• H Röpcke, H Lier, A Hoeft, and H Schwilden.
• Department of Anesthesiology and Intensive Care Medicine, University of Bonn, Germany. roepcke@mailer.meb.uni-bonn.de
• J Clin Anesth. 1999 Nov 1;11(7):555-62.

Study ObjectiveTo identify and quantify the simultaneous interactions of isoflurane, nitrous oxide (N2O), and fentanyl during surgical procedures. The slowing of the EEG to a median power frequency of 2 Hz to 3 Hz was chosen as the measure of pharmacodynamic drug effect.DesignProspective, randomized, open label.SettingOperating room of a university hospital.Patients65 ASA physical status I and II patients undergoing gynecological laparatomies.Interventions25 patients received no fentanyl. 20 patients received a loading dose of 100 micrograms fentanyl and a continuous infusion of 70 micrograms.h-1 fentanyl. Calculated effect compartment concentrations were 0.7 ng.ml-1 between the first and second hours after induction of anesthesia. Another 20 patients received a loading dose of 200 micrograms fentanyl and a continuous infusion of 150 micrograms.h-1 fentanyl; the respective effect compartment concentrations were 1.5 ng.ml-1. N2O was randomly administered in concentrations of 0, 20, 40, and 60 vol%; in the group that did not receive fentanyl, we additionally investigated 75 vol% N2O. Each patient received two different N2O concentrations, with each combination of N2O and fentanyl finally applied to ten patients. Isoflurane vaporizer settings were chosen so that the median power frequency was held between 2 Hz and 3 Hz. The type and degree of interaction among the three anesthetic drugs was analyzed based on a generalized isobole approach.Measurements And Main ResultsThe interaction of isoflurane, N2O, and fentanyl is compatible with additivity. A model with regard to the relative potencies and age dependency is given by: [formula: see text] with C0,iso = 1.30 vol%, C0,N2O = 177 vol%, C0,fen = 10.6 ng.ml-1, and a = -0.0031 yr-1. where conc. = end-tidal or effect compartment concentrations.ConclusionThe potency of N2O and fentanyl to substitute isoflurane in maintaining a median power frequency of 2 Hz to 3 Hz during surgery is less than anticipated from minimum alveolar concentration studies.

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