Effect of immediate initiation of invasive ventilation on mortality in acute hypoxemic respiratory failure: a target trial emulation

Abstract

Purpose: Invasive ventilation is a fundamental treatment in intensive care but its precise timing is difficult to determine. This study aims at assessing the effect of initiating invasive ventilation versus waiting, in patients with hypoxemic respiratory failure without immediate reason for intubation on one-year mortality. Methods: Emulation of a target trial to estimate the benefit of immediately initiating invasive ventilation in hypoxemic respiratory failure, versus waiting, among patients within the first 48-hours of hypoxemia. The eligible population included non-intubated patients with SpO₂/FiO₂ ≤ 200 and SpO₂ ≤97%. The target trial was emulated using the MIMIC-IV database which contains granular information about clinical status. The hourly probability to receive mechanical ventilation was continuously estimated. The hazard ratios for the primary outcome, one-year mortality, and the secondary outcome, 30-day mortality, were estimated using weighted Cox models with stabilized inverse probability weights used to adjust for measured confounding. Results: 2996 patients fulfilled the inclusion criteria of whom 792 were intubated within 48 hours. Among the non-invasive support devices, the use of oxygen through facemask was the most common (75%). Compared to patients with the same probability of intubation but who were not intubated, intubation decreased the hazard of dying for the first year after ICU admission (HR 0.81 (95% CI 0.68–0.96, p = 0.018). Intubation was associated with a 30-day mortality HR of 0.80 (95% CI 0.64–0.99, p = 0.046). Conclusion: The initiation of mechanical ventilation in patients with acute hypoxemic respiratory failure reduced the hazard of dying in this emulation of a target trial.