Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial
Abstract Background Generalised 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 hospitali...
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| Language: | English |
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BMC
2023-01-01
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| Series: | Critical Care |
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| Online Access: | https://doi.org/10.1186/s13054-022-04292-7 |
| _version_ | 1797952484147200000 |
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| author | 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 the Valse investigators and for the Groupe d’Explorations Neurologiques en Reanimation (GENER) |
| author_facet | 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 the Valse investigators and for the Groupe d’Explorations Neurologiques en Reanimation (GENER) |
| author_sort | Tarek Sharshar |
| collection | DOAJ |
| description | Abstract Background Generalised 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. Methods This 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. Results A 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. Conclusions VPA 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 No. NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012. |
| first_indexed | 2024-04-10T22:48:10Z |
| format | Article |
| id | doaj.art-6a2fe9e93d4d4045a22ecd187f82b16f |
| institution | Directory Open Access Journal |
| issn | 1364-8535 |
| language | English |
| last_indexed | 2024-04-10T22:48:10Z |
| publishDate | 2023-01-01 |
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| series | Critical Care |
| spelling | doaj.art-6a2fe9e93d4d4045a22ecd187f82b16f2023-01-15T12:13:17ZengBMCCritical Care1364-85352023-01-0127111210.1186/s13054-022-04292-7Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trialTarek Sharshar0Raphaël Porcher1Pierre Asfar2Lamiae Grimaldi3Julien Jabot4Laurent Argaud5Christine Lebert6Pierre-Edouard Bollaert7Marie Line Harlay8Patrick Chillet9Eric Maury10Francois Santoli11Pascal Blanc12Romain Sonneville13Dinh Chuyen Vu14Benjamin Rohaut15Aurelien Mazeraud16Jean-Claude Alvarez17Vincent Navarro18Bernard Clair19Hervé Outin20the 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 CitéUniversité Paris Cité and Université Sorbonne Paris Nord, Inserm, INRAE, Center for Research in Epidemiology and StatisticS (CRESS)Department of Medical Intensive Care, University HospitalClinical Research Unit, Assistance Publique - Hôpitaux de Paris University Paris-Saclay. Faculty of medicine, University of Versailles Saint-Quentin en Yvelines. Inserm U1018 Team Anti-infective evasion and pharmacoepidemiologyMedical-Surgical Intensive Care Unit, CHU Felix-GuyonService de Médecine Intensive-Réanimation, Hospices Civils de Lyon, Hôpital Edouard HerriotMédecine Intensive Réanimation, Centre Hospitalier Départemental de VendéeCHRU-Nancy, Service de Médecine Intensive Réanimation, Université de LorraineMédecine Intensive Réanimation, Hôpital de Hautepierre, Hôpitaux Universitaires de StrasbourgService de Médecine Intensive - Réanimation, Centre hospitalier Léon BourgeoisService de Médecine Intensive et Réanimation Hôpital Saint-Antoine, Paris-Sorbonne UniversitéMédecine Intensive—Réanimation, Centre Hospitalier Robert BallangerRéanimation Médico Chirurgicale, Centre Hospitalier René DubosUniversité de Paris Cité, INSERM UMR1137General Intensive Care Unit, Sud-Essonne HospitalDepartment of Neurology, Neuro-ICU & Brain institute - ICM, Pitié-Salpêtrière Hospital APHP, Sorbonne UniversitéAnaesthesiology and ICU Department, GHU-Psychiatry and Neurosciences, Pole Neuro, Sainte-Anne Hospital, Perception and Memory Unit, Neurosciences Department, Institut Pasteur, Université Paris CitéDepartment of Pharmacology and Toxicology, Inserm U-1173, Raymond Poincare Hospital, AP-HP, Versailles Saint-Quentin-en-Yvelines University, Paris-Saclay UniversityAP-HP, Epilepsy Unit, Pitié-Salpêtrière Hospital, Sorbonne Université, and Paris Brain InstituteGeneral Intensive Care Unit, APHP, Raymond Poincaré Hospital, University of Versailles Saint-Quentin en YvelinesIntensive Care Unit Centre Hospitalier IntercommunalAbstract Background Generalised 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. Methods This 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. Results A 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. Conclusions VPA 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 No. NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.https://doi.org/10.1186/s13054-022-04292-7Generalised convulsive status epilepticusIntensive care unitSeizureValproic acid |
| spellingShingle | 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 the Valse investigators and for the Groupe d’Explorations Neurologiques en Reanimation (GENER) Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial Critical Care Generalised convulsive status epilepticus Intensive care unit Seizure Valproic acid |
| title | Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial |
| title_full | Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial |
| title_fullStr | Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial |
| title_full_unstemmed | Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial |
| title_short | Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial |
| title_sort | valproic acid as adjuvant treatment for convulsive status epilepticus a randomised clinical trial |
| topic | Generalised convulsive status epilepticus Intensive care unit Seizure Valproic acid |
| url | https://doi.org/10.1186/s13054-022-04292-7 |
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