title: Neurobehavioral and physiologic effects of trifluoromethane in humans.
abstract: Nuclear magnetic resonance (NMR) imaging shows promise in the measurement of human cerebral blood flow (CBF) in that nonradioactive indicators may be used. Our earlier investigations with trifluoromethane (FC-23) gas have shown that this compound can be used to safely and effectively measure CBF in anesthetized animal models. In this Phase I dose-escalation study we set out to determine the maximal tolerated concentration (MTC) of FC-23 in normal healthy male volunteers and to assess its feasibility as an NMR indicator. Five subjects were exposed in a blinded fashion to escalating concentrations of FC-23 between 10% and 60%, randomly interleaved with exposures to both room air and 40% nitrous oxide. On each study day, the subjects breathed the test gas for eight pulses of 3 min each with 2-min clearance periods between the pulses. The subjects underwent intensive physiologic and neurobehavioral monitoring throughout the study period. The first subject experienced an anesthetic response to 60% FC-23, and the second subject experienced "discomfort" and requested discontinuation at the initiation of 40% FC-23. The MTC was subsequently determined to be 30% FC-23 (all subjects tolerated the gas), although a small (37.6 vs. 40.5) but statistically significant retention of carbon dioxide was found (p = .003). When one subject received 30% FC-23 during an NMR imaging study, a pronounced anesthetic effect with intolerable hyperacusis was demonstrated. Human studies of FC-23 have been discontinued in our laboratory.
authors.affiliation: College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, MI 48202, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Fagan
authors.forename: A A
authors.initials: AA
authors.lastname: Rahill
authors.forename: G
authors.initials: G
authors.lastname: Balakrishnan
authors.forename: J R
authors.initials: JR
authors.lastname: Ewing
authors.forename: C A
authors.initials: CA
authors.lastname: Branch
authors.forename: G G
authors.initials: GG
authors.lastname: Brown
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001774:Blood Chemical Analysis; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005617:Chlorofluorocarbons, Methane / Q000009:adverse effects* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010100:Oxygen / Q000097:blood; D012119:Respiration / Q000187:drug effects
chemical_list: D005617:Chlorofluorocarbons, Methane; D002245:Carbon Dioxide; D010100:Oxygen; C009554:fluoroform