CO2-RESPONSE CURVES AS A MEASURE OF OPIATE INDUCED RESPIRATORY DEPRESSION - A REVIEW BASED ON STUDIES WITH FENTANYL IN VOLUNTEERS

  • 1 January 1983
    • journal article
    • review article
    • Vol. 32  (6) , 242-258
Abstract
The ventilatory response to CO2 after fentanyl 4 .mu.g/kg was studied in a group of 10 healthy volunteers of both sexes, aged 20-41 yr. Following randomized i.v. premedication with either placebo, diazepam 5 mg, droperidol 5 mg of etomidate 10 mg, a total of 4 tests series were performed with each individual in 2-wk intervals to assess the additive effect of central depressants on opiate-induced respiratory depression. CO2-response curves were obtained during 6-min rebreathing periods up to 60 min after fentanyl. Respiratory frequency, slope and position of the curves were compared with pre-drug control values. After fentanyl, CO2-response curves usually showed combined decreases in slope and displacements to the right, which had not completely returned to control levels after 1 h. Due to enormous inter- and intra-individual variations, no clearly significant differences were observed between premedication groups. Fentanyl plasma concentrations, determined by radioimmunoasay at 1, 3, 6, 10, 20, 30, 45, 60, 75 and 120 min after injection, showed only a poor correlation to the changes of the CO2-response curves. To assess the clinical relevance of results derived from CO2-stimulation studies, the literature is reviewed with respect to the respiratory control system and the interactions of various anesthetic drugs (including opiate analgesics) with respiratory regulation. Apparently, the activity of the reticular formation at lower brain stem level is important for adequate ventilation. Despite quite different action sites, most central depressant drugs reduce reticular activity, thus inhibiting compensatory mechanisms whcih usually help control respiration. Therefore CO2-response tests may be unable to give sufficient clinical information about the respiratory regulation system.