Alfentanil Dose-Response Relationships for Relief of Postoperative Pain

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Abstract
The aim of this study was to characterize within-patient alfentanil dose-response curves for the relief of spontaneous postoperative pain and to test the closeness of relationships 1) between pain intensity and alfentanil analgesic requirements, and 2) between alfentanil requirements for analgesic and nonanalgesic (sedative and miotic) effects. The effects of alfentanil were studied in 23 patients after elective abdominal surgery. During a 40- to 60-min testing session, the patient received two intravenous (i.v.) injections of saline (placebo) and up to six 3-micrograms/kg increments of alfentanil at 5-min intervals. The patient rated the pain intensity with a visual analog scale, and in a subgroup of 15 patients the blinded observer rated patients' sedation and measured pupil diameter. Spontaneous postoperative pain was completely relieved in all patients with cumulative doses of alfentanil ranging from 6 to 8 micrograms/kg. The within-patient alfentanil dose-analgesic response curves were primarily quantal in nature: a precipitous decrease in pain intensity (representing > or = 2/3 of the total effect) after the injection of only one of the increments of alfentanil was observed in 15 of 23 patients. When the analgesic effect of alfentanil was presented as the collective response of a group of individuals, the quantal nature of the response was concealed by the wide interindividual variability of the response. No statistically significant relationship was noted between predrug pain intensity and the cumulative dose of alfentanil necessary to produce pain relief. A strong correlation was found between interpatient variabilities in the analgesic and sedative effects of alfentanil (r = 0.75, P < 0.002). At the same time, the relationship between alfentanil requirements for pain relief and that for pupil constriction did not demonstrate any significant correlation. The results suggest that, in a population of patients with postoperative pain, the intensity of spontaneous pain cannot be the primary factor determining the dose of alfentanil necessary for its relief.