According to research published early online in the Annals of Emergency Medicine, when administration of oral midazolam is difficult in children, intranasal or buccal administration are useful alternatives.

The randomised controlled trial involved 180 children aged 0.5 to 7 years (median age 3.1 years) who needed non-parenteral sedation for laceration repair (169 evaluated for the primary outcome). Patients were randomised to receive either intranasal (n=60), buccal (n=60) or oral (n=60) midazolam.

The primary outcome was the first Children’s Hospital of Eastern Ontario Pain Score (CHEOPS) score after the laceration repair procedure began, comparing each of the 2 aerosolised midazolam groups (buccal and intranasal) individually relative to the standard oral midazolam group.

The following results were reported:

• The CHEOPS score at the beginning of the procedure demonstrated statistically significantly less distress in the buccal group compared with the oral group (P=0.04; difference -2; 95% CI -4 to 0) and exhibited a non-significant trend in the intranasal group (P=0.08; difference -1; -3 to 1).

• Sedation onset was faster with intranasal administration and more patients in this group achieved adequate sedation (85.5%) than with oral delivery (66.7%) or buccal administration (59.6%).

• The intranasal route, however, demonstrated the most irritation and the smallest proportion of patients who accepted the medication easily (difference -20%; -38% to -2% compared with oral midazolam)

• Adverse events were similar between groups: One patient in the oral midazolam group was deeply sedated, and the treating provider administered supplementary oxygen as a precaution; however, there was no respiratory depression or oxygen desaturation. One subject in each of the 3 groups vomited before discharge, with post-discharge vomiting in 1 patient in the oral group, 1 in the buccal group, and 2 in the intranasal group. Parents described post-discharge nightmares in 1 child in the oral group and 1 child in the intranasal group.

The researchers concluded that “Physicians are still searching for a non-invasive route of drug administration for common minor procedures in young children who require sedation and anxiolysis. Oral midazolam is unreliable because of first-pass hepatic metabolism and a reported efficacy of 60% to 76%.  The intranasal route now appears more reliable as a result of more effective drug delivery by atomiser.