Journal Logo

Reasonable Doubt

Reasonable Doubt

Opioids No Better than NSAID-APAP Combo for Extremity Pain

Runde, Dan MD

Emergency Medicine News: June 2019 - Volume 41 - Issue 6 - p 5
doi: 10.1097/01.EEM.0000559971.47157.d1
    opioids, NSAIDs, APA, pain
    opioids, NSAIDs, APA, pain:
    opioids, NSAIDs, APA, pain

    It will come as news to no one that the United States is in the grips of an opioid epidemic that by some estimates could claim the lives of a half-million more Americans within the next decade. (STAT. June 27, 2017; It's important for clinicians to be mindful of the potential harms at play and consider reasonable alternatives to opioids whenever appropriate because the data suggest that simply curbing opioid prescription rates is going to be nowhere near enough to mitigate the overdose crisis. (Recent data show that opioid overdose deaths have continued to accelerate despite the fact that prescription rates have declined and national morphine milligram equivalents prescribed per person are largely unchanged. [CDC. Dec. 19, 2018;])

    Keeping all of that in mind, we see patients in acute pain dozens of times each shift, and we need to choose analgesics that can adequately treat that pain. Wouldn't it be excellent if we had some guidance about what to do in situations we encounter all the time in clinical practice, like patients with acute extremity injuries? Enter an oft-cited article by Chang, et al., that addresses this topic head on, examining the efficacy of oral opioid and nonopioid medications. (JAMA. 2017;318[17]:1661

    This trial randomized 411 ED patients presenting with acute extremity pain (defined as pain from the shoulder or hip and down, respectively) and needing an x-ray (technically “a clinical indication for radiologic imaging” based on provider judgment) to one of four different treatment arms:

    • 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
    • 30 mg of codeine and 300 mg of acetaminophen

    The authors noted that they chose the need for imaging to build in a delay that would allow them to assess the patients' pain at one and two hours after being given one of these combos. They took the blinding seriously, with all patients getting three identical pills no matter what they were actually receiving, and the treating clinicians had no indication of the exact treatment they were giving.

    Solid Results

    Pain outcomes were measured using a verbal numerical rating scale of 0-10, with scores being obtained immediately before the meds were given and then one and two hours later, with the primary outcome being the average change in pain score at two hours for each of the various treatment arms. There are approximately one billion different pain scales out there, so it's appropriate to be at least a little bit skeptical of studies using them as primary outcome markers, but in this case the authors chose a single score (always be wary of studies that throw up 12 different scales and then emphasize the ones that stick) and predefined what they considered to be clinically significant score change, which was a 1.3 point average difference on the numerical rating scale (a number that was based on prior studies, not just chosen at random) among the various pain regimens. Those rare patients who made it home from the ED before the two-hour mark were called at that time to assess their pain.

    The topline results: The ibuprofen-acetaminophen combination was just as effective as any of the opioid options. All four treatment groups showed similar and significant improvements in pain for most patients (4.3 in the ibuprofen-acetaminophen group, 4.4 in the oxycodone-acetaminophen group, 3.5 in the hydrocodone-acetaminophen group, and by 3.9 in the codeine-acetaminophen group), and no group hit the threshold for performing clinically better (or worse) than the others. This is a solid result for those of us who would like a nonopioid option for patients presenting with acute extremity pain. We can give ibuprofen and acetaminophen without worrying that we are short-changing these folks with our initial attempt at pain control.

    Caveat corner: This study was well done, but that doesn't mean it was perfect, as shown, first off, in the dosage choice for the various treatment arms. Decent evidence has shown that 5 mg of oxycodone isn't a high enough initial dose to bring about pain relief for most patients, (Cochrane Database Syst Rev. 2013 26;[6]:CD010289;, and codeine in general has been found to offer little to no benefit over NSAIDs or acetaminophen. (Cochrane Database Syst Rev. 2013 28;[3]:CD010107; This means that the most ungenerous take is that this trial compared one effective treatment regimen (ibuprofen-acetaminophen) with three arms where the dosing was going to be demonstrably inadequate.

    One counterpoint might be to note that, whatever the underlying evidence, giving a patient a single Lortab or Percocet in the emergency department is common and reflective of the dosing choices made in this study. Another important point: The pain appears to have been adequately controlled for many of the patients enrolled in this trial, but 17 percent (about one in six people) required rescue analgesia, though there were no significant differences observed among the four analgesic regimens.

    In any case, aches, pains, and extremity injuries are painful and common. This nicely designed trial showed once again that ibuprofen and acetaminophen are going to get the job done for many of our patients.

    Dr. Rundeis the assistant residency director and an assistant professor of emergency medicine at the University of Iowa Hospitals and Clinics, where he serves as co-director for the associate fellowship in medical education. He creates content for and is a member of the editorial board, and is a content contributor Follow him on Twitter@Runde_MC, and read his past articles at

    Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.