The goal of this project is to deliver enhanced bedside microdialysis for monitoring interstitial brain glucose and K+ levels in patients in intensive care after neurosurgery for severe traumatic brain injury. The ultimate objective is to quantify, in real time, the magnitude and duration of metabolic crises caused by spreading depolarization (SD), which are prevalent in the injured brain and underlie the secondary injury responsible for poor patient outcomes, including severe disability, vegetative state, and death. Electrocorticography (ECoG) shows that the injured brain is highly susceptible to SD but ECoG is not designed to detect or quantify the impact of SD on brain metabolism. Repolarization of tissues after SD requires such vast amounts of energy that glucose levels can be driven dangerously low, especially in injured tissue where blood flow to resupply glucose may be compromised. By quantifying the magnitude and duration of hypoglycemic episodes in the injury penumbra, we will deliver a diagnostic for secondary injury. The present absence of diagnostic technology is a roadblock to therapeutic strategies for managing secondary injury. Although clinical microdialysis has the demonstrated ability to quantify metabolic crisis after SD, substantial technical enhancements are urgently needed. Patients need to be monitored for 10 days after surgery but, due to gliosis at the probe track, conventional microdialysis is of limited value after 2-3 days. Preclinical studies in the Michael laboratory have demonstrated that retrodialysis of dexamethasone, a potent anti-inflammatory agent, is a simple yet highly effective means of extending functional microdialysis to at least 10 days. Microdialysis will be further enhanced by new technology, developed by the Boutelle group, for continuous, rapid, on-line, wireless, automated assays of glucose and K+ with 1-min temporal resolution. With the aid of expert neurosurgeons, we propose to translate enhanced microdialysis to patients with severe traumatic brain injury, to determine the statistical significance of correlations between chemical recordings and patient outcomes, and to continue the preclinical refinement of our enhanced microdialysis approaches.
Traumatic brain injury (TBI) is an epidemic in the US: 1.7 million TBIs annually lead to 270,000 hospitalizations, 80,000 cases of severe disability, and 53,000 deaths. Waves of cortical spreading depolarization are implicated in the mechanism of secondary brain injury, which significantly contributes to poor patient outcomes, including death, vegetative state, and severe disability after 6-months. Current neuromonitoring technologies report the incidence of the waves but not the magnitude of the threat they pose for secondary injury. This project will deliver enhanced microdialysis to fill this critically important technological gap.
