When Lung-Protective Ventilation Isn’t Brain-Protective? A Look at the PROLABI Trial

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Mascia L, et al. "Lung-Protective Mechanical Ventilation in Patients with Severe Acute Brain Injury." *Am J Respir Crit Care Med*. 2024.

Background

Lung-protective ventilation (LPV), characterized by low tidal volumes and appropriate PEEP, is a cornerstone in managing patients with acute respiratory distress syndrome (ARDS). However, its application in patients with severe acute brain injury raises concerns. The potential for lung protective ventilation to increase intracranial pressure due to hypercapnia and elevated PEEP levels necessitates a closer examination of its safety and efficacy in this unique patient population.

The Study

To explore this, a team of Italian researchers conducted a multicenter, randomized controlled trial involving 190 mechanically ventilated patients with severe brain injuries. These were critically ill patients with traumatic brain injury (TBI) , subarachnoid hemorrhage, intracerebral hemorrhage, or large ischemic strokes. All patients were comatose, unable to follow commands or open their eyes, and were enrolled within 24 hours of ICU admission.

Intervention:

  • Protective Ventilation Group: Tidal volume of 6 mL/kg predicted body weight (PBW), PEEP 8 cm H₂O

  • Conventional Ventilation Group: Tidal volume >8 mL/kg PBW, PEEP 4 cm H₂O

Results 

Primary Outcome was defined as the composite of mortality, ventilator dependency, or development of ARDS at 28 days

  • Primary Outcome: Occurred in 61.5% of the protective group vs. 45.3% in the conventional group (RR=1.35; p=0.026)

  • Mortality: 28.9% in the protective group vs. 15.1% in the conventional group (p=0.02)

  • Ventilator Dependency: Higher in the protective group (42% vs. 28%)

  • ARDS Incidence: No significant difference between groups

  • Neurologic Outcomes: Worse in the protective group at both discharge and 6 months, assessed by the Modified Oxford Handicap Scale and Glasgow Outcome Scale.

Discussion

The results of the PROLABI trial were both surprising and thought-provoking. Contrary to expectations, the group receiving “lung-protective” ventilation not only failed to benefit, they actually did worse. Higher mortality, more ventilator dependence, and worse long-term neurologic outcomes.

What protects the lungs, low tidal volume, higher PEEP,  can inadvertently harm the brain. Even with tight control of PaCO₂ in both groups, the lung-protective group had slightly higher PaCO₂ levels and central venous pressures. While these differences seem modest on paper, even small increases in carbon dioxide can dilate cerebral blood vessels, raising intracranial pressure. Higher PEEP can impair cerebral venous return, especially in patients with compliant lungs who transmit more intrathoracic pressure to the brain.

In essence, the PROLABI trial challenges our reflexive use of ARDS ventilator settings and reminds us that protecting one organ may come at the expense of another.

Limitations

While the PROLABI trial offers important insights, it’s not without its caveats. The study was terminated early after enrolling only 190 of the planned 524 patients due to funding constraints. This early stop means the trial was underpowered, raising the possibility of both type I and type II error. Other limitations worth noting include the open-label design where clinicians knew which group patients were in, which introduces potential bias in management or weaning decisions.

Additionally, these findings apply specifically to patients with brain injury without ARDS. We don’t know if lung-protective strategies are similarly harmful in brain-injured patients with concurrent ARDS.

Authorship

Written by: Diana Rodriguez, MD, PGY-3 University of Cincinnati Department of Emergency Medicine

Editing and Posting by Jeffery Hill, MD MEd, Assistant Professor, University of Cincinnati Department of Emergency Medicine

Audio Editing by Anita Goel, MD Adjunct Assistant Professor, University of Cincinnati Department of Emergency Medicine.

Cite as: Rodriguez, D., Hill, J, Goel, A. When Lung-Protective Ventilation Isn’t Brain-Protective? A Look at the PROLABI Trial. TamingtheSRU.com. www.tamingthesru.com/blog/journal-club-PROLABI. 6/25/2025.