Intracerebral Glutamate and Glycerol in Severe Acute Brain Injury: Retrospective Study of Association With Neuroworsening and Outcome

ABSTRACT Background Glutamate is the main excitatory neurotransmitter in the brain, and extracellular levels of glutamate and glycerol (a breakdown product of cell damage) increase after severe acute brain injury. Previous studies report that increased intracerebral glutamate—measured using cerebral microdialysis (CMD)—is associated with unfavorable outcome, and that both increased glutamate and glycerol are associated with mortality in patients with severe acute brain injury. We investigated the association between CMD levels of glutamate and glycerol to episodes of neuroworsening, in‐hospital mortality, and functional outcome at 6 months postinjury. Methods This single‐center retrospective cohort study included patients with subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI) monitored with CMD and in whom at least five vials of microdialysate were analyzed. Using mixed‐effects linear regression, we compared CMD‐glutamate and ‐glycerol leading up to episodes of neurological worsening (9–12 h vs. 0–3 h before) as well as 0–3 h before and after episodes of neurological worsening. Additionally, CMD‐glutamate and ‐glycerol were analyzed for an association with in‐hospital mortality and functional outcome 6 months after injury, and we explored predictive thresholds of CMD‐glutamate and ‐glycerol for unfavorable functional outcome 6 months after brain injury. Results A total of 172 patients were included. Neither CMD‐glutamate nor ‐glycerol changed up to or after a neuroworsening episode, nor were they associated with unfavorable outcome at 6 months. We could not establish a predictive threshold of neither CMD‐glutamate or ‐glycerol for 6‐month clinical outcomes. However, CMD‐glycerol was increased in patients who died during hospitalization compared to those who survived (mean difference: 55; 95% CI: 30–81 μmol/L). Conclusion CMD‐glutamate and ‐glycerol did not predict episodes of neuroworsening or 6‐month functional outcome in patients with SAH or TBI. CMD‐glycerol was associated to in‐hospital mortality. Editorial Comment Serial measurements of local markers after acute brain injury might help to understand if brain condition is worsening or improving. This study assessed localized microdialysis‐based collection and measurement of a neurotransmitter and cell injury marker to test how well serial measures of these follow clinical brain recovery after injury. Findings confirm that more extracellular glycerol as sampled here is common in more severe brain injuries. Trail Registration: Clinicaltrials.gov identifier: NCT06302244.