• Tarek Sharshar, Raphaël Porcher, Pierre Asfar, Lamiae Grimaldi, Julien Jabot, Laurent Argaud, Christine Lebert, Pierre-Edouard Bollaert, Marie Line Harlay, Patrick Chillet, Eric Maury, Francois Santoli, Pascal Blanc, Romain Sonneville, Dinh Chuyen Vu, Benjamin Rohaut, Aurelien Mazeraud, Jean-Claude Alvarez, Vincent Navarro, Bernard Clair, Hervé Outin, and Valse investigators and for the Groupe d’Explorations Neurologiques en Reanimation (GENER).
• Neuro-Intensive Care Medicine, Anaesthesiology and ICU Department, GHU-Psychiatry and Neurosciences, Pole Neuro, Sainte-Anne Hospital, Institute of Psychiatry and Neurosciences of Paris, INSERM U1266, Université Paris Cité, Paris, France. t.sharshar@ghu-paris.fr.
• Crit Care. 2023 Jan 9; 27 (1): 88.

BackgroundGeneralised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20-40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE.MethodsThis was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90.ResultsA total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89-1.19); p = 0.58]. There were no between-group differences for secondary outcomes.ConclusionsVPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15.Trial Registration NoNCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.© 2023. The Author(s).

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