Study 1: Barnaby et al. Randomized controlled trial of intravenous acetaminophen versus intravenous hydromorphone for the treatment of acute pain in the emergency department. Annals of Emergency Medicine 2019;73(2):133-140.

• Double blinded RCT of 220 adults 21-64 in 2 urban EDs with acute pain <7 days in duration severe enough to warrant consideration of IV opioids per ED physician
• Comparing 1g IV acetaminophen and 1mg IV hydromorphone
• Primary outcome was between-group difference in change in numeric rating scale (NRS 0-10 “no pain” to “worst pain”) from baseline to 60 minutes after administration of study meds.
• At 60 mins, mean decrease in NRS difference was 2.0 (95% CI 1.2-2.7) favoring IV hydromorphone.
• Significant proportion of pts with nausea after IV hydromorphone – 19% vs 3% of IV acetaminophen with a difference of 16% (95% CI 4-28).
• No significant difference in groups of rates of major adverse effects.

Study 2: Chang et al. Randomized clinical trial of intravenous acetaminophen as an analgesic adjunct for older adults with acute severe pain. Academic Emergency Medicine 2019;26(4):402-409.

• Double blinded RCT of 159 older adults aged 65+ in 2 urban EDs presenting with acute pain <7 days in duration severe enough to warrant consideration of IV opioids per ED physician
• Comparing 0.5mg IV hydromorphone + 1g IV acetaminophen vs 0.5mg IV hydromorphone + 100ml normal saline placebo
• Primary outcome was between-group improvement in NRS pain score from baseline to 60 mins.
• Difference of 0.6 NRS units of improvement between the two groups, deemed to be neither statistically nor clinically significant than the previously validated minimum difference of 1.3 NRS units.
• Nausea common in both groups, adverse effects rare.

Similar limitations in both studies:

• Enrollment subject to clinical judgement of ED physician with wide variation in opioid prescribing practices
• No recorded diagnoses or other medications that may be confounders
• The majority of patients initially reported pain scores of 9-10 therefore data skewed toward more severe pain

Note: 1g of IV acetaminophen costs $34 versus less than 10 cents per 1g of oral or rectal acetaminophen!

Bottom line: IV acetaminophen is not likely to be helpful. When compared with IV hydromorphone either alone or as an adjunct, there is no significant difference in patients’ reported improvement in pain.