We searched the Cochrane Bone, Joint and Muscle
Trauma Group Specialised Register (12 September 2014), the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2014 Issue 8), MEDLINE (1966 to September 2014), EMBASE (1980 to September 2014), CINAHL (1937 to November 2012), AMED (1985 to November 2012), International
Pharmaceutical Abstracts (1970 to November 2012), PEDro (1929 to November 2012), and SPORTDiscus (1985 to November 2012), plus internet search engines, trial registries and other databases. We also searched reference lists of relevant articles and contacted authors of retrieved studies and
pharmaceutical companies to obtain relevant unpublished data.
SELECTION CRITERIA: At least two review authors independently assessed studies for eligibility, extracted data and assessed risk of bias. We assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.
MAIN RESULTS: We included 16 trials, with a total of 2144 participants. Two studies included children only. The other 14 studies included predominantly young adults, of whom over 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, one was at high risk of bias due to incomplete outcome data, and four were at high risk of selective outcome reporting bias. The evidence was usually either low quality or very low quality, reflecting study limitations, indirectness such from as suboptimal dosing of single comparators, imprecision, or one or more of these. Thus we are either uncertain or very uncertain of the estimates.Nine studies, involving 991 participants, compared
NSAIDs with
paracetamol. While tending to favour
paracetamol, there was a lack of clinically important differences between the two groups in
pain at less than 24 hours (377 participants, 4 studies; moderate-quality evidence), at days 1 to 3 (431 participants, 4 studies; low quality), and at day 7 or over (467 participants, 4 studies; low quality). A similar lack of difference between the two groups applied to swelling at day 3 (86 participants, 1 study; very low quality) and at day 7 or over (77 participants, 1 study; low quality). There was little difference between the two groups in return to function at day 7 or over (316 participants, 3 studies; very low quality): based on an assumed recovery of function of 804 per 1000 participants in the
paracetamol group, 8 fewer per 1000 recovered in the
NSAID group (95% confidence interval (CI) 80 fewer to 73 more). There was low-quality evidence of a lower risk of gastrointestinal adverse events in the
paracetamol group: based on an assumed risk of gastrointestinal adverse events of 16 per 1000 participants in the
paracetamol group, 13 more participants per 1000 had a gastrointestinal adverse event in the
NSAID group (95% CI 0 to 35 more).Four studies, involving 958 participants, compared
NSAIDs with
opioids. Since a study of a selective
COX-2 inhibitor NSAID (
valdecoxib) that was subsequently withdrawn from the market dominates the evidence for this comparison (706 participants included in the analyses for
pain, function and gastrointestinal adverse events), the applicability of these results is in doubt and we give only a brief summary. There was low quality evidence for a lack of clinically important differences between the two groups regarding
pain at less than 24 hours, at days 4 to 6, and at day 7. Evidence from single studies showed a similar lack of difference between the two groups for swelling at day 3 (68 participants) and day 10 (84 participants). Return to function at day 7 or over favoured the
NSAID group (low-quality), and there were fewer gastrointestinal adverse events in the selective
COX-2 inhibitor NSAID group (very low quality).Four studies, involving 240 participants, compared
NSAIDs with the combination of
paracetamol and an
opioid. The applicability of findings from these studies is partly in question because the
dextropropoxyphene combination
analgesic agents used are no longer in general use. While the point estimates favoured
NSAID, the very low-quality evidence did not show a difference between the two interventions in the numbers with little or no
pain at day 1 (51 participants, 1 study), day 3 (149 participants, 2 studies), or day 7 (138 participants, 2 studies). Very low-quality evidence showed a similar lack of difference between the two groups applied to swelling at day 3 (reported in two studies) and at day 7 (reported in two studies), in return to function at day 7 (89 participants, 1 study), and in gastrointestinal adverse events (141 participants, 3 studies).No studies compared
NSAIDs with complementary and alternative medicines, and no study reported
re-injury rates.
AUTHORS' CONCLUSIONS: