Article Citation                                                                                                                            

Chang AK et. al. Effect of a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Extremity Pain in the Emergency Department: A Randomized Clinical Trial.JAMA. 2017 Nov 7;318(17):1661-1667. doi: 10.1001/jama.2017.16190.


What we already know about the topic

According to the latest CDC data from 2015, opioids were involved in 33,091 deaths.1 This number has quadrupled since 1999.1 Concurrently with this rapid rise in opioid-related deaths, there has been a widespread increase in the opioid prescriptions provided to patients with moderate to severe pain. Data from the National Hospital Ambulatory Medical Care Survey from 2006-2010 indicate that opioids were prescribed for 18.7% of ED discharges.2 As emergency physicians, we are at the front line of this current epidemic.

Why this study is important

Prior to this study, few data existed that have compared combination opioids to combination non-opioid medications in treating acute pain in the emergency department.


Brief overview of the study

This was a randomized double-blind clinical trial of patients age 21 to 64 with acute extremity pain that required imaging. Patients were randomized to a single dose of oral combination: (1) ibuprofen 400mg and acetaminophen 1g, (2) oxycodone 5mg and acetaminophen 325mg, (3) hydrocodone 5mg and acetaminophen 300mg, or (4) codeine 30mg and acetaminophen 300mg and asked to rate their pain from 0 to 10  at times 0, 1, and 2 hours from ingestion. Patients were excluded if they had (1)already taken non-opioid medication in the previous 8 hours, (2) had history of methadone use or prior recreational narcotic use, (3) a chronic pain syndrome (eg. sickle cell disease, fibromyalgia), (4)pregnant, (5)hx of adverse reaction to/or contraindication to medications in study.  

Primary outcome was the mean change in pain score at 2 hours. A statistically significant mean change in pain score was calculated to be a difference between the arms of 1.3 points.

411 patients were randomized in this study. A mean initial pain score was 8.7 and did not differ between the groups. At 2 hours, the mean reduction  pain score was between 3.5-4.3 points across the treatment arms. However, there was no statistically significant difference between the groups. The number of patients receiving rescue medication (oxycodone 5mg po or other) did not differ between the groups nor did the dose equivalent of morphine that these patients received as a rescue. A subgroup analysis of patients who initially rated their pain as 10/10 or had a final diagnosis of extremity fracture also found no difference between the groups; at 2 hours these patients on average had reduction in mean pain score of between 4.7-5.7 points.



Patients with chronic pain needs were excluded from this study. These patients often have many factors that contribute to their ongoing pain needs, such that when they have an acute pain episode can pose a challenge to clinicians. Further research needs to be done targeting this group of patients. As noted by the authors, the follow up time was limited to 2 hours, mostly due to the quick turnover of many of these patients who are seen “fast track” or urgent care-like areas of the ED, so we don’t really know with certainty how these medications compare at 3-4 hours prior to redosing of these medications. There is also some argument to be made that these were also small doses of opiates (5mg of oxycodone = 2mg of IV morphine) that at baseline may be an insufficient dose to treat acute pain. There was also no adverse effect data collected on these patients.

Take home points

For patients without any contraindication to acetaminophen or NSAIDs, a trial of tylenol 1g PO + ibuprofen 400mg PO is a reasonable approach in the initial management of acute extremity related pain.


Additional Sources:

  1. Center for Disease Control and Prevention. Drug Overdose Death Data. Accessed Nov 13, 2017.

  2. Kea B, Fu R, Lowe RA, Sun BC. Interpreting the National Hospital Ambulatory Medical Care Survey: United States emergency department opioid prescribing, 2006-2010. Acad Emerg Med. 2016;23 (2):159-165.
May 2024