Impact of Autonomic Dysfunction on Multi-Organ Dysfunction following Severe TBI: The AUTO-BOOST Study
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PROJECT SUMMARY/ABSTRACT Traumatic brain injury (TBI) is a major public health concern, affecting more than 1.5 million individuals annually in the United States. Extracranial multi-organ dysfunction (MODS) occurs in approximately 60% of severe TBI patients and contributes to secondary brain injuries, increased risk for mortality, and poor functional outcomes over the year following TBI. Our prior research has demonstrated that the prevalence of early autonomic nervous system dysfunction is high following severe TBI and associated with cerebral metabolic crisis and MODS development. Although treatments for autonomic dysfunction following severe TBI are readily available, a complete characterization of the course of autonomic dysfunction following severe TBI that would be adequate to guide therapy is lacking. Therefore, a comprehensive characterization of autonomic dysfunction after TBI and an understanding of how early autonomic dysfunction contributes to episodes of cerebral metabolic crisis and extracranial organ injury are urgently needed to guide the development of therapies to improve patient outcomes following TBI. To address this, we propose the following specific aims using unique and granular waveform data from the BOOST-3 (Brain Oxygen Optimization in Severe TBI Phase 3 trial, U01 NS099946) clinical trial: 1) Determine the burden of early autonomic dysfunction and its relationship to cerebral metabolic crisis following severe TBI, 2) Determine the relationship of early autonomic dysfunction with extracranial MODS and functional neurologic outcomes following severe TBI, and 3) Assess the uniqueness and added value of cardiac waveform data in predicting risk for MODS and functional neurologic outcomes following severe TBI. Successful completion of this study will solidify our understanding of the effects of autonomic dysfunction after severe TBI, and inform trials to determine the impact of modulating autonomic dysfunction on the development of MODS and poor outcomes following severe TBI. Our long-term goal is to develop strategies to personalize critical care management in order to improve clinical outcomes after severe TBI in adults.
