Opioid analgesics remain the first-line treatment for moderate-to-severe acute pain in emergency departments. But a study published in JAMA 2017 showed that, for patients presenting to the emergency department with acute extremity pain, there were no statistically significant nor clinically important differences in pain reduction at 2 hours after single treatment with ibuprofen and acetaminophen compared with three different opioid and acetaminophen combination analgesics.

Despite these findings, the study authors reiterated that opioid analgesics remain the first-line treatment for moderate-to-severe acute pain in emergency departments. Data from 2006-2010 confirm that opioids were prescribed for 18.7% of ED discharges.

The full study can be accessed at: Chang AK, et al. “Effect of a single dose of oral and non-opioid analgesics on acute extremity pain in the emergency department.” JAMA 2017; 318(17):1661-1667.doi10.100/jama2017; 16190.

Study Objectives

A common, painful condition seen in emergency departments is extremity injuries. The condition is often treated with a single dose of an oral analgesic while awaiting further care. 

Although there are many analgesic options available in emergency departments, there is very little evidence with which to guide clinical choice of medication.

The study objective was to compare the degree of pain reduction at 2 hours after ingestion of four oral combination analgesics. Three of these combinations contained an opioid, one was non-opioid, and all four were combined with acetaminophen.

METHODS

The study was conducted in two urban emergency departments at the Montefiore Medical Center, Bronx, NY. Study authors were from Albany Medical College, Albany, NY, and Albert Einstein College of Medicine at Montefiore Medical Center.

This was a prospective study, in which a randomized clinical trial included 415 patients, aged between 21 to 64 years, with moderate-to-severe acute extremity pain and enrolled from July 2015 to August 2016.

Extremity pain was defined as pain originating to and including shoulder joint in the upper extremity and distal to and including the hip joint in the lower extremities.

The primary outcome examined was the difference in decline of pain 2 hours after taking the assigned drug per group. The degree of pain was assessed using a numerical rating scale in which 0 indicated no pain and 10, the worst possible pain. Subjects were asked to rate their pain intensity using the numerical scale before taking analgesics and then at 1 hour and 2 hours following ingestion.

The investigators assigned a predefined minimum importance difference of 1.3, stating that this difference on a numerical rating scale is considered to be a standard previously derived and independently validated, based on reports, to indicate statistical significance. They added that a difference of 1.3 is a commonly used criterion to define minimal clinically important difference in pain. Analysis of variance was used to test the overall between group difference at P = 0.05%.

For the assigned drugs, there were 104 participants for each of four combination analgesic groups:

  • Group 1: 400 mg ibuprofen + 1000 mg acetaminophen
  • Group 2: 5 mg oxycodone + 325 mg acetaminophen
  • Group 3: 5 mg hydrocodone + 300 mg acetaminophen
  • Group 4: 30 mg codeine + 300 mg acetaminophen

All drugs were formulated in opaque capsules so that they looked identical.

Subjects who required a rescue analgesic based on the discretion of the attending physician received an unblended 5 mg dose of oxycodone, which could be administered at any point during the 2-hour study period.

RESULTS

Out of 416 patients included in the study and randomized, 411 were selected for analysis. The sample included:

  • Female: 48%
  • Latino: 60%
  • Black: 31%

Baseline pain intensity was initially high (mean score 8.7 out of 10) and did not differ between medication groups.

Pain intensity declined over time in all groups. The magnitudes of decline were as follows:

  • Group 1 (ibuprofen): pain decreased by 4.3 over 2 hours
  • Group 2 (oxycodone): pain decreased by 4.4 over 2 hours
  • Group 3 (hydrocodone): pain decreased by 3.5 over 2 hours
  • Group 4 (codeine): pain decreased by 3.9 over 2 hours

The largest difference in decline in the NRS pain score from baseline to 2 hours was between the oxycodone and acetaminophen group and the hydrocodone and acetaminophen group (0.9), and that was less than the minimally important difference in NRS pain score of 1.3.

Seventy-three patients (17.8%) received rescue analgesics within the 2-hour period. The distribution of receipt of rescue analgesia was not statistically significant, nor was the amount received in morphine equivalent units any different across groups.

Study Limitations and Conclusion

The follow-up time was limited to only 2 hours. A longer follow-up would have provided additional information, but the study goal was to determine if a single dose of analgesic would provide superior pain relief for patients while in the emergency department.

Another limitation was that it was unknown whether the duration of analgesia differed among the analgesics, although the half-lives are similar and range between 3 and 4 hours. Yet another limitation was that adverse effect information was not collected. The degree of adverse effects could influence the analgesic selection, especially if one group had significantly more adverse effects than another group.

Be that as it may, this study showed that for patients presenting to the emergency department with acute extremity pain, there were no statistically significant or clinically important differences in pain reduction at 2 hours among single-dose treatment with ibuprofen and acetaminophen or with three different opioid and acetaminophen combination analgesics.

Author: Richard L. Wynn, BS Pharm, PhD, is professor of pharmacology at the Baltimore College of Dental Surgery, Dental School, University of Maryland Baltimore.