Non-opioid combo offers similar pain control to 3 opioid combos in ED after 2 hours

Patients with moderate to severe acute extremity pain were randomly assigned to receive ibuprofen and acetaminophen, oxycodone and acetaminophen, hydrocodone and acetaminophen, or codeine and acetaminophen.


There were no important differences in pain reduction from ibuprofen-acetaminophen compared to three opioid-acetaminophen (paracetamol) combination pills in ED patients with acute extremity pain, a study found.

The study involved 416 patients ages 21 to 64 years who presented to two urban EDs with moderate to severe acute extremity pain from July 2015 to August 2016. They were randomly assigned (104 per group) to receive 400 mg of ibuprofen and 1,000 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.

The primary outcome was the between-group difference in decline in pain after two hours. Pain intensity was assessed using the 11-point pain rating scale. The predefined minimum clinically important difference was 1.3 points on the scale. Patients with chronic pain conditions were excluded. Results were published Nov. 7 by JAMA.

Four hundred eleven of the 416 patients assigned to treatment were included in the analysis. After two hours, all patients had less pain and no important difference in effect was observed among the four groups. The baseline mean pain score was 8.7 points (standard deviation, 1.3). At two hours, the mean pain score decreased by 4.3 points (95% CI, 3.6 to 4.9 points) in the ibuprofen and acetaminophen group, by 4.4 points (95% CI, 3.7 to 5.0 points) in the oxycodone and acetaminophen group, by 3.5 points (95% CI, 2.9 to 4.2 points) in the hydrocodone and acetaminophen group; and by 3.9 points (95% CI, 3.2 to 4.5 points) in the codeine and acetaminophen group (P=0.053). The largest difference in decline in the pain score from baseline to two hours was between the oxycodone-acetaminophen group and the hydrocodone-acetaminophen group (0.9 point; 99.2% CI, −0.1 to 1.8 points), which was less than the minimum clinically important difference of 1.3 points. Of note, 17.8% of patients were given “rescue” opioids, although the distribution and amount were not significantly different between the groups.

The researchers wrote that ibuprofen-acetaminophen may be a reasonable alternative to opioid management of acute extremity pain due to sprain, strain, or fracture but said that further research to assess longer-term effects, adverse events, and dosing may be warranted.

“This change in prescribing habit could potentially help mitigate the ongoing opioid epidemic by reducing the number of people initially exposed to opioids and the subsequent risk of addiction, as shown in a recent study that found long-term opioid use was significantly higher among patients treated by high-intensity ED opioid prescribers than among patients treated by low-intensity ED opioid prescribers,” the authors wrote.

An editorial said the results from a study in the ED may translate to other clinical settings. “Stemming the opioid addiction crisis will also require reexamination of the long-standing assumptions that opioids are superior to nonopioids in most clinical situations requiring management of moderate to severe pain,” it stated. “Genuine efforts should be made to reduce overall opioid prescribing in the ED setting while still providing adequate pain relief.”