title: Dose-response characteristics of midazolam for reducing diaphragmatic contractility.
abstract: A sedative dose of midazolam decreases contractility of the diaphragm, but no data are available concerning the relationship between dose and diaphragmatic contractility. We studied the dose-response characteristics of midazolam for reducing the diaphragmatic contractility in dogs. Animals were divided into three groups of eight each: Group 1 received no study drug, Group 2 was infused with a sedative dose of midazolam (0.1 mg/kg initial dose plus 0.1 mg x kg(-1) x h(-1) maintenance dose), and Group 3 was infused with an anesthetic dose of midazolam (0.1 mg/kg initial dose plus 0.5 mg x kg(-1) x h(-1) maintenance dose). We assessed the diaphragmatic contractility by transdiaphragmatic pressure (Pdi). With an infusion of midazolam in Groups 2 and 3, Pdi at low-frequency (20 Hz) and high-frequency (100 Hz) stimulation decreased from the baseline values (P < 0.05), and the integrated electrical activity of diaphragm (Edi) at 100-Hz stimulation decreased from the baseline values, whereas Edi at 20-Hz stimulation did not change. Compared with Group 1, Pdi and Edi for each stimulus decreased during midazolam infusion in Groups 2 and 3 (P < 0.05). The decrease in Pdi and Edi was more in Group 3 than in Group 2 (P < 0.05). We conclude that midazolam decreases, in a dose-dependent manner, contractility of the diaphragm in dogs.
authors.affiliation: Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba City, Ibaraki, Japan. yfujii@igaku.md.tsukuba.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Fujii
authors.forename: T
authors.initials: T
authors.lastname: Hoshi
authors.forename: A
authors.initials: A
authors.lastname: Uemura
authors.forename: H
authors.initials: H
authors.lastname: Toyooka
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D003964:Diaphragm / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D011312:Pressure
chemical_list: D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D008874:Midazolam