Oxygenation thresholds for invasive ventilation in hypoxemic respiratory failure: a target trial emulation in two cohorts
Christopher J. Yarnell,
Federico Angriman,
Bruno L. Ferreyro,
Kuan Liu,
Harm Jan De Grooth,
Lisa Burry,
Laveena Munshi,
Sangeeta Mehta,
Leo Celi,
Paul Elbers,
Patrick Thoral,
Laurent Brochard,
Hannah Wunsch,
Robert A. Fowler,
Lillian Sung,
George Tomlinson
Affiliations
Christopher J. Yarnell
Interdepartmental Division of Critical Care Medicine, University of Toronto
Federico Angriman
Interdepartmental Division of Critical Care Medicine, University of Toronto
Bruno L. Ferreyro
Interdepartmental Division of Critical Care Medicine, University of Toronto
Kuan Liu
Institute of Health Policy, Management and Evaluation, University of Toronto, Medical-Surgical ICU
Harm Jan De Grooth
Department of Intensive Care Medicine, Laboratory for Critical Care Computational Intelligence, Amsterdam Medical Data Science, Amsterdam UMC, Vrije Universiteit
Lisa Burry
Interdepartmental Division of Critical Care Medicine, University of Toronto
Laveena Munshi
Interdepartmental Division of Critical Care Medicine, University of Toronto
Sangeeta Mehta
Interdepartmental Division of Critical Care Medicine, University of Toronto
Leo Celi
Institute for Medical Engineering and Science, Massachusetts Institute of Technology
Paul Elbers
Department of Intensive Care Medicine, Laboratory for Critical Care Computational Intelligence, Amsterdam Medical Data Science, Amsterdam UMC, Vrije Universiteit
Patrick Thoral
Department of Intensive Care Medicine, Laboratory for Critical Care Computational Intelligence, Amsterdam Medical Data Science, Amsterdam UMC, Vrije Universiteit
Laurent Brochard
Keenan Research Centre for Biomedical Research, Li Ka Shing Knowledge Institute, St Michael’s Hospital, Unity Health Toronto
Hannah Wunsch
Institute for Clinical Evaluative Sciences
Robert A. Fowler
Interdepartmental Division of Critical Care Medicine, University of Toronto
Lillian Sung
Institute of Health Policy, Management and Evaluation, University of Toronto, Medical-Surgical ICU
George Tomlinson
Department of Medicine, University Health Network and Sinai Health System
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.
