Time-varying intensity of mechanical ventilation and mortality in patients with acute respiratory failure: a registry-based, prospective cohort study

Abstract

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.Methods In 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.Findings Of 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.Interpretation Cumulative 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.

Early experience with critically ill patients with COVID-19 in Montreal

“…The median [IQR] day 1 sequential organ failure assessment score was 6 [3][4][5][6][7]. Invasive mechanical ventilation (IMV) was used in 57% of patients for a median [IQR] of 11 [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] mL/ cmH 2 O) and very elevated estimated dead space fraction (day 1 = 0.60 [0.53-0.67]; day 10 = 0.72 [0.69-0.79]). Overall hospital mortality was 25%, and 21% in the IMV patients.…”

Individualized Mechanical power-based ventilation strategy for acute respiratory failure formalized by finite mixture modeling and dynamic treatment regimen

“…These variables were chosen because they were commonly used for assessing disease severity as was used in the sequential organ failure assessment (SOFA) score. MP was calculated as follows [ 14 , 26 ]: where TV is the tidal volume and is the peak inspiratory pressure and is the end-inspiratory plateau pressure. Missing values were imputed by the Last observation carried forward (LOCF) method for longitudinal data [27] , sensitivity analysis by using hot deck method was performed to ensure stability of the results (results not shown) [28] .…”

“…These variables were chosen because they were commonly used for assessing disease severity as was used in the sequential organ failure assessment (SOFA) score. MP was calculated as follows [14,26]:…”

Current and evolving standards of care for patients with ARDS

“…The simplified version of this calculation allows one to estimate mechanical power with only V T , respiratory rate, peak pressure and ΔP [21], and day 1 mechanical power calculated in this manner has been associated with mortality [22]. Furthermore, a recent analysis of a large registry of over 13,000 patients with hypoxemic respiratory failure showed that exposure to higher intensity of mechanical ventilation (higher driving pressure or mechanical power), even for relatively brief periods, was independently associated with increased mortality over the entire duration of ventilation; with stronger association in those with worse baseline hypoxemia [23]. Nevertheless, randomized trials demonstrating the superiority of a ventilatory strategy focused on limiting driving pressure or mechanical power are still needed, and a recent small trial (n = 31) suggest a ΔP-limited strategy may be feasible [24].…”