title: Prediction of Hemodynamic Response to Epinephrine via Model-Based System Identification.
abstract: In this study, we present a system identification approach to the mathematical modeling of hemodynamic responses to vasopressor-inotrope agents. We developed a hybrid model called the latency-dose-response-cardiovascular (LDC) model that incorporated 1) a low-order lumped latency model to reproduce the delay associated with the transport of vasopressor-inotrope agent and the onset of physiological effect, 2) phenomenological dose-response models to dictate the steady-state inotropic, chronotropic, and vasoactive responses as a function of vasopressor-inotrope dose, and 3) a physiological cardiovascular model to translate the agent's actions into the ultimate response of blood pressure. We assessed the validity of the LDC model to fit vasopressor-inotrope dose-response data using data collected from five piglet subjects during variable epinephrine infusion rates. The results suggested that the LDC model was viable in modeling the subjects' dynamic responses: After tuning the model to each subject, the r (2) values for measured versus model-predicted mean arterial pressure were consistently higher than 0.73. The results also suggested that intersubject variability in the dose-response models, rather than the latency models, had significantly more impact on the model's predictive capability: Fixing the latency model to population-averaged parameter values resulted in r(2) values higher than 0.57 between measured versus model-predicted mean arterial pressure, while fixing the dose-response model to population-averaged parameter values yielded nonphysiological predictions of mean arterial pressure. We conclude that the dose-response relationship must be individualized, whereas a population-averaged latency-model may be acceptable with minimal loss of model fidelity.
authors.forename: Ramin
authors.initials: R
authors.lastname: Bighamian
authors.forename: Sadaf
authors.initials: S
authors.lastname: Soleymani
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Reisner
authors.forename: Istvan
authors.initials: I
authors.lastname: Seri
authors.forename: Jin-Oh
authors.initials: JO
authors.lastname: Hahn
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D008955:Models, Cardiovascular; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D004837:Epinephrine