title: Combinations of dexmedetomidine and alfaxalone with butorphanol in cats: application of an innovative stepwise optimisation method to identify optimal clinical doses for intramuscular anaesthesia.
abstract: The aim of this study was to optimise dexmedetomidine and alfaxalone dosing, for intramuscular administration with butorphanol, to perform minor surgeries in cats.
  
  
  
  Initially, cats were assigned to one of five groups, each composed of six animals and receiving, in addition to 0.3 mg/kg butorphanol intramuscularly, one of the following: (A) 0.005 mg/kg dexmedetomidine, 2 mg/kg alfaxalone; (B) 0.008 mg/kg dexmedetomidine, 1.5 mg/kg alfaxalone; (C) 0.012 mg/kg dexmedetomidine, 1 mg/kg alfaxalone; (D) 0.005 mg/kg dexmedetomidine, 1 mg/kg alfaxalone; and (E) 0.012 mg/kg dexmedetomidine, 2 mg/kg alfaxalone. Thereafter, a modified 'direct search' method, conducted in a stepwise manner, was used to optimise drug dosing. The quality of anaesthesia was evaluated on the basis of composite scores (one for anaesthesia and one for recovery), visual analogue scales and the propofol requirement to suppress spontaneous movements. The medians or means of these variables were used to rank the treatments; 'unsatisfactory' and 'promising' combinations were identified to calculate, through the equation first described by Berenbaum in 1990, new dexmedetomidine and alfaxalone doses to be tested in the next step. At each step, five combinations (one new plus the best previous four) were tested.
  
  
  
  None of the tested combinations resulted in adverse effects. Four steps and 120 animals were necessary to identify the optimal drug combination (0.014 mg/kg dexmedetomidine, 2.5 mg/kg alfaxalone and 0.3 mg/kg butorphanol).
  
  
  
  The investigated drug mixture, at the doses found with the optimisation method, is suitable for cats undergoing minor clinical procedures.
authors.affiliation: Department of Clinical Sciences and Services, Royal Veterinary College, University of London, Hatfield, UK cadami@rvc.ac.uk.
authors.forename: Chiara
authors.initials: C
authors.lastname: Adami
authors.affiliation: Tierarztpraxis Bachtelwald AG, Wald, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Imboden
authors.affiliation: Department of Veterinary Clinical Science, Anaesthesiology and Pain Therapy Division, Vetsuisse Faculty of the University of Bern, Bern, Switzerland.
authors.forename: Annalisa Elena
authors.initials: AE
authors.lastname: Giovannini
authors.affiliation: Department of Veterinary Clinical Science, Anaesthesiology and Pain Therapy Division, Vetsuisse Faculty of the University of Bern, Bern, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Spadavecchia
mesh_terms: D000758:Anesthesia / Q000662:veterinary; D000762:Anesthesia Recovery Period; D019162:Anesthetics, Combined / Q000008:administration & dosage*; D000818:Animals; D002077:Butorphanol / Q000008:administration & dosage*; D002415:Cats / Q000502:physiology* / Q000601:surgery; D020927:Dexmedetomidine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D007273:Injections, Intramuscular / Q000662:veterinary; D008297:Male; D011277:Pregnanediones / Q000008:administration & dosage*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D019162:Anesthetics, Combined; D011277:Pregnanediones; D020927:Dexmedetomidine; C006477:alphaxalone; D002077:Butorphanol