Sepsis: the Evolution in Definition, Pathophysiology, and Management

There has been a significant evolution in the definition and management of sepsis over the last three decades. This is driven in part due to the advances made in our understanding of its pathophysiology. There is evidence to show that the manifestations of sepsis can no longer be attributed only to the infectious agent and the immune response it engenders, but also to significant alterations in coagulation, immunosuppression, and organ dysfunction. A revolutionary change in the way we manage sepsis has been the adoption of early goal-directed therapy. This involves the early identification of at-risk patients and prompt treatment with antibiotics, hemodynamic optimization, and appropriate supportive care. This has contributed significantly to the overall improved outcomes with sepsis. Investigation into clinically relevant biomarkers of sepsis are ongoing and have yet to yield effective results. Scoring systems such as the sequential organ failure assessment and Acute Physiology and Chronic Health Evaluation help risk-stratify patients with sepsis. Advances in precision medicine techniques and the development of targeted therapy directed at limiting the excesses of the inflammatory and coagulatory cascades offer potentially viable avenues for future research. This review summarizes the progress made in the diagnosis and management of sepsis over the past two decades and examines promising avenues for future research.