Abstract
Introduction
Injury of the lateral ligament complex of the ankle joint occurs in about one in 10,000 people per day, accounting for a quarter of all sports injuries.
Methods and outcomes
We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of acute ankle sprains? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).
Results
At this update, searching of electronic databases retrieved 158 studies. After deduplication and removal of conference abstracts, 97 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 48 studies and the further review of 49 full publications. Of the 49 full articles evaluated, one systematic review and four RCTs were added. We performed a GRADE evaluation for four PICO combinations.
Conclusions
In this systematic overview, we categorised the efficacy for three interventions, based on information relating to the effectiveness and safety of oral NSAIDs versus placebo, oral versus topical NSAIDs, selective COX-2 inhibitors versus other NSAIDs, and topical NSAIDs versus placebo.
Key Points
Injury of the lateral ligament complex of the ankle joint occurs in about one in 10,000 people per day, accounting for a quarter of all sports injuries.
Pain may be localised to the lateral side of the ankle.
Residual complaints include joint instability, stiffness, and intermittent swelling, and are more likely to occur after more extensive cartilage damage.
Recurrent sprains can add new damage and increase the risk of long-term degeneration of the joint.
In this overview, we have searched for RCTs and systematic reviews of RCTs on the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in people with acute ankle sprain.
NSAIDs might be beneficial when used in combination with immobilisation for people with ankle sprain, although possible side effects should be taken into consideration.
Oral NSAIDs may be more effective than placebo at improving pain and swelling in the short term up to 2 weeks, but we don't know about longer-term effects.
We found insufficient evidence on the effects of selective COX-2 inhibitors versus other NSAIDs.
Topical NSAIDs may be more effective than placebo at reducing pain in the short term at up to 2 weeks, but we don't know about swelling, or about longer-term effects.
We found no RCTs comparing oral NSAIDs with topical NSAIDs.
Clinical context
General background
Ankle sprain is an injury of the lateral ligament complex of the ankle joint. The injury is graded on the basis of severity. Grade 1 is a mild stretching of the ligament complex without joint instability; grade 2 is a partial rupture of the ligament complex with mild instability of the joint (such as isolated rupture of the anterior talofibular ligament); and grade 3 involves complete rupture of the ligament complex with instability of the joint.
Focus of the review
NSAIDS are commonly prescribed. The effectiveness and adverse events are important factors to take into account when NSAIDs are considered as an additive treatment in ankle sprains.
Comments on evidence
We found one systematic review with 28 included RCTs. Quality was limited, and the number of trials per comparison was limited as well. Therefore, conclusions should be drawn with care.
Search and appraisal summary
The literature search was carried out in April 2014. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the overview, please see the Methods section. Searching of electronic databases retrieved 158 studies. After deduplication and removal of conference abstracts, 97 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 48 studies and the further review of 49 full publications. Of the 49 full articles evaluated, one systematic review and four RCTs were added.
Additional information
NSAIDs could be beneficial for treatment of ankle sprains, especially over the short-term.
About this condition
Definition
Ankle sprain is an injury of the lateral ligament complex of the ankle joint. The injury is graded on the basis of severity. Grade 1 is a mild stretching of the ligament complex without joint instability; grade 2 is a partial rupture of the ligament complex with mild instability of the joint (such as isolated rupture of the anterior talofibular ligament); and grade 3 involves complete rupture of the ligament complex with instability of the joint. This gradation has limited practical consequences because both grade 2 and 3 injuries are treated similarly, and grade 1 injuries need no specific treatment after diagnosis. In this review, we have included acute ankle injury in people who are skeletally mature (adults, >16 years of age), and excluded studies undertaken in children, in people with chronic ankle instability, or in people with congenital deformities or degenerative conditions.
Incidence/ Prevalence
Ankle sprain is a common problem in acute medical care, occurring at a rate of about one injury per 10,000 people per day. Injuries of the lateral ligament complex of the ankle form a quarter of all sports injuries.
Aetiology/ Risk factors
The usual mechanism of injury is inversion and adduction (usually referred to as supination) of the plantar flexed foot. Predisposing factors are a history of ankle sprains, ligament hyperlaxity syndrome, and specific malalignment, such as crus varum and pes cavo-varus.
Prognosis
Some sports (e.g., basketball, football/soccer, volleyball) are associated with a particularly high incidence of ankle injuries. Pain and intermittent swelling are the most frequent residual problems, often localised on the lateral side of the ankle. Other residual complaints include mechanical instability and stiffness. People with more extensive cartilage damage have a higher incidence of residual complaints. In the long term, the initial traumatic cartilage damage can lead to degenerative changes, especially if there is persistent or recurrent instability. Every further sprain has the potential to add new damage.
Aims of intervention
To reduce swelling and pain; to restore the stability of the ankle joint; to regain full functional status.
Outcomes
Symptom improvement ability to walk/bear weight, ankle mobility/range of movement, pain, swelling, patient perception of improvement/satisfaction; return to normal activities return to pre-injury level of sports; return to pre-injury level of work; quality of life; adverse effects, including post-intervention complications.
Methods
Search strategy BMJ Clinical Evidence search and appraisal April 2014. Databases used to identify studies for this systematic review include: Medline 1966 to April 2014, Embase 1980 to April 2014, The Cochrane Database of Systematic Reviews 2014, issue 3 (1966 to date of issue), the Database of Abstracts of Reviews of Effects (DARE), and the Health Technology Assessment (HTA) database. Inclusion criteria Study design criteria for inclusion in this review were systematic reviews and RCTs published in English, at least single-blinded, and containing 20 or more individuals (10 in each arm), of whom more than 90% were followed up. There was no minimum length of follow-up. We excluded all studies described as 'open', 'open label', or not blinded unless blinding was impossible. BMJ Clinical Evidence does not necessarily report every study found (e.g., every systematic review). Rather, we report the most recent, relevant and comprehensive studies identified through an agreed process involving our evidence team, editorial team, and expert contributors. Evidence evaluation A systematic literature search was conducted by our evidence team, who then assessed titles and abstracts, and finally selected articles for full text appraisal against inclusion and exclusion criteria agreed a priori with our expert contributors. In consultation with the expert contributors, studies were selected for inclusion and all data relevant to this overview extracted into the benefits and harms section of the overview. In addition, information that did not meet our predefined criteria for inclusion in the benefits and harms section, may have been reported in the 'Further information on studies' or 'Comment' section. Adverse effects All serious adverse effects, or those adverse effects reported as statistically significant, were included in the harms section of the overview. Pre-specified adverse effects identified as being clinically important were also reported, even if the results were not statistically significant. Although BMJ Clinical Evidence presents data on selected adverse effects reported in included studies, it is not meant to be, and cannot be, a comprehensive list of all adverse effects, contraindications, or interactions of included drugs or interventions. A reliable national or local drug database must be consulted for this information. Comment and Clinical guide sections In the Comment section of each intervention, our expert contributors may have provided additional comment and analysis of the evidence, which may include additional studies (over and above those identified via our systematic search) by way of background data or supporting information. As BMJ Clinical Evidence does not systematically search for studies reported in the Comment section, we cannot guarantee the completeness of the studies listed there or the robustness of methods. Our expert contributors add clinical context and interpretation to the Clinical guide sections where appropriate. Data and quality To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). BMJ Clinical Evidence does not report all methodological details of included studies. Rather, it reports by exception any methodological issue or more general issue that may affect the weight a reader may put on an individual study, or the generalisability of the result. These issues may be reflected in the overall GRADE analysis. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table.
GRADE Evaluation of interventions for Ankle sprain: the effects of non-steroidal anti-inflammatory drugs.
| Important outcomes | Quality of life, Return to normal activities, Symptom improvement | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of acute ankle sprains? | |||||||||
| 5 (at least 364) | Symptom improvement | Oral non-steroidal anti-inflammatory drugs (NSAIDs) versus placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for weak methods and incomplete reporting of results |
| 2 (at least 762) | Symptom improvement | Oral selective COX-2 inhibitors versus other oral non-steroidal anti-inflammatory drugs (NSAIDs) | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results; directness point deducted for small numbers of comparators (2 RCTs both studying celecoxib) |
| 2 (at least 762) | Return to normal activities | Oral selective COX-2 inhibitors versus other oral non-steroidal anti-inflammatory drugs (NSAIDs) | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results; directness point deducted for small numbers of comparators (2 RCTs both studying celecoxib) |
| at least 6 (at least 1284) | Symptom improvement | Topical non-steroidal anti-inflammatory drugs (NSAIDs) versus placebo | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for weak methods; consistency point deducted for significant heterogeneity |
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.
Glossary
- Crus varum
Varus of the lower leg (O-leg).
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Pes cavo-varus
Severe high arched, varus foot.
- Visual Analogue Scale (VAS)
A commonly used scale in pain assessment. It is a 10-cm horizontal or vertical line with word anchors at each end, such as 'no pain' and 'pain as bad as it could be'. The person is asked to make a mark on the line to represent pain intensity. This mark is converted to distance in either centimetres or millimetres from the 'no pain' anchor to give a pain score that can range from 0–10 cm or 0–100 mm.
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
Contributor Information
Peter A. A. Struijs, Academic Medical Center, Amsterdam, The Netherlands.
Gino M. M. J. Kerkhoffs, Academic Medical Center, Amsterdam, The Netherlands.
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