Buccal, intranasal or intravenous lorazepam for the treatment of acute convulsions in children in Malawi: An open randomized trial

Abstract

Introduction: Acute convulsions in children are a common emergency worldwide. Benzodiazepines are the recommended first line treatment. Intravenous lorazepam is inexpensive, long acting and the first line drug in resource-rich settings. However, comparable efficacy by other routes of administration is unknown. We wished to compare the efficacy of lorazepam by the buccal, intranasal or intravenous route in the treatment of acute seizures in Malawian children. Methods:A prospective, open-label, randomised, non-inferiority trial was performed in children aged 2 months to 14 years presenting to the Queen Elizabeth Central Hospital in Blantyre, Malawi with acute seizures lasting longer than 5 min. Children were randomly assigned to receive lorazepam, 0.1 mg/kg, by the buccal, intranasal or intravenous route. The primary endpoint was seizure cessation within 10 min of drug administration. Results: There were 761 seizures analysed, with 252 patients in the buccal, 245 in the intranasal and 264 in the intravenous groups. Intravenous lorazepam stopped seizures within 10 min in 83%, intranasal lorazepam in 57% (RR 2.46, CI 1.82-3.34), and the buccal route in 46% (RR 3.14, CI 2.35-4.20; p = 0.001) of children. There were no significant cardio-respiratory events and no difference in mortality or neurological deficits. The study was halted after an interim analysis showed that the primary endpoint had exceeded the protocol-stopping rule. Conclusions: Intravenous lorazepam effectively treats most childhood seizures in this setting. Intranasal and buccal routes are less effective but may be useful in prehospital care or when intravenous access cannot be obtained. Further studies comparing intranasal lorazepam to other benzodiazepines, or alternative doses by a nonintravenous route are warranted.Introduction: dans le monde entier, les convulsions aigues constituent une urgence fre´quente. Il est recommande´d'utiliser des benzodiaze´pines en traitement de premie`re intention. Le loraze´pam administre´par voie intraveineuse est peu couˆteux, a une action prolonge´e, et constitue le traitement de premie`re intention dans les re´gions riches en ressources. L'efficacite´comparable de ce traitement par d'autres voies d'administration est cependant inconnue. Nous souhaitions comparer l'efficacite´du loraze´pam par voie orale, intranasale ou intraveineuse dans le traitement des attaques aigue¨s chez les enfants au Malawi. Me´thodes: Une e´tude prospective, ouverte, randomise´e et de non infe´riorite´a e´te´re´alise´e sur des enfants aˆge´s de deux mois a`14 ans se pre´sentant a`l'hoˆpital central Queen Elizabeth a`Blantyre, au Malawi, souffrant d'attaques aigue¨s de plus de cinq minutes. Les enfants e´taient re´partis de manie`re ale´atoire pour se voir administrer 0.1 mg/kg de loraze´pam par voie orale, intranasale ou intraveineuse. Le point final primaire e´tait l'interruption de l'attaque dans les 10 min suivant l'administration du me´dicament. Re´sultats: 761 attaques ont e´te´analyse´es, dont 252 patients dans le groupe d'administr...

A Comparative Study on Intranasal Versus Intravenous Lorazepam in the Management of Acute Seizure in Children

“…The mean weights in our study were 24.06 kg and 24.51 kg in the IN and IV groups, respectively. In Lissauer et al 19 , the mean weights were 10 kg and 10.4 kg in the IN and IV groups, respectively. 19 The studied children aged 2 months to 14 years had shown that intranasal lorazepam was less effective than the IV lorazepam as a first-line treatment for acute seizures but may be useful in children without or with difficult IV access.…”

“…In Lissauer et al 19 , the mean weights were 10 kg and 10.4 kg in the IN and IV groups, respectively. 19 The studied children aged 2 months to 14 years had shown that intranasal lorazepam was less effective than the IV lorazepam as a first-line treatment for acute seizures but may be useful in children without or with difficult IV access. 19 In our study, with respect to seizure control, INLOR is not inferior to the current standard of practice IVLOR.…”

“…According to Lissauer et al 19 also, there were no significant cardio-respiratory events and no difference in mortality or neurological deficits. Wermeling DP et al has shown intranasal lorazepam to be a suitable alternative if recurrence of seizures is a potential concern.…”

“…19 The studied children aged 2 months to 14 years had shown that intranasal lorazepam was less effective than the IV lorazepam as a first-line treatment for acute seizures but may be useful in children without or with difficult IV access. 19 In our study, with respect to seizure control, INLOR is not inferior to the current standard of practice IVLOR. The INLOR arm of the study by Ahmad et al included 80 children aged 2 months to 12 years.…”

Leserbrief zum Artikel: M. Müller, R. Löb: Medikamentenapplikation im akuten epileptischen Anfall des Kindes. Notarzt 2019; 35: 119 – 121

“…Zudem ist Buccolam ® seinerseits nicht für Erwachsene zugelassen und lässt sich nicht auf das Milligramm genau, sondern nur in festgelegten Dosierungsschritten applizieren [11]. Es mehren sich zudem Hinweise, dass die bukkale Resorption und konsekutiv die klinische Wirkung im Vergleich zur nasalen langsamer verläuft [12,13].…”