Out-of-Hospital Intranasal Ketamine as an Adjunct to Fentanyl for the Treatment of Acute Traumatic Pain: A Randomized Clinical Trial

Abstract

ObjectiveTo evaluate if prehospital administration of fentanyl and intranasal ketamine, compared to fentanyl alone, improves early pain control after injury. MethodsWe conducted a prehospital randomized, placebo-controlled, blinded, parallel group clinical trial from October 2017 to December 2021. Participants were male, aged 18-65 years, receiving fentanyl to treat acute traumatic pain prior to hospital arrival, treated by an urban fire-based EMS agency, and transported to the region’s only adult Level I Trauma Center. Participants randomly received 50mg intranasal ketamine or placebo. The primary outcome was the proportion with a minimum two-point reduction in self-described pain on the Verbal Numerical Rating Scale thirty minutes after study drug administration assessed by 95% confidence interval overlap. Secondary outcomes were side effects, pain ratings, and additional pain medications through the first three hours of care. ResultsIn the 192 enrolled, 89 (46%) were White, 36 [27, 53] (median [IQR]) years old, with 103 receiving ketamine and 89 receiving placebo. There was no difference in the proportion experiencing improved pain 30-minutes after treatment (46/103 [44.7%] ketamine vs. 32/89 [36.0%] placebo, difference in proportions 8.7% [95% CI -5.1% to 22.5%]. p=0.22) or at any timepoint through three hours. There was no difference in secondary outcomes or side effects. ConclusionsIn our sample, we did not detect an analgesic benefit of adding 50mg intranasal ketamine to fentanyl in prehospital trauma patients.