Simple SummaryStanding surgery and diagnostic procedures in equine patients under deep sedation reduce the risk associated with general anesthesia. Sedation protocols must be safe, provide a good quality of sedation without producing cardiorespiratory depression and severe ataxia. The use of adrenergic alpha-2 receptors agonist in combination with opioids and/or ketamine can achieve an adequate sedation and provide sufficient analgesia for surgical procedures. Medetomidine and medetomidine with morphine in intravenous constant rate infusion have been evaluated for standing sedation but have not been compared directly. Although ketamine has been combined with other alpha-2 agonists successfully, it has not been evaluated in combination with medetomidine. The objective of this study was to compare four medetomidine-based protocols with the addition of morphine and/or ketamine, including cardiorespiratory, sedative and mechanical antinociceptive variables. All four protocols produced a similar degree of sedation and mechanical antinociception without clinically relevant impact on cardiorespiratory variables.Standing surgery under sedation reduces anesthetic-related mortality in horses. Medetomidine, alone and combined with morphine in a constant rate infusion (CRI), has been described for standing surgery but their cardiorespiratory, sedative and antinociceptive effects have never been compared. The addition of ketamine could improve analgesia in these procedures with minimal cardiorespiratory consequences. The objectives were to compare the cardiorespiratory effects, quality of sedation, antinociception and ataxia produced by administration of a medetomidine-based CRI with morphine, ketamine or both, in standing horses. A prospective, blind, randomized crossover, experimental design with six healthy adult horses was performed, in which four treatments were administered to all horses with at least two weeks of washout period: medetomidine (M); medetomidine and ketamine (MK); medetomidine and morphine (MMo); and medetomidine, morphine and ketamine (MMoK). Dosages were the same in all treatment groups: medetomidine at 5 µg/kg bwt followed by 5 µg/kg bwt/h, ketamine at 0.4 mg/kg/h and morphine at 50 µg/kg bwt, followed by morphine 30 µg/kg bwt/h. Drug infusions were maintained for 120 min. Cardiorespiratory variables, sedation degree and antinociceptive effects were evaluated during the procedure. All combinations produced similar sedation and antinociceptive effects and no clinically relevant alterations in cardiorespiratory variables occurred. Medetomidine CRI combined with morphine, ketamine or both are suitable and safe protocols for standing sedation in horses and the addition of morphine and/or ketamine did not cause any negative effect but no improving effect on sedation and antinociception was detected.