T. Saari, J. Fechner, H. Ihmsen, J. Schüttler, C. Jeleazcov
Department of Anaesthesiology, University of Erlangen-Nürnberg, Erlangen, Germany
Objectives: Target controlled infusion (TCI) with sufentanil is usually performed with Gepts model [1], which was derived from patients undergoing general surgery. We studied the performance of TCI during coronary artery bypass surgery with cardiopulmonary bypass (CPB) with a special emphasis on the effect of CPB on the protein binding.
Methods: After IRB approval, written informed consent was obtained from 13 male patients undergoing coronary artery bypass surgery. Anaesthesia was managed with propofol and TCI of sufentanil, using the Gepts model. Six timed arterial samples were drawn from each patient. The accuracy of the TCI model was assessed by the prediction error (PE) and a pharmacokinetic model was determined by population analysis (NONMEM 7.2) using linear multicompartment models. The influence of demographic and clinical characteristics on the elimination clearance and volumes of distribution were examined.
Results: The median prediction error of the TCI with Gepts model before, during and after CPB was 59.6%, 3.9 % and -10.4 %, respectively. The unbound sufentanil concentrations increased significantly during CPB. Pharmacokinetics were adequately described by a two-compartment model (median PE=-2.2%, median absolute PE=21.2%). The elimination clearance CL1 was significantly higher during and after CPB when compared to the pre-bypass phase. Volumes of distribution increased slightly during and after CPB. CL1 could be modelled as a function of hepatic blood flow and free fraction ("well-stirred" model). V1 and V2 could be modelled as a function of free fraction.
Conclusion: Dosing based on Gepts model led to an overshoot of total sufentanil concentrations at the beginning of cardiac anaesthesia. Also, the observed higher unbound sufentanil concentrations during CPB may have an impact in postoperative pain therapy. Significant changes of sufentanil pharmacokinetics during CPB could be attributed to changes in protein binding and hepatic blood flow. However, because of a sparse sampling in the present trial, further studies are warranted to confirm the present results.
References:
[1] Anesthesiology 1995;83:1194-204.
Reference: PAGE 21 (2012) Abstr 2331 [www.page-meeting.org/?abstract=2331]
Poster: Other Drug/Disease Modelling