Isoflurane, nitrous oxide, and fentanyl pharmacodynamic interactions in surgical patients as measured by effects on median power frequency

Abstract

Study Objective: To 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.Design: Prospective, randomized, open label.Setting: Operating room of a university hospital.Patients: 65 ASA physical status I and II patients undergoing gynecological laparatomies.Interventions: 25 patients received no fentanyl. 20 patients received a loading dose of 100 μg fentanyl and a continuous infusion of 70 μg · 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 μg fentanyl and a continuous infusion of 150 μg · 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 Results: The interaction of isoflurane, N2O, and fentanyl is compatible with additivity. A model with regard to the relative potencies and age dependency is given by:Isoflurane conc.c0,iso·10a·(age−35)+N2O conc.c0,N2O·10a·(age−35)+Fentanyl conc.c0,fen·10a·(age−35)=1.0