Evaluation of the perioperative analgesic efficacy of buprenorphine, compared with butorphanol, in cats

• Autores: Leon N. Warne
• Localización: JAVMA: Journal of the American Veterinary Medical Association, ISSN-e 0003-1488, Vol. 245, Nº. 2, 2014, págs. 195-202
• Idioma: inglés
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• Resumen

  • Objective—To compare the analgesic effects of buprenorphine and butorphanol in domestic cats.

    Design—2-phase positive-controlled randomized masked clinical trial.

    Animals—39 healthy female cats (10 in phase 1 and 29 in phase 2).

    Procedures—Cats admitted for ovariohysterectomy received buprenorphine (4 in phase 1; 14 in phase 2) or butorphanol (6 in phase 1; 15 in phase 2). In phase 1, cats were premedicated with buprenorphine (0.02 mg/kg [0.009 mg/lb], IM) or butorphanol (0.4 mg/kg [0.18 mg/lb], IM), in combination with medetomidine. Anesthesia was induced with propofol (IV) and maintained with isoflurane in oxygen. After extubation, medetomidine was antagonized with atipamezole. A validated multidimensional composite scale was used to assess signs of pain after surgery starting 20 minutes after extubation and continuing for up to 360 minutes, and pain score comparisons were made between the 2 groups. Phase 2 proceeded similar to phase 1 with the following addition: during wound closure, cats from the butorphanol and buprenorphine groups received butorphanol (0.4 mg/kg, IM) or buprenorphine (0.02 mg/kg, IM), respectively.

    Results—Phase 1 of the study was stopped after 10 cats were ovariohysterectomized because 9 of 10 cats required rescue analgesia at the first evaluation. In phase 2, at the first pain evaluation, pain scores from the buprenorphine group were lower, and all cats from the butorphanol group required rescue analgesia. None of the cats from the buprenorphine group required rescue analgesia at any time.

    Conclusions and Clinical Relevance—Buprenorphine (0.02 mg/kg, IM) given before surgery and during wound closure provided adequate analgesia for 6 hours following ovariohysterectomy in cats, whereas butorphanol did not.

    Buprenorphine, a partial μ-opioid (OP3) receptor agonist and κ-opioid (OP2) receptor antagonist, is frequently used in dogs and cats during the postoperative period to manage signs of pain of mild to moderate intensity.1 It also has the advantage of only rarely causing dysphoria or vomiting in cats.2 Butorphanol is a κ-opioid (OP2) receptor agonist and μ-opioid (OP3) receptor antagonist.3 Butorphanol induces analgesia through its κ-opioid receptor agonist activity; however, its analgesic properties have been questioned.4 Butorphanol is believed to provide adequate visceral but poor somatic analgesia.5 Notwithstanding variation in response among populations and individual cats, butorphanol has a fast onset but short duration of antinociception.5–9 Butorphanol is not suitable as a sole pain-relieving drug for the treatment of moderate to severe signs of pain following surgery.1 As a partial μ-opioid receptor agonist, buprenorphine is likely to provide greater analgesia than butorphanol, a κ-opioid receptor agonist. This is supported by the findings of Robertson et al,6 who reported that, in cats, buprenorphine administered IM increased thermal threshold in both intensity and duration (< 12 hours), compared with butorphanol (< 30 minutes). This is also in agreement with a large prospective clinical trial10 of 153 cats, which found lower postoperative pain scores in cats that received buprenorphine (0.01 to 0.02 mg/kg [0.0045 to 0.009 mg/lb], IM) as premedication prior to surgery, compared with cats premedicated with butorphanol (0.4 mg/kg [0.18 mg/lb], IM). Bortolami et al11 reported that buprenorphine provided comparable sedation and analgesia to both methadone and butorphanol when combined with acepromazine. In a recent publication,12 authors have challenged part of that study, finding that methadone provided more effective analgesia of longer duration, compared with butorphanol, in cats following ovariohysterectomy. Intravenous administration and IM administration of buprenorphine provide superior postoperative analgesia to SC or oral transmucosal administration of the drug.13 As a result of this finding, IV administration and IM administration were recommended as the preferred routes for buprenorphine in cats. In laboratory animals, buprenorphine has a bell-shaped dose-response curve, suggesting that higher doses decrease the analgesic effect.14 This has led to label restrictions on the dose and the administration interval, but clinical relevance has never been determined.2,14 Buprenorphine is registered for use in the treatment of pain in cats in Canada, the United Kingdom, and other parts of Europe, with a labeled IM dose recommendation of 0.02 mg/kg, and is available for extralabel veterinary use in the United States.15 In the United States, although butorphanol is approved for use in cats, use of buprenorphine is considered extralabel usage in veterinary patients and special regulations for its use apply.12,16 Pain expression is considered to be multidimensional, and tools that evaluate multiple dimensions of signs of pain are more accurate than those that measure only 1 dimension, such as intensity (eg, VAS, numeric rating scale, or simple descriptive scale).17,18 The purpose of the study reported here was to evaluate the analgesic effect of buprenorphine, compared with butorphanol, in cats by use of a validated multidimensional composite pain scale.12,19,20 To the authors' knowledge, no other validated pain assessment scale has been described for use in cats. The hypothesis was that buprenorphine provides greater analgesia than butorphanol in the postoperative period following ovariohysterectomy in cats.