fracture surgery: weak opiates after discharge as good as oxycodone

 Patients sent home after surgical management of orthopedic fractures do as well with acetaminophen with codeine as with oxycodone (see opiates after fracture mild as good jama2021 in dropbox or doi:10.1001/jamanetworkopen.2021.34988) 

  

Details:  

-- 120 patients in Australia with one or more acute orthopedic fractures requiring surgical fixation were randomized into the oxycodone group versus acetaminophen plus codeine, from July 2016 to August 2017 

-- mean age 37, 45% men, BMI 28, at least one comorbidity 22%, recreational drug user 2%, weekly alcohol consumption 39%, premorbid pain medication use 7%, non-smoker 70% 

-- one fracture in 87%/more than one 13%; mechanism of injury road-related 29%, fall 35%, blunt or crush trauma 34%; upper extremity fracture 29%, lower extremity 56%, pelvis 3%, multiple regions 12% 

-- all patients had sustained a non-pathological fracture of a long bone, or the pelvis, patella, calcaneus, or talus, all treated with surgical fixation 

-- patients were discharged with either oxycodone 5 mg or acetaminophen 500 mg with codeine 8 mg, to take one or two tablets four times daily for maximum duration of two weeks, with titration down and cessation at three weeks 

-- data collection was done in-person at baseline and by telephone on days 3, 7, 14, and 21 post-discharge 

-- main outcome: the mean of daily pain scores collected days 1-7 of treatment measured by the Numerical Pain Rating Scale (NRS), with the patient rating their pain from 0 to 10 for the previous 24 hours 

    -- baseline NRS score: mean pain 4.2, worst pain 6.5 

-- key secondary outcomes: EuroAol 5-Dimernsion 5-Level Questionnaire (EQ-5D-5L, a scale measuring the five dimensions of mobility, self-care, usual activities, pain and discomfort, and anxiety and depression), worst pain, medication adverse event, Global Perceived Effect [the patient compared their pain to what it was when the injury first occurred, from a score of -5 (vastly worse) to 0 (no change), to 5 (completely recovered), measured on days 7, 14, and 21)], and return to work 

    -- baseline EQ-5D-5L: mobility problems in 70%, self-care problems in 93%, usual activities problems in 100%, pain problems in 98%

    -- baseline anxiety and depression: problems in 36% 

 

Results: 

-- medications taken for days 1-7: 

    -- oxycodone: mean morphine equivalent (MME) 32.9 mg  

    -- acetaminophen plus codeine: MME 5.5 mg 

 

--22 patients ended the study at week 1: 

    -- oxycodone group: 10 patients (3 for side effects, 7 for pain manageable with OTC or no analgesics) 

    -- acetaminophen with codeine group: 12 patients (4 for side effects, 4 for pain manageable with OTC or no analgesics, and 4 for uncontrolled pain) 

-- 83 continued treatment into week 2: 

    -- oxycodone group: 14 recovered, 1 received alternate analgesic, 2 were readmitted for infection 

    -- acetaminophen with codeine group: 14 recovered, 1 was readmitted for infection 

--50 continue treatment into week 3: 

    -- oxycodone group: 1 recovered, 2 were readmitted 

    -- acetaminophen with codeine group: 4 recovered, 1 was readmitted 

 

-- Primary outcome, Numerical Pain Rating Scale: 

    -- oxycodone: 4.04 (3.67-4.41) 

    -- acetaminophen with codeine: 4.54 (4.17-4.90) 

        -- between-group difference was not statistically significant 

        -- no significant difference if individuals were excluded who never started the pain meds, or those who discontinued meds because of adverse effects, or those who discontinued meds for any other reason 

 

-- Secondary outcomes: 

    -- none of the following reached clinical significance:

        -- mean pain NRS score, days 1-7 or days 1- 21 

        -- worst pain NRS score, days 1-7 or days 1- 21 

        -- mean daily tablet use: 4.36 for oxycodone vs 4.59 for acetaminophen with codeine 

        -- mean daily adverse effects , days 1-7 or days 1- 21 

            -- however, for days 1- 21, there were 8.68 adverse effects with oxycodone versus 5.66 with acetaminophen plus codeine, with p=0.06   (ie, almost statistically significant with more adverse effects with oxycodone) 

        -- EQ-5D-5L: day 3 or day 7 

        -- return to work: day 3 or 7 or 14 or 21 

        -- Global Perceived Effect: day 7 or 14 or 21 

        -- overall satisfaction 

        -- overall complications (includes infection, reoperation, readmission, DVT, or PE 

 

-- at the end of the study patients were asked what medication they thought they were taking: 

    -- those on oxycodone: 8 patients (13.5%) correctly thought they were taking oxycodone, 18 patients (30.5%) incorrectly thought that they were taking acetaminophen with codeine, and 33 patients (56%) could not guess 

    -- those on acetaminophen with  codeine: 21 patients (34.5%) correctly thought they were taking this combination, 16 (26.2%) incorrectly thought they were taking oxycodone, and 24 (39.3%) could not guess 

 

Commentary: 

-- it was pretty clear in the study that oxycodone provided no benefit over low-dose acetaminophen with codeine (only 8mg) in the first week after surgery, despite its six-fold increased dose of morphine equivalents, and this was true after three weeks of treatment. Throughout the analysis, it was clear that there was no clinically important benefit to the stronger opiate 

-- 31% of patients did not require any study treatment beyond day 7 (though, by the design of this study where patients were given a set number of pills, patients may have continued to take the pill "doctor-prescribed" instead of trialing a non-opiate earlier: ie, possibly many more patients could have switched to a non-opiate at a much earlier date..)

-- and majority could not guess which med they were taking, and only 13.5% on the much stronger oxycodone thought they were on that stronger med...

 

-- there are many studies suggesting that the benefit of opiates is questionable and the addictive potential quite high for the patient and those around them (see http://gmodestmedblogs.blogspot.com/search?q=opiates for a general search on the slew of blogs on opiate-related articles):

-- some articles on opiate use for surgery:

    -- a study found that adding acetaminophen plus ibuprofen decreased the need for morphine in the 1^st 24 hours after total hip arthroplasty (see http://gmodestmedblogs.blogspot.com/2019/03/decreasing-opiates-after-total-hip.html ) 

    -- a study finding that  clinicians are way overprescribing opiates, much more than the patients need, with left-over opiates (on average 80% of what was prescribed); and each additional opiate refill was associated with a 44% increase in opiate misuse (defined as having a subsequent diagnostic code for opioid dependence, abuse, or overdose): see http://gmodestmedblogs.blogspot.com/2018/01/post-op-surgery-opiates-and-subsequent.html 

    --a surgery study found that a cancer center using an ultra-restrictive opioid prescription protocol for patients getting major gyn surgery led to dramatically fewer opiates given but found no difference in post-op pain compared to before this intervention:  http://gmodestmedblogs.blogspot.com/2019/01/restrictive-postop-opioids-fewer-given.html

--some articles on opiate use in EDs:

    -- ED study finding that patients with acute extremity pain did not seem to have much difference if given an opiate vs ibuprofen 400 plus acetaminophen 1000: http://gmodestmedblogs.blogspot.com/2017/11/opioids-not-better-than-nsaids-for.html

    -- ED study finding that opiates were no better than naproxen for patients with acute low back pain: http://gmodestmedblogs.blogspot.com/2015/10/opiates-for-acute-low-back-pain.html 

    -- systematic review of 20 trials with 1613 pateints finding that there was greater pain reduction with NSAIDs than opiates and less need for rescue analgesia for acute pain from kidney stones (typically considered one of the worst pains). eg see https://www.ncbi.nlm.nih.gov/pubmed/15178585 , or see for example: Teichman J. N Engl J Med 2004; 350:684)

    -- dental societies have pushed to decrease opiate prescribing, noting that ibuprofen 400 mg plus acetaminophen 1000 mg was superior to opioid-containing meds: http://gmodestmedblogs.blogspot.com/2018/04/new-opioid-guidelines-or-directives.html

    -- and simply letting ED clinicians know about the frequency of their opiate prescriptions (which they often underestimated, by 65% in this study) led to significantly fewer subsequent prescriptions 12 months later: http://gmodestmedblogs.blogspot.com/2018/03/ed-intervention-to-decrease-opioids.html

-- article on opiate use for chronic pain:

    --opiates are not better for chronic back/hip/knee pain http://gmodestmedblogs.blogspot.com/2018/03/opioids-not-better-for-chronic.html . and many non-drug modalities work (eg yoga, tai chi, mindfulness training, home-based CBT)

-- some other articles on the striking addiction potential of opiates after short courses of prescribed opiates, and subsequent opiate misuse:

    -- the future misuse of opiates after surgery was more related to the length of opiate prescriptions than the dose prescribed (blog noted above): http://gmodestmedblogs.blogspot.com/2018/01/post-op-surgery-opiates-and-subsequent.html

    -- an interesting/pretty powerful retrospective study in older patients who were naive to opiates (mean age 69) finding that those seeing high-intensity opiate prescribing ED physicians vs low-intensity ones for similar clinical conditions had a 30% increased likelihood of long-term use of opiates (see http://gmodestmedblogs.blogspot.com/2017/02/opiate-prescribing-in-elderly-and.html /)

    --12th graders at low-risk of future subsequent substance use disorder but were prescribed opiates for a clinical indication were at a 3-fold increased risk of SUD by age 23 (see http://gmodestmedblogs.blogspot.com/2015/10/prescribed-opioids-and-future.html)

--and, bottom line: an article noting that there is a much higher opiate prescription rate post-op in the US than in the rest of the world: http://gmodestmedblogs.blogspot.com/2021/01/opioids-very-high-rate-of-prescriptions.html

-- one reason opiates are prescribed so readily postoperatively is that many surgeons feel that patients should not be in pain after they go home, and they should have access to very strong pain medications at two in the morning when they may be in a lot of pain. Certainly a legitimate concern, but the above studies/data suggest otherwise. Perhaps, for the outlier individuals who may benefit from opiates, there could be a mechanism to give a very small number of opiates to selected people (eg a few pills of a lower potency opiate), with the warnings about their addictive potential and the benefit of nonopiates, and a mechanism for close followup/interaction with those needing the opiates (one needs to be careful in applying aggregate results from studies to individual patients: there are likely to be "outliers" who actually do benefit from opiates)

 

Limitations: 

-- the study was done in a single hospital in a region in Australia with a high level of associated economic disadvantage, which could limit generalizability to other areas

    --these patients in the study were pretty young, healthy, and did not use lots of recreational drugs or alcohol, also limiting generalizability

-- they used a very low dose of codeine: 8mg. there was an available med in the US (Tylenol #1) which had acetaminophen 300mg and codeine 7.5mg, though i cannot find that it is still available. maybe it should be???? or based on this study having the 500mg dose of acetaminophen bundled with 8mg codeine should be available??

-- these results also did not include fragility fractures in older people, which also might limit generalizability to older folks

-- they did not include non-opiates as a potentially viable alternative to even the mild opiate acetaminophen with codeine 

-- adverse effects for oxycodone were almost significantly more than to acetaminophen plus codeine, and a larger study might find them statistically significantly increased 

  

So, bottom line from the above Australian study, as well as the aggregate of other cited studies: opiates are largely not indicated for the treatment of noncancer acute or chronic pain, even in the setting of surgery, and when needed could be a lower potency and for short periods of time.  the adverse personal, family, and broader social effects of prescribed opiates are profound (eg more than 1/2 of those with future misuse started on opiates from pills that happen to be at home; and 4 of 5 new heroin users started out misusing prescription painkillers: https://www.asam.org/docs/default-source/advocacy/opioid-addiction-disease-facts-figures.pdf). the risks outweigh the benefits, and there should be systems developed to make sure that those (likely few) patients requiring opiates for pain control can receive them in a controlled way. And there should be much weaker forms of opiates available: eg the acetaminophen 500mg/codeine 8mg, used in this study

geoff

 

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