Resumen de Analgesic effect of intra-articularly administered morphine, dexmedetomidine, or a morphine-dexmedetomidine combination immediately following stifle joint surgery in dogs
Objective—To compare the analgesic effects of intra-articularly administered saline (0.9% NaCl) solution, morphine, dexmedetomidine, and a morphine-dexmedetomidine combination in dogs undergoing stifle joint surgery for cranial cruciate ligament rupture.
Design—Randomized, controlled, clinical trial.
Animals—44 dogs with cranial cruciate ligament rupture that underwent tibial tuberosity advancement (TTA) or tibial plateau leveling osteotomy (TPLO).
Procedures—Dogs received intra-articular injections of saline solution (0.2 mL/kg [0.09 mL/lb]), morphine (0.1 mg/kg [0.045 mg/lb]), dexmedetomidine (2.5 μg/kg [1.14 μg/lb]), or a combination of morphine (0.1 mg/kg) and dexmedetomidine (2.5 μg/kg). Intra-articular injections of the stifle joint were performed after completion of the corrective osteotomy procedure, just prior to skin closure. Signs of pain were assessed every 2 hours thereafter on the basis of mean behavioral and objective pain scores. Dogs with pain scores exceeding predetermined thresholds were given hydromorphone (0.05 mg/kg [0.023 mg/lb], SC) as rescue analgesia.
Results—Time to rescue analgesia did not significantly differ between dogs that underwent TTA versus TPLO. No significant difference in time to rescue analgesia was found among dogs receiving intra-articular injections of dexmedetomidine (median, 6 hours; range, 2 to 10 hours), morphine (median, 7 hours; range, 4 to 10 hours), or saline solution (median, 5 hours; range, 4 to 10 hours). However, time to rescue analgesia for dogs receiving intra-articular injection of the morphine-dexmedetomidine combination (median, 10 hours; range, 6 to 14 hours) was significantly longer than the time to rescue analgesia for other treatment groups.
Conclusions and Clinical Relevance—Intra-articular administration of the morphine-dexmedetomidine combination provided longer-lasting postoperative analgesia, compared with either morphine or dexmedetomidine alone, in dogs undergoing TTA or TPLO. (J Am Vet Med Assoc 2014;244:1291–1297) Cranial cruciate ligament rupture is one of the most common orthopedic injuries in dogs.1 Many surgical techniques have been proposed for stifle joint stabilization, including osteotomy techniques such as TTA and TPLO. As with many other orthopedic surgeries, patients can have moderate to severe pain following these procedures. Traditionally, in the immediate postoperative period, opioid medications are administered via oral, SC, IM, or IV routes. However, opioid-related adverse effects such as ileus, nausea, vomiting, constipation, bradycardia, hypotension, respiratory depression, sedation, and dysphoria can occur.2–5 These adverse effects can prolong patient recovery and hospitalization. Repeated dosing can also be labor-intensive, increase financial cost to the owner, and increase patient stress.
Epidural analgesia has been suggested as an alternative to overcome systemic opioid-related adverse effects. Disadvantages of epidural analgesia include technical difficulty, especially for overweight dogs in which the landmarks might be more difficult to localize; CSF or blood contamination; neurologic complications; urinary retention; pruritus; and slow hair regrowth at the injection site.4,6,7 Also, if the epidural injection is administered incorrectly, inadequate analgesia will result. In a series of 636 dogs receiving epidural pain management, it was reported that signs of pain persisted in 12% of the dogs treated.8 The intra-articular use of local anesthetic drugs has been shown to improve postoperative pain scores and reduce opioid administration and its related adverse effects.9 However, multiple studies have shown that several of the most commonly used local anesthetics, such as bupivacaine, lidocaine, and ropivacaine, are toxic to human and animal chondrocytes both in vitro and in vivo, which raises concerns about their inclusion in an ideal pain management protocol.10–13 Opioids have been administered intra-articularly in humans and dogs. In humans, an intra-articular injection of morphine has been reported to have a 24- to 48-hour duration of effect after knee arthroscopy.14,15 In comparison, intra-articular morphine administration in dogs has been reported to have a 6-hour duration of effect after lateral extracapsular stabilization of the stifle joint.16 A recent study17 on humans revealed that intra-articular administration of dexmedetomidine enhanced postoperative pain relief, decreased the need for postoperative rescue analgesia, and prolonged the time to the first rescue analgesic protocol after arthroscopic knee surgery. In humans, intra-articular administration of morphine and clonidine, an α2-adrenoceptor agonist, in combination resulted in longer postoperative pain relief, compared with each drug given alone.18 That clinical study18 revealed the potential peripheral analgesic effect of the combination of an opioid and α2-adrenoceptor agonist after intra-articular administration. A study19 on rats also supports a longer analgesic duration of action when coadministering these 2 drugs. In a canine study,20 a combination of medetomidine and morphine epidurally had a synergistic effect, producing a superior duration of effect than did either drug used alone.
To the authors' knowledge, intra-articular use of dexmedetomidine alone or in combination with morphine for postoperative pain management following TPLO or TTA in dogs has not been evaluated. The objective of the study reported here was to compare the analgesic effects of intra-articularly administered morphine, dexmedetomidine, and their combination versus saline (0.9% NaCl) solution (control). It was hypothesized that morphine and dexmedetomidine in combination would provide a longer duration of analgesia than morphine or dexmedetomidine alone. It was further hypothesized that morphine would produce a longer analgesic duration than dexmedetomidine.
