Prospective Evaluation of Icu Neurostimulant Use for Acute Brain Injury (Prevail): A Pragmatic Observational Cohort Study

Introduction: Amantadine, an effective neurostimulant for traumatic brain injury, has limited data supporting its use for other acute brain injuries (ABI). This pragmatic study evaluated amantadine for nontraumatic ABI monitored in the ICU with the Coma Recovery Scale-Revised (CRS-R). Methods: This prospective open-label cohort study developed a protocol to treat impaired consciousness after ABI with amantadine, assessing participants with CRS-R as 0-100 Rasch units, monitoring feasibility, safety, and effectiveness. Results: 40 patients (age 64 [52-73] years, 25 [62%] female) were included during this protocol development phase: 13 ischemic stroke, 10 intracerebral hemorrhage, 7 subarachnoid hemorrhage, 4 hypoxic-ischemic encephalopathy, 3 other ABI. The median baseline CRS-R was 11 (IQR 7-16), including 16 meeting criteria for Disorder of Consciousness. Among 30 participants with an adequate amantadine treatment trial, 27 (90%) responded, with disposition to home (1,4%), skilled nursing facility (6,22%), acute inpatient rehabilitation (15,56%), or withdrawal of life support (5,18%). Pre- versus post-treatment CRS-R increased for responders by 8 (6-11), equivalent to 26 (15-45) Rasch units. Among 10 untreated or inadequate trial patients, 3 (30%) were discharged to rehab, 7 (70%) had support withdrawn. Conclusions: It is feasible to measure responsiveness to amantadine using the CRS-R for ICU patients with ABI.