Associations between changes in oxygenation, dead space and driving pressure induced by the first prone position session and mortality in patients with acute respiratory distress syndrome

Background: Outcome prediction in acute respiratory distress syndrome (ARDS) is challenging, especially in patients with severe hypoxemia. The aim of the current study was to determine the prognostic capacity of changes in PaO2/FiO2, dead space fraction (VD/VT) and respiratory system driving pressure (\u394PRS) induced by the first prone position (PP) session in patients with ARDS. Methods: This was a post hoc analysis of the conveniently-sized 'Molecular Diagnosis and Risk Stratification of Sepsis' study (MARS). The current analysis included ARDS patients who were placed in the PP. The primary endpoint was the prognostic capacity of the PP-induced changes in PaO2/FiO2, VD/VT, and \u394PRS for 28-day mortality. PaO2/FiO2, VD/VT, and \u394PRS was calculated using variables obtained in the supine position before and after completion of the first PP session. Receiving operator characteristic curves (ROC) were constructed, and sensitivity, specificity positive and negative predictive value were calculated based on the best cutoffs. Results: Ninety patients were included; 28-day mortality was 46%. PP-induced changes in PaO2/FiO2 and VD/VT were similar between survivors vs. non-survivors [+83 (+24 to +137) vs. +58 (+21 to +113) mmHg, and -0.06 (-0.17 to +0.05) vs. -0.08 (-0.16 to +0.08), respectively]. PP-induced changes in \u394PRS were different between survivors vs. non-survivors [-3 (-7 to 2) vs. 0 (-3 to +3) cmH2O; P=0.03]. The area under the ROC of PP-induced changes in \u394PRS for mortality, however, was low [0.63 (95% confidence interval (CI), 0.50 to 0.75]; PP-induced changes in \u394PRS had a sensitivity and specificity of 76% and 56%, and a positive and negative predictive value of 60% and 73%. Conclusions: Changes in PaO2/FiO2, VD/VT, and \u394PRS induced by the first PP session have poor prognostic capacities for 28-day mortality in ARDS patients

Utilization of mechanical power and associations with clinical outcomes in brain injured patients. a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

BackgroundThere is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes.MethodsIn this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale <= 12 before intubation) who required mechanical ventilation (MV) >= 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS).ResultsWe included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22).ConclusionsExposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

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

BACKGROUNDThe 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.OBJECTIVETo investigate the association of mechanical power with mortality in ICU patients without ARDS.DESIGNThis was an individual patient data analysis that uses the data of three multicentre randomised trials.SETTINGThis study was performed in academic and nonacademic ICUs in the Netherlands.PATIENTSOne 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 MEASURESThe 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.RESULTSAt 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.CONCLUSIONIn 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 REGISTRATIONClinicalTrials.gov Identifier: NCT02159196, ClinicalTrials.gov Identifier: NCT02153294, ClinicalTrials.gov Identifier: NCT03167580

Associations of dynamic driving pressure and mechanical power with postoperative pulmonary complications–posthoc analysis of two randomised clinical trials in open abdominal surgery

Background: While an association of the intraoperative driving pressure with postoperative pulmonary complications has been described before, it is uncertain whether the intraoperative mechanical power is associated with postoperative pulmonary complications. Methods: Posthoc analysis of two international, multicentre randomised clinical trials (ISRCTN70332574 and NCT02148692) conducted between 2011–2013 and 2014–2018, in patients undergoing open abdominal surgery comparing the effect of two different positive end–expiratory pressure (PEEP) levels on postoperative pulmonary complications. Time–weighted average dynamic driving pressure and mechanical power were calculated for individual patients. A multivariable logistic regression model adjusted for confounders was used to assess the independent associations of driving pressure and mechanical power with the occurrence of a composite of postoperative pulmonary complications, the primary endpoint of this posthoc analysis. Findings: In 1191 patients included, postoperative pulmonary complications occurrence was 35.9%. Median time–weighted average driving pressure and mechanical power were 14·0 [11·0–17·0] cmH2O, and 7·6 [5·1–10·0] J/min, respectively. While driving pressure was not independently associated with postoperative pulmonary complications (odds ratio, 1·06 [95% CI 0·88–1·28]; p=0.534), the mechanical power had an independent association with the occurrence of postoperative pulmonary complications (odds ratio, 1·28 [95% CI 1·05–1·57]; p=0.016). These findings were independent of body mass index or the level of PEEP used, i.e., independent of the randomisation arm. Interpretation: In this merged cohort of surgery patients, higher intraoperative mechanical power was independently associated with postoperative pulmonary complications. Mechanical power could serve as a summary ventilatory biomarker for the risk for postoperative pulmonary complications in these patients, but our findings need confirmation in other, preferably prospective studies. Funding: The two original studies were supported by unrestricted grants from the European Society of Anaesthesiology and the Amsterdam University Medical Centers, Location AMC. For this current analysis, no additional funding was requested. The funding sources had neither a role in the design, collection of data, statistical analysis, interpretation of data, writing of the report, nor in the decision to submit the paper for publication

Associations of dynamic driving pressure and mechanical power with postoperative pulmonary complications–posthoc analysis of two randomised clinical trials in open abdominal surgery

Background While an association of the intraoperative driving pressure with postoperative pulmonary complications has been described before, it is uncertain whether the intraoperative mechanical power is associated with postoperative pulmonary complications. Methods Posthoc analysis of two international, multicentre randomised clinical trials (ISRCTN70332574 and NCT02148692) conducted between 2011–2013 and 2014–2018, in patients undergoing open abdominal surgery comparing the effect of two different positive end–expiratory pressure (PEEP) levels on postoperative pulmonary complications. Time–weighted average dynamic driving pressure and mechanical power were calculated for individual patients. A multivariable logistic regression model adjusted for confounders was used to assess the independent associations of driving pressure and mechanical power with the occurrence of a composite of postoperative pulmonary complications, the primary endpoint of this posthoc analysis. Findings In 1191 patients included, postoperative pulmonary complications occurrence was 35.9%. Median time–weighted average driving pressure and mechanical power were 14·0 [11·0–17·0] cmH2O, and 7·6 [5·1–10·0] J/min, respectively. While driving pressure was not independently associated with postoperative pulmonary complications (odds ratio, 1·06 [95% CI 0·88–1·28]; p=0.534), the mechanical power had an independent association with the occurrence of postoperative pulmonary complications (odds ratio, 1·28 [95% CI 1·05–1·57]; p=0.016). These findings were independent of body mass index or the level of PEEP used, i.e., independent of the randomisation arm. Interpretation In this merged cohort of surgery patients, higher intraoperative mechanical power was independently associated with postoperative pulmonary complications. Mechanical power could serve as a summary ventilatory biomarker for the risk for postoperative pulmonary complications in these patients, but our findings need confirmation in other, preferably prospective studies. Funding The two original studies were supported by unrestricted grants from the European Society of Anaesthesiology and the Amsterdam University Medical Centers, Location AMC. For this current analysis, no additional funding was requested. The funding sources had neither a role in the design, collection of data, statistical analysis, interpretation of data, writing of the report, nor in the decision to submit the paper for publication

Effectiveness, safety and efficacy of INTELLiVENT–adaptive support ventilation, a closed–loop ventilation mode for use in ICU patients–a systematic review

Introduction: INTELLiVENT–Adaptive Support Ventilation (INTELLiVENT–ASV), an advanced closed–loop ventilation mode for use in intensive care unit (ICU) patients, is equipped with algorithms that automatically adjust settings on the basis of physiologic signals and patient’s activity. Here we describe its effectiveness, safety, and efficacy in various types of ICU patients. Areas covered: A systematic search conducted in MEDLINE, EMBASE, the Cochrane Central register of Controlled Trials (CENTRAL), and in Google Scholar identified 10 randomized clinical trials. Expert opinion: Studies suggest INTELLiVENT–ASV to be an effective automated mode with regard to the titrations of tidal volume, airway pressure, and oxygen. INTELLiVENT–ASV is as safe as conventional modes. However, thus far studies have not shown INTELLiVENT–ASV to be superior to conventional modes with regard to duration of ventilation and other patient–centered outcomes. Future studies are needed to test its efficacy

Associations of dynamic driving pressure and mechanical power with postoperative pulmonary complications–posthoc analysis of two randomised clinical trials in open abdominal surgery

Background While an association of the intraoperative driving pressure with postoperative pulmonary complications has been described before, it is uncertain whether the intraoperative mechanical power is associated with postoperative pulmonary complications. Methods Posthoc analysis of two international, multicentre randomised clinical trials (ISRCTN70332574 and NCT02148692) conducted between 2011–2013 and 2014–2018, in patients undergoing open abdominal surgery comparing the effect of two different positive end–expiratory pressure (PEEP) levels on postoperative pulmonary complications. Time–weighted average dynamic driving pressure and mechanical power were calculated for individual patients. A multivariable logistic regression model adjusted for confounders was used to assess the independent associations of driving pressure and mechanical power with the occurrence of a composite of postoperative pulmonary complications, the primary endpoint of this posthoc analysis. Findings In 1191 patients included, postoperative pulmonary complications occurrence was 35.9%. Median time–weighted average driving pressure and mechanical power were 14·0 [11·0–17·0] cmH2O, and 7·6 [5·1–10·0] J/min, respectively. While driving pressure was not independently associated with postoperative pulmonary complications (odds ratio, 1·06 [95% CI 0·88–1·28]; p=0.534), the mechanical power had an independent association with the occurrence of postoperative pulmonary complications (odds ratio, 1·28 [95% CI 1·05–1·57]; p=0.016). These findings were independent of body mass index or the level of PEEP used, i.e., independent of the randomisation arm. Interpretation In this merged cohort of surgery patients, higher intraoperative mechanical power was independently associated with postoperative pulmonary complications. Mechanical power could serve as a summary ventilatory biomarker for the risk for postoperative pulmonary complications in these patients, but our findings need confirmation in other, preferably prospective studies. Funding The two original studies were supported by unrestricted grants from the European Society of Anaesthesiology and the Amsterdam University Medical Centers, Location AMC. For this current analysis, no additional funding was requested. The funding sources had neither a role in the design, collection of data, statistical analysis, interpretation of data, writing of the report, nor in the decision to submit the paper for publication

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

Longitudinal respiratory subphenotypes in patients with COVID-19-related acute respiratory distress syndrome: results from three observational cohorts

Background: Patients with COVID-19-related acute respiratory distress syndrome (ARDS) have been postulated to present with distinct respiratory subphenotypes. However, most phenotyping schema have been limited by sample size, disregard for temporal dynamics, and insufficient validation. We aimed to identify respiratory subphenotypes of COVID-19-related ARDS using unbiased data-driven approaches. Methods: PRoVENT–COVID was an investigator-initiated, national, multicentre, prospective, observational cohort study at 22 intensive care units (ICUs) in the Netherlands. Consecutive patients who had received invasive mechanical ventilation for COVID-19 (aged 18 years or older) served as the derivation cohort, and similar patients from two ICUs in the USA served as the replication cohorts. COVID-19 was confirmed by positive RT-PCR. We used latent class analysis to identify subphenotypes using clinically available respiratory data cross-sectionally at baseline, and longitudinally using 8-hourly data from the first 4 days of invasive ventilation. We used group-based trajectory modelling to evaluate trajectories of individual variables and to facilitate potential clinical translation. The PRoVENT-COVID study is registered with ClinicalTrials.gov, NCT04346342. Findings: Between March 1, 2020, and May 15, 2020, 1007 patients were admitted to participating ICUs in the Netherlands, and included in the derivation cohort. Data for 288 patients were included in replication cohort 1 and 326 in replication cohort 2. Cross-sectional latent class analysis did not identify any underlying subphenotypes. Longitudinal latent class analysis identified two distinct subphenotypes. Subphenotype 2 was characterised by higher mechanical power, minute ventilation, and ventilatory ratio over the first 4 days of invasive mechanical ventilation than subphenotype 1, but PaO2/FiO2, pH, and compliance of the respiratory system did not differ between the two subphenotypes. 185 (28%) of 671 patients with subphenotype 1 and 109 (32%) of 336 patients with subphenotype 2 had died at day 28 (p=0·10). However, patients with subphenotype 2 had fewer ventilator-free days at day 28 (median 0, IQR 0–15 vs 5, 0–17; p=0·016) and more frequent venous thrombotic events (109 [32%] of 336 patients vs 176 [26%] of 671 patients; p=0·048) compared with subphenotype 1. Group-based trajectory modelling revealed trajectories of ventilatory ratio and mechanical power with similar dynamics to those observed in latent class analysis-derived trajectory subphenotypes. The two trajectories were: a stable value for ventilatory ratio or mechanical power over the first 4 days of invasive mechanical ventilation (trajectory A) or an upward trajectory (trajectory B). However, upward trajectories were better independent prognosticators for 28-day mortality (OR 1·64, 95% CI 1·17–2·29 for ventilatory ratio; 1·82, 1·24–2·66 for mechanical power). The association between upward ventilatory ratio trajectories (trajectory B) and 28-day mortality was confirmed in the replication cohorts (OR 4·65, 95% CI 1·87–11·6 for ventilatory ratio in replication cohort 1; 1·89, 1·05–3·37 for ventilatory ratio in replication cohort 2). Interpretation: At baseline, COVID-19-related ARDS has no consistent respiratory subphenotype. Patients diverged from a fairly homogenous to a more heterogeneous population, with trajectories of ventilatory ratio and mechanical power being the most discriminatory. Modelling these parameters alone provided prognostic value for duration of mechanical ventilation and mortality. Funding: Amsterdam UMC