For acute musculoskeletal injuries in the emergency department setting, paracetamol monotherapy is a suitable first-line analgesic. Its combination with other oral analgesics does not provide better pain relief. 

This systematic review and meta-analysis investigated if the combination of oral analgesics offers any major benefit over paracetamol alone in treating patients with acute musculoskeletal injuries.

EMBASE, MEDLINE (via PubMed), and Cochrane electronic databases were extensively searched by two reviewers. Randomized controlled clinical trials that compared the analgesic efficacy of paracetamol plus other oral analgesics and paracetamol alone in treating acute musculoskeletal injuries were detected.

The decline in pain score, adverse effects, and the requirement for additional analgesia were the study outcomes. Utilizing Cochrane Risk of Bias Assessment Tool and RevMAN meta-analysis software, assessment of the data was done.

Overall, six studies were included (n = 1254), in which no paediatric study was detected. In five studies, paracetamol was compared to paracetamol plus NSAID. In one study, an opioid was included in the combination group. 

No significant difference was witnessed between the groups for the decrease in pain score in the first 2 hr, 24 hr or 72 hr. The  mean difference in decline in pain score at rest on 100 mm VAS and activity is shown in the following table:

The risk of noxious adverse events in the emergency department was found to be -0.00. More individuals receiving combination therapy were found to need additional analgesia in the first two hours.

For relieving pain in acute soft tissue injuries, adding other oral analgesic agents to paracetamol does not improve analgesia on average. The addition of NSAID to paracetamol did not elevate adverse events. But adding opioid and NSAID to paracetamol considerably raised adverse events.

For managing musculoskeletal injuries, paracetamol monotherapy is an appropriate first-line analgesic as combining it with oral pain-relieving agents does not cause any major additional analgesic effect.