Physiological and pharmacological modelling in neurological intensive care and anaesthesia

R Medicine (General)

Hawthorne, Christopher ; The National Institute of Academic Anaesthesia ; Kinsella, John

University:University of Glasgow

Department:School of Medicine, Dentistry & Nursing

关键词: Physiological modelling, pharmacokinetic pharmacodynamic modelling, traumatic brain injury, intracranial pressure, total intravenous anaesthesia, target controlled infusion.;   

Others  :  http://theses.gla.ac.uk/8721/1/2017HawthorneMD.pdf

来源: University of Glasgow

【 摘 要 】

Mathematical models of physiological processes can be used in critical care and anaesthesia to improve the understanding of disease processes and to guide treatment. This thesis provides a detailed description of two studies that are related through their shared aim of modelling different aspects of brain physiology.The Relationship Between Transcranial Bioimpedance and Invasive Intracranial Pressure Measurement in Traumatic Brain Injury Patients (BioTBI) Study describes an attempt to model intracranial pressure (ICP) in patients admitted with severe traumatic brain injury (TBI). It is introduced with a detailed discussion of the monitoring and modelling of ICP in patients with TBI alongside the rationale for considering transcranial bioimpedance (TCB) as a non-invasive approach to estimating ICP. The BioTBI Study confirmed a significant relationship between TCB and invasively measured ICP in ten patients admitted to the neurological intensive care unit (NICU) with severe TBI. Even when using an adjusted linear modelling technique to account for patient covariates, the magnitude of the relationship was small (r-squared = 0.32) and on the basis of the study, TCB is not seen as a realistic technique to monitor ICP in TBI.Target controlled infusion (TCI) of anaesthetic drugs exploit known pharmacokinetic pharmacodynamic (PKPD) models to achieve set concentrations in the plasma or an effect site. Following a discussion of PKPD model development for the anaesthetic drug propofol, the Validation Study of the Covariates Model (VaSCoM) describes a joint PKPD study of the Covariates Model. Pharmacokinetic validation of plasma concentrations predicted by the model in forty patients undergoing general anaesthesia confirmed a favourable overall bias (3%) and inaccuracy (25%) compared to established PKPD models. The first description of the pharmacodynamic behaviour of the Covariates Model is provided with an estimated rate constant for elimination from the effect site compartment (ke0) of 0.21 to 0.27 min-1.