Efficacy of naloxone in reducing hypoxemia and duration of immobility following focal to bilateral tonic–clonic seizures
Abstract Objective Evaluating the efficacy of an opioid antagonist, naloxone (NLX), to reduce the severity of post‐ictal hypoxemia and immobility after focal to bilateral tonic–clonic seizures (FBTCS). Methods ENALEPSY is a double‐blind placebo (PCB)‐controlled trial conducted in patients with focal...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-06-01
|
| Series: | Epilepsia Open |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/epi4.70046 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850126608839475200 |
|---|---|
| author | Sylvain Rheims Fatima Chorfa Véronique Michel Edouard Hirsch Louis Maillard Luc Valton Fabrice Bartolomei Philippe Derambure Vincent Navarro Julien Biberon Arielle Crespel Anca Nica Martine Lemesle Martin Laure Mazzola Jerome Petit Vincent Rossero Sébastien Boulogne Mathilde Leclercq Laurent Bezin Catherine Mercier Pascal Roy Philippe Ryvlin the ENALEPSY Study Group |
| author_facet | Sylvain Rheims Fatima Chorfa Véronique Michel Edouard Hirsch Louis Maillard Luc Valton Fabrice Bartolomei Philippe Derambure Vincent Navarro Julien Biberon Arielle Crespel Anca Nica Martine Lemesle Martin Laure Mazzola Jerome Petit Vincent Rossero Sébastien Boulogne Mathilde Leclercq Laurent Bezin Catherine Mercier Pascal Roy Philippe Ryvlin the ENALEPSY Study Group |
| author_sort | Sylvain Rheims |
| collection | DOAJ |
| description | Abstract Objective Evaluating the efficacy of an opioid antagonist, naloxone (NLX), to reduce the severity of post‐ictal hypoxemia and immobility after focal to bilateral tonic–clonic seizures (FBTCS). Methods ENALEPSY is a double‐blind placebo (PCB)‐controlled trial conducted in patients with focal epilepsy undergoing long‐term video‐EEG monitoring (LTM). Patients with a FBTCS during LTM were randomized 1:1 to receive intravenous NLX or PCB within the 2 min following the end of FBTCS. After database lock, a discrepancy between the allocated arm and the received treatment was detected, resulting in a 4:1 NLX:PCB ratio. To further explore the efficacy of NLX, we used historical control (HC) data collected in patients included in the REPO2MSE study whose characteristics matched those of patients randomized in ENALEPSY. The efficacy of NLX was then assessed versus PCB and versus HC. The primary endpoint was the delay between the end of the seizure and recovery of SpO2 ≥ 90%. Secondary efficacy outcomes included desaturation nadir and duration of the post‐ictal immobility. Results 33 patients contributed to the NLX group, 7 to the PCB group, and 43 to the HC group. The proportion of FBTCS type 1 or 3 was 84% in NLX, 100% in PCB, and 84% in HC. NLX did not improve the delay of recovery of SpO2 ≥ 90% or the desaturation nadir. By contrast, the duration of the post‐ictal immobility differed across groups. The time to mobility recovery within the first 5 min post‐ictal was very similar in the PCB (200.3 ± 215.8 s) and HC (194.4 ± 192.0 s) groups, and significantly shorter in the NLX group (128.9 ± 151.1 s) when compared to HC (Hazard Ratio, 1.84; 95% CI, 1.11–3.05; p = 0.021). Significance NLX did not prevent post‐ictal respiratory dysfunction but might reduce the duration of post‐ictal immobility. Confirmation of this effect and its impact on SUDEP risk will require additional studies. Plain Language Summary Release of endogenous opioids might participate in the severity of post‐ictal hypoxemia and immobility after focal to bilateral tonic–clonic seizures (FBTCS). We conducted a multicenter double‐blind randomized placebo‐controlled trial evaluating the efficacy of an opioid antagonist, naloxone (NLX), administered within 2 min following the end of FBTCS. The efficacy of NLX was further explored with a comparison with historical control. NLX did not improve the delay of recovery or the severity of post‐ictal hypoxemia. Post‐ictal immobility was significantly shorter in the NLX group when compared to historical control. The impact of these results on SUDEP prevention will require additional studies. |
| format | Article |
| id | doaj-art-41fb752791f34dd494fcb3f3e9a1f0f7 |
| institution | OA Journals |
| issn | 2470-9239 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Epilepsia Open |
| spelling | doaj-art-41fb752791f34dd494fcb3f3e9a1f0f72025-08-20T02:33:54ZengWileyEpilepsia Open2470-92392025-06-0110388089310.1002/epi4.70046Efficacy of naloxone in reducing hypoxemia and duration of immobility following focal to bilateral tonic–clonic seizuresSylvain Rheims0Fatima Chorfa1Véronique Michel2Edouard Hirsch3Louis Maillard4Luc Valton5Fabrice Bartolomei6Philippe Derambure7Vincent Navarro8Julien Biberon9Arielle Crespel10Anca Nica11Martine Lemesle Martin12Laure Mazzola13Jerome Petit14Vincent Rossero15Sébastien Boulogne16Mathilde Leclercq17Laurent Bezin18Catherine Mercier19Pascal Roy20Philippe Ryvlin21the ENALEPSY Study GroupDepartment of Functional Neurology and Epileptology Hospices Civils de Lyon and Lyon 1 University Lyon FranceDepartment of Biostatistics Hospices Civils de Lyon and University of Lyon Lyon FranceDepartment of Neurology Hôpital Pellegrin Bordeaux FranceDepartment of Neurology University Hospital of Strasbourg Strasbourg FranceNeurology Department University Hospital of Nancy Nancy FranceDepartment of Neurology University Hospital of Toulouse Toulouse FranceAPHM Timone Hospital, Epileptology and Cerebral Rhythmology Marseille FranceDepartment of Clinical Neurophysiology Lille University Medical Center, EA 1046, University of Lille2 Lille FranceAP‐HP, Epilepsy Unit, Pitié‐Salpêtrière Hospital Sorbonne Université Paris FranceDepartment of Clinical Neurophysiology University Hospital of Tours Tours FranceEpilepsy Unit Montpellier FranceDepartment of Neurology University Hospital of Rennes Rennes FranceDepartment of Neurology University Hospital of Dijon Dijon FranceDepartment of Neurology University Hospital of Saint‐Etienne Saint‐Etienne FranceLa Teppe Epilepsy Center Tain l'Hermitage FranceLyon's Neuroscience Research Center INSERM U1028/CNRS UMR 5292/Lyon 1 University Lyon FranceDepartment of Functional Neurology and Epileptology Hospices Civils de Lyon and Lyon 1 University Lyon FranceDepartment of Functional Neurology and Epileptology Hospices Civils de Lyon and Lyon 1 University Lyon FranceLyon's Neuroscience Research Center INSERM U1028/CNRS UMR 5292/Lyon 1 University Lyon FranceDepartment of Biostatistics Hospices Civils de Lyon and University of Lyon Lyon FranceDepartment of Biostatistics Hospices Civils de Lyon and University of Lyon Lyon FranceDepartment of Clinical Neurosciences Centre Hospitalo‐Universitaire Vaudois Lausanne SwitzerlandAbstract Objective Evaluating the efficacy of an opioid antagonist, naloxone (NLX), to reduce the severity of post‐ictal hypoxemia and immobility after focal to bilateral tonic–clonic seizures (FBTCS). Methods ENALEPSY is a double‐blind placebo (PCB)‐controlled trial conducted in patients with focal epilepsy undergoing long‐term video‐EEG monitoring (LTM). Patients with a FBTCS during LTM were randomized 1:1 to receive intravenous NLX or PCB within the 2 min following the end of FBTCS. After database lock, a discrepancy between the allocated arm and the received treatment was detected, resulting in a 4:1 NLX:PCB ratio. To further explore the efficacy of NLX, we used historical control (HC) data collected in patients included in the REPO2MSE study whose characteristics matched those of patients randomized in ENALEPSY. The efficacy of NLX was then assessed versus PCB and versus HC. The primary endpoint was the delay between the end of the seizure and recovery of SpO2 ≥ 90%. Secondary efficacy outcomes included desaturation nadir and duration of the post‐ictal immobility. Results 33 patients contributed to the NLX group, 7 to the PCB group, and 43 to the HC group. The proportion of FBTCS type 1 or 3 was 84% in NLX, 100% in PCB, and 84% in HC. NLX did not improve the delay of recovery of SpO2 ≥ 90% or the desaturation nadir. By contrast, the duration of the post‐ictal immobility differed across groups. The time to mobility recovery within the first 5 min post‐ictal was very similar in the PCB (200.3 ± 215.8 s) and HC (194.4 ± 192.0 s) groups, and significantly shorter in the NLX group (128.9 ± 151.1 s) when compared to HC (Hazard Ratio, 1.84; 95% CI, 1.11–3.05; p = 0.021). Significance NLX did not prevent post‐ictal respiratory dysfunction but might reduce the duration of post‐ictal immobility. Confirmation of this effect and its impact on SUDEP risk will require additional studies. Plain Language Summary Release of endogenous opioids might participate in the severity of post‐ictal hypoxemia and immobility after focal to bilateral tonic–clonic seizures (FBTCS). We conducted a multicenter double‐blind randomized placebo‐controlled trial evaluating the efficacy of an opioid antagonist, naloxone (NLX), administered within 2 min following the end of FBTCS. The efficacy of NLX was further explored with a comparison with historical control. NLX did not improve the delay of recovery or the severity of post‐ictal hypoxemia. Post‐ictal immobility was significantly shorter in the NLX group when compared to historical control. The impact of these results on SUDEP prevention will require additional studies.https://doi.org/10.1002/epi4.70046epilepsygeneralized convulsive seizuresnaloxonepost‐ictal EEG hypoxemiapost‐ictal immobilitySUDEP |
| spellingShingle | Sylvain Rheims Fatima Chorfa Véronique Michel Edouard Hirsch Louis Maillard Luc Valton Fabrice Bartolomei Philippe Derambure Vincent Navarro Julien Biberon Arielle Crespel Anca Nica Martine Lemesle Martin Laure Mazzola Jerome Petit Vincent Rossero Sébastien Boulogne Mathilde Leclercq Laurent Bezin Catherine Mercier Pascal Roy Philippe Ryvlin the ENALEPSY Study Group Efficacy of naloxone in reducing hypoxemia and duration of immobility following focal to bilateral tonic–clonic seizures Epilepsia Open epilepsy generalized convulsive seizures naloxone post‐ictal EEG hypoxemia post‐ictal immobility SUDEP |
| title | Efficacy of naloxone in reducing hypoxemia and duration of immobility following focal to bilateral tonic–clonic seizures |
| title_full | Efficacy of naloxone in reducing hypoxemia and duration of immobility following focal to bilateral tonic–clonic seizures |
| title_fullStr | Efficacy of naloxone in reducing hypoxemia and duration of immobility following focal to bilateral tonic–clonic seizures |
| title_full_unstemmed | Efficacy of naloxone in reducing hypoxemia and duration of immobility following focal to bilateral tonic–clonic seizures |
| title_short | Efficacy of naloxone in reducing hypoxemia and duration of immobility following focal to bilateral tonic–clonic seizures |
| title_sort | efficacy of naloxone in reducing hypoxemia and duration of immobility following focal to bilateral tonic clonic seizures |
| topic | epilepsy generalized convulsive seizures naloxone post‐ictal EEG hypoxemia post‐ictal immobility SUDEP |
| url | https://doi.org/10.1002/epi4.70046 |
| work_keys_str_mv | AT sylvainrheims efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT fatimachorfa efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT veroniquemichel efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT edouardhirsch efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT louismaillard efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT lucvalton efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT fabricebartolomei efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT philippederambure efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT vincentnavarro efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT julienbiberon efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT ariellecrespel efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT ancanica efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT martinelemeslemartin efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT lauremazzola efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT jeromepetit efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT vincentrossero efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT sebastienboulogne efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT mathildeleclercq efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT laurentbezin efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT catherinemercier efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT pascalroy efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT philipperyvlin efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures AT theenalepsystudygroup efficacyofnaloxoneinreducinghypoxemiaanddurationofimmobilityfollowingfocaltobilateraltonicclonicseizures |