Multimodal Monitoring of Cerebral Autoregulation After Pediatric Brain Injury

A. Background and Purpose

Acute neurologic injury (ANI) is an important and common cause of mortality and morbidity in pediatrics such as traumatic brain injury (TBI), stoke and hypoxic-ischemic encephalopathy (HIE). Advances have been made in the intensive care management of children with ANI improving mortality rates but survivors are often left with long-term neurologic and neuropsychological disabilities. It is estimated that as many as 50-60% of children who sustain a severe TBI will suffer from some long-term neurologic sequela such as cognitive, behavioral, psychiatric and psychological defects despite modern advanced care. Survivors of ANI may also sustain a reduction in their quality of life and ability to participate in daily activities and their long-term care can results in a considerable socioeconomic burden. The brain is a highly metabolic organ representing 2% of the total body weight but consuming 20% of the oxygen. The dependence of the brain on a high rate of aerobic cellular metabolism necessitates a continuous supply of oxygen and glucose. However, this large energy requirement also means that brain cells are particularly vulnerable to injury when nutrients are deprived even for very short periods. The delivery of cerebral energy nutrients is a highly controlled process maintained through an intricately balanced cerebrovascular system, which regulates cerebral blood flow (CBF) at a constant rate to meet tissue demand. In the simplest model CBF is proportional to the pressure differential across the cerebrovascular system and is inversely proportional to the cerebral vascular resistance (CVR). The driving pressure differential or cerebral perfusion pressure (CPP) represents the vascular pressure difference across the brain tissue, expressed as the mean arterial pressure (MAP) minus the intracranial pressure (ICP).

In normal physiologic states CBF is largely independent of CPP over a wide range of pressure by altering CVR, a process known as cerebral autoregulation (CA). Cerebral autoregulation is controlled by the complex interplay of neurogenic, metabolic and myogenic mechanisms. During CA arterioles in the brain dilate (decreasing resistance) or constrict (increasing resistance) maintaining an adequate CBF to meet tissue metabolic demands (Figure 1). After ANI the endogenous autoregulatory mechanisms may be impaired predisposing vulnerable tissue to ischemia or vasogenic edema. In the normal state CA maintains a constant CBF over a wide rage of perfusion pressures but with loss of CA CBF becomes linear with perfusion pressure such that any reduction in CPP or MAP will cause a corresponding fall in blood flow. After severe TBI, cardiac arrest or spontaneous intracranial hemorrhage, children may suffer from a combination of cerebral and systemic pathophysiologic alterations such as hypotension, shock, cerebral edema, increased intracranial pressure, acute blood loss anemia and respiratory failure. Therefore, the biologic system of CA is a clinically important mechanism that functions to protect against cerebral hypoperfusion or hyperperfusion during the pathophysiologic changes that occur commonly in neurocritical illness where patients may have rapid changes in blood pressure, intracranial pressure or systemic oxygen delivery.

Cerebral blood flow is not directly measured at the bedside in clinical practice hence either CPP (if ICP is measured) or MAP is used to target an age-based goal in clinical practice. However, there are several limitations with this approach, 1) the optimal MAP/CPP threshold is unknown in children across age groups, 2) the optimal MAP/CPP value is very likely to not only be reflected by age-based target but be highly dependent on individual patient and injury-type factors and 3) due to this uncertainty there exists wide clinical variability is what value medical providers choose to target MAP/CPP after ANI. Moreover, since autoregulation is a continuous spectrum dependent on the adaptive response of CVR to regulate flow, disturbances may change over time and may also differ in the same patient with varying degrees of physiological derangement. Since CBF is not measured in clinical practice the actual ability of the patient to maintain an adequate CBF at a given MAP/CPP is assumed but not known. Relying on perfusion pressure alone fails to account for alterations in CA that occur after brain injury hindering the clinician's ability to determine if CBF is adequate to meet metabolic needs at a given MAP/CPP

There are emerging studies supporting the theory that impaired CA is an important factor in ANI. In adults impairments in CA are associated with a worse outcome and have been demonstrated to occur after a wide-spectrum of neurologic injuries, including TBI, HIE, subarachnoid hemorrhage and stroke.