Does IV Acetaminophen Reduce Morphine Use?

Written by Jonathan Brewer

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A 1g dose of IV acetaminophen (APAP) had no additional effect on pain control or reduction in overall morphine dosage.

Why does this matter?
Pain is one of the most common reasons for presentation to the emergency department (ED). For years, we have searched for opioid alternatives due to their adverse effects. The PANSAID trial found ibuprofen + APAP reduced opioid consumption for post-op pain, but it seemed ibuprofen was providing most of the benefit. JournalFeed has looked at IV APAP vs hydromorphone; we have covered IV APAP + hydromorphone vs hydromorphone + placebo; and we have covered IV vs PO APAP. All three studies showed no benefit to IV APAP. Shall we try again?

Does APAP take the power from the pain?
This was a double-blinded, randomized controlled trial in which ED patients > 18 years with acute pain (Numerical Rating Scale, NRS > 4) were split in a 1:1 ratio to receive morphine 0.1 mg/kg with either 1g APAP IV or placebo IV. Additional morphine doses of 0.05 mg/kg IV were administered every 15 minutes until pain relief was achieved (defined as NRS < 4).

The primary outcome of the study was the mean morphine dose to achieve pain relief, with secondary outcomes of total morphine given, time to pain relief, and adverse events being recorded as well. Out of the 220 patients that were randomized, the mean morphine dose for pain relief was similar in both groups (APAP group: 0.15 +/- 0.07 mg/kg, placebo: 0.16 +/- 0.07 mg/kg). There were no differences in the total amount of morphine given (APAP 0.19 +/- 0.09 mg/kg, placebo 0.19 +/- 0.1 mg/kg), the time to achieve pain relief (APAP 30 min [95% CI 17-31], placebo 30 min [95% CI 30-35]), and the frequency of adverse events (overall 27.4%). Time to pain recurrence also did not differ significantly between the two groups (HR 1.23 [0.76-1.98], p=0.40).

On the other hand, there were many limitations to this study. There are various causes of pain, and there was no subgroup analysis based on the etiology of pain. Another caveat is that the dose of morphine utilized (0.1 mg/kg) was different than what is commonly administered in many emergency departments (4 mg is often given). Finally, they only included patients with severe pain (NRS ≥ 8/10), so this may not have been the the right patient population to detect a benefit from IV APAP. Unfortunately, this was another negative IV APAP study. It is possible IV APAP may find a role as a component of a multimodal cocktail, but we don’t seem to have found the right indication to date.

Intravenous acetaminophen does not reduce morphine use for pain relief in emergency department patients: A multicenter, randomized, double-blind, placebo-controlled trial. Acad Emerg Med. 2022 May 2. doi: 10.1111/acem.14517. Epub ahead of print.

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