Abstract

Objectives: We sought to evaluate whether there is a sex difference in the analgesic response to μ versus κ opioids in the management of acute moderate to severe pain of injury in the emergency department.

Methods: The study was a randomized, double-blind, clinical trial comparing the prototypical μ-receptor agonist, morphine sulfate, to the prototypical κ agonist, butorphanol. The primary endpoints were degree of relief by visual analog scores at 30 and 60 minutes. Statistical analysis was performed using Mann-Whitney U test for nonparametric analysis and repeated-measures analysis of variance.

Results: Ninety-four patients were entered in the study, with 49 (52%) males and 45 (48%) females. Forty-six received morphine sulfate and 48 received butorphanol. There was no difference in demographics in the two groups. At 60 minutes, females had significantly lower visual analog scores with butorphanol compared with morphine (P = 0.046). At 60 minutes, there was a trend for a difference in response of males versus females to morphine, with males responding better than females (P = 0.06).

Conclusion: Females had better pain scores with butorphanol than morphine at 60 minutes.

Acute painful injuries due to trauma are frequent presenting complaints in the emergency department (ED). Treatment for these patients is paramount for several reasons. Pain accounts for more than 30 million ED visits annually in the United States, and inadequate relief of pain is a frequent cause of return visits to the ED. Pain is often referred to as the fifth vital sign. Assessment of pain, as well as aggressive and effective relief of pain, is mandated by new standards published by the Joint Commission on Accreditation of Healthcare Organizations. ^1,2 Unrelieved pain has adverse physical and psychological effects. The consequences of ineffective pain control may include further injury to an already compromised limb, difficulty with reduction of a fracture or other definitive treatment, and the inability of a patient to participate in his or her medical care.

Two commonly used opioid analgesics for uncomplicated patients are morphine sulfate and butorphanol. Both are opioids; however, their mechanism of action differs in that morphine acts as a μ receptor agonist and butorphanol primarily as a κ agonist. ³ Preliminary studies suggest that there may be a sex difference in response to the site of action of these two medications. Females may receive more relief and fewer side effects from those acting at κ sites. Past studies comparing male versus female responses to κ agonists have involved oral and IV medications for dental pain. ^4–6 There are no previous studies comparing the two medications between the sexes for acute injury.

The purpose of the present study is to evaluate the overall sex differences in the analgesic response to the parenteral agents morphine and butorphanol for the relief of moderate to severe painful injuries secondary to trauma in the ED. The main outcome measures were degree of relief at 30 and 60 minutes in males and females. The null hypothesis was that morphine and butorphanol would be equally effective in relief of pain in males and females.

Key Points

* Butorphanol and morphine are commonly used pain medications in the emergency department.

* Butorphanol is a κ agonist and morphine is a μ agonist.

* Females preferred butorphanol (κ agonist) to morphine for pain management in acute injury.