Glucocorticoids induce a maladaptive epithelial stress response to aggravate acute kidney injury.

Acute kidney injury (AKI) is a frequent and challenging clinical condition associated with high morbidity and mortality and represents a common complication in critically ill patients with COVID-19. In AKI, renal tubular epithelial cells (TECs) are a primary site of damage, and recovery from AKI depends on TEC plasticity. However, the molecular mechanisms underlying adaptation and maladaptation of TECs in AKI remain largely unclear. Here, our study of an autopsy cohort of patients with COVID-19 provided evidence that injury of TECs by myoglobin, released as a consequence of rhabdomyolysis, is a major pathophysiological mechanism for AKI in severe COVID-19. Analyses of human kidney biopsies, mouse models of myoglobinuric and gentamicin-induced AKI, and mouse kidney tubuloids showed that TEC injury resulted in activation of the glucocorticoid receptor by endogenous glucocorticoids, which aggravated tubular damage. The detrimental effect of endogenous glucocorticoids on injured TECs was exacerbated by the administration of a widely clinically used synthetic glucocorticoid, dexamethasone, as indicated by experiments in mouse models of myoglobinuric- and folic acid-induced AKI, human and mouse kidney tubuloids, and human kidney slice cultures. Mechanistically, studies in mouse models of AKI, mouse tubuloids, and human kidney slice cultures demonstrated that glucocorticoid receptor signaling in injured TECs orchestrated a maladaptive transcriptional program to hinder DNA repair, amplify injury-induced DNA double-strand break formation, and dampen mTOR activity and mitochondrial bioenergetics. This study identifies glucocorticoid receptor activation as a mechanism of epithelial maladaptation, which is functionally important for AKI.

Intensive care unit cardiac arrest among very elderly critically ill patients - is cardiopulmonary resuscitation justified?

INTRODUCTION: The proportion of very elderly patients in the intensive care unit (ICU) is expected to rise. Furthermore, patients are likely more prone to suffer a cardiac arrest (CA) event within the ICU. The occurrence of intensive care unit cardiac arrest (ICU-CA) is associated with high mortality. To date, the incidence of ICU-CA and its clinical impact on outcome in the very old (≥ 90 years) patients treated is unknown. METHODS: Retrospective analysis of all consecutive critically ill patients ≥ 90 years admitted to the ICU of a tertiary care university hospital in Hamburg (Germany). All patients suffering ICU-CA were included and CA characteristics and functional outcome was assessed. Clinical course and outcome were assessed and compared between the subgroups of patients with and without ICU-CA. RESULTS: 1,108 critically ill patients aged ≥ 90 years were admitted during the study period. The median age was 92.3 (91.0-94.2) years and 67% (n = 747) were female. 2% (n = 25) of this cohort suffered ICU-CA after a median duration 0.5 (0.2-3.2) days of ICU admission. The presumed cause of ICU-CA was cardiac in 64% (n = 16). The median resuscitation time was 10 (2-15) minutes and the initial rhythm was shockable in 20% (n = 5). Return of spontaneous circulation (ROSC) could be achieved in 68% (n = 17). The cause of ICU admission was primarily medical in the total cohort (ICU-CA: 48% vs. No ICU-CA: 34%, p = 0.13), surgical - planned (ICU-CA: 32% vs. No ICU-CA: 37%, p = 0.61) and surgical - unplanned/emergency (ICU-CA: 43% vs. No ICU-CA: 28%, p = 0.34). The median Charlson Comorbidity Index (CCI) was 2 (1-3) points for patients with ICU-CA and 1 (0-2) for patients without ICU-CA (p = 0.54). Patients with ICU-CA had a higher disease severity according to SAPS II (ICU-CA: 54 vs. No ICU-CA: 36 points, p < 0.001). Patients with ICU-CA had a higher rate of mechanically ventilation (ICU-CA: 64% vs. No ICU-CA: 34%, p < 0.01) and required vasopressor therapy more often (ICU-CA: 88% vs. No ICU-CA: 41%, p < 0.001). The ICU and in-hospital mortality was 88% (n = 22) and 100% (n = 25) in patients with ICU-CA compared to 17% (n = 179) and 28% (n = 306) in patients without ICU-CA. The mortality rate for patients with ICU-CA was observed to be 88% (n = 22) in the ICU and 100% (n = 25) in-hospital. In contrast, patients without ICU-CA had an in-ICU mortality rate of 17% (n = 179) and an in-hospital mortality rate of 28% (n = 306) (both p < 0.001). CONCLUSION: The occurrence of ICU-CA in very elderly patients is rare but associated with high mortality. Providing CPR in this cohort did not lead to long-term survival at our centre. Very elderly patients admitted to the ICU likely benefit from supportive care only and should probably not be resuscitated due to poor chance of survival and ethical considerations. Providing personalized assurances that care will remain appropriate and in accordance with the patient's and family's wishes can optimise compassionate care while avoiding futile life-sustaining interventions.

Association of early changes in arterial carbon dioxide with acute brain injury in adult patients with extracorporeal membrane oxygenation: A ten-year retrospective study in a German tertiary care hospital.

PURPOSE: To assess the association between fluctuations of arterial carbon dioxide early after start of extracorporeal membrane oxygenation (ECMO) with intracranial hemorrhage (ICH) or ischemic stroke (IS). MATERIALS AND METHODS: This single-center retrospective study included patients who required ECMO for circulatory or respiratory failure between January 2011 and April 2021 and for whom a cerebral computed tomography (cCT) scan was available. Multivariable logistic regression models were fitted to evaluate the association between the relative change of arterial carbon dioxide (RelΔPaCO2) and ICH, IS or a composite of ICH, IS, and mortality. RESULTS: In 618 patients (venovenous ECMO: n = 295; venoarterial ECMO: n = 323) ICH occurred more frequently in patients with respiratory failure (19.0%) compared with patients with circulatory failure (6.8%). Conversely, the incidence of IS was higher in patients with circulatory failure (19.2%) compared with patients with respiratory failure (4.7%). While patients with ECMO for respiratory failure were more likely to have ICH (OR 3.683 [95% CI: 1.855;7.309], p < 0.001), they had a lower odds for IS (OR 0.360 [95%CI: 0.158;0.820], p = 0.015) compared with patients with circulatory failure. There was no significant association between RelΔPaCO2 and ICH or IS. CONCLUSIONS: Irrespective of the indication for ECMO, we did not find a significant association between the relative change in PaCO2 early after ECMO initiation and acute brain injury. Aside from early PaCO2 decline at cannulation, future studies should address fluctuations of PaCO2 throughout the course of ECMO support and their effect on acute brain injury.

[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.

Acute kidney injury predicts mortality in very elderly critically-ill patients.

BACKGROUND: The increasing admissions of very elderly patients to intensive care units (ICUs) over recent decades highlight a growing need for understanding acute kidney injury (AKI) in this population. Although these individuals are potentially at high risk for AKI and adverse outcomes, data on AKI in this population is scarce. This study investigates the AKI incidence and outcomes of critically-ill patients aging at least 90 years. METHODS: This retrospective cohort study conducted at the Department of Intensive Care Medicine, University Medical Centre Hamburg-Eppendorf, Germany (2008-2020), investigates AKI incidence and outcomes between 2008 and 2020 in critically-ill patients aged ≥ 90 years. AKI was defined according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria using creatinine dynamics and/or urine output. Primary endpoint was overall mortality after 1 year. Secondary endpoints were in-hospital mortality, length of ICU and hospital stay. RESULTS: During the study period 92,958 critically-ill patients were treated and 1108 were ≥ 90 years. Of these, 1054 patients had available creatinine values and were included in the present study. AKI occurred in 24.4%, mostly classified as mild (17.5%). AKI was independently associated with a significant increase in overall mortality (HR 1.21, 95 %-CI: 1.01-1.46), in-hospital mortality (OR 2, 1.41-2.85), length of ICU (+2.8 days, 2.3-3.3) and hospital stay (+2.3 days, 0.9-3.7). Severity escalated these effects, but even mild AKI showed significance. Introducing urine-based criteria increased incidence but compromised mortality prediction. CONCLUSIONS: AKI is a frequent complication in very elderly critically-ill patients. Occurrence of AKI at any stage was associated with increased mortality. Predictive ability applied to AKI defined by creatinine but not urine output. Careful attention of creatinine dynamics is essential in very elderly ICU-patients.

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.

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.

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.

Outcomes in very elderly ICU patients surgically treated for proximal femur fractures.

Proximal femur fractures (PFF) are a common injury in elderly patients that significantly impact mobility and daily living activities. Mortality rates in this population are also high, making effective treatment essential. Recent advances in intensive and geriatric care have enabled complex surgical interventions that were previously not feasible. However, there is a lack of studies focusing on outcome parameters in very elderly patients (≥ 90 years) who receive intensive care treatment following PFFs. In this retrospective study, we analyzed multi-layered data of 148 patients who were 90 years or older and received intensive care after trauma and orthopedic surgical treatment for PFFs or periprosthetic fractures between 2009 and 2019. All patients received a 365-day follow-up. To identify potential predictors of mortality, all deceased and surviving patients were subjected to multiple logistic regression analyses. We found that 22% of patients deceased during in-hospital care, and one-year survival was 44%. Independent predictors of one-year all-cause mortality included higher CCI and SOFA scores at ICU admission. Overall, 53% of patients who resided in private dwellings prior to admission were able to return home. Our study highlights the utility of using CCI and SOFA scores at ICU admission as prognostic indicators in critically ill very elderly patients who undergo surgical treatment for PFFs. These scores can provide valuable insight into the severity of illness and potential outcomes, which can inform resource allocation, prioritize endangered patients, and aid in end-of-life discussions and planning with patients and their families. Our findings can help improve the management of PFFs in very elderly patients and contribute to optimized patient care.

Early acute kidney injury and transition to renal replacement therapy in critically ill patients with SARS-CoV-2 requiring veno-venous extracorporeal membrane oxygenation.

BACKGROUND: Critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requiring veno-venous extracorporeal membrane oxygenation (vv-ECMO) are at risk for acute kidney injury (AKI). Currently, the incidence of AKI and progression to kidney replacement therapy (RRT) in critically ill patients with vv-ECMO for severe COVID-19 and implications on outcome are still unclear. METHODS: Retrospective analysis at the University Medical Center Hamburg-Eppendorf (Germany) between March 1st, 2020 and July 31st, 2021. Demographics, clinical parameters, AKI, type of organ support, length of ICU stay, mortality and severity scores were assessed. RESULTS: Ninety-one critically ill patients with SARS-CoV-2 requiring ECMO were included. The median age of the study population was 57 (IQR 49-64) years and 67% (n = 61) were male. The median SAPS II and SOFA Score on admission were 40 (34-46) and 12 (10-14) points, respectively. We observed that 45% (n = 41) developed early-AKI, 38% (n = 35) late-AKI and 16% (n = 15) no AKI during the ICU stay. Overall, 70% (n = 64) of patients required RRT during the ICU stay, 93% with early-AKI and 74% with late-AKI. Risk factors for early-AKI were younger age (OR 0.94, 95% CI 0.90-0.99, p = 0.02) and SAPS II (OR 1.12, 95% CI 1.06-1.19, p < 0.001). Patients with and without RRT were comparable regarding baseline characteristics. SAPS II (41 vs. 37 points, p < 0.05) and SOFA score (13 vs. 12 points, p < 0.05) on admission were significantly higher in patients receiving RRT. The median duration of ICU (36 vs. 28 days, p = 0.27) stay was longer in patients with RRT. An ICU mortality rate in patients with RRT in 69% (n = 44) and in patients without RRT of 56% (n = 27) was observed (p = 0.23). CONCLUSION: Critically ill patients with severe SARS-CoV-2 related ARDS requiring vv-ECMO are at high risk of early acute kidney injury. Early-AKI is associated with age and severity of illness, and presents with high need for RRT. Mortality in patients with RRT was comparable to patients without RRT.

Association between Red Cell Distribution Width and Outcomes of Nonagenarians Admitted to the Intensive Care Unit-A Retrospective Cohort Study.

The red cell distribution width (RDW) measures the heterogeneity of the erythrocyte volume. Different clinical conditions are associated with increased RDW, and high levels (>14.5%) have been described as a predictive marker for unfavorable outcomes and mortality in critically ill patients. However, there is a lack of data on very elderly critically ill patients. Therefore, we aimed to investigate the association of RDW with outcomes in critically ill patients ≥ 90 years. A retrospective analysis was conducted for all consecutive critically ill patients ≥ 90 years who were admitted to the Department of Intensive Care Medicine of the Medical University Centre Hamburg-Eppendorf (Hamburg, Germany) with available RDW on admission. Clinical course and laboratory were analyzed for all patients with eligible RDW. High RDW was defined as (>14.5%). We clinically assessed factors associated with mortality. Univariable and multivariable Cox regression analysis was performed to determine the prognostic impact of RDW on 28-day mortality. During a 12-year period, we identified 863 critically ill patients ≥ 90 years old with valid RDW values and complete clinical data. In total, 32% (n = 275) died within 28 days, and 68% (n = 579) survived for 28 days. Median RDW levels on ICU admission were significantly higher in non-survivors compared with survivors (15.6% vs. 14.8%, p < 0.001). Overall, 38% (n = 327) had low, and 62% (n = 536) had high RDW. The proportion of high RDW (>14.5%) was significantly higher in non-survivors (73% vs. 57%, p < 0.001). Patients with low RDW presented with a lower Charlson Comorbidity Index (p = 0.014), and their severity of illness on admission was lower (SAPS II: 35 vs. 38 points, p < 0.001). In total, 32% (n = 104) in the low and 35% (n = 190) in the high RDW group were mechanically ventilated (p = 0.273). The use of vasopressors (35% vs. 49%, p < 0.001) and renal replacement therapy (1% vs. 5%, p = 0.007) was significantly higher in the high RDW group. Cox regression analysis demonstrated that high RDW was significantly associated with 28-day mortality [crude HR 1.768, 95% CI (1.355-2.305); p < 0.001]. This association remained significant after adjusting for multiple confounders [adjusted HR 1.372, 95% CI (1.045-1.802); p = 0.023]. High RDW was significantly associated with mortality in critically ill patients ≥ 90 years. RDW is a useful simple parameter for risk stratification and may aid guidance for the therapy in very elderly critically ill patients.

Comparative analysis of characteristics and outcomes in hospitalized COVID-19 patients infected with different SARS-CoV-2 variants between January 2020 and April 2022 - A retrospective single-center cohort study.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, the roll-out of vaccines and therapeutic agents, as well as the emergence of novel SARS-CoV-2 variants, have shown significant effects on disease severity. METHODS: Patients hospitalized at our center between January 2020 and April 2022 were attributed to subgroups depending on which SARS-CoV-2 variant was predominantly circulating in Germany: (i) Wild-type: January 1, 2020, to March 7, 2021, (ii) Alpha variant: August 3, 2021, to June 27, 2021, (iii) Delta variant: June 28, 2021, to December 26, 2021, and (iv) Omicron variant: December 27, 2021, to April 30, 2022. RESULTS: Between January 2020 and April 2022, 1500 patients with SARS-CoV-2 infections were admitted to the University Medical Center Hamburg-Eppendorf. The rate of patients who were admitted to the intensive care unit (ICU) decreased from 31.2% (n = 223) in the wild-type group, 28.5% (n = 72) in the Alpha variant group, 18.8% (n = 67) in the Delta variant group, and 13.4% (n = 135) in the Omicron variant group. Also, in-hospital mortality decreased from 20.6% (n = 111) in the wild-type group, 17.5% (n = 30) in the Alpha variant group, 16.8% (n = 33) in the Delta variant group, and 6.6% (n = 39) in the Omicron variant group. The median duration of hospitalization was similar in all subgroups and ranged between 11 and 15 days throughout the pandemic. CONCLUSIONS: In-hospital mortality and rate of ICU admission among hospitalized COVID-19 patients steadily decreased throughout the pandemic. However, the practically unchanged duration of hospitalization demonstrates the persistent burden of COVID-19 on the healthcare system.

[Procedure after successful cardiopulmonary resuscitation-Cooling or no more cooling?] / Vorgehen nach erfolgreicher Reanimation ­ kühlen oder nicht mehr kühlen?

Approximately 84 out of 100,000 inhabitants in Europe suffer from an out of hospital cardiac arrest (OHCA) each year. The mortality after cardiac arrest (CA) is high and is particularly determined by the predominant cardiogenic shock condition and hypoxic ischemic encephalopathy. For almost two decades hypothermic temperature control was the only neuroprotective intervention recommended in guidelines for postresuscitation care; however, recently published studies failed to demonstrate any improvement in the neurological outcome with hypothermia in comparison to strict normothermia in postresuscitation treatment. According to the European Resuscitation Council (ERC) and European Society of Intensive Care Medicine (ESICM) guidelines published in 2022, unconscious adults after CA should be treated with temperature management and avoidance of fever; however, many questions remain open regarding the optimal target temperature, the cooling methods and the optimal duration. Despite these currently unanswered questions, a structured and high-quality postresuscitation care that includes a targeted temperature management should continue to be provided for all patients in the postresuscitation phase, independent of the selected target temperature. Furthermore, fever avoidance remains an important component of postresuscitation care.

Incidence of hypoxic hepatitis in patients with cardiogenic shock and association with mortality.

AIMS: Shock of any cause leads to end-organ damage due to ischaemia, especially in perfusion-sensitive organs such as the liver. In septic shock, hypoxic hepatitis (S-HH) is defined as the 20-fold increase of the upper normal limit of aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) and is associated with a mortality of up to 60%. However, as pathophysiology, dynamics, and treatment differ between septic and cardiogenic shock (CS), the S-HH definition may not be suitable for CS. Therefore, we aim to evaluate if the S-HH definition is applicable in CS patients. METHODS AND RESULTS: This analysis was based on a registry of all-comer CS patients treated between 2009 and 2019 at a tertiary care centre with exclusion of minors and patients without all necessary ASAT and ALAT values. N = 698. During in-hospital follow-up, 386 (55.3%) patients died. The S-HH was not significantly associated with in-hospital mortality in CS patients. To define HH among patients with CS (C-HH), optimal cut-off values were found to be ≥1.34-fold increase for ASAT and ≥1.51-fold increase for ALAT in serial measurements. The incidence of C-HH was 254/698 patients (36%) and C-HH showed a strong association with in-hospital mortality (odds ratio 2.36, 95% confidence interval: 1.61, 3.49). CONCLUSION: The C-HH is a frequent and relevant comorbidity in patients with CS, although its definition varies from the established definition of HH in patients with septic shock. As C-HH contributed to excess mortality risk, these findings emphasize the need for further investigation of therapies reducing the occurrence of C-HH and also improving the associated outcome.

Residual risk identified in routine noninvasive follow-up assessments in pulmonary arterial hypertension.

Background: The 2022 ESC/ERS guidelines on pulmonary hypertension recommend noninvasive risk assessments based on three clinical variables during follow-up in patients with pulmonary arterial hypertension (PAH). We set out to test whether residual risk can be captured from routinely measured noninvasive clinical variables during follow-up in PAH. Methods: We retrospectively studied 298 incident PAH patients from a German pulmonary hypertension centre who underwent routine noninvasive follow-up assessments including exercise testing, echocardiography, electrocardiography, pulmonary function testing and biochemistry. To select variables, we used least absolute shrinkage and selection operator (LASSO)-regularised Cox regression models. Outcome was defined as mortality or lung transplant after first follow-up assessment. Results: 12 noninvasive variables that were associated with outcomes in a training sub-cohort (n=208) after correction for multiple testing entered LASSO modelling. A model combining seven variables discriminated 1-year (area under the curve (AUC) 0.83, 95% confidence interval (CI) 0.68-0.99, p=8.4×10-6) and 3-year (AUC 0.81, 95% CI 0.70-0.92, p=2.9×10-8) outcome status in a replication sub-cohort (n=90). The model's discriminatory ability was comparable to that of the guideline approach in the replication sub-cohort. From the individual model components, World Health Organization functional class, 6-min walking distance and the tricuspid annular plane systolic excursion to systolic pulmonary arterial pressure (TAPSE/sPAP) ratio were sensitive to treatment initiation. Addition of TAPSE/sPAP ratio to the guideline approach numerically increased its ability to discriminate outcome status. Conclusion: Our real-world data suggest that residual risk can be captured by noninvasive clinical procedures during routine follow-up assessments in patients with PAH and highlights the potential use of echocardiographic imaging to refine risk assessment.

Impact of COVID-19 on Sedation Requirements during Veno-Venous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome.

COVID-19-associated ARDS (C-ARDS) is mentioned to express higher analgosedation needs, in comparison to ARDS of other etiologies. The objective of this monocentric retrospective cohort study was to compare the analgosedation needs between C-ARDS and non-COVID-19 ARDS (non-C-ARDS) on veno-venous extracorporeal membrane oxygenation (VV-ECMO). Data were collected from the electronic medical records of all adult patients treated with C-ARDS in our Department of Intensive Care Medicine between March 2020 and April 2022. The control group included patients treated with non-C-ARDS between the years 2009 and 2020. A sedation sum score was created in order to describe the overall analgosedation needs. A total of 115 (31.5%) patients with C-ARDS and 250 (68.5%) with non-C-ARDS requiring VV-ECMO therapy were included in the study. The sedation sum score was significantly higher in the C-ARDS group (p < 0.001). COVID-19 was significantly associated with analgosedation in the univariable analysis. By contrast, the multivariable model did not show a significant association between COVID-19 and the sum score. The year of VV-ECMO support, BMI, SAPS II and prone positioning were significantly associated with sedation needs. The potential impact of COVID-19 remains unclear, and further studies are warranted in order to evaluate specific disease characteristics linked with analgesia and sedation.

Clinical surrogates of dysautonomia predict lethal outcome in COVID-19 on intensive care unit.

BACKGROUND: Unpredictable vegetative deteriorations made the treatment of patients with acute COVID-19 on intensive care unit particularly challenging during the first waves of the pandemic. Clinical correlates of dysautonomia and their impact on the disease course in critically ill COVID-19 patients are unknown. METHODS: We retrospectively analyzed data collected during a single-center observational study (March 2020-November 2021) which was performed at the University Medical Center Hamburg-Eppendorf, a large tertiary medical center in Germany. All patients admitted to ICU due to acute COVID-19 disease during the study period were included (n = 361). Heart rate variability (HRV) and blood pressure variability (BPV) per day were used as clinical surrogates of dysautonomia and compared between survivors and non-survivors at different time points after admission. Intraindividual correlation of vital signs with laboratory parameters were calculated and corrected for age, sex and disease severity. RESULTS: Patients who deceased in ICU had a longer stay (median days ± IQR, survivors 11.0 ± 27.3, non-survivors 14.1 ± 18.7, P = 0.85), in contrast time spent under invasive ventilation was not significantly different (median hours ± IQR, survivors 322 ± 782, non-survivors 286 ± 434, P = 0.29). Reduced HRV and BPV predicted lethal outcome in patients staying on ICU longer than 10 days after adjustment for age, sex, and disease severity. Accordingly, HRV was significantly less correlated with inflammatory markers (e.g. CRP and Procalcitonin) and blood carbon dioxide in non-survivors in comparison to survivors indicating uncoupling between autonomic function and inflammation in non-survivors. CONCLUSIONS: Our study suggests autonomic dysfunction as a contributor to mortality in critically ill COVID-19 patients during the first waves of the pandemic. Serving as a surrogate for disease progression, these findings could contribute to the clinical management of COVID-19 patients admitted to the ICU. Furthermore, the suggested measure of dysautonomia and correlation with other laboratory parameters is non-invasive, simple, and cost-effective and should be evaluated as an additional outcome parameter in septic patients treated in the ICU in the future.

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.