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Heart rate (HR) or mean arterial blood pressure (MAP) may increase in response to incision despite the absence of a motor response. The authors hypothesized that the MAC-BAR (minimum alveolar concentration of an anesthetic that blocks adrenergic response to incision) for isoflurane would exceed that for desflurane, and that fentanyl would decrease the MAC-BAR for each anesthetic in a dose-dependent manner.Seventy-one patients were randomly allocated to one of six groups: desflurane or isoflurane without fentanyl or with 1.5 or 3 micro gram/kg fentanyl given intravenously 5 min before surgical incision. Anesthesia was induced with 2 mg/kg propofol given intravenously, and tracheal intubation facilitated with 0.1 mg/kg given intravenously. The first patient in each group received 1 MAC (end-tidal) of the inhaled anesthetic in 60% nitrous oxide (0.55 MAC), balance oxygen, maintained for at least 10 min before incision. The response was considered positive if the HR or MAP increased 15% or more. If the response was positive, the end-tidal concentration given to the next patient was 0.3 MAC greater; if the response was negative, the end-tidal concentration was 0.3 MAC less. The MAC-BAR level was calculated as the mean of four independent cross-over responses in each group.Desflurane and isoflurane anesthesia with 60% nitrous oxide did not change HR (P > 0.05) and decreased MAP (P < 0.05) before incision. Plasma epinephrine and norepinephrine concentrations after anesthesia and before incision were normal in all groups. The MAC-BAR level, without fentanyl, did not differ (P > 0.05) between desflurane (1.30 +/- 0.34 MAC [mean +/- SD]) and isoflurane (1.30 +/- 0.18 MAC). Fentanyl given at 1.5 micro gram/kg intravenously equivalently (P > 0.05) reduced the MAC-BAR for desflurane (to 0.40 +/- 0.18 MAC; P <0.05) and isoflurane (to 0.55 +/- 0.00 MAC; P < 0.05), but a further increase in fentanyl to 3 micro gram/kg caused no greater decrease in the MAC-BAR for desflurane (0.48 +/- 0.16 MAC) and isoflurane (0.40 +/- 0.30 MAC).Clinically attainable doses of desflurane and isoflurane, in 60% nitrous oxide (0.55 MAC), block the cardiovascular response to surgical incision at 1.3 MAC. Fentanyl given at 1.5 micro gram/kg decreases the MAC-BAR for each agent with no further decrease produced by 3 micro gram/kg fentanyl.