Pharmacodynamic response modelling of arterial blood pressure in adult volunteers during propofol anaesthesia C. Jeleazcov, M. Lavielle, J. Schüttler,

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Presentation transcript:

Pharmacodynamic response modelling of arterial blood pressure in adult volunteers during propofol anaesthesia C. Jeleazcov, M. Lavielle, J. Schüttler, H. Ihmsen British Journal of Anaesthesia Volume 115, Issue 2, Pages 213-226 (August 2015) DOI: 10.1093/bja/aeu553 Copyright © 2015 The Author(s) Terms and Conditions

Fig 1 Time courses of the measured plasma concentrations of propofol (a) and measured arterial blood pressure (b–d) after start of the infusion of propofol at time zero. Each line depicts the data of one volunteer. SAP, systolic arterial blood pressure; MAP, mean arterial blood pressure; DAP, diastolic arterial blood pressure. British Journal of Anaesthesia 2015 115, 213-226DOI: (10.1093/bja/aeu553) Copyright © 2015 The Author(s) Terms and Conditions

Fig 2 Time course of measured divided by predicted plasma concentrations of propofol for individual (a) and population (b) model predictions. Each blue line depicts the data of one volunteer. British Journal of Anaesthesia 2015 115, 213-226DOI: (10.1093/bja/aeu553) Copyright © 2015 The Author(s) Terms and Conditions

Fig 3 Goodness-of-fit plots: measured arterial blood pressure vs the individual Bayesian (a, d and g) and the population predictions (b, e and h), and the population-weighted residuals vs time after start of the infusion of propofol at time zero (c, f and i) as obtained with the final pharmacodynamic model (direct response model 4 with two effect compartments). The solid black diagonal line represents the line of identity (measured=predicted). PWRES, population-weighted residuals. British Journal of Anaesthesia 2015 115, 213-226DOI: (10.1093/bja/aeu553) Copyright © 2015 The Author(s) Terms and Conditions

Fig 4 Visual prediction checks of the final pharmacodynamic model (direct response model 4 with two effect compartments) with the median of model predictions (blue line) and the 90% confidence interval (pink shaded area). Superimposed are the measured values of arterial blood pressure (black circles). SAP, systolic arterial blood pressure; MAP, mean arterial blood pressure; DAP, diastolic arterial blood pressure. British Journal of Anaesthesia 2015 115, 213-226DOI: (10.1093/bja/aeu553) Copyright © 2015 The Author(s) Terms and Conditions

Fig 5 Arterial blood pressure as a function of the effect site concentrations of propofol. Data were simulated for a 23 yr old individual using the final pharmacodynamic model (direct response model 4 with two effect compartments). The function is shown as 3D surface plot of SAP (a), MAP (b) and DAP (c). Superimposed are the measured blood pressure data in each volunteer (blue and green dots for values above and below the 3D surface, respectively) plotted vs the effect site concentrations, as calculated with the individual pharmacokinetic and pharmacodynamic parameters. EC1, effect site concentration in effect compartment 1; EC2, effect site concentration in effect compartment 2; SAP, systolic arterial blood pressure; MAP, mean arterial blood pressure; DAP, diastolic arterial blood pressure. British Journal of Anaesthesia 2015 115, 213-226DOI: (10.1093/bja/aeu553) Copyright © 2015 The Author(s) Terms and Conditions

Fig 6 Simulated time course of plasma and effect site concentrations of propofol and arterial blood pressure. Propofol infusion started with a bolus dose of 1.5 mg kg−1 at time zero, followed immediately by 10 mg kg−1 h−1 for 10 min, 8 mg kg−1 h−1 for the next 10 min, and 6 mg kg−1 h−1 for the remaining 60 min. The simulations were based on the final pharmacokinetic/-dynamic model for a 23 yr old individual of 70 kg body weight. Cp, plasma concentration; EC1, effect site concentration in effect compartment 1; EC2, effect site concentration in effect compartment 2; SAP, systolic arterial blood pressure; MAP, mean arterial blood pressure; DAP, diastolic arterial blood pressure. British Journal of Anaesthesia 2015 115, 213-226DOI: (10.1093/bja/aeu553) Copyright © 2015 The Author(s) Terms and Conditions