Non-Invasive Neuromonitoring to Quantify Cerebral Autoregulation and Delirium: A Framework for Precision Medicine in the Intensive Care Unit

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Khan, Jasmine
Keyword
critical illness , intensive care unit , near-infrared spectroscopy , cerebral oxygenation , cerebral autoregulation , delirium , cognitive outcomes , precision medicine
Abstract
Nearly a quarter million Canadians are admitted to Intensive Care Units (ICUs) annually. Of those, up to 80% will experience delirium, which is an acute disturbance in neurological function characterized by impaired attention and disorganized thinking. The pathophysiologic mechanisms are unknown. However, impaired cerebral perfusion may be a contributing factor. Cerebral autoregulation is a mechanism that acts to maintain consistent cerebral perfusion despite fluctuations in blood pressure. Emerging evidence suggests that impaired cerebral autoregulation is associated with delirium development, and personalized resuscitation targets based on cerebral autoregulation monitoring may reduce neurological morbidity. Despite high rates of delirium, neuromonitoring of critically adults is not part of routine care. Therefore, the aim of this thesis was to develop a framework for near-infrared spectroscopy (NIRS) based non-invasive cerebral autoregulation monitoring in critically ill adults, and to investigate its association with delirium. I conducted a systematic review of NIRS, demonstrating a 71% sensitivity and 92% specificity in detecting cerebral ischemia. I subsequently optimized an algorithm to remove signal contamination in blood pressure data required for cerebral autoregulation analysis. The modified algorithm had 98% sensitivity and 99% specificity to detect artifacts. Then, in a retrospective study of 42 patients I defined personalized cerebral autoregulation-based mean arterial pressure (MAP) targets and assessed the association between deviations from targets with delirium. Personalized MAP targets were highly variable between patients but were higher than current treatment guidelines in the majority (69%). Deviations were not associated with delirium. I then performed a multicentre feasibility study. Fifty-nine participants were recruited across 4 sites, and barriers to MAP/NIRS data collection were identified and addressed. Finally, the current state of the multicentre study of cerebral autoregulation and delirium is summarized. Overall, this thesis evaluated the accuracy of NIRS as a non-invasive neuromonitoring tool, identified barriers to implementation of cerebral autoregulation monitoring, optimized cleaning of data for use at the bedside, and defined personalized blood pressure targets in non-brain injured critically ill adults. This work has laid the foundation for a personalized brain-based resuscitation approach to the care of critically ill patients.
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