Oxygenation thresholds for invasive ventilation in hypoxemic respiratory failure: a target trial emulation in two cohorts

Abstract

Background The optimal thresholds for the initiation of invasive ventilation in patients with hypoxemic respiratory failure are unknown. Using the saturation-to-inspired oxygen ratio (SF), we compared lower versus higher hypoxemia severity thresholds for initiating invasive ventilation. Methods This target trial emulation included patients from the Medical Information Mart for Intensive Care (MIMIC-IV, 2008–2019) and the Amsterdam University Medical Centers (AmsterdamUMCdb, 2003–2016) databases admitted to intensive care and receiving inspired oxygen fraction ≥ 0.4 via non-rebreather mask, noninvasive ventilation, or high-flow nasal cannula. We compared the effect of using invasive ventilation initiation thresholds of SF < 110, < 98, and < 88 on 28-day mortality. MIMIC-IV was used for the primary analysis and AmsterdamUMCdb for the secondary analysis. We obtained posterior means and 95% credible intervals (CrI) with nonparametric Bayesian G-computation. Results We studied 3,357 patients in the primary analysis. For invasive ventilation initiation thresholds SF < 110, SF < 98, and SF < 88, the predicted 28-day probabilities of invasive ventilation were 72%, 47%, and 19%. Predicted 28-day mortality was lowest with threshold SF < 110 (22.2%, CrI 19.2 to 25.0), compared to SF < 98 (absolute risk increase 1.6%, CrI 0.6 to 2.6) or SF < 88 (absolute risk increase 3.5%, CrI 1.4 to 5.4). In the secondary analysis (1,279 patients), the predicted 28-day probability of invasive ventilation was 50% for initiation threshold SF < 110, 28% for SF < 98, and 19% for SF < 88. In contrast with the primary analysis, predicted mortality was highest with threshold SF < 110 (14.6%, CrI 7.7 to 22.3), compared to SF < 98 (absolute risk decrease 0.5%, CrI 0.0 to 0.9) or SF < 88 (absolute risk decrease 1.9%, CrI 0.9 to 2.8). Conclusion Initiating invasive ventilation at lower hypoxemia severity will increase the rate of invasive ventilation, but this can either increase or decrease the expected mortality, with the direction of effect likely depending on baseline mortality risk and clinical context.

Costs, quality-adjusted life years, and value-of-information of different thresholds for the initiation of invasive ventilation in hypoxemic respiratory failure

“…The increase in predicted long-term disability resulted from increased predicted use of invasive ventilation, which shifted patients to higher long-term disability risk groups. Prior work has investigated the mortality associated with particular thresholds for invasive ventilation but has not incorporated functional outcomes or costs (10,11,48). It is somewhat reassuring that small improvements in survival associated with increased use of invasive ventilation can be cost-effective.…”

“…(24,25) These thresholds have been recently evaluated in an observational study that provides estimates of 28-day invasive ventilation rates and survival for each threshold. (11) We also included a "usual care" strategy, where invasive ventilation occurred at clinical discretion without the use of specified thresholds.…”

“…The probabilities of invasive ventilation and hospital survival followed a beta distribution with mean event probability based on an observational study of oxygenation thresholds for initiating invasive ventilation. (11) Although the study estimated 28-day outcomes, we used these estimates for hospital outcomes because more comprehensive estimates were not available. 10 We increased the standard deviation in the estimates from the observational study 5-fold from 0.02 to 0.1, because the data came from a single center.…”

“…However, recent research has suggested that initiating invasive ventilation at less severe hypoxemia in populations with high baseline mortality risk, which would increase the use of invasive ventilation, may improve 28-day survival. (10,11) The provision of invasive ventilation is resource-intensive. (12)(13)(14) Prior efforts to study the cost-effectiveness of invasive ventilation have focused on adjunct therapies such as ventilator management, proning, pulmonary artery catheters, or extracorporeal membrane oxygenation (ECMO).…”

“…However, recent research has suggested that initiating invasive ventilation at less severe hypoxemia in populations with high baseline mortality risk, which would increase the use of invasive ventilation, may improve 28-day survival. (10,11)…”