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A review of studies using buprenorphine

Steagall PVM, Monteiro-Steagall BP, and Taylor PM.  A review of the studies using buprenorphine in cats. J Vet Intern Med 2014;28:762-70.

Buprenorphine, a potent semisynthetic, highly lipophilic opioid, is a popular analgesic in cats due to its relatively long-acting, moderate analgesic properties with few adverse effects. Pain management in veterinary species in general, including felines, has taken center stage in the last decade as a crucial component in the delivery of comprehensive, compassionate medical and surgical care. 

These researchers conducted a literature search comprising articles published in peer-reviewed journals in English regarding studies of the use of buprenorphine in cats, including original research using thermal and mechanical threshold testing devices, clinical investigations, and retrospective studies and case series.  Several of the studies demonstrated that the route of administration of buprenorphine influences the onset, duration, and magnitude of antinociception and analgesia in cats.  In pharmacokinetic (PK) and pharmacodynamic (PD) studies, poor correlation was found between antinociception and the plasma concentration of buprenorphine after intravenous (IV) and intramuscular (IM) administration. This is due to the amount of time required for the drug to diffuse into the effect compartment and slow association of the drug with its receptor. Once bound, however, in cats buprenorphine dissociates slowly with the receptor, providing persistence of antinociception.  Clinically, then, immediate analgesia should not be expected after buprenorphine administration, as the drug has a longer onset of action compared with other opioids.  The subcutaneous (SC) route of administration is considered unreliable; at typical clinical dosages (0.02 mg/kg), SC buprenorphine has not been shown to provide adequate analgesia. The results of a clinical trial using SC sustained release buprenorphine was published in 2011, but additional PK and PD studies of this formulation need to be done.

The oral-transmucosal (OTM) route of administration of buprenorphine to cats is popular because it allows pain- and stress-free delivery of the drug.  A review of the studies of the antinociceptive and analgesic effects of OTM buprenorphine demonstrates significant controversy, and this route may not be as efficacious as previously thought.  The sampling site (carotid artery versus jugular vein) has a significant impact on the drug concentration-time profile of OTM buprenorphine.  Regarding transdermal (TD) administration of buprenorphine, randomized, controlled, prospective studies evaluating TD buprenorphine with and without an IV or IM loading dose are required before any recommendation regarding this route can be made.  Interestingly, some studies have shown that SC or TD administration of buprenorphine produced euphoric behavior in cats without changes in thermal antinociception.

Co-administration of buprenorphine with other opioids is of interest to many clinicians.  Some have used a combination of buprenorphine with butorphanol (a κ-receptor antagonist and -receptor antagonist) with the rationale that the former has a slow onset of action and the latter would provide analgesia in the interim; this assumption may not be correct as the interactions at the receptor level are unknown.  The article did not address the concurrent use of buprenorphine with full µ-agonist opioids.

The review concluded with guidelines for the clinical use of buprenorphine in felines:

(1) IV injection of buprenorphine is associated with a much greater magnitude of antinociception, speed of onset (up to 30-45 minutes), and duration of action compared to other routes of administration.  Whenever an IV catheter is in place, the drug should be given IV; the authors recommend a dosage of 0.02 mg/kg for acute pain.  The next best route of administration is IM.  Analgesia from SC administration of buprenorphine is unreliable.

(2) The duration of action of buprenorphine may be shorter than is commonly published in textbooks. One recent clinical trial showed that cats undergoing ovariohysterectomy may require a second dose of buprenorphine 4 hours after surgery, especially if an NSAID had not also been given.  Therefore, cats receiving buprenorphine should be routinely reassessed for rescue analgesia needs after buprenorphine administration.

(3) Cats who are going to receive OTM buprenorphine should be given a dose of a full agonist opioid or even injectable buprenorphine beforehand as premedication.

(4) Optimal pain relief usually is obtained when buprenorphine is combined with an NSAID, loco-regional anesthesia, or both.  Multi-modal analgesia is the best approach to feline pain management.  As none of the clinical trials reviewed were really consistent regarding the analgesic effects noted with buprenorphine use, routine and regularly scheduled pain assessment is needed to confirm its efficacy and evaluate any need for further analgesic treatment.

(5) No studies evaluating the inhalant-sparing effects of buprenorphine were found.  Clinicians using buprenorphine in feline patients should not expect a reduction in anesthetic requirements during general anesthesia, as neither systemic nor epidural administration of the drug has been shown to decrease the MAC of isoflurane in cats.

(6) The role of buprenorphine in the management of chronic pain in cats is yet to be elucidated.

(7) Cats may have great individual variability with respect to the number, morphology, and distribution of opioid receptors relative to other species; this variability may have a genetic basis and may affect both PK and PD, so buprenorphine may not provide sufficient analgesia in some cats, and it may be very effective in others.  Analgesic protocols should be tailored to the individual patient.  [PJS]

See also:
Steagall PVM, Pelligand L, et al. Pharmacokinetic and pharmacodynamic modeling of intravenous, intramuscular, and subcutaneous buprenorphine in conscious cats. Vet Anaesth Analg 2013;40:83-95.

Steagall PVM, Monteiro-Steagall BP.  Multimodal analgesia for perioperative pain in three cats.  J Feline Med Surg 2013;15:737-43.