Low-Tidal-Volume Ventilation and Mortality in Patients With Acute Brain Injury: A Secondary Analysis of an International Observational Study

Affiliations

¹ Division of General Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
² Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada.
³ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁴ Department of Neurology, University of Washington School of Medicine, Seattle, WA; Department of Neurosurgery, University of Washington School of Medicine, Seattle, WA; Department of Anesthesiology and Pain Medicine, University of Washington School of Medicine, Seattle, WA.
⁵ IRCCS Policlinico San Martino, Genoa, Italy; Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy.
⁶ Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Biomedical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD.
⁷ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
⁸ UMR 1246 (Methods in Patient-Centered Outcomes and Health Research; SPHERE), Nantes Université (Nantes) and Tours Université (Tours), Nantes, France; Department of Anesthesia and Critical Care, CHU Nantes, Nantes Université, Hôtel-Dieu, Nantes, France.
⁹ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada. Electronic address: shaurya.taran@mail.utoronto.ca.

PMID: 40639639
DOI: 10.1016/j.chest.2025.06.042

Free article

Low-Tidal-Volume Ventilation and Mortality in Patients With Acute Brain Injury: A Secondary Analysis of an International Observational Study

Julian F Daza et al. Chest. 2025.

Free article

. 2025 Jul 8:S0012-3692(25)00829-3.

doi: 10.1016/j.chest.2025.06.042. Online ahead of print.

Affiliations

¹ Division of General Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
² Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada.
³ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁴ Department of Neurology, University of Washington School of Medicine, Seattle, WA; Department of Neurosurgery, University of Washington School of Medicine, Seattle, WA; Department of Anesthesiology and Pain Medicine, University of Washington School of Medicine, Seattle, WA.
⁵ IRCCS Policlinico San Martino, Genoa, Italy; Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy.
⁶ Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Biomedical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD.
⁷ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
⁸ UMR 1246 (Methods in Patient-Centered Outcomes and Health Research; SPHERE), Nantes Université (Nantes) and Tours Université (Tours), Nantes, France; Department of Anesthesia and Critical Care, CHU Nantes, Nantes Université, Hôtel-Dieu, Nantes, France.
⁹ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada. Electronic address: shaurya.taran@mail.utoronto.ca.

PMID: 40639639
DOI: 10.1016/j.chest.2025.06.042

Abstract

Background: Low-tidal-volume ventilation (LTVV) improves outcomes in critically ill patients, but its impact in patients with acute brain injuries (ABIs) is less certain.

Research question: What is the association between LTVV and mortality in mechanically ventilated patients with ABI?

Study design and methods: We did a secondary analysis of a prospective observational study (NCT03400904; https://clinicaltrials.gov/study/NCT03400904). We compared LTVV (≤ 8 mL/kg predicted body weight [PBW]) with tidal volumes > 8 mL/kg PBW over the first 7 days of mechanical ventilation. Alternate analyses used lower thresholds for LTVV. Marginal structural Cox models were used to evaluate the association between LTVV and ICU mortality up to 60 days. Stabilized inverse probability treatment and censoring weights were generated using multivariable logistic regression adjusted for baseline and time-dependent confounders.

Results: A total of 1,510 patients from 73 ICUs across 18 countries were included. The mean age was 52 years, 513 patients (34.0%) were female, and the most common ABI etiology was traumatic brain injury (n = 726; 48.1%). ARDS developed in 137 patients (9.2%). In patients receiving LTVV, adjusted incidence of ICU mortality was 40.2% (95% CI, 19.2%-61.1%), vs 59.7% (95% CI, 44.0%-75.4%) in patients receiving tidal volumes > 8 mL/kg PBW (marginal hazard ratio, 0.54; 95% CI, 0.33-0.88). There was no heterogeneity of treatment effect in subgroup analyses, and sensitivity analyses for unmeasured confounding yielded similar results. However, associations were less clear at lower thresholds of LTVV.

Interpretation: In this predominantly non-ARDS cohort of patients with ABI, LTVV over the first 7 days of mechanical ventilation was associated with lower ICU mortality up to 60 days, vs tidal volumes > 8 mL/kg PBW. Future research should investigate effects in patients with ABI and ARDS, use of lower LTVV thresholds, and impact on additional end points including functional outcomes and adverse events.

Keywords: acute brain injury; low-tidal-volume ventilation; lung-protective ventilation; neurocritical care.

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Conflict of interest statement

Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: C. R. received fees as speaker for Edwards and BT. R. D. S. received consulting fees from Ceribell Inc. and speaker honoraria from the University of Texas MD Anderson Cancer Center. R. C. received consulting fees from Viatris. S. T. received speaker fees from the Mechanical Ventilation Symposium, Interdepartmental Division of Critical Care Medicine, University of Toronto. None declared (J. F. D., D. M. H., M. U., K. L., S. W., and V. A. McC.).

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Low-Tidal-Volume Ventilation and Mortality in Patients With Acute Brain Injury: A Secondary Analysis of an International Observational Study

Affiliations

Low-Tidal-Volume Ventilation and Mortality in Patients With Acute Brain Injury: A Secondary Analysis of an International Observational Study

Authors

Affiliations

Abstract

Conflict of interest statement

Associated data

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Medical