Intranasal ketorolac versus intravenous ketorolac for treatment of migraine headaches in children: A randomized clinical trial

Abstract

Background Intravenous ketorolac is commonly used for treating migraine headaches in children. However, the prerequisite placement of an intravenous line can be technically challenging, time‐consuming, and associated with pain and distress. Intranasal ketorolac may be an effective alternative that is needle‐free and easier to administer. We aimed to determine whether intranasal ketorolac is non‐inferior to intravenous ketorolac for reducing pain in children with migraine headaches. Methods We conducted a randomized double‐blind non‐inferiority clinical trial. Children aged 8–17 years with migraine headaches, moderate to severe pain, and requiring parenteral analgesics received intranasal ketorolac (1 mg/kg) or intravenous ketorolac (0.5 mg/kg). Primary outcome was reduction in pain at 60 min after administration measured using the Faces Pain Scale‐Revised (scored 0–10). Non‐inferiority margin was 2/10. Secondary outcomes included time to onset of clinically meaningful decrease in pain; ancillary emergency department outcomes (e.g. receipt of rescue medications, headache relief, headache freedom, percentage improvement); 24‐h follow‐up outcomes; functional disability; and adverse events. Results Fifty‐nine children were enrolled. We analyzed 27 children who received intranasal ketorolac and 29 who received intravenous ketorolac. The difference in mean pain reduction at 60 min between groups was 0.2 (95% CI −0.9, 1.3), with the upper limit of the 95% CI being less than the non‐inferiority margin. There were no statistical differences between groups for secondary outcomes. Conclusions Intranasal ketorolac was non‐inferior to intravenous ketorolac for reducing migraine headache pain in the emergency department.

Clinically significant differences in self‐reported pain scores in children with headaches

“…The sample size was based on the availability of eligible patients from the two parent studies, for which this study was a secondary analysis. 3,8 Statistical analyses were conducted using SPSS (Version 26), R (Version 4.0.3), and the R cutpointr package. 14…”

“…8 The second was a randomized clinical trial (RCT) comparing intranasal ketorolac to intravenous ketorolac for reducing pain in children with migraine headaches; this cohort represented children with migraine headaches. 3 Both studies were conducted in the same urban pediatric ED, with an annual census of approximately 55,000 visits. Our institutional review board approved the observational study with verbal informed consent and the RCT with written informed consent.…”

“…The RCT enrolled children aged 8 to 17 years presenting with a migraine headache as defined by the modified Irma's ED criteria (Table S1) with a self-reported pain score of ≥4/10 during one of three recruitment periods between June 2015 and March 2021, all of whom were included in this current study. 3 Patients presenting during the overlapping period of time were enrolled in only one of the two studies. Exclusion criteria common to both studies included inability to complete self-report measures of pain (e.g., developmental delay, neurological impairment, altered mental status, intoxication), chronic disease associated with pain other than migraine headaches, underlying medical condition necessitating multiple painful procedures (e.g., malignancy), or not being able to speak English or Spanish.…”

“…1,2 A reduction in pain intensity of at least 50% has also been used as an outcome in headache trials. [3][4][5] These outcomes have been commonly used as desired endpoints for patients with headaches, but it is unclear if the changes in pain scores associated with these outcomes align with what a child or adolescent may consider to be clinically meaningful. There are differences in how children and adolescents perceive and report pain compared to adults, and these differences must be considered when deciding what change in pain score should be considered a clinically significant difference in the pediatric population.…”

“…Recommended outcomes for trials have included pain freedom at 2 h or headache relief based on an ordinal 4‐point scale representing no headache, mild, moderate, or severe headache 1,2 . A reduction in pain intensity of at least 50% has also been used as an outcome in headache trials 3–5 …”