Tokushige et al. Acta Vet Scand (2018) 60:50 https://doi.org/10.1186/s13028-018-0406-4 Acta Veterinaria Scandinavica RESEARCH Open Access Clinical evaluation of constant rate infusion of alfaxalone–medetomidine combined with sevofurane anesthesia in Thoroughbred racehorses undergoing arthroscopic surgery Hirotaka Tokushige1* , Asuka Kushiro1, Atsushi Okano1, Tatsuya Maeda1, Hideki Ito1, Ai Wakuno2, Shun‑ichi Nagata3 and Minoru Ohta4 Abstract Background: Alfaxalone has a number of pharmacological properties which are desirable for constant rate infu‑ sion (CRI). Previously, the co-administration of alfaxalone and medetomidine is shown to be suitable for short-term anesthesia in horses. However, the use of alfaxalone–medetomidine CRI with inhalational anesthesia under surgical procedures have not been investigated in clinical cases. The aim of the present study was to evaluate the clinical efcacy of alfaxalone–medetomidine CRI in sevofurane-anesthetized Thoroughbred racehorses undergoing arthro‑ scopic surgery. Sevofurane requirement, cardiovascular function, and induction/recovery quality were compared between horses maintained with sevofurane in combination with medetomidine CRI (3 µg/kg/h) (Group M; n 25) and those maintained with sevofurane in combination with alfaxalone–medetomidine CRI (0.5 mg/kg/h and 3= µg/ kg/h, respectively) (Group AM; n 25). = Results: The mean end-tidal sevofurane concentrations were signifcantly lower in Group AM (1.8 0.2%) than in Group M (2.4 0.1%). The mean dobutamine infusion rate required for maintaining mean arterial blood± pressure within the target± values (60–80 mmHg) was signifcantly lower in Group AM (0.53 0.20 µg/kg/min) than in Group M (0.85 0.32 µg/kg/min). Induction and recovery scores were not signifcantly diferent± between two groups. However, excitatory± response during recovery were observed in fve horses in Group AM. The mean plasma alfaxalone concen‑ trations were stable throughout the maintenance period (0.77 0.12 to 0.85 0.13 µg/mL), and decreased signif‑ cantly immediately after standing (0.32 0.07 µg/mL). ± ± ± Conclusions: Alfaxalone–medetomidine CRI reduced sevofurane requirement by approximately 26% with good maintenance of cardiopulmonary function in Thoroughbred racehorses undergoing arthroscopic surgery. Sevofurane in combination with alfaxalone–medetomidine CRI may be a clinically efective anesthetic technique for Thorough‑ bred racehorses. However, 20% of horses administered alfaxalone showed remarkable excitatory response during recovery. Greater attention to excitatory response may be advisable if alfaxalone is used for induction or maintenance of anesthesia. A larger study is needed to explore the clinical relevance of these fndings. Keywords: Alfaxalone–medetomidine, Constant rate infusion, Equine anesthesia, Racehorse, Recovery, Sevofurane *Correspondence: [email protected] 1 Racehorse Clinic, Miho Training Center, Japan Racing Association (JRA), 2500‑2 Mikoma, Miho‑mura, Inashiki‑gun, Ibaraki 300‑0493, Japan Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat​iveco​mmons​.org/licen​ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat​iveco​mmons​.org/ publi​cdoma​in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Tokushige et al. Acta Vet Scand (2018) 60:50 Page 2 of 7 Background (Group M) and those maintained with sevofurane in Among the volatile anesthetic agents commonly used combination with alfaxalone–medetomidine CRI (Group in equine anesthesia, sevofurane has the advantages of AM). rapid induction of anesthesia, easy control of anesthetic depth and rapid recovery due to its low blood solubil- Methods ity [1–3]. However, sevofurane is known to cause dose- Animals dependent cardiopulmonary depression, which increases Our study included 50 Toroughbred racehorses with the risk of peri-anesthetic mortality and death [4–7]. chip fractures of the carpal bones undergoing arthro- Terefore, balanced anesthesia is often used to reduce scopic surgery. Te surgery was performed on a single the requirements of inhalation anesthetics and to thereby leg or both legs by randomly assigned experienced sur- minimize their cardiovascular depressant efects in geons. Te horses were assigned randomly to Group M equine practice [8]. or Group AM (25 horses in each group). In Group M, Most balanced anesthetic protocols include the use of anesthesia was maintained with sevofurane in combina- an α2-adrenoceptor agonist because of their potent seda- tion with medetomidine CRI; in Group AM, anesthesia tive and analgesic efects [8]. One such α2-adrenoceptor was maintained with sevofurane in combination with agonist is medetomidine, whose short half-life, selectiv- alfaxalone plus medetomidine CRI. Te mean ± stand- ity, and potency make it suitable for use as a constant rate ard deviation (SD) age and body weight were, respec- infusion (CRI) for balanced anesthesia in horses [9–12]. tively, 3.3 ± 0.5 years old and 470 ± 21 kg in Group M In a previous study, we found that medetomidine CRI and 3.1 ± 0.7 years old and 465 ± 28 kg in Group AM. All (3.0 µg/kg/h) reduced the sevofurane requirement for horses were subjected to preanesthetic blood testing and arthroscopic surgery by approximately 10% in Torough- electrocardiography. Food, but not water, was withheld bred racehorses, resulting in good maintenance of cardi- for 12 h prior to anesthesia. opulmonary function, and an improvement in the quality of recovery from anesthesia [13]. However, the anesthetic Experimental protocol sparing efect of medetomidine CRI on sevofurane was All horses were premedicated with medetomidine (Dor- insufcient to minimize the negative cardiovascular bene; Vetcare Oy, Salo, Finland) (5.0 µg/kg, IV) and efects of sevofurane, and cardiovascular depression dur- midazolam (Dormicum; Astellas Pharma Inc., Tokyo, ing the maintenance period still remained a concern. Japan) (20 µg/kg, IV) together. Anesthesia was induced in Alfaxalone is a synthetic neuroactive steroid that acts the horses in Group M by a rapid injection of 5% guaifen- on the gamma aminobutyric acid (GABA)A receptors in esin (5% Guaifenesin; Shinyo Pure Chemicals Co., Ltd., the central nervous system and produces unconscious- Osaka, Japan) (100 mg/kg, IV) with thiopental sodium ness and muscle relaxation. Several experimental tri- (Ravonal; Mitsubishi Tanabe Pharma Co., Osaka, Japan) als of alfaxalone in horses have been reported [14–18]. (4.0 mg/kg, IV); anesthesia in Group AM was induced It is reported that the efects of alfaxalone in relation to by guaifenesin (the same volume as in Group M) with induction of anesthesia, recovery quality, and cardiopul- alfaxalone (Alfaxan; Jurox Pty Ltd., Rutherford, Aus- monary response in Toroughbred horses are similar tralia) (1.0 mg/kg, IV). A scoring scale of 1–5 (G1: poor, to the efects of ketamine and thiopental [18], and that G2: marginal, G3: fair, G4: good, G5: excellent) was used alfaxalone has a number of pharmacological properties for the subjective assessment of induction of anesthesia which are desirable for CRI in horses [14, 19]. It is also [21]. After induction of anesthesia, horses were intubated reported that the co-administration of alfaxalone and endotracheally and positioned in dorsal recumbency. medetomidine as CRI after induction of anesthesia with Anesthesia was maintained with sevofurane (Sevofrane; alfaxalone is suitable for short-term anesthesia in horses Maruishi Pharmaceutical Co., Ltd., Osaka, Japan) and undergoing feld castration [20]. Terefore, a further oxygen (approximately 5 L/min) using an intermittent reduction in sevofurane requirement would be expected positive pressure ventilator (MOK 94; Silver Medical Co., if alfaxalone–medetomidine CRI was combined with Tokyo, Japan) with a peak airway pressure of 25 cmH2O sevofurane anesthesia. to maintain the arterial carbon dioxide tension (PaCO 2) Te purpose of this study was to assess the clinical between 45 and 55 mmHg. efcacy of alfaxalone–medetomidine CRI in sevofu- A base-apex lead electrocardiogram was used to moni- rane-anesthetized Toroughbred racehorses undergoing tor heart rate (HR) and rhythm. A 20-G catheter was arthroscopic surgery. In this study, sevofurane require- placed in the facial artery for arterial blood pressure ment, cardiopulmonary function, and induction/recov- measurements and arterial blood sample collections. ery quality were compared between horses maintained Arterial blood pressures were measured directly through with sevofurane in combination with medetomidine CRI the catheter by a transducer system. Respiratory gas was Tokushige et al. Acta Vet Scand (2018) 60:50 Page 3 of 7 collected continuously, and the end-tidal sevofurane using methyl tert-butyl ether. Te extracted substance concentrations (ETSEVO) was determined by infrared was analyzed using liquid chromatography–tandem mass absorption. Te ETSEVO was recorded throughout anes- spectrometry consisted of Shimadzu prominence HPLC thesia, and HR, systolic arterial blood pressure (SAP), system (Shimadzu Co., Tokyo, Japan) and AB Sciex diastolic arterial blood pressure