RESEARCH ARTICLE
Model-Based Prediction of the Patient-Specific Response to Adrenaline
J. Geoffrey Chase1, Christina Starfinger1, Christopher E Hann*, 1, James A Revie1, Dave Stevenson1, Geoffrey M Shaw2, Thomas Desaive3
Article Information
Identifiers and Pagination:
Year: 2010Volume: 4
First Page: 149
Last Page: 163
Publisher Id: TOMINFOJ-4-149
DOI: 10.2174/1874431101004010149
Article History:
Received Date: 18/09/2009Revision Received Date: 02/02/2010
Acceptance Date: 03/05/2010
Electronic publication date: 29/07/2010
Collection year: 2010
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
Abstract
A model for the cardiovascular and circulatory systems has previously been validated in simulated cardiac and circulatory disease states. It has also been shown to accurately capture the main hemodynamic trends in porcine models of pulmonary embolism and PEEP (positive end-expiratory pressure) titrations at different volemic levels. In this research, the existing model and parameter identification process are used to study the effect of different adrenaline doses in healthy and critically ill patient populations, and to develop a means of predicting the hemodynamic response to adrenaline. The hemodynamic effects on arterial blood pressures and stroke volume (cardiac index) are simulated in the model and adrenaline-specific parameters are identified. The dose dependent changes in these parameters are then related to adrenaline dose using data from studies published in the literature. These relationships are then used to predict the future, patient-specific response to a change in dose or over time periods from 1-12 hours. The results are compared to data from 3 published adrenaline dosing studies comprising a total of 37 data sets. Absolute percentage errors for the identified model are within 10% when re-simulated and compared to clinical data for all cases. All identified parameter trends match clinically expected changes. Absolute percentage errors for the predicted hemodynamic responses (N=15) are also within 10% when re-simulated and compared to clinical data. Clinically accurate prediction of the effect of inotropic circulatory support drugs, such as adrenaline, offers significant potential for this type of model-based application. Overall, this work represents a further clinical, proof of concept, of the underlying fundamental mathematical model, methods and approach, as well as providing a template for using the model in clinical titration of adrenaline in a decision support role in critical care. They are thus a further justification in support of upcoming human clinical trials to validate this model.
