Randomized double-blind placebo controlled crossover study of acetaminophen, ibuprofen, acetaminophen/hydrocodone, and placebo for the relief of pain from a standard painful stimulus.

OBJECTIVES: The objective was to compare subjects' change in perceived acute pain from an identical painful stimulus after receiving three separate, commonly used pain medications and placebo.
METHODS: This was an institutional review board-approved, randomized, double-blind crossover study of healthy human volunteers. Subjects received 1000 mg of acetaminophen, 800 mg of ibuprofen, the combination of 650 mg of acetaminophen with 10 mg of hydrocodone, or placebo (800 mg of lactose) in a randomized order over four separate occasions each 1 week apart. Prior to receiving the drug on each study day, subjects placed their nondominant hand in a bath of 0 degrees C water for 45 seconds. The bath was divided into two sections; the larger was the reservoir of cooled water monitored at 0 degrees C, and the other half was filled from constant overflow. Water drained from the overflow section into the cooling unit and was then pumped up into the base of the reservoir through a diffusion grid. Subjects completed a 100-mm visual analog scale (VAS) representing perceived pain during the exposure. The cold water exposure and VAS were repeated 1 hour after receiving the study drug, and then subjects were observed for side effects for 4 hours. Data were compared using descriptive statistics, 95% confidence intervals (CIs), and repeated-measures analysis of variance (ANOVA).
RESULTS: Twenty-five subjects were enrolled. The mean VAS preexposure was 56.9 mm (+/-15.1 mm; range = 5 to 92 mm). The mean decrease in VAS after receiving the study drug for acetaminophen was 10.2% (95% CI = -1.4 to 20.4), for ibuprofen was -6.6% (95% CI = -16.5 to 3.20), for acetaminophen/hydrocodone was 9.5% (95% CI = 1.4 to 20.4), and for placebo was -6.9% (95% CI = -15.2 to 1.4). The range in change in pain scores for all agents was -91.3% to 57.6%. Mild side effects (nausea, dizziness, or somnolence) were reported in 11 subjects (44%) after receiving acetaminophen/hydrocodone; no other side effects were reported.
CONCLUSIONS: There was a wide range of changes in pain scores from this identical painful stimulus after receiving the study medications. Acetaminophen and acetaminophen/hydrocodone resulted in a similar decrease in pain (10.2 and 9.5%), while ibuprofen and placebo had a similar lack of effect (-6.6 and -6.9%). Forty-four percent of subjects receiving acetaminophen/hydrocodone reported mild side effects; no other side effects were seen. In this noninflammatory pain model, the VAS is not able to distinguish differences in pain relief between acetaminophen and acetaminophen/hydrocodone or ibuprofen and placebo. (c) 2009 by the Society for Academic Emergency Medicine.

RCT Entities:   Population Interventions Outcomes