Edited by: Dr Yong-Ming Yao and Dr Jie Fan
Sepsis is life-threatening organ dysfunction caused by dysregulated host response to infection according to the 2016 guidelines issued by the Surviving Sepsis Campaign. It is one of the leading causes of ICU admissions, which affects patients of all ages with multiple comorbidities and underlying diagnoses, and is the result of infection by many potential pathogens infecting various organs or sites.
The pathogenesis of sepsis remains poorly understood although it is attributable to dysregulated immune responses orchestrated by innate immune cells that sequentially release early and late pro-inflammatory mediators. Recent studies proved that VE-cadherin cleavage, weak or absent type IV collagen expression and elevated L-arginine and ADMA levels appear to be of clinical relevance in patients with severe sepsis or septic shock. These many molecules have been clinically tested, however, no beneficial effects on outcomes in heterogeneous populations of patients have been determined.
Mounting evidence in both animal models and human studies suggests that sepsis induces a higher mortality, cognitive decline (e.g. dementia), progressive immunosuppression, cholinergic anti-inflammatory deficiency, metabolic and hydroelectrolyte imbalance. As thus, it causes a great global healthcare burden, especially to the developing and under-developed countries and regions.
Septic shock is a subset of sepsis with circulatory and cellular/metabolic dysfunction. It is one of the most challenging medical problems and carries a higher mortality than sepsis, ranging from 20% to 50%, in general ICU populations. Despite adequate and emergent fluid resuscitation, septic shock affects between 10% and 30% of patients managed in the ICU, and its incidence is still increasing.
Although most of the patients were managed in ICU, a series of questions remained. A rapid diagnosis and accurate diagnosis of sepsis and septic shock is still difficult in routine clinical practice. Current sepsis therapies are largely supportive and limited to a few clinical interventions, including antibiotics, steroidal anti-inflammatory drugs (e.g., hydrocortisone) and early goal-directed therapies (EGDT). Despite improved overall management for sepsis, no strategies have yet been persistently shown to have beneficial effects on outcomes, and therefore mortality and morbidity rates remain high. Moreover, three trials, ARISE, ProCESS and ProMISe, revealed that EGDT did not lead to an improvement in outcome in septic patients.
In this thematic series, we would like to raise an early and rapid recognition of sepsis and septic shock across the globe.
This series was published in Military Medical Research.