#Grand Rounds

Do Non-Opioids Work as Well as Opioids for Acute Extremity Pain?

BACKGROUND AND PURPOSE:

Almost 500,000 people have died since 2000 from drug overdoses
Opioid analgesics still remain a first line choice for moderate to severe acute pain in emergency departments
The choice of analgesic to treat acute extremity pain lacks a clear evidence base
Chang et al. (JAMA, 2017) compared the efficacy of 4 opioid and non-opioid oral analgesics

Randomized blinded clinical trial (RCT)
Inclusion
- Adults 21 – 64 years
- Acute extremity pain, sufficient to require radiological imaging
Participants were randomized into the following groups
- 400 mg ibuprofen and 1000 mg acetaminophen
- 5 mg oxycodone and 325 mg acetaminophen
- 5 mg hydrocodone and 300 mg acetaminophen
- 30 mg codeine and 300 mg acetaminophen
After randomization, patients rated their pain before and after taking the study medication at 1 and 2 hours
Pain intensity was measured using an 11-point numerical rating scale (NRS), with 0 indicating no pain and 10 worst possible pain
- Minimum clinically important difference – 1.3
Primary outcome: Between-group difference in decline in mean NRS score at 2 hours after ingestion
Secondary outcomes: Between-group differences in mean NRS scores at 1 hour and responses to a 4-point Likert scale rating pain as none, mild, moderate, or severe

Data from 411 patients were analyzed
- Mean age 37 years; 199 (48%) women; 247 (60%) Latino
The baseline mean NRS pain score was 8.7 (SD, 1.3)
After 2 hours the NRS score decreased by
- 4.3 (95% CI, 3.6 to 4.9) in the ibuprofen and acetaminophen group
- 4.4 (95% CI, 3.7 to 5.0) in the oxycodone and acetaminophen group
- 3.5 (95% CI, 2.9 to 4.2) in the hydrocodone and acetaminophen group
- 3.9 (95% CI, 3.2 to 4.5) in the codeine and acetaminophen group
Primary Outcome: There was no statistical difference in change in pain by treatment group from baseline to 2 hours (P=0.53)
- Nor was there difference at 1 hour (P=0.13)
The largest difference in decline (between the oxycodone and acetaminophen group and the hydrocodone and acetaminophen group) was still less than the minimum clinically relevant difference of 1.3

There was no measured difference in efficiency of analgesic treatment between combination opioid/acetaminophen and ibuprofen/acetaminophen
Previous studies were undertaken in the post-op or dental setting and likewise did not find opioid/acetaminophen to be superior to ibuprofen/acetaminophen
- Authors therefore suggest that this study may be generalizable beyond acute extremality pain
Future research is needed to assess adverse events and alternative dosing

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