Determination of a safe sedative combination of dexmedetomidine, ketamine and butorphanol for minor procedures in dogs by use of a stepwise optimization method

Abstract

Background: In veterinary practice, most minor procedures such as radiographs, skin biopsies and wound treatments require sedation. The combination of butorphanol, ketamine and dexmedetomidine is commonly used, but the ideal dosages for this combination have not been reported. This randomized prospective clinical trial initially tested 8 clinically relevant combinations in a blinded procedure in 50 dogs. The quality of each combination was rated using a purposefully developed negative score (NS; 0-21.5, the lower the NS the better the quality of sedation), to judge the quality of sedation, the occurrence of side effects, and need for additional anaesthetics. Then the combinations were divided into "promising" and "unsatisfactory" subgroups and their centroids Pc and Uc were determined before a new combination (N) was calculated using the formula N=Pc+α*(Pc-Uc). The combination N was tested in 6 dogs and then it replaced the worst of the previous 8 combinations. The same procedure was repeated after each new combination until the NS did not improve any further. As a last step, the best combination was tested in 100 adult dogs undergoing diagnostic or therapeutic procedures. Results: The optimal combination found was dexmedetomidine 0.005 mg/kg, ketamine 1 mg kg-1, and butorphanol 0.3 mg kg-1 with a median NS of 1.5 (interquartile range 1.5-2.4). In all 112 dogs receiving this combination, the quality of sedation was satisfactory and no severe side effects were detected. Conclusions: The application of this optimization method allowed the calculation of an optimal drug combination for sedation in healthy dogs. This combination revealed safe after being tested in 100 animals. This combination can now be used in daily clinical practice for healthy adult dogs undergoing minor procedures.