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Uncertainty remains about the best level of intraoperative positive end–expiratory pressure (PEEP). An ongoing RCT ('DESIGNATION') compares an 'individualized high PEEP' strategy ('iPEEP')—titrated to the lowest driving pressure (ΔP) with recruitment maneuvers (RM), with a 'standard low PEEP' strategy ('low PEEP')—using 5 cm H2O without RMs with respect to the incidence of postoperative pulmonary complications. This report is an interim analysis of safety and feasibility. From September 2018 to July 2022, we enrolled 743 patients. Data of 698 patients were available for this analysis. Hypotension occurred more often in 'iPEEP' vs. 'low PEEP' (54.7 vs. 44.1%; RR, 1.24 (95% CI 1.07 to 1.44); p < 0.01). Investigators were compliant with the study protocol 285/344 patients (82.8%) in 'iPEEP', and 345/354 patients (97.5%) in 'low PEEP' (p < 0.01). Most frequent protocol violation was missing the final RM at the end of anesthesia before extubation; PEEP titration was performed in 99.4 vs. 0%; PEEP was set correctly in 89.8 vs. 98.9%. Compared to 'low PEEP', the 'iPEEP' group was ventilated with higher PEEP (10.0 (8.0–12.0) vs. 5.0 (5.0–5.0) cm H2O; p < 0.01). Thus, in patients undergoing general anesthesia for open abdominal surgery, an individualized high PEEP ventilation strategy is associated with hypotension. The protocol is feasible and results in clear contrast in PEEP. DESIGNATION is expected to finish in late 2023. [ABSTRACT FROM AUTHOR]

The aim of this analysis was to compare ventilation management and outcomes in invasively ventilated patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) between the first and second wave in the Netherlands. This is a post hoc analysis of two nationwide observational COVID-19 studies conducted in quick succession. The primary endpoint was ventilation management. Secondary endpoints were tracheostomy use, duration of ventilation, intensive care unit (ICU) and hospital length of stay (LOS), and mortality. We used propensity score matching to control for observed confounding factors. This analysis included 1122 patients from the first and 568 patients from the second wave. Patients in the second wave were sicker, had more comorbidities, and had worse oxygenation parameters. They were ventilated with lower positive end-expiratory pressure and higher fraction inspired oxygen, had a lower oxygen saturation, received neuromuscular blockade more often, and were less often tracheostomized. Duration of ventilation was shorter, but mortality rates were similar. After matching, the fraction of inspired oxygen was lower in the second wave. In patients with acute hypoxemic respiratory failure due to COVID-19, aspects of respiratory care and outcomes rapidly changed over the successive waves. [ABSTRACT FROM AUTHOR]

Background: Outcome prediction in critically ill patients under invasive ventilation remains extremely challenging. The driving pressure (ΔP) and the mechanical power of ventilation (MP) are associated with patient-centered outcomes like mortality and duration of ventilation. The objective of this study was to assess the predictive validity for mortality of the ΔP and the MP at 24 h after start of invasive ventilation. Methods: This is a post hoc analysis of an observational study in intensive care unit patients, restricted to critically ill patients receiving invasive ventilation for at least 24 h. The two exposures of interest were the modified ΔP and the MP at 24 h after start of invasive ventilation. The primary outcome was 90-day mortality; secondary outcomes were ICU and hospital mortality. The predictive validity was measured as incremental 90-day mortality beyond that predicted by the Acute Physiology, Age and Chronic Health Evaluation (APACHE) IV score and the Simplified Acute Physiology Score (SAPS) II. Results: The analysis included 839 patients with a 90-day mortality of 42%. The median modified ΔP at 24 h was 15 [interquartile range 12 to 19] cm H2O; the median MP at 24 h was 206 [interquartile range 145 to 298] 10−3 J/min/kg predicted body weight (PBW). Both parameters were associated with 90-day mortality (odds ratio (OR) for 1 cm H2O increase in the modified ΔP, 1.05 [95% confidence interval (CI) 1.03 to 1.08]; P < 0.001; OR for 100 10−3 J/min/kg PBW increase in the MP, 1.20 [95% CI 1.09 to 1.33]; P < 0.001). Area under the ROC for 90-day mortality of the modified ΔP and the MP were 0.70 [95% CI 0.66 to 0.74] and 0.69 [95% CI 0.65 to 0.73], which was neither different from that of the APACHE IV score nor that of the SAPS II. Conclusions: In adult patients under invasive ventilation, the modified ΔP and the MP at 24 h are associated with 90 day mortality. Neither the modified ΔP nor the MP at 24 h has predictive validity beyond the APACHE IV score and the SAPS II. [ABSTRACT FROM AUTHOR]

We describe the incidence and practice of prone positioning and determined the association of use of prone positioning with outcomes in invasively ventilated patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) in a national, multicenter observational study, performed at 22 intensive care units in the Netherlands. Patients were categorized into 4 groups, based on indication for and actual use of prone positioning. The primary outcome was 28-day mortality. Secondary endpoints were 90-day mortality, and ICU and hospital length of stay. In 734 patients, prone positioning was indicated in 60%—the incidence of prone positioning was higher in patients with an indication than in patients without an indication for prone positioning (77 vs. 48%, p = 0.001). Patients were left in the prone position for median 15.0 (10.5–21.0) hours per full calendar day—the duration was longer in patients with an indication than in patients without an indication for prone positioning (16.0 (11.0–23.0) vs. 14.0 (10.0–19.0) hours, p < 0.001). Ventilator settings and ventilation parameters were not different between the four groups, except for FiO2 which was higher in patients having an indication for and actually receiving prone positioning. Our data showed no difference in mortality at day 28 between the 4 groups (HR no indication, no prone vs. no indication, prone vs. indication, no prone vs. indication, prone: 1.05 (0.76–1.45) vs. 0.88 (0.62–1.26) vs. 1.15 (0.80–1.54) vs. 0.96 (0.73–1.26) (p = 0.08)). Factors associated with the use of prone positioning were ARDS severity and FiO2. The findings of this study are that prone positioning is often used in COVID-19 patients, even in patients that have no indication for this intervention. Sessions of prone positioning lasted long. Use of prone positioning may affect outcomes. [ABSTRACT FROM AUTHOR]

Uncertainty remains about the best level of intraoperative positive end-expiratory pressure (PEEP). An ongoing RCT ('DESIGNATION') compares an 'individualized high PEEP' strategy ('iPEEP')-titrated to the lowest driving pressure (ΔP) with recruitment maneuvers (RM), with a 'standard low PEEP' strategy ('low PEEP')-using 5 cm H 2 O without RMs with respect to the incidence of postoperative pulmonary complications. This report is an interim analysis of safety and feasibility. From September 2018 to July 2022, we enrolled 743 patients. Data of 698 patients were available for this analysis. Hypotension occurred more often in 'iPEEP' vs. 'low PEEP' (54.7 vs. 44.1%; RR, 1.24 (95% CI 1.07 to 1.44); p < 0.01). Investigators were compliant with the study protocol 285/344 patients (82.8%) in 'iPEEP', and 345/354 patients (97.5%) in 'low PEEP' ( p < 0.01). Most frequent protocol violation was missing the final RM at the end of anesthesia before extubation; PEEP titration was performed in 99.4 vs. 0%; PEEP was set correctly in 89.8 vs. 98.9%. Compared to 'low PEEP', the 'iPEEP' group was ventilated with higher PEEP (10.0 (8.0-12.0) vs. 5.0 (5.0-5.0) cm H 2 O; p < 0.01). Thus, in patients undergoing general anesthesia for open abdominal surgery, an individualized high PEEP ventilation strategy is associated with hypotension. The protocol is feasible and results in clear contrast in PEEP. DESIGNATION is expected to finish in late 2023.

Background: In hospitalized patients with COVID-19, the dosing and timing of corticosteroids vary widely. Low-dose dexamethasone therapy reduces mortality in patients requiring respiratory support, but it remains unclear how to treat patients when this therapy fails. In critically ill patients, high-dose corticosteroids are often administered as salvage late in the disease course, whereas earlier administration may be more beneficial in preventing disease progression. Previous research has revealed that increased levels of various biomarkers are associated with mortality, and whole blood transcriptome sequencing has the ability to identify host factors predisposing to critical illness in patients with COVID-19., Objective: Our goal is to determine the most optimal dosing and timing of corticosteroid therapy and to provide a basis for personalized corticosteroid treatment regimens to reduce morbidity and mortality in hospitalized patients with COVID-19., Methods: This is a retrospective, observational, multicenter study that includes adult patients who were hospitalized due to COVID-19 in the Netherlands. We will use the differences in therapeutic strategies between hospitals (per protocol high-dose corticosteroids or not) over time to determine whether high-dose corticosteroids have an effect on the following outcome measures: mechanical ventilation or high-flow nasal cannula therapy, in-hospital mortality, and 28-day survival. We will also explore biomarker profiles in serum and bronchoalveolar lavage fluid and use whole blood transcriptome analysis to determine factors that influence the relationship between high-dose corticosteroids and outcome. Existing databases that contain routinely collected electronic data during ward and intensive care admissions, as well as existing biobanks, will be used. We will apply longitudinal modeling appropriate for each data structure to answer the research questions at hand., Results: As of April 2023, data have been collected for a total of 1500 patients, with data collection anticipated to be completed by December 2023. We expect the first results to be available in early 2024., Conclusions: This study protocol presents a strategy to investigate the effect of high-dose corticosteroids throughout the entire clinical course of hospitalized patients with COVID-19, from hospital admission to the ward or intensive care unit until hospital discharge. Moreover, our exploration of biomarker and gene expression profiles for targeted corticosteroid therapy represents a first step towards personalized COVID-19 corticosteroid treatment., Trial Registration: ClinicalTrials.gov NCT05403359; https://clinicaltrials.gov/ct2/show/NCT05403359., International Registered Report Identifier (irrid): DERR1-10.2196/48183., (©Katrijn Daenen, Jilske A Huijben, Anders Boyd, Lieuwe D J Bos, Sara C M Stoof, Hugo van Willigen, Diederik A M P J Gommers, Hazra S Moeniralam, Corstiaan A den Uil, Nicole P Juffermans, Merijn Kant, Abraham J Valkenburg, Janesh Pillay, David M P van Meenen, Frederique Paulus, Marcus J Schultz, Virgil A S H Dalm, Eric C M van Gorp, Janke Schinkel, Henrik Endeman, PRoVENT- and PRoAcT-COVID Collaborative Group. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 02.06.2023.)

Background: High intensity of ventilation has an association with mortality in patients with acute respiratory failure. It is uncertain whether similar associations exist in patients with acute respiratory distress syndrome (ARDS) patients due to coronavirus disease 2019 (COVID-19). We investigated the association of exposure to different levels of driving pressure (ΔP) and mechanical power (MP) with mortality in these patients. Methods: PRoVENT-COVID is a national, retrospective observational study, performed at 22 ICUs in the Netherlands, including COVID-19 patients under invasive ventilation for ARDS. Dynamic ΔP and MP were calculated at fixed time points during the first 4 calendar days of ventilation. The primary endpoint was 28-day mortality. To assess the effects of time-varying exposure, Bayesian joint models adjusted for confounders were used. Results: Of 1,122 patients included in the PRoVENT-COVID study, 734 were eligible for this analysis. In the first 28 days, 29.2% of patients died. A significant increase in the hazard of death was found to be associated with each increment in ΔP (HR 1.04, 95% CrI 1.01-1.07) and in MP (HR 1.12, 95% CrI 1.01-1.36). In sensitivity analyses, cumulative exposure to higher levels of ΔP or MP resulted in increased risks for 28-day mortality. Conclusion: Cumulative exposure to higher intensities of ventilation in COVID-19 patients with ARDS have an association with increased risk of 28-day mortality. Limiting exposure to high ΔP or MP has the potential to improve survival in these patients. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04346342., Competing Interests: AS reports personal fees from Dräger, outside of the submitted work. MaS reports personal fees from Hamilton and Xenios/Novalung, outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schuijt, van Meenen, Martin–Loeches, Mazzinari, Schultz, Paulus and Serpa Neto.)