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Peer-reviewed article

Intra-nasal ketamine compared to intravenous morphine for acute pain in the emergency department: a prospective, triple blind, controlled study.

Shopen NiD, Cohen NiD, Mizrahi M, Aviv Mordechai R, Ritter O, Werthein J, Cohen LA, Zeltser D, Halpern P

Pain medicine (Malden, Mass.)Jul 1, 2026Israel0 citationsDOI: 10.1093/pm/pnag012

Abstract

<h4>Objective</h4>Evidence on intranasal (IN) ketamine as an alternative to opioids for acute pain is limited. We compared the efficacy and safety of IN ketamine to intravenous (IV) morphine in emergency department (ED) patients.<h4>Methods</h4>This triple-blinded, placebo-controlled, randomized trial included consenting adult patients with moderate-to-severe pain (≥70 mm on a visual analog scale [VAS]) who were given either 0.1 mg/kg IV morphine and IN placebo or 1 mg/kg IN ketamine and IV placebo and were monitored for vital signs, pain levels, and adverse events (AEs) for 120 minutes. The primary outcome was the efficacy of IN ketamine compared with IV morphine in reducing pain, defined as achieving a ≥ 15-mm decrease in the VAS pain score. The secondary outcomes were AEs and overall patient satisfaction.<h4>Results</h4>Sixty-eight participants (mean age 43.5 ± 12.2 years, 48 male) were randomized equally. Groups were similar at baseline in mean age, sex, and pre-treatment median pain levels. There were no significant differences between IV morphine and IN ketamine groups in the median [intraquartile range (IQR)] values of time to onset of significant pain reduction (10.0 [5.0-20.0] vs. 10.0 [5.0-15.0] minutes, P = .92), maximal pain reduction (30.0 [10.0-57.0] vs. 20.5 [4.2-39.5] mm VAS, P = .18) and time to maximal pain reduction (105.0 [63.7-120.0] vs. 90.0 [45.0-120.0] minutes, P = .35). There were no significant differences in frequency of adverse effects at 0, 60, and 120 minutes.<h4>Conclusions</h4>This study did not demonstrate a statistically significant difference in efficacy or safety between IN ketamine and IV morphine for the management of acute pain in the ED. Moreover, the findings indicate that IN ketamine may be a viable, and potentially superior, alternative to IV morphine.

Topics & conditions

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KetaminePain

Keywords

MorphineIntranasalefficacyPain Levels

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