Importance: Multimodal postoperative analgesia is widely used but lacks evidence of benefit.
Objective: Investigate beneficial and harmful effects of 4 nonopioid analgesics regimens.
Design, Setting, and Participants: Randomized, blinded, placebo-controlled, 4-group trial in 6 Danish hospitals with 90-day follow-up that included 556 patients undergoing total hip arthroplasty (THA) from December 2015 to October 2017. Final date of follow-up was January 1, 2018.
Interventions: Participants were randomized to receive paracetamol (acetaminophen) 1000 mg plus ibuprofen 400 mg (n?=?136; PCM?+?IBU), paracetamol 1000 mg plus matched placebo (n?=?142; PCM), ibuprofen 400 mg plus matched placebo (n?=?141; IBU), or half-strength paracetamol 500 mg plus ibuprofen 200 mg (n?=?140; HS-PCM?+?IBU) orally every 6 hours for 24 hours postoperatively, starting 1 hour before surgery.
Main Outcomes and Measures: Two co-primary outcomes: 24-hour morphine consumption using patient-controlled analgesia in pairwise comparisons between the 4 groups (multiplicity-adjusted thresholds for statistical significance, P?<?.0042; minimal clinically important difference, 10 mg), and proportion of patients with 1 or more serious adverse events (SAEs) within 90 days (multiplicity-adjusted thresholds for statistical significance, P?<?.025).
Results: Among 559 randomized participants (mean age, 67 years; 277 [50%] women), 556 (99.5%) completed the trial and were included in the analysis. Median 24-hour morphine consumption was 20 mg (99.6% CI, 0-148) in the PCM?+?IBU group, 36 mg (99.6% CI, 0-166) for PCM alone, 26 mg (99.6% CI, 2-139) for IBU alone, and 28 mg (99.6% CI, 2-145) for HS-PCM?+?IBU. The median difference in morphine consumption between the PCM?+?IBU group vs PCM alone was 16 mg (99.6% CI, 6.5 to 24; P?<?.001); for the PCM-alone group vs HS-PCM?+?IBU, 8 mg (99.6% CI, -1 to 14; P?=?.001); and for the PCM?+?IBU group vs IBU alone, 6 mg (99.6% CI, -2 to 16; P?=?.002). The difference in morphine consumption was not statistically significant for the PCM?+?IBU group vs HS-PCM?+?IBU (8 mg [99.6% CI, -2 to 16]; P?=?.005) or for the PCM-alone group vs IBU alone (10 mg [99.6% CI, -2 to 16]; P?=?.004) after adjustment for multiple comparisons and 2 co-primary outcomes. There was no significant difference between the IBU-alone group vs HS-PCM?+?IBU (2 mg [99.6% CI, -10 to 7]; P?=?.81). The proportion of patients with SAEs in groups receiving IBU was 15%, and in the PCM-alone group, was 11%. The relative risk of SAE was 1.44 (97.5% CI, 0.79 to 2.64; P?=?.18).
Conclusions and Relevance: Among patients undergoing THA, paracetamol plus ibuprofen significantly reduced morphine consumption compared with paracetamol alone in the first 24 hours after surgery; there was no statistically significant increase in SAEs in the pooled groups receiving ibuprofen alone vs with paracetamol alone. However, the combination did not result in a clinically important improvement over ibuprofen alone, suggesting that ibuprofen alone may be a reasonable option for early postoperative oral analgesia.
Trial Registration: ClinicalTrials.gov Identifier: NCT02571361.
|Tidsskrift||JAMA - Journal of the American Medical Association|
|Status||Udgivet - 12 feb. 2019|