Interaction Between Nitrous Oxide, Sevoflurane, and Opioids: A Response Surface Approach

Vereecke, Hugo E M; Proost, Johannes H; Heyse, Bjorn; Eleveld, Douglas J; Katoh, Takasumi; Luginbühl, Martin; Struys, Michel M R F (2013). Interaction Between Nitrous Oxide, Sevoflurane, and Opioids: A Response Surface Approach. Anesthesiology, 118(4), pp. 894-902. Hagerstown, Md.: Lippincott Williams & Wilkins 10.1097/ALN.0b013e3182860486

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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. 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.% N2O.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic and Policlinic for Anaesthesiology and Pain Therapy

UniBE Contributor:

Luginbühl, Martin




Lippincott Williams & Wilkins




Jeannie Wurz

Date Deposited:

04 Oct 2013 14:33

Last Modified:

23 Jan 2018 12:16

Publisher DOI:


PubMed ID:


Web of Science ID:


URI: (FactScience: 219509)

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