Analgesic Efficacy of Morphine, Methadone, & Tramadol for Feline Spay

Bruno H. Pypendop, DrMedVet, DrVetSci, DACVAA, University of California, Davis

ArticleLast Updated September 20243 min read
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In the Literature

Goich M, Bascuñán A, Faúndez P, Siel D. Comparison of analgesic efficacy of tramadol, morphine and methadone in cats undergoing ovariohysterectomy. J Feline Med Surg. 2024;26(3):1098612X231224662. doi:10.1177/1098612X231224662


The Research …

Surveys in several countries have suggested inconsistency in postoperative pain management of dogs and cats, with multiple surveys showing cats receive less analgesia than dogs following similar surgeries.1-5 In addition, less information on opioid use is available for cats compared with dogs. For example, a recent search of a biomedical literature database with opioids and cats as major topics returned 61 results, while a search for opioids and dogs returned 133 results.

In this study, analgesic efficacy of morphine, methadone, and tramadol was compared in healthy cats undergoing ovariohysterectomy. Morphine is a mu-opioid receptor agonist often considered the prototype opioid to which other drugs are compared. Methadone is a mu-opioid receptor agonist and N-methyl-D-aspartate (NMDA) receptor antagonist. Tramadol is a mu-opioid receptor agonist with effects primarily due to the active metabolite O-desmethyltramadol. Each cat received one of the drugs IM as anesthetic premedication (morphine, 0.2 mg/kg; methadone, 0.2 mg/kg; tramadol, 3 mg/kg IM), with 10 cats in each treatment group. Anesthesia was induced with propofol and maintained with isoflurane. Pain was scored using a validated pain scale before surgery and at 1, 2, 4, and 6 hours after surgery. Rescue analgesia was administered during surgery if increasing depth of anesthesia did not adequately control changes in heart rate, respiratory rate, and/or blood pressure and after surgery if pain scores exceeded a predetermined threshold.

Most cats required intraoperative rescue analgesia (ie, fentanyl, 2.5 micrograms/kg IV) as a result of large increases (>20%) in heart rate, respiratory rate, and/or blood pressure, primarily during ligation of the ovarian pedicles. Approximately 27% of cats required postoperative rescue analgesia (ie, an additional administration of the same drug, dose, and route as premedication), with the highest number of cats needing rescue 2 hours after surgery. No statistically significant difference in frequency of postoperative rescue was noted between treatments. Adverse effects, including bradycardia and hyperthermia, were frequently observed. The analgesic effects of tramadol did not significantly differ from those of morphine or methadone.


… The Takeaways

Key pearls to put into practice:

  • Frequent need for intraoperative rescue analgesia in this study is not unexpected, as exposure of the ovarian pedicles is considered a strongly painful stimulus, and inhalant anesthetics, including isoflurane, do not effectively block autonomic responses at concentrations that produce surgical depth of anesthesia.

  • The peak in number of cats requiring rescue analgesia noted 2 hours after surgery highlights the importance of continued assessment in cats given the study drugs. The lack of statistically significant difference in frequency of postoperative rescue between treatments indicates that any differences were not consistent or large enough to reach statistical significance with the number of cats studied, not that treatments are similar or equivalent.

  • When needed, rescue analgesia can consist of additional doses of a drug used as anesthetic premedication or a different opioid. Multimodal analgesia (ie, concurrent use of different classes of drugs that produce analgesia via different mechanisms) is desirable and may reduce the need for rescue analgesia.

  • Frequent observation of adverse effects in this study highlights the importance of monitoring.

  • Although the effects of tramadol did not significantly differ from those of morphine or methadone, it is important to note tramadol was administered IM. Injectable tramadol is not available in the United States, and whether oral administration of tramadol produces similar effects is unknown. In addition, results should not be extrapolated to different doses of the study drugs, as effects may differ.