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Pulmonary distribution of alfentanil and sufentanil studied with system dynamics analysis
Authors:Fred Boer  Andreas Hoeft  Martin Scholz  James G. Bovill  Antoin G. L. Burm  Adrie Hak
Affiliation:1. Department of Anaesthesiology, University Hospital Leiden, P.O. Box 9600, 2300 RC, Leiden, The Netherlands
2. Department of Anaesthesiology, Reanimation and Critical Care, University Hospital G?ttingen, Robert Kochstrasse 40, D3400, G?ttingen, Germany
3. Department of Clinical Chemistry, University Hospital Leiden, P.O. Box 9600, 2300 RC, Leiden, The Netherlands
Abstract:We applied a system dynamics approach to the study of the pulmonary distribution of alfentanil and sufentanil in anesthetized pigs and patients, respectively. This method allows estimation of the mean transit time through the lungs and calculation of the volume of distribution of alfentanil in the lungs. In the first part of the study the pulmonary distribution of alfentanil was studied in six anesthetized pigs during three hemodynamic states (control, partial clamping of the inferior vena cave, and complete clamping of the right pulmonary artery). In the second part of the study the pulmonary distribution of sufentanil was studied in 10 patients, scheduled for elective CABG, during and after a constant rate infusion of 10 min. Pulmonary passage of the opioids was characterized by functions of transit times, derived from the pulmonary arterial and systemic arterial concentration curves. Pulmonary distribution volumes were calculated from the mean transit time and pulmonary blood flow. Pulmonary distribution volume of alfentanil during the control measurement was significantly higher (486±88 ml) than during either partial caval clamping (346±89 ml, p<0.05) or right pulmonary artery clamping (336±56 ml, p<0.05). There was no change in the extravascular volume of distribution of alfentanil with each hemodynamic state. Pulmonary volume of distribution of sufentanil in the patients was 22.6 (10.9) L. Pulmonary distribution of opioids can be studied using system dynamics analysis, both after bolus injection and during and after infusion. This method can be used for periods beyond the initial passage of the drug through the lungs.
Keywords:alfentanil  sufentanil  lung metabolism  pharmacokinetic tissue distribution  indocyanine green  humans  pigs  convolution analysis
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