Outcomes and assessment
super-refractory, abnormal movements, seizure
ADVERSE EVENTS, RECURRENCE
The primary outcome was the proportion of living patients discharged from hospital to their home or to a long-term care facility on day 15. The primary endpoint (i.e. hospital status at day 15) was collected by a local investigator, blinded to group assignment (Additional file Secondary outcomes were recurrence of seizure during ICU stay, occurrence of refractory and super-refractory GCSE during ICU stay, occurrence of adverse events whilst in hospital, and cognitive status at day 90 assessed with the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Glasgow Outcome Scale-Extended (GOSE). Follow-up visits occurred at day 15, at ICU and hospital discharge, and at day 90.Patients were assessed neurologically every 4 h whilst in the ICU, notably for awakening, focal neurological signs, and abnormal movements. In both groups, serum samples were obtained prior to, and 15 min and 12 h after, administration of the study drug load in order to measure serum VPA concentrations. Samples were stored at − 20 °C in the participating centres before being sent to the Department of Pharmacology and Toxicology of the Raymond Poincaré Teaching Hospital (Garches, France) for centralised VPA measurements. In every patient, administration of a standard EEG was recommended within 24 h of ICU admission and again between day 2 and day 7. EEGs were interpreted by the referring neurophysiological team of the participating centre, which was blinded to study drug groups.Up to hospital discharge, we collected the time to awakening, length of ICU and hospital stays, in-ICU and in-hospital mortality, and changes in the maintenance ASMs. At day 90, the referring neurologist or intensivist assessed MMSE and FAB through a medical examination and the GOSE by phone.