The Effects of Hyper- and Hypoventilation on Cerebral Physiology in a Healthy and Compromised Brain State: An Experimental Pig Model with State-of-the-Art Neuromonitoring

Abstract

Arterial carbon dioxide (pCO₂) strongly affects cerebrovascular tone and cerebral physiology. While moderate hyperventilation is often used to reduce intracranial pressure (ICP) in acute brain injury, its broader physiological effects remain unclear. In this experimental study, 10 anesthetized pigs underwent multimodal neuromonitoring, including ICP, cerebral perfusion pressure, common autoregulatory indices (pressure reactivity index [PRx], cerebral blood flow index [CBFx], oxygen reactivity index), CBF, brain tissue oxygenation (pbtO₂), and microdialysis. Animals were exposed to four ventilatory intervals (normoventilation, moderate and severe hyperventilation, and hypoventilation), first in a healthy state and then following induction of intracranial hypertension (ICP 30–40 mmHg) via epidural balloon inflation. In the healthy brain, moderate and severe hyperventilation numerically, but non-significantly, reduced CBF without affecting pbtO₂ or cerebral energy metabolism, while hypoventilation increased CBF and pbtO₂. Under intracranial hypertension, moderate hyperventilation improved PRx and preserved CBF, pbtO₂, and metabolism, but severe hyperventilation reduced pbtO₂. Hypoventilation produced variable responses: Animals with higher baseline blood pressure showed improved perfusion and oxygenation, whereas those with lower pressure experienced reduced CBF, impaired oxygenation, and metabolic distress. These findings underscore the complex and context-dependent effects of pCO₂ on cerebral physiology, indicating that ventilatory strategies may both benefit and harm the injured brain depending on individual vulnerability and hemodynamic status.