Interaction between nitrous oxide, sevoflurane, and opioids: a response surface approach.
BACKGROUND
The interaction of sevoflurane and opioids can be described by response surface modeling using the hierarchical model. We expanded this for combined administration of sevoflurane, opioids, and 66 vol.% nitrous oxide (N2O), using historical data on the motor and hemodynamic responsiveness to incision, the minimal alveolar concentration, and minimal alveolar concentration to block autonomic reflexes to nociceptive stimuli, respectively.


METHODS
Four potential actions of 66 vol.% N2O were postulated: (1) N2O is equivalent to A ng/ml of fentanyl (additive); (2) N2O reduces C50 of fentanyl by factor B; (3) N2O is equivalent to X vol.% of sevoflurane (additive); (4) N2O reduces C50 of sevoflurane by factor Y. These four actions, and all combinations, were fitted on the data using NONMEM (version VI, Icon Development Solutions, Ellicott City, MD), assuming identical interaction parameters (A, B, X, Y) for movement and sympathetic responses.


RESULTS
Sixty-six volume percentage nitrous oxide evokes an additive effect corresponding to 0.27 ng/ml fentanyl (A) with an additive effect corresponding to 0.54 vol.% sevoflurane (X). Parameters B and Y did not improve the fit.


CONCLUSIONS
The effect of nitrous oxide can be incorporated into the hierarchical interaction model with a simple extension. The model can be used to predict the probability of movement and sympathetic responses during sevoflurane anesthesia taking into account interactions with opioids and 66 vol.% N2O.
Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. h.e.m.vereecke@umcg.nl
Hugo E M
HE
Vereecke
Johannes H
JH
Proost
Bjorn
B
Heyse
Douglas J
DJ
Eleveld
Takasumi
T
Katoh
Martin
M
Luginbühl
Michel M R F
MM
Struys
D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005283:Fentanyl / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008875:Middle Aged; D009609:Nitrous Oxide / Q000494:pharmacology*; D000077149:Sevoflurane; D055815:Young Adult
D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D009609:Nitrous Oxide; D005283:Fentanyl