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The hemodynamic changes, plasma norepinephrine levels, pupil size, and rapidity of postoperative mental recovery were measured and compared in 72 patients randomly assigned in a double-blind manner to receive either morphine, meperidine, fentanyl, or sufentanil as supplements to nitrous oxide anesthesia. Meperidine, unlike the other opioids, which did not change heart rate, consistently increased it. Hemodynamic responses to laryngoscopy and intubation were suppressed by fentanyl and sufentanil, but not by morphine or meperidine. The sufentanil group was the only group in which median norepinephrine levels remained consistently below preinduction values. The frequency with which opioids had to be administered (doses/hr) was significantly less with sufentanil than with morphine and meperidine. Meperidine produced less constriction of the pupils than the other opioids and the duration of miosis was shorter. Fentanyl and sufentanil were associated with a more rapid return of mental function than morphine and meperidine. Meperidine caused deleterious effects on objective tests of psychomotor and cognitive skills that were not reflected by subjective evaluation of rate of recovery from anesthesia. The authors conclude that moderate doses of fentanyl and sufentanil are better supplements to nitrous oxide anesthesia than morphine or meperidine and that fentanyl and sufentanil are equally satisfactory. Subjective effects of the opioids correlated well with changes in pupil diameter.