title: The effect of midazolam on the end-tidal concentration of isoflurane necessary to prevent movement in dogs.
abstract: OBJECTIVE
  To determine the possible additive effect of midazolam, a GABA(A) agonist, on the end-tidal concentration of isoflurane that prevents movement (MAC(NM) ) in response to noxious stimulation.
  
  
  METHODS
  Randomized cross-over experimental study.
  
  
  METHODS
  Six healthy, adult intact male, mixed-breed dogs.
  
  
  METHODS
  After baseline isoflurane MAC(NM) (MAC(NM-B) ) determination, midazolam was administered as a low (LDS), medium (MDS) or high (HDS) dose series of midazolam. Each series consisted of two dose levels, low and high. The LDS was a loading dose (Ld) of 0.2 mg kg(-1) and constant rate infusion (CRI) (2.5 μg kg(-1) minute(-1)) (LDL), followed by an Ld (0.4 mg kg(-1)) and CRI (5 μg kg(-1) minute(-1)) (LDH). The MDS was an Ld (0.8 mg kg(-1)) and CRI (10 μg kg(-1) minute(-1)) (MDL) followed by an Ld (1.6 mg kg(-1)) and CRI (20 μg kg(-1) minute(-1)) (MDH). The HDS was an Ld (3.2 mg kg(-1)) and CRI (40 μg kg(-1) minute(-1)) (HDL) followed by an Ld (6.4 mg kg(-1)) and CRI (80 μg kg(-1) minute(-1)) (HDH). MAC(NM) was re-determined after each dose in each series (MAC(NM-T)).
  
  
  RESULTS
  The median MAC(NM-B) was 1.42. MAC(NM-B) did not differ among groups (p > 0.05). Percentage reduction in MAC(NM) was significantly less in the LDS (11 ± 5%) compared with MDS (30 ± 5%) and HDS (32 ± 5%). There was a weak correlation between the plasma midazolam concentration and percentage MAC(NM) reduction (r = 0.36).
  
  
  CONCLUSIONS
  Midazolam doses in the range of 10-80 μg kg(-1) minute(-1) significantly reduced the isoflurane MAC(NM) . However, doses greater than 10 μg kg(-1) minute(-1) did not further decrease MAC(NM) indicating a ceiling effect.
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA. mrsed@utk.edu
authors.forename: Reza
authors.initials: R
authors.lastname: Seddighi
authors.forename: Christine M
authors.initials: CM
authors.lastname: Egger
authors.forename: Barton W
authors.initials: BW
authors.lastname: Rohrbach
authors.forename: Sherry K
authors.initials: SK
authors.lastname: Cox
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Doherty
mesh_terms: D000769:Anesthesia, Inhalation / Q000379:methods / Q000662:veterinary*; D018685:Anesthetics, Inhalation / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D018592:Cross-Over Studies; D004285:Dogs / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D007530:Isoflurane / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008874:Midazolam / Q000493:pharmacokinetics / Q000494:pharmacology*; D009068:Movement / Q000187:drug effects*
chemical_list: D018685:Anesthetics, Inhalation; D006993:Hypnotics and Sedatives; D007530:Isoflurane; D008874:Midazolam