Alterations in intracranial pressure and cerebral blood volume in endotoxemia.
Academic Article
Overview
abstract
Marked deterioration of neurologic function accompanies organ dysfunction in systemic sepsis. Although previous hypotheses have suggested that cerebral hypoperfusion, anoxia or progressive edema of the brain may be causative, the pathogenesis remains unknown. Patients with sepsis with stable or supported hemodynamics and adequate oxygenation may manifest confusion, stupor or coma. Recent evidence has demonstrated that the brain is the source of many classical mediators of inflammation after various forms of injury. These mediators, including the leukotrienes, have pronounced effect on cerebrovascular function. Endotoxin is known to stimulate the release of arachidonate from cell membranes, the rate limiting step in leukotriene synthesis. The current studies were performed to test the hypothesis that neurologic dysfunction associated with endotoxemia is characterized by alterations in cerebrovascular permeability or vasomotor function manifested by intracranial hypertension, or both. We studied the response of miniature swine to experimental endotoxemic shock and compared this response with hemorrhagic hypotension. We observed a dramatic elevation of intracranial pressure in swine subjected to endotoxemic shock, despite arterial hypotension. Moreover, estimation of cerebral blood volume (CBV) by reflectance infrared photoplethysmography demonstrated a dramatic increase in CBV, which corresponded to this elevation in intracranial pressure. However, cerebral cortical oxygen saturation was significantly reduced despite this net increase in CBV, indicative of an increase in the venous volume of the brain, while arterial volume remained the same or decreased from baseline levels. Oxygen extraction across the brain decreased during this same period compared with baseline and control values. These results demonstrate that endotoxemia is associated with the development of intracranial hypertension and an increase in CBV secondary to elevation of cerebrovascular venous volume coupled with reduced oxygen extraction across the brain. This evidence of cerebrovascular dysfunction probably represents blood flow maldistribution, similar to that seen in other organs with sepsis, suggesting a cause for altered neurologic function in systemic sepsis.
