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Life sciences · Preprint
arXiv · September 18, 2026
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This paper presents a novel framework integrating Bayesian physiological modeling with optimal control strategies to achieve uncertainty-aware, personalized hemodynamic regulation during fluid resuscitation. An uncertainty-aware variational autoencoder state-space model (UVAE-SSM) was first developed to capture the dynamical relationship between mean arterial pressure (MAP) and fluid infusion using limited data, while explicitly modeling aleatoric uncertainty (i.e., randomness in the measurements, such as sensor noise). Then, a Bayesian nonlinear state-space model (BNSSM) was developed by utilizing Bayesian neural networks (BNNs) to capture epistemic uncertainty arising from physiological and patient-specific variability, enabling the creation of a virtual patient generator (VPG). Building on this uncertainty-aware modeling framework, a stochastic radial basis function model predictive control (sRBF-MPC) algorithm was designed to track the MAP target while satisfying physiological constraints. Finally, an online fine-tuning algorithm was developed to adapt the nominal UVAE-SSM using streaming VPG data, enabling progressive personalization during closed-loop therapy. Simulation results across unseen animal subjects and an independent human clinical dataset demonstrated the strong predictive accuracy and cross-population generalizability of the UVAE-SSM and BNSSM models. Closed-loop evaluations confirmed that the proposed sRBF-MPC framework achieved stable MAP regulation while providing better risk-aware control compared to quadratic MPC (Q-MPC) and stochastic quadratic MPC (sQ-MPC). Overall, the proposed framework accounts for inter- and intra-patient variability through online model adaptation, offering a promising step toward uncertainty-aware, personalized hemodynamic modeling and control in critical care.