Mathematical modeling of septic shock based on clinical data 11 Medical and Health Sciences 1103 Clinical Sciences

Yukihiro Yamanaka, Kenko Uchida, Momoka Akashi, Yuta Watanabe, Arino Yaguchi, Shuji Shimamoto, Shingo Shimoda, Hitoshi Yamada, Masashi Yamashita, Hidenori Kimura

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    Background: Mathematical models of diseases may provide a unified approach for establishing effective treatment strategies based on fundamental pathophysiology. However, models that are useful for clinical practice must overcome the massive complexity of human physiology and the diversity of patients' environmental conditions. With the aim of modeling a complex disease, we choose sepsis, which is highly complex, life-threatening systemic disease with high mortality. In particular, we focused on septic shock, a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. Our model includes cardiovascular, immune, nervous system models and a pharmacological model as submodels and integrates them to create a sepsis model based on pathological facts. Results: Model validation was done in two steps. First, we established a model for a standard patient in order to confirm the validity of our approach in general aspects. For this, we checked the correspondence between the severity of infection defined in terms of pathogen growth rate and the ease of recovery defined in terms of the intensity of treatment required for recovery. The simulations for a standard patient showed good correspondence. We then applied the same simulations to a patient with heart failure as an underlying disease. The model showed that spontaneous recovery would not occur without treatment, even for a very mild infection. This is consistent with clinical experience. We next validated the model using clinical data of three sepsis patients. The model parameters were tuned for these patients based on the model for the standard patient used in the first part of the validation. In these cases, the simulations agreed well with clinical data. In fact, only a handful parameters need to be tuned for the simulations to match with the data. Conclusions: We have constructed a model of septic shock and have shown that it can reproduce well the time courses of treatment and disease progression. Tuning of model parameters for each patient could be easily done. This study demonstrates the feasibility of disease models, suggesting the possibility of clinical use in the prediction of disease progression, decisions on the timing of drug dosages, and the estimation of time of infection.

    Original languageEnglish
    Article number5
    JournalTheoretical Biology and Medical Modelling
    Volume16
    Issue number1
    DOIs
    Publication statusPublished - 2019 Mar 6

    Fingerprint

    Septic Shock
    Mathematical Modeling
    Shock
    Health
    Sepsis
    Model
    Infection
    Disease Progression
    Recovery
    Cardiovascular Models
    Progression
    Mortality
    Simulation
    Feasibility Studies
    Therapeutics
    Correspondence
    Drug dosage
    Pathophysiology
    Nervous System
    Heart Failure

    Keywords

    • Blood pressure
    • Immune system
    • Inflammation
    • Model-based therapy
    • Septic shock

    ASJC Scopus subject areas

    • Modelling and Simulation
    • Health Informatics

    Cite this

    Mathematical modeling of septic shock based on clinical data 11 Medical and Health Sciences 1103 Clinical Sciences. / Yamanaka, Yukihiro; Uchida, Kenko; Akashi, Momoka; Watanabe, Yuta; Yaguchi, Arino; Shimamoto, Shuji; Shimoda, Shingo; Yamada, Hitoshi; Yamashita, Masashi; Kimura, Hidenori.

    In: Theoretical Biology and Medical Modelling, Vol. 16, No. 1, 5, 06.03.2019.

    Research output: Contribution to journalArticle

    Yamanaka, Y, Uchida, K, Akashi, M, Watanabe, Y, Yaguchi, A, Shimamoto, S, Shimoda, S, Yamada, H, Yamashita, M & Kimura, H 2019, 'Mathematical modeling of septic shock based on clinical data 11 Medical and Health Sciences 1103 Clinical Sciences', Theoretical Biology and Medical Modelling, vol. 16, no. 1, 5. https://doi.org/10.1186/s12976-019-0101-9
    Yamanaka, Yukihiro ; Uchida, Kenko ; Akashi, Momoka ; Watanabe, Yuta ; Yaguchi, Arino ; Shimamoto, Shuji ; Shimoda, Shingo ; Yamada, Hitoshi ; Yamashita, Masashi ; Kimura, Hidenori. / Mathematical modeling of septic shock based on clinical data 11 Medical and Health Sciences 1103 Clinical Sciences. In: Theoretical Biology and Medical Modelling. 2019 ; Vol. 16, No. 1.
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    AU - Akashi, Momoka

    AU - Watanabe, Yuta

    AU - Yaguchi, Arino

    AU - Shimamoto, Shuji

    AU - Shimoda, Shingo

    AU - Yamada, Hitoshi

    AU - Yamashita, Masashi

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