acute musculoskeletal pain: topical NSAIDs as first-line

 The Am College of Physicians and Am Acad of Family Physicians just released their joint clinical guidelines on the non-pharmacologic and pharmacologic treatment of acute non-low back injuries in adults (see pain guidelines acute non-low back AIM2020 in dropbox, or doi:10.7326/M19-3602).

Details:

--they used a network meta-analysis to compare the effectiveness of different therapies, including 207 trials with 32,959 patients, evaluating:

    --pain relief at <2hrs and at 1-7 days

    --physical function

    --symptom relief, typically defined as reaching full resolution of symptoms, or >50% reduction in pain score (differed in studies)

    --treatment satisfaction (varied in the different studies, but typically the patient's overall assessment of treatment satisfaction or efficacy)

    --GI tract, dermatologic, and neurologic adverse effects

--causes of acute pain varied in the studies: 48% had mix of musculoskeletal injuries, 29% patients with sprains, 6% with whiplash, 5% muscle stains

--sites of injuries: isolated ankle injuries in 29%, various injuries in 26%, neck injuries 11%, limb injuries 9%

--median pain score: on 10-cm visual analog scale (VAS) was 6.5 of 10cm

Results (will highlight the most significant ones):

--pain relief <2 hours:

    --nonpharm:

        --acupressure WMD (weighted mean difference, vs placebo) -1.59 cm (1 cm difference considered clinically significant); joint manipulation WMD -1.75; TENS WMD -1.94

    --pharm:

        --acetaminophen WMD -1.03; acetaminophen plus oral diclofenac WMD -1.11; topical NSAID -1.02 (oral NSAIDs almost made the cut, with WMD -0.93); topical NSAID plus menthol gel WMD -1.68

--pain relief 1-7 days

    --nonpharm:

        --acupressure WMD -2.09 cm; TENS WMD -1.18; of interest, supervised rehab increased pain with WMD 1.06

    --pharm:

        --acetaminophen WMD -1.07; acetaminophen plus opioids WMD -1.71; topical NSAID -1.08 (oral NSAIDs almost made the cut, with WMD -0.99)

--physical function:

    --nonpharm:

        --acupressure WMD 1.59 cm

    --pharm:

        --topical NSAID WMD 1.66 (oral NSAIDs did not make the cut, with WMD 0.73)

--treatment satisfaction:

    --nonpharm:

        --none

    --pharm:

        --topical NSAID OR 5.20 (OR=odds ratio)

--symptom relief:

    --nonpharm:

        --laser therapy OR 32.08; mobilization OR 7.99

    --pharm:

        --acetaminophen plus opioids OR 1.44; acetaminophen plus oral diclofenac OR 3.72; oral NSAIDs OR 3.10; topical NSAIDs OR 6.39; topical NSAIDs plus menthol gel OR 13.34

--Adverse events:

    --derm: none

    --GI: only with oral NSAIDs OR 1.77, and opiates

    --neuro: opiates, but also ibuprofen plus cyclobenzaprine OR 4.91

Recommendations:

1. clinicians should treat acute pain from non-low back musculoskeletal injuries with topical NSAIDs, with or without menthol gel, as first-line therapy to reduce or relieve symptoms, including pain; improve physical functioning; and improve the patient's treatment satisfaction (strong recommendation; moderate-certainty evidence)

    --topical NSAIDs were the only intervention that improved all outcomes in patients and were among the most effective treatments for pain reduction in <2hours, and at 1-7 days; function; and symptom relief (full resolution of symptoms). of note, topical menthol gel also improved pain at <2 hours, and the guideline writers thought there might be improved benefit adding this to topical NSAIDs and unlikely harm (though no clear evidence for this)

2a. use oral NSAIDs to reduce or relieve symptoms, including pain, and to improve physical function, or with oral acetaminophen to reduce pain (conditional recommendation; moderate-certainty evidence)

    --oral NSAIDs reduced pain at <2hrs and at 1-7 days, similarly for acetaminophen

        --there were more GI adverse events with oral NSAIDs

2b. use specific acupressure to reduce pain and improve physical function, or transcutaneous electrical nerve stimulation (TENS) to reduce pain (conditional recommendation; low-certainty evidence)

    --specific acupressure improved pain at 1-7 days (moderate certainty evidence), and <2 hrs (low-certainty evidence). TENS improved pain at <2hrs and 1-7days

    

3. not use opioids, including tramadol (conditional recommendation; low-certainty evidence)

    --acetaminophen plus opioids reduced pain at 1-7 days with high-certainty evidence, with only a small effect in <2 hrs. but none of these opioid studies found benefit in more than 1 outcome, which was the writers' threshold of benefit. and there were lots of GI and neurologic adverse effects. and we do all know the potential for patients continuing to use opiates in the long-term (there have been myriad blogs in the past on opiate overuse: see http://gmodestmedblogs.blogspot.com/2019/01/restrictive-postop-opioids-fewer-given.html

Restrictive postop opioids: fewer given, no diff in pain Another article came out on the feasibility of prescribing fewer opiates post-surgery, this one finding equivalent pain control after gynec... gmodestmedblogs.blogspot.com

 for example, which also references some prior important studies). as a result of the limited benefit and profound long-term potential effects, the decision was to NOT prescribe opiates.

Commentary:

--as we all know (only too well), musculoskeletal injuries are remarkably common: in 2010 there were 65 million health care visits for them in the US and estimated annual cost of $176.1 billion

-- since there are not actual randomized controlled trials directly comparing all of the different therapies, a network meta-analysis provides a mathematical comparison of the relative effectiveness of different therapies vs placebo, for example, and compares the extent of the benefit found from these actual studies to see if one therapy were likely more effective than another and by how much. this type of analysis is clearly less rigorous than actual head-to-head comparisons, since the actual individual studies analyzed were likely very different in patient selection, patient demographics, types of injuries, measured outcomes, etc

--it was pretty striking in this analysis both that topical NSAIDs (the only one used in the studies was diclofenac gel 1%) were so multidimensionally effective, but also that in the context of the large numbers of studies done, that some meds or combinations were not assessed: eg cyclobenzaprine or other "muscle relaxants", topical lidocaine or capsaicin). also, it does seem that the combo of topical diclofenac with menthol is pretty good

--my own bias is that nonpharmacologic therapies and nonsystemic pharmacologic ones are optimal: fewer systemic adverse events. for the meds, i personally try to use topical meds (eg diclofenac 1%, capsaicin, and/or lidocaine) over systemic meds (i am particularly concerned about NSAIDs, which are over-the-counter but associated with so many adverse effects, especially in older people, including hypertension, heart failure, kidney disease, GI distress and bleeds, as well as many less common ones). avoiding systemic meds has also led me to be very aggressive with injections (steroids plus lidocaine) for trigger points, muscle spasms, etc, and with pretty spectacular results

--also, i did not include all of their notations in the results section above about the quality of the studies or the strength of their recommendations. or even the confidence intervals. too much data. but the article has it all....

limitations:

--as noted above, network meta-analyses are complex mathematical approaches to try to simulate head-to-head comparisons, but are very limited by the discordant designs of the actual studies.

--and, meta-analyses themselves are fraught: in the above review, there were varying definitions for pain relief, or symptom relief. so, combining the studies is adding pretty different animals together (no offense to the animals)

--and, there was no analysis (?from lack of studies) of some pretty commonly used approaches, including other topical meds, muscle relaxants, heat/cold, supports (ACE wraps, boots, etc), injections...

--no ability to differentiate the efficacy of the different treatment for different musculoskeletal sites

so, overall an impressive conclusion that topical NSAIDs are the best. and, though many of the individual studies were not the best (leading to many of the writers noting that there was low-certainty evidence), i think this should really inform our practice of not jumping to oral NSAIDs and muscle relaxants as the optimal combination of initial therapy (as seems to be the standard, at least from what i see in Boston). too many adverse effects and too little evidence of benefit...

but, the real benefit of such a network meta-analysis is that it really should prompt high quality RCTs to give the best answers. eg, comparing diclofenac 1% gel with that in combo with menthol gel

geoff

 

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