 0.008)., Conclusion: The prevalence of clinically relevant cerebral oedema was low (4%) but fatal. Death was attributable to tonsillar herniation. An increased prevalence of ICH was seen in ACLF patients and remains an important differential., (© 2013 John Wiley & Sons A/S. Publishing by John Wiley & Sons Ltd.)

Objective: Hypoxemia is a feared complication of acute liver failure, and high oxygen requirements will frequently lead to removal of patients from the transplant list. As data regarding the prevalence and outcome of acute respiratory distress syndrome in acute liver failure are scant and hypoxemia being a commonly encountered systemic complication, we analyzed radiological, gas exchange, and ventilator data in consecutive patients admitted with acute liver failure., Patients: Acute liver failure patients receiving mechanical ventilation admitted between January 2007 and February 2011 were included., Interventions: Patients were categorized according to the Berlin definition as: no acute respiratory distress syndrome, acute respiratory distress syndrome (PaO2/FIO2 < 300 mm Hg), and subdivisions of mild, moderate, and severe acute respiratory distress syndrome (200-300 mm Hg, 100-200 mm Hg, and < 100 mm Hg, respectively). Chest radiographs were independently assessed by two observers for the presence or absence of acute respiratory distress syndrome. Absence of left atrial pressure elevation was based on combined hemodynamic and echocardiographic assessment., Measurements and Main Results: Two hundred acute liver failure patients were admitted during the study period of whom 148, median age 39 years (16-74 yr), were included. Thirty-one (21%) had acute respiratory distress syndrome (17 mild acute respiratory distress syndrome [12%], 9 moderate acute respiratory distress syndrome [12%], and 5 severe acute respiratory distress syndrome) within the first 72 hours following admission. Acute respiratory distress syndrome patients required higher positive end-expiratory pressure (7 vs 6 vs 10 vs 15 cm H2O for no, mild, moderate, or severe acute respiratory distress syndrome, p = 0.014), had reduced respiratory system compliance (34 vs 29 vs 30 vs 23 L/cm H2O, p = 0.028), and an increased number of ventilator days (no acute respiratory distress syndrome, 10 d; mild acute respiratory distress syndrome acute lung injury, 12 d; moderate acute respiratory distress syndrome, 23 d; severe acute respiratory distress syndrome, 22 d; p = 0.097). Duration of liver intensive therapy unit stay (p = 0.175), survival (p = 0.877), inotrope requirements (p = 0.495), need for extracorporeal renal support (p = 0.565), and severity of organ failure scores were not affected. Extravascular lung water index had a moderate sensitivity of 65% and specificity of 77% for the prediction of acute respiratory distress syndrome., Conclusion: The prevalence of lung injury is relatively low in acute liver failure, where 21% fulfilled acute respiratory distress syndrome criteria. Overall presence of acute respiratory distress syndrome appeared to have a limited impact on outcome.

Background & Aims: Ammonia is recognized as a toxin central to complications of liver failure. Hyperammonaemia has important clinical consequences, but optimal means to reduce circulating levels are uncertain. In patients with liver disease, continuous renal replacement therapy (CRRT) with haemofiltration (HF) is often required to treat concurrent kidney injury, but its effects upon ammonia levels are poorly characterized. To evaluate the effect of HF at different treatment intensities on ammonia clearance (AC) and arterial ammonia concentration., Methods: Prospective study of adult patients with liver failure and arterial ammonia >100 μmol/L requiring CRRT using veno-venous HF. Arterial ammonia concentration and AC measured at 1 and 24 h after initiation of low (35 ml/kg/h) or high (90 ml/kg/h) filtration volume., Results: Twenty-four patients (10 acute liver failure, 10 chronic liver disease and 4 following liver resection) were studied. Clearance of urea and ammonia solutes correlated closely (r = 0.819, P = 0.007). Ammonia clearance correlated closely with ultrafiltration rate (r = 0.86, P < 0.001). At 1 h, AC was 39 (34-54) ml/min (low volume) vs 85 (62-105) ml/min (high volume) CRRT, (P < 0.001) and at 24 h 44 (34-63) vs 105 (82-109) ml/min, (P = 0.01). Overall, a 22% reduction in median arterial ammonia concentration was observed over 24 h of HF from 156 (137-176) to 122 (85-133) μmol/L, (P ≤ 0.0001)., Conclusion: Clinically significant ammonia clearance can be achieved in adult patients with hyperammonaemia utilizing continuous VVHF. Ammonia clearance is closely correlated with ultrafiltration rate. HF was associated with a fall in arterial ammonia concentration., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Chronic liver disease (CLD) is associated with muscle wasting, reduced exercise tolerance and aerobic capacity (AC). Measures of AC determined with cardiopulmonary exercise testing (CPET) may predict survival after liver transplantation (LT), but the relationship with nontransplant outcomes is uncertain. In patients assessed for LT, we examined the relationship of CPET AC parameters with the severity of liver disease, nutritional state, and survival with and without LT. Patients assessed for elective first LT who underwent CPET and an anthropometric assessment at a single center were studied. CPET-derived measures of AC that were evaluated included the peak oxygen consumption (VO2 peak) and the anaerobic threshold (AT). Three hundred ninety-nine patients underwent CPET, and 223 underwent LT; 45% of the patients had a VO2 peak < 50% of the predicted value, and 31% had an AT < 9 mL/kg/minute. The VO2 peak and AT values correlated with the Model for End-Stage Liver Disease score, but they more closely correlated with serum sodium and albumin levels. The handgrip strength correlated strongly with the VO2 peak. Patients with impaired AC had prolonged hospitalization after LT, and nonsurvivors had lower AT values than survivors 1 year after transplantation (P < 0.05); this was significant in a multivariate analysis. One hundred seventy-six patients did not undergo LT; the 1-year mortality rate was 34.6%. The AT (P < 0.05) and VO2 peak values (P < 0.001) were lower for nonsurvivors. In a multivariate analysis, AT was independently associated with nonsurvival. In conclusion, AC was markedly impaired in many patients with CLD. In patients who did not undergo transplantation, impaired AT was predictive of mortality, and in patients undergoing LT, it was related to postoperative hospitalization and survival. AC should be evaluated as a modifiable factor for improving patient survival whether or not LT is anticipated., (© 2013 American Association for the Study of Liver Diseases.)

Unlabelled: There are no studies regarding to these effects in patients with severe liver dysfunction., Objectives: The aims of this study were to characterize voriconazole hepatotoxicity in patients with severe liver dysfunction and to compare it with a matched cohort treated with liposomal amphotericin B., Methods: This is an observational study, in which adults patients treated with at least 4 doses of voriconazole were included. Patients treated with liposomal amphotericin B were used as control group., Results: Sixty nine percent of patients treated with voriconazole showed changes in liver function tests (LFTs) during therapy. They showed elevated transaminases in 35%, cholestasis in 15% or a combination of both in 45%. According to the CTC classification, all patients with hepatotoxicity had a severe reaction. The Roussel Uclaf Causality Assessment Method score in all patients with hepatotoxicity was greater than 8. There was a correlation between initial loading dose greater than 300 mg (4.5 mg/kg) and the risk of hepatotoxicity (p < 0.001). The control group developed alterations in the LFTs in only 10.3% of patients., Conclusion: Voriconazole should be used with caution in patients with severe liver dysfunction and following liver transplantation, with frequent monitoring of LFTs or using liposomal amphotericin B instead., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

Introduction: Acute liver failure (ALF) is a life-threatening multisystem illness complicated by multiple organ failure (MOF) and haemodynamic disturbances. Morbidity and mortality remains high and various prognostic and scoring models are in use to predict outcome. A recent observation in a large cohort of ALF patients suggested a prognostic value of troponin I (cTnI) and its role as a marker of subclinical myocardial injury and outcome., Methods: Data from consecutive ALF patients over a four-year period from January 2007 to March 2011 were included. The aim of this study was to correlate any relationship that may exist between cTnI, mortality, severity of illness and non-hepatic organ failure., Results: A total of 218 subjects (age 36 (16 to 90) years, M:F 103:115) were studied, of which 136 had an elevated cTnI > 0.05 μg/L. Higher organ failure scores were found with positive cTnI: APACHE II (19.5 (3 to 51) vs 14 (2 to 51), P = 0.001), APACHE III (81 (15 to 148) vs 59 (8 to 172), P = < 0.001) SOFA (15 (4 to 20) vs 13 (2 to 21), P = 0.027) and SAPS (48 (12 to 96) vs 34 (12 to 97), P = 0.001). Patients with positive cTnI had higher serum creatinine (192 μmol/l (38 to 550) vs 117 μmol/l (46 to 929), P < 0.001), arterial lactate (0.25, P < 0.001) and a lower pH (-0.21, P = 0.002). Also a higher proportion required renal replacement therapy (78% vs 60%, P = 0.006). Patients with elevated cTnI more frequently required vasopressors-norepinephrine (73% vs 50%, P = 0.008). Elevated cTnI did not predict outcome as effectively as other models (AUROC 0.61 (95% CI 0.52 to 0.68))., Conclusions: More than 60% of ALF patients in this study demonstrated elevated cTnI. Despite a close correlation with organ failure severity, cTnI was a poor independent predictor of outcome. cTnI may not represent true myocardial injury and may be better viewed as a marker of metabolic stress.

Background: There is growing evidence that optimal peri-operative fluid management in high-risk surgical patients improves their post-operative outcome. Functional haemodynamic parameters such as SVV (stroke volume variation), PPV (pulse pressure variation) and SPV (systolic pressure variation) have been shown to be superior to CVP (central venous pressure) and ΔCVP in predicting fluid responsiveness. The aim of this study was to determine the accuracy and threshold values of these dynamic parameters using the minimally invasive LiDCORapid™ in high-risk surgical patients., Methods: Fluid therapy in 70 patients undergoing vascular surgery was based on parameters derived from the LiDCORapid™. All patients received TIVA (total intravenous anaesthesia) and were ventilated with ≥7 ml/kg tidal volume. Haemodynamic data before and after fluid boluses were recorded and analyzed retrospectively. ΔSVI (stroke volume index) ≥10% was determined to be a positive response to a fluid challenge. The AUROCs (area under the receiver-operator curves) and confidence intervals thereof were used to assess the ability of each parameter to predict fluid responsiveness., Results: 32/43 fluid challenges were positive (74.4%). The correlation coefficients between baseline SVV, PPV, and SPV with ΔSVI were: 0.27 (p = 0.08), 0.18 (p = 0.25) and -0.01 (p = 0.96) whilst the AUROCs were 0.75 (0.57-0.93), 0.67 (0.48-0.85) and 0.58 (0.35-0.81) respectively. The best cut-off for SVV using Youden's index was 13.5%, with J = 0.48. At this level, the LR+ (positive likelihood ratio) = 2.74, LR- (negative likelihood ratio) = 0.34 and the DOR (diagnostic odds ratio) = 8.06., Conclusion: Only the SVV was an adequate predictor of fluid responsiveness in this cohort of high risk surgical patients. Whereas PPV and SPV may be obtained from the arterial trace, estimation of the SVV requires a cardiac output monitor which is able to convert an arterial pressure trace into an estimation of stroke volume., (Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose of Review: The incidence of cirrhosis is growing steadily and this cohort of patients will present in ever-greater numbers to critical care with acute decompensation, usually secondary to an inter-current event or following elective surgery. This review examines the evidence for treatment options and outcomes., Recent Findings: Outcome of cirrhotics presenting with end-organ dysfunction is steadily improving and their outcomes are not as poor as sometimes suggested. Treatment options for variceal bleeding and renal dysfunction are evolving and outcomes improving., Summary: Critical care support should be offered to patients with cirrhosis and in high-risk variceal bleed patients transhepatic portosystemic shunt should be considered.