Feasibility Trial of Spreading Depolarization Monitoring to Guide Management of Severe Traumatic Brain Injury: Initial Results
Jed Hartings1, Laura Ngwenya1, Jennifer Goldthwait1, Danielle Sandsmark2, Edilberto Amorim3, Britta Lindquist3, Anthony DiGiorgio4, Jens Dreier5, Brandon Foreman1
1University of Cincinnati, 2University of Pennsylvania, 3UCSF Neurology, 4University of California San Francisco, 5Charite University Medicine
Objective:
To determine the feasibility of real-time monitoring of spreading depolarizations (SD) to guide management of severe traumatic brain injury (TBI).
Background:
SDs are waves of mass depolarization that propagate slowly through cerebral gray matter in response to injury and are a known causal mechanism of lesion development. Clinical studies have shown that SDs occur with high incidence in TBI and are associated with worse outcomes, but real-time diagnosis of SDs to guide intensive care management has not been tested.
Design/Methods:
We are conducting a prospective interventional study of patients who undergo electrocorticography (ECoG) as standard care for surgically treated TBI. Patients with SDs are randomized 1:1 to (A) standard care with blinding to further SDs or (B) a three-tiered intervention protocol aimed at SD prevention and suppression. Tier1 includes targets for physiological variables while Tiers2-3 add ketamine infusion at 1 and 2-4 mg/kg/hr.
Results:
Since January 2023, 48 patients were enrolled at 3 sites and 26 (54%) with SDs were randomized. Prior to randomization, the rate of SDs was 6.4 SDs/day in the control group (n=12) and 7.5 SDs/day in the treatment group (n=13). After randomization, the control group had 10.2 SDs/day over 4.0 days (median) of ECoG, while the treatment group had 4.7 SDs/day over 5.6 days. Nearly all patients (12/13) in the treatment group were escalated to Tier2, and 8/13 were escalated to Tier3 due to continuing SDs. Median SD rates for Tiers 1-3 were 5.6, 2.8, and 3.0 SD/day, respectively. Individual cases evidenced a strong efficacy of ketamine to block SDs in Tiers 2-3, though some patients were more refractory.
Conclusions:
Results to date suggest that a conservative, tiered treatment protocol can reduce SD incidence during intensive care by 54% (10.2 to 4.7 SD/day). The study aims to randomize 42 total patients, and outcomes are being collected.
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