Category: Orthopedics

We do love to give out opiates in the emergency department. Kidney stone? Opiates. Broken arm? Opiates. Gunshot wound? Opiates. Sore throat? Dexamethasone. And opiates.

So of course we’re here with opiates for your back pain.

In this modern day, we are far, far more judicious than in times of yore, back when pharma had lobbied for pain to become the “fifth vital sign”. But, nonetheless, those patients who are struggling to manage despite non-opiate analgesia frequently end up with some sort of small supply to try and resolve an acutely painful condition.

The OPAL trial, published in The Lancet, is yet another in a series of trials decrying the disutility of virtually anything for back pain – in the context of prior work diminishing the efficacy of skeletal muscle relaxants, as well as even acetaminophen added to ibuprofen. In this trial, patients with “acute” low back pain were prescribed an oxycodone-based opiate or matching placebo, and their functional recovery was assessed in follow up. Unfortunately, no advantage was seen for patients randomized to oxycodone, while there were small, but likely real, risks for opiate misuse at later intervals.

However, does this trial apply to the emergency department?

• Patients were eligible if they had low back pain for up to 3 months. This is not exactly “acute” – especially since early versions of the protocol excluded patients whose back pain had been ongoing for less than 2 weeks.
• Modified-release oxycodone-naloxone was the opiate of choice in this Australian trial. The naloxone itself does not exert much influence on the analgesic effect, but the preparation itself differs from preparation used commonly in the emergency department.
• The follow-up interval was at six weeks, a good patient-oriented timeframe for long-term clinical resolution. However, emergency department treatment tends to choose opiate analgesia with the goal of short-term mobilization and return to activity, so 48- or 72- hour relief or functioning may be more relevant.

The most notable problem with this trial is not, in fact, the trial itself. Rather, the issue remains the paucity of true short-term data regarding any added benefit for the minimally effective quantity of opiates usually dispensed from the emergency department. Spring into action, team!

“Opioid analgesia for acute low back pain and neck pain (the OPAL trial): a randomised placebo-controlled trial”

The new hotness of the day is the piece out of JAMA comparing our various oral analgesic treatment options for acute pain the Emergency Department. This relatively mundane line of research has been relatively fertile over the last few years, so, what do we have in store here?

This was a double-blind, placebo-controlled trial of four different analgesic combinations for acute extremity pain. To enter the trial, one of the criteria was receipt of an imaging study, which served twofold: an assumed proxy for more serious injuries and pain, and because it increased ED length-of-stay enough to reduce patients lost to follow-up for their primary outcome. The primary outcome, then, was reduction in pain on a 0 to 10 numerical rating scale at the 2-hour mark, with an interim 1-hour mark recorded as well.

The study drugs were as follows: 400 mg of ibuprofen and 1000 mg of acetaminophen; 5 mg of oxycodone and 325 mg of acetaminophen; 5 mg of hydrocodone and 300 mg of acetaminophen; or 30 mg of codeine and 300 mg of acetaminophen. Approximately 100 patients per arm were targeted from their sample size calculations, and they ultimately randomized 416 into generally similar groups with respect to final diagnoses.

The outcomes are essentially a wash – raising a question of whether there is any advantage to opiate therapy for this indication.  In our beautiful public health tapestry of increasing opiate misuse and addiction, any opportunity to reduce opiate prescribing is important.  There are some reasonable takeaways with respect to the relative efficacy of ibuprofen/acetaminophen, oxycodone/acetaminophen,  hydrocodone/acetaminophen and codeine/acetaminophen combinations, but their clinical relevance is highly questionable considering the doses tested in this study.  This is, unfortunately, essentially a straw-man comparison between an adequate dose of non-opiate analgesia compared with the least-adequate preparation of each of the commonly used combination opiate products.  A proper comparison in patients with severe pain ought to use a more typical maximal dose, which would probably be twice as much of each of the combination opiate products.

There are a few other small oddities relating to this study, of course. As an unavoidable consequence of the study setting, 60% of their study cohort identified as Latino and another 31% identified as black. There are potential genetic differences in pharmacokinetics relating to ethnicity, as well as cultural factors relating to the cohort enrolled at the study site, so the generalization of these data requires some caution. The study protocol states patients were to be asked whether they were satisfied with their pain control and side effects were to be recorded (nausea, vomiting, itchiness, etc.), but these are not reported in the final manuscript or supplement. Finally, these data are also limited, essentially, to sprains, fractures, and contusions. This represents an important slice of outpatients seeking analgesia, but may not be applicable to other types of pain.

Overall, however, this is reasonable evidence to support strategies of combination non-opiate therapy in patients without contraindications to both acetaminophen and ibuprofen.  It should not, however, be offered as evidence of the disutility of commonly used combination opiate preparations.

“Effect of a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Extremity Pain in the Emergency Department”

https://jamanetwork.com/journals/jama/article-abstract/2661581

Now that physicians can be convicted of murder for irresponsible opiate prescribing, it’s worth reviewing precisely how we’re fulfilling our felonious destiny.

This is a brief look at the prescription drug-related deaths in San Diego County for the year 2013.  These authors identified each patient death, performed a pharmacy query for all the medications prescribed in the year prior, and then compiled descriptive statistics regarding the providers and specialties involved.  The results are disturbing, yet unsurprising.

• Primary care provided the bulk of prescriptions related to the 254 deaths, whether opiates, benzodiazepines, or sleep aids.
• Regarding opiates, 190 patients amassed 2,350 prescriptions totaling 205,700 pills – over 1,000 per patient.
• Emergency providers were not terribly over-represented, and provided among the fewest pills per prescription, at 22.9.
• The sample sizes of many subspecialties were small, but the 22 orthopedists captured by this analysis provided an average 169 pills each refill.
• “Doctor shoppers” constituted 28% of patients, but received 51% of the total prescriptions.  Various surgical specialties seemed to be their primary target.

As irritating as unnecessary antibiotic prescriptions and their ilk may be, this is far more gruesome and disappointing a spectacle.

“Who is prescribing controlled medications to patients who die from prescription drug abuse?”
http://www.ncbi.nlm.nih.gov/pubmed/26476578

There were almost 3 million visits to U.S. Emergency Departments last year for low back pain – and, yet, it is fair to say we manage these visits poorly.  Patients typically continue to have pain at discharge, at long-term follow-up, and we inject a vast number of opiates into circulation in the course of treatment.

This trial, appropriately, looks at a few of our most common prescriptions: scheduled NSAID (naprosyn), an anticholinergic smooth-muscle relaxant (cyclobenzaprine), and an opiate (oxycodone-acetaminophen).  Patients presenting to Montefiore hospital in the Bronx were randomized into three arms, and medications distributed in placebo-controlled, blinded fashion.

However, the primary outcome was not exactly what you might expect.  These authors used a questionnaire describing functional impairment, and used the change in impairment from enrollment to 1 week as their primary outcome.  This is an interesting choice as, while it doesn’t encounter some of the subjectiveness of pain scales, level of function is a technically surrogate outcome for pain relief.  Then, since it can be reasonably suggested the simple passage of time is the curative element in most cases of acute low back pain, it reasonable to expect such disability to regress to the mean, regardless of therapy, by one week.  I wonder if these authors did not inadvertently choose an outcome likely to show no difference.

And, that is precisely what they found.  At 1 week and – in another odd timeframe choice – 3 months.

However, that’s not the entirety of the story.  They measured many different outcomes, including adherence, utilization of the as-needed study medication, desire for same medication, days of return to work, and self-reported pain.  None of these secondary outcomes can be parsed reliably, but the general signal throughout is one of increased relief with the use of opiates.  It should be noted the authors’ conclusion is worded carefully – simply stating these data “do not support the use” of the therapies tested.  I am all for the avoidance of opiates, but the outcome measurement in this study probably obfuscates any potential benefit, and may rather mask their utility.

Lastly, these authors screened 2,588 patients with a complaint of low back pain in order to identify 390 meeting their inclusion criteria.  Radicular pain, traumatic pain, long-standing back pain, and elderly patients were all excluded – and, clearly, make up the bulk of visits to the Emergency Department.  These data apply to only a very small subset of patients, and they were enrolled at a single center.  The generalizability of their findings is not ideal.

It’s not a sexy topic, but its prevalence certainly makes it an important one.  If a fraction of the hundreds of millions of dollars devoted to the development of me-too blockbuster copycat drugs were devoted to such common issues, we would have far better data to guide the bulk of our practice.  I love that these authors did this trial – I just wish their measurements and timeframes differed.

“Naproxen With Cyclobenzaprine, Oxycodone/Acetaminophen, or Placebo for Treating Acute Low Back Pain: A Randomized Clinical Trial”
http://jama.jamanetwork.com/article.aspx?articleid=2463257