Efficacy of Sublingual Lorazepam Versus Intrarectal Diazepam for Prolonged Convulsions in Sub-Saharan Africa

Abstract

In Sub-Saharan Africa, intrarectal diazepam is the first-line anticonvulsant mostly used in children. We aimed to assess this standard care against sublingual lorazepam, a medication potentially as effective and safe, but easier to administer. A randomized controlled trial was conducted in the pediatric emergency departments of 9 hospitals. A total of 436 children aged 5 months to 10 years with convulsions persisting for more than 5 minutes were assigned to receive intrarectal diazepam (0.5 mg/kg, n = 202) or sublingual lorazepam (0.1 mg/kg, n = 234). Sublingual lorazepam stopped seizures within 10 minutes of administration in 56% of children compared with intrarectal diazepam in 79% (P < .001). The probability of treatment failure is higher in case of sublingual lorazepam use (OR = 2.95, 95% CI = 1.91-4.55). Sublingual lorazepam is less efficacious in stopping pediatric seizures than intrarectal diazepam, and intrarectal diazepam should thus be preferred as a first-line medication in this setting.

Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society

“…This class III RCT was conducted across nine hospitals in SubSaharan Africa and involved 436 children. The efficacy of sublingual lorazepam (131/234, 56%) was significantly lower than that for rectal diazepam (160/202, 79%; p < 0.001) for terminating seizures within 10 minutes of study drug administration (54).…”

New Non-Intravenous Routes for Benzodiazepines in Epilepsy: A Clinician Perspective

“…It appears, therefore, evident that the sublingual delivery is not ideal for patients having a convulsive seizure and this is further supported by the only published randomised controlled trial in 436 children showing that sublingual LZP is less efficacious than rectal DZP in controlling seizures [38].…”

Quick treatment with the most appropriate benzodiazepine formulation is vital when treating acute repetitive seizures in the outpatient setting

“…Intranasal midazolam vs. IV diazepam in infants and children with prolonged seizures (n = 50) [14] No BGD in efficacy; mean time from drug administration to seizure control was shorter with midazolam than with diazepam (2.67 vs. 3.01 min); no significant ADRs IM midazolam vs. IV lorazepam in paediatric and adult patients with prolonged seizures (n = 1023) [15] Following pre-hospital treatment by paramedics, 73 vs. 63 % of seizures had stopped by arrival at emergency department with midazolam and lorazepam, respectively (p \ 0.001); ADR rates were similar Buccal midazolam vs. rectal diazepam in children and adolescents with prolonged seizures (n = 42) [16] 75 and 59 % of seizures were stopped by midazolam and diazepam, respectively; midazolam was more convenient and socially acceptable Buccal midazolam vs. rectal diazepam in infants and children with active seizures (n = 177) [17] 56 and 27 % of midazolam and of diazepam recipients, respectively, achieved therapeutic success (seizure cessation within 10 min for at least 1 h); midazolam was not associated with increased respiratory depression Buccal midazolam vs. IV diazepam in children with active seizures (n = 120) [18] Mean time for seizure control after drug administration was significantly shorter with diazepam than with midazolam (p \ 0.001); mean time for seizure control after diagnosis was significantly shorter with midazolam (p = 0.004); midazolam was safe and easier to administer Lorazepam Sublingual lorazepam vs. rectal diazepam in infants and children with prolonged seizures (n = 436) [19] 79 and 56 % of seizures ceased within 10 min of administration of diazepam and lorazepam, respectively (p \ 0.001); probability of treatment failure was higher with lorazepam than diazepam Intranasal lorazepam vs. IM paraldehyde in infants and children with prolonged seizures (n = 160) [20] 75 and 61 % of seizures ceased within 10 min of administration of lorazepam and paraldehyde, respectively; lorazepam was less invasive and easy to administer; preferred method for pre-hospital treatment ADR adverse drug reaction, ARS acute repetitive seizures, BGD between-group difference, IM intramuscular, IV intravenous experience more seizures over a longer period of time may prefer a longer-acting benzodiazepine, such as diazepam. Ease of use, effectiveness and tolerability should all be considered when selecting a benzodiazepine and an appropriate mode of administration [1].…”