Adding acetaminophen to Morphine provides additional benefit in the management of acute ED Pain: JAMA
Researchers have found in a new randomized clinical trial of adults presenting to the emergency department with acute pain that morphine plus placebo failed to demonstrate noninferiority compared with morphine combined with acetaminophen during initial pain management. These results suggest that adding acetaminophen to morphine may provide additional benefit and support its use in individualized acute pain treatment strategies in the ED. The study was published in JAMA Network Open by Guillaume C. and colleagues.
The use of IV acetaminophen has become an integral part of multimodal analgesia regimens with opioids for the management of acute pain. Morphine has remained a cornerstone in the management of severe pain, but the value of adding IV acetaminophen to titrated morphine has remained unclear, especially during the early phase.
This trial was carried out in 11 French EDs from December 3, 2019, to December 31, 2024, with a follow-up of 60 minutes. Eligible participants were adults aged 18 years or older with severe acute pain, as indicated by a numeric rating scale (NRS) score of 5 or higher on a scale of 0 to 10. Both traumatic and non-traumatic pain etiologies were allowed, with subgroup analyses for each type of etiology predetermined.
Key findings:
A total of 430 patients were randomized in this study. The median age of the patients was 42 years (interquartile range: 29 to 57 years), and 220 (51.2%) were men.
Of these, 424 were included in the modified intention-to-treat (mITT) population, with 213 receiving morphine plus placebo and 211 receiving morphine plus acetaminophen.
In this population, 181 (42.7%) had traumatic pain, while 243 (57.3%) had nontraumatic pain.
In the per-protocol (PP) population, 393 were included, with 197 receiving morphine plus placebo and 196 receiving morphine plus acetaminophen.
In this population, 169 (43.0%) had traumatic pain, while 224 (57.0%) had nontraumatic pain.
For traumatic pain, the per-protocol between-group difference in pain reduction was 0.32 points (95% CI: -0.29 to 0.94), while for nontraumatic pain it was 0.80 points (95% CI: 0.19 to 1.41).
In the modified intention-to-treat population, it was 0.36 points (95% CI: -0.28 to 1.01) for traumatic pain, while for nontraumatic pain it was 0.76 points (95% CI: 0.11 to 1.41).
Morphine plus placebo did not meet the noninferiority margin of 1 point compared with morphine plus acetaminophen.
When used in adults presenting to the ED with severe acute pain, the combination of morphine and placebo did not meet the noninferiority criteria compared to the combination of morphine and IV acetaminophen for early pain relief. These studies indicate that IV acetaminophen may offer an enhanced pain benefit when combined with titrated morphine, highlighting its place as part of an individualized multimodal pain approach.
Reference:
Cattin G, Viglino D, Segard J, et al. Morphine Plus Placebo vs Morphine Plus Acetaminophen for Acute Pain in the Emergency Department: A Randomized Clinical Trial. JAMA Netw Open. 2026;9(2):e2560250. doi:10.1001/jamanetworkopen.2025.60250
