Alternatives to Opioids for Perianesthetic Analgesia Management

This article was originally published in 2018 and has been updated as of November 2024.

Editor's Note: Although the underlying circumstances can vary, a shortage of opioids due to manufacturing delays or government restrictions occur periodically, which makes this guide to alternative analgesics universally germane.

Historic opioid shortages have resulted in challenges providing perioperative analgesia to dogs and cats. Although direct substitution is not appropriate for all situations, many alternatives are available.

To calm patients before and/or after anesthesia, gabapentin (5-10 mg/kg PO) or trazodone (3-5 mg/kg PO) may be used in cats and dogs, respectively.^1,2 To the authors’ knowledge, serotonin syndrome has not been reported with trazodone use in veterinary medicine. 

Oromucosal dexmedetomidine may also be considered for prearrival sedation (125 micrograms/m² oromucosal).³ Oral acepromazine tends to have inconsistent effects, but injectable acepromazine (0.01-0.05 mg/kg IV, IM, or SC) is more reliable and may be used in patients that cannot receive oral medications.⁴ Other options, including alprazolam (0.01-0.02 mg/kg PO), may be viable for some patients.⁵

Oral Analgesia

Tramadol (5-10 mg/kg PO) has not been consistently reported to have good efficacy for pain management in dogs, as this drug has only weak opioid effects⁶; however, tramadol may provide a sense of well-being based on nonopioid (serotonergic- and norepinephrine-based) actions.^7,8 A serotonin-like syndrome has not been well documented in animals but the possibility remains, especially when this drug is combined with similar medications (eg, trazodone, fluoxetine) or certain opioids (most notably meperidine).⁷

Perioperative NSAIDs (eg, carprofen [2.2-4.4 mg/kg PO or SC], meloxicam [0.1-0.2 mg/kg PO or SC], robenacoxib [1-2 mg/kg PO or SC]) may also be considered in patients with no GI or renal disease and in the absence of corticosteroid administration.^9-11 These medications are likely to be more effective for postoperative pain management when administered early in the course of anesthesia so tissue levels are reached; however, hypotension under anesthesia may adversely affect renal blood flow and compound renal adverse effects.¹² Grapiprant (2 mg/kg PO) is a noncyclooxygenase prostaglandin-receptor antagonist shown to have efficacy in treating osteoarthritis pain in dogs.¹³ Its utility as a perioperative analgesic may be similar to that of carprofen, and an improved adverse effect profile may prove advantageous.^13,14

Injectable Analgesia

Many mu-opioid agonists (eg, morphine, hydromorphone, oxymorphone, methadone, fentanyl, alfentanil, remifentanil, sufentanil) have been sporadically available. In addition to analgesia and variable degrees of sedation, anesthetic-sparing effects are provided while cardiovascular safety is maintained. For premedication and intraoperative use by infusion, these drugs are largely interchangeable, provided the clinician has knowledge of their relative potency, onset and duration of action, and adverse effect profile.⁶ 

Buprenorphine (20-30 micrograms/kg IV, IM, or buccal), a partial mu agonist, may be used alone or in combination with other medications as a substitute for other mu agonists in dogs and cats for mildly to moderately painful procedures.^6,14 Buprenorphine may also be used with other drugs for more complex and painful surgical procedures to minimize pain. An administration interval of ≈6 to 8 hours has been suggested in the perioperative period.¹⁵ Salivation, bradycardia, and respiratory depression may be observed with use; drug effects are generally not thought to be reversible. Sustained-release or long-acting formulations of buprenorphine for SC administration are available and reported to provide 24 to 72 hours of analgesia.^16,17

Butorphanol (0.1-0.5 mg/kg IV, IM, or SC), a kappa agonist and mu antagonist, is best used as a sedative and analgesic for presumed mildly painful procedures (eg, gastroduodenoscopy, colonoscopy, subcutaneous mass removal) or with adjunct analgesic techniques (eg, as a nerve block).⁶

Premedication with dexmedetomidine (3-10 micrograms/kg IM) can be considered for sedation and analgesia in healthy dogs and cats. Cardiovascular adverse effects may occur and present challenges with monitoring. Partial reversal with atipamezole can lessen these effects if significant; however, alternative analgesia should be provided prior to reversal. Dexmedetomidine may also be administered as a CRI in healthy dogs and cats; an initial maintenance dose of 1 microgram/kg/hr IV has been suggested to provide analgesia and anesthesia-sparing effects.¹⁸

Infusion Analgesia

Ketamine is an N-methyl-D-aspartate–receptor antagonist that has been shown at subanesthetic doses to mitigate or prevent spinal facilitation of pain (ie, the wind-up effect). Although this drug is administered during anesthesia, the greatest benefit is thought to occur postoperatively¹⁹; however, even at low doses (eg, 10-20 micrograms/kg/minute IV after a loading dose of 0.5 mg/kg IV), ketamine can reduce anesthetic requirements up to 25%.²⁰ Higher doses in dogs and cats have been reported to further reduce inhaled anesthesia requirements but exhibit a ceiling effect.²¹ Although reports of benefits are largely anecdotal, ketamine infusions may be continued into the postoperative period in conscious patients. Doses of 1 to 3 micrograms/kg/minute IV have been suggested to minimize behavior changes.¹⁹ In patients for which preventing or reducing spinal facilitation is desirable but oral administration is preferred, amantadine (3 mg/kg PO every 24 hours) may be considered.²²

Intravenous lidocaine (2%) may be a cost-effective source of background analgesia and inhaled anesthetic dose reduction.²³ Adverse effects include seizures but are rare if clinically appropriate doses are used. Nausea may also be noticed at high doses in conscious patients. Anesthetic dose reduction with 50 micrograms/kg/minute CRI IV (low end of the antiarrhythmic dose range) has been reported in dogs²⁰; however, the authors' experience suggests doses as low as 20 to 30 micrograms/kg/minute IV can be beneficial in clinical patients. Lidocaine is not routinely recommended for use in cats, as, despite a reduction in isoflurane dose, cardiovascular depression is greater with a combination of lidocaine and isoflurane than with an equivalent dose of isoflurane alone.²⁴ 

Combinations of an opioid, lidocaine, and ketamine (opioid and ketamine for cats) may be used for anesthesia-sparing effects to provide analgesia and reduce spinal facilitation of pain in dogs. When morphine, lidocaine, and ketamine are combined in dogs, the isoflurane dose is reduced by ≈45%.²⁰ Respiratory depression is generally less than with high doses of opioids alone.

Regional Anesthesia

When shortages of drugs for systemic administration occur, use of regional techniques (eg, injecting lidocaine [2%; up to 2 mg/kg] into the testicle prior to castration, providing a line block to the abdominal wall during an ovariectomy/ovariohysterectomy) when possible can be of significant benefit. Targeted nerve blocks and intra-articular or epidural administration provide other options for localized pain relief. Longer-acting local anesthetics (eg, ropivacaine, bupivacaine) may be used as warranted by the procedure and with consideration to duration of motor effects and toxicity. 

Liposomal bupivacaine is another alternative for long-acting pain relief following surgery when injected into tissues at the surgical site.²⁵ Label directions should be followed if this drug is being used with other regionally or systemically administered local anesthetics.