Clinically Interpretable Sepsis Early Warning via LLM-Guided Simulation of Temporal Physiological Dynamics

Sepsis management in the ICU requires sequential treatment decisions under rapidly evolving patient physiology. Although large language models (LLMs) encode broad clinical knowledge and can reason over guidelines, they are not inherently grounded in action-conditioned patient dynamics. We introduce SepsisAgent, a world model-augmented LLM agent for sepsis treatment recommendation. SepsisAgent uses a learned Clinical World Model to simulate patient responses under candidate fluid--vasopressor interventions, and follows a propose--simulate--refine workflow before committing to a prescription. We first show that world-model access alone yields inconsistent LLM decision performance, motivating agent-specific training. We then train SepsisAgent through a three-stage curriculum: patient-dynamics supervised fine-tuning, propose--simulate--refine behavior cloning, and world-model-based agentic reinforcement learning. On MIMIC-IV sepsis trajectories, SepsisAgent outperforms all traditional RL and LLM-based baselines in off-policy value while achieving the best safety profile under guideline adherence and unsafe-action metrics. Further analysis shows that repeated interaction with the Clinical World Model enables the agent to learn regularities in patient evolution, which remain useful even when simulator access is removed.

Early sepsis prediction from electronic health records is challenged by irregular sampling, high missingness, and class imbalance. We systematically compare four modeling paradigms -- self-supervised Joint Embedding Predictive Architecture (JEPA) via masked latent prediction, self-supervised VICReg (variance-invariance-covariance regularization) with two-view augmentation, semi-supervised fine-tuning of a VICReg-pretrained encoder, and supervised Temporal Convolutional Network (TCN) -- alongside raw-feature baselines. All models share a common preprocessing pipeline of hourly binning with forward-fill imputation applied to 7 biomarkers selected via sparsity analysis from the MIMIC-III dataset. Our best model (JEPA + XGBoost + mean pooling) achieves AUPRC 0.636 at the time of onset (H0), approaching the SupMix benchmark (0.667) while using 83% fewer biomarkers. The Tier 1 pipeline -- VICReg pretraining followed by semi-supervised fine-tuning and XGBoost -- achieves AUPRC 0.510 at H0, a 3.1$\times$ improvement over the raw-feature baseline (0.165) and a 7.6% improvement over the end-to-end supervised TCN (0.474). Crucially, the fine-tuned VICReg encoder exhibits the most temporally persistent representations, degrading only 16.8% from H0 to H10 compared to 47.5% for supervised TCN and 65.3% for JEPA, demonstrating that self-supervised pretraining with task-aware fine-tuning yields features that are both sharp near onset and robust across prediction horizons.

Despite strong predictive results in the clinical machine learning literature, the translation of these models into bedside use remains limited by systems-level barriers: heterogeneous data representations, the absence of standardized deployment workflows, and a mismatch between research prototypes and the concurrency and latency requirements of hospital environments. We present the SepsisAI-Orchestrator, an open-source modular platform that addresses this deployment gap for early sepsis detection. The platform integrates HL7 FHIR-inspired Clinical Document Architecture (CDA) preprocessing, NoSQL storage, a containerized LightGBM classifier served via REST APIs, and a Streamlit clinical dashboard, orchestrated with Docker and Kubernetes. A previously validated LightGBM model (F1 0.87-0.94 on PhysioNet 2019) is reused without modification; the contribution lies in the surrounding infrastructure and its empirical characterization under load. Using k6 with 50-1000 concurrent virtual users, we find that replica count must be matched to the physical CPU thread count of the host: scaling from 3 to 12 replicas on a 12-thread CPU reduces p95 latency from 3.3s to 1.41s (57.3% reduction) and eliminates all request failures, while over-provisioning to 24 or 48 replicas degrades performance due to scheduler contention. To our knowledge this U-shaped scaling behavior has not been quantified previously for clinical AI inference workloads. We do not claim prospective clinical validation. Source code and deployment manifests are available at https://github.com/nucleusai/sepsisai-orchestrator.