In-human subject-specific evaluation of a control-theoretic plasma volume regulation model

• Published in: Computers in biology and medicine Vol. 91; pp. 96 - 102
• Main Authors: Bighamian, Ramin, Kinsky, Michael, Kramer, George, Hahn, Jin-Oh
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.12.2017; Elsevier Limited
• Subjects: Accuracy; Adult; Anesthesiology; Blood; Blood volume; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - pharmacology; Circulatory resuscitation; Computer Simulation; Control; Control-theoretic model; Controllers; Extracellular Fluid - physiology; Female; Fluids; Human subjects; Humans; In-silico evaluation; Isoproterenol - administration & dosage; Isoproterenol - pharmacology; Male; Mathematical model; Mathematical models; Middle Aged; Models, Biological; Physiological closed-loop control; Physiological model; Physiology; Plasma; Plasma volume; Plasma Volume - drug effects; Plasma Volume - physiology; Pre-clinical evaluation; Regulation; Regulatory approval; Ultrasonic imaging; Urine; Young Adult; Pre-clinical evaluation; Blood volume; In-silico evaluation; Plasma volume; Physiological closed-loop control; Circulatory resuscitation; Mathematical model; Physiological model; Control-theoretic model
• ISSN: 0010-4825; 1879-0534; 1879-0534
• DOI: 10.1016/j.compbiomed.2017.10.006

The goal of this study was to conduct a subject-specific evaluation of a control-theoretic plasma volume regulation model in humans. We employed a set of clinical data collected from nine human subjects receiving fluid bolus with and without co-administration of an inotrope agent, including fluid infusion rate, plasma volume, and urine output. Once fitted to the data associated with each subject, the model accurately reproduced the fractional plasma volume change responses in all subjects: the error between actual versus model-reproduced fractional plasma volume change responses was only 1.4 ± 1.6% and 1.2 ± 0.3% of the average fractional plasma volume change responses in the absence and presence of inotrope co-administration. In addition, the model parameters determined by the subject-specific fitting assumed physiologically plausible values: (i) initial plasma volume was estimated to be 36 ± 11 mL/kg and 37 ± 10 mL/kg in the absence and presence of inotrope infusion, respectively, which was comparable to its actual counterpart of 37 ± 4 mL/kg and 43 ± 6 mL/kg; (ii) volume distribution ratio, specifying the ratio with which the inputted fluid is distributed in the intra- and extra-vascular spaces, was estimated to be 3.5 ± 2.4 and 1.9 ± 0.5 in the absence and presence of inotrope infusion, respectively, which accorded with the experimental observation that inotrope could enhance plasma volume expansion in response to fluid infusion. We concluded that the model was equipped with the ability to reproduce plasma volume response to fluid infusion in humans with physiologically plausible model parameters, and its validity may persist even under co-administration of inotropic agents. •A control-theoretic model of plasma volume regulation was validated in humans.•The model could reproduce subject-specific plasma volume response accurately.•The model could reproduce plasma volume response despite inotrope infusion.•The parameters determined from model identification were physiologically plausible.•The model may serve as a basis for closed-loop fluid resuscitation control design.