Opioids not better than NSAIDs for acute pain

​​Just to add to my stream of blogs on opiates, JAMA just published an ED study of patients with pretty severe extremity pain, where a single dose of an opioid was no better than ibuprofen after 2 hours (see doi:10.1001/jama.2017.16190).

Details:

--411 patients aged 21 to 64 seen in the emergency department of Montefiore Hospital in New York, presenting with acute extremity pain (shoulder or hip, and distally) in 2015-16

--48% female, mean age 37, 60% Latino, 60% had sprain or strain/21% extremity fracture/10% muscle pain/4% contusion

--35% treated with elastic bandage/15% splint/10% cast/8% ice

--randomized to ibuprofen 400 mg with acetaminophen 1000mg; oxycodone 5mg with 325 mg of acetaminophen; hydrocodone 5mg with acetaminophen 300mg, or codeine 30mg with acetaminophen 300mg.

--pain was rated initially, then 1 and 2 hours after med, using the standard Numerical Rating Scale (NRS) of 0-10. A difference of at least 1.3 was considered to be clinically important (a commonly used criterion)

Results:

--mean baseline NRS was 8.7

--about 18% of the patients received rescue analgesics, which was the equivalent of approx 2 morphine equivalents for each group (about 1/4 of an oxycodone 5mg tablet)

--at 2 hours (primary endpoint):

    ​--ibuprofen: NRS pain score decreased by 4.3 (3.6-4.9)

    --oxycodone: NRS decreased by 4.4 (3.7-5.0)

    ​--hydrocodone: NRS decreased by 3.5 (2.9-4.2)

    ​--codeine: NRS decreased by 3.9 (3.2-4.5)

--largest difference in NRS at 2 hours was between the oxycodone and codeine groups (not statistically significant, and did not reach clinically meaningful significance)

--pain difference at 1 hour was also not statistically significant. all of the NRS differences were in the 2.4 to 3.1 range (ie, around 2/3 of the improvement vs the 2 hour scores)

--for patients who received rescue analgesics, there remained no difference in results either statistically or clinically

--there was no difference in NRS scores if patients rated their initial score as a "10" or if they had a documented fracture on xray

--adverse events were not assessed

Commentary:

--there are several studies assessing opioids vs nonopioid analgesia for acute pain coming to the same conclusion: eg post-operative or dental studies not finding codeine/acetaminophen (30-60mg codeine) to be better than ibuprofen/acetaminophen (400/1000mg); another assessed 10mg oxycodone vs 400mg ibuprofen vs 1000mg acetaminophen in the ED, with no analgesic difference at 30 min.  and several studies found no benefit of opiates over NSAIDs for acute renal colic.

--there are some unexpected findings here: the general pain control ladder usually starts with NSAIDs/acetaminophen (sometimes acetaminophen first), then elevating to codeine or other mild opiates (eg tramadol), then to the bigger guns (hydrocodone and oxycodone). the current study found no difference between the opiates (and, if anything, codeine was nonsignficantly better than hydrocodone).

--and, concerns about opiates for acute pain:

    --an ED article found that elderly patients seeing high-opiate-prescribing physicians were 30% more likely to still be getting opiates 6 months later, vs those seeing low-opiate-prescribing physicians for similar problems. see blog http://gmodestmedblogs.blogspot.com/2017/02/opiate-prescribing-in-elderly-and.html 

    ​--and, one of the most powerful to me, was study in 12th-graders who were "legitimately" put on short-term opiates by a physician, who then had a 33% increased likelihood of opioid misuse, with 69% doing so to feel good/get high, or relax/relieve tensions at age 23​. And notably, for those with a  pre-test probability (through a validated questionnaire) of using future opiates had been in the 1.5-3% range​, there was a 3-fold increase in opiate misuse at age 23.  see blog http://gmodestmedblogs.blogspot.com/2015/10/prescribed-opioids-and-future.html 

so,

--this article adds substantially to the several other ED studies, in particular by choosing the commonly used different opiates and strengths and comparing them all to ibuprofen/acetaminophen, again finding no real benefit of the opiates

--and this article fits in with these other studies finding that using opiates in the acute ED setting may well increase the likelihood of opiate use disorder later on

--of course, it is not appropriate to extend these findings to patients with chronic pain.  we really do need more and better studies of this remarkably common situation. i think we have really gone too far in limiting opiate use in these patients (eg , see http://gmodestmedblogs.blogspot.com/2015/12/new-cdc-recommendations-for-opiate.html , a guideline among others pushing for a max morphine equivalent dosing), since

    ​--most of these patients (at least the ones i've seen) have already tried and had no success with the non-opiate pain meds, as well as several non-pharmacologic interventions, and most have very severe injuries/chronic pain that seriously limits their ability to function. and many have used street drugs (much more dangerous) to treat their pain

    ​--there are no studies looking at different opiate doses: eg, taking patients on, for example, 60 morphine equivalents but not responding adequately, then randomizing them to another 60 morphine-equivalents vs placebo)

    --and, there are clearly mu receptor variants which can affect endorphin binding and pain relief (eg, see http://gmodestmedblogs.blogspot.com/2015/03/feelgood-gene.html  ).  the same dose of opiates can have dramatically different effects in different people: one size does not fit all.

--but, it seems to be quite clear from these articles on acute pain, that at least many patients do just fine with non-opiate meds. and, i think at least in Boston, that ED clinicians are prescribing many fewer opiate prescriptions than a few years ago (when it was unusual for anyone with pain to leave the ER without one).  and, this ED shift is likely to decrease opioid use disorder in the future. would be great to see surgeons and dentists decrease their opiate prescribing more. but, still waiting for studies on chronic pain.