[Liver diseases in the intensive care unit]. / Lebererkrankungen auf der Intensivstation.

The frequency of liver diseases in the intensive care unit has increased significantly in recent years and is now observed in up to 20% of critically ill patients. The occurrence of liver disease is associated with significantly increased morbidity and mortality. Two groups of liver diseases in the intensive care unit can be distinguished. First, the group of "primary hepatic dysfunctions", which includes primary acute liver failure as well as acute-on-chronic liver failure in patients with pre-existing liver cirrhosis. The second group of "secondary or acquired liver diseases" includes cholestatic liver diseases, as well as hypoxic liver injury and mixed forms, as well as other rarer liver diseases. Due to the diversity of liver diseases and the very different triggers, sufficient knowledge of the underlying changes (including hemodynamic changes, inflammatory states or drug-related) is essential. Early recognition, diagnosis, and treatment of the underlying disease are essential for all liver dysfunction in critically ill patients in the intensive care unit. This review article aims to take a closer look at liver diseases in the intensive care unit and provides insight into diagnostics and treatment options.

Clinical Presentation and Outcome of Critically Ill Patients with Inflammatory Bowel Disease.

Introduction: Admission to the intensive care unit severely affects inflammatory bowel disease (IBD) patients. This study aimed to determine factors associated with mortality in IBD patients admitted to the intensive care unit. Methods: A retrospective cohort study was performed, analyzing data of all IBD patients admitted to the Department of Intensive Care Medicine at the University Medical Center Hamburg-Eppendorf between 2013 and 2022. Bivariate comparisons and multivariate regression analyses were performed to identify factors associated with mortality. Results: Overall, 439 IBD patients were admitted to the intensive care unit, representing 0.56% of total admissions. In 98 of these patients, IBD-associated complications were accountable for admission (22.3%). In detail, 39 (40.8%) patients were admitted after IBD-related surgery, 36 (35.7%) due to infections, and 23 (23.5%) due to medical conditions such as bleeding or electrolyte derangement. A total of 16 (16.3%) of these patients died within 90 days after admission. Parameters associated with increased mortality were age (p < 0.001), later age at diagnosis (p 0.026), catecholamine therapy (p 0.003), mechanical ventilation (p < 0.001), renal replacement therapy (p < 0.001), and parenteral nutrition (p 0.002). Prior treatment with anti-TNF therapy was associated with a higher chance of survival (p 0.018). There was no association between prior immunosuppressant therapy and admission because of infections (p 0.294). Conclusions: 16.3% of IBD patients admitted to the intensive care unit died within 90 days after admission. Prior treatment with anti-TNF therapy was associated with a higher chance of survival.

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.

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.

High estradiol and low testosterone levels are associated with critical illness in male but not in female COVID-19 patients: a retrospective cohort study.

Male sex was repeatedly identified as a risk factor for death and intensive care admission. However, it is yet unclear whether sex hormones are associated with disease severity in COVID-19 patients. In this study, we analysed sex hormone levels (estradiol and testosterone) of male and female COVID-19 patients (n = 50) admitted to an intensive care unit (ICU) in comparison to control non-COVID-19 patients at the ICU (n = 42), non-COVID-19 patients with the most prevalent comorbidity (coronary heart diseases) present within the COVID-19 cohort (n = 39) and healthy individuals (n = 50). We detected significantly elevated estradiol levels in critically ill male COVID-19 patients compared to all control cohorts. Testosterone levels were significantly reduced in critically ill male COVID-19 patients compared to control cohorts. No statistically significant differences in sex hormone levels were detected in critically ill female COVID-19 patients, albeit similar trends towards elevated estradiol levels were observed. Linear regression analysis revealed that among a broad range of cytokines and chemokines analysed, IFN-γ levels are positively associated with estradiol levels in male and female COVID-19 patients. Furthermore, male COVID-19 patients with elevated estradiol levels were more likely to receive ECMO treatment. Thus, we herein identified that disturbance of sex hormone metabolism might present a hallmark in critically ill male COVID-19 patients.

Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients.

Hyperinflammation contributes to lung injury and subsequent acute respiratory distress syndrome (ARDS) with high mortality in patients with severe coronavirus disease 2019 (COVID-19). To understand the underlying mechanisms involved in lung pathology, we investigated the role of the lung-specific immune response. We profiled immune cells in bronchoalveolar lavage fluid and blood collected from COVID-19 patients with severe disease and bacterial pneumonia patients not associated with viral infection. By tracking T cell clones across tissues, we identified clonally expanded tissue-resident memory-like Th17 cells (Trm17 cells) in the lungs even after viral clearance. These Trm17 cells were characterized by a a potentially pathogenic cytokine expression profile of IL17A and CSF2 (GM-CSF). Interactome analysis suggests that Trm17 cells can interact with lung macrophages and cytotoxic CD8+ T cells, which have been associated with disease severity and lung damage. High IL-17A and GM-CSF protein levels in the serum of COVID-19 patients were associated with a more severe clinical course. Collectively, our study suggests that pulmonary Trm17 cells are one potential orchestrator of the hyperinflammation in severe COVID-19.

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.