Objectives: Acetaminophen (APAP) is a mainstay for pain management worldwide. The intravenous (IV) formulation has been widely used in Europe for more than 20 years in adults and children. In the United States, IV APAP obtained full approval from the Food and Drug Administration in 2010. There is emerging literature to suggest the use of IV APAP for pain reduction in the emergency department (ED). This evidence-based review examines the evidence pertaining to the use of IV APAP for acute pain control in the ED.Methods: The MEDLINE and EMBASE databases were searched. Randomized controlled trials (RCTs) that described or evaluated the use of IV APAP for acute pain in the ED were included. Duplicate articles, unpublished reports, abstracts, review articles, and non-English literature were excluded. The primary outcome of interest in this review was the difference in pain score between IV APAP and active comparator or placebo from baseline to a cutoff time specified in the original trials. Secondary outcome measures were the incidence of adverse events and reduction in the amount of adjuvant analgesics consumed by patients who received IV APAP. Methodologic quality of the trials was assessed using the Grading of Recommendations Assessment, Development, and Evaluation criteria.Results: Fourteen RCTs with various methodologic flaws, which enrolled a total of 1,472 patients, met the inclusion criteria. The level of evidence for the individual trials ranged from very low to moderate. In three of the 14 trials, a significant reduction in pain scores was observed in patients who received IV APAP. The first trial found a significant reduction in mean pain scores when IV APAP was compared to IV morphine at 30 minutes after drug administration (4.7 AE 2.3 vs. 2.9 AE 2.2). In the second trial, patients who received IV APAP reported of lower pain scores (31.7 AE 18 mm, 95% confidence interval [CI] = 8.2 to 25.2 mm) compared to those who received IV morphine (48.3 AE 14.1 mm, 95% CI = 8.2 to 25.2 mm), 15 minutes after drug administration. A third trial found a significant reduction (p = 0.005) in the mean pain scores when IV APAP was compared to intramuscular piroxicam at 90 minutes after drug administration. In the remaining eight trials, pain scores were not statistically different when IV APAP was compared to other pain medications. The incidence of side effects associated with IV APAP was very low. Conclusions

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