Authors' objectives: Paramedics frequently administer analgesic medications for pain following trauma. Morphine is the most commonly administered strong analgesic. However, it may not be the best option as it may lower blood pressure, depress respiration and there is a risk of dependency. Ketamine might be a better option. We sought to compare clinical and cost-effectiveness of paramedic administered ketamine and morphine in patients with severe pain following trauma.

Authors' results and conclusions: We randomised 449 participants: 219 (49%) received ketamine and 230 (51%) received morphine. The Sum of Pain Intensity Difference score was 3.5 (standard deviation 2.8) for ketamine and 3.4 (standard deviation 3.0) for morphine. We found no significant difference in efficacy between drugs (adjusted mean difference 0.1, 95% confidence interval −0.4 to 0.6; p = 0.7). Ketamine was more likely to achieve ‘very much improvement’ (odds ratio 1.58, 95% confidence interval 1.08 to 2.31; p = 0.019) and to do so more rapidly than morphine (hazard ratio 1.42, 95% confidence interval 1.09 to 1.84; p = 0.009). However, morphine was likely to last longer than ketamine (hazard ratio 1.28, 95% confidence interval 1.05 to 1.56; p = 0.013). There was no evidence of a significant difference in serious adverse events. Ketamine does not provide superior analgesia than morphine when treating acute severe trauma pain. Ketamine is a suitable alternative that is safe for use by paramedics.

Authors' methods: PACKMaN was a double-blinded, randomised controlled, superiority trial. Eligible patients were 16 years of age or over, had an acute injury, and articulated a pain score of 7 or greater on a 0–10 numeric rating score. We excluded pregnant patients, prisoners, those unable to articulate a pain score and anyone lacking capacity. The maximum dose of morphine was 20 mg while the maximum dose of ketamine was 30 mg. The trial drug was titrated to effect. The primary outcome was the Sum of Pain Intensity Difference score. Patients were required to provide verbal assent to participate, consequently we were only able to recruit patients who had capacity to understand what was being asked of them. It is also therefore probable that we were unable to recruit the most severely injured patients. These factors may limit generalisability of our results. Furthermore, we were unable to complete a planned sensitivity analysis to determine if there was a difference in treatment response between patients with more minor injuries and those who were more severely injured. Finally, we experienced a loss to follow-up at 3 and 6 months, so our findings for long term outcomes may have been underpowered.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/NIHR136206

Year Published: 2026

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/KGTO6391

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/KGTO6391

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk