The second study involved patients undergoing breast resection,or mastectomy with or withouta xillary resection, with a 1-g dose 20 minutes before the end of surgery and pain followed for 24 hours (reference 13 in Table 1). Although no difference in total morphine use was detected, 42% of IV acetaminophen patients did not receive any morphine, compared with 4% in placebo group. The authors also found that 2 of the 13 patients with more extensive surgical procedures (eg, axillary dissection) that received IV acetaminophen did not request morphine in the first 24 hours postopera-tively, whereas all placebo patients did. IV acetaminophen patients did have significantly less pain only at the 1-hour measurement when compared with placebo, but from 2 to 24 hours postopera-tively, average pain rating swere below2.5in both groups and did not differ.
Five of the studies analyzed had opioid reduction as the primary end point. However, this end point has several limitations including inter-individual variability in sensitivity to opioids and variability in the level of tolerable pain.8 For opioid delivered by patient-controlled analgesia, other confounders include an initial learning curve for proper pump use, and patients may worry that they are pushing the button too often, creating a self-imposed maximum. In addition, when morphine consumption is used as an end point, the sample sizes required for 80% power are approximately twice that predicted unless one adjusts for age.9