Topical morphine in a canine model: A pilot study

Abstract

Objective: To determine if topical morphine can enter the synovial cavity and the effect of ultrasound on this process. Design: A randomized control trial to investigate which body fluids morphine enters after topical application. Setting: A university animal laboratory. Subjects: Ten mongrol dogs raised by the Comparative Medicine Department. All animals were certified to be free of disease, all had received standard scheduled immunizations, and none had been used for any other research. Intervention: Topical morphine and ultrasound or topical morphine and sham ultrasound was applied to the knees of the dogs. Samples were obtained afterward from synovial fluid, serum, and urine, and were analyzed for the presence of morphine. Main Outcome Measures: Blood samples were collected every 60 minutes for 240 minutes, urine samples were collected at 120 minutes and 240 minutes, and synovial joint fluid was collected at 120 minutes and 240 minutes. The process of collection and analysis was the same for dogs treated with topical morphine and ultrasound and those treated with topical morphine and sham ultrasound. Fisher's exact test was used to test for an association between the use of ultrasound and the presence of morphine in the synovial fluid, serum, or urine. Two-sample t tests were used to test for group differences in mean body weight. Results: All samples (synovial fluid, serum, and urine) were negative at time zero. All of the subsequent serum samples were negative for morphine. Two or three of the dogs in each group of five (ultrasound or sham ultrasound) had positive urine and synovial fluid samples at 120 and 240 minutes. Ultrasound did not affect the results. Body weight of the dogs influenced the results, with lighter animals having a significantly larger percentage ( p = .03) of synovial fluid samples positive for morphine. Conclusion: Ultrasound did not affect the absorption of topical morphine in this canine model. Body weight may have influenced the results. Dogs that tested positive for morphine in synovial fluid had a lower mean body weight than dogs that did not test positive ( p = .03).