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Isoflurane, nitrous oxide, and fentanyl pharmacodynamic interactions in surgical patients as measured by effects on
1Department of Anesthesiology and Intensive Care Medicine, University of Bonn, Germany. roepcke@mailer.meb.uni-bonn.de
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 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 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: [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.
Conclusion:
The 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.
Insights
This study found that isoflurane, nitrous oxide (N2O), and fentanyl interactions are additive during surgery. Their potency to replace isoflurane is lower than expected from minimum alveolar concentration studies.
Area of Science:
- Anesthesiology
- Pharmacology
- Neuroscience
Background:
- Understanding drug interactions is crucial for safe anesthesia.
- Isoflurane, nitrous oxide (N2O), and fentanyl are commonly used anesthetic agents.
- Quantifying their combined effects guides clinical practice.
Purpose of the Study:
- To quantify the simultaneous interactions of isoflurane, N2O, and fentanyl.
- To determine the pharmacodynamic effects of these agents on EEG median power frequency.
- To develop a model for their combined anesthetic potency.
Main Methods:
- Prospective, randomized, open-label study in 65 patients undergoing gynecological laparotomies.
- Varying doses of fentanyl and concentrations of N2O were administered.
- Isoflurane was adjusted to maintain EEG median power frequency between 2-3 Hz.
Main Results:
- The interaction between isoflurane, N2O, and fentanyl was found to be additive.
- A mathematical model was developed to describe their relative potencies and age dependency.
- The potency of N2O and fentanyl to substitute isoflurane was less than predicted.
Conclusions:
- The combined effect of isoflurane, N2O, and fentanyl is additive.
- The anesthetic potency of N2O and fentanyl is lower than suggested by MAC studies.
- Findings provide a quantitative model for these drug interactions in clinical settings.