Randomized Trial of Adding Parenteral Acetaminophen to Prochlorperazine and Diphenhydramine to Treat Headache in the Emergency Department

Abstract

Introduction: Headaches represent over three million emergency department (ED) visits per year, comprising 2.4% of all ED visits. There are many proposed methods and clinical guidelines of treating acute headache presentations. However, data on intravenous acetaminophen usage in these settings are lacking. In this study, we sought to determine the efficacy of intravenous (IV) acetaminophen as an adjunct to a standard therapy for the treatment of patients who present to the ED with a chief complaint of "headache."

Methods: We conducted a single site, randomized, double-blind, placebo-controlled trial investigating the clinical efficacy of IV acetaminophen as an adjunct to a standard therapy with prochlorperazine and diphenhydramine for the treatment of patients who present to the ED with a chief complaint of "headache" or variants thereof. (See below for variants). The primary outcome measure of the efficacy of parenteral acetaminophen as an adjunct treatment for headache in addition to a standard therapy was a threshold two-point reduction in visual analog scale (VAS) pain scores on a 1-10 level at 90 minutes. Secondary outcomes measures included assessment of decreased requirement of "rescue" pain medicines, defined as any analgesic medications outside of diphenhydramine, prochlorperazine and acetaminophen, with particular interest to potential opioid-sparing effects with parenteral acetaminophen. Additional secondary outcome measure included time to disposition from arrival in the ED.

Results: For the acetaminophen group the initial mean pain score was 8.67, for the placebo group 8.61. At 90 minutes pain score was 2.23 for the acetaminophen group and 3.99 for placebo (p<0.01, 95% confidence interval (CI) [0.8%-16%]. Of 45 patients in each group, we observed at least a threshold two-point decrease in pain score 36/45 (80%) with acetaminophen vs. 25/45 (55%) with placebo (p <0.01) 95% CI [5%-41%], number needed to treat (NNT) = 4). Secondary outcome measure did not demonstrate a difference in length of stay (161 minutes for acetaminophen arm and 159 minutes for placebo). However, 17/45 (38%) of patients who received IV acetaminophen required rescue analgesia, opposed to 24/45 (53%) of patients in the placebo group (p=0.13) 95% CI [-5%-34%].

Conclusion: IV acetaminophen when used with prochlorperazine and diphenhydramine to treat acute headaches in the ED resulted in statistically significant pain reduction compared with prochlorperazine and diphenhydramine alone as measured by both threshold of lowering VAS pain score by at least two points (NNT = 4) and overall decline in VAS pain score. Further study is required to validate these results.

Figure 1

Demographics of patients in age range categories.

Figure 2

Improvement of visual analog scale pain score reporting ≥ 2 decrease from presentation at the 90-minute mark. IV, intravenous

Figure 3

Comparative percentages of those requiring rescue analgesia in both IV (intravenous) acetaminophen and placebo.

Figure 4

Numeric comparison of rescue analgesics for both intravenous acetaminophen and placebo arms. (p=0.13) 95% CI (−5%–34%) NSAIDS, non-steroidal anti-inflammatory drugs

Figure 5

Distributions of the mean visual analog pain scores at predefined intervals from time of patient arrival in intravenous (IV) acetaminophen and placebo arms. (p=0.13), 95% CI [−5%–34%].