Search

Aims Cardiac involvement in COVID-19 is associated with adverse outcome. However, it is unclear whether cell-specific consequences are associated with cardiac SARS-CoV-2 infection. Therefore, we investigated heart tissue utilizing in situ hybridization, immunohistochemistry, and RNA-sequencing in consecutive autopsy cases to quantify virus load and characterize cardiac involvement in COVID-19. Methods and results In this study, 95 SARS-CoV-2-positive autopsy cases were included. A relevant SARS-CoV-2 virus load in the cardiac tissue was detected in 41/95 deceased (43%). Massive analysis of cDNA ends (MACE)-RNA-sequencing was performed to identify molecular pathomechanisms caused by the infection of the heart. A signature matrix was generated based on the single-cell dataset ‘Heart Cell Atlas’ and used for digital cytometry on the MACE-RNA-sequencing data. Thus, immune cell fractions were estimated and revealed no difference in immune cell numbers in cases with and without cardiac infection. This result was confirmed by quantitative immunohistological diagnosis. MACE-RNA-sequencing revealed 19 differentially expressed genes (DEGs) with a q-value, Graphical Abstract

Was ist neu? Charakteristiken und Ursachen des präklinischen und innerklinischen Herz-Kreislauf-Stillstands Eine große dänische Studie verglich die Charakteristiken von mehr als 12 000 Patienten mit präklinischem oder innerklinischem Herz-Kreislauf-Stillstand. Interessanterweise zeigten sich zwischen den beiden Gruppen eine ähnliche Demografie sowie eine ähnliche Anzahl an Vorerkrankungen. Die Ergebnisse legen nahe, dass sich Unterschiede vor allem durch die Charakteristiken des Herz-Kreislauf-Stillstands erklären lassen. Dies ist vor allem im Hinblick auf die derzeit noch unzureichende Studienlage zum innerklinischen Herz-Kreislauf-Stillstand interessant. Herz-Kreislauf-Stillstand auf der Intensivstation Etwa die Hälfte der innerklinischen Herz-Kreislauf-Stillstände ereignet sich auf der Intensivstation. Zwei kürzlich publizierte Studien befassten sich genauer mit dem Vorkommen, den Ursachen sowie der Prognose von Patienten mit Herz-Kreislauf-Stillstand auf der Intensivstation. COVID-19 und Auswirkung auf den innerklinischen Herz-Kreislauf-Stillstand Mehrere Studien zeigten während der COVID-19-Pandemie eine höhere Inzidenz von präklinischen Herz-Kreislauf-Stillständen mit schlechterer Prognose. Aktuell ist unklar, wie oft hospitalisierte Patienten mit COVID-19 einen innerklinischen Herz-Kreislauf-Stillstand erleiden. Publizierte Arbeiten zeigten eine sehr eingeschränkte Überlebenswahrscheinlichkeit. Als führende Ursache zeigte sich überwiegend ein hypoxisch getriggerter Herz-Kreislauf-Stillstand mit nicht schockbaren EKG-Rhythmen (Asystolie/PEA). Eine kardiale Ursache fand sich nur selten. Aufgrund der schlechten Prognose wurde von einigen Autoren sogar die Sinnhaftigkeit von Reanimationsmaßnahmen bei COVID-19-Patienten diskutiert.

While several studies have described the clinical course of patients with coronavirus disease 2019 (COVID-19), direct comparisons with patients with seasonal influenza are scarce. We compared 166 patients with COVID-19 diagnosed between February 27 and June 14, 2020, and 255 patients with seasonal influenza diagnosed during the 2017–18 season at the same hospital to describe common features and differences in clinical characteristics and course of disease. Patients with COVID-19 were younger (median age [IQR], 59 [45–71] vs 66 [52–77]; P

Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), an emerging virus, has caused a global pandemic. Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has led to high hospitalization rates worldwide. Little is known about the occurrence of in-hospital cardiac arrest (IHCA) and high mortality rates have been proposed. The aim of this study was to investigate the incidence, characteristics and outcome of IHCA during the pandemic in comparison to an earlier period. Methods This was a retrospective analysis of data prospectively recorded during 3-month-periods 2019 and 2020 at the University Medical Centre Hamburg-Eppendorf (Germany). All consecutive adult patients with IHCA were included. Clinical parameters, neurological outcomes and organ failure/support were assessed. Results During the study period hospital admissions declined from 18,262 (2019) to 13,994 (2020) (− 23%). The IHCA incidence increased from 4.6 (2019: 84 IHCA cases) to 6.6 (2020: 93 IHCA cases)/1000 hospital admissions. Median stay before IHCA was 4 (1–9) days. Demographic characteristics were comparable in both periods. IHCA location shifted towards the ICU (56% vs 37%, p p = 0.05) and defibrillation were more frequent in the pandemic period (20% vs 35%, p p Conclusion Hospital admissions declined during the pandemic, but a higher incidence of IHCA was observed. IHCA in patients with COVID-19 was a common finding. Compared to patients with non-COVID-19-related respiratory failure, the outcome was improved.

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.

ZUSAMMENFASSUNGIm Dezember 2019 kam es zur Ausbreitung von SARS-CoV-2, welches zu einer weltweiten Pandemie führte. Neben den Einschränkungen im täglichen Alltag sah sich die Medizin mit bisher nicht dagewesenen Problemen konfrontiert. In einigen Ländern führte ein rasanter Anstieg an SARS-CoV-2 bzw. Erkrankungen mit COVID-19 zu einer Überforderung der Gesundheitssysteme, unter anderem aufgrund eines Mangels an Intensivbetten und Beatmungsgeräten. In der Intensivmedizin bestanden initial große Unsicherheiten bezüglich des Einsatzes von nichtinvasiven Beatmungsformen aufgrund der potenziellen Aerosolbelastung. Ca. 5 % der infizierten Patienten mussten zur weiteren Therapie auf die Intensivstation aufgenommen werden, im Regelfall aufgrund einer schweren Pneumonie. Es kann sich im Verlauf der Erkrankung das Vollbild eines akuten Lungenversagens ausbilden, welches mit einer hohen Mortalität vergesellschaftet ist. Da es sich bei COVID-19 um eine gänzlich unerforschte virale Erkrankung handelt, war die Erforschung der Todesursache und die Charakterisierung von Organschäden sehr wichtig. Mehrere Obduktionsstudien konnten zeigen, dass es bei Patienten mit COVID-19 zu einem vermehrten Auftreten von venösen und arteriellen Thrombosen kommt. Neben klassischen Lungenembolien kommt es auch zur Ausbildung von Mikrothromben in der pulmonalen Endstrombahn. Zudem ließ sich eine Neoangiogenese nachweisen, die bisher im Rahmen des diffusen Alveolarschadens bei pathologischen Untersuchungen noch nicht beschrieben wurde.

Background Prevalence of multiple organ failure (MOF) in critically ill patients is increasing and associated mortality remains high. Extracorporeal organ support is a cornerstone in the management of MOF. We report data of an advanced hemodialysis system based on albumin dialysis (ADVOS multi device) that can regulate acid–base balance in addition to the established properties of renal replacement therapy and albumin dialysis systems in critically ill patients with MOF. Methods 34 critically ill patients with MOF received 102 ADVOS treatment sessions in the Department of Intensive Care Medicine of the University Medical Center Hamburg-Eppendorf. Markers of metabolic detoxification and acid–base regulation were collected and blood gas analyses were performed. A subgroup analyses were performed in patients with severe acidemia (pH Results Median number of treatment sessions was 2 (range 1–9) per patient. Median duration of treatment was 17.5 (IQR 11–23) hours per session. Treatment with the ADVOS multi-albumin dialysis device caused a significant decrease in bilirubin levels, serum creatinine, BUN and ammonia levels. The relative elimination rate of bilirubin was concentration dependent. Furthermore, a significant improvement in blood pH, HCO3− and PaCO2, was achieved during ADVOS treatment including six patients that suffered from severe metabolic acidosis refractory to continuous renal replacement therapy. Delta pH, HCO3− and PaCO2 were significantly affected by the ADVOS blood flow rate and pH settings. This improvement in the clinical course during ADVOS treatments allowed a reduction in norepinephrine during ADVOS therapy. Treatments were well tolerated. Mortality rates were 50% and 62% for 28 and 90 days, respectively. Conclusions In this case series in patients with MOF, ADVOS was able to eliminate water-soluble and albumin-bound substances. Furthermore, the device corrected severe metabolic and respiratory acid–base disequilibrium. No major adverse events associated with the ADVOS treatments were observed.

Extracorporeal membrane oxygenation (ECMO) represents a viable therapy option for patients with refractory acute respiratory distress syndrome (ARDS). Currently, veno-venous (vv) ECMO is frequently used in patients suffering from coronavirus disease 2019 (COVID-19). VV-ECMO was also frequently utilised during the influenza pandemic and experience with this complex and invasive treatment has increased worldwide since. However, data on comparison of clinical characteristics and outcome of patients with COVID-19 and influenza-related severe ARDS treated with vv-ECMO are scarce. This is a retrospective analysis of all consecutive patients treated with vv/(veno-arterial)va-ECMO between January 2009 and January 2021 at the University Medical Centre Hamburg-Eppendorf in Germany. All patients with confirmed COVID-19 or influenza were included. Patient characteristics, parameters related to ICU and vv/va-ECMO as well as clinical outcomes were compared. Mortality was assessed up to 90 days after vv/va-ECMO initiation. Overall, 113 patients were included, 52 (46%) with COVID-19 and 61 (54%) with influenza-related ARDS. Median age of patients with COVID-19 and influenza was 58 (IQR 53–64) and 52 (39–58) years (p < 0.001), 35% and 31% (p = 0.695) were female, respectively. Charlson Comorbidity Index was 3 (1–5) and 2 (0–5) points in the two groups (p = 0.309). Median SAPS II score pre-ECMO was 27 (24–36) vs. 32 (28–41) points (p = 0.009), and SOFA score was 13 (11–14) vs. 12 (8–15) points (p = 0.853), respectively. Median P/F ratio pre-ECMO was 64 (46–78) and 73 (56–104) (p = 0.089); pH was 7.20 (7.16–7.29) and 7.26 (7.18–7.33) (p = 0.166). Median days on vv/va-ECMO were 17 (7–27) and 11 (7–20) (p = 0.295), respectively. Seventy-one percent and sixty-nine percent had renal replacement therapy (p = 0.790). Ninety-four percent of patients with COVID-19 and seventy-seven percent with influenza experienced vv/va-ECMO-associated bleeding events (p = 0.004). Thirty-four percent and fifty-five percent were successfully weaned from ECMO (p = 0.025). Ninety-day mortality was 65% and 57% in patients with COVID-19 and influenza, respectively (p = 0.156). Median length of ICU stay was 24 (13–44) and 28 (16–14) days (p = 0.470), respectively. Despite similar disease severity, the use of vv/va-ECMO in ARDS related to COVID-19 and influenza resulted in similar outcomes at 90 days. A significant higher rate of bleeding complications and thrombosis was observed in patients with COVID-19.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA loads in patient specimens may act as a clinical outcome predictor in critically ill patients with coronavirus disease 2019 (COVID-19). Methods We evaluated the predictive value of viral RNA loads and courses in the blood compared with the upper and lower respiratory tract loads of critically ill COVID-19 patients. Daily specimen collection and viral RNA quantification by reverse transcription quantitative polymerase chain reaction were performed in all consecutive 170 COVID-19 patients between March 2020 and February 2021 during the entire intensive care unit (ICU) stay (4145 samples analyzed). Patients were grouped according to their 90-day outcome as survivors (n=100) or nonsurvivors (n=70). Results In nonsurvivors, blood SARS-CoV-2 RNA loads were significantly higher at the time of admission to the ICU (P=.0009). Failure of blood RNA clearance was observed in 33/50 (66%) of the nonsurvivors compared with 12/64 (19%) survivors (P Conclusions Blood SARS-CoV-2 load is an important independent outcome predictor and should be further evaluated for treatment allocation and patient monitoring.

Infection and sepsis are a main cause of acute-on-chronic liver failure (ACLF). Besides bacteria, molds play a role. Voriconazole (VRC) is recommended but its pharmacokinetics (PK) may be altered by ACLF. Because ACLF patients often suffer from concomitant acute renal failure, we studied the PK of VRC in patients receiving continuous renal replacement therapy (RRT) with ACLF and compared it to PK of VRC in critically ill patients with RRT without concomitant liver failure (NLF). In this prospective cohort study, patients received weight-based VRC. Pre- and post-dialysis membrane, and dialysate samples obtained at different time points were analyzed by high-performance liquid chromatography. An integrated dialysis pharmacometric model was used to model the available PK data. The recommended, 50% lower, and 50% higher doses were analyzed by Monte-Carlo simulation (MCS) for day 1 and at steady-state with a target trough concentration (TC) of 0.5–3mg/L. Fifteen patients were included in this study. Of these, 6 patients suffered from ACLF. A two-compartment model with linear clearance described VRC PK. No difference for central (V1) or peripheral (V2) volumes of distribution or clearance could be demonstrated between the groups. V1 was 80.6L (95% confidence interval: 62.6–104) and V2 106L (65–166) with a body clearance of 4.7L/h (2.87–7.81) and RRT clearance of 1.46L/h (1.29–1.64). MCS showed TC below/within/above target of 10/74/16% on day 1 and 9/39/52% at steady-state for the recommended dose. A 50% lower dose resulted in 26/72/1% (day 1) and 17/64/19% at steady-state and 7/57/37% and 7/27/67% for a 50% higher dose. VRC pharmacokinetics are not significantly influenced by ACLF in critically ill patients who receive RRT. Maintenance dose should be adjusted in both groups. Due to the high interindividual variability, therapeutic drug monitoring seems inevitable.

Hypoxic liver injury (HLI) is a frequent and life-threatening complication in critically ill patients that occurs in up to ten percent of critically ill patients. However, there is a lack of data on HLI following cardiac arrest and its clinical implications on outcome. Aim of this study was to investigate incidence, outcome and functional outcome of patients with HLI after in-hospital cardiac arrest (IHCA) and out-of-hospital cardiac arrest (OHCA).We conducted an analysis of a cardiac arrest registry data over a 7-year period. All patients with non-traumatic OHCA and IHCA with return of spontaneous circulation (ROSC) treated at the emergency department of a tertiary care hospital were included in the study. HLI was defined according to established criteria. Predictors of HLI, occurrence, clinical and neurological outcome were assessed using multivariable regression.Out of 1068 patients after IHCA and OHCA with ROSC, 219 (21%) patients developed HLI. Rate of HLI did not differ significantly in IHCA and OHCA patients. Multivariate regression analysis identified time-to-ROSC [OR 1.18, 95% CI (1.01-1.38); p 0.05], presence of cardiac failure [OR 2.57, 95% CI (1.65-4.01); p 0.001] and Charlson comorbidity index [OR 0.83, 95% CI (0.72-0.95); p 0.01] as independent predictors for occurrence of HLI. Good functional outcome was significantly lower in patients suffering from HLI after 28-days (35% vs. 48%, p 0.001) and 1-year (34% vs. 44%, p 0.001). Occurrence of HLI was associated with unfavourable neurological outcome [OR 1.74, 95% CI (1.16-2.61); p 0.01] in multivariate regression analysis.New onset of HLI is a frequent finding after IHCA and OHCA. HLI is associated with increased mortality, unfavourable neurological and overall outcome.

Background Neuron-specific-enolase (NSE) is frequently used to predict the neurologic outcome in persistently unconscious patients after cardiopulmonary resuscitation (CPR). However, its predictive value is unclear in the setting of veno-arterial extracorporeal membrane oxygenation therapy (ECMO). Aim of this project is to evaluate the predictive value of NSE in ECMO patients. Methods NSE was measured after 24, 48, and 72 h in post-CPR ECMO patients. Neurologic status was evaluated using the best Cerebral Performance Categories Score (CPC) during the hospital stay. Patients who deceased within the first 24 h and patients who were awake during the first 24 h were excluded. ROC curves were calculated to assess the discriminative ability of single NSE measurements. Trajectories of serial NSE values were investigated using latent class mixed models. Results The derivation cohort consisted of 65 patients, 30-day all-cause mortality was 47.7% and a poor neurological outcome with a CPC score of 4–5 was seen 30.7%. NSE measurement after 48 h showed the best discrimination for poor neurological outcome (AUC of 0.87 in the ROC curve; cut-off value of 70 μg/L). Specificity was highest if using serial NSE measurements at all three time points. These results could be validated in an external cohort of 64 patients. Conclusion In post-CPR patients on ECMO, NSE can be used to assess the neurologic outcome. Importantly, specificity was highest if using serial NSE measurements. Further research using prospective datasets is needed to verify these findings.

Purpose: Immunomodulatory therapies have shown beneficial effects in patients with severe COVID-19. Patients with hypercytokinemia might benefit from 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 mmHg), IL-6≥500 ng/l and an indication for renal replacement therapy (RRT) or extracorporeal membrane oxygenation (ECMO) 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 hours. The primary endpoint was sustained hemodynamic improvement (norepinephrine ≤0.05 µg/kg/min≥24h). Secondary endpoints included 28-day mortality, SOFA, and reduction of IL-6, PCT, and MR-proADM. 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). At randomization, 22 (92%) patients were on RRT and 11 (46%) had vv-ECMO. Median IL-6 levels were 2269 (IQR 948–3679) and 3747 (1301–5415) ng/l in the HT and SMT group at baseline, respectively (p=0.378). Serum IL-6 reduction in the first 24h of treatment compared between both groups was 83% vs. 46% (p=0.235). Shock resolution (primary endpoint) was reached in 33% (4/12) vs. 17% (2/12) in the HT and SMT group, respectively (p=0.640). 28-day mortality was 58% (7/12) in the HT compared to 67% (8/12) in the SMT group (p=1.0).Conclusion: HT was associated with a non-significant trend towards clinical improvement within the intervention period including reduction of IL-6 levels and shock resolution. In selected patients, HT might therefore be an option for stabilization and bridge to transfer and decision. (Trial registration: ClinicalTrials.gov: NCT04344080, https://clinicaltrials.gov/ct2/show/NCT04344080, trial registration date 04/14/2020)]

BACKGROUNDMale 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. We sought to characterize sex differences in hormone levels and cytokine responses in critically ill COVID-19 patients.METHODSWe performed a retrospective cohort study of critically ill COVID-19 patients. Males and females were compared. Multivariate regression was performed to assess the association between sex hormones, cytokine responses and the requirement for extracorporeal membrane oxygenation (ECMO) treatment.RESULTSWe analyzed sex hormone levels (estradiol and testosterone) of n=181 male and female individuals. These consisted of n=50 critically ill COVID-19 patients (n=39 males, n=11 females), n=42 critically ill non-COVID-19 patients (n=27 males, n=15 females), n=39 non-COVID-19 patients with coronary heart diseases (CHD) (n=25 males, n=14 females) and n=50 healthy individuals (n=30 males, n=20 females). We detected highest estradiol levels in critically ill male COVID-19 patients compared to non-COVID-19 patients (p=0.0123), patients with CHD (p=0.0002) or healthy individuals (p=0.0007). Lowest testosterone levels were detected in critically ill male COVID-19 patients compared to non-COVID-19 patients (p=0.0094), patients with CHD (p=0.0068) or healthy individuals (pp=0.0301; IL-1RA, p=0.0160; IL-6, p=0.0145; MCP-1, p=0.0052; MIP-1α, p=0.0134) were significantly elevated in those with higher Sequential Organ Failure Assessment (SOFA) scores (8-11). Linear regression analysis revealed that herein IFN-γ levels correlate with estradiol levels in male and female COVID-19 patients (R2=0.216, =0.0009). Male COVID-19 patients with elevated estradiol levels were more likely to receive ECMO treatment in the course of their ICU stay (p=0.0009). CONCLUSIONS We identified high estradiol and low testosterone levels as a hallmark of critically ill male COVID-19 patients. Elevated estradiol levels in critically ill male COVID-19 patients were positively associated with IFN-γ levels and increased risk for ECMO requirement.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) led to an ongoing pandemic with a surge of critically ill patients. Very little is known about the occurrence and characteristic of cardiac arrest in critically ill patients with COVID-19 treated at the intensive care unit (ICU). The aim was to investigate the incidence and outcome of intensive care unit cardiac arrest (ICU-CA) in critically ill patients with COVID-19. This was a retrospective analysis of prospectively recorded data of all consecutive adult patients with COVID-19 admitted (27 February 2020–14 January 2021) at the University Medical Centre Hamburg-Eppendorf (Germany). Of 183 critically ill patients with COVID-19, 18% (n = 33) had ICU-CA. The median age of the study population was 63 (55–73) years and 66% (n = 120) were male. Demographic characteristics and comorbidities did not differ significantly between patients with and without ICU-CA. Simplified Acute Physiological Score II (SAPS II) (ICU-CA: median 44 points vs. no ICU-CA: 39 points) and Sequential Organ Failure Assessment (SOFA) score (median 12 points vs. 7 points) on admission were significantly higher in patients with ICU-CA. Acute respiratory distress syndrome (ARDS) was present in 91% (n = 30) with and in 63% (n = 94) without ICU-CA (p = 0.002). Mechanical ventilation was more common in patients with ICU-CA (97% vs. 67%). The median stay in ICU before CA was 6 (1–17) days. A total of 33% (n = 11) of ICU-CAs occurred during the first 24 h of ICU stay. The initial rhythm was non-shockable (pulseless electrical activity (PEA)/asystole) in 91% (n = 30), 94% (n = 31) had sustained return of spontaneous circulation (ROSC). The median time to ROSC was 3 (1–5) minutes. Patients with ICU-CA had significantly higher ICU mortality (61% vs. 37%). Multivariable logistic regression showed that the presence of ARDS (odds ratio (OR) 4.268, 95% confidence interval (CI) 1.211–15.036, p = 0.024) and high SAPS II (OR 1.031, 95% CI 0.997–1.065, p = 0.077) were independently associated with the occurrence of ICU-CA. A total of 18% of critically ill patients with COVID-19 suffered from a cardiac arrest within the intensive care unit. The occurrence of ICU-CA was associated with presence of ARDS and severity of illness.

In this study, we directly compared coronavirus disease 2019 (COVID-19) patients hospitalized during the first (27 February–28 July 2020) and second (29 July–31 December 2020) wave of the pandemic at a large tertiary center in northern Germany. Patients who presented during the first (n = 174) and second (n = 331) wave did not differ in age (median [IQR], 59 years [46, 71] vs. 58 years [42, 73], p = 0.82) or age-adjusted Charlson Comorbidity Index (median [IQR], 2 [1, 4] vs. 2 [0, 4], p = 0.50). During the second wave, a higher proportion of patients were treated as outpatients (11% [n = 20] vs. 20% [n = 67]), fewer patients were admitted to the intensive care unit (43% [n = 75] vs. 29% [n = 96]), and duration of hospitalization was significantly shorter (median days [IQR], 14 [8, 34] vs. 11 [5, 19], p &lt, 0.001). However, in-hospital mortality was high throughout the pandemic and did not differ between the two periods (16% [n = 27] vs. 16% [n = 54], p = 0.89). While novel treatment strategies and increased knowledge about the clinical management of COVID-19 may have resulted in a less severe disease course in some patients, in-hospital mortality remained unaltered at a high level. These findings highlight the unabated need for efforts to hamper severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) transmission, to increase vaccination coverage, and to develop novel treatment strategies to prevent mortality and decrease morbidity.

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.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.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;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.

Background SARS-CoV-2 caused a pandemic and global threat for human health. Presence of liver injury was commonly reported in patients with coronavirus disease 2019 (COVID-19). However, reports on severe liver dysfunction (SLD) in critically ill with COVID-19 are lacking. We evaluated the occurrence, clinical characteristics and outcome of SLD in critically ill patients with COVID-19. Methods Clinical course and laboratory was analyzed from all patients with confirmed COVID-19 admitted to ICU of the university hospital. SLD was defined as: bilirubin ≥ 2 mg/dl or elevation of aminotransferase levels (> 20-fold ULN). Results 72 critically ill patients were identified, 22 (31%) patients developed SLD. Presenting characteristics including age, gender, comorbidities as well as clinical presentation regarding COVID-19 overlapped substantially in both groups. Patients with SLD had more severe respiratory failure (paO2/FiO2: 82 (58–114) vs. 117 (83–155); p p p = 0.106), vasopressor (95% vs. 72%; p p p p = 0.002). Occurrence of SLD was independently associated with presence of viremia [OR 6.359; 95% CI 1.336–30.253; p p p p Conclusion One-third of critically ill patients with COVID-19 suffer from SLD, which is associated with high mortality. Occurrence of viremia and severity of illness seem to contribute to occurrence of SLD and underline the multifactorial cause.

Background SARS-CoV-2 molecular diagnostics is facing material shortages and long turnaround times due to exponential increase of testing demand. Objective We evaluated the analytic performance and handling of four rapid Antigen Point of Care Tests (AgPOCTs) I-IV (Distributors: (I) Roche, (II) Abbott, (III) MEDsan and (IV) Siemens). Methods 100 RT-PCR negative and 84 RT-PCR positive oropharyngeal swabs were prospectively collected and used to determine performance and accuracy of these AgPOCTs. Handling was evaluated by 10 healthcare workers/users through a questionnaire. Results The median duration from symptom onset to sampling was 6 days (IQR 2–12 days). The overall respective sensitivity were 49.4 % (CI95 %: 38.9–59.9), 44.6 % (CI95 %: 34.3–55.3), 45.8 % (CI95 %: 35.5–56.5) and 54.9 % (CI95 %: 43.4−65.9) for tests I, II, III and IV, respectively. In the high viral load subgroup (containing >106 copies of SARS-CoV-2 /swab, n = 26), AgPOCTs reached sensitivities of 92.3 % or more (range 92.3 %–100 %). Specificity was 100 % for tests I, II (CI95 %: 96.3–100 for both tests) and IV (CI95 %: 96.3–100) and 97 % (CI95 %: 91.5–98.9) for test III. Regarding handling, test I obtained the overall highest scores, while test II was considered to have the most convenient components. Of note, users considered all assays, with the exception of test I, to pose a significant risk for contamination by drips or spills. Discussion Besides some differences in sensitivity and handling, all four AgPOCTs showed acceptable performance in high viral load samples. However, due to the significantly lower sensitivity compared to RT-qPCR, a careful consideration of pro and cons of AgPOCT has to be taken into account before clinical implementation.

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.

1AbstractBackgroundAnalyses in hospitalized patients and small autopsy series suggest that severe SARS-CoV-2 infection may affect the heart. We investigated heart tissue by in situ hybridization, immunohistochemistry and RNA sequencing in consecutive autopsy cases to quantify virus load and characterize cardiac involvement in COVID-19.MethodsLeft ventricular tissue from 95 deceased with diagnosed SARS-CoV-2 infection undergoing autopsy was analyzed and clinical data were collected. RNA was isolated to examine virus load of SARS- CoV-2 and its replication in the heart. A virus load >1000 copies per µg RNA was defined as relevant. Viral RNA and inflammatory cells were assessed using histology. RNA sequencing and gene ontology (GO) enrichment were performed in 10 cases with high cardiac virus load and 10 age-matched cases without cardiac infection.ResultsA relevant SARS-CoV-2 virus load was detected in 41 out of 95 deceased (43%). The median cardiac virus load was 7952 copies per µg RNA (IQR 2507, 32 005). In situ hybridization revealed SARS- CoV-2 RNA primarily in the interstitium or interstitial cells. Virus detection was not associated with increased inflammatory cells. Relevant cardiac infection was associated with increased expression of the entry factor TMPRSS2. Cardiac virus replication was found in 14/95 hearts (15%). Remarkably, cardiac virus replication was associated with shorter time between diagnosis and death. RNA sequencing revealed clear activation of immune response pathways to virus infection and destruction of cardiomyocytes. Hearts with high virus load showed activation of the GO term “extracellular exosomes”.ConclusionSARS-CoV-2 infection including virus replication and distinct transcriptomic alterations without signs of myocarditis demonstrate a cardiac involvement. In this autopsy series, cardiac replication of SARS-CoV-2 was associated with early death.

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.

Recently, the stabilization of the endothelium has been explicitly identified as a therapeutic goal in coronavirus disease 2019 (COVID-19). Adrecizumab (HAM8101) is a first-in-class humanized monoclonal anti-Adrenomedullin (anti-ADM) antibody, targeting the sepsis- and inflammation-based vascular and capillary leakage. Within a &ldquo, treatment on a named-patient basis&rdquo, approach, Adrecizumab was administered to eight extreme-critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS). The patients received a single dose of Adrecizumab, which was administered between 1 and 3 days after the initiation of mechanical ventilation. The SOFA (median 12.5) and SAPS-II (median 39) scores clearly documented the population at highest risk. Moreover, six of the patients suffered from acute renal failure, of whom five needed renal replacement therapy. The length of follow-up ranged between 13 and 27 days. Following the Adrecizumab administration, one patient in the low-dose group died at day 4 due to fulminant pulmonary embolism, while four were in stable condition, and three were discharged from the intensive care unit (ICU). Within 12 days, the SOFA score, as well as the disease severity score (range 0&ndash, 16, mirroring critical resources in the ICU, with higher scores indicating more severe illness), decreased in five out of the seven surviving patients (in all high-dose patients). The PaO2/FiO2 increased within 12 days, while the inflammatory parameters C-reactive protein, procalcitonin, and interleukin-6 decreased. Importantly, the mortality was lower than expected and calculated by the SOFA score. In conclusion, in this preliminary uncontrolled case series of eight shock patients with life-threatening COVID-19 and ARDS, the administration of Adrecizumab was followed by a favorable outcome. Although the non-controlled design and the small sample size preclude any definitive statement about the potential efficacy of Adrecizumab in critically ill COVID-19 patients, the results of this case series are encouraging.

Key Points Patients with acute leukemia present with a prolonged and severe course of COVID-19, which is paralleled by high rates of viremia. Low-intensive chemotherapy seems to be more feasible in patients with acute myeloid leukemia and concomitant SARS-CoV-2 infection., Visual Abstract

Critically ill patients in intensive care units can frequently suffer from cardiac arrest (ICU-CA), the incidence of ICU-CA is associated with high mortality. Most studies on ICU-CA focused on risk factors and intra-arrest determinants. However, there is a lack of data on organ failure after ICU-CA and its clinical implications for outcome. This study aimed to investigate ICU-CA incidence, outcome and the occurrence of organ failure after ICU-CA.We conducted a prospective observational study over a 1-year at 12 intensive care units of a tertiary care university hospital. We included all consecutive adult patients suffering cardiac arrest (CA) during the ICU stay. Incidence, clinical and neurological outcome, as well as organ failure and support were assessed.Out of 7690 patients, 176 (2%) with ICU-CA were identified during the study period. Male patients comprised 63% and the median age was 70 (58-78) years. The median ICU stay before ICU-CA was 3 (1-8) days. The initial cardiac rhythm was shockable (VT/VF) in 23% of patients; defibrillation during CPR was performed in 19%. The presumed cause of CA was cardiac in 24%, and sustained ROSC was observed in 80% of patients. Before CA 57% (n = 100) of patients were sedated, 63% (n = 110) mechanically ventilated, 70% needed vasopressor therapy and renal replacement therapy was necessary in 27% (n = 48) of patients. Organ failure after ICU-CA was common, 70% suffered from post-CA cardiac failure, renal replacement therapy was newly initiated in 26% of patients and liver failure occurred in 24% of patients. Mortality at ICU-discharge and at hospital discharge was 66 % and 68 %, respectively. Multivariate regression analysis identified the SOFA score [HR 1.09, 95% CI (0.92-3.18); p 0.05] and liver failure [HR 2.44, 95% CI (1.39-4.26); p 0.001] after ICU-CA as independent predictors of mortality.The incidence of ICU-CA is rare in critically ill patients. Organ failure before and after ICU-CA is common; liver failure incidence and severity of illness after ICU-CA are independent predictors of mortality and should be considered in further decisions on ICU therapy.

Background Organ failure increases mortality in patients with liver cirrhosis. Data about resuscitated cardiac arrest patients with liver cirrhosis are missing. This study aims to assess aetiology, survival and functional outcome in patients after successful cardiopulmonary resuscitation (CPR) with and without liver cirrhosis. Methods Analysis of prospectively collected cardiac arrest registry data of consecutively hospital-admitted patients following successful CPR was performed. Patient’s characteristics, admission diagnosis, severity of disease, course of disease, short- and long-term mortality as well as functional outcome were assessed and compared between patients with and without cirrhosis. Results Out of 1068 patients with successful CPR, 47 (4%) had liver cirrhosis. Acute-on-chronic liver failure (ACLF) was present in 33 (70%) of these patients on admission, and four patients developed ACLF during follow-up. Mortality at 1 year was more than threefold increased in patients with liver cirrhosis (OR 3.25; 95% CI 1.33–7.96). Liver cirrhosis was associated with impaired neurological outcome (OR for a favourable cerebral performance category: 0.13; 95% CI 0.04–0.36). None of the patients with Child–Turcotte–Pugh (CTP) C cirrhosis survived 28 days with good neurological outcome. Overall nine (19%) patients with cirrhosis survived 28 days with good neurological outcome. All patients with ACLF grade 3 died within 28 days. Conclusion Cardiac arrest survivors with cirrhosis have worse outcome than those without. Although one quarter of patients with liver cirrhosis survived longer than 28 days after successful CPR, patients with CTP C as well as advanced ACLF did not survive 28 days with good neurological outcome. Electronic supplementary material The online version of this article (doi:10.1186/s13613-017-0322-1) contains supplementary material, which is available to authorized users.

Alterations of the kidney function can be observed often in patients with liver diseases. Different mechanisms are leading to alterations in kidney funciton in these patients. New onset of kidney function alterations in patients with acute- or chronic liver disease often leads to acute kidney injury. This Review will inform you about the most importatant clinical interactions of the kidneys and the liver.

Interactions between the hepatic portal and cardiovascular systems are frequently found in patients with liver disease. Cirrhotic cardiomyopathy (CCMP) is defined as reduced cardiac function in patients with liver cirrhosis in the absence of other known causes of cardiac disease. The typical hyperdynamic circulatory state by means of increased cardiac output and reduced systemic vascular resistance may mask left ventricular failure. Portopulmonary hypertension (POPH) is defined as increased pulmonary arterial pressure and the presence of portal hypertension, and is associated with increased mortality. Targeted medical therapies include vasodilators such as prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors. Hypoxic or ischaemic hepatitis (HH) is defined by a sharp increase of serum aminotransferase levels due to liver cell necrosis as result of cardiac, circulatory or respiratory failure. An overview of these diseases is provided in this article.

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

Due to medical advances, an increasing number of patients are surviving the acute critical illness. However, some patients require a prolonged critical care treatment. Data on outcome and functional status of patients with an ICU-stay ≥90 days are scarce.Single-center retrospective study including all adult patients with ICU stay ≥90 days treated at the department of intensive care medicine at the university medical center Hamburg-Eppendorf, Germany, between January 1st 2008 and December 31st 2016.Out of 65,249 patients, we identified 96 (0.1%) patients with a very prolonged ICU stay. Median age was 61 (49.8-67) years, 30 (31%) patients were female. Patients were admitted to ICU due to abdominal (28%) reasons, followed by sepsis (23%) and transplantation (15%). Fourteen patients received organ-transplantation: 9 received liver-, 4 lung- and 1 heart-transplantation. All patients needed mechanical ventilation (MV), median duration was 74.1 (55-95.1) days. Sixty-Three (66%) patients survived the ICU-stay and 1-Year survival rate was 28%. Overall eight (8%) patients had a favourable outcome after 1-Year. Severity of illness (SOFA, SAPS II) on admission were comparable. Length of MV, use of renal replacement therapy (both p .01) and maximum lactate (5.3 vs 11.5 mmol/l; p .001) were significantly higher in ICU non-survivors. ICU-stay was significantly longer in ICU non-survivors (137 vs 107 days; p .05). Cox-regression-model revealed age (HR 1.02, 95% CI 1.00-1.04, p .05) and surgical admission (HR 0.50, 95% CI 0.28-0.90, p .05) as independent predictors of 1-year mortality.Only a small number of patients requires a very prolonged ICU stay. Two-third of patients survive the ICU stay and about one-third 1-Year. However, about 10% of patients have a remarkable recovery with a favourable overall outcome after 1-Year.

COVID-19 is a respiratory tract infection that can affect multiple organ systems. Predicting the severity and clinical outcome of individual patients is a major unmet clinical need that remains challenging due to intra- and inter-patient variability. Here, we longitudinally profiled and integrated more than 150 clinical, laboratory and immunological parameters of 173 patients with mild to fatal COVID-19. Using systems biology, we detected progressive dysregulation of multiple parameters indicative of organ damage that correlated with disease severity, particularly affecting kidneys, hepatobiliary system, and immune landscape. By performing unsupervised clustering and trajectory analysis, we identified T and B cell depletion as early indicators of a complicated disease course. In addition, markers of hepatobiliary damage emerged as robust predictor of lethal outcome in critically ill patients. This allowed us to propose a novel clinical COVID-19 SeveriTy (COST) score that distinguishes complicated disease trajectories and predicts lethal outcome in critically ill patients., Graphical Abstract

Fragestellung Das hepatopulmonale Syndrom (HPS) ist eine Storung der arteriellen Oxygenierung, welche bei bis zu 30 % der Patienten mit Leberzirrhose auftritt und mit deutlich erhohter Sterblichkeit einhergeht. Ikterus und cholestatische Dysfunktion sind von zentraler pathogenetischer Rolle in akuter als auch chronischer Lebererkrankung. Ziel Deshalb war es Ziel dieser Studie den Stellenwert der Serum-Gallensauren bei Patienten mit HPS zu untersuchen. Methodik 74 Patienten mit Leberzirrhose wurden in diese Studie eingeschlossen. Cholestasemarker, Gesamt- als auch individuelle Gallensauren wurden bestimmt und alle Patienten auf das Vorhandensein von HPS gescreent. 26 Patienten (35 %) erfullten die Kriterien fur HPS. Ergebnisse Serum-Gallensauren waren signifikant hoher bei Patienten mit HPS im Vergleich zu denen ohne (mediane Gesamt-Gallensauren 83,5 μmol/l, IQR 43,1 – 148,9 vs. 26,9 μmol/l, 11 – 75,6; p Schlussfolgerung Serum-Gallensauren sind mit dem Vorhandensein von HPS assoziiert und korrelieren mit dem Schweregrad der Butgasaustauschstorung. Zukunftige Studien sollten den Stellenwert der Gallensauren bei HPS sowie den Einfluss einer direkten Regulation des Gallensaure-Metabolismus untersuchen. 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 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.

Background Jaundice and cholestatic hepatic dysfunction are frequent findings in critically ill patients associated with increased mortality. Cholestasis in critically ill patients is closely associated with stimulation of pro-inflammatory cytokines resulting in impaired bile secretion and subsequent accumulation of bile acids. Aim of this study was to evaluate the clinical role of circulating bile acids in critically ill patients. Methods Total and individual serum bile acids were assessed via high-performance liquid chromatography in 320 critically ill patients and 19 controls. Results Total serum bile acids were threefold higher in septic than cardiogenic shock patients and sixfold higher than in post-surgical patients or controls (p

Background Acid–base disturbances are frequently observed in critically ill patients at the intensive care unit. To our knowledge, the acid–base profile of patients with acute-on-chronic liver failure (ACLF) has not been evaluated and compared to critically ill patients without acute or chronic liver disease. Results One hundred and seventy-eight critically ill patients with liver cirrhosis were compared to 178 matched controls in this post hoc analysis of prospectively collected data. Patients with and without liver cirrhosis showed hyperchloremic acidosis and coexisting hypoalbuminemic alkalosis. Cirrhotic patients, especially those with ACLF, showed a marked net metabolic acidosis owing to increased lactate and unmeasured anions. This metabolic acidosis was partly antagonized by associated respiratory alkalosis, yet with progression to ACLF resulted in acidemia, which was present in 62% of patients with ACLF grade III compared to 19% in cirrhosis patients without ACLF. Acidemia and metabolic acidosis were associated with 28-day mortality in cirrhosis. Patients with pH values

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.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.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); p0.05). Cardiogenic shock (p0.001), septic shock (p0.001) and active alcohol consumption (p0.01) 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 (p0.05), but did not affect 90-day- and 1-year-mortality, respectively.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.

Leberfunktionsstorungen konnen haufig bei kritisch kranken Patienten auf der Intensivstation (ICU) beobachtet werden und haben eine hohe Morbiditat und Mortalitat zur Folge. Die haufigsten Formen der Leberfunktionsstorung an der ICU sind die Schockleber und die cholestatische Leberfunktionsstorung mit Inzidenzraten bis zu 10 % bzw. 30 %. Beide Erkrankungen treten haufig als Folge einer Ischamie/Hypoxie meist im Rahmen eines kardiogenen Schocks, einer Sepsis oder eines septischen Schocks auf. Speziell im Fall der cholestatischen Leberdysfunktion wurden jedoch auch andere potenzielle Verursacher identifiziert. Dazu gehoren neben zugrunde liegenden Krankheiten, wie chronische Lebererkrankungen oder Malignome, auch iatrogene Faktoren, wie z. B. parenterale Ernahrung, hohe Beatmungsdrucke, chirurgische Eingriffe, verschiedene Medikamente und Bluttransfusionen. Fruhzeitiges Erkennen und Behandeln der zugrunde liegenden Ursache stellen bislang die einzigen etablierten Therapiemasnahmen bei Schockleber und cholestatischer Leberfunktionsstorung dar.

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 Therefore, 143 patients with established 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 as well as 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

Background Hypoxic hepatitis (HH) is a frequent and potentially life-threatening event typically occurring in critically ill patients as a consequence of hemodynamic impairment. While acute kidney injury (AKI) has been well described in patients with acute liver failure, incidence and outcome of AKI accompanying HH are unclear. The aim of this study was to assess incidence, clinical implications and outcome of AKI and renal replacement therapy (RRT) in critically ill patients with HH. Methods A total of 1948 consecutive critically ill admissions were studied at the Medical University of Vienna. Laboratory and clinical parameters as well as the presence of HH and AKI were assessed on a daily basis. Outcome, renal recovery and length of stay were assessed and documented, and patients were followed for 1 year. Results A total of 295 admissions (15 %) developed HH. Main precipitators were cardiogenic (44 %) and septic shock (36 %). Occurrence of HH was significantly associated with AKI [OR 4.50 (95 % CI 3.30–6.12)] and necessity of renal replacement therapy [RRT; OR 3.36 (95 % CI 2.58–4.37)], p

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 (P0.001 for all). Moreover, fibrinogen, platelets, and activated partial thromboplastin time (but not prothrombin index) differed significantly between cirrhosis patients with and without major bleeding (P0.01 for all). Bleeding on admission, platelet count3010(9) /L, fibrinogen level60 mg/dL, and activated partial thromboplastin time values100 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 (P0.05 between groups).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).

Background Hepatic impairment is found in up to 20 % in critically ill patients. Hypoxic/ischemic hepatitis (HH) is a diffuse hepatic damage associated with high morbidity and mortality. Indocyanine green plasma disappearance rate (ICG-PDR) is an effective tool assessing liver function in acute and chronic hepatic diseases. Aim of this study was to evaluate the prognostic impact of ICG-PDR in comparison to established parameters for risk stratification. Methods Patients with HH were included in this prospective observational study and compared to cirrhosis, acute liver failure (ALF) and patients without underlying liver disease. ICG-PDR, measured non-invasively by finger pulse densitometry, was assessed on admission and in patients with HH serially and results were compared between groups. Diagnostic test accuracy of ICG-PDR predicting 28-day mortality was analyzed by receiver operating characteristics (ROC). Results ICG-PDR on admission was significantly lower in patients with liver diseases than in patients without hepatic impairment (median 5.7 %/min, IQR 3.8–7.9 vs. 20.7 %/min, IQR 14.1–25.4 %/min; p

Hepatopulmonary syndrome (HPS) occurs in 20-30% of patients with liver cirrhosis and is associated with a2 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.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.vWF-Ag levels were significantly higher in patients with HPS compared to patients without HPS (p0.001). Furthermore, vWF-Ag correlated significantly with gas exchange in HPS positive patients (p0.05). 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, p0.05). 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%.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.

Increased arterial ammonia levels are associated with high mortality in patients with acute liver failure (ALF). Data on the prognostic impact of arterial ammonia is lacking in hypoxic hepatitis (HH) and scarce in critically ill patients with cirrhosis.The patient cohort comprised 72 patients with HH, 43 patients with ALF, 100 patients with liver cirrhosis and 45 patients without evidence for liver disease. Arterial ammonia concentrations were assessed on a daily basis in all patients and the results were compared among these four patient groups and between 28-day survivors and 28-day non-survivors overall and in each group.Overall 28-day mortality rates in patients with HH, ALF and cirrhosis and in the control group were 54, 30, 49 and 27 %, respectively. Peak arterial ammonia levels differed significantly between transplant-free 28-day survivors and non-survivors in the HH and ALF groups (p 0.01 for both). Multivariate regression identified peak arterial ammonia concentrations as an independent predictor of 28-day mortality or liver transplantation in patients with HH and ALF, respectively (p 0.01). There was no association between mortality and arterial ammonia in patients with liver cirrhosis and in the control group. Admission arterial ammonia levels were independently linked to hepatic encephalopathy grades 3/4 in patients with HH (p 0.01), ALF (p 0.05) and cirrhosis (p 0.05), respectively.Elevated arterial ammonia levels indicate a poor prognosis in acute liver injury and are associated with advanced HE in HH, ALF and cirrhosis. Arterial ammonia levels provide additional information in the risk assessment of critically ill patients with liver disease.

The disseminated intravascular coagulation (DIC) score is a predictor of outcome in critically ill patients [1,2]. Yet disturbances of coagulation and hemostasis, as reflected by the DIC score, are a common finding in patients with liver cirrhosis. Thus, it is unclear whether the DIC score has prognostic value in critically ill patients with liver cirrhosis. The aim of this study was to assess the applicability and prognostic impact of the DIC score in critically ill patients with liver cirrhosis.

Hypoxic hepatitis (HH) is a frequent cause of acute hepatocellular damage in critically ill patients associated with high mortality. Indocyanine green, a medical dye, is removed solely by the liver without entering enterohepatic circulation. Therefore its plasma disappearance rate (ICG-PDR) is an effective clinical tool for assessment of liver function in acute and chronic hepatic disease.

The disseminated intravascular coagulation (DIC) score is a predictor of outcome in critically ill patients [1]. Yet, disturbances of coagulation are a common finding in patients with liver cirrhosis. Thus, the prognostic value of the DIC score and its subcomponents in patients with liver cirrhosis is unclear.