Evolution of Clinical Characteristics and Outcomes of Critically Ill Patients 90 Years Old or Older Over a 12-Year Period: A Retrospective Cohort Study.

OBJECTIVES: The global population is aging, and the proportion of very elderly patients 90 years old or older in the ICU is expected to increase. The changes in the comorbidities and outcomes of very elderly patients hospitalized in the ICU that have occurred over time are unknown. DESIGN: Retrospective observational cohort study. SETTING: ICUs at a single academic hospital in Germany. PATIENTS: Ninety years old or older and admitted to the ICU between January 1, 2008, and April 30, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 92,958 critically ill patients, 1,108 were 90 years old or older. The study period was divided into two halves: January 1, 2008-August 30, 2013, and September 1, 2013-April 30, 2019. The number of patients 90 years old or older increased from the first period ( n = 391; 0.90% of total admissions) to the second period ( n = 717; 1.44%). The patients' demographic characteristics were similar between the both time periods. The median Charlson Comorbidity Index was higher during the first period (1 [interquartile range, 1-3]) than compared with the second time period (1 [0-2]; p = 0.052). The Simplified Acute Physiology Score (SAPS) II was higher during the first time period (38 [29-49]) than during the second period (35 [27-45]; p = 0.005). Vasopressor therapy was necessary in 40% ( n = 158) and 43% ( n = 310) of patients in each time period, respectively ( p = 0.363). Invasive mechanical ventilation was administered in 37% ( n = 146) and 34% ( n = 243) of patients in each time period, respectively ( p = 0.250). The median length of the ICU stay was significantly lower in the first time period than in the second time period (1.4 vs. 1.7 d; p = 0.002). The ICU (18% vs. 18%; p = 0.861) and hospital (31% vs. 29%; p = 0.395) mortality rates were comparable between the two groups. The 1-year mortality was significantly lower during the second time period than during the first time period (61% vs. 56%; p = 0.029). Cox regression analysis revealed that the SAPS II, medical cause of admission, mechanical ventilation requirement, and vasopressor use were associated with 1-year mortality. CONCLUSIONS: The number of patients 90 years old or older who were treated in the ICU has increased in recent years. While the patients' clinical characteristics and short-term outcomes have not changed significantly, the long-term mortality of these patients has improved in recent years.

Dual-Energy CT muscle fat fraction as a new imaging biomarker of body composition and survival predictor in critically ill patients.

OBJECTIVE: To analyze changes in the muscular fat fraction (FF) during immobilization at the intensive care unit (ICU) using dual-energy CT (DECT) and evaluate the predictive value of the DECT FF as a new imaging biomarker for morbidity and survival. METHODS: Immobilized ICU patients (n = 81, 43.2% female, 60.3 ± 12.7 years) were included, who received two dual-source DECT scans (CT1, CT2) within a minimum interval of 10 days between 11/2019 and 09/2022. The DECT FF was quantified for the posterior paraspinal muscle by two radiologists using material decomposition. The skeletal muscle index (SMI), muscle radiodensity attenuation (MRA), subcutaneous-/ visceral adipose tissue area (SAT, VAT), and waist circumference (WC) were assessed. Reasons for ICU admission, clinical scoring systems, therapeutic regimes, and in-hospital mortality were noted. Linear mixed models, Cox regression, and intraclass correlation coefficients were employed. RESULTS: Between CT1 and CT2 (median 21 days), the DECT FF increased (from 20.9% ± 12.0 to 27.0% ± 12.0, p = 0.001). The SMI decreased (35.7 cm2/m2 ± 8.8 to 31.1 cm2/m2 ± 7.6, p < 0.001) as did the MRA (29 HU ± 10 to 26 HU ± 11, p = 0.009). WC, SAT, and VAT did not change. In-hospital mortality was 61.5%. In multivariable analyses, only the change in DECT FF was associated with in-hospital mortality (hazard ratio (HR) 9.20 [1.78-47.71], p = 0.008), renal replacement therapy (HR 48.67 [9.18-258.09], p < 0.001), and tracheotomy at ICU (HR 37.22 [5.66-245.02], p < 0.001). Inter-observer reproducibility of DECT FF measurements was excellent (CT1: 0.98 [0.97; 0.99], CT2: 0.99 [0.96-0.99]). CONCLUSION: The DECT FF appears to be suitable for detecting increasing myosteatosis. It seems to have predictive value as a new imaging biomarker for ICU patients. CLINICAL RELEVANCE STATEMENT: The dual-energy CT muscular fat fraction appears to be a robust imaging biomarker to detect and monitor myosteatosis. It has potential for prognosticating, risk stratifying, and thereby guiding therapeutic nutritional regimes and physiotherapy in critically ill patients. KEY POINTS: The dual-energy CT muscular fat fraction detects increasing myosteatosis caused by immobilization. Change in dual-energy CT muscular fat fraction was a predictor of  in-hospital morbidity and mortality. Dual-energy CT muscular fat fraction had a predictive value superior to established CT body composition parameters.

Temperature Control After In-Hospital Cardiac Arrest: A Randomized Clinical Trial.

BACKGROUND: This study was conducted to determine the effect of hypothermic temperature control after in-hospital cardiac arrest (IHCA) on mortality and functional outcome as compared with normothermia. METHODS: An investigator initiated, open-label, blinded-outcome-assessor, multicenter, randomized controlled trial comparing hypothermic temperature control (32-34°C) for 24 h with normothermia after IHCA in 11 hospitals in Germany. The primary endpoint was all-cause mortality after 180 days. Secondary end points included in-hospital mortality and favorable functional outcome using the Cerebral Performance Category scale after 180 days. A Cerebral Performance Category score of 1 or 2 was defined as a favorable functional outcome. RESULTS: A total of 1055 patients were screened for eligibility and 249 patients were randomized: 126 were assigned to hypothermic temperature control and 123 to normothermia. The mean age of the cohort was 72.6±10.4 years, 64% (152 of 236) were male, 73% (166 of 227) of cardiac arrests were witnessed, 25% (57 of 231) had an initial shockable rhythm, and time to return of spontaneous circulation was 16.4±10.5 minutes. Target temperature was reached within 4.2±2.8 hours after randomization in the hypothermic group and temperature was controlled for 48 hours at 37.0°±0.9°C in the normothermia group. Mortality by day 180 was 72.5% (87 of 120) in hypothermic temperature control arm, compared with 71.2% (84 of 118) in the normothermia group (relative risk, 1.03 [95% CI, 0.79-1.40]; P=0.822). In-hospital mortality was 62.5% (75 of 120) in the hypothermic temperature control as compared with 57.6% (68 of 118) in the normothermia group (relative risk, 1.11 [95% CI, 0.86-1.46, P=0.443). Favorable functional outcome (Cerebral Performance Category 1 or 2) by day 180 was 22.5% (27 of 120) in the hypothermic temperature control, compared with 23.7% (28 of 118) in the normothermia group (relative risk, 1.04 [95% CI, 0.78-1.44]; P=0.822). The study was prematurely terminated because of futility. CONCLUSIONS: Hypothermic temperature control as compared with normothermia did not improve survival nor functional outcome at day 180 in patients presenting with coma after IHCA. The HACA in-hospital trial (Hypothermia After Cardiac Arrest in-hospital) was underpowered and may have failed to detect clinically important differences between hypothermic temperature control and normothermia. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique Identifier: NCT00457431.

The Independent Impact of Peripheral Arterial Disease on Mortality in Nonagenarians and Centenarians Who Were Treated in an Intensive Care Unit: A Consecutive Cohort of 1 108 Patients.

OBJECTIVE: To investigate the clinical characteristics, risk factors, and outcomes of inpatients with peripheral arterial disease (PAD) including lower extremity PAD, abdominal aortic aneurysm (AAA), and carotid artery disease in a large cohort of critically ill patients aged ≥ 90 years. METHODS: A retrospective analysis was conducted of all adult patients aged ≥ 90 years consecutively admitted to the intensive care unit at a tertiary care centre in Hamburg, Germany, between 1 January 2008 and 30 April 2019. Multivariable regression and Kaplan-Meier methods were used to determine the independent impact of PAD on short and long term mortality endpoints. The analyses were adjusted for confounding by several sociodemographic and clinical parameters including Charlson Comorbidity Index (CCI) and established clinical risk scores. RESULTS: A total of 1 108 eligible patients were identified (92.3 years, 33% men). Of these, 24% had PAD (9% lower extremity PAD, 2% AAA, 15% coronary artery disease) and 76% did not have any history of PAD and were used as a comparison group. When compared with the comparison group, patients with PAD had a higher CCI (2 vs. 1, p < .001), more often had chronic kidney disease (28% vs. 21%, p = .019), and renal replacement therapy (5% vs. 2%, p = .016). Furthermore, they needed vasopressors (48% vs. 40%, p = .027) and parenteral nutrition (10% vs. 6%, p = .041) more often. After adjusting for confounding, PAD was independently associated with increased in hospital (hazard ratio [HR] 1.97, 95% confidence interval [CI] 1.39 - 2.81, p < .001) and long term mortality rates (HR 1.32, 95% CI 1.05 - 1.66, p = .019). CONCLUSION: One of four critically ill nonagenarians and centenarians in an ICU in Germany had PAD. PAD was associated with both higher short and long term mortality rates while its impact outweighed higher age. Future studies should address this increasingly important population beyond 89 years of age.

Temperature control in adults after cardiac arrest: a survey of current clinical practice in Germany.

BACKGROUND: Temperature control is recommended after out of hospital cardiac arrest (OHCA) by international guidelines. This survey aimed to investigate current clinical practice and areas of uncertainty. METHODS: Online survey targeting members of three medical emergency and critical care societies in Germany (April 21-June 6, 2022) assessing post-cardiac arrest temperature control management. RESULTS: Of 341 completed questionnaires 28% (n = 97) used temperature control with normothermic target and 72% (n = 244) temperature control with hypothermic target. The definition of fever regarding patients with cardiac arrest ranged from ≥ 37.7 to 39.0 °C. Temperature control was mainly started in the ICU (80%, n = 273) and most commonly core cooling (74%, n = 254) and surface cooling (39%, n = 134) with feedback were used. Temperature control was maintained for 24 h in 18% (n = 61), 48 h in 28% (n = 94), 72 h in 42% (n = 143) and longer than 72 h in 13% (n = 43). 7% (n = 24) were using different protocols for OHCA with initial shockable and non-shockable rhythm. Additional 14% (n = 48) were using different temperature control protocols after in-hospital cardiac arrest (IHCA) compared with OHCA. Overall, 37% (n = 127) changed practice after the publication of the ERC-2021 guidelines and 33% (n = 114) after the recent publication of the revised ERC-ESICM guideline on temperature control. CONCLUSIONS: One-third of the respondents changed clinical practice since recent guideline update. However, a majority of physicians further trusts in temperature control with a hypothermic target. Of interest, 14% used different temperature control strategies after IHCA compared with OHCA and 7% for shockable and non-shockable initial rhythm. A more individualized approach in post resuscitation care may be warranted.

Occurrence, Characteristics, and Outcome of Hypoxic Liver Injury among Patients Aged ≥90 Years Admitted to the Intensive Care Unit: A Retrospective Cohort Study.

INTRODUCTION: Hypoxic liver injury (HLI) is a frequent and life-threatening complication occurring in up to 10% of critically ill patients. Heart failure and age were previously identified as risk factors for occurrence of HLI. However, there is lack of data on incidence of HLI and its clinical implications on outcome in very old (≥90 years) patients. The aim of this study was to investigate occurrence, clinical characteristics, and outcome of HLI in critically ill patients ≥90 years. METHODS: This is a retrospective analysis of all consecutive critically ill patients ≥90 years admitted to the intensive care unit (ICU) of a tertiary care university hospital in Hamburg, Germany. Clinical course and laboratory data were analyzed for all patients. HLI was defined according to established criteria as elevation of aminotransferase levels (>20-fold upper limit of normal). Predictors of HLI occurrence, clinical course, and outcome were assessed and compared to those of patients without HLI. RESULTS: In total, 1,065 critically ill patients ≥90 years were included. During the ICU stay, 3% (n = 35) developed HLI. Main causes of HLI were cardiogenic shock (51%, n = 18), septic shock (23%, n = 8), and cardiac arrest (20%, n = 7). Presenting characteristics including age, gender, and BMI were comparable between patients with and without HLI. The admission cause was primary medical (HLI: 49% vs. No-HLI: 34%, p = 0.07), surgical - planned (9% vs. 38%, p < 0.001), and surgical - emergency (43% vs. 28%, p = 0.06). The median Charlson Comorbidity Index (CCI) and the median updated CCI were 2 (1-3) and 2 (1-2) points in patients with HLI and 1 (0-2) and 1 (0-2) in patients without HLI (p < 0.01 and p = 0.08). Patients with HLI presented with higher SAPS II (55 vs. 36 points p < 0.001) score on admission and required mechanical ventilation (66% vs. 34%, p < 0.001), vasopressor therapy (91% vs. 40%, p < 0.001), renal replacement therapy (20% vs. 2%, p < 0.001), and parenteral nutrition (29% vs. 7%, p < 0.001). The ICU mortality and hospital mortality in patients with HLI were 66% (n = 23) and 83% (n = 29) compared with 17% (n = 170) and 28% (n = 292) in patients without HLI, respectively (both p < 0.001). Regression analysis identified SAPS II (OR 1.05, 95% CI: [1.02-1.07]; p < 0.001) and vasopressor therapy (OR 9.21, 95% CI: [2.58-32.86]; p < 0.01) as factors significantly associated with new onset of HLI. Occurrence of HLI was independently associated with mortality (HR 2.23, 95% CI: [1.50-3.30]; p < 0.001). CONCLUSION: HLI is an uncommon but not rare condition in critically ill patients aged ≥90 years. Occurrence of HLI is associated with high mortality and is mainly caused by cardiogenic or septic shock. HLI may serve as early prognostic marker in critically ill patients aged ≥90 years.

Effect of Hemadsorption Therapy in Critically Ill Patients with COVID-19 (CYTOCOV-19): A Prospective Randomized Controlled Pilot Trial.

INTRODUCTION: Immunomodulatory therapies have shown beneficial effects in patients with severe COVID-19. Patients with hypercytokinemia might benefit from the removal of inflammatory mediators via hemadsorption. METHODS: Single-center prospective randomized trial at the University Medical Center Hamburg-Eppendorf (Germany). Patients with confirmed COVID-19, refractory shock (norepinephrine ≥0.2 µg/kg/min to maintain a mean arterial pressure ≥65 mm Hg), interleukin-6 (IL-6) ≥500 ng/L, and an indication for renal replacement therapy or extracorporeal membrane oxygenation were included. Patients received either hemadsorption therapy (HT) or standard medical therapy (SMT). For HT, a CytoSorb® adsorber was used for up to 5 days and was replaced every 18-24 h. The primary endpoint was sustained hemodynamic improvement (norepinephrine ≤0.05 µg/kg/min ≥24 h). RESULTS: Of 242 screened patients, 24 were randomized and assigned to either HT (N = 12) or SMT (N = 12). Both groups had similar severity as assessed by SAPS II (median 75 points HT group vs. 79 SMT group, p = 0.590) and SOFA (17 vs. 16, p = 0.551). Median IL-6 levels were 2,269 (IQR 948-3,679) and 3,747 (1,301-5,415) ng/L in the HT and SMT groups at baseline, respectively (p = 0.378). Shock resolution (primary endpoint) was reached in 33% (4/12) versus 17% (2/12) in the HT and SMT groups, respectively (p = 0.640). Twenty-eight-day mortality was 58% (7/12) in the HT compared to 67% (8/12) in the SMT group (p = 1.0). During the treatment period of 5 days, 6/12 (50%) of the SMT patients died, in contrast to 1/12 (8%) in the HT group. CONCLUSION: HT was associated with a non-significant trend toward clinical improvement within the intervention period. In selected patients, HT might be an option for stabilization before transfer and further therapeutic decisions. This finding warrants further investigation in larger trials.

The prevalence of early- and late-onset bacterial, viral, and fungal respiratory superinfections in invasively ventilated COVID-19 patients.

The role of respiratory superinfections in patients with coronavirus disease 2019 (COVID-19) pneumonia remains unclear. We investigated the prevalence of early- and late-onset superinfections in invasively ventilated patients with COVID-19 pneumonia admitted to our department of intensive care medicine between March 2020 and November 2020. Of the 102 cases, 74 (72.5%) received invasive ventilation and were tested for viral, bacterial, and fungal pathogens on Days 0-7, 8-14, and 15-21 after the initiation of mechanical ventilation. Approximately 45% developed one or more respiratory superinfections. There was a clear correlation between the duration of invasive ventilation and the prevalence of coinfecting pathogens. Male patients with obesity and those suffering from chronic obstructive pulmonary disease and/or diabetes mellitus had a significantly higher probability to develop a respiratory superinfection. The prevalence of viral coinfections was high, with a predominance of the herpes simplex virus (HSV), followed by cytomegalovirus. No respiratory viruses or intracellular bacteria were detected in our cohort. We observed a high coincidence between Aspergillus fumigatus and HSV infection. Gram-negative bacteria were the most frequent pathogen group. Klebsiella aerogenes was detected early after intubation, while Klebsiella pneumoniae and Pseudomonas aeruginosa were related to a prolonged respiratory weaning.

MR-proAdrenomedullin as a predictor of renal replacement therapy in a cohort of critically ill patients with COVID-19.

BACKGROUND: About 20% of ICU patients with COVID-19 require renal replacement therapy (RRT). Mid-regional pro-adrenomedullin (MR-proADM) might be used for risk assessment. This study investigates MR-proADM for RRT prediction in ICU patients with COVID-19. METHODS: We analysed data of consecutive patients with COVID-19, requiring ICU admission at a university hospital in Germany between March and September 2020. Clinical characteristics, details on AKI, and RRT were assessed. MR-proADM was measured on admission. RESULTS: 64 patients were included (49 (77%) males). Median age was 62.5y (54-73). 47 (73%) patients were ventilated and 50 (78%) needed vasopressors. 25 (39%) patients had severe ARDS, and 10 patients needed veno-venous extracorporeal membrane oxygenation. 29 (45%) patients required RRT; median time from admission to RRT start was 2 (1-9) days. MR-proADM on admission was higher in the RRT group (2.491 vs. 1.23 nmol/l; p = 0.002) and showed the highest correlation with renalSOFA. ROC curve analysis showed that MR-proADM predicts RRT with an AUC of 0.69 (95% CI: 0.543-0.828; p = 0.019). In multivariable logistic regression MR-proADM was an independent predictor (OR: 3.813, 95% CI 1.110-13.102, p<0.05) for RRT requirement. CONCLUSION: AKI requiring RRT is frequent in ICU patients with COVID-19. MR-proADM on admission was able to predict RRT requirement, which may be of interest for risk stratification and management.

Mechanical ventilation and mortality among 223 critically ill patients with coronavirus disease 2019: A multicentric study in Germany.

BACKGROUND: There are large uncertainties with regard to the outcome of patients with coronavirus disease 2019 (COVID-19) and mechanical ventilation (MV). High mortality (50-97%) was proposed by some groups, leading to considerable uncertainties with regard to outcomes of critically ill patients with COVID-19. OBJECTIVES: The aim was to investigate the characteristics and outcomes of critically ill patients with COVID-19 requiring intensive care unit (ICU) admission and MV. METHODS: A multicentre retrospective observational cohort study at 15 hospitals in Hamburg, Germany, was performed. Critically ill adult patients with COVID-19 who completed their ICU stay between February and June 2020 were included. Patient demographics, severity of illness, and ICU course were retrospectively evaluated. RESULTS: A total of 223 critically ill patients with COVID-19 were included. The majority, 73% (n = 163), were men; the median age was 69 (interquartile range = 58-77.5) years, with 68% (n = 151) patients having at least one chronic medical condition. Their Sequential Organ Failure Assessment score was a median of 5 (3-9) points on admission. Overall, 167 (75%) patients needed MV. Noninvasive ventilation and high-flow nasal cannula were used in 31 (14%) and 26 (12%) patients, respectively. Subsequent MV, due to noninvasive ventilation/high-flow nasal cannula therapy failure, was necessary in 46 (81%) patients. Renal replacement therapy was initiated in 33% (n = 72) of patients, and owing to severe respiratory failure, extracorporeal membrane oxygenation was necessary in 9% (n = 20) of patients. Experimental antiviral therapy was used in 9% (n = 21) of patients. Complications during the ICU stay were as follows: septic shock (40%, n = 90), heart failure (8%, n = 17), and pulmonary embolism (6%, n = 14). The length of ICU stay was a median of 13 days (5-24), and the duration of MV was 15 days (8-25). The ICU mortality was 35% (n = 78) and 44% (n = 74) among mechanically ventilated patients. CONCLUSION: In this multicentre observational study of 223 critically ill patients with COVID-19, the survival to ICU discharge was 65%, and it was 56% among patients requiring MV. Patients showed high rate of septic complications during their ICU stay.

Lactate Improves Prediction of Short-Term Mortality in Critically Ill Patients With Cirrhosis: A Multinational Study.

Lactate levels and lactate clearance are known predictors of outcome in critically ill patients in the intensive care unit (ICU). The prognostic value of lactate is not well established in liver cirrhosis and acute-on-chronic liver failure (ACLF). The aim of this study was to assess the prognostic value of lactate levels and clearance in critically ill patients with cirrhosis. Patients with cirrhosis admitted to the ICU were studied at the University Medical Center Hamburg-Eppendorf (n = 566, derivation cohort) and the Medical University of Vienna and the University Hospitals Leuven (n = 250, validation cohort). Arterial lactate was measured on admission and during the first 24 hours. Patients were followed for 1 year and outcome was assessed. Admission lactate was directly related to the number of organs failing and to 28-day mortality (area under receiver operating characteristic [AUROC] 0.72; P < 0.001). This also applied to lactate follow-up measurements after 6, 12, and 24 hours (P < 0.001 for all, AUROC > 0.70 for all). Lactate clearance had significant predictive ability for 28-day mortality in patients with elevated serum lactate ≥5 mmol/L. Admission lactate and 12-hour lactate clearance (in patients with admission lactate ≥5 mmol/L), respectively, were identified as significant predictors of 1-year mortality, independent of Chronic Liver Failure Consortium acute-on-chronic liver failure score (CLIF-C ACLFs). A lactate-adjusted CLIF-C ACLFs was developed (CLIF-C ACLFsLact ), which performed significantly better than the original CLIF-C ACLFs in prediction of 28-day mortality in the derivation and validation cohort. Conclusion: Lactate levels appropriately reflect severity of disease and organ failure and were independently associated with short-term mortality in critically ill patients with liver cirrhosis. Lactate is a simple but accurate prognostic marker, and its incorporation improved performance of CLIF-C ACLFs significantly.

Coagulation parameters and major bleeding in critically ill patients with cirrhosis.

UNLABELLED: Disturbances of coagulation and hemostasis are common in patients with liver cirrhosis. The typical laboratory pattern mimics disseminated intravascular coagulation (DIC). The aim of this study was to assess the impact of routine coagulation parameters in critically ill cirrhosis patients with regard to new onset of major bleeding and outcome. A total of 1,493 critically ill patients were studied prospectively. Routine coagulation parameters were assessed, and the DIC score was calculated based on platelets, fibrinogen, d-dimer, and prothrombin index. New onset of major bleeding during the stay at the intensive care unit and mortality were assessed. Patients were followed for 1 year. Two hundred eleven patients of the cohort had liver cirrhosis. Platelets, fibrinogen, prothrombin index, activated partial thromboplastin time, and d-dimer as well as the DIC score differed significantly between patients with and without cirrhosis (P < 0.001 for all). Moreover, fibrinogen, platelets, and activated partial thromboplastin time (but not prothrombin index) differed significantly between cirrhosis patients with and without major bleeding (P < 0.01 for all). Bleeding on admission, platelet count <30 < 10(9) /L, fibrinogen level <60 mg/dL, and activated partial thromboplastin time values >100 seconds were the strongest independent predictors for new onset of major bleeding in multivariate regression analysis. One-year mortality in cirrhosis patients with and without major bleeding was 89% and 68%, respectively (P < 0.05 between groups). CONCLUSION: Abnormal coagulation parameters and high DIC scores (primarily due to fibrinogen and platelets) correspond to increased bleeding risk in patients with liver cirrhosis in the intensive care unit, and fibrinogen and platelet count were identified as the best routine coagulation parameters for prediction of new onset of major bleeding; however, further studies are required to evaluate the potential therapeutic implications of these findings. (Hepatology 2016;64:556-568).

Serum bile acids as marker for acute decompensation and acute-on-chronic liver failure in patients with non-cholestatic cirrhosis.

BACKGROUND & AIMS: Retention of bile acids (BAs) plays a central role in hepatic damage and disturbed BA signalling in liver disease. However, there is lack of data regarding the association of BAs with clinical complications, acute decompensation (AD) and acute-on-chronic liver failure (ACLF). Thus, we aimed to evaluate the impact of circulating serum BAs for complications in patients with cirrhosis. METHODS: One hundred and forty-three patients with cirrhosis were included in this prospective cohort-type observational study. Total serum BAs and individual BA composition were assessed in all patients on admission via high-performance liquid chromatography. Clinical complications with respect to AD, ACLF and 1-year transplant-free survival were recorded. RESULTS: Total BAs and individual serum BAs were significantly higher in patients with bacterial infection, AD and ACLF (P<.001) and correlated significantly with model of end-stage liver disease (MELD) and hepatic venous pressure gradient (P<.001). Total BAs predicted new onset of AD or ACLF during follow-up (OR 1.025, 95% CI: 1.012-1.038, P<.001). Best cut-off predicting new onset of AD/ACLF and survival during course of time was total BAs ≥36.9 µmol/L. CONCLUSIONS: Serum total and individual BAs are associated with AD and ACLF in patients with cirrhosis. Assessment of total BAs could serve as additional marker for risk stratification in cirrhotic patients with respect to new onset of AD and ACLF.

Renal replacement therapy in critically ill liver cirrhotic patients-outcome and clinical implications.

BACKGROUND & AIMS: Current guidelines discourage renal replacement therapy (RRT) in critically ill cirrhotics in the lack of liver transplant (LT) options. This study aimed to identify patients who benefit from RRT in the short and long-term. METHODS: Critically ill cirrhotics were included over a time period of 6 years and followed for at least 1 year. CLIF-C ACLF, CLIF-SOFA, SOFA and MELD scores on admission, 24 h prior to RRT, 24 and 48 hours after start of RRT were analysed for their predictive value of ICU-mortality. Additionally, long-term renal recovery and successful bridging to LT was assessed. RESULTS: In total, 40% (78/193) of patients required RRT. ICU-, 28 days-, 90 days-, and 1 year-mortality was 71%, 83%, 91%, and 92%, respectively, and was significantly higher than in patients without need for RRT (4%, 30%, 43%, and 50%), P<.001. CLIF-C ACLF and CLIF - SOFA scores within 24 hours prior to RRT showed good discriminant power to predict ICU-mortality. CLIF-C ACLF calculated 48 hours after commencing RRT was the most suitable predictor of ICU-mortality in RRT-patients irrespective of LT options (AUC: 0.866). In patients with ≥5 organ failure assessed by CLIF-SOFA at any time point showed 100% ICU-mortality. 13% of patients with RRT showed renal recovery; 14% of patients could be bridged to LT. CONCLUSIONS: Mortality in critically ill cirrhotics with need for RRT is substantially high independent of LT options. Only a small proportion showed renal recovery after ICU discharge. CLIF-C ACLF and CLIF-SOFA score may assist in identifying patients who would not benefit from RRT.

Serum bile acids in patients with hepatopulmonary syndrome.

Background Hepatopulmonary syndrome (HPS) occurs in 20 - 30 % of patients with cirrhosis and is associated with increased mortality. Cholestasis and accumulation of bile acids (BAs) play a major role in chronic liver disease. Aim We aimed to evaluate the clinical role of serum BAs in patients with HPS. Methods Seventy-four patients with cirrhosis were included in this prospective study. Marker for cholestasis as total and individual serum BAs, bilirubin, alkaline phosphatase (AP), and gamma-glutamyl transpeptidase (GGT) were analyzed in patients screened for HPS. Criteria of HPS were fulfilled in 26 patients (35 %). Results In contrast to AP and GGT, bilirubin and serum BAs were significantly elevated in patients with HPS (median total BAs in HPS 83.5 µmol/L, IQR 43.1 - 148.9 vs. no HPS 26.9 µmol/L, 11 - 75.6; p < 0.001). Total BAs correlated with gas exchange by means of PaO2 / AaPO2 (r: -0.28, p < 0.05; r: 0.24, p < 0.05) and portal pressure (r: 0.33, p < 0.05). BAs were associated with HPS independently severity of underlying liver disease (OR: 1.012, 95 % CI: 1.001 - 1.023, p < 0.05). Conclusion BA retention is associated with HPS and gas exchange abnormalities. Future studies should assess whether modulation of BAs signaling may impact the course of HPS.

Statin therapy is associated with reduced incidence of hypoxic hepatitis in critically ill patients.

BACKGROUND & AIMS: Hypoxic hepatitis (HH) is a frequent and life-threatening complication associated with states of oxygen depletion in critically ill patients. Ischemia and reperfusion contribute to liver injury in HH. Experimental data suggest beneficial effects of statins in hepatic ischemia/reperfusion injury. This study was conducted to investigate whether statin treatment prior to intensive care unit (ICU) admission affects incidence rates and severity of HH. METHODS: Eight hundred fifty-one patients admitted consecutively to three medical ICUs between December 2008 and December 2009 were prospectively screened for new occurrence of HH within 48 h following ICU admission. Statin treatment prior to ICU admission was assessed. 28-day-, 90-day-, and 1-year-survival as well as new-onset of complications in HH patients were prospectively documented. RESULTS: Eighty-seven patients (10%) developed HH. Statin treatment prior to ICU admission was significantly associated with decreased incidence of HH within 48 h after ICU admission in the multivariate analysis (adjusted OR=0.42 (95% CI 0.19-0.95); p<0.05). Cardiogenic shock (p<0.001), septic shock (p<0.001) and active alcohol consumption (p<0.01) were identified as independent risk factors for development of HH. 28-day-, 90-day-, and 1-year-mortality rates in HH were 58%, 67%, and 74%, respectively. Statins were associated with improved 28-day-survival in the total study cohort (p<0.05), but did not affect 90-day- and 1-year-mortality, respectively. CONCLUSIONS: Cardiogenic shock, septic shock, and active alcohol consumption were independent factors predisposing patients to new onset of HH. Statin treatment prior to ICU admission was the only protective factor regarding the new occurrence of HH in critically ill patients.

Von Willebrand factor antigen for detection of hepatopulmonary syndrome in patients with cirrhosis.

BACKGROUND & AIMS: Hepatopulmonary syndrome (HPS) occurs in 20-30% of patients with liver cirrhosis and is associated with a >2 fold increased mortality. Endothelial dysfunction seems to play a central role in its pathogenesis. von Willebrand factor antigen (vWF-Ag), an established marker of endothelial dysfunction, is significantly elevated in patients with liver cirrhosis, portal hypertension, and in experimental HPS. Aim of the present study was to evaluate the impact of vWF-Ag as a screening marker for presence of HPS in patients with stable cirrhosis. METHODS: 145 patients with stable liver cirrhosis were screened for presence of HPS in this prospective cohort type cross sectional diagnostic study. vWF-Ag and SaO2 levels were assessed at time of screening for HPS. Criteria of HPS were fulfilled in 31 (21%) patients. RESULTS: vWF-Ag levels were significantly higher in patients with HPS compared to patients without HPS (p<0.001). Furthermore, vWF-Ag correlated significantly with gas exchange in HPS positive patients (p<0.05). vWF-Ag is an independent predictor of HPS after correction for sex, age, model for endstage-liver disease (MELD), and hepatic venous pressure gradient (HVPG) (OR per 1% increase of vWF-Ag: 1.02, 95% CI: 1.00-1.04, p<0.05). The best cut-off was 328% at a sensitivity of 100% and specificity of 53.5%; positive predictive value: 36.9%; negative predictive value: 100%. CONCLUSIONS: HPS is associated with elevated vWF-Ag levels. vWF-Ag may be a useful screening tool for early detection of HPS. Further studies investigating vWF-Ag in HPS will be needed to confirm our findings.