Three-drug combination best stemmed morphine use after total hip arthroplasty
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Key takeaways:
- Combination therapy with paracematol, ibuprofen and dexamethasone led to the lowest morphine intake and fewest safety events after hip replacement.
- None of the between-group comparisons met the minimal important threshold.
Patients who receive combination therapy with paracematol, ibuprofen and dexamethasone demonstrate the lowest morphine consumption in the 24 hours following total hip arthroplasty, according to data published in The Lancet Rheumatology.
Morphine consumption in the 24 hours following total hip arthroplasty was lowest in patients treated with a combination of paracematol, ibuprofen and dexamethasone, according to data published in The Lancet Rheumatology.
“Guidelines for postoperative analgesia following total hip arthroplasty are conflicting,” Joakim Steiness, MD, of Zealand University Hospital, in Denmark, and colleagues wrote. “Despite frequent recommendations for the use of paracematol, ibuprofen and glucocorticoids, evidence of the benefits and harms of their various combinations is scarce, and the optimal combination is uncertain.”
To investigate the optimal combination of paracetamol, ibuprofen and dexamethasone to mitigate post-operative morphine use, Steiness and colleagues conducted a randomized controlled trial across nine Danish hospitals. Between March 5, 2020, and Nov. 15, 2022, the reserachers randomly assigned participants scheduled for hip arthroplasty to receive one of the following treatments:
- paracematol 1,000 mg, ibuprofen 400 mg and dexamethasone placebo (n = 261);
- ibuprofen 400 mg, single-dose intravenous dexamethasone 24 mg and paracematol placebo (n = 262);
- paracematol 1,000 mg, single-dose intravenous dexamethasone 24 mg and ibuprofen placebo (n = 262); or
- paracematol 1,000 mg, ibuprofen 400 mg and single-dose intravenous dexamethasone 24 mg (n = 258).
A dose of oral medication was given an hour before surgery, and three more doses were provided at 6-hour intervals throughout the subsequent 24 hours. The predefined minimal important difference in morphine consumption during that time was 8 mg, based on findings from previous trials. Differences between the groups were calculated as Hodges-Lehmann median differences with 99% confidence intervals.
According to the researchers, morphine consumption was significantly reduced in the group receiving paracematol, ibuprofen and dexamethasone compared with the paracematol plus ibuprofen group (Hodges-Lehmann median difference: –6 mg; 95% CI, –10 to –3) and the paracematol plus dexamethasone group (median difference: –4 mg; 95% CI, –8 to –1).
The group that received all three drugs additionally demonstrated the lowest proportion of patients experiencing one or more adverse events (35%), with the highest being 63% in the paracematol plus ibuprofen group.
The researchers noted that “none of the comparisons showed differences reaching the minimal important threshold of 8 mg” of intravenous morphine. However, they added that the 8 mg value was “arbitrary” due to the lack of a “universally accepted standard for minimal important differences in postoperative opioid reduction.”
“When balancing the beneficial and harmful effects, the combination including all three drugs (paracematol plus ibuprofen plus dexamethasone) ranked highest among the four combinations,” Steiness and colleagues wrote.