title: Pulmonary distribution of alfentanil and sufentanil studied with system dynamics analysis.
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.
authors.affiliation: Department of Anaesthesiology, University Hospital Leiden, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Boer
authors.forename: A
authors.initials: A
authors.lastname: Hoeft
authors.forename: M
authors.initials: M
authors.lastname: Scholz
authors.forename: J G
authors.initials: JG
authors.lastname: Bovill
authors.forename: A G
authors.initials: AG
authors.lastname: Burm
authors.forename: A
authors.initials: A
authors.lastname: Hak
mesh_terms: D015760:Alfentanil / Q000493:pharmacokinetics*; D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D000818:Animals; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008954:Models, Biological; D017409:Sufentanil / Q000493:pharmacokinetics*; D013552:Swine; D014018:Tissue Distribution
chemical_list: D000701:Analgesics, Opioid; D015760:Alfentanil; D017409:Sufentanil