Sepsis remains a leading cause of preventable morbidity and mortality worldwide, and adherence to the Centers for Medicare & Medicaid Services Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) remains modest and variable across institutions. Simultaneously, controversy persists regarding fixed-volume fluid resuscitation mandates, particularly given the increasing emphasis on individualized, physiology-guided management. Artificial intelligence (AI) has emerged as a potential strategy to address both operational and clinical gaps in sepsis care. This review examines the current state of SEP-1 implementation, key barriers to compliance, and ongoing debates surrounding early fluid administration. We then discuss contemporary evidence on AI-enabled tools designed to accelerate bundle processes and support personalized fluid management. Early warning systems, natural language processing-augmented models, and telemedicine-integrated platforms have demonstrated improvements in process measures such as time-to-antibiotics and bundle component completion when embedded within defined clinical workflows. Reinforcement learning, causal machine learning, and predictive models offer promise for individualized fluid strategies, although most data remain retrospective and hypothesis-generating. Successful integration will require prospective validation, clinician-in-the-loop oversight, governance frameworks, and continuous monitoring for safety, equity, and model drift. AI should augment—rather than replace—clinical judgment to improve reliability, timeliness, and personalization in sepsis management.
Nguyen et al. (2026) studied this question.