Over the years, our understanding of the complex pathophysiology of sepsis has improved, and so has our ability to define sepsis. A multicenter study in Australia and New Zealand that included 101,064 critical patients showed that the mortality rate in sepsis has decreased over the years from around 35% in 2000 to about 20% in 2012. 3 This implies that the mortality in sepsis varies according to patient characteristics as well. 3 This difference however disappeared when adjusted for disease severity. Mortality rates from sepsis, as per the data from the Surviving Sepsis Campaign 2012, were approximately 41% in Europe versus approximately 28.3% in the United States. It is estimated that more than 30 million people are affected by sepsis every year worldwide, resulting in potentially 6 million deaths annually. The global epidemiological burden of sepsis is, however, difficult to ascertain. Sepsis is also the most expensive healthcare problem in the United States, accounting for more than $20 million (about 5.2% of the total hospital cost) in 2011 alone. 1 The annual incidence of severe sepsis and septic shock in the United States is up to 300 cases per 100,000 people. Despite significant advancements in the understanding of the pathophysiology of this clinical syndrome, advancements in hemodynamic monitoring tools, and resuscitation measures, sepsis remains one of the major causes of morbidity and mortality in critically ill patients. Sepsis is a medical emergency that describes the bodyвЂ™s systemic immunological response to an infectious process that can lead to end-stage organ dysfunction and death. 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. 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. Scoring systems such as the sequential organ failure assessment and Acute Physiology and Chronic Health Evaluation help risk-stratify patients with sepsis. Investigation into clinically relevant biomarkers of sepsis are ongoing and have yet to yield effective results. This has contributed significantly to the overall improved outcomes with sepsis. This involves the early identification of at-risk patients and prompt treatment with antibiotics, hemodynamic optimization, and appropriate supportive care. A revolutionary change in the way we manage sepsis has been the adoption of early goal-directed therapy. 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. This is driven in part due to the advances made in our understanding of its pathophysiology. There has been a significant evolution in the definition and management of sepsis over the last three decades.

Directed evolution review