Shin-Ichiro Hamano1, Kenji Sugai2, Masuo Miki3, Toshiyuki Tabata4, Takako Fukuyama5, Makiko Osawa6. 1. Division of Neurology, Saitama Children's Medical Center, 1-2 Shintoshin, Chuo-ku, Saitama 330-8777, Japan. Electronic address: hamano.shinichiro@scmc.pref.saitama.jp. 2. Department of Child Neurology, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan. Electronic address: sugaik@ncnp.go.jp. 3. Alfresa Pharma Corporation, R&D Headquarters, 2-2-9 Koku-machi, Chuo-ku, Osaka 540-8575, Japan. Electronic address: ms-miki@alfresa-pharma.co.jp. 4. Alfresa Pharma Corporation, R&D Headquarters, 2-2-9 Koku-machi, Chuo-ku, Osaka 540-8575, Japan. Electronic address: to-tabata@alfresa-pharma.co.jp. 5. Alfresa Pharma Corporation, R&D Headquarters, 2-2-9 Koku-machi, Chuo-ku, Osaka 540-8575, Japan. Electronic address: takako-fukuyama@alfresa-pharma.co.jp. 6. Department of Pediatrics, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. Electronic address: hmosawa@vesta.dti.ne.jp.
Abstract
BACKGROUND: No dosing regimen has been established for the initial treatment of pediatric status epilepticus with intravenous midazolam. We therefore evaluated the efficacy, safety, and pharmacokinetics of bolus and continuous midazolam infusion. METHODS: This open-label, prospective, multicenter study involved 34 Japanese children with status epilepticus unresponsive to diazepam. An initial bolus of 0.15 mg/kg midazolam was given, with additional doses of 0.1-0.3 mg/kg up to a cumulative dose of 0.6 mg/kg. A continuous infusion was initiated at 0.1 mg/kg/h (maximum 0.4 mg/kg/h) for patients at high risk of recurrence or in whom seizure reduction was achieved, and continued for 24 h after seizure cessation. Seizure cessation was assessed based on clinical observation (disappearance of motor symptoms regardless of recovery of consciousness), rather than the disappearance of electroencephalography abnormalities. RESULTS: The seizure cessation rate with bolus midazolam was 88%. The cumulative dose was ≤0.3 mg/kg in 90% of patients who responded to bolus administration. Adverse events were observed in three patients; one had mild respiratory depression that required supplemental oxygen and bag-valve-mask ventilation. Elimination half-life was 0.999 ± 0.241 h in seven patients. Total body clearance ranged from 423 to 1220 mL/h/kg in older children but was notably higher in a 10-month-old infant (2010 mL/h/kg). CONCLUSIONS: The efficacy and safety of midazolam were demonstrated in children with status epilepticus, suggesting that intravenous midazolam is suitable as first-line treatment.
BACKGROUND: No dosing regimen has been established for the initial treatment of pediatric status epilepticus with intravenous midazolam. We therefore evaluated the efficacy, safety, and pharmacokinetics of bolus and continuous midazolam infusion. METHODS: This open-label, prospective, multicenter study involved 34 Japanese children with status epilepticus unresponsive to diazepam. An initial bolus of 0.15 mg/kg midazolam was given, with additional doses of 0.1-0.3 mg/kg up to a cumulative dose of 0.6 mg/kg. A continuous infusion was initiated at 0.1 mg/kg/h (maximum 0.4 mg/kg/h) for patients at high risk of recurrence or in whom seizure reduction was achieved, and continued for 24 h after seizure cessation. Seizure cessation was assessed based on clinical observation (disappearance of motor symptoms regardless of recovery of consciousness), rather than the disappearance of electroencephalography abnormalities. RESULTS: The seizure cessation rate with bolus midazolam was 88%. The cumulative dose was ≤0.3 mg/kg in 90% of patients who responded to bolus administration. Adverse events were observed in three patients; one had mild respiratory depression that required supplemental oxygen and bag-valve-mask ventilation. Elimination half-life was 0.999 ± 0.241 h in seven patients. Total body clearance ranged from 423 to 1220 mL/h/kg in older children but was notably higher in a 10-month-old infant (2010 mL/h/kg). CONCLUSIONS: The efficacy and safety of midazolam were demonstrated in children with status epilepticus, suggesting that intravenous midazolam is suitable as first-line treatment.
Authors: David G Vossler; Jacquelyn L Bainbridge; Jane G Boggs; Edward J Novotny; Tobias Loddenkemper; Edward Faught; Marta Amengual-Gual; Sarah N Fischer; David S Gloss; Donald M Olson; Alan R Towne; Dean Naritoku; Timothy E Welty Journal: Epilepsy Curr Date: 2020-08-21 Impact factor: 7.500
Authors: Marios Charalambous; Holger A Volk; Andrea Tipold; Johannes Erath; Enrice Huenerfauth; Antonella Gallucci; Gualtiero Gandini; Daisuke Hasegawa; Theresa Pancotto; John H Rossmeisl; Simon Platt; Luisa De Risio; Joan R Coates; Mihai Musteata; Federica Tirrito; Francesca Cozzi; Laura Porcarelli; Daniele Corlazzoli; Rodolfo Cappello; An Vanhaesebrouck; Bart J G Broeckx; Luc Van Ham; Sofie F M Bhatti Journal: J Vet Intern Med Date: 2019-10-03 Impact factor: 3.333