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

ABSTRACT: 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.

SUBMITTER: Schuijt MTU

PROVIDER: S-EPMC8637438 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Mortality in acute respiratory failure remains high despite the use of lung-protective ventilation. Recent studies have shown an association between baseline ventilation parameters (driving pressure or mechanical power) and outcomes for patients with acute respiratory distress syndrome. Strategies focused on limiting these parameters have been proposed to further improve outcomes. However, it remains unknown whether driving pressure and mechanical power should be limited over the entire duration of mechanical ventilation and in all patients with acute respiratory failure. We aimed to estimate the association between exposure to different intensities of mechanical ventilation over time and intensive care unit (ICU) mortality in patients with acute respiratory failure.MethodsIn this registry-based, prospective cohort study, we obtained data from the Toronto Intensive Care Observational Registry, which includes all patients receiving mechanical ventilation for 4 h or more in nine ICUs that are affiliated with the University of Toronto (Toronto, ON, Canada). We included all adult (≥18 years) patients who received invasive mechanical ventilation between April 11, 2014, and June 5, 2019. Patients were excluded if they received treatment with extracorporeal life support. The primary outcome was ICU mortality. Bayesian joint models were used to estimate the strength of associations, accounting for informative censoring due to death during follow-up.FindingsOf 13 939 patients recorded in the registry, 13 408 (96·2%) were eligible for descriptive analysis. The primary analysis comprised 7876 (58·7%) patients with complete baseline characteristics, and a secondary analysis included all 13 408 patients after multiple imputation in the joint model analysis. 2409 (18·0%) of 13 408 patients died in the ICU. After adjustment for baseline characteristics, including age and severity of illness, a significant increase in the hazard of death was found to be associated with each daily increment in driving pressure (hazard ratio 1·064, 95% credible interval 1·057-1·071) or mechanical power (hazard ratio 1·060, 95% credible interval 1·053-1·066). These associations persisted over the duration of mechanical ventilation.InterpretationCumulative exposure to higher intensities of mechanical ventilation was harmful, even for short durations. Limiting exposure to driving pressure or mechanical power should be evaluated in further studies as promising ventilation strategies to reduce mortality in patients with acute respiratory failure.FundingCanadian Institutes of Health Research.

Project description:BackgroundLung-protective ventilation is key in bridging patients suffering from COVID-19 acute respiratory distress syndrome (ARDS) to recovery. However, resource and personnel limitations during pandemics complicate the implementation of lung-protective protocols. Automated ventilation modes may prove decisive in these settings enabling higher degrees of lung-protective ventilation than conventional modes.MethodProspective study at a Swiss university hospital. Critically ill, mechanically ventilated COVID-19 ARDS patients were allocated, by study-blinded coordinating staff, to either closed-loop or conventional mechanical ventilation, based on mechanical ventilator availability. Primary outcome was the overall achieved percentage of lung-protective ventilation in closed-loop versus conventional mechanical ventilation, assessed minute-by-minute, during the initial 7 days and overall mechanical ventilation time. Lung-protective ventilation was defined as the combined target of tidal volume <8 ml per kg of ideal body weight, dynamic driving pressure <15 cmH2O, peak pressure <30 cmH2O, peripheral oxygen saturation ≥88% and dynamic mechanical power <17 J/min.ResultsForty COVID-19 ARDS patients, accounting for 1,048,630 minutes (728 days) of cumulative mechanical ventilation, allocated to either closed-loop (n = 23) or conventional ventilation (n = 17), presenting with a median paO2/ FiO2 ratio of 92 [72-147] mmHg and a static compliance of 18 [11-25] ml/cmH2O, were mechanically ventilated for 11 [4-25] days and had a 28-day mortality rate of 20%. During the initial 7 days of mechanical ventilation, patients in the closed-loop group were ventilated lung-protectively for 65% of the time versus 38% in the conventional group (Odds Ratio, 1.79; 95% CI, 1.76-1.82; P < 0.001) and for 45% versus 33% of overall mechanical ventilation time (Odds Ratio, 1.22; 95% CI, 1.21-1.23; P < 0.001).ConclusionAmong critically ill, mechanically ventilated COVID-19 ARDS patients during an early highpoint of the pandemic, mechanical ventilation using a closed-loop mode was associated with a higher degree of lung-protective ventilation than was conventional mechanical ventilation.

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

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