title: Model-based prediction of the patient-specific response to adrenaline.
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.
authors: Centre for Bioengineering, University of Canterbury, Christchurch, New Zealand.
authors: J Geoffrey
authors: JG
authors: Chase
authors: Christina
authors: C
authors: Starfinger
authors: Christopher E
authors: CE
authors: Hann
authors: James A
authors: JA
authors: Revie
authors: Dave
authors: D
authors: Stevenson
authors: Geoffrey M
authors: GM
authors: Shaw
authors: Thomas
authors: T
authors: Desaive
references: Am J Hosp Pharm. 1993 Aug;50(8 Suppl 4):S6-8
references: 8213862
references: Crit Care. 2007;11(2):R51
references: 17470271
references: Comput Methods Programs Biomed. 2007 Jul;87(1):46-60
references: 17478006
references: Crit Care Resusc. 2007 Sep;9(3):264-9
references: 17767454
references: Med Eng Phys. 2004 Mar;26(2):131-9
references: 15036180
references: Comput Methods Programs Biomed. 2008 Aug;91(2):135-44
references: 18466998
references: Crit Care Nurse. 2002 Apr;22(2):60-4, 66-70, 73 passim
references: 11961944
references: J Clin Pharmacol. 2006 Aug;46(8):945-51
references: 16855079
references: Intensive Care Med. 2002 May;28(5):599-608
references: 12029409
references: Comput Methods Programs Biomed. 2008 Aug;91(2):128-34
references: 18472180
references: Comput Methods Programs Biomed. 2006 Feb;81(2):181-92
references: 16413632
references: CMAJ. 2003 Aug 19;169(4):307-11
references: 12925426
references: Circulation. 2005 Dec 13;112(24 Suppl):IV1-203
references: 16314375
references: Br J Clin Pharmacol. 1997 Apr;43(4):407-14
references: 9146853
references: Intensive Care Med. 1997 Mar;23(3):282-7
references: 9083230
references: Chest. 2001 Oct;120(4):1322-6
references: 11591577
references: J Cardiothorac Vasc Anesth. 1992 Oct;6(5):535-41
references: 1421064
references: Curr Opin Crit Care. 2002 Jun;8(3):236-41
references: 12386503
references: Annu Int Conf IEEE Eng Med Biol Soc. 2007;2007:2976-9
references: 18002620
references: Crit Care Med. 2003 Jan;31(1 Suppl):S17-24
references: 12544972
references: Comput Methods Programs Biomed. 2007 May;86(2):153-60
references: 17350711
references: Math Biosci. 2008 Dec;216(2):132-9
references: 18817788