Effects of Combining Propofol and Alfentanil on Ventilation, Analgesia, Sedation, and Emesis in Human Volunteers

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Abstract
Background: Propofol and alfentanil frequently are administered together for intravenous sedation. This study investigated pharmacokinetic and pharmacodynamic interactions between propofol and alfentanil, at sedative concentrations, with specific regard to effects on ventilation, analgesia, sedation, and nausea. Methods: Ten male volunteers underwent steady-state infusions on 3 separate days consisting of propofol alone, alfentanil alone, or a combination of the two. Target plasma concentrations for propofol were 150, 300, and 600 ng/ml for 1 h at each concentration; for alfentanil it was 40 ng/ml for 3 h. Assessment included serial measurements of (1) ventilatory function (minute ventilation, carbon dioxide production, end-tidal carbon dioxide, ventilatory response to rebreathing 7% CO2); (2) analgesia (subjective pain report in response to graded finger shock and evoked potential amplitude); (3) sedation (subjective rating, observer scores, and digit symbol substitution test); (4) nausea (visual analog scale, 0-100 mm). Results: During combination treatment, propofol plasma concentration was 22% greater than during propofol alone using replicate infusion schemes (P < 0.009). End-tidal carbon dioxide was unchanged by propofol, and increased equally by alfentanil and alfentanil/propofol combined (delta end-tidal carbon dioxide 7.5 and 6.2 mmHg, respectively). Analgesia with propofol/alfentanil combined was greater than with alfentanil alone. (Pain report decreased 50% by PA vs. 28% for alfentanil, P < 0.05). Sedation was greater with propofol/alfentanil combined than with alfentanil or propofol alone (digit symbol substitution test 30 for propofol/alfentanil combined vs. 57 for alfentanil, and 46 for propofol, P < 0.05). Nausea occurred in 50% of subjects during alfentanil, but in none during propofol/alfentanil combination treatment. Conclusions: The combination of propofol and alfentanil produced greater sedation and analgesia than that with either drug alone. Propofol offset the emetic effects of alfentanil. Equivalent depression of the carbon dioxide response curve, and elevation of end-tidal carbon dioxide occurred with propofol/alfentanil combined and alfentanil.