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


METHODS
Prospective, randomized, open label.


METHODS
Operating room of a university hospital.


METHODS
65 ASA physical status I and II patients undergoing gynecological laparatomies.


METHODS
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.


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.


CONCLUSIONS
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.
Röpcke
H
H
Department of Anesthesiology and Intensive Care Medicine, University of Bonn, Germany. roepcke@mailer.meb.uni-bonn.de
Lier
H
H
Hoeft
A
A
Schwilden
H
H
D000328:Adult; D000367:Age Factors; D000465:Algorithms; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D016001:Confidence Intervals; D004347:Drug Interactions; D004357:Drug Synergism; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology*; D007813:Laparotomy; D008875:Middle Aged; D008956:Models, Chemical; D009330:Nebulizers and Vaporizers; D009609:Nitrous Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D011446:Prospective Studies
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D007530:Isoflurane; D009609:Nitrous Oxide; D005283:Fentanyl