title: IV ATP potentiates midazolam sedation as assessed by bispectral index.
abstract: In this study, by measuring bispectral index (BIS), we tested the hypothesis that intravenous adenosine 5'-triphosphate (ATP) infusion would deepen the level of midazolam-induced sedation. Ten healthy volunteers underwent 2 experiments with at least 2 weeks' interval: immediately after intravenous bolus administration of midazolam (0.04 mg/kg), they received continuous infusion of either ATP infusion (100 μg/kg/min) or placebo (saline) for 40 minutes in a double-blind, randomized, crossover manner. Changes in BIS values and responsiveness to verbal command as well as cardiorespiratory variables were observed throughout the study periods. Administration of midazolam alone reduced BIS value from control: 97 ± 1 to 68 ± 18 at 25 minutes, which was accompanied by significant cardiopulmonary depressant effects, while maintaining responsiveness to verbal command (consciousness) throughout the study period. Coadministration of ATP with midazolam further reduced BIS value to 51 ± 13, associated with complete loss of consciousness without adverse effect on the cardiorespiratory systems. We conclude that the addition of ATP infusion to midazolam significantly enhances midazolam sedation without disturbing cardiorespiratory functions.
authors.affiliation: Assistant Professor, Department of Dental Anesthesiology, Tokyo Dental College, Chiba, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Sakurai
authors.forename: Atsuo
authors.initials: A
authors.lastname: Fukunaga
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ichinohe
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kaneko
mesh_terms: D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000627:therapeutic use*; D061605:Administration, Intravenous; D001794:Blood Pressure / Q000187:drug effects; D019296:Capnography; D002245:Carbon Dioxide / Q000032:analysis; D016292:Procedural Sedation / Q000379:methods*; D003243:Consciousness / Q000187:drug effects; D056805:Consciousness Monitors; D018592:Cross-Over Studies; D054810:Deep Sedation / Q000379:methods; D004311:Double-Blind Method; D004357:Drug Synergism; D004569:Electroencephalography; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D008297:Male; D008874:Midazolam / Q000008:administration & dosage*; D010092:Oximetry; D010100:Oxygen / Q000097:blood; D010919:Placebos; D012119:Respiration / Q000187:drug effects; D013990:Tidal Volume / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects
chemical_list: D006993:Hypnotics and Sedatives; D010919:Placebos; D002245:Carbon Dioxide; D000255:Adenosine Triphosphate; D008874:Midazolam; D010100:Oxygen
keywords: ATP; Central adenosine receptors; Midazolam sedation