Abstract
Background and Objective
We recently developed a new population pharmacokinetic model for hydromorphone in patients including age and bodyweight as covariates. The aim of the present study was to evaluate prospectively the predictive performance of this new model during postoperative pain therapy.
Methods
This was a prospective, single-blinded, randomized, single-center study with two parallel arms. Fifty patients aged 40–85 years undergoing cardiac surgery involving thoracotomy were enrolled. Hydromorphone was administered postoperatively on the intensive care unit as target controlled infusion (TCI) for patient controlled analgesia (TCI-PCA) using the new pharmacokinetic model, or as conventional patient controlled analgesia (PCA). Arterial blood samples were taken for measurement of the hydromorphone plasma concentration. The predictive performance of the pharmacokinetic model was assessed by the median performance error (MDPE), the median absolute performance error (MDAPE), wobble and divergence. For comparison, the performance indices were also determined for three older models from the literature.
Results
903 plasma concentrations of 41 patients were analyzed. The mean values (95 % CI) of MDPE, MDAPE, wobble and divergence for the new pharmacokinetic model were 11.2 % (3.9 to 18.7 %), 28.5 % (23.9 to 33.0 %), 21.4 % (18.0 to 24.9 %) and −1.6 %/h (–2.3 to –0.8 %/h). When compared with older models from the literature, performance was better with less overshoot after bolus doses.
Conclusion
The new pharmacokinetic model of hydromorphone showed a good precision and a better performance than older models. It is therefore suitable for TCI with hydromorphone during postoperative pain therapy.
Trial Registration
EudraCT 2013-002875-16, Clinical Trials NCT02035709.
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Acknowledgments
The authors thank Rainer Knoll, Dipl. Bioingenieur (Department of Anesthesiology, University of Erlangen-Nürnberg, Erlangen, Germany) for conducting the drug analysis. Else Huprich, M.A. (Department of Anesthesiology, University of Erlangen-Nürnberg, Erlangen, Germany), and Tobias Fuchte, Michael Kim, Sven Kremer and Alexander Weiß, Medical Students (Department of Anesthesiology, University of Erlangen-Nürnberg, Erlangen, Germany) are thanked for their assistance in data collection. Gabriele Göhring-Waldeck, Laboratory Technician (Department of Anesthesiology, University of Erlangen-Nürnberg, Erlangen, Germany) for her invaluable help in patient recruitment and study organization.
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This work has been supported by a grant of the German Federal Ministry of Education and Research, Berlin, Germany (Bundesministerium für Bildung und Forschung, Grant no: FKZ 13EX1015B).
Conflict of interest
Harald Ihmsen, Doris Rohde, Jürgen Schüttler and Christian Jeleazcov declare that they have no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Written informed consent was obtained from all individual participants included in the study.
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Ihmsen, H., Rohde, D., Schüttler, J. et al. External Validation of a Recently Developed Population Pharmacokinetic Model for Hydromorphone During Postoperative Pain Therapy. Eur J Drug Metab Pharmacokinet 42, 17–28 (2017). https://doi.org/10.1007/s13318-015-0318-x
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DOI: https://doi.org/10.1007/s13318-015-0318-x