Research Project
10216102
Project Summary The broad objective of this research is to use neuroimaging to understand the hemodynamic responses to anesthesia and sedation. Anesthesia and sedation, commonly used in pediatric patients, cause profound and rapid changes in cerebral blood flow and metabolism. Under normal conditions in adults, these changes are tightly coupled to one another to protect the brain from hypoxia and ischemia. However, the extent to which flow and metabolism are coupled during anesthesia and sedation in pediatric patients is unknown. The aims of this project are (1) to quantify the hemodynamic and metabolic responses to anesthesia in infants, and (2) to compare those responses during the administration of specific anesthetics in infants with differing disease states that may make them more vulnerable to the uncoupling of flow from metabolism. If our hypotheses are borne out and infants are particularly vulnerable to this uncoupling, our findings will lead to future studies to assess hemodynamic responses as potential biomarkers that predict and mediate adverse outcomes in infants exposed to anesthesia. Therefore, this project is relevant to the NHLBI's strategic objective to identify factors that account for individual differences in pathobiology and treatment response. This project requires an opportunity for making simultaneous flow and metabolism measurements in anesthetized infants. Clinical MR imaging provides this opportunity. Therefore, we will enroll into a Naturalistic Cohort Study 120 infants younger than 1 year of age who require a clinical MRI scan, half receiving anesthesia and half not. Enrolled infants will be imaged with MRI sequences that measure cerebral blood flow and metabolism. In addition, we will enroll 30 additional infants of the same age into a Pilot Randomized Comparator Trial (RCT), in which the infants will be randomized to receive either propofol or sevoflurane anesthesia. Randomization will dramatically reduce potential confounding of diseases and anesthetic agents present in the naturalistic study. Learning to design RCTs (Goal 1) is addressed with didactics and a practicum to advance my translational research skills. This project requires my learning how anesthetics and sedatives alter hemodynamics and fluid dynamics (Goal 2) and how the known and putative mechanisms of neurotoxicity and flow-metabolism uncoupling affect the developing brain (Goal 3). This project and my research career will help infants who require anesthesia or sedation. It creates a paradigm in which the hemodynamic response to anesthesia can be explored safely in pediatric critical care patients. It requires the combination of MRI and image processing know-how - skills that I already have - with a deeper understanding of the pathophysiological consequences of altered hemodynamic responses to anesthesia in infants. It also requires that I develop an improved ability to design research projects that fit within a rigorous and narrow clinical opportunity - skills that I will gain with this K25 support.
