Out-of-Hospital Intranasal Ketamine as an Adjunct to Fentanyl for the Treatment of Acute Traumatic Pain: A Randomized Clinical Trial - 12/06/24

Doi : 10.1016/j.annemergmed.2024.04.018

Jason T. McMullan, MD, MS ^a,^⁎ , Christopher A. Droege, PharmD ^b,^c, Kathleen M. Chard, PhD ^d,^e, Edward J. Otten, MD ^f, Kim Ward Hart, MA ^g, Christopher J. Lindsell, PhD ^h, Richard J. Strilka, MD, PhD ^i,^j
^a Division of EMS, Department of Emergency Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH
^b Department of Pharmacy Services, UC Health, University of Cincinnati Medical Center, Cincinnati, OH
^c Division of Pharmacy Practice and Administration, University of Cincinnati James L. Winkle College of Pharmacy, Cincinnati, OH
^d Cincinnati Department of Veterans Affairs Medical Center, Cincinnati, OH
^e Department of Psychiatry and Behavioral Neuroscience, College of Medicine, University of Cincinnati, Cincinnati, OH
^f Department of Emergency Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH
^g Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN
^h Duke Clinical Research Institute, Duke University, Durham, NC
ⁱ 711 HPW/USAFSAM, Center for Sustainment of Trauma and Readiness Skills, Wright-Patterson Air Force Base, OH
^j Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH

^∗Corresponding Author.

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Wednesday 12 June 2024

Abstract

Study objective

To evaluate if out-of-hospital administration of fentanyl and intranasal ketamine, compared to fentanyl alone, improves early pain control after injury.

Methods

We conducted an out-of-hospital randomized, placebo-controlled, blinded, parallel group clinical trial from October 2017 to December 2021. Participants were male, aged 18 to 65 years, receiving fentanyl to treat acute traumatic pain prior to hospital arrival, treated by an urban fire-based emergency medical services agency, and transported to the region’s only adult Level I trauma center. Participants randomly received 50 mg intranasal ketamine or placebo. The primary outcome was the proportion with a minimum 2-point reduction in self-described pain on the verbal numerical rating scale 30 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 3 hours of care.

Results

Among the 192 participants enrolled, 89 (46%) were White, (median age, 36 years; interquartile range, 27 to 53 years), 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 versus 32/89 [36.0%] placebo; difference in proportions, 8.7%; 95% confidence interval, −5.1% to 22.5%; P=.22) or at any time point through 3 hours. There was no difference in secondary outcomes or side effects.

Conclusion

In our sample, we did not detect an analgesic benefit of adding 50 mg intranasal ketamine to fentanyl in out-of-hospital trauma patients.

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Plan

Introduction

Background

Importance

Goals of This Investigation

Materials and Methods

Study Design, Setting, and Organization

Selection of Participants

Interventions

Randomization and Blinding

Outcomes and Measurements

Data Collection and Data Sources

Analysis

Results

Characteristics of Study Subjects

Primary Outcome

Secondary Outcomes

Per-Protocol Analysis

Limitations

Discussion

	Please see page XX for the Editor’s Capsule Summary of this article.
	Supervising editor: Steven M. Green, MD. Specific detailed information about possible conflicts of interest for individual editors is available at editors.
	Author contributions: JTM, EJO, and CJL conceived the study. All authors contributed to trial design. JTM and RJS obtained research funding. CJL and KWH provided statistical advice on study design and analyzed the data. JTM drafted the manuscript, and all authors contributed substantially to its revision. JTM takes responsibility for the paper as a whole.
	Data sharing statement: Data can be made available, on a case by case basis, through the contact author; because of the regulatory and consent process of this trial, data can only be released after institutional review board approval.
	All authors attest to meeting the four ICMJE.org authorship criteria: (1) Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND (2) Drafting the work or revising it critically for important intellectual content; AND (3) Final approval of the version to be published; AND (4) Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
	Funding and support: By Annals’ policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org/). The authors have stated that no such relationships exist. This trial was funded by the United States Air Force (grant number FA8650-16-2-6G02, issued May 2, 2016).
	Trial registration number: ClinicalTrials.gov NCT02866071
	Presentation information: We have presented our primary outcome as an abstract at the 2023 National Association of EMS Physicians annual meeting (Tampa, FL; January 26-28, 2023).
	Disclaimer: The views expressed in this manuscript are those of the author and do not reflect the official policy or position of the United States Air Force, Department of Defense, Department of Veterans Affairs, or the United States Government. This material is declared a work of the US Government and is not subject to copyright protection in the United States.