Hyperoxia-induced lung injury in acute respiratory distress syndrome: what is its relative impact?

Over the past decade, the interest in oxygen toxicity has led to various observational studies and randomized clinical trials in critically ill patients, assessing the association with outcomes and the potential benefit of restrictive oxygenation targets. Yet to date, no consensus has been reached regarding the clinical impact of hyperoxia and hyperoxemia. In this perspective article, we explore the experimental and clinical evidence on hyperoxia-induced lung injury (HILI) and assess its relative impact in current critical care practice, specifically in patients who require oxygen therapy due to acute respiratory distress syndrome (ARDS). Here, we suggest that in current clinical practice in the setting of ARDS HILI may actually be of less importance than other ventilator-related factors.

Effect of mechanical power on mortality in invasively ventilated ICU patients without the acute respiratory distress syndrome: An analysis of three randomised clinical trials.

BACKGROUND: The mechanical power of ventilation (MP) has an association with outcome in invasively ventilated patients with the acute respiratory distress syndrome (ARDS). Whether a similar association exists in invasively ventilated patients without ARDS is less certain. OBJECTIVE: To investigate the association of mechanical power with mortality in ICU patients without ARDS. DESIGN: This was an individual patient data analysis that uses the data of three multicentre randomised trials. SETTING: This study was performed in academic and nonacademic ICUs in the Netherlands. PATIENTS: One thousand nine hundred and sixty-two invasively ventilated patients without ARDS were included in this analysis. The median [IQR] age was 67 [57 to 75] years, 706 (36%) were women. MAIN OUTCOME MEASURES: The primary outcome was the all-cause mortality at day 28. Secondary outcomes were the all-cause mortality at day 90, and length of stay in ICU and hospital. RESULTS: At day 28, 644 patients (33%) had died. Hazard ratios for mortality at day 28 were higher with an increasing MP, even when stratified for its individual components (driving pressure ( P  < 0.001), tidal volume ( P  < 0.001), respiratory rate ( P  < 0.001) and maximum airway pressure ( P  = 0.001). Similar associations of mechanical power (MP) were found with mortality at day 90, lengths of stay in ICU and hospital. Hazard ratios for mortality at day 28 were not significantly different if patients were stratified for MP, with increasing levels of each individual component. CONCLUSION: In ICU patients receiving invasive ventilation for reasons other than ARDS, MP had an independent association with mortality. This finding suggests that MP holds an added predictive value over its individual components, making MP an attractive measure to monitor and possibly target in these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02159196, ClinicalTrials.gov Identifier: NCT02153294, ClinicalTrials.gov Identifier: NCT03167580.

Effect of On-Demand vs Routine Nebulization of Acetylcysteine With Salbutamol on Ventilator-Free Days in Intensive Care Unit Patients Receiving Invasive Ventilation: A Randomized Clinical Trial.

Importance: It remains uncertain whether nebulization of mucolytics with bronchodilators should be applied for clinical indication or preventively in intensive care unit (ICU) patients receiving invasive ventilation. Objective: To determine if a strategy that uses nebulization for clinical indication (on-demand) is noninferior to one that uses preventive (routine) nebulization. Design, Setting, and Participants: Randomized clinical trial enrolling adult patients expected to need invasive ventilation for more than 24 hours at 7 ICUs in the Netherlands. Interventions: On-demand nebulization of acetylcysteine or salbutamol (based on strict clinical indications, n = 471) or routine nebulization of acetylcysteine with salbutamol (every 6 hours until end of invasive ventilation, n = 473). Main Outcomes and Measures: The primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for a difference between groups of -0.5 days. Secondary outcomes included length of stay, mortality rates, occurrence of pulmonary complications, and adverse events. Results: Nine hundred twenty-two patients (34% women; median age, 66 (interquartile range [IQR], 54-75 years) were enrolled and completed follow-up. At 28 days, patients in the on-demand group had a median 21 (IQR, 0-26) ventilator-free days, and patients in the routine group had a median 20 (IQR, 0-26) ventilator-free days (1-sided 95% CI, -0.00003 to ∞). There was no significant difference in length of stay or mortality, or in the proportion of patients developing pulmonary complications, between the 2 groups. Adverse events (13.8% vs 29.3%; difference, -15.5% [95% CI, -20.7% to -10.3%]; P < .001) were more frequent with routine nebulization and mainly related to tachyarrhythmia (12.5% vs 25.9%; difference, -13.4% [95% CI, -18.4% to -8.4%]; P < .001) and agitation (0.2% vs 4.3%; difference, -4.1% [95% CI, -5.9% to -2.2%]; P < .001). Conclusions and Relevance: Among ICU patients receiving invasive ventilation who were expected to not be extubated within 24 hours, on-demand compared with routine nebulization of acetylcysteine with salbutamol did not result in an inferior number of ventilator-free days. On-demand nebulization may be a reasonable alternative to routine nebulization. Trial Registration: clinicaltrials.gov Identifier: NCT02159196.

High PEEP/low FiO2 ventilation is associated with lower mortality in COVID-19.

RATIONALE: The positive end-expiratory pressure (PEEP) strategy in patients with coronavirus 2019 (COVID-19) acute respiratory distress syndrome (ARDS) remains debated. Most studies originate from the initial waves of the pandemic. Here we aimed to assess the impact of high PEEP/low FiO2 ventilation on outcomes during the second wave in the Netherlands. METHODS: Retrospective observational study of invasively ventilated COVID-19 patients during the second wave. Patients were categorized based on whether they received high PEEP or low PEEP ventilation according to the ARDS Network tables. The primary outcome was ICU mortality, and secondary outcomes included hospital and 90-day mortality, duration of ventilation and length of stay, and the occurrence of kidney injury. Propensity matching was performed to correct for factors with a known relationship to ICU mortality. RESULTS: This analysis included 790 COVID-ARDS patients. At ICU discharge, 32 (22.5%) out of 142 high PEEP patients and 254 (39.2%) out of 848 low PEEP patients had died (HR 0.66 [0.46-0.96]; P = 0.03). High PEEP was linked to improved secondary outcomes. Matched analysis did not change findings. CONCLUSIONS: High PEEP ventilation was associated with improved ICU survival in patients with COVID-ARDS.

Different ventilation intensities among various categories of patients ventilated for reasons other than ARDS--A pooled analysis of 4 observational studies.

PURPOSE: We investigated driving pressure (ΔP) and mechanical power (MP) and associations with clinical outcomes in critically ill patients ventilated for reasons other than ARDS. MATERIALS AND METHODS: Individual patient data analysis of a pooled database that included patients from four observational studies of ventilation. ΔP and MP were compared among invasively ventilated non-ARDS patients with sepsis, with pneumonia, and not having sepsis or pneumonia. The primary endpoint was ΔP; secondary endpoints included MP, ICU mortality and length of stay, and duration of ventilation. RESULTS: This analysis included 372 (11%) sepsis patients, 944 (28%) pneumonia patients, and 2040 (61%) patients ventilated for any other reason. On day 1, median ΔP was higher in sepsis (14 [11-18] cmH2O) and pneumonia patients (14 [11-18]cmH2O), as compared to patients not having sepsis or pneumonia (13 [10-16] cmH2O) (P < 0.001). Median MP was also higher in sepsis and pneumonia patients. ΔP, as opposed to MP, was associated with ICU mortality in sepsis and pneumonia patients. CONCLUSIONS: The intensity of ventilation differed between patients with sepsis or pneumonia and patients receiving ventilation for any other reason; ΔP was associated with higher mortality in sepsis and pneumonia patients. REGISTRATION: This post hoc analysis was not registered; the individual studies that were merged into the used database were registered at clinicaltrials.gov: NCT01268410 (ERICC), NCT02010073 (LUNG SAFE), NCT01868321 (PRoVENT), and NCT03188770 (PRoVENT-iMiC).

Differences in Ventilation Management and Outcomes between the Two First Waves of the COVID-19 Pandemic-A Comparison between Two Nationwide Observational Studies in The Netherlands.

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.

A closed-loop ventilation mode that targets the lowest work and force of breathing reduces the transpulmonary driving pressure in patients with moderate-to-severe ARDS.

INTRODUCTION: The driving pressure (ΔP) has an independent association with outcome in patients with acute respiratory distress syndrome (ARDS). INTELLiVENT-Adaptive Support Ventilation (ASV) is a closed-loop mode of ventilation that targets the lowest work and force of breathing. AIM: To compare transpulmonary and respiratory system ΔP between closed-loop ventilation and conventional pressure controlled ventilation in patients with moderate-to-severe ARDS. METHODS: Single-center randomized cross-over clinical trial in patients in the early phase of ARDS. Patients were randomly assigned to start with a 4-h period of closed-loop ventilation or conventional ventilation, after which the alternate ventilation mode was selected. The primary outcome was the transpulmonary ΔP; secondary outcomes included respiratory system ΔP, and other key parameters of ventilation. RESULTS: Thirteen patients were included, and all had fully analyzable data sets. Compared to conventional ventilation, with closed-loop ventilation the median transpulmonary ΔP with was lower (7.0 [5.0-10.0] vs. 10.0 [8.0-11.0] cmH2O, mean difference - 2.5 [95% CI - 2.6 to - 2.1] cmH2O; P = 0.0001). Inspiratory transpulmonary pressure and the respiratory rate were also lower. Tidal volume, however, was higher with closed-loop ventilation, but stayed below generally accepted safety cutoffs in the majority of patients. CONCLUSIONS: In this small physiological study, when compared to conventional pressure controlled ventilation INTELLiVENT-ASV reduced the transpulmonary ΔP in patients in the early phase of moderate-to-severe ARDS. This closed-loop ventilation mode also led to a lower inspiratory transpulmonary pressure and a lower respiratory rate, thereby reducing the intensity of ventilation. Trial registration Clinicaltrials.gov, NCT03211494, July 7, 2017. https://clinicaltrials.gov/ct2/show/NCT03211494?term=airdrop&draw=2&rank=1 .

Epidemiology, Ventilation Management and Outcomes of COPD Patients Receiving Invasive Ventilation for COVID-19-Insights from PRoVENT-COVID.

Chronic obstructive pulmonary disease (COPD) is a risk factor for death in patients admitted to intensive care units (ICUs) for respiratory support. Previous reports suggested higher mortality in COPD patients with COVID-19. It is yet unknown whether patients with COPD were treated differently compared to non-COPD patients. We compared the ventilation management and outcomes of invasive ventilation for COVID-19 in COPD patients versus non-COPD patients. This was a post hoc analysis of a nation-wide, observational study in the Netherlands. COPD patients were compared to non-COPD patients with respect to key ventilation parameters. The secondary endpoints included adjunctive treatments for refractory hypoxemia, and 28-day mortality. Of a total of 1090 patients, 88 (8.1%) were classified as having COPD. The ventilation parameters were not different between COPD patients and non-COPD patients, except for FiO2, which was higher in COPD patients. Prone positioning was applied more often in COPD patients. COPD patients had higher 28-day mortality than non-COPD patients. COPD had an independent association with 28-day mortality. In this cohort of patients who received invasive ventilation for COVID-19, only FiO2 settings and the use of prone positioning were different between COPD patients and non-COPD patients. COPD patients had higher mortality than non-COPD patients.

Broadening the Berlin definition of ARDS to patients receiving high-flow nasal oxygen: an observational study in patients with acute hypoxemic respiratory failure due to COVID-19.

BACKGROUND: High-flow nasal oxygen (HFNO) is increasingly used in patients with acute hypoxemic respiratory failure. It is uncertain whether a broadened Berlin definition of acute respiratory distress syndrome (ARDS), in which ARDS can be diagnosed in patients who are not receiving ventilation, results in similar groups of patients receiving HFNO as in patients receiving ventilation. METHODS: We applied a broadened definition of ARDS in a multicenter, observational study in adult critically ill patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19), wherein the requirement for a minimal level of 5 cm H2O PEEP with ventilation is replaced by a minimal level of airflow rate with HFNO, and compared baseline characteristics and outcomes between patients receiving HFNO and patients receiving ventilation. The primary endpoint was ICU mortality. We also compared outcomes in risk for death groups using the PaO2/FiO2 cutoffs as used successfully in the original definition of ARDS. Secondary endpoints were hospital mortality; mortality on days 28 and 90; need for ventilation within 7 days in patients that started with HFNO; the number of days free from HFNO or ventilation; and ICU and hospital length of stay. RESULTS: Of 728 included patients, 229 patients started with HFNO and 499 patients with ventilation. All patients fulfilled the broadened Berlin definition of ARDS. Patients receiving HFNO had lower disease severity scores and lower PaO2/FiO2 than patients receiving ventilation. ICU mortality was lower in receiving HFNO (22.7 vs 35.6%; p = 0.001). Using PaO2/FiO2 cutoffs for mild, moderate and severe arterial hypoxemia created groups with an ICU mortality of 16.7%, 22.0%, and 23.5% (p = 0.906) versus 19.1%, 37.9% and 41.4% (p = 0.002), in patients receiving HFNO versus patients receiving ventilation, respectively. CONCLUSIONS: Using a broadened definition of ARDS may facilitate an earlier diagnosis of ARDS in patients receiving HFNO; however, ARDS patients receiving HFNO and ARDS patients receiving ventilation have distinct baseline characteristics and mortality rates. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov (identifier NCT04719182).

Closed-Loop ventilation using sidestream versus mainstream capnography for automated adjustments of minute ventilation-A randomized clinical trial in cardiac surgery patients.

BACKGROUND: INTELLiVENT-Adaptive Support Ventilation (ASV) is a closed-loop ventilation mode that uses capnography to adjust tidal volume (VT) and respiratory rate according to a user-set end-tidal CO2 (etCO2) target range. We compared sidestream versus mainstream capnography with this ventilation mode with respect to the quality of breathing in patients after cardiac surgery. METHODS: Single-center, single-blinded, non-inferiority, randomized clinical trial in adult patients scheduled for elective cardiac surgery that were expected to receive at least two hours of postoperative ventilation in the ICU. Patients were randomized 1:1 to closed-loop ventilation with sidestream or mainstream capnography. Each breath was classified into a zone based on the measured VT, maximum airway pressure, etCO2 and pulse oximetry. The primary outcome was the proportion of breaths spent in a predefined 'optimal' zone of ventilation during the first three hours of postoperative ventilation, with a non-inferiority margin for the difference in the proportions set at -20%. Secondary endpoints included the proportion of breaths in predefined 'acceptable' and 'critical' zones of ventilation, and the proportion of breaths with hypoxemia. RESULTS: Of 80 randomized subjects, 78 were included in the intention-to-treat analysis. We could not confirm the non-inferiority of closed-loop ventilation using sidestream with respect to the proportion of breaths in the 'optimal' zone (mean ratio 0.87 [0.77 to ∞]; P = 0.116 for non-inferiority). The proportion of breaths with hypoxemia was higher in the sidestream capnography group versus the mainstream capnography group. CONCLUSIONS: We could not confirm that INTELLiVENT-ASV using sidestream capnography is non-inferior to INTELLiVENT-ASV using mainstream capnography with respect to the quality of breathing in subjects receiving postoperative ventilation after cardiac surgery. TRIAL REGISTRATION: NCT04599491 (clinicaltrials.gov).

Oxygen Consumption with High-Flow Nasal Oxygen versus Mechanical Ventilation- An International Multicenter Observational Study in COVID-19 Patients (PROXY-COVID).

The COVID-19 pandemic led to local oxygen shortages worldwide. To gain a better understanding of oxygen consumption with different respiratory supportive therapies, we conducted an international multicenter observational study to determine the precise amount of oxygen consumption with high-flow nasal oxygen (HFNO) and with mechanical ventilation. A retrospective observational study was conducted in three intensive care units (ICUs) in the Netherlands and Spain. Patients were classified as HFNO patients or ventilated patients, according to the mode of oxygen supplementation with which a patient started. The primary endpoint was actual oxygen consumption; secondary endpoints were hourly and total oxygen consumption during the first two full calendar days. Of 275 patients, 147 started with HFNO and 128 with mechanical ventilation. Actual oxygen use was 4.9-fold higher in patients who started with HFNO than in patients who started with ventilation (median 14.2 [8.4-18.4] versus 2.9 [1.8-4.1] L/minute; mean difference = 11.3 [95% CI 11.0-11.6] L/minute; P < 0.01). Hourly and total oxygen consumption were 4.8-fold (P < 0.01) and 4.8-fold (P < 0.01) higher. Actual oxygen consumption, hourly oxygen consumption, and total oxygen consumption are substantially higher in patients that start with HFNO compared with patients that start with mechanical ventilation. This information may help hospitals and ICUs predicting oxygen needs during high-demand periods and could guide decisions regarding the source of distribution of medical oxygen.

Safety and Feasibility of Intraoperative High PEEP Titrated to the Lowest Driving Pressure (ΔP)-Interim Analysis of DESIGNATION.

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.

Optimal Dosing and Timing of High-Dose Corticosteroid Therapy in Hospitalized Patients With COVID-19: Study Protocol for a Retrospective Observational Multicenter Study (SELECT).

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.

Practice of Awake Prone Positioning in Critically Ill COVID-19 Patients-Insights from the PRoAcT-COVID Study.

We describe the incidence, practice and associations with outcomes of awake prone positioning in patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) in a national multicenter observational cohort study performed in 16 intensive care units in the Netherlands (PRoAcT−COVID-study). Patients were categorized in two groups, based on received treatment of awake prone positioning. The primary endpoint was practice of prone positioning. Secondary endpoint was 'treatment failure', a composite of intubation for invasive ventilation and death before day 28. We used propensity matching to control for observed confounding factors. In 546 patients, awake prone positioning was used in 88 (16.1%) patients. Prone positioning started within median 1 (0 to 2) days after ICU admission, sessions summed up to median 12.0 (8.4−14.5) hours for median 1.0 day. In the unmatched analysis (HR, 1.80 (1.41−2.31); p < 0.001), but not in the matched analysis (HR, 1.17 (0.87−1.59); p = 0.30), treatment failure occurred more often in patients that received prone positioning. The findings of this study are that awake prone positioning was used in one in six COVID-19 patients. Prone positioning started early, and sessions lasted long but were often discontinued because of need for intubation.

Association of Time-Varying Intensity of Ventilation With Mortality in Patients With COVID-19 ARDS: Secondary Analysis of the PRoVENT-COVID Study.

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.

Incidence and Practice of Early Prone Positioning in Invasively Ventilated COVID-19 Patients-Insights from the PRoVENT-COVID Observational Study.

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.

The predictive validity for mortality of the driving pressure and the mechanical power of ventilation.

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.

Practice of mechanical ventilation in cardiac arrest patients and effects of targeted temperature management: A substudy of the targeted temperature management trial.

AIMS: Mechanical ventilation practices in patients with cardiac arrest are not well described. Also, the effect of temperature on mechanical ventilation settings is not known. The aims of this study were 1) to describe practice of mechanical ventilation and its relation with outcome 2) to determine effects of different target temperatures strategies (33 °C versus 36 °C) on mechanical ventilation settings. METHODS: This is a substudy of the TTM-trial in which unconscious survivors of a cardiac arrest due to a cardiac cause were randomized to two TTM strategies, 33 °C (TTM33) and 36 °C (TTM36). Mechanical ventilation data were obtained at three time points: 1) before TTM; 2) at the end of TTM (before rewarming) and 3) after rewarming. Logistic regression was used to determine an association between mechanical ventilation variables and outcome. Repeated-measures mixed modelling was performed to determine the effect of TTM on ventilation settings. RESULTS: Mechanical ventilation data was available for 567 of the 950 TTM patients. Of these, 81% was male with a mean (SD) age of 64 (12) years. At the end of TTM median tidal volume was 7.7 ml/kg predicted body weight (PBW)(6.4-8.7) and 60% of patients were ventilated with a tidal volume ≤ 8 ml/kg PBW. Median PEEP was 7.7cmH2O (6.4-8.7) and mean driving pressure was 14.6 cmH2O (±4.3). The median FiO2 fraction was 0.35 (0.30-0.45). Multivariate analysis showed an independent relationship between increased respiratory rate and 28-day mortality. TTM33 resulted in lower end-tidal CO2 (Pgroup = 0.0003) and higher alveolar dead space fraction (Pgroup = 0.003) compared to TTM36, while PCO2 levels and respiratory minute volume were similar between groups. CONCLUSIONS: In the majority of the cardiac arrest patients, protective ventilation settings are applied, including low tidal volumes and driving pressures. High respiratory rate was associated with mortality. TTM33 results in lower end-tidal CO2 levels and a higher alveolar dead space fraction compared to TTTM36.

Risk prediction models for postoperative delirium: a systematic review and meta-analysis.

Postoperative delirium (POD) is a common neuropsychiatric disorder characterized by inattention, fluctuating levels of consciousness, and disorganized thinking. POD can have serious consequences, including institutionalization and death. Risk stratification may target prevention to individuals at greater risk of POD. The objective of this study was to identify all published POD risk prediction models (RPMs) and to compare them with regard to their clinical practicability and predictive and discriminative performance. PubMed and EMBASE were searched from inception to January 1, 2013, for articles describing POD RPMs. Studies were included if they presented data from a cohort study, examined one or more RPMs, examined POD as an outcome, and assessed the performance of the RPM(s). Thirty of 2,246 articles were included, and 37 RPMs were found. Sixteen and six studies described individuals who had undergone cardiovascular and orthopedic surgery, respectively. The Confusion Assessment Method (CAM) for the intensive care unit checklist was the most often used diagnostic method (65%), followed by the Diagnostic and Statistical Manual of Mental Disorders (DSM), Fourth Edition criteria (16%). Predictors most often used in RPMs were age (20), preoperative Mini-Mental State Examination score (10), and preoperative increased alcohol use (7). Thirty RPMs were not validated, three were validated internally, and four were validated externally. Size of the models was not associated with their discriminatory performance. Instead of creating steadily new RPMs, existing RPMs should be further tested, improved, and meta-analytically integrated. It may be too early to implement a particular PODRPM in clinical practice with confidence.