Interaction between Nitrous Oxide, Sevoflurane, and Opioids

Abstract

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 sevoflu- rane, opioids, and 66 vol.% nitrous oxide (N2 O), using historical data on the motor and hemodynamic responsiveness to incision, the minimal alveolar concentration, and minimal alveolar con- centration to block autonomic reflexes to nociceptive stimuli, respectively. Methods: Four potential actions of 66 vol.% N2 O were pos- tulated: (1) N2 O is equivalent to A ng/ml of fentanyl (addi- tive); (2) N2O reduces C50 of fentanyl by factor B; (3) N2 O is equivalent to X vol.% of sevoflurane (additive); (4) N2 O reduces C50 of sevoflurane by factor Y. These four actions, and all combinations, were fitted on the data using NON- MEM (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. Conclusion: 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.% N2 O.