[CO2-response curves as a measure of opiate-induced respiratory depression. Studies with fentanyl]

The ventilatory response to CO2 after fentanyl 4 micrograms/kg was studied in a group of 10 healthy volunteers of both sexes, aged 20 to 41 years. Following randomization intravenous premedication with either placebo, diazepam 5 mg, droperidol 5 mg or etomidate 10 mg, a total of four test series were performed with each individual in two-week intervals, in order to assess the additive effect of central depressants on opiate-induced respiratory depression. CO2-response curves were obtained during six-minute rebreathing periods up to 60 min after fentanyl. Respiratory frequency as well as 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 one hour. Due to enormous inter- and intra-individual variations, no clearly significant differences could be observed between the premedication groups. Fentanyl plasma concentrations, determined by radioimmunoassay 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 anaesthetics drugs (including opiate analgesics) with respiratory regulation. The activity of the reticular formation at lower brain stem level seems to be of decisive importance to guarantee adequate ventilation. Despite quite different action sites, most central depressant drugs reduce reticular activity, thus inhibiting compensatory mechanisms which usually help control respiration. CO2-response tests are therefore suggested to be unable to give sufficient clinical information about the respiratory regulation system.