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

Abstract

Introduction: The acute seizure in childhood is a medical emergency which is usually managed by benzodiazepines used as a first line of therapy. There are no strict guidelines of using intranasal lorazepam in India. Many paediatricians use it in an emergency situation as it is inexpensive, easy to administer and even treatment can be started at home. Very few studies are available to compare efficacy and safety of intravenous lorazepam with intranasal lorazepam in childhood seizure, though both routes have comparable pharmacokinetic profile. Intravenous lorazepam (0.1 mg/kg) is already recommended as a first-line treatment of acute childhood seizures in India. There are very few studies regarding the usefulness of intranasal lorazepam. With this background, we compared intranasal lorazepam with the more widely accepted intravenous lorazepam for control of acute seizure. Aim: To compare effectiveness and safety of intranasal and intravenous lorazepam in acute seizure in children aged 5-12 years. Materials and methods: This is an analytical observational cross-sectional study involving patients with acute seizure who received lorazepam via either the intravenous or intranasal route. Formulation and dosage of lorazepam were the same in both routes. Results: Distributions of patient groups according to sex, age, and weight were statistically not significant (p=0.42, p=0.391, and p=0.605, respectively). Time to control seizure within 10 min and persistent cessation of seizure activity were similar in both groups. Safety parameters showed no differences statistically. Conclusions: Though intravenous lorazepam is recommended as first-line treatment, intranasal lorazepam may be a good alternative choice in a convulsing child.

Treatment of pediatric convulsive status epilepticus

“…Previous studies, however, have suggested that IN midazolam (0.2 mg/kg/dose) is more effective than rectal diazepam (0.5 mg/kg/dose) ( 35 – 37 ). McTague et al highlighted that in general buccal and IN application of ASMs resulted in similar seizure cessation rates as IV-applied ASMs ( 15 , 38 – 44 ). The anticonvulsant effect of sublingual lorazepam has been reported to start with a delay of about 20 min after drug application, and this treatment is therefore inappropriate for acute SE treatment ( 45 ).…”

Benzodiazepines for the Treatment of Seizure Clusters

“…Lorazepam is available as tablets (0.5, 1, and 2 mg), an intravenous injection (2 and 4 mg/mL), an oral concentrate (2 mg/mL) [ 71 – 73 ], and a sublingual tablet, which is available in Europe and Canada. Two studies have shown that up to 4-mg doses of intravenous and a non-atomized intranasal solution of lorazepam (directly instilled into one nostril) produced remission of acute seizure within 10 min in pediatric populations (aged 5–14 years) in India [ 74 , 75 ]. The effectiveness (time to onset, duration) of lorazepam for seizure clusters specifically has not been formally confirmed in large clinical trials [ 62 ].…”

Translational Considerations in the Development of Intranasal Treatments for Epilepsy

“…Finally, lorazepam is reported to be 4 to 6 times less lipid soluble than midazolam and diazepam, and it has been found to have a peak effect time of 30 min and a half-life of 18.5 h after intranasal administration [ 65 , 66 ]. Intranasal lorazepam has been evaluated in studies in children and found to be comparable to intravenous lorazepam, with the same median onset time [ 67 , 68 ]. However, it is uncertain whether any benefit is obtained from lorazepam compared with midazolam, other than perhaps having an extended duration of action and being easier to formulate than diazepam.…”