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

Abstract

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 6Danishhospitalswith90-dayfollow-upthatincluded556patientsundergoingtotalhiparthroplasty (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.

Development of evidence‐based recommendations for procedure‐specific pain management: PROSPECT methodology

“…The opioid‐sparing effects of paracetamol and NSAIDs or COX‐2 inhibitors are well described for all surgical procedures . The PROSPECT group assesses if the addition of an analgesic intervention would further improve pain relief when combined with simple, effective, non‐opioid analgesics (i.e.…”

Post‐operative opioid‐related adverse events with intravenous oxycodone compared to morphine: A randomized controlled trial

“…In the literature, the incidence of PONV with oxycodone vary according to dose‐related studies and route of administration (PO, IV, SC) 15,19,23 . Indeed, no studies appear to ultimately demonstrate the superiority of IV oxycodone vs IV morphine 27‐29 . Urinary retention was the most frequent ORAE reported at the PACU.…”

Revision Total Knee Arthroplasty Is Associated With Significantly Higher Opioid Consumption as Compared With Primary Total Knee Arthroplasty in the Acute Postoperative Period

“…The patients who underwent rTKA experience more pain and have a higher narcotic requirement. Further research is needed into better methods to control pain for our revision patients postoperatively, including nerve blocks, additional doses of steroids, intravenous acetaminophen, ibuprofen injections, more robust periarticular injections, ketamine, and cryoanalgesia [33][34][35][36][37][38]. These adjuncts have been studied with respect to primary total joint arthroplasty, but we feel that they may also be effective in treating patients who underwent rTKA who may not be adequately treated with low-dose opioid protocols.…”