Background Little is known about the practice of ventilation management in patients with COVID-19. We aimed to describe the practice of ventilation management and to establish outcomes in invasively ventilated patients with COVID-19 in a single country during the first month of the outbreak.Methods PRoVENT-COVID is a national, multicentre, retrospective observational study done at 18 intensive care units (ICUs) in the Netherlands. Consecutive patients aged at least 18 years were eligible for participation if they had received invasive ventilation for COVID-19 at a participating ICU during the first month of the national outbreak in the Netherlands. The primary outcome was a combination of ventilator variables and parameters over the first 4 calendar days of ventilation: tidal volume, positive end-expiratory pressure (PEEP), respiratory system compliance, and driving pressure. Secondary outcomes included the use of adjunctive treatments for refractory hypoxaemia and ICU complications. Patient-centred outcomes were ventilator-free days at day 28, duration of ventilation, duration of ICU and hospital stay, and mortality. PRoVENT-COVID is registered at ClinicalTrials.gov (NCT04346342). FindingsBetween March 1 and April 1, 2020, 553 patients were included in the study. Median tidal volume was 6•3 mL/kg predicted bodyweight (IQR 5•7-7•1), PEEP was 14•0 cm H 2 O (IQR 11•0-15•0), and driving pressure was 14•0 cm H 2 O (11•2-16•0). Median respiratory system compliance was 31•9 mL/cm H 2 O (26•0-39•9). Of the adjunctive treatments for refractory hypoxaemia, prone positioning was most often used in the first 4 days of ventilation (283 [53%] of 530 patients). The median number of ventilator-free days at day 28 was 0 (IQR 0-15); 186 (35%) of 530 patients had died by day 28. Predictors of 28-day mortality were gender, age, tidal volume, respiratory system compliance, arterial pH, and heart rate on the first day of invasive ventilation. Interpretation In patients with COVID-19 who were invasively ventilated during the first month of the outbreak in the Netherlands, lung-protective ventilation with low tidal volume and low driving pressure was broadly applied and prone positioning was often used. The applied PEEP varied widely, despite an invariably low respiratory system compliance. The findings of this national study provide a basis for new hypotheses and sample size calculations for future trials of invasive ventilation for COVID-19. These data could also help in the interpretation of findings from other studies of ventilation practice and outcomes in invasively ventilated patients with COVID-19. Funding Amsterdam University Medical Centers, location Academic Medical Center.

Background: The current severe acute respiratory syndrome coronavirus 2 pandemic is unprecedented in its impact. It is essential to shed light on patient characteristics that predispose to a more severe disease course. Obesity, defined as a BMI>30 kg/m 2 , is suggested to be one of these characteristics. However, BMI does not differentiate between fat mass and lean body mass, or the distribution of fat tissue. The aim of the present study was to assess the body composition of COVID-19 patients admitted to the ward or the ICU and identify any associations with severity of disease. Methods: We performed an observational cross-sectional cohort study. Bioelectric impedance analysis was conducted amongst all confirmed COVID-19 patients admitted to the ward or ICU of our hospital in the Netherlands, between April 10 and 17, 2020. Body water measurements and derived values were recalculated to dry weight, using a standard ratio of extracellular water to total body water of 0.38. Data were compared between the ward and ICU patients, and regression models were used to assess the associations between baseline characteristics, body composition, and several indicators of disease severity, including a composite score composed of mortality, morbidity, and ICU admission. Results: Fifty-four patients were included, of which 30 in the ward and 24 in the ICU. The mean age was 67 years (95%-CI 64e71), and 34 (63%) were male. Mean BMI was 29.7 (95%-CI 28.2e31.1) kg/m 2 and did not differ between groups. Body composition values were not independently associated with disease severity. In multiple logistic regression analyses, a low phase angle was associated with COVID-19 severity in the composite score (OR 0.299, p ¼ 0.046). Conclusion: We found no significant associations between body composition, including fat mass, visceral fat area, and fat-free mass, and disease severity in our population of generally overweight COVID-19 patients. A lower phase angle did increase the odds of severe COVID-19. We believe that factors other than body composition play a more critical role in the development of severe COVID-19.

Background The intensity of ventilation, reflected by driving pressure (ΔP) and mechanical power (MP), has an association with outcome in invasively ventilated patients with or without acute respiratory distress syndrome (ARDS). It is uncertain if a similar association exists in coronavirus disease 2019 (COVID-19) patients with acute respiratory failure. Methods We aimed to investigate the impact of intensity of ventilation on patient outcome. The PRoVENT-COVID study is a national multicenter observational study in COVID-19 patients receiving invasive ventilation. Ventilator parameters were collected a fixed time points on the first calendar day of invasive ventilation. Mean dynamic ΔP and MP were calculated for individual patients at time points without evidence of spontaneous breathing. A Cox proportional hazard model, and a double stratification analysis adjusted for confounders were used to estimate the independent associations of ΔP and MP with outcome. The primary endpoint was 28-day mortality. Results In 825 patients included in this analysis, 28-day mortality was 27.5%. ΔP was not independently associated with mortality (HR 1.02 [95% confidence interval 0.88–1.18]; P = 0.750). MP, however, was independently associated with 28-day mortality (HR 1.17 [95% CI 1.01–1.36]; P = 0.031), and increasing quartiles of MP, stratified on comparable levels of ΔP, had higher risks of 28-day mortality (HR 1.15 [95% CI 1.01–1.30]; P = 0.028). Conclusions In this cohort of critically ill invasively ventilated COVID-19 patients with acute respiratory failure, we show an independent association of MP, but not ΔP with 28-day mortality. MP could serve as one prognostic biomarker in addition to ΔP in these patients. Efforts aiming at limiting both ΔP and MP could translate in a better outcome. Trial registration Clinicaltrials.gov (study identifier NCT04346342).

To review the pros and cons of indirect calorimetry (IC) to estimate resting energy expenditure (REE) and define individual nutritional energy targets among critically ill patients. We evaluate pros, (relative) cons and when adjustments of REE are needed (Fig. 1).

Purpose of reviewTo summarize the incidence, features, pathogenesis, risk factors, and evidence-based therapies of prolonged intensive care unit (ICU) acquired weakness (ICU-AW). We aim to provide an updated overview on aspects of poor physical recovery following critical illness.Recent findingsNew physical problems after ICU survival, such as muscle weakness, weakened condition, and reduced exercise capacity, are the most frequently encountered limitations of patients with postintensive care syndrome. Disabilities may persist for months to years and frequently do not fully recover. Hormonal and mitochondrial disturbances, impaired muscle regeneration due to injured satellite cells and epigenetic differences may be involved in sustained ICU-AW. Although demographics and ICU treatment factors appear essential determinants for physical recovery, pre-ICU health status is also crucial. Currently, no effective treatments are available. Early mobilization in the ICU may improve physical outcomes at ICU-discharge, but there is no evidence for benefit on long-term physical recovery.SummaryImpaired physical recovery is observed frequently among ICU survivors. The pre-ICU health status, demographic, and ICU treatment factors appear to be important determinants for physical convalescence during the post-ICU phase. The pathophysiological mechanisms involved are poorly understood, thereby resulting in exiguous evidence-based treatment strategies to date.

Background Increasing evidence indicates the potential benefits of restricted fluid management in critically ill patients. Evidence lacks on the optimal fluid management strategy for invasively ventilated COVID-19 patients. We hypothesized that the cumulative fluid balance would affect the successful liberation of invasive ventilation in COVID-19 patients with acute respiratory distress syndrome (ARDS). Methods We analyzed data from the multicenter observational ‘PRactice of VENTilation in COVID-19 patients’ study. Patients with confirmed COVID-19 and ARDS who required invasive ventilation during the first 3 months of the international outbreak (March 1, 2020, to June 2020) across 22 hospitals in the Netherlands were included. The primary outcome was successful liberation of invasive ventilation, modeled as a function of day 3 cumulative fluid balance using Cox proportional hazards models, using the crude and the adjusted association. Sensitivity analyses without missing data and modeling ARDS severity were performed. Results Among 650 patients, three groups were identified. Patients in the higher, intermediate, and lower groups had a median cumulative fluid balance of 1.98 L (1.27–7.72 L), 0.78 L (0.26–1.27 L), and − 0.35 L (− 6.52–0.26 L), respectively. Higher day 3 cumulative fluid balance was significantly associated with a lower probability of successful ventilation liberation (adjusted hazard ratio 0.86, 95% CI 0.77–0.95, P = 0.0047). Sensitivity analyses showed similar results. Conclusions In a cohort of invasively ventilated patients with COVID-19 and ARDS, a higher cumulative fluid balance was associated with a longer ventilation duration, indicating that restricted fluid management in these patients may be beneficial. Trial registration Clinicaltrials.gov (NCT04346342); Date of registration: April 15, 2020. Graphical abstract

Background Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. Methods We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. Results Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference − 0.40 [95% CI − 0.71 to − 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference − 1.6% [95% CI − 4.3% to 1.2%]; P = 0.42) between groups. Conclusions In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. Trial registration: ISRCTN, ISRCTN12233792. Registered November 20th, 2017.

Background The Dutch Working Party on Antibiotic Policy (SWAB) in collaboration with relevant professional societies, has updated their evidence-based guidelines on empiric antibacterial therapy of sepsis in adults. Methods Our multidisciplinary guideline committee generated ten population, intervention, comparison, and outcome (PICO) questions relevant for adult patients with sepsis. For each question, a literature search was performed to obtain the best available evidence and assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The quality of evidence for clinically relevant outcomes was graded from high to very low. In structured consensus meetings, the committee formulated recommendations as strong or weak. When evidence could not be obtained, recommendations were provided based on expert opinion and experience (good practice statements). Results Fifty-five recommendations on the antibacterial therapy of sepsis were generated. Recommendations on empiric antibacterial therapy choices were differentiated for sepsis according to the source of infection, the potential causative pathogen and its resistance pattern. One important revision was the distinction between low, increased and high risk of infection with Enterobacterales resistant to third generation cephalosporins (3GRC-E) to guide the choice of empirical therapy. Other new topics included empirical antibacterial therapy in patients with a reported penicillin allergy and the role of pharmacokinetics and pharmacodynamics to guide dosing in sepsis. We also established recommendations on timing and duration of antibacterial treatment. Conclusions Our multidisciplinary committee formulated evidence-based recommendations for the empiric antibacterial therapy of adults with sepsis in The Netherlands.