A Whole-Body Mathematical Model of Sepsis Progression and Treatment Designed in the BioGears Physiology Engine

Abstract

Sepsis is a debilitating condition associated with a high mortality rate that greatly strains hospital resources. Though advances have been made in improving sepsis diagnosis and treatment, our understanding of the disease is far from complete. Mathematical modeling of sepsis has the potential to explore underlying biological mechanisms and patient phenotypes that contribute to variability in septic patient outcomes. We developed a comprehensive, whole-body mathematical model of sepsis pathophysiology using the BioGears Engine, a robust open-source virtual human modeling project. We describe the development of a sepsis model and the physiologic response within the BioGears framework. We then define and simulate scenarios that compare sepsis treatment regimens. As such, we demonstrate the utility of this model as a tool to augment sepsis research and as a training platform to educate medical staff.

BurnCare tablet trainer to enhance burn injury care and treatment

“…BioGears maintains a dynamic model of acute inflammation based on the work of Chow [ 13 ], Reynolds [ 14 ], and Dominguez-Huttinger [ 15 ] that accounts for interactions between numerous pro- and anti-inflammatory mediators associated with burns—such as tumor necrosis factor (TNF) and interleukins-6 and 10 (IL-6, IL-10) [ 10 , 14 ]—and their collective contribution to endothelial damage. We have described the BioGears inflammation model previously in an in silico study of sepsis onset and treatment [ 6 ]. We calibrated this model to burn-mediated inflammation by setting all infection states to zero and introducing a thermal trauma term to the equations describing blood macrophage, blood neutrophil, and tissue integrity kinetics (Equations 6–9, 18 in [ 6 ]).…”

“…We have described the BioGears inflammation model previously in an in silico study of sepsis onset and treatment [ 6 ]. We calibrated this model to burn-mediated inflammation by setting all infection states to zero and introducing a thermal trauma term to the equations describing blood macrophage, blood neutrophil, and tissue integrity kinetics (Equations 6–9, 18 in [ 6 ]).…”

“…To mitigate the problem of inexperience, in 2006, the Burn Care clinical practice guideline (CPG) was developed by burn providers at the United States Army Institute of Surgical Research (USAISR) Burn Center and disseminated via the Joint Theater Trauma System, to provide recommendations for optimal care of patients burned while involved in combat operations. Improvement in patient outcomes has been demonstrated when providers adhere to guidelines and utilize the burn flow sheet, but repeated and specialized training is still needed [ 5 , 6 ].…”

A physiological model of the inflammatory‐thermal‐pain‐cardiovascular interactions during an endotoxin challenge

“…McDaniel et al . (2019) and Yamanaka et al . (2019) explored the effects of systemic inflammation on blood pressure (BP) and HR.…”

“…Several studies have used models to examine inflammatory-cardiovascular communication in humans (Foteinou et al 2011;Scheff et al 2011;McDaniel et al 2019;Yamanaka et al 2019). Foteinou et al (2011) employed a multiscale model to predict the parasympathetic activity and HR in human subjects who received a bolus dose of LPS (2 ng kg −1 of body weight) alone or combined with an epinephrine infusion.…”