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-h of hypoxemia. The eligible population included non-intubated patients with SpO₂/FiO₂ ≤ 200 and SpO₂ ≤ 97%. The target trial was emulated using a single-center database (MIMIC-IV) 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 h. 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.

Keywords: Artificial respiration; Critical care; Respiratory insufficiency.

Fig. 1

Study flowchart. Patients could be included if they had been admitted in any of the following ICUs: Medical, Medical/Surgical or Coronary ICU, had not been intubated previously and did not present any exclusion criteria. Afterwards, if they presented with all the inclusion criteria, it was considered that they had met eligibility and they were included in target trial number 1. Each patient could later contribute to future observations in the following 48 h, provided he/she did not receive intubation in the current target trial and that he/she continued to present eligibility in the following hours. For example, 723 patients were excluded from target trial number 2 with 469 patients having received intubation and 254 patients not presenting with further eligibility (either because of any new exclusion criteria, not further inclusion criteria or both). A total of 38,272 patient-observations were included of which 747 corresponded to observations where intubation took place. SF: SpO₂/FiO₂, RR: respiratory rate, GCS: Glasgow Coma Scale

Fig. 2

Survival curves estimated from the weighted Cox model. After IPW estimation, the population at study comprised of 38,272 patient-observations of whom 747 and 37,525 received and did not receive invasive ventilation. Kaplan–Meier curves for these weighted population showed that invasive ventilation was associated with a decreased hazard of dying over the following year. Dashed lines represent 28 and 60 days respectively after first-met eligibility

Fig. 3

Kaplan–Meier curves for 7588 patient-observations with ROX ≤ 4.88 at eligibility of whom 348 were intubated. Dashed lines represent 28 and 60 days respectively