In a double-blind, placebo-controlled trial, 50 intensive care unit patients with acute disorders of consciousness after brain injury received apomorphine, methylphenidate, or placebo. Automated pupillometry measured pupillary responses to verbal commands; neither drug significantly increased these responses overall. However, 20% of patients showed improved clinical arousal at least once after drug administration, with methylphenidate linked to more arousal events than placebo. Patients with greater baseline pupillary responsiveness were more likely to show arousal, suggesting this may predict stimulant effects. No adverse events occurred. The findings need replication but may guide future trials on consciousness recovery.
Cortical spreading depolarisation (SD) is a pathological wave of brain cell activity that occurs frequently after severe acute brain injury and can worsen damage by reducing blood flow and increasing energy demand. Ketamine appears to inhibit SDs in laboratory and patient studies. The KETA-BID trial is a randomized, blinded feasibility and pilot study testing S-ketamine for SDs in adults undergoing surgery for traumatic brain injury, aneurysmal subarachnoid hemorrhage, or spontaneous intracerebral hemorrhage. Participants who develop SD clusters receive either continuous S-ketamine or placebo, with dosing adjusted based on SD occurrence. The primary outcome is SDs per hour after randomization. The trial will provide insight into SD and ketamine's clinical effects, potentially offering a new treatment.