computer methods and programs in biomedicine 83 ( 2 0 0 6 ) 211–221 journal homepage: www.intl.elsevierhealth.com/journals/cmpb Parameter identification and sedative sensitivity analysis of an agitation–sedation model Andrew D. Rudge a,* , J. Geoffrey Chase a , Geoffrey M. Shaw b , Dominic Lee c , Christopher E. Hann a a Centre for Bioengineering, Department of Mechanical Engineering, University of Canterbury, Christchurch, New Zealand b Department of Intensive Care Medicine, Christchurch Hospital, University of Otago School of Medicine and Health Sciences, Christchurch, New Zealand c Centre for Bioengineering, Department of Mathematics and Statistics, University of Canterbury, Christchurch, New Zealand article info Article history: Received 28 April 2005 Received in revised form 26 June 2006 Accepted 28 June 2006 Keywords: Parameter fitting System identification Integral-based Physiological models Dynamic modelling Agitation Sedation abstract Sedation administration and agitation management are fundamental activities in any intensive care unit. A lack of objective measures of agitation and sedation, as well as poor understanding of the underlying dynamics, contribute to inefficient outcomes and expensive healthcare. Recent models of agitation–sedation dynamics have enhanced under- standing of the underlying dynamics and enable development of advanced protocols for semi-automated sedation administration. In this research, the agitation–sedation model parameters are identified using an integral- based fitting method developed in this work. Parameter variance is then analysed over 37 intensive care unit patients. The parameter identification method is shown to be effective and computationally inexpensive, making it suited to real-time clinical control applications. Sedative sensitivity, an important model parameter, is found to be both patient-specific and time-varying. However, while the variation between patients is observed to be as large as a factor 10, the observed variation in time is smaller, and varies slowly over a period of days rather than hours. The high fitted model performance across all patients show that the agitation–sedation model presented captures the fundamental dynamics of the agitation–sedation system. Overall, these results provide additional insight into the system and clinical dynamics of sedation management. © 2006 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Effective delivery of sedation in the intensive care unit (ICU) is fundamental to providing comfort and relief to the critically ill. A Midazolam and Morphine combination, given by intermit- tent bolus or infusion, is the mainstay of many ICU regimens ∗ Corresponding author at: Centre for Bioengineering, Department of Mechanical Engineering, University of Canterbury, Private Bag 4800, Christchurch, New Zealand. Tel.: +64 21 147 5582; fax: +64 3 364 2078. E-mail address: a.rudge@mail.com (A.D. Rudge). [1]. Midazolam is a sedative agent used to induce a state of conscious sedation and Morphine is a powerful opioid anal- gesic with mild sedative effects. Insufficient sedation exacerbates anxiety and agitation and increases the risk of self-extubation. Over-sedation is a com- mon outcome, is damaging to patient health, and increases 0169-2607/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.cmpb.2006.06.011