Bedside Cerebrovascular Autoregulation Monitoring in Children Under General Anesthesia

Cerebral autoregulation (CA) is a mechanism that maintains cerebral flood flow (CBF) despite the fluctuations in the arterial blood pressure. This process protects the brain from ischemic or hemorrhagic insults during events of hypo- or hyperperfusion, respectively. Children under general anesthesia (GA) are particularly vulnerable to these events because anesthetic agents profoundly impact cerebral metabolic supply and demand. At the same time, to varying degrees, anesthetic agents can compromise respiration, produce hypotension, and even inhibit cerebral autoregulation function. General anesthesia-induced cerebral hypoperfusion can occur during routine GA and is associated with deleterious neurological outcomes in children. Thus, primary goals in managing GA are therefore to maintain adequate hemodynamics and cerebral perfusion under intact CA.

A recent large retrospective study demonstrated that blood pressure ranges in anesthetized children are significantly lower than in awake, healthy children. However, the safe limits of blood pressure that maintains adequate cerebral perfusion in infants and children are not clear and my vary depending on the age and disease severity. Currently, bedside CBF monitoring had been impractical. Transcranial Doppler ultrasound (TCD) is the only clinically available tool to measure cerebral blood flow velocity in larger arteries. Although TCD has been used for obtaining cerebral hemodynamics including autoregulation for clinical use, it is not practical for long-term monitoring due to the difficulty to secure the probe on the patient's head. Furthermore, the accuracy of the TCD measurement is highly operator-dependent which impedes its general use.

Cerebral oximeters, based on near-infrared spectroscopy (NIRS) have become popular means of assessing cerebral hemoglobin oxygen saturation (cStO2) during GA, but its use has not become routine. Clinically relevant desaturation (generally below 50-60 percent) implies a mismatch between brain oxygen supply and demand. When presenting persistently, they can serve as an intraoperative warning sign of hemodynamic and metabolic comprise. A recent study with 453 healthy infants undergoing general anesthesia for non-cardiac surgery found the episodes of desaturation is rare (2%) despite that critically low blood pressure (MAP <35 mmHg) was observed in almost 40% of subjects. Because desaturation events are relatively rare, they are unlikely to be responsible for adverse outcomes in non-cardiac surgery. However, the magnitude of the change in cStO2 from the awake to anesthetized state was associated with the range of MAP experienced during GA, suggesting systematic changes in cerebral perfusion may be more important than desaturation events for assessing hemodynamic risk.

To address the critical public health issues associated with the safe use of anesthesia in children, the investigators propose to develop new beside tools to monitor cerebral hemodynamics and perfusion continuously during anesthesia. The investigators aim to quantify cStO2, CBF, CMRO2, and its coupling relationship in children with and without neurologic impairments while awake and during different phases of GA (aim1). With continuous measures of arterial blood pressure, the investigators will further determine CA functions by studying the relationship between CBF and ABP simultaneously with anesthesia-related physiological events, including hypercapnia (aim2). Ultimately, the investigators aim to integrate our technology into perioperative monitoring to enable age-appropriate, goal-directed cerebral hemodynamic management to spare infant brains from the potentially deleterious effects of anesthesia.