NEW YORK (Reuters Health)—Combining paracetamol (acetaminophen) with ibuprofen does not cut postoperative use of morphine in a clinically meaningful way relative to ibuprofen alone, in patients undergoing total hip arthroplasty (THA), results of a Danish randomized trial suggest.
“Although the combined use of paracetamol and ibuprofen reduced immediate postoperative morphine consumption compared with paracetamol alone in patients undergoing THA, ibuprofen alone resulted in comparable pain control without increasing serious adverse events,” the researchers report in JAMA, online Feb. 12.1
Dr. Kasper Højgaard Thybo from Naestved Hospital and colleagues evaluated the beneficial and harmful effects of four oral nonopioid analgesic regimens taken every six hours for 24 hours following THA and starting one hour before surgery.
By random allocation, 136 patients received 1,000 mg of paracetamol (acetaminophen) plus 400 mg of ibuprofen, 142 received 1,000 mg of paracetamol plus placebo, 141 received 400 mg of ibuprofen plus placebo and 140 received half-strength 500 mg of paracetamol plus 200 mg of ibuprofen.
The two co-primary outcomes were 24-hour morphine consumption using patient-controlled analgesia and the proportion of patients with one or more serious adverse events within 90 days.
Median 24-hour morphine consumption was 20 mg in the paracetamol/ibuprofen group, 36 mg for paracetamol alone, 26 mg for ibuprofen alone and 28 mg for half-strength paracetamol/ibuprofen.
Morphine consumption in the first 24 hours was statistically significantly lower for the combination of 1,000 mg of paracetamol plus 400 mg of ibuprofen than for either agent alone, the investigators report, findings that “support the principle of multi-modal analgesia with paracetamol plus ibuprofen compared with paracetamol alone for the first postoperative day.”
However, compared with ibuprofen alone, the morphine-sparing effect of the combination was below the prespecified threshold for a clinically important postoperative morphine reduction (10 mg), “suggesting that ibuprofen alone may be a reasonable option for early postoperative oral analgesia,” they say.
There was no statistically significant difference in the percentage of patients with serious adverse events in any of the ibuprofen groups vs. paracetamol alone (15% vs. 11%).
The authors say a limitation of the trial is that the intervention period was only 24 hours, “and a prolonged intervention period could have been more appropriate as treatment with paracetamol plus ibuprofen seldom is used for only 24 hours in a clinical context.”
The study had no commercial funding and the authors made no relevant disclosures.
Dr. Thybo did not respond to a request for comment by press time.
- Thybo KH, Hägi-Pedersen D, Dahl JB, et al. Effect of combination of paracetamol (acetaminophen) and ibuprofen vs. either alone on patient-controlled morphine consumption in the first 24 hours after total hip arthroplasty: The PANSAID randomized clinical trial. JAMA. 2019 Feb 12;321(6):562–571. doi: 10.1001/jama.2018.22039.