decreasing opiates after total hip arthroplasty

A recent study found that acetaminophen plus ibuprofen significantly decreased the need for morphine in the 1^st 24 hours after a total hip arthroplasty (see hip arthroplasty ibup apap jama2019 in dropbox, or doi:10.1001/jama.2018.22039).

Details:

-- 556 patients in 6 Danish hospitals receiving total hip arthroplasty (THA)

-- mean age 67, 50% women

-- randomized to acetaminophen 1000 mg plus ibuprofen 400 mg, acetaminophen 1000 mg plus matched placebo, ibuprofen 400 mg plus matched placebo, or acetaminophen 500 mg plus ibuprofen 200 mg (1/2 dose). All started one hour prior to surgery.

-- Primary outcomes: 24-hour morphine consumption using patient-controlled analgesia (PCA), and proportion of patients with one or more serious adverse events within 90 days

Results:

-- median 24-hour morphine consumption

    -- acetaminophen 1000 plus ibuprofen 400: 20 mg of morphine (0-148 mg)

    -- acetaminophen 1000 mg alone: 36 mg (0-166 mg)

    -- ibuprofen 400 mg alone: 26 mg (2-139 mg)

    -- acetaminophen 500 plus ibuprofen 200: 28 mg (2-145 mg)

-- the median difference between groups:

    -- acetaminophen plus ibuprofen vs acetaminophen alone was 16 mg less morphine (6.5-24 mg), p<0.001

    -- half strength acetaminophen plus ibuprofen vs acetaminophen alone: 8 mg less morphine (-1 to 14 mg), p=0.001

    -- acetaminophen 1000 mg plus ibuprofen 400 mg vs ibuprofen alone: 6 mg less morphine (-2 to 16 mg), p=0.002

-- the difference in morphine consumption was not statistically significant for the acetaminophen plus ibuprofen group vs half-strength acetaminophen plus ibuprofen (8mg morphine, p=0.005) , or for the acetaminophen alone group vs ibuprofen alone (10 mg p=0.004). [their a priori definition for these comparisons was p=0.0042, so not sure why this last one did not make it as statistically significant; and the first one was pretty close…]

-- there was no significant difference in the ibuprofen alone group vs the half strength acetaminophen plus ibuprofen group

-- Pain scores by visual analog scale of 0-100:

    -- at 6 hours, the pain score was lower in those on ibuprofen 400 mg plus acetaminophen 1000 mg vs just acetaminophen (decrease of 8mm)

    -- at 24 hours the resting pain score on this combo was 11 mm lower than on acetaminophen, 8mm less than on ibuprofen alone, and 6 mm less than the ½ dose regimen

    -- And these lower pain scores were with the addition of less morphine by PCA.

-- the proportion of patients with serious adverse events receiving ibuprofen was 15% and in the acetaminophen alone was 11%, not statistically significant difference

Commentary:

-- the reason i am bringing up this study is that it reflects a real shift in our general approach to pain management, and provides more evidence-based backing to the approach of minimizing opiate use as much as possible. In this study, morphine usage by patient-controlled analgesia was cut in half by taking ibuprofen 400 mg plus acetaminophen 1000 mg, and the pain scores of these patients was significantly lower than those on just acetaminophen and with the increased morphine. the old model of automatically prescribing lots of  opioids is pretty rapidly changing:

    -- ED studies have shown than non-opioid pain meds works as well as opiates; eg one 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

    -- an 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 

    -- another ED study finding that prescribing opiates by high-opiate prescribers led to 30% increase in long-term opiate use, when compared to low-opiate prescribers seeing similar patients: http://gmodestmedblogs.blogspot.com/2017/02/opiate-prescribing-in-elderly-and.html 

    --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

    --a number of surgery articles have found 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 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

    --NSAIDs may be more effective than opiates for acute pain from kidney stones (typically considered one of the worst pains). eg see https://www.ncbi.nlm.nih.gov/pubmed/15178585 for a systematic review of 20 trials with 1613 pateints finding that there was greater pain reduction with NSAIDs and less need for rescue analgesia.

   --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

-- the CDC has reported on decreasing opiate prescriptions as of 2015: see http://gmodestmedblogs.blogspot.com/2017/07/decreasing-opiate-prescriptions.html

--and, yesterday's New England Journal had an article on initial opiate prescriptions among US commercially-insured patients in Blue Cross-Blue Shield from 2012 to 2017, from administrative claims data (see opiate prescribing decreasing NEJM2019 in dropbox, or DOI: 10.1056/NEJMsa1807069), finding that

    -- the monthly initial opiate prescripitons decreased by 54% from 2012 to 2018

    -- the number of opiate-prescribing physicians decreased 29% from 114,043 to 80,462

    -- prescribing >3 day supply of opiates decreased by 57% and the number of initial prescripitons with duration >7 days decreased 68%

    -- the incidence of prescribing >50 MME/d of opiates decreased 57% and >90 MME/d by 67%

    -- but the number of physiciians prescribing >3-day supply or >50 MME/d did not change much

    -- primary care physicians were the most likely to write long-duration opioid therapy (approx 80% of initial scripts were >3-day supply, 40% were >7-day supply)

    -- dentists were the least likely to write long-duration prescriptions

    -- high-dose initial scripts were mostly from specialists, esp for surgery-related pain

    -- there were important regional differences in prescribing patterns, eg: more long-duration scripts in the South; higher-dose initial pscripts in the West

so, a pretty positive situation. there does seem to be an increasing consciousness about avoiding or limiting opiate prescribing 

However, as mentioned in prior blogs, it is really hard to get patients who are already on opiates off them. often difficult even just to reduce doses. so, the primary goal is really to avoid starting them in the first place whenever possible. for those already on opiates, it really is essential to develop much more extensive and supportive programs to help them.  for example, it really seems unethical/unconscionable that there is not much easier access to buprenorphine/naltrexone/methadone for patients. and monitored, regulated programs for transitioning patients to these meds (eg, see http://gmodestmedblogs.blogspot.com/2018/01/immediate-access-to-opioid-agonist.html )

geoff

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