Peripherally acting α-adrenoceptor antagonist MK-467 with intramuscular medetomidine and butorphanol in dogs: A prospective, randomised, clinical trial

•The clinical usefulness of MK-467 in healthy dogs sedated with medetomidine–butorphanol for diagnostic imaging was assessed.•A combination of medetomidine, butorphanol and MK-467 provided reliable sedation for short clinical procedures.•Intramuscular MK-467 was associated with increased early stage...

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Published in:	The veterinary journal (1997) Vol. 240; pp. 22 - 26
Main Authors:	Kallio-Kujala, I.J., Turunen, H.A., Raekallio, M.R., Honkavaara, J.M., Salla, K.M., Casoni, D., Hautajärvi, H.J., Vainio, O.M.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-10-2018
Subjects:	Adrenergic alpha-Antagonists - therapeutic use Anaesthesia Animals Butorphanol Butorphanol - administration & dosage Canine Conscious Sedation - methods Conscious Sedation - veterinary Diagnostic Imaging - veterinary Dogs Drug Combinations Female Hypnotics and Sedatives - administration & dosage Injections, Intramuscular - veterinary Male Medetomidine Medetomidine - administration & dosage MK-467 Prospective Studies Quinolizines - therapeutic use Random Allocation Treatment Outcome Anaesthesia Medetomidine MK-467 Butorphanol Canine
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Summary:	•The clinical usefulness of MK-467 in healthy dogs sedated with medetomidine–butorphanol for diagnostic imaging was assessed.•A combination of medetomidine, butorphanol and MK-467 provided reliable sedation for short clinical procedures.•Intramuscular MK-467 was associated with increased early stage plasma concentrations of medetomidine and butorphanol.•Increased plasma concentrations of medetomidine–butorphanol were associated with earlier onset deeper initial sedation. The aim of this study was to investigate the clinical usefulness of MK-467 (vatinoxan; L-659’066) in dogs sedated for diagnostic imaging with medetomidine-butorphanol. It was hypothesised that MK-467 would alleviate bradycardia, hasten drug absorption and thus intensify the early-stage sedation. In a prospective, randomised, blinded clinical trial, 56 client-owned dogs received one of two IM treatments: (1) 0.5mg/m2 medetomidine+0.1mg/kg butorphanol (MB, n=29); or (2) 0.5mg/m2 medetomidine+0.1mg/kg butorphanol+10mg/m2 MK-467 (MB-MK, n=27). Heart rates and visual sedation scores were recorded at intervals. Plasma drug concentrations were determined in venous samples obtained approximately 14min after injection. Additional sedation (50% of original dose of medetomidine IM) and/or IM atipamezole for reversal were given when needed. The area under the sedation score-time curve for visual analogue scale (AUCVAS30) was calculated for the first 30min after treatment using the trapezoidal method. Repeated ANOVA, Mann–Whitney U test and Fisher’s exact test were used for parametric, non-parametric and dichotomous data. Heart rate was significantly higher from 10 to 40min with MB-MK than with MB. AUCVAS30 was significantly higher after MB-MK. More dogs treated with MB-MK required additional sedation after 30min, but fewer needed atipamezole for reversal compared with MB. Plasma concentrations of both medetomidine and butorphanol were higher after MB-MK. All procedures were successfully completed. MK-467 alleviated the bradycardia, intensified the early stage sedation and shortened its duration in healthy dogs that received IM medetomidine-butorphanol.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	1090-0233 1532-2971
DOI:	10.1016/j.tvjl.2018.08.007