Pharmacokinetic/pharmacodynamic model for unfractionated heparin dosing during cardiopulmonary bypass X. Delavenne, E. Ollier, S. Chollet, F. Sandri,

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Pharmacokinetic/pharmacodynamic model for unfractionated heparin dosing during cardiopulmonary bypass X. Delavenne, E. Ollier, S. Chollet, F. Sandri, J. Lanoiselée, S. Hodin, A. Montmartin, J.-F. Fuzellier, P. Mismetti, L. Gergelé British Journal of Anaesthesia Volume 118, Issue 5, Pages 705-712 (May 2017) DOI: 10.1093/bja/aex044 Copyright © 2017 The Author(s) Terms and Conditions

Fig 1 First row: goodness of fits for the pharmacokinetic model. Left, observed anti-factor Xa activities vs population predictions; centre, observed anti-factor Xa activities vs individual predictions; and right, normalized prediction distribution error (NPDE) vs time. The black dashed line corresponds to the identity line and the orange line to the regression line. Second row: goodness of fits for the pharmacodynamic model. Left, observed activated clotting time values vs population predictions; centre, observed ACT values vs individual predictions; and right, NPDE vs time. The black dashed line corresponds to the identity line and the blue line to the regression line. British Journal of Anaesthesia 2017 118, 705-712DOI: (10.1093/bja/aex044) Copyright © 2017 The Author(s) Terms and Conditions

Fig 2 Visual predictive check of the pharmacokinetic/pharmacodynamic relationship. The orange curve represents the median of the simulated activated clotting time (ACT). The coloured, shaded envelope represents the 90% confidence interval for the simulations. The black dots represent the observed ACT values. British Journal of Anaesthesia 2017 118, 705-712DOI: (10.1093/bja/aex044) Copyright © 2017 The Author(s) Terms and Conditions

Fig 3 Population model simulation of anti-factor Xa activity and activated clotting time profile for different types of administration based on a patient weighing 70 kg. The black curve corresponds to the median of the simulations. The coloured, shaded envelopes represent the 80, 60, 40, and 20% confidence intervals, respectively. (A) Simulated anti-factor Xa activities for the bolus-plus-infusion strategy. (B) Simulated activated clotting time (ACT) values for the bolus-plus-infusion strategy. (C) Simulated anti-factor Xa activities for the repeated bolus strategy. (D) Simulated ACT values for the repeated bolus strategy. British Journal of Anaesthesia 2017 118, 705-712DOI: (10.1093/bja/aex044) Copyright © 2017 The Author(s) Terms and Conditions

Fig 4 Prediction of individual activated clotting time (ACT) values for three patients not included in the development of the population pharmacokinetic/pharmacodynamic model. The black curves correspond to the prediction based on the mean population parameters. The green and blue curves correspond to the prediction based on individual parameters estimated using only the first and only the first two observed ACT values, respectively. The orange curves correspond to the prediction based on individual parameters estimated using all available anti-factor Xa activities and ACT values. British Journal of Anaesthesia 2017 118, 705-712DOI: (10.1093/bja/aex044) Copyright © 2017 The Author(s) Terms and Conditions