Comparison of carprofen and tramadol for postoperative analgesia in dogs undergoing enucleation

• Autores: Cherlene Delgado
• Localización: JAVMA: Journal of the American Veterinary Medical Association, ISSN-e 0003-1488, Vol. 245, Nº. 12, 2014, págs. 1375-1381
• Idioma: inglés
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• Resumen

  • Objective—To compare analgesia provided by carprofen and tramadol in dogs after enucleation.

    Design—Randomized, masked clinical trial.

    Animals—43 dogs.

    Procedures—Client-owned dogs admitted for routine enucleation were randomly assigned to receive either carprofen or tramadol orally 2 hours prior to surgery and 12 hours after the first dose. Dogs were scored for signs of pain at baseline (ie, before carprofen or tramadol administration) and at 0.25, 0.5, 1, 2, 4, 6, 8, 24, and 30 hours after extubation. Dogs received identical premedication and inhalation anesthesia regimens, including premedication with hydromorphone. If the total pain score was ≥ 9 (maximum possible score of 20), there was a score ≥ 3 in any of 5 behavioral categories (highest score possible per category was 3 or 4), or the visual analog scale (VAS) score was ≥ 35 (maximum possible score of 100) combined with a palpation score > 0, rescue analgesia (hydromorphone) was administered and treatment failure was recorded.

    Results—No differences were found in age, sex, or baseline pain scores between groups. Significantly more dogs receiving tramadol required rescue analgesia (6/21), compared with dogs receiving carprofen (1/22). Pain and VAS scores decreased linearly over time. No significant differences were found in pain or VAS scores between groups at any time point (dogs were excluded from analysis after rescue).

    Conclusions and Clinical Relevance—Results of this study suggested that carprofen, with opioid premedication, may provide more effective postoperative analgesia than tramadol in dogs undergoing enucleation.

    Enucleation is one of the more common ophthalmic surgeries performed in both general and specialty veterinary practices. This procedure is often performed in dogs in response to an intractably painful eye secondary to glaucoma, corneal rupture, and other causes. The surgical procedure itself is also painful for dogs, considering that the adnexa, globe, and orbit are richly innervated with sensory nerves.1 Animals with postoperative ocular pain may self-traumatize, which can lead to undesirable postoperative complications such as dehiscence or secondary infection. Few studies have addressed the management of postoperative pain in ocular surgery; however, local anesthetic infiltration of the retrobulbar space has been shown to provide excellent analgesia after enucleation in dogs.2 The published retrobulbar injection technique3 requires some technical skill and may not be an analgesic method that many veterinarians would feel competent in without prior training.

    Among analgesic drugs, NSAIDs remain the most popular for oral administration in dogs. However, several oral analgesic medications with various mechanisms of action are gaining popularity for the treatment of postsurgical pain in dogs, but studies of their actual efficacy are limited. Among those medications, tramadol is the most intriguing because its metabolites have mechanisms of action that suggest it is a multimodal analgesic that targets many points along the pain processing pathway. Tramadol is legally available in the oral formulation in the United States and has quickly gained popularity as an analgesic for dogs with both acute and chronic pain. As of recently, the Drug Enforcement Administration published (docket No. DEA-351) its decision to schedule tramadol as a schedule IV controlled substance. Tramadol is an isomeric drug, of which the (+)-enantiomer is a weak μ-opioid receptor agonist with analgesic potency approximately one-tenth that of morphine.4,5 In addition, the (+)-eantiomer acts within the spinal cord dorsal horn to inhibit serotonin reuptake, thereby providing analgesia in much the same way that the SSRI drugs do.5 The (–)-enantiomer of tramadol inhibits norepinephrine reuptake in the spinal cord dorsal horn, thus providing yet another mechanism for analgesia.6 Early research indicated when given orally to dogs at doses of 4 mg/kg (1.8 mg/lb), tramadol achieves therapeutic plasma concentrations within 5 minutes and persists in plasma at measurable concentrations for between 5 and 10 hours.7 More recent research showed that at a dose of 10 mg/kg (4.5 mg/lb) given orally to dogs, many of the metabolites thought to be important for opioidmediated analgesia achieved low plasma concentrations, suggesting that the reported analgesic effects may be independent of opioid activity.8 Despite tramadol's interesting mechanisms of action, little is published regarding its analgesic efficacy in dogs when given orally for either postsurgical pain or chronic pain. Because of its ease of use and safety profile, many practitioners prescribe tramadol, despite limited and conflicting data as to its efficacy.

    Many published reports do exist, however, on the efficacy of carprofen to treat moderate postsurgical pain in dogs. All of these studies9–12 compare carprofen with analgesic drugs that are generally considered to be of moderate effectiveness. Carprofen provides analgesia by reducing prostaglandin synthesis in injured tissues by virtue of cyclooxygenase II inhibition.13 Because this drug may also inhibit cyclooxygenase I, there is the potential for carprofen to have toxic effects on the kidneys and liver, cause gastrointestinal ulceration or upset, and inhibit platelet adhesion. Because of these adverse effects and because of its relatively moderate analgesic effects, carprofen should not be used in animals with renal or hepatic disease or as the single analgesic in those undergoing major surgical procedures.

    Although it is reasonable to assume that enucleation is a painful procedure, evaluation of this pain in canine patients can be challenging.14–16 Veterinarians must use clinical impressions of pain, expectations of potential pain, and careful observation to assess true levels of discomfort. Single-observer, subjective observation and interpretation of specific pain-related behaviors17,18 is the best way to evaluate pain in animals, despite the potential for observer bias.15,19,20 A pain scoring system has been validated in a previous study2 by our group.

    The objective of the study reported here was to compare tramadol with another commonly administered oral analgesic, the NSAID carprofen, for analgesic efficacy in dogs following enucleation. Because of its multiple proposed mechanisms of action, we hypothesized that tramadol would be a superior analgesic, compared with carprofen, in dogs undergoing this type of surgery.