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A Comparison of Nalbuphine, Butorphanol, & Morphine in Dogs

Andrew K. Claude, DVM, DACVAA, Michigan State University

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In the Literature

Gomes VH, Barbosa D, Motta AS, Corrêa CG, Moreno DJ, da Silva MF. Evaluation of nalbuphine, butorphanol and morphine in dogs during ovariohysterectomy and on early postoperative pain. Vet Anaesth Analg. 2020;47(6):803-809.


Although other analgesic drugs have increased in popularity, opioids continue to be extensively used for pre-, intra-, and postoperative analgesic periods in veterinary medicine.1 Opioid analgesic drugs are classified according to the opioid receptor(s) at which they exert agonistic action.2 μ-opioid analgesic drugs include morphine, hydromorphone, methadone, and fentanyl; buprenorphine is classified as a partial μ agonist. Mixed agonist/antagonist drugs include butorphanol and nalbuphine; these are κ agonists and predominately μ antagonists. 

Morphine and butorphanol are commonly used in veterinary practice, but nalbuphine (a noncontrolled, human opioid drug3) is not. Butorphanol and nalbuphine have similar pharmacologic and adverse effects in dogs and cats. However, there is conflicting evidence as to whether nalbuphine has equal or greater sedative and analgesic effects as compared with butorphanol or morphine, and extensive analgesic studies involving nalbuphine in veterinary medicine are lacking.4 Butorphanol as an analgesic in small animals is less effective than μ agonists, partial μ agonists, and NSAIDs, primarily because of its short duration of action and ability to control only mild to moderate degrees of pain.5 As compared with morphine, neither butorphanol nor nalbuphine have been shown to reduce the minimum alveolar concentration of inhalant anesthetics.6 In addition, butorphanol should be used judiciously in patients with the multidrug sensitivity gene (MDR1 gene, also known as ABCB1 gene).7

This study compared the analgesic effects of intra- and postoperative nalbuphine (either 0.5 mg/kg or 1 mg/kg), butorphanol, and morphine administered with acepromazine for premedication in dogs undergoing ovariohysterectomy. The authors believed that morphine would provide the most effective analgesia as compared with nalbuphine and butorphanol and that nalbuphine would provide a dose-dependent degree of analgesia. The number of rescue doses of propofol needed to maintain an adequate level of anesthesia was used to assess intraoperative analgesia. The dynamic and interactive visual analog scale and the modified Glasgow composite measure pain scale were used to assess postoperative pain. No difference in the degree of analgesia was observed among the 3 opioids, and the effects of a higher and lower dose of nalbuphine were similar. All 3 opioids, when combined with acepromazine, provided insufficient analgesia for all dogs during the surgical procedure. In addition, none of the 4 premedication protocols provided acceptable analgesia within the first 6 hours postoperatively. The authors speculated that the morphine dose (0.2 mg/kg IV) may have been insufficient to provide adequate analgesia; however, the butorphanol and nalbuphine doses were comparable with those in other studies.


Key pearls to put into practice:


This study did not fully illustrate the antinociceptive advantages of morphine, butorphanol, and nalbuphine. However, opioid drugs are valuable analgesics for surgical procedures and should be administered pre-emptively to help control surgical nociception.


Increasing the dose of nalbuphine or butorphanol may not provide increased analgesia because of their ceiling effects. Increasing the dose of morphine (0.4-0.5 mg/kg) can increase analgesia but may also increase adverse effects. μ-agonist opioids (eg, morphine, hydromorphone) or partial μ-agonist opioids (eg, buprenorphine) may provide better analgesia for surgical patients as compared with butorphanol or nalbuphine.


Administering maropitant prior to μ-agonist opioid drugs can decrease the incidence of vomiting in dogs and may provide additional analgesia.8,9



Butorphanol and nalbuphine are κ agonists and μ antagonists; therefore, either can be used as a nonemergent, μ-opioid–reversing drug.


For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

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