One high quality study (Thybo 2019) and one moderate quality study (Gupta 2016) evaluated the effect of combination acetaminophen with NSAID vs. NSAID alone. In a multi-center study evaluating morphine use after THA, the authors noted statistically significant reductions in morphine usage in the combination group vs. NSAIDs alone, however this did not meet the pre-defined MCID of 10mg (Thybo 2019).
A moderate quality study evaluating combination therapy after TKA or THA found significantly lower pain scores up to day 3 and decreased opioid consumption in the combination ibuprofen/acetaminophen group vs. ibuprofen alone (Gupta).
The Acetaminophen/NSAID Combination recommendation has been downgraded one level because of inconsistent evidence.
Benefits/Harms of Implementation
Potential harms are related to the risk profile of the individual medications. Combination therapy does not offer additional risk of harm to the medications given in isolation.
Cost Effectiveness/Resource Utilization
There are minimal additional costs associated with this intervention. The use of acetaminophen and NSAIDs are commonplace and most medications are now generic. Combination therapy does not require a novel combination medication.
Acceptability
No anticipated issues. Patients and clinicians should be aware of the presenting signs and treatments required for adverse events related to both classes of medications.
Feasibility
Both acetaminophen and NSAIDs are used commonly and are readily available in most pharmacies.
Future Research
The ideal combination and dosing strategy are unclear at this point. Future research should focus on identifying the most efficacious and safest combination medication strategy and expand studies to include orthopaedic surgery patients undergoing non-arthroplasty procedures.
- 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;321(6):562–571. doi:10.1001/jama.2018.22039
- Gupta, A., Abubaker, H., Demas, E., Ahrendtsen, L. A Randomized Trial Comparing the Safety and Efficacy of Intravenous Ibuprofen versus Ibuprofen and Acetaminophen in Knee or Hip Arthroplasty. Pain Physician 2016; 6: 349-56