Sepsis Without Biomarkers: A Physiology-Based Approach to Diagnosis and Management in Resource-Limited Settings

Sepsis remains a leading cause of mortality worldwide, with a disproportionate burden in low- and middle-income countries and resource-limited healthcare environments. Contemporary definitions and management strategies increasingly rely on biomarkers such as lactate, procalcitonin, and inflammatory mediators to guide diagnosis, risk stratification, and therapeutic decisions. However, in many clinical settings, these tools are unavailable, delayed, or economically inaccessible, raising a fundamental question: can sepsis be effectively managed without biomarkers? This review explores sepsis as a dynamic physiological syndrome rather than a laboratory-defined condition and proposes a pragmatic, physiology-based framework for its recognition and management in low-resource settings. By emphasizing bedside clinical assessment, perfusion markers, hemodynamic reasoning, and adaptive therapeutic strategies, we argue that effective sepsis care can be delivered without reliance on advanced diagnostics. Furthermore, we discuss the ethical implications of protocol-driven care in contexts where resources differ substantially from those in which guidelines are developed. Re-centering clinical physiology as the interpretive foundation of sepsis management not only enhances adaptability and patient-centered care but also promotes equity in global critical care practice.

Keywords: Sepsis, biomarkers, physiology-based medicine, resource-limited settings, tissue perfusion, septic shock, clinical assessment, critical care