{
  "abstract": "Background During point-of-injury and en route care, pain after traumatic injuries is frequently treated with parenteral fentanyl. Ketamine is increasingly used and may offer opioid-sparing effects, but the dose of ketamine recommended by Tactical Combat Casualty Care (TCCC), and the combination with fentanyl, is inadequately studied. Combination therapy may offer longer-lasting analgesia, even if initial pain relief is no different. Early pain management with ketamine may decrease the risk of developing posttraumatic stress disorder (PTSD) symptoms and chronic pain, but these long-term benefits are unconfirmed. This prehospital trial evaluates if fentanyl and intranasal ketamine, compared to fentanyl alone, improves early analgesia after injury, increases the duration of adequate analgesia, and decreases the rate of developing symptoms of PTSD or chronic pain. This abstract includes, and builds upon, previously published work. 1 Methods We conducted a prehospital randomized, placebo-controlled, blinded, parallel group clinical trial between October 2017 and December 2021. Detailed methods have been published. 2 Paramedics of an urban, fire department-based EMS agency in the United States screened, consented, and enrolled men, ages 18–65 years, who received fentanyl to treat acute traumatic pain during transport to the region’s only adult Level I Trauma Center. Of 569 eligible participants, 199 were randomized, and 192 underwent primary analysis. Participants received 50mg intranasal ketamine or a matching volume (1mL) of placebo. Fentanyl route and dose was determined by the treating paramedic. All other prehospital and emergency department treatments were at clinician discretion. The primary outcome was a two-point reduction in self-described pain on the Verbal Numerical Rating Scale thirty minutes after intervention. Secondary outcomes were pain control and additional pain medications through the first three hours of care. Exploratory outcomes included development of PTSD and chronic pain at 90-days. Analyses used descriptive statistics and Chi-square testing.Results 192 men, 89 (46%) White, 36 [27, 53] (median [IQR]) years old were included; 27% suffered penetrating injury, 5% had an Injury Severy Score >15, and 14% were taken directly to the operating room from the emergency department. 103 received ketamine and 89 received placebo, with no statistical difference in the proportion experiencing improved pain 30 minutes after treatment ( figure 1; 45% ketamine vs. 36% placebo) or at any timepoint through 180 minutes. The proportion requiring additional pain medications or experiencing side effects through three hours were similar. Of 154 participants consenting for follow-up, 96 (54 ketamine, 42 placebo) completed the 90-day assessments, with no difference in the proportion developing PTSD (18% placebo vs. 14% ketamine) or chronic pain at follow-up.Conclusions Adding 50mg intranasal ketamine to fentanyl prior to hospital arrival did not improve early analgesia or reduce the risk of developing symptoms of PTSD or chronic pain at 90-day follow-up. TCCC has updated intranasal ketamine dosing recommendations to 100mg, which may be more effective.Abstract P02 Figure 1Absolute change from baseline stated verbal numerical rating scale, assessed 30-minutes after receiving study drug. The central parallel line plot shows the VNRS for each participant at baseline and 30 minutes after receiving study drug. The box-whisker plots demonstrate within- and between-group differences. (P: placebo; K: ketamine) (Used with permission from McMullan et al.1)References McMullan JT, Droege CA, Chard KM, Otten EJ, Hart KW, Lindsell CJ, Strilka RJ. Out-of-hospital intranasal ketamine as an adjunct to fentanyl for the treatment of acute traumatic pain: a randomized clinical trial. Ann Emerg Med. 2024 Oct;84(4):363–373. doi: 10.1016/j.annemergmed.2024.04.018.McMullan J, Droege C, Strilka R, Hart K, Lindsell C. Intranasal ketamine as an adjunct to fentanyl for the prehospital treatment of acute traumatic pain: design and rationale of a randomized controlled trial. Prehosp Emerg Care. 2021 Jul-Aug;25(4):519–529. doi: 10.1080/10903127.2020.1808746.",
  "authors": [
    {
      "affiliations": [
        "Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, OH"
      ],
      "name": "Jason McMullan"
    },
    {
      "affiliations": [
        "Department of Pharmacy Services, UC Health, University of Cincinnati Medical Center, Cincinnati, OH; Division of Pharmacy Practice and Administration, University of Cincinnati James L. Winkle College of Pharmacy, Cincinnati, OH"
      ],
      "name": "Christopher Droege"
    },
    {
      "affiliations": [
        "Cincinnati Department of Veterans Affairs Medical Center; University of Cincinnati, College of Medicine, Department of Psychiatry and Behavioral Neuroscience"
      ],
      "name": "Kathleen M Chard"
    },
    {
      "affiliations": [
        "Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, OH"
      ],
      "name": "Edward Otten"
    },
    {
      "affiliations": [
        "Cincinnati Department of Veterans Affairs Medical Center; University of Cincinnati, College of Medicine, Department of Psychiatry and Behavioral Neuroscience"
      ],
      "name": "Eric Mueller"
    },
    {
      "affiliations": [
        "Duke Clinical Research Institute, Duke University"
      ],
      "name": "Kimberly W Hart"
    },
    {
      "affiliations": [
        "Duke Clinical Research Institute, Duke University"
      ],
      "name": "Christopher J Lindsell"
    },
    {
      "affiliations": [
        "Lt Col MC USAF (Ret.); Department of Surgery, Div of General Surgery, University of Cincinnati College of Medicine, Cincinnati, OH"
      ],
      "name": "Richard Strilka"
    }
  ],
  "title": "P02 Prehospital intranasal ketamine as an adjunct to fentanyl for the treatment of acute traumatic pain: a randomized clinical trial",
  "uid": "fb01fd04-a87e-594d-8268-6764b51cf4dc"
}