RCT – APAP Only vs APAP-Ibuprofen-Codeine Combo

September 30, 2019

Written by Alex Chen

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For acute musculoskeletal (MSK) injuries, the combination of oral paracetamol (aka acetaminophen or APAP), ibuprofen, and codeine was not superior to paracetamol alone in regards to pain reduction at 60 minutes or need for rescue analgesia. The combo group had more adverse effects.

Why does this matter?
MSK injuries are painful, and we have the tools to make them less so. The question is, how do we treat pain effectively while minimizing side effects and the use of opioids? The data that has been coming out in this field has largely demonstrated that opioids are no better than their non-opioid counterparts.

If A=B, B=C, and A=C, does A+B+C = A? –obviously not Pythagoras
This was a prospective, double-blind, randomized, active-controlled, parallel-arm study at an urban ED in Auckland, NZ. They randomized adults (18-65yo) who presented with acute (<48h) closed MSK injuries with moderate pain (>3/10) to either combination APAP (1g), ibuprofen (400mg), and codeine (60mg), or APAP plus two placebo pills. The primary outcome was a difference in pain relief at rest at 60 minutes. Secondary outcomes included difference in pain relief at 60 minutes with activity, rest and activity pain at 120 minutes, need for rescue analgesia, and rate of adverse events between groups. 

They approached 832 patients; however, 713 were excluded. They ended up with 60 in the combo group and 59 in the APAP-only group. The mean baseline pain score of both groups was 5.8, with the APAP group actually having more fractures (14 vs 7). In terms of the primary outcome, the combo group had a reduction of -2.0 compared to -1.6 in the APAP group (mean difference -0.4, 95% CI -1.1 to 0.3). In terms of secondary outcomes, there was a significant difference in the number of adverse effects in the combo group compared to the APAP group (23.3% vs 8.5% for a RR of 2.8, 95% CI 1.1-7.2). Ultimately, this study adds more data that 1 gram of APAP is pretty darn good. And I am going to go out on a limb and say that adding more stuff to your pain cocktail is not going to lead to better outcomes (…unless it’s haloperidol – it always works).

Source
Oral Paracetamol Versus Combination Oral Analgesics for Acute Musculoskeletal Injuries. Ann Emerg Med. 2019 Aug 1. pii: S0196-0644(19)30442-1. doi: 10.1016/j.annemergmed.2019.05.030. [Epub ahead of print]

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Reviewed by Clay Smith and Thomas Davis