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Grand Rounds

2020 Cochrane Review Update: NSAIDs vs Other Analgesics for Soft Tissue Injury

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BACKGROUND AND PURPOSE:

  • The best drug treatment for acute soft tissue injuries (bruise, sprains, strains, etc.) is not well known
    • NSAIDs are commonly recommended
    • Oral opioids for acute pain management may be leading to dependence
  • In an update to a 2015 Cochrane review, Jones et al. (Cochrane Database Syst. Rev. 2020) assessed the benefits or harms of NSAIDs compared with other oral analgesics for treating acute soft tissue injuries

METHODS:

  • Systematic review and meta-analysis
  • Data sources
    • CENTRAL | MEDLINE | Embase to January 2020
    • Other databases were searched to February 2019
  • Inclusion criteria
    • Randomized or quasi-randomized controlled trials
    • Trials included individuals soft tissue injury
    • Compared oral NSAIDs vs
      • Paracetamol (acetaminophen)
      • Opioid
      • Paracetamol plus opioid
      • Complementary and alternative medicine
  • Study design
    • Acute soft tissue injury definition: Sprain, strain, or contusion of a joint, ligament, tendon, or muscle occurring within 48 hours of inclusion in the study
    • Two review authors independently assessed studies for eligibility, extracted data, and assessed risk of bias
    • Quality of the evidence was assessed using GRADE criteria
  • Primary outcomes
    • Pain
    • Swelling
    • Function
    • Adverse effects
    • Early re-injury

RESULTS:

  • 20 studies included | Combined total of 3305 participants
    • 3 studies included children only | Remainder included predominantly young adults
    • Approximately 60% were male | 40% female
    • 7 studies recruited only people with ankle sprains
  • Certainty
    • Evidence related to pain relief was generally high certainty
    • There was a combination of certainty with most outcomes
  • No studies reported re-injury rates
  • No studies compared NSAIDs with oral complementary and alternative medicines

NSAIDs vs Paracetamol  

  • 11 studies | 1853 participants
  • No differences between the two groups for pain at
    • 2 hours (1178 participants, 6 studies; high-certainty evidence)
    • Days 1 to 3 (1232 participants, 6 studies; high-certainty evidence)
    • ≥7 days (467 participants, 4 studies; low-certainty evidence)
  • Little difference between the groups in numbers of participants with minimal swelling at ≥7 days 
    • 77 participants, 1 study; low-certainty evidence
  • Little difference between the groups for return to function at ≥7 days
    • 386 participants, 3 studies; very low-certainty evidence
  • NSAIDs may slightly increase the risk of GI adverse events compared with paracetamol
    • 1504 participants, 10 studies; low-certainty evidence
  • There was little difference in neurological adverse events between the NSAID and paracetamol groups
    • 1679 participants, 9 studies; low-certainty evidence

NSAIDs vs Opioids

  • 6 studies | 1212 participants
  • There was no difference between the groups in pain at
    • 1 hour (1058 participants, 4 studies; moderate-certainty evidence)
    • Days 4 to 7 (706 participants, 1 study; low-certainty evidence)
  • No important difference between the groups in swelling
    • 84 participants, 1 study, very low-certainty evidence
  • NSAID group were more likely to return to function in 7 to 10 days
    • 542 participants, 2 studies; low-certainty evidence
  • NSAIDs use less likely to result in GI or neurological adverse events compared with opioids
    • 1143 participants, 5 studies; moderate-certainty evidence

NSAIDS vs Paracetamol and Opioid Combination

  • 4 studies | 240 participants
  • The applicability of findings from these studies is questionable
    • The dextropropoxyphene combination analgesic agents used are no longer in general use (used in 2 of 4 studies)
    • The paracetamol doses were suboptimal
  • No difference between the groups in pain at
    • Day 1 (51 participants, 1 study; very low-certainty evidence)
    • Day 3 (149 participants, 2 studies; very low-certainty evidence)
    • Day 7 (138 participants, 2 studies; very low-certainty evidence)
  • No difference between groups for the following  
    • Swelling (230 participants, 3 studies; very low-certainty evidence)
    • Return to function at day 7 (89 participants, 1 study; very low-certainty evidence)
    • Risk of GI or neurological adverse events (141 participants, 3 studies; very low-certainty evidence)

CONCLUSION:

  • In the context of soft tissue injuries
    • No differences were found between NSAIDs and paracetamol at 1 to 2 hours and 2 to 3 days | There may also be no difference in pain at day 7 and beyond
    • NSAIDs may be slightly associated with more GI upset compared to paracetamol  
    • There is probably no difference between NSAIDs and opioids in pain at 1 hour, and there may be no difference at days 4 or 7
    • NSAIDs probably result in fewer GI and neurological adverse effects compared with opioids
  • The authors note that participants tended to be younger and these results really are not generalizable to adults ≥65 years of age

Learn More – Primary Sources:

Oral non-steroidal anti-inflammatory drugs versus other oral analgesic agents for acute soft tissue injury

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