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Modeling of a safety threshold for remifentanil as adjunct to locoregional anesthesia

par Camu, Frédéric ;Lauwers, Marylin;VAN LERSBERGHE, Caroline
Référence Regional Anesthesia, 21, 4, page (388)
Publication Publié, 1996

Article révisé par les pairs

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Résumé :

Remifentanil, a selective esterase - metabolised u-opioid agonist has potent analgesic and sedative activity in humans, with a pharmacokinetic/pharmacodynamic profile that facilitates rapid control of clinical end-points. These properties can be helpful during locoregional anesthetic procedures. This study investigated the margin of safety of remifentanil infusions using oxygen saturation as clinical end-point. Methods : Pulse oximetry (SpO2) was continuously monitored during remifentanil infusions varying from 0.04 to 0.1 ug/kg/min in 12 patients treated for hand surgery under axillary block. Changes of infusion rate were noted to the nearest minute. The predicted remifentanil plasma concentrations (Cp) were derived from the dosing infusion schemes using published pharmacokinetic parameters'. The hysteresis loops of SpO, vs predicted Cp were then collapsed using a semi-parametric modeling approach2. This allowed to further define the effect-site concentration (C6) - SpO2 relationship. SpO2 of 90 % was defined as a threshold, i.e. a potential safety issue, and the corresponding remifentanil C. read. We then calculated the infusion rate needed to reach this threshold in the population. Data are expressed as log mean + 95 % confidence intervals. Results : The data yielded a rate constant k>0 of 0.066/min (0.045 0.099). The half-time for equilibration between Cp and drug effect was 10.4 min (7 - 15.5). The target plasma concentration corresponding to the set threshold was 3.2 ng/ml (2.2 - 4.8) which would be reached in 10 min at an infusion rate of 0.046 ug/kg/min (0.031 - 0.067). Conclusion : These preliminary results indicate that remifentanil infusions given at a rate up to 0.046 ug/kg/min can be administered without excessive oxygen desaturation. as adjunct treatment to locoregional blocks.__________________________.