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

Abstract

Background: Acute soft tissue injuries are common and costly. The best drug treatment for such injuries is not certain, although non-steroidal anti-inflammatory drugs (NSAIDs) are often recommended. There is concern about the use of oral opioids for acute pain leading to dependence. This is an update of a Cochrane Review published in 2015.

Objectives: To assess the benefits or harms of NSAIDs compared with other oral analgesics for treating acute soft tissue injuries.

Search methods: We searched the CENTRAL, 2020 Issue 1, MEDLINE (from 1946), and Embase (from 1980) to January 2020; other databases were searched to February 2019.

Selection criteria: We included randomised or quasi-randomised controlled trials involving people with acute soft tissue injury (sprain, strain, or contusion of a joint, ligament, tendon, or muscle occurring within 48 hours of inclusion in the study), and comparing oral NSAIDs versus paracetamol (acetaminophen), opioid, paracetamol plus opioid, or complementary and alternative medicine. The outcomes were pain, swelling, function, adverse effects, and early re-injury.

Data collection and analysis: Two review authors independently assessed studies for eligibility, extracted data, and assessed risk of bias. We assessed the quality of the evidence using GRADE methodology.

Main results: We included 20 studies, with 3305 participants. Three studies included children only. The others included predominantly young adults; approximately 60% were male. Seven studies recruited people with ankle sprains only. Most studies were at low or unclear risk of bias; however, two were at high risk of selection bias, three were at high risk of bias from lack of blinding, and five were at high risk of selective outcome reporting bias. Some evidence relating to pain relief was high certainty. Other evidence was either moderate, low or very low certainty, reflecting study limitations, indirectness, imprecision, or combinations of these. Thus, we are certain or moderately certain about some of the estimates, and uncertain or very uncertain of others. Eleven studies, involving 1853 participants compared NSAIDs with paracetamol. There were no differences between the two groups in pain at one to two hours (1178 participants, 6 studies; high-certainty evidence), at days one to three (1232 participants, 6 studies; high-certainty evidence), and at day seven or later (467 participants, 4 studies; low-certainty evidence). There was little difference between the groups in numbers of participants with minimal swelling at day seven or later (77 participants, 1 study; low-certainty evidence). Very low-certainty evidence from three studies (386 participants) means we are uncertain of the finding of little difference between the two groups in return to function at day seven or later. There was low-certainty evidence from 10 studies (1504 participants) that NSAIDs may slightly increase the risk of gastrointestinal adverse events compared with paracetamol. There was low-certainty evidence from nine studies (1679 participants) of little difference in neurological adverse events between the NSAID and paracetamol groups. Six studies, involving 1212 participants compared NSAIDs with opioids. There was moderate-certainty evidence of no difference between the groups in pain at one hour (1058 participants, 4 studies), and low-certainty evidence for no difference in pain at days four or seven (706 participants, 1 study). There was very low-certainty evidence of no important difference between the groups in swelling (84 participants, 1 study). Participants in the NSAIDs group were more likely to return to function in 7 to 10 days (542 participants, 2 studies; low-certainty evidence). There was moderate-certainty evidence (1143 participants, 5 studies) that NSAIDs were less likely to result in gastrointestinal or neurological adverse events compared with opioids. Four studies, involving 240 participants, compared NSAIDs with the combination of paracetamol and an opioid. The applicability of findings from these studies is in question because the dextropropoxyphene combination analgesic agents used are no longer in general use. Very low-certainty evidence means we are uncertain of the findings of no differences between the two interventions in the numbers with little or no pain at day one (51 participants, 1 study), day three (149 participants, 2 studies), or day seven (138 participants, 2 studies); swelling (230 participants, 3 studies); return to function at day seven (89 participants, 1 study); and the risk of gastrointestinal or neurological adverse events (141 participants, 3 studies). No studies reported re-injury rates. No studies compared NSAIDs with oral complementary and alternative medicines, AUTHORS' CONCLUSIONS: Compared with paracetamol, NSAIDs make no difference to pain at one to two hours and at two to three days, and may make no difference at day seven or beyond. NSAIDs may result in a small increase in gastrointestinal adverse events and may make no difference in neurological adverse events compared with paracetamol. Compared with opioids, NSAIDs probably make no difference to pain at one hour, and may make no difference at days four or seven. NSAIDs probably result in fewer gastrointestinal and neurological adverse effects compared with opioids. The very low-certainly evidence for all outcomes for the NSAIDs versus paracetamol with opioid combination analgesics means we are uncertain of the findings of no differences in pain or adverse effects. The current evidence should not be extrapolated to adults older than 65 years, as this group was not well represented in the studies.

Trial registration: ClinicalTrials.gov NCT01827475 NCT00446797 NCT00140933 NCT01189773 NCT00954785.

Conflict of interest statement

Peter Jones: employed by the Auckland District Health Board, and has received unrelated research support from the Health Research Council of New Zealand; the Green Lane Research and Education Fund; and the Auckland District Health Board Charitable Trust, known as A+ Trust.

Rain Lamdin: nothing to declare

Stuart R Dalziel: employed by the Auckland District Health Board; is an advisor for the Pharmaceutical Management Agency (PHARMAC), New Zealand; and receives research support (unrelated to this manuscript) from the Health Research Council of New Zealand; Cure Kids New Zealand; Auckland Medical Research Foundation; the Auckland District Health Board Charitable Trust, known as A+ Trust (New Zealand); and the National Health and Medical Research Council (NHMRC) (Australia).

Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Figures

1

Study flow diagram for update

2

'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study

3

'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies

4

Forest plot of comparison: 4 NSAID versus other oral analgesics, outcome: 4.1 Pain at

5

Forest plot of comparison: 4 NSAID versus other oral analgesics, outcome: 4.2 Gastrointestinal adverse events.

6

Forest plot of comparison: 4 NSAID versus other oral analgesics, outcome: 4.3 Neurological adverse events.

1.1. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 1: Pain

1.2. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 2: Little or no pain

1.3. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 3: Pain on days 1 to 3 (VAS: 0 to 100 mm: worst)

1.4. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 4: Little or no pain on days 1 to 3

1.5. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 5: Pain on days 4 to 6 (VAS: 0 to 100 mm: worst)

1.6. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 6: Pain on day 7 or later (VAS: 0 to 100 mm: worst)

1.7. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 7: Little or no pain on day 7 or later

1.8. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 8: Swelling on days 0 to 3

1.9. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 9: Swelling on days 4 to 6 (VAS: 0 to 100 mm: worst)

1.10. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 10: Swelling on day 7 or later

1.11. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 11: Little or no swelling on day 7 or later

1.12. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 12: Return to function within 7 days

1.13. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 13: Return to function in 7 days or later

1.14. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 14: Time to return to full activity (days)

1.15. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 15: Range of motion (degrees)

1.16. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 16: Gastrointestinal adverse events

1.17. Analysis

Comparison 1: NSAIDs versus paracetamol, Outcome 17: Neurological adverse events

2.1. Analysis

Comparison 2: NSAID versus opioid, Outcome 1: Pain

2.2. Analysis

Comparison 2: NSAID versus opioid, Outcome 2: Little or no pain

2.3. Analysis

Comparison 2: NSAID versus opioid, Outcome 3: Pain on days 4 to 6 (VAS: 0 to 100 mm: worst)

2.4. Analysis

Comparison 2: NSAID versus opioid, Outcome 4: Pain on day 7 or later (VAS: 0 to 100 mm: worst)

2.5. Analysis

Comparison 2: NSAID versus opioid, Outcome 5: Swelling on day 7 or later

2.6. Analysis

Comparison 2: NSAID versus opioid, Outcome 6: Return to function within 7 days

2.7. Analysis

Comparison 2: NSAID versus opioid, Outcome 7: Return to function in 7 days or later

2.8. Analysis

Comparison 2: NSAID versus opioid, Outcome 8: Gastrointestinal adverse events

2.9. Analysis

Comparison 2: NSAID versus opioid, Outcome 9: Neurological adverse events

3.1. Analysis

Comparison 3: NSAID versus combination analgesic (paracetamol + opioid), Outcome 1: Little or no pain

3.2. Analysis

Comparison 3: NSAID versus combination analgesic (paracetamol + opioid), Outcome 2: Little or no pain on days 1 to 3

3.3. Analysis

Comparison 3: NSAID versus combination analgesic (paracetamol + opioid), Outcome 3: Little or no pain on days 4 to 6

3.4. Analysis

Comparison 3: NSAID versus combination analgesic (paracetamol + opioid), Outcome 4: Little or no pain on day 7 or later

3.5. Analysis

Comparison 3: NSAID versus combination analgesic (paracetamol + opioid), Outcome 5: Return to function in 7 days or later

3.6. Analysis

Comparison 3: NSAID versus combination analgesic (paracetamol + opioid), Outcome 6: Gastrointestinal adverse events

3.7. Analysis

Comparison 3: NSAID versus combination analgesic (paracetamol + opioid), Outcome 7: Neurological adverse events

4.1. Analysis

Comparison 4: NSAID versus other oral analgesics, Outcome 1: Pain at

4.2. Analysis

Comparison 4: NSAID versus other oral analgesics, Outcome 2: Gastrointestinal adverse events

4.3. Analysis

Comparison 4: NSAID versus other oral analgesics, Outcome 3: Neurological adverse events

References

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