Introduction #
Opioids remain cornerstone analgesics in veterinary anesthesia, offering potent pain management across diverse species. They bind to μ, κ, and δ opioid receptors within the central nervous system, producing analgesia, sedation, and various physiological effects. Their reversibility and minimal impact on cardiovascular function make them particularly valuable in compromised patients. This summary examines common veterinary opioids, their pharmacological properties, and clinical selection criteria.
Morphine #
Morphine serves as the prototypical full μ-receptor agonist against which other opioids are compared. Despite being one of the oldest opioids, it maintains clinical relevance.
Pharmacology: Morphine exhibits moderate lipid solubility with relatively slow blood-brain barrier penetration. It produces analgesia lasting 3-4 hours in most species through primarily μ-receptor activation. Histamine release may occur with rapid IV administration, potentially causing vasodilation and hypotension.
Clinical Applications: Morphine proves especially valuable for moderate to severe pain and premedication, particularly in dogs. The standard dosage ranges from 0.1-1.0 mg/kg depending on species. For canine patients, 0.2-0.5 mg/kg IM is a common dose. Feline patients often receive 0.2 mg/kg IM. Epidural morphine provides excellent post-operative analgesia lasting 12-24 hours due to its hydrophilic nature, which extends spinal cord residence time.
Considerations: Horses may experience CNS excitation with morphine, limiting its use in this species. Cats may demonstrate dysphoria when given high doses, necessitating careful titration.
Hydromorphone #
Hydromorphone offers greater potency (5-7× morphine) with fewer adverse effects.
Pharmacology: As a semi-synthetic μ-agonist, hydromorphone produces reliable analgesia for approximately 2-6 hours with minimal histamine release. It undergoes hepatic metabolism with primary excretion via urine.
Clinical Applications: Hydromorphone works well for perioperative pain management across species at 0.05-0.2 mg/kg. Its reduced histamine-releasing properties make it suitable for cardiovascularly compromised patients.
Considerations: Like other μ-agonists, hydromorphone can cause respiratory depression, particularly at higher doses or in brachycephalic breeds. It should be used cautiously in patients with respiratory compromise.
Fentanyl #
Fentanyl provides high potency (100× morphine) with rapid onset and short duration.
Pharmacology: This synthetic μ-agonist features high lipid solubility enabling rapid CNS penetration and effect onset (1-2 minutes IV). Its short half-life (20-30 minutes) results from rapid redistribution rather than elimination, making it ideal for continuous infusion.
Clinical Applications: Fentanyl serves as excellent perioperative analgesia during painful procedures at 2-10 μg/kg IV bolus. Continuous rate infusions (CRIs) at 5-20 μg/kg/hr maintain steady analgesia. Transdermal patches deliver extended analgesia (72+ hours) after a 12-24 hour onset period.
Considerations: The short action duration necessitates frequent redosing if not using CRI. Chest wall rigidity may occasionally occur with rapid high-dose administration.
Methadone #
Methadone offers μ-agonism with NMDA receptor antagonism, providing enhanced analgesia.
Pharmacology: Methadone’s unique dual-mechanism produces approximately 4-hour analgesia with minimal cardiovascular effects. It demonstrates good oral bioavailability compared to most opioids.
Clinical Applications: At 0.1-0.5 mg/kg, methadone effectively controls moderate to severe pain. Its NMDA antagonism proves particularly useful for chronic or neuropathic pain conditions.
Considerations: Methadone’s extended elimination half-life requires careful monitoring for cumulative effects with repeated dosing. It causes less respiratory depression than equianalgesic doses of morphine.
Buprenorphine #
Buprenorphine functions as a partial μ-agonist with unique pharmacodynamics.
Pharmacology: With high receptor affinity but lower efficacy, buprenorphine produces moderate analgesia with extended duration (6-12 hours). Its “ceiling effect” limits both analgesia and adverse effects at higher doses.
Clinical Applications: At 0.01-0.03 mg/kg, buprenorphine effectively manages mild to moderate pain, particularly in cats where it demonstrates excellent efficacy. Buccal administration in cats provides comparable bioavailability to parenteral routes.
Considerations: Buprenorphine may not provide sufficient analgesia for severe pain. Its high receptor affinity can displace full agonists, potentially reducing analgesia if administered after a full agonist.
Butorphanol #
Butorphanol acts as a κ-agonist and μ-antagonist with limited analgesic properties.
Pharmacology: Through predominantly κ-receptor activation, butorphanol produces mild analgesia for visceral pain but minimal somatic analgesia. Duration typically ranges from 1-2 hours.
Clinical Applications: Butorphanol (0.1-0.4 mg/kg) works well for mild visceral pain and sedation, often combined with alpha-2 agonists or acepromazine. It effectively reverses unwanted μ-agonist effects while maintaining some analgesia.
Considerations: Inadequate for moderate to severe pain management. The μ-antagonist properties can reverse effects of previously administered full agonists.
Tramadol #
Tramadol represents an atypical opioid with multiple mechanisms.
Pharmacology: Tramadol produces analgesia through serotonin/norepinephrine reuptake inhibition, and conversion to active metabolite O-desmethyltramadol in some species. The metabolite has some opioid effects. Efficacy varies significantly between species based on metabolic differences.
Clinical Applications: Dogs may receive 2-5 mg/kg orally for mild pain, while cats often respond well at 1-2 mg/kg. It serves primarily as an adjunctive analgesic.
Considerations: Limited evidence supports tramadol’s efficacy in many veterinary species. Excitation may occur in cats with high doses. Drug interactions with serotonergic medications can cause serotonin syndrome.
Clinical Selection Criteria #
Veterinary anesthetists select appropriate opioids based on multiple factors:
Species Considerations: Species differences dramatically influence opioid response. Cats generally experience prolonged elimination and enhanced sedation. Horses may demonstrate excitation with μ-agonists, while ruminants require higher doses for equivalent effects. Factors include:
- Receptor distribution variations
- Metabolic pathway differences
- Species-specific adverse effects
Pain Severity: Pain intensity guides opioid selection:
- Severe pain typically requires full μ-agonists (morphine, hydromorphone, fentanyl)
- Moderate pain may respond to lower-dose full agonists or partial agonists (buprenorphine)
- Mild pain may be managed with butorphanol or adjunctive analgesics
Cardiovascular Status: Hemodynamically unstable patients benefit from opioids with minimal cardiovascular effects:
- Fentanyl and hydromorphone provide excellent cardiovascular stability
- Morphine should be administered slowly to minimize histamine release
- All opioids can reduce sympathetic tone, potentially unmasking underlying hypotension
Procedural Duration: Procedure length influences opioid selection:
- Short procedures: fentanyl bolus
- Intermediate procedures: hydromorphone, methadone
- Long procedures: morphine, extended-release formulations, or CRIs
Route of Administration: Available routes impact selection:
- IV: All mentioned opioids
- IM/SC: All except fentanyl (unless in CRI or patch form)
- Oral: Primarily tramadol, methadone (limited bioavailability for others)
- Epidural: Morphine, preservative-free formulations
- Transdermal: Fentanyl patches
- Buccal: Buprenorphine (particularly in cats)
Anticipated Adverse Effects: Risk assessment guides selection:
- Respiratory concerns: Avoid high-dose full agonists, consider butorphanol
- Gastrointestinal motility issues: Implement prophylactic motility enhancers
- Dysphoria risk: Select methadone or buprenorphine over morphine
- Urinary retention: Monitor output, especially with epidural administration
Conclusion #
Opioid selection in veterinary anesthesia requires balancing analgesic requirements against patient-specific factors. The ideal selection optimizes pain control while minimizing adverse effects. Multimodal analgesia incorporating NSAIDs, local anesthetics, and adjunctive medications often allows opioid dose reduction while maintaining effective pain management.
References #
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- Lamont LA, Mathews KA. Opioids, nonsteroidal anti-inflammatories, and analgesic adjuvants. In: Tranquilli WJ, Thurmon JC, Grimm KA, eds. Lumb and Jones’ Veterinary Anesthesia and Analgesia. 4th ed. Blackwell Publishing; 2007:241-271.
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- Plumb DC. Plumb’s Veterinary Drug Handbook. 9th ed. Wiley Blackwell; 2018.
- Papich MG. Saunders Handbook of Veterinary Drugs. 4th ed. Elsevier; 2016.
- Taylor PM, Hoare HR, de Vries A, et al. A multicentre, prospective, randomised, blinded clinical trial to compare some perioperative effects of buprenorphine or butorphanol premedication before equine elective general anaesthesia and surgery. Equine Vet J. 2016;48(4):442-450.
- Bortolami E, Love EJ. Practical use of opioids in cats: a state-of-the-art, evidence-based review. J Feline Med Surg. 2015;17(4):283-311.
