Neurobehavioral and physiologic effects of trifluoromethane in humans.
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.
Fagan
S C
SC
College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, MI 48202, USA.
Rahill
A A
AA
Balakrishnan
G
G
Ewing
J R
JR
Branch
C A
CA
Brown
G G
GG
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
D005617:Chlorofluorocarbons, Methane; D002245:Carbon Dioxide; D010100:Oxygen; C009554:fluoroform