Even minor procedures may cause significant pain or anxiety in children. Sedative drugs such as diazepam or chloral hydrate have been given rectally or orally to ease pain and anxiety, but these medications have a slow onset and variable effects. Ljungman and colleagues studied midazolam, a benzodiazepine that can be given orally, nasally, rectally, intramuscularly or intravenously, and has a short onset and a half-life of about two hours. They administered the drug in an intranasal spray to see if it would reduce anxiety, pain and procedure problems in children who were receiving injections for cancer treatment.

Infants and children who were at least six months of age were included if there was a need for at least three needle insertions during the study period. Patients were randomized to receive a placebo nasal spray or midazolam nasal spray (1.2 mL of 5 mg per mL) in one of two patterns: midazolam-placebo-placebo or placebo-midazolam-midazolam. The placebo nasal spray contained citric acid to produce a burning sensation similar to that caused by midazolam spray in order to preserve blinding. All children were given a patch of eutectic mixture of local anesthetic (EMLA), because midazolam does not have analgesic properties, and later were given the nasal spray. The needle insertion occurred one to two hours after application of the EMLA and about 10 minutes after administration of the nasal spray. A visual analog scale was used to evaluate discomfort and pain. Children, parents and nurses completed a scale for each of seven questions.

When midazolam spray was used, children, parents and nurses reported a significant reduction in children's anxiety. Parents and nurses reported decreased discomfort and pain when children were given midazolam nasal spray. However, the children did not report a significant reduction in their discomfort and pain. No serious adverse events were noted, although nasal discomfort, bad taste and crying were reported. These effects occurred in the placebo and active groups. Crying occurred significantly more often in the midazolam group, because of midazolam's reduction of affect control. Parents and nurses all indicated that they would like the children to use the midazolam again for future procedures.

The authors conclude that midazolam nasal spray can reduce the anxiety and discomfort experienced by children undergoing procedures such as needle insertion. Younger children may perceive more nasal discomfort and may therefore require use of oral or rectal routes of administration.