Paramedic analgesia comparing ketamine and morphine in trauma. A synopsis of the PACKMaN double-blind RCT

Background

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.

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.

Results

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.

Conclusion

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.

Limitations 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.

Future work

Future research should focus on identification of the optimal drug (or combination of drugs), dosing and drug route to achieve rapid control of pain. In addition, it would be valuable to explore the relationship between paramedic analgesia and the development of chronic pain.

Funding

This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128086.