Defining metabolic abnormalities in acute human traumatic brain injury with cerebral microdialysis and multimodality monitoring

Abstract

Objective We aimed to compare the prevalence and multimodal associations of mitochondrial dysfunction as defined by published cerebral-microdialysis-based criteria versus our novel multimodality-monitoring-based criteria in acute traumatic brain injury patients. Methods We retrospectively analyzed neurocritical care monitoring data from 619 acute traumatic brain injury patients. Monitoring modalities included cerebral microdialysis, intracranial pressure, brain tissue oxygenation, cerebral perfusion pressure, and the pressure reactivity index. The cerebral-microdialysis-based criteria we compared combine an elevated lactate/pyruvate ratio (25 or 30) with raised concentrations of lactate (2.5 mM) or pyruvate (70 μM or 120 μM). Our multimodality-monitoring-based criteria comprise a consistent lactate/pyruvate ratio > 25 with intracranial pressure ≤ 20 mmHg, brain tissue oxygenation ≥ 15 mmHg, a pressure reactivity index ≤ 0.3, and cerebral glucose ≥ 1.0 mM. Results Across 592 analyzable patients, a lactate/pyruvate ratio > 25 was common, with a median prevalence of 48.9% (41.5% with consistency) and a U-shaped, bimodal distribution. A lactate/pyruvate ratio > 25 was associated with lower glucose and higher glycerol, and when accompanied by high pyruvate (> 120 μM), this derangement was further distinguished by higher glutamate and cerebral perfusion pressure. Using multimodal criteria on a cohort of 268 patients, consistent mitochondrial dysfunction was identified in 25.7% to 41.0% of patients, often in the absence of other physiological derangements. Conclusions Many acute traumatic brain injury patients constantly demonstrate neurometabolic derangements, among which clinical mitochondrial dysfunction is highly prevalent despite normal cerebral pressure, oxygenation, and perfusion. There is necessity for targeted, neurometabolic therapies in neurocritical care that address this abnormality.