Randomised Controlled Trial of Intravenous Dexamethasone to Prevent Relapse in the Treatment of Migraine in a Pediatric Emergency Department

Study design This was a randomised, double-blind, placebo-controlled clinical trial among children with a presumptive diagnosis of acute migraine in the ED. The study was approved by the institutional IRB and written informed assent and consent were obtained by the patient and a parent respectively, prior to enrolment.

Study setting All patients were treated in the ED of the CHU Ste-Justine, a tertiary care pediatric hospital with approximately 70 000 visits annually. For over 10 years, the members of this ED have been using a standardized protocol for the treatment of migraine. (7) This protocol suggests the administration of prochlorperazine and diphenhydramine, to decrease the rate of akathisia, if the patient is 8 years of age or more and presents with severe migraine (unable to perform normal activities) or status migrainosus (migraine that last more than 72 hours) to be followed by a few day-course of naproxen. Unfortunately, there was a shortage of prochlorperazine at the moment of the study, so a decision was made to use metoclopramide instead, another dopamine (D2) receptor antagonist known to be effective in the treatment of migraine in adults. (15) To minimize the impact of this research on the clinical management of patients, it was decided that migraine would be treated according to the standardized local protocol depending on the availability or not of prochlorperazine. This means that the treating physician did use the prochlorperazine protocol when possible and metoclopramide if not. This was accounted for in the randomization to insure balance distribution between groups. While using dual intervention decreased the homogeneity of the participants, it improved drastically our external validity.

Participants Inclusion criteria Patients were eligible if they were between 8 and 17 years of age and if they were presenting a diagnosis of acute migraine requiring treatment with an intravenous rescue therapy (either metoclopramide or prochlorperazine) because of the severity of the migraine according to the treating physician. In a prior study, the same group of pediatric emergency physicians had their migraine diagnosis confirmed by a pediatric neurologist in 64 of 68 patients.(16) Exclusion criteria Patients were excluded if they had a known allergy to any study drugs or a component or absolute contraindication to receiving corticosteroids such as: active untreated infections, systemic fungal infections, cerebral malaria, respiratory tuberculosis, hypertension, heart failure, renal or hepatic impairment, GI diseases, myasthenia gravis, diabetes, cataracts, glaucoma, seizure disorder, thyroid dysfunction, and thromboembolic tendencies. Also, patients who were already on corticosteroids were not eligible. Finally, patients who were initially recruited but who did not respond to the abortive migraine therapy (no modification in the pain level) were not randomized to receive the intervention or placebo. Information about these patients was kept but it was not included in the primary analysis.

Intervention/procedure As mentioned, all participants received a standardized treatment consisting of metoclopramide (0.5 mg/kg IV, maximum 10 mg, q 1h prn, maximum of 3 doses) or prochlorperazine (0.15 mg/kg IV over 2-3 minutes, maximum 10 mg) and diphenhydramine (0.5 mg/kg IV, maximum 25 mg). The intervention of interest was the administration of dexamethasone 0.6 mg/kg IV (max 24 mg) before departure from the ED. The control group received a similar looking placebo (NaCl 0,9% IV) with the same volume. All patients received a perfusion of D5% NaCl 0.9% at basal requirements during their stay in the ED and were discharged on a 48-hour course of naproxen (Naprosyn® 5 mg/kg/dose BID, max 500 mg) provided by our pharmacy.

Primary Outcome The primary outcome was the incidence of relapse following discharge from the ED and up to 48 hours after metoclopramide or prochlorperazine initial administration. Relapse was defined as either occurrence of any headache pain, regardless of its severity, after a pain free status, or any increase in the pain intensity in participants who left the ED with residual pain.