EFFECTS OF COMBINING PROPOFOL AND ALFENTANIL ON VENTILATION, ANALGESIA SEDATION AND EMESIS IN HUMAN VOLUNTEERS

Background: Propofol and alfentanil frequently are administered togeth er for intravenous sedation. This study investigated pharmacokinetic a nd pharmacodynamic interactions between propofol and alfentanil, at se dative concentrations, with specific regard to effects on ventilation, analgesia, sedation, and nausea. Methods: Ten male volunteers underwe nt steady-state infusions on 3 separate days consisting of propofol al one, alfentanil alone, or a combination of the two. Target plasma conc entrations for propofol were 150, 300, and 600 ng/ml for 1 h at each c oncentration; for alfentanil it was 40 ng/ml for 3 h. Assessment inclu ded serial measurements of (1) ventilatory function (minute ventilatio n, carbon dioxide production, end-tidal carbon dioxide, ventilatory re sponse to rebreathlng 7% CO2); (2) analgesia (subjective pain report i n response to graded finger shock and evoked potential amplitude); (3) sedation (subjective rating, observer scores, and digit symbol substi tution test); (4) nausea (visual analog scale, 0-100 mm). Results: Dur ing combination treatment, propofol plasma concentration was 22% great er than during propofol alone using replicate infusion schemes (P < 0. 009). End-tidal carbon dioxide was unchanged by propofol, and increase d equally by alfentanil and alfentanil/propofol combined (Delta end-ti dal carbon dioxide 7.5 and 6.2 mmHg, respectively). Analgesia with pro pofol/alfentanil combined was greater than with alfentanil alone. (Pai n report decreased 50% by PA vs. 28% for alfentanil, P < 0.05). Sedati on was greater with propofol/alfentanil combined than with alfedtanil or propofol alone (digit symbol substitution test 30 for propofol/alfe ntanil combined us. 57 for alfentanil, and 46 for propofol, P < 0.05). Nausea occurred in 50% of subjects during alfentanil, but in none dur ing propofol/alfentanil combination treatment. Conclusions: The combin ation of propofol and alfentanil produced greater sedation and analges ia than that with either drug alone. Propofol offset the emetic effect s of alfentanil. Equivalent depression of the carbon dioxide response curve, and elevation of end-tidal carbon dioxide occurred with propofo l/alfentanil combined and alfentanil.