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Abstract Postoperative fluid overload (FO) after cardiac surgery is common and affects recovery. Predicting FO could help optimize fluid management. This post-hoc analysis of the HERACLES randomized controlled trial evaluated the predictive value of MR-proADM for FO post-cardiac surgery. MR-proADM levels were measured at four different timepoints in 33 patients undergoing elective cardiac surgery. Patients were divided into FO (> 5% weight gain) and no-FO at ICU discharge. The primary outcome was the predictive power of MR-proADM at ICU admission for FO at discharge. Secondary outcomes included the predictive value of MR-proADM for FO on day 6 post-surgery and changes over time. The association between MR-proADM and FO at ICU discharge or day 6 post-surgery was not significant (crude odds ratio (cOR): 4.3 (95% CI 0.5–40.9, p = 0.201) and cOR 1.1 (95% CI 0.04–28.3, p = 0.954)). MR-proADM levels over time did not differ significantly between patients with and without FO at ICU discharge (p = 0.803). MR-proADM at ICU admission was not associated with fluid overload at ICU discharge in patients undergoing elective cardiac surgery. MR-proADM levels over time were not significantly different between groups, although elevated levels were observed in patients with FO.

Abstract Background Premorbid conditions influence the outcome of acutely ill adult patients aged 80 years and over who are admitted to the ICU. The aim of this study was to determine the influence of such premorbid conditions on 6 month survival. Methods Prospective cohort study in 242 ICUs from 22 countries including patients 80 years or above, admitted over a 6 months period to an ICU between May 2018 and May 2019. Only emergency (acute) ICU admissions in adult patients ≥ 80 years of age were eligible. Patients who were admitted after planned/elective surgery were excluded. We measured the Clinical Frailty Scale (CFS), the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), disability with the Katz activities of daily living (ADL) score, comorbidities and a Polypharmacy Score (CPS). Results Overall, the VIP2 study included 3920 patients. During ICU stay 1191 patients died (30.9%), and another 436 patients (11.1%) died after ICU discharge but within the first 30 days of admission, and an additional 895 patients died hereafter but within the first 6 months after admission (22.8%). The 6 months mortality was 64%. The median CFS was 4 (IQR 3–6). Frailty (CFS ≥ 5) was present in 26.6%. Cognitive decline (IQCODE above 3.5) was found in 30.2%. The median IQCODE was 3.19. A Katz ADL of 4 or less was present in 27.7%. Patients who surviving > 6 months were slightly younger (median age survivors 84 with IQR 81–86) than patients dying within the first 6 months (median age 84, IQR 82–87, p = 0.013), were less frequently frail (CFS > 5 in 19% versus 34%, p

Severe COVID-19 is characterized by systemic inflammation and multiple organ dysfunction syndrome (MODS). Arterial and venous thrombosis are involved in the pathogenesis of MODS and fatality in COVID-19. There is evidence that complement and neutrophil activation in the form of neutrophil extracellular traps are main drivers for development of microvascular complications in COVID-19. Plasma and serum samples were collected from 83 patients infected by SARS-CoV-2 during the two first waves of COVID-19, before the availability of SARS-CoV-2 vaccination. Samples were collected at enrollment, day 11, and day 28; and patients had differing severity of disease. In this comprehensive study, we measured cell-free DNA, neutrophil activation, deoxyribonuclease I activity, complement activation, and D-dimers in longitudinal samples of COVID-19 patients. We show that all the above markers, except deoxyribonuclease I activity, increased with disease severity. Moreover, we provide evidence that in severe disease there is continued neutrophil and complement activation, as well as D-dimer formation and nucleosome release, whereas in mild and moderate disease all these markers decrease over time. These findings suggest that neutrophil and complement activation are important drivers of microvascular complications and that they reflect immunothrombosis in these patients. Neutrophil activation, complement activation, cell-free DNA, and D-dimer levels have the potential to serve as reliable biomarkers for disease severity and fatality in COVID-19. They might also serve as suitable markers with which to monitor the efficacy of therapeutic interventions in COVID-19.

Abstract Background Non-invasive ventilation (NIV) has been commonly used to treat acute respiratory failure due to COVID-19. In this study we aimed to compare outcomes of older critically ill patients treated with NIV before and during the COVID-19 pandemic. Methods We analysed a merged cohort of older adults admitted to intensive care units (ICUs) due to respiratory failure. Patients were enrolled into one of two prospective observational studies: before COVID-19 (VIP2—2018 to 2019) and admitted due to COVID-19 (COVIP—March 2020 to January 2023). The outcomes included: 30-day mortality, intubation rate and NIV failure (death or intubation within 30 days). Results The final cohort included 1986 patients (1292 from VIP2, 694 from COVIP) with a median age of 83 years. NIV was used as a primary mode of respiratory support in 697 participants (35.1%). ICU admission due to COVID-19 was associated with an increased 30-day mortality (65.5% vs. 36.5%, HR 2.18, 95% CI 1.71 to 2.77), more frequent intubation (36.9% vs. 17.5%, OR 2.63, 95% CI 1.74 to 3.99) and NIV failure (76.2% vs. 45.3%, OR 4.21, 95% CI 2.84 to 6.34) compared to non-COVID causes of respiratory failure. Sensitivity analysis after exclusion of patients in whom life supporting treatment limitation was introduced during primary NIV confirmed higher 30-day mortality in patients with COVID-19 (52.5% vs. 23.4%, HR 2.64, 95% CI 1.83 to 3.80). Conclusion The outcomes of patients aged ≥80 years treated with NIV during COVID-19 pandemic were worse compared then those treated with NIV in the pre-pandemic era.

Abstract Background In the early COVID-19 pandemic concerns about the correct choice of analgesics in patients with COVID-19 were raised. Little data was available on potential usefulness or harmfulness of prescription free analgesics, such as paracetamol. This international multicentre study addresses that lack of evidence regarding the usefulness or potential harm of paracetamol intake prior to ICU admission in a setting of COVID-19 disease within a large, prospectively enrolled cohort of critically ill and frail intensive care unit (ICU) patients. Methods This prospective international observation study (The COVIP study) recruited ICU patients ≥ 70 years admitted with COVID-19. Data on Sequential Organ Failure Assessment (SOFA) score, prior paracetamol intake within 10 days before admission, ICU therapy, limitations of care and survival during the ICU stay, at 30 days, and 3 months. Paracetamol intake was analysed for associations with ICU-, 30-day- and 3-month-mortality using Kaplan Meier analysis. Furthermore, sensitivity analyses were used to stratify 30-day-mortality in subgroups for patient-specific characteristics using logistic regression. Results 44% of the 2,646 patients with data recorded regarding paracetamol intake within 10 days prior to ICU admission took paracetamol. There was no difference in age between patients with and without paracetamol intake. Patients taking paracetamol suffered from more co-morbidities, namely diabetes mellitus (43% versus 34%, p

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic demands reliable prognostic models for estimating the risk of long COVID. We developed and validated a prediction model to estimate the probability of known common long COVID symptoms at least 60 days after acute COVID-19. Methods The prognostic model was built based on data from a multicentre prospective Swiss cohort study. Included were adult patients diagnosed with COVID-19 between February and December 2020 and treated as outpatients, at ward or intensive/intermediate care unit. Perceived long-term health impairments, including reduced exercise tolerance/reduced resilience, shortness of breath and/or tiredness (REST), were assessed after a follow-up time between 60 and 425 days. The data set was split into a derivation and a geographical validation cohort. Predictors were selected out of twelve candidate predictors based on three methods, namely the augmented backward elimination (ABE) method, the adaptive best-subset selection (ABESS) method and model-based recursive partitioning (MBRP) approach. Model performance was assessed with the scaled Brier score, concordance c statistic and calibration plot. The final prognostic model was determined based on best model performance. Results In total, 2799 patients were included in the analysis, of which 1588 patients were in the derivation cohort and 1211 patients in the validation cohort. The REST prevalence was similar between the cohorts with 21.6% (n = 343) in the derivation cohort and 22.1% (n = 268) in the validation cohort. The same predictors were selected with the ABE and ABESS approach. The final prognostic model was based on the ABE and ABESS selected predictors. The corresponding scaled Brier score in the validation cohort was 18.74%, model discrimination was 0.78 (95% CI: 0.75 to 0.81), calibration slope was 0.92 (95% CI: 0.78 to 1.06) and calibration intercept was −0.06 (95% CI: −0.22 to 0.09). Conclusion The proposed model was validated to identify COVID-19-infected patients at high risk for REST symptoms. Before implementing the prognostic model in daily clinical practice, the conduct of an impact study is recommended.

Abstract Aims Continuous‐flow left ventricular assist devices (CF‐LVADs) have become a standard of care in end‐stage heart failure. Limited data exist comparing outcomes of HeartMate3 (HM3) and HeartWare HVAD (HW). We aimed to compare midterm outcomes of these devices. Methods and results Investigator‐initiated retrospective‐observational comparative analysis of all patients who underwent primary LVAD implantation of either HM3 or HW at our centre between January 2010 and December 2020. Data were derived from a prospective registry. Primary endpoints were all‐cause mortality and heart transplantation. Secondary endpoints included device‐related major adverse cardiac and cerebrovascular events, which included major bleeding, major neurological dysfunction (defined as persisting neurological impairment for ≥24 h), device‐related major infection (excluding driveline infections), major device malfunctions leading to re‐intervention or partial device exchange (pump failure, outflow‐graft twist or failure, controller failure, battery failure, patient cable failure, but excluding pump thrombosis), and pump thrombosis. Further secondary endpoints included right heart failure, gastrointestinal bleeding, driveline infections, and surgical re‐interventions. The secondary outcomes were analysed not only for the first event but also for recurrent events. The analysis included competing risks analysis and recurrent event regression analysis, with adjustment for confounders age, gender, body mass index (BMI), and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level. Out of 106 primary CF‐LVAD implantations, 36 (34%) received HM3 and 70 (66%) received HW. Median follow‐up was 1.48 years [interquartile range 0.67, 2.41]. HM3 was more often implanted in men (91.7% vs. 72.9%, P = 0.024); patients were older (median 61 years [54, 66.5] vs. 52.5 years [43, 60], P

Abstract In Europe, tax-based healthcare systems (THS) and social health insurance systems (SHI) coexist. We examined differences in 30-day mortality among critically ill patients aged ≥ 70 years treated in intensive care units in a THS or SHI. Retrospective cohort study. 2406 (THS n = 886; SHI n = 1520) critically ill ≥ 70 years patients in 129 ICUs. Generalized estimation equations with robust standard errors were chosen to create population average adjusted odds ratios (aOR). Data were adjusted for patient-specific variables, organ support and health economic data. The primary outcome was 30-day-mortality. Numerical differences between SHI and THS in SOFA scores (6 ± 3 vs. 5 ± 3; p = 0.002) were observed, but clinical frailty scores were similar (> 4; 17% vs. 14%; p = 0.09). Higher rates of renal replacement therapy (18% vs. 11%; p

BackgroundExposure to elevated sound pressure levels within the intensive care unit is known to negatively affect patient and staff health. In the past, interventions to address this problem have been unsuccessful as there is no conclusive evidence on the severity of each sound source and their role on the overall sound pressure levels. Therefore, the goal of the study was to perform a continuous 1 week recording to characterize the sound pressure levels and identify negative sound sources in this setting.MethodsIn this prospective, systematic, and quantitative observational study, the sound pressure levels and sound sources were continuously recorded in a mixed medical–surgical intensive care unit over 1 week. Measurements were conducted using four sound level meters and a human observer present in the room noting all sound sources arising from two beds.ResultsThe mean 8 h sound pressure level was significantly higher during the day (52.01 ± 1.75 dBA) and evening (50.92 ± 1.66 dBA) shifts than during the night shift (47.57 ± 2.23; F(2, 19) = 11.80, p

Abstract Background The objective was to investigate the role of gene expression and plasma levels of the muscular protein myostatin in intensive care unit-acquired weakness (ICUAW). This was performed to evaluate a potential clinical and/or pathophysiological rationale of therapeutic myostatin inhibition. Methods A retrospective analysis from pooled data of two prospective studies to assess the dynamics of myostatin plasma concentrations (day 4, 8 and 14) and myostatin gene (MSTN) expression levels in skeletal muscle (day 15) was performed. Associations of myostatin to clinical and electrophysiological outcomes, muscular metabolism and muscular atrophy pathways were investigated. Results MSTN gene expression (median [IQR] fold change: 1.00 [0.68–1.54] vs. 0.26 [0.11–0.80]; p = 0.004) and myostatin plasma concentrations were significantly reduced in all critically ill patients when compared to healthy controls. In critically ill patients, myostatin plasma concentrations increased over time (median [IQR] fold change: day 4: 0.13 [0.08/0.21] vs. day 8: 0.23 [0.10/0.43] vs. day 14: 0.40 [0.26/0.61]; p

Abstract Background Noninvasive ventilation (NIV) is a promising alternative to invasive mechanical ventilation (IMV) with a particular importance amidst the shortage of intensive care unit (ICU) beds during the COVID-19 pandemic. We aimed to evaluate the use of NIV in Europe and factors associated with outcomes of patients treated with NIV. Methods This is a substudy of COVIP study—an international prospective observational study enrolling patients aged ≥ 70 years with confirmed COVID-19 treated in ICU. We enrolled patients in 156 ICUs across 15 European countries between March 2020 and April 2021.The primary endpoint was 30-day mortality. Results Cohort included 3074 patients, most of whom were male (2197/3074, 71.4%) at the mean age of 75.7 years (SD 4.6). NIV frequency was 25.7% and varied from 1.1 to 62.0% between participating countries. Primary NIV failure, defined as need for endotracheal intubation or death within 30 days since ICU admission, occurred in 470/629 (74.7%) of patients. Factors associated with increased NIV failure risk were higher Sequential Organ Failure Assessment (SOFA) score (OR 3.73, 95% CI 2.36–5.90) and Clinical Frailty Scale (CFS) on admission (OR 1.46, 95% CI 1.06–2.00). Patients initially treated with NIV (n = 630) lived for 1.36 fewer days (95% CI − 2.27 to − 0.46 days) compared to primary IMV group (n = 1876). Conclusions Frequency of NIV use varies across European countries. Higher severity of illness and more severe frailty were associated with a risk of NIV failure among critically ill older adults with COVID-19. Primary IMV was associated with better outcomes than primary NIV. Clinical Trial Registration NCT04321265 , registered 19 March 2020, https://clinicaltrials.gov .

Abstract Background The COVID‐19 pandemic has greatly increased the incidence and clinical importance of critical illness myopathy (CIM), because it is one of the most common complications of modern intensive care medicine. Current diagnostic criteria only allow diagnosis of CIM at an advanced stage, so that patients are at risk of being overlooked, especially in early stages. To determine the frequency of CIM and to assess a recently proposed tool for early diagnosis, we have followed a cohort of COVID‐19 patients with acute respiratory distress syndrome and compared the time course of muscle excitability measurements with the definite diagnosis of CIM. Methods Adult COVID‐19 patients admitted to the Intensive Care Unit of the University Hospital Bern, Switzerland requiring mechanical ventilation were recruited and examined on Days 1, 2, 5, and 10 post‐intubation. Clinical examination, muscle excitability measurements, medication record, and laboratory analyses were performed on all study visits, and additionally nerve conduction studies, electromyography and muscle biopsy on Day 10. Muscle excitability data were compared with a cohort of 31 age‐matched healthy subjects. Diagnosis of definite CIM was made according to the current guidelines and was based on patient history, results of clinical and electrophysiological examinations as well as muscle biopsy. Results Complete data were available in 31 out of 44 recruited patients (mean [SD] age, 62.4 [9.8] years). Of these, 17 (55%) developed CIM. Muscle excitability measurements on Day 10 discriminated between patients who developed CIM and those who did not, with a diagnostic precision of 90% (AUC 0.908; 95% CI 0.799–1.000; sensitivity 1.000; specificity 0.714). On Days 1 and 2, muscle excitability parameters also discriminated between the two groups with 73% (AUC 0.734; 95% CI 0.550–0.919; sensitivity 0.562; specificity 0.857) and 82% (AUC 0.820; CI 0.652–0.903; sensitivity 0.750; specificity 0.923) diagnostic precision, respectively. All critically ill COVID‐19 patients showed signs of muscle membrane depolarization compared with healthy subjects, but in patients who developed CIM muscle membrane depolarization on Days 1, 2 and 10 was more pronounced than in patients who did not develop CIM. Conclusions This study reports a 55% prevalence of definite CIM in critically ill COVID‐19 patients. Furthermore, the results confirm that muscle excitability measurements may serve as an alternative method for CIM diagnosis and support its use as a tool for early diagnosis and monitoring the development of CIM.

Abstract Aims Chronic heart failure (CHF) is a major risk factor for mortality in coronavirus disease 2019 (COVID‐19). This prospective international multicentre study investigates the role of pre‐existing CHF on clinical outcomes of critically ill old (≥70 years) intensive care patients with COVID‐19. Methods and results Patients with pre‐existing CHF were subclassified as having ischaemic or non‐ischaemic cardiac disease; patients with a documented ejection fraction (EF) were subclassified according to heart failure EF: reduced (HFrEF, n = 132), mild (HFmrEF, n = 91), or preserved (HFpEF, n = 103). Associations of heart failure characteristics with the 30 day mortality were analysed in univariate and multivariate logistic regression analyses. Pre‐existing CHF was reported in 566 of 3917 patients (14%). Patients with CHF were older, frailer, and had significantly higher SOFA scores on admission. CHF patients showed significantly higher crude 30 day mortality [60% vs. 48%, P

Abstract Purpose Critically ill old intensive care unit (ICU) patients suffering from Sars-CoV-2 disease (COVID-19) are at increased risk for adverse outcomes. This post hoc analysis investigates the association of the Activities of Daily Living (ADL) with the outcome in this vulnerable patient group. Methods The COVIP study is a prospective international observational study that recruited ICU patients ≥ 70 years admitted with COVID-19 (NCT04321265). Several parameters including ADL (ADL; 0 = disability, 6 = no disability), Clinical Frailty Scale (CFS), SOFA score, intensive care treatment, ICU- and 3-month survival were recorded. A mixed-effects Weibull proportional hazard regression analyses for 3-month mortality adjusted for multiple confounders. Results This pre-specified analysis included 2359 patients with a documented ADL and CFS. Most patients evidenced independence in their daily living before hospital admission (80% with ADL = 6). Patients with no frailty and no disability showed the lowest, patients with frailty (CFS ≥ 5) and disability (ADL

Abstract Worldwide, health care professionals working in operating rooms (ORs) are exposed to electrocautery smoke on a daily basis. Aims of this study were to determine composition and concentrations of electrocautery smoke in the OR using mass spectrometry. Prospective observational study at a tertiary care academic center, involving 122 surgical procedures of which 84 were 1:1 computer randomized to smoke evacuation system (SES) versus no SES use. Irritating, toxic, carcinogenic and mutagenic VOCs were observed in OR air, with some exceeding permissible exposure limits (OSHA/NIOSH). Mean total concentration of harmful compounds was 272.69 ppb (± 189 ppb) with a maximum total concentration of harmful substances of 8991 ppb (at surgeon level, no SES). Maximum total VOC concentrations were 1.6 ± 1.2 ppm (minimally-invasive surgery) and 2.1 ± 1.5 ppm (open surgery), and total maximum VOC concentrations were 1.8 ± 1.3 ppm at the OR table ‘at surgeon level’ and 1.4 ± 1.0 ppm ‘in OR room air’ away from the operating table. Neither difference was statistically significant. In open surgery, SES significantly reduced maximum concentrations of specific VOCs at surgeon level, including aromatics and aldehydes. Our data indicate relevant exposure of health care professionals to volatile organic compounds in the OR. Surgical technique and distance to cautery devices did not significantly reduce exposure. SES reduced exposure to specific harmful VOC’s during open surgery. Trial Registration Number: NCT03924206 (clinicaltrials.gov).

Abstract Background Noise exposure leads to a reduction in cognitive abilities in diverse settings, however, only limited data exist examining the effects of environmental ICU noise on the cognitive performance of ICU professionals. A frequently occurring and demanding retention task in ICUs are ward rounds, which are considered key for the provision of medical care. Here, we investigate the influence of noise on information retention in a simulated ward round. Methods ICU professionals were exposed to a recorded, ICU ward round, simulated partly with and partly without environmental ICU noise. Ward rounds were followed by specific questions about previously provided information. Results 56 ICU professionals (aged 26–59 years) were included. A logistic mixed model showed a reduction of 27% (P

Abstract Background Intensive care unit (ICU) patients age 90 years or older represent a growing subgroup and place a huge financial burden on health care resources despite the benefit being unclear. This leads to ethical problems. The present investigation assessed the differences in outcome between nonagenarian and octogenarian ICU patients. Methods We included 7900 acutely admitted older critically ill patients from two large, multinational studies. The primary outcome was 30-day-mortality, and the secondary outcome was ICU-mortality. Baseline characteristics consisted of frailty assessed by the Clinical Frailty Scale (CFS), ICU-management, and outcomes were compared between octogenarian (80–89.9 years) and nonagenarian (> 90 years) patients. We used multilevel logistic regression to evaluate differences between octogenarians and nonagenarians. Results The nonagenarians were 10% of the entire cohort. They experienced a higher percentage of frailty (58% vs 42%; p

Abstract Background The primary aim of this study was to assess the outcome of elderly intensive care unit (ICU) patients treated during the spring and autumn COVID-19 surges in Europe. Methods This was a prospective European observational study (the COVIP study) in ICU patients aged 70 years and older admitted with COVID-19 disease from March to December 2020 to 159 ICUs in 14 European countries. An electronic database was used to register a number of parameters including: SOFA score, Clinical Frailty Scale, co-morbidities, usual ICU procedures and survival at 90 days. The study was registered at ClinicalTrials.gov (NCT04321265). Results In total, 2625 patients were included, 1327 from the first and 1298 from the second surge. Median age was 74 and 75 years in surge 1 and 2, respectively. SOFA score was higher in the first surge (median 6 versus 5, p

Abstract Background During the COVID-19 pandemic, suspension of visits by next of kin to patients in intensive care units (ICU), to prevent spread of the SARS-CoV-2 virus, has been a common practice. This could impede established family-centered care and may affect the mental health of the next of kin. The aim of this study was to explore symptoms of post-traumatic stress syndrome (PTSD) in the next of kin of ICU patients. Methods In this prospective observational single-center study, next of kin of ICU patients were interviewed by telephone, using the Impact of Event Scale-Revised (IES-R), to assess symptoms of acute stress disorder during the ICU stay and PTSD symptoms at 3 months after the ICU stay. The primary outcome was the prevalence of severe PTSD symptoms (IES-R score ≥ 33) at 3 months. The secondary outcomes comprised the IES-R scores during the ICU stay, at 3 months, and the prevalence of severe symptoms of acute stress disorder during ICU stay. An inductive content analysis was performed of the next of kin’s comments regarding satisfaction with patient care and the information they were given. Results Of the 411 ICU patients admitted during the study period, 62 patients were included together with their next of kin. An IES-R score > 33 was observed in 90.3% (56/62) of next of kin during the ICU stay and in 69.4% (43/62) 3 months later. The median IES-R score was 49 (IQR 40–61) during the ICU stay and 41 (IQR 30–55) at 3 months. The inductive content analysis showed that communication/information (55%), support (40%), distressing emotions (32%), and suspension of ICU visits (24%) were mentioned as relevant aspects by the next of kin. Conclusions During the suspension of ICU visits in the COVID-19 pandemic, high prevalence and severity of both symptoms of acute stress disorder during the ICU stay and PTSD symptoms 3 months later were observed in the next of kin of ICU patients.

Background COVID-19 remains a complex disease in terms of its trajectory and the diversity of outcomes rendering disease management and clinical resource allocation challenging. Varying symptomatology in older patients as well as limitation of clinical scoring systems have created the need for more objective and consistent methods to aid clinical decision making. In this regard, machine learning methods have been shown to enhance prognostication, while improving consistency. However, current machine learning approaches have been limited by lack of generalisation to diverse patient populations, between patients admitted at different waves and small sample sizes. Objectives We sought to investigate whether machine learning models, derived on routinely collected clinical data, can generalise well i) between European countries, ii) between European patients admitted at different COVID-19 waves, and iii) between geographically diverse patients, namely whether a model derived on the European patient cohort can be used to predict outcomes of patients admitted to Asian, African and American ICUs. Methods We compare Logistic Regression, Feed Forward Neural Network and XGBoost algorithms to analyse data from 3,933 older patients with a confirmed COVID-19 diagnosis in predicting three outcomes, namely: ICU mortality, 30-day mortality and patients at low risk of deterioration. The patients were admitted to ICUs located in 37 countries, between January 11, 2020, and April 27, 2021. Results The XGBoost model derived on the European cohort and externally validated in cohorts of Asian, African, and American patients, achieved AUC of 0.89 (95% CI 0.89–0.89) in predicting ICU mortality, AUC of 0.86 (95% CI 0.86–0.86) for 30-day mortality prediction and AUC of 0.86 (95% CI 0.86–0.86) in predicting low-risk patients. Similar AUC performance was achieved also when predicting outcomes between European countries and between pandemic waves, while the models showed high calibration quality. Furthermore, saliency analysis showed that FiO2 values of up to 40% do not appear to increase the predicted risk of ICU and 30-day mortality, while PaO2 values of 75 mmHg or lower are associated with a sharp increase in the predicted risk of ICU and 30-day mortality. Lastly, increase in SOFA scores also increase the predicted risk, but only up to a value of 8. Beyond these scores the predicted risk remains consistently high. Conclusion The models captured both the dynamic course of the disease as well as similarities and differences between the diverse patient cohorts, enabling prediction of disease severity, identification of low-risk patients and potentially supporting effective planning of essential clinical resources. Trial registration number NCT04321265. Author summary COVID-19 remains a complex disease, making it challenging to estimate the risk of deterioration of critically ill patients and consequently allocation of clinical resources, such as ventilators. As a result, there is a need to support clinical decision making through objective methods and address some of the limitations of the current clinical scoring systems. In response, we developed machine learning models using routine clinical data of patients from 37 countries worldwide, including 18 European countries. We find that: i) machine learning models can predict outcomes in patients from diverse European countries, that is which patients have a low risk of deterioration and which may require increased care such that resources are allocated efficiently; ii) routine clinical data from European patients can be used to predict outcomes in non-European patients, namely those admitted in Asian, African, and American intensive care units, without significantly affecting the performance, and iii) routine clinical data collected during the first COVID-19 pandemic wave, can be used to predict the risk of deterioration of patients admitted during subsequent waves. Our study is the first step towards improving standardisation and equity of critical care across healthcare institutions and further afield across diverse countries and territories.

Abstract Purpose Lactate is an established prognosticator in critical care. However, there still is insufficient evidence about its role in predicting outcome in COVID-19. This is of particular concern in older patients who have been mostly affected during the initial surge in 2020. Methods This prospective international observation study (The COVIP study) recruited patients aged 70 years or older (ClinicalTrials.gov ID: NCT04321265) admitted to an intensive care unit (ICU) with COVID-19 disease from March 2020 to February 2021. In addition to serial lactate values (arterial blood gas analysis), we recorded several parameters, including SOFA score, ICU procedures, limitation of care, ICU- and 3-month mortality. A lactate concentration ≥ 2.0 mmol/L on the day of ICU admission (baseline) was defined as abnormal. The primary outcome was ICU-mortality. The secondary outcomes 30-day and 3-month mortality. Results In total, data from 2860 patients were analyzed. In most patients (68%), serum lactate was lower than 2 mmol/L. Elevated baseline serum lactate was associated with significantly higher ICU- and 3-month mortality (53% vs. 43%, and 71% vs. 57%, respectively, p

Abstract Diaphragm weakness affects up to 60% of ventilated patients leading to muscle atrophy, reduction of muscle fiber force via muscle fiber injuries and prolonged weaning from mechanical ventilation. Electromagnetic stimulation of the phrenic nerve can induce contractions of the diaphragm and potentially prevent and treat loss of muscular function. Recommended safety distance of electromagnetic coils is 1 m. The aim of this study was to investigate the magnetic flux density in a typical intensive care unit (ICU) setting. Simulation of magnetic flux density generated by a butterfly coil was performed in a Berlin ICU training center with testing of potential disturbance and heating of medical equipment. Approximate safety distances to surrounding medical ICU equipment were additionally measured in an ICU training center in Bern. Magnetic flux density declined exponentially with advancing distance from the stimulation coil. Above a coil distance of 300 mm with stimulation of 100% power the signal could not be distinguished from the surrounding magnetic background noise. Electromagnetic stimulation of the phrenic nerve for diaphragm contraction in an intensive care unit setting seems to be safe and feasible from a technical point of view with a distance above 300 mm to ICU equipment from the stimulation coil.

Abstract Background The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. Methods We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient’s age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. Results The median age in the sample of 7487 consecutive patients was 84 years (IQR 81–87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p

BackgroundDespite many studies in the field examining excessive noise in the intensive care unit, this issue remains an ongoing problem. A limiting factor in the progress of the field is the inability to draw conclusions across studies due to the different and poorly reported approaches used. Therefore, the first goal is to present a method for the general measurement of sound pressure levels and sound sources, with precise details and reasoning, such that future studies can use these procedures as a guideline. The two procedures used in the general method will outline how to record sound pressure levels and sound sources, using sound level meters and observers, respectively. The second goal is to present the data collected using the applied method to show the feasibility of the general method and provide results for future reference.MethodsThe general method proposes the use of two different procedures for measuring sound pressure levels and sound sources in the intensive care unit. The applied method uses the general method to collect data recorded over 24-h, examining two beds in a four-bed room, via four sound level meters and four observers each working one at a time.ResultsThe interrater reliability of the different categories was found to have an estimate of >0.75 representing good and excellent estimates, for 19 and 16 of the 24 categories, for the two beds examined. The equivalent sound pressure levels (LAeq) for the day, evening, and night shift, as an average of the sound level meters in the patient room, were 54.12, 53.37, and 49.05 dBA. In the 24-h measurement period, talking and human generated sounds occurred for a total of 495 (39.29% of the time) and 470 min (37.30% of the time), at the two beds of interest, respectively.ConclusionA general method was described detailing two independent procedures for measuring sound pressure levels and sound sources in the ICU. In a continuous data recording over 24 h, the feasibility of the proposed general method was confirmed. Moreover, good and excellent interrater reliability was achieved in most categories, making them suitable for future studies.

OBJECTIVES:. Data on long-term effects of post-extubation dysphagia is lacking. We investigate mid- and long-term clinical outcomes in a large sample of ICU patients with systematic dysphagia screening. DESIGN:. Outcome analysis with a follow-up of 6 years or death (whichever occurred earlier) of ICU patients from a prospective observational trial (Dysphagia in Mechanically Ventilated ICU Patients study) with systematic dysphagia screening. SETTING:. ICU of a tertiary care academic center. PATIENTS:. Nine-hundred thirty-three mixed medical-surgical ICU patients (median age, 66 yr; interquartile range [IQR], 54–74, Acute Physiology and Chronic Health Evaluation II score 19 [IQR, 14–24], 71% male). INTERVENTIONS:. ICU patients were followed up for a mean follow-up period of 1,731 ± 772 days (4.7 ± 2.1 yr). Primary outcome measures were 180-day and 360-day all-cause mortality in ICU patients with versus without dysphagia. MEASUREMENTS AND MAIN RESULTS:. Two-hundred seventy-three patients died (29.3%) during the observational interval (n = 76 lost to follow-up). In dysphagia screening positive versus negative ICU patients, mortality at 180 days was 16% versus 5.8% (excess mortality 10.2%), whereas mortality at 360 days was 25% versus 9.1% (excess mortality 15.9%). Adjustment for confounders in a Cox model revealed a significant association of dysphagia with all-cause mortality in a time-dependent manner. The risk of death in ICU patients with versus without post-extubation dysphagia declined from about 2.5 times higher to about equal risk for both groups over the first year (i.e. 1.03 yr) post-ICU admission (at 360 d: hazard ratio [HR], 1.03; 95% CI, 0.42–3.70). The mean mortality HR for the first year post-ICU admission was HR 2.09 (95% CI, 1.34–3.24; p = 0.0009). CONCLUSIONS:. Long-term follow-up of a large cohort of medical-surgical adult ICU patients systematically screened for dysphagia showed that dysphagia is associated with increased hazards for death for up to 1 year after ICU admission. Our data underline effects of post-extubation dysphagia on long-term clinical outcomes in affected critically ill patients.

Abstract Introduction Neurogenic dysphagia defines swallowing disorders caused by diseases of the central and peripheral nervous system, neuromuscular transmission, or muscles. Neurogenic dysphagia is one of the most common and at the same time most dangerous symptoms of many neurological diseases. Its most important sequelae include aspiration pneumonia, malnutrition and dehydration, and affected patients more often require long-term care and are exposed to an increased mortality. Based on a systematic pubmed research of related original papers, review articles, international guidelines and surveys about the diagnostics and treatment of neurogenic dysphagia, a consensus process was initiated, which included dysphagia experts from 27 medical societies. Recommendations This guideline consists of 53 recommendations covering in its first part the whole diagnostic spectrum from the dysphagia specific medical history, initial dysphagia screening and clinical assessment, to more refined instrumental procedures, such as flexible endoscopic evaluation of swallowing, the videofluoroscopic swallowing study and high-resolution manometry. In addition, specific clinical scenarios are captured, among others the management of patients with nasogastric and tracheotomy tubes. The second part of this guideline is dedicated to the treatment of neurogenic dysphagia. Apart from dietary interventions and behavioral swallowing treatment, interventions to improve oral hygiene, pharmacological treatment options, different modalities of neurostimulation as well as minimally invasive and surgical therapies are dealt with. Conclusions The diagnosis and treatment of neurogenic dysphagia is challenging and requires a joined effort of different medical professions. While the evidence supporting the implementation of dysphagia screening is rather convincing, further trials are needed to improve the quality of evidence for more refined methods of dysphagia diagnostics and, in particular, the different treatment options of neurogenic dysphagia. The present article is an abridged and translated version of the guideline recently published online ( https://www.awmf.org/uploads/tx_szleitlinien/030-111l_Neurogene-Dysphagie_2020-05.pdf ).

Abstract Background The COVID-19 pandemic has led highly developed healthcare systems to the brink of collapse due to the large numbers of patients being admitted into hospitals. One of the potential prognostic indicators in patients with COVID-19 is frailty. The degree of frailty could be used to assist both the triage into intensive care, and decisions regarding treatment limitations. Our study sought to determine the interaction of frailty and age in elderly COVID-19 ICU patients. Methods A prospective multicentre study of COVID-19 patients ≥ 70 years admitted to intensive care in 138 ICUs from 28 countries was conducted. The primary endpoint was 30-day mortality. Frailty was assessed using the clinical frailty scale. Additionally, comorbidities, management strategies and treatment limitations were recorded. Results The study included 1346 patients (28% female) with a median age of 75 years (IQR 72–78, range 70–96), 16.3% were older than 80 years, and 21% of the patients were frail. The overall survival at 30 days was 59% (95% CI 56–62), with 66% (63–69) in fit, 53% (47–61) in vulnerable and 41% (35–47) in frail patients (p

Abstract Purpose Frailty is a valuable predictor for outcome in elderly ICU patients, and has been suggested to be used in various decision-making processes prior to and during an ICU admission. There are many instruments developed to assess frailty, but few of them can be used in emergency situations. In this setting the clinical frailty scale (CFS) is frequently used. The present study is a sub-study within a larger outcome study of elderly ICU patients in Europe (the VIP-2 study) in order to document the reliability of the CFS. Materials and methods From the VIP-2 study, 129 ICUs in 20 countries participated in this sub-study. The patients were acute admissions ≥ 80 years of age and frailty was assessed at admission by two independent observers using the CFS. Information was obtained from the patient, if not feasible, from the family/caregivers or from hospital files. The profession of the rater and source of data were recorded along with the score. Interrater variability was calculated using linear weighted kappa analysis. Results 1923 pairs of assessors were included and background data of patients were similar to the whole cohort (n = 3920). We found a very high inter-rater agreement (weighted kappa 0.86), also in subgroup analyses. The agreement when comparing information from family or hospital records was better than using only direct patient information, and pairs of raters from same profession performed better than from different professions. Conclusions Overall, we documented a high reliability using CFS in this setting. This frailty score could be used more frequently in elderly ICU patients in order to create a more holistic and realistic impression of the patient´s condition prior to ICU admission.

Abstract Background The application of manual emergency skills is essential in intensive care medicine. Simulation training on cadavers may be beneficial. The aim of this study was to analyze a skill-training aiming to enhance ICU-fellows´ performance. Methods A skill-training was prepared for chest tube insertion, pericardiocentesis, and cricothyroidotomy. Supervision levels (SL) for entrustable professional activities (EPA) were applied to evaluate skill performance. Pre- and post-training, SL and fellows´ self- versus consultants´ external assessment was compared. Time on skill training was compared to conventional training in the ICU-setting. Results Comparison of pre/post external assessment showed reduced required SL for chest tube insertion, pericardiocentesis, and cricothyroidotomy. Self- and external assessed SL did not significantly correlate for pre-training/post-training pericardiocentesis and post-training cricothyroidotomy. Correlations were observed for self- and external assessment SL for chest tube insertion and pre-assessment for cricothyroidotomy. Compared to conventional training in the ICU-setting, chest tube insertion training may further be time-saving. Conclusions Emergency skill training separated from a daily clinical ICU-setting appeared feasible and useful to enhance skill performance in ICU fellows and may reduce respective SL. We observed that in dedicated skill-training sessions, required time resources would be somewhat reduced compared to conventional training methods.

Background: In coronavirus disease-2019 (COVID-19) patients, there is increasing evidence of neuronal injury by the means of elevated serum neurofilament light chain (sNfL) levels. However, the role of systemic inflammation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific immune response with regard to neuronal injury has not yet been investigated. Methods: In a prospective cohort study, we recruited patients with mild–moderate ( n = 39) and severe ( n = 14) COVID-19 and measured sNfL levels, cytokine concentrations, SARS-CoV-2-specific antibodies including neutralizing antibody titers, and cell-mediated immune responses at enrollment and at 28(±7) days. We explored the association of neuro-axonal injury as by the means of sNfL measurements with disease severity, cytokine levels, and virus-specific immune responses. Results: sNfL levels, as an indicator for neuronal injury, were higher at enrollment and increased during follow-up in severely ill patients, whereas during mild–moderate COVID-19, sNfL levels remained unchanged. Severe COVID-19 was associated with increased concentrations of cytokines assessed [interleukin (IL)-6, IL-8, interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α)], higher anti-spike IgG and anti-nucleocapsid IgG concentrations, and increased neutralizing antibody titers compared with mild–moderate disease. Patients with more severe disease had higher counts of defined SARS-CoV-2-specific T cells. Increases in sNfL concentrations from baseline to day 28(±7) positively correlated with anti-spike protein IgG antibody levels and with titers of neutralizing antibodies. Conclusion: Severe COVID-19 is associated with increased serum concentration of cytokines and subsequent neuronal injury as reflected by increased levels of sNfL. Patients with more severe disease developed higher neutralizing antibody titers and higher counts of SARS-CoV-2-specific T cells during the course of COVID-19 disease. Mounting a pronounced virus-specific humoral and cell-mediated immune response upon SARS-CoV-2 infection did not protect from neuro-axonal damage as by the means of sNfL levels.

Abstract Background Skeletal muscle wasting is an extremely common feature in patients with heart failure, affecting approximately 20% of ambulatory patients with even higher values during acute decompensation. Its occurrence is associated with reduced exercise capacity, muscle strength, and quality of life. We sought to investigate if the presence of muscle wasting carries prognostic information. Methods Two hundred sixty‐eight ambulatory patients with heart failure (age 67.1 ± 10.9 years, New York Heart Association class 2.3 ± 0.6, left ventricular ejection fraction 39 ± 13.3%, and 21% female) were prospectively enrolled as part of the Studies Investigating Co‐morbidities Aggravating Heart Failure. Muscle wasting as assessed using dual‐energy X‐ray absorptiometry was present in 47 patients (17.5%). Results During a mean follow‐up of 67.2 ± 28.02 months, 95 patients (35.4%) died from any cause. After adjusting for age, New York Heart Association class, left ventricular ejection fraction, creatinine, N‐terminal pro‐B‐type natriuretic peptide, and iron deficiency, muscle wasting remained an independent predictor of death (hazard ratio 1.80, 95% confidence interval 1.01–3.19, P = 0.04). This effect was more pronounced in patients with heart failure with reduced than in heart failure with preserved ejection fraction. Conclusions Muscle wasting is an independent predictor of death in ambulatory patients with heart failure. Clinical trials are needed to identify treatment approaches to this co‐morbidity.

Abstract Background Noise levels on intensive care units (ICUs) are typically elevated. While many studies reported negative effects of ICU ambient sounds on patients, only few investigated noise as a factor to influence well-being or performance in healthcare professionals. Methods An online survey in the German-speaking part of Switzerland was conducted to assess how ICU soundscapes are subjectively perceived by healthcare professionals. The questionnaire was answered by 348 participants. Additionally, effects of noise on working memory performance were evaluated in an experimental noise exposure setting. Twenty-six healthcare professionals and 27 healthy controls performed a 2-back object-location task while being exposed to either ICU or pink noise. Results Survey results demonstrate that a majority of participants was aware of heightened noise levels. Participants reported that mostly well-being, performance, and attention could be reduced, along with subjective annoyance and fatigue by ICU ambient sounds. Although no significant effects of noise exposure on working memory performance was observed, self-assessments revealed significantly higher stress levels, increased annoyance and distraction ratings as well as decreased confidence in performance after ICU-noise exposure. Conclusion Subjective assessments indicate that heightened noise levels on ICUs induce annoyance, with heightened stress levels, impaired well-being, and reduced performance being potential consequences. Empirical evidence with objective and physiological measures is warranted.

AIMS OF THE STUDY: Minimally invasive extracorporeal circulation (MiECC) is an established alternative to conventional extracorporeal circulation (CECC) in coronary artery bypass graft surgery (CABG), but data on its use in cardiac reoperations are limited. We aimed to analyse perioperative morbidity and mortality in adult patients undergoing reoperations for isolated CABG using either CECC or MiECC circuits at our centre. METHODS AND RESULTS: In a single centre retrospective observational study of all adult patients undergoing cardiac reoperations for isolated CABG between 2004 and 2016, we identified 310 patients, and excluded those who received concomitant cardiac procedures (n = 205). Of the remaining 105 patients, 47 received isolated redo-CABG using MiECC, and 58 received CECC. Propensity score modelling was performed, and inversed probability treatment analysis was used between the treatment groups. Primary endpoint was 30-day all-cause mortality. Secondary endpoints included major adverse cardiac or cerebrovascular events or need for conversion to CECC. Groups were comparable, apart from a higher incidence of NYHA class III or higher in CECC group (33.5% vs 8.6%, p= 0.004). Shorter times for operation, cardiopulmonary bypass and aortic cross-clamp were observed in the MiECC group. The incidence of postoperative atrial fibrillation was significantly lower with MiECC (22.1%, p = 0.012). No significant difference was observed in all-cause 30-day mortality between the MiECC and CECC groups (6.8% vs. 8.3%, p = 0.81). CONCLUSION: We found no difference in overall mortality between CECC and MiECC in patients undergoing reoperation for isolated CABG. Furthermore, we found no indication of differences in most outcomes between extracorporeal circuit types. In the case of redo-CABG, MiECC could provide an alternative strategy.

Abstract Background We report a case of successful prolonged cardiopulmonary resuscitation (5 hours and 44 minutes) following severe accidental hypothermia with cardiac arrest treated without rewarming on extracorporeal life support. Case presentation A 52-year-old Italian mountaineer, was trapped in a crevasse and rescued approximately 7 hours later by a professional rescue team. After extrication, he suffered a witnessed cardiac arrest with ventricular fibrillation. Immediate defibrillation and cardiopulmonary resuscitation were started. His core temperature was 26.0 °C. Due to weather conditions, air transport to an extracorporeal life support center was not possible. Thus, he was rewarmed with conventional rewarming methods in a rural hospital. Auto-defibrillation occurred at a core temperature of 29.8 °C after 5 hours and 44 minutes of continued cardiopulmonary resuscitation. With a core temperature of 33.4 °C, he was finally admitted to a level 1 trauma center and extracorporeal life support was no longer required. Seven weeks following the accident, he was discharged home with complete neurological recovery. Conclusions Successful rewarming from severe hypothermia without extracorporeal life support use as performed in this case suggests that patients with primary hypothermic cardiac arrest have a chance of a favorable neurological outcome even after several hours of cardiac arrest when cardiopulmonary resuscitation and conventional rewarming are performed continuously. This may be especially relevant in remote areas, where extracorporeal life support rewarming is not available.

Background: Delayed cerebral ischemia and cerebral vasospasm remain the leading causes of poor outcome in survivors of aneurysmal subarachnoid hemorrhage. Refractory cerebral vasospasms can be treated with endovascular vasodilator therapy, which can either be performed in conscious sedation or general anesthesia. The aim of this study is to compare the effect of the anesthesia modality on long-term clinical outcomes in patients undergoing endovascular vasodilator therapy due to cerebral vasospasm and hypoperfusion. Methods: Modified Rankin Scale (mRS) scores were retrospectively analyzed at time of discharge from the hospital and six months after aneurysmal subarachnoid hemorrhage. Additionally, National Institutes of Health Stroke Scale (NIHSS) was assessed 24 hours before, immediately before, immediately after, and 24 hours after endovascular vasodilator therapy, and at discharge and six months. Interventional parameters such as duration of intervention, choice and dosage of vasodilator and number of arteries treated were also recorded. Results: A total of 98 patients were included in this analysis and separated into patients who had interventions in conscious sedation, general anesthesia and a mix of both. Neither mRS at discharge nor at six months showed a significant difference for functionally independent outcomes (mRS 0-2) between groups. NIHSS before endovascular vasodilator therapy was significantly higher in patients receiving interventions in general anesthesia but did not differ anymore between groups six months after the initial bleed. Conclusion: This study did not observe a difference in outcome whether patients underwent endovascular vasodilator therapy in general anesthesia or conscious sedation for refractory cerebral vasospasms. Hence, the choice should be made for each patient individually.

Abstract Even in the absence of disease‐specific radiological signs of granulomatosis with polyangiitis (GPA), severe intrapulmonary GPA may be present. Rapidly establishing the diagnosis with a confirmatory biopsy is key to initiate lifesaving therapy.

Abstract Background Intraoperative and postoperative management of cardiac surgery patients is complex, involving the application of differential vasopressors and volume therapy. It has been shown that a positive fluid balance has a major impact on postoperative outcome. Today, the advantages and disadvantages of buffered crystalloid solutes are a topic of controversy, with no consensus being reached so far. The use of hypertonic saline (HS) has shown promising results with respect to lower total fluid balance and postoperative weight gain in critically ill patients in preliminary studies. However, collection of more data on HS in critically ill patients seems warranted. This preliminary study aims to investigate whether fluid resuscitation using HS in patients following cardiac surgery results in less total fluid volume being administered. Methods In a prospective double-blind randomised controlled clinical trial, we aim to recruit 96 patients undergoing elective cardiac surgery for ischaemic and/or valvular heart disease. After postoperative admission to the intensive care unit (ICU), patients will be randomly assigned to receive 5 ml/kg ideal body weight HS (7.3% NaCl) or normal saline (NS, 0.9% NaCl) infused within 60 min. Blood and urine samples will be collected preoperatively and postoperatively up to day 6 to assess changes in renal, cardiac, inflammatory, acid-base, and electrolyte parameters. Additionally, we will perform renal ultrasonography studies to assess renal blood flow before, during, and after infusion, and we will measure total body water using preoperative and postoperative body composition analysis (bioimpedance). Patients will be followed up for 90 days. Discussion The key objective of this study is to assess the cumulative amount of fluid administered in the intervention (HS) group versus control (NS) group during the ICU stay. In this preliminary, prospective, randomised controlled clinical trial we will test the hypothesis that use of HS results in less total fluids infused and less postoperative weight gain when compared to the standard of intensive care in cardiac surgery patients. Trial registration ClinicalTrials.gov, NCT03280745. Registered on 12 September 2017.

Abstract Background Body weight loss is a frequent complication after stroke, and its adverse effect on clinical outcome has been shown in several clinical trials. The purpose of this prospective longitudinal single‐centre observational study was to investigate dynamical changes of body composition and body weight after ischemic stroke and an association with functional outcome. Methods Sixty‐seven consecutive patients (age 69 ± 11 years, body mass index 27.0 ± 4.1 kg/m2, 42% female patient, mean ± SD) with acute ischemic stroke with mild to moderate neurological deficit (National Institute of Health Stroke Scale median 4, ranged 0–12) were analysed in the acute phase (4 ± 2 days) and at 12 months (389 ± 26 days) follow‐up. Body composition was examined by dual energy X‐ray absorptiometry. Cachexia was defined according to the consensus definition by body weight loss ≥5% within 1 year and additional clinical signs. Lean tissue wasting was considered if a ratio of upper and lower limbs lean mass sum to squared height (kg/m2) was ≤5.45 kg/m2 for female patient and ≤7.25 kg/m2 for male patient. Results According to the body weight changes after 12 months, 42 (63%) patients had weight gain or stable weight, 11 (16%) patients had moderate weight loss, and 14 (21%) patients became cachectic. A relative decline of 19% of fat tissue and 6.5% of lean tissue was observed in cachectic patients, while no changes of lean tissue were observed in non‐cachectic patients after 12 months. The modified Rankin Scale was 48% higher (2.1 ± 1.6, P

Abstract Dysphagia may present in all critically ill patients and large-scale clinical data show that e.g. post-extubation dysphagia (PED) is commonly observed in intensive care unit (ICU) patients. Recent data demonstrate that dysphagia is mostly persisting and that its presence is independently associated with adverse patient-centered clinical outcomes. Although several risk factors possibly contributing to dysphagia development were proposed, the underlying exact mechanisms in ICU patients remain incompletely understood and no current consensus exists on how to best approach ICU patients at risk. From a clinical perspective, dysphagia is well-known to be associated with an increased risk of aspiration and aspiration-induced pneumonia, delayed resumption of oral intake/malnutrition, decreased quality of life, prolonged ICU and hospital length of stay, and increased morbidity and mortality. Moreover, the economic burden on public health care systems is high. In light of high mortality rates associated with the presence of dysphagia and the observation that dysphagia is not systematically screened for on most ICUs, this review describes epidemiology, terminology, and potential mechanisms of dysphagia on the ICU. Furthermore, the impact of dysphagia on affected individuals, health care systems, and society is discussed in addition to current and future potential therapeutic approaches.

Many milestones in medical history rest on animal modeling of human diseases. The SARS-CoV-2 pandemic has evoked a tremendous investigative effort primarily centered on clinical studies. However, several animal SARS-CoV-2/COVID-19 models have been developed and pre-clinical findings aimed at supporting clinical evidence rapidly emerge. In this review, we characterize the existing animal models exposing their relevance and limitations as well as outline their utility in COVID-19 drug and vaccine development. Concurrently, we summarize the status of clinical trial research and discuss the novel tactics utilized in the largest multi-center trials aiming to accelerate generation of reliable results that may subsequently shape COVID-19 clinical treatment practices. We also highlight areas of improvement for animal studies in order to elevate their translational utility. In pandemics, to optimize the use of strained resources in a short time-frame, optimizing and strengthening the synergy between the preclinical and clinical domains is pivotal.

Background: During descending aortic repair, critically decreased blood flow to the myelum can result in ischemic spinal cord injury and transient or permanent paraplegia. Assessment of motor evoked potentials (MEPs) has been shown to be a valuable tool which allows to detect spinal cord ischemia (SCI) intraoperatively within a therapeutic window suitable to prevent progression to paraparesis or paraplegia. MEP monitoring is not feasible during postoperative care in the awakening patient. Therefore, ancillary techniques to monitor integrity of spinal cord function are needed to detect delayed spinal cord ischemia. Objective: The purpose of this study is to evaluate whether assessment of long loop reflexes (LLR; F-waves) and paraspinal muscle oximetry using Near-Infrared Spectroscopy (NIRS) are feasible and valid in detecting delayed SCI. Methods: We aim to include patients from three tertiary referral centers undergoing aortic repair with MEP monitoring in this study.F-wave measurements and paraspinal NIRS oximetry will be operated intra- and postoperatively. Measurement characteristics and feasibility will be assessed in the first 25 patients. Subsequently, a second cohort of 75 patients will be investigated to determine the sensitivity and specificity of F-waves and NIRS in detecting perioperative SCI. In this context for the MEP group SCI is defined intraoperatively as significant MEP changes and postoperatively as newly developed paraplegia. Conclusions: A clinical study design and protocol is proposed to assess if F-waves and/or NIRS-based paraspinal oximetry are feasible and valid in detecting and monitoring for occurrences of delayed SCI. Keywords: Spinal cord ischemia, Neurophysiological monitoring techniques, NIRS oximetry, Descending aortic repair, Thoracoabdominal aortic aneurysm repair

Abstract Background Microembolism is a frequent pathological event during extracorporeal renal replacement therapy (RRT). Some previous data indicate that microemboli are generated in patients who are undergoing RRT and that these may contribute to increased cerebrovascular and neurocognitive morbidity in patients with end-stage renal disease. The current trial aims to quantify the microembolic load and respective qualitative composition that effectively reaches the intracerebral circulation in critically ill patients treated with different RRT modalities for acute kidney injury (AKI). Methods/design The COMET-AKI trial is a prospective, randomized controlled clinical trial with a 2-day clinical assessment period and follow-up visits at 6 and 12 months. Consecutive critically ill patients with AKI on continuous renal replacement therapy (CRRT) scheduled for a switch to intermittent renal replacement therapy (IRRT) will be randomized to either switch to IRRT within the next 24 h or continued CRRT for an additional 24 h. Cerebral microembolic load will be determined at baseline, i.e., before switch (on CRRT for both groups) and on IRRT versus CRRT, whichever group they were randomized to. The primary endpoint is defined as the difference in mean total cerebral microemboli count during the measurement period on CRRT versus IRRT following randomization. Microemboli will be assessed within the RRT circuit by a 1.5-MHz ultrasound detector attached to the venous RRT tubing and cerebral microemboli will be measured in the middle cerebral artery using a 1.6-MHz robotic transcranial Doppler system with automatic classification of Doppler signals as solid or gaseous. In addition to Doppler measurements, patients will be examined by magnetic resonance imaging and neurocognitive tests to gain better understanding into the potential morphological and clinical consequences of embolization. Discussion The results of COMET-AKI may help to gain a better insight into RRT modality-associated differences regarding microbubble generation and the cerebral microembolic burden endured by RRT recipients. Furthermore, identification of covariates of microbubble formation and distribution may help to encourage the evolution of next-generation RRT circuits including machinery and/or filters. Trial registration ClinicalTrials.gov, ID: NCT02621749. Registered on 3 December 2015.

Abstract Background Acute kidney injury (AKI) is often observed in critically ill patients and is associated with high morbidity and mortality. Non-recovery from AKI has a negative impact on the prognosis of affected patients and early risk stratification seems key to improve clinical outcomes. We analyzed metabolites of a conserved key inflammatory pathway (i.e. tryptophan degradation pathway) in serial urine samples of patients with AKI. Methods One hundred twelve ICU patients with AKI were included in a prospective observational analysis. After exclusion criteria, 92 patients were eligible for analysis. Serial urine samples were collected and tryptophan levels including key tryptophan metabolites were measured using tandem mass spectrometry. Results Sixty-seven patients recovered in the first 7 days of AKI (early recovery, ER) whereas n = 25 had late−/non-recovery (LNR). Urinary concentrations of tryptophan, kynurenine, 3-OH anthranillic acid, serotonine, and kynurenine/tryptophan were significantly lower in LNR patients. In contrast, creatinine normalized excretion of kynurenic acid (KynA) was substantially increased in LNR patients (7.59 ± 6.81 vs. 3.19 ± 3.44 (ER) μmol/mmol, p

Abstract Background Proton pump inhibitors are often used in critically ill patients to prevent gastrointestinal bleeding despite limited evidence for benefit. Patients with acute kidney injury requiring renal replacement therapy (RRT) are at high risk of gastrointestinal bleeding as (pre-)uremia induces coagulopathy through effects on platelets and coagulation cascades. No high-quality randomized clinical trials have previously assessed the benefits and harms of prophylactic proton pump inhibitor use in this high-risk population of adult critically ill patients. Methods/design Among the 3350 patients included in the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial—an investigator-initiated international randomized clinical trial on prophylactic proton pump inhibitor versus placebo in acutely admitted adult ICU patients at risk of gastrointestinal bleeding—we will compare the benefits and harms of prophylactic use of proton pump inhibitor in patients in need of RRT versus those not requiring this treatment. We will determine the proportion of patients with clinically important bleeding, the proportion of patients with adverse events including pneumonia, Clostridium difficile enteritis, or acute myocardial ischemia in the ICU, as well as transfusion requirements. Moreover, 90 day and 365 day mortality post-randomization will be investigated. As a secondary analysis, we will examine the association between acute kidney injury and RRT during ICU stay and gastrointestinal bleeding. Discussion With the outlined predefined analysis, we will characterize the balance between the benefits and harms of stress ulcer prophylaxis in acutely admitted adult ICU patients in need of RRT, including the potential interaction of allocation to proton pump inhibitor versus placebo. Trial registration ClinicalTrials.gov, NCT02718261 . Registered on 14 March 2016.

Patients undergoing cardiac surgery are at increased cardiovascular risk, which includes altered lipid status. However, data on the effect of cardiac surgery and cardiopulmonary bypass (CPB) on plasma levels of key lipids are scarce. We investigated potential effects of CPB on plasma lipid levels and associations with early postoperative clinical outcomes. This is a prospective bio-bank study of patients undergoing elective cardiac surgery at our center January to December 2019. The follow-up period was 1 year after surgery. Blood sampling was performed before induction of general anesthesia, upon weaning from cardiopulmonary bypass (CPB), and on the first day after surgery. Clinical end points included the incidence of postoperative stroke, myocardial infarction, and death of any cause at 30 days after surgery as well as 1-year all-cause mortality. A total of 192 cardiac surgery patients (75% male, median age 67.0 years (interquartile range 60.0–73.0), median BMI 26.1 kg/m2 (23.7–30.4)) were included. A significant intraoperative decrease in plasma levels compared with preoperative levels (all p < 0.0001) was observed for total cholesterol (TC) (Cliff’s delta d: 0.75 (0.68–0.82; 95% CI)), LDL-Cholesterol (LDL-C) (d: 0.66 (0.57–0.73)) and HDL-Cholesterol (HDL-C) (d: 0.72 (0.64–0.79)). At 24h after surgery, the plasma levels of LDL-C (d: 0.73 (0.650.79)) and TC (d: 0.77 (0.69–0.82)) continued to decrease compared to preoperative levels, while the plasma levels of HDL-C (d: 0.46 (0.36–0.55)) and TG (d: 0.40 (0.29–0.50)) rebounded, but all remained below the preoperative levels (p < 0.001). Mortality at 30 days was 1.0% (N = 2/192), and 1-year mortality was 3.8% (N = 7/186). Postoperative myocardial infarction occurred in 3.1% of patients (N = 6/192) and postoperative stroke in 5.8% (N = 11/190). Adjusting for age, sex, BMI, and statin therapy, we noted a protective effect of postoperative occurrence of stroke for pre-to-post-operative changes in TC (adjusted odds ratio (OR) 0.29 (0.07–0.90), p = 0.047), in LDL-C (aOR 0.19 (0.03–0.88), p = 0.045), and in HDL-C (aOR 0.01 (0.00–0.78), p = 0.039). No associations were observed between lipid levels and 1-year mortality. In conclusion, cardiac surgery induces a significant sudden drop in levels of key plasma lipids. This effect was pronounced during the operation, and levels remained significantly lowered at 24 h after surgery. The intraoperative drops in LDL-C, TC, and HDL-C were associated with a protective effect against occurrence of postoperative stroke in adjusted models. We demonstrate that the changes in key plasma lipid levels during surgery are strongly correlated, which makes attributing the impact of each lipid to the clinical end points, such as postoperative stroke, a challenging task. Large-scale analyses should investigate additional clinical outcome measures.