Ventilating the injured brain: Balancing lung protection and cerebral physiology

This review summarizes mechanical ventilation in acute brain injury (ABI) through the lens of integrated brain–lung interactions, with a focus on how gas exchange, ventilatory mechanics, and hemodynamics influence cerebral physiology and clinical outcomes. Among these interactions, the effects of arterial blood gases on the cerebral circulation are particularly important. Carbon dioxide is a key determinant of cerebrovascular tone. Hypocapnia reduces cerebral blood flow (CBF), blood volume, and intracranial pressure (ICP), whereas hypercapnia increases CBF and may exacerbate intracranial hypertension. Observational data demonstrate a U-shaped association between arterial partial pressure of carbon dioxide (PaCO₂) and mortality, with increased risk at both low and high values. Current evidence supports targeting normocapnia (approximately 35–45 mm Hg) in most patients, with transient hypocapnia reserved for short-term management of intracranial hypertension. Oxygenation is similarly associated with outcomes. Hypoxemia is consistently associated with increased mortality and worse neurological outcomes, while hyperoxemia leads to oxidative injury and is associated with adverse outcomes in observational studies. Data from large cohorts suggest lowest mortality at intermediate arterial partial pressure of oxygen (PaO₂) levels. Beyond gas exchange, ventilatory mechanics may also influence cerebral physiology. Positive pressure ventilation affects intracranial dynamics through changes in pleural pressure, venous return, and cardiac output. The effect of positive end-expiratory pressure (PEEP) on ICP is variable and depends on lung and chest wall compliance, intracranial compliance, and hemodynamic status. Despite these physiologic considerations, evidence for specific ventilator targets in ABI remains limited. Observational studies suggest associations between higher tidal volume (Vt), plateau pressure (Pplat), driving pressure (ΔP), and mechanical power (MP) with increased mortality; however, randomized data are sparse, and results are heterogeneous. In patients with concomitant acute respiratory distress syndrome (ARDS), lung-protective ventilation strategies improve respiratory outcomes but may influence cerebral physiology, particularly through effects on PaCO₂ and intrathoracic pressure. Future research should focus on integrating multimodal neuromonitoring with respiratory physiology to define patient-specific ventilatory targets and evaluate their impact on neurological outcomes in prospective studies.