THE COMPARATIVE AMNESTIC EFFECTS OF MIDAZOLAM, PROPOFOL, THIOPENTAL, AND FENTANYL AT EQUISEDATIVE CONCENTRATIONS

Background The authors evaluated the effects of midazolam, propofol th iopental, and fentanyl on volunteer participants' memory for words and pictures at equisedative concentrations. Methods: Sixty-seven healthy volunteers were randomized to receive intravenous infusions of midazo lam (n = 11), propofol (n = 11), thiopental (n = 10), fentanyl with on dansetron pretreatment (n = 11), ondansetron alone (n = 8), or placebo (n = 16) in a double-blind design. Three increasing and then two decr easing sedative concentrations were achieved by computer-controlled in fusion in each volunteer. Measures of sedation, memory, and drug conce ntration were obtained at each target concentration. Drug concentratio ns were normalized to equisedative effects using both Emax and logisti c regression methods of pharmacodynamic modeling. The serum concentrat ions at 50% memory effect (Cp50s) were determined using four different memory end points. The relative potencies compared with midazolam for memory impairment mere determined. Results: Equisedative concentratio ns were midazolam, 64.5 +/- 9.4 ng/ml; propofol, 0.7 +/- 0.2 mu g/ml; thiogental, 2.9 +/- 1.0 mu g/ml; and fentanyl, 0.9 +/- 0.2 ng/ml. The Cp50s for 50% loss of memory for words were midazolam, 56 +/- 4 ng/ml; propofol, 0.62 +/- 0.04 mu g/ml; thiopental, 4.5 +/- 0.3 mu g/ml and fentanyl, 3.2 +/- 0.4 ng/ml. Compared with midazolam, relative potenci es (with 95% confidence intervals) were propofol, 0.96 (0.44-1.78); th iopental, 0.76 (0.52-0.94); and fentanyl, 0.34 (0.05-0.76). Large effe cts on memory were only produced by propofol and midazolam. Conclusion s: At equal sedation, propofol produces the same degree of memory impa irment as midazolam. Thiopental has mild memory effects whereas fentan yl has none. Ondansetron alone has no sedative or amnesic effects.