Original Contributions
Interaction modeling of propofol and sufentanil on loss of consciousness

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Abstract

Study Objectives: To examine the possible pharmacodynamic interaction of propofol and sufentanil with respect to the induction of loss of consciousness.

Design: Prospective, randomized, double-blinded study.

Setting: University hospital.

Patients: 30 female, ASA physical status I and II patients undergoing elective gynecologic surgery.

Interventions: Patients were allocated randomly to receive an individual combination of propofol (1, 2, 3, 4, 5, or 6 μg/ml) and sufentanil (0.1, 0.2, 0.3, 0.5, or 1.0 ng/ml) target blood concentrations using target-controlled infusions.

Measurements and Main Results: Study endpoint was loss of consciousness, which was tested by response to verbal commands and classified as responder or nonresponder, as assessed by the anesthetist, who was blinded to the drugs’ target blood concentrations. Nonlinear association (interaction) of both drugs was accomplished with logistic regression analysis using the maximum likelihood method, based principally on the hypothesis of interaction: ln [p/(1 − p)] = β0 + β1 · Cprop + β2 · Csuf + β3 · Cprop · Csuf with a p-value <0.05 for coefficient estimates considered significant. In the logistic regression model, sufentanil and propofol showed no supra-additive interaction regarding loss of consciousness (p = 0.5916).

Conclusions: Our results give no evidence of additional hypnotic properties of sufentanil compared to the other fentanyl congeners, although logistic regression may be of limited value in modeling interaction of hypnotic-analgesic combinations.

Introduction

Propofol and sufentanil frequently are combined to provide general anesthesia. The interactions between propofol and fentanyl,1 as well as alfentanil2 for different endpoints, have been characterized previously. It has been proposed that sufentanil’s hypnotic properties are more pronounced than those of other opioids when using equianalgesic doses.3 This theory was attributed mainly to a characteristic increase in the relative delta power of the electroencephalogram (EEG) seen with sufentanil infusion.4 Thus, sufentanil has been suggested to offer a favorable hypnotic profile for sedation in intensive care patients and to decrease the consumption of hypnotic drugs when used during anesthesia. However, apart from anecdotal reports, there are, to date, no controlled studies to support this hypothesis. The aim of this study, therefore, was to determine the hypnotic component of sufentanil by investigating the interaction of propofol and sufentanil on loss of consciousness.

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Materials and methods

After we obtained University of Ulm Institutional Ethics Committee approval and written informed consent, we studied 30 consecutive, unpremedicated, ASA physical status I and II female patients undergoing elective gynecologic laparatomy or body surface surgery. Patients older than 71 years, or with a known history of chronic drug or alcohol abuse, were excluded from the study, as were those obese patients whose body mass index was greater than 30 kg (m2)−1.

Acknowledgements

We would like to thank Dr. Martin Hirsch from the Department of Forensic Medicine for providing the assays and analysis of sufentanil.

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