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What is Sepsis in 2021?


Sepsis is a life-threatening organ dysfunction that results from the body’s response to infection. If not recognized early and managed promptly, it can lead to septic shock, multiple organ failure and death. It is most frequently a serious complication of infection, particularly in low- and middle-income countries where it represents a major cause of maternal and neonatal morbidity and mortality.

According to the World Health Organization (WHO) (2020), “Sepsis is a syndromic response to infection and is frequently a final common pathway to death from many infectious diseases worldwide.”

Sepsis requires prompt recognition, appropriate antibiotics, careful hemodynamic support, and control of the source of infection. The largest contributors to sepsis cases and sepsis-related mortality across all ages are diarrheal diseases and lower respiratory infections. However, non-communicable diseases are on the rise; one-third of sepsis cases and nearly half of all sepsis-related deaths are due to an underlying injury or chronic disease.

Maternal disorders are the most common non-communicable disease complicated by sepsis. Among children, the most common causes of sepsis-related deaths are neonatal disorders, lower respiratory infections, and diarrheal diseases. Group B streptococcus is the leading cause of both neonatal and maternal sepsis, though Escherichia coli is an emerging threat. Both of these pathogens have displayed considerable resistance to treatment and are considered priority pathogens for research and development (R&D) of new antibiotics.

Sepsis is a medical emergency and can present with various signs and symptoms at different times. Warning signs and symptoms include: fever or low temperature and shivering, altered mental status, difficulty breathing/rapid breathing, increased heart rate, weak pulse/low blood pressure, low urine output, cyanotic or mottled skin, cold extremities, and extreme body pain or discomfort. Suspecting sepsis is the first major step towards early recognition and diagnosis.

Identifying the signs and symptoms, along with the detection of biomarkers, are crucial elements for the early diagnosis of sepsis.

After early recognition, diagnostics to help identify a causal pathogen of infection leading to sepsis are important to guide targeted antimicrobial treatment. Once the infection source is determined, source control, such as drainage of an abscess, is critical. Antimicrobial resistance (AMR) can jeopardize the clinical management of sepsis because empirical antibiotic treatment is often required.

Prevention of sepsis involves two main steps: Prevention of microbial transmission and infection and prevention of an infection evolving into sepsis. Updated definitions and clinical criteria facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing it. But there are challenges for fast diagnosis of sepsis as it is based on highly complex pathophysiological pathways that may show varying clinical signs and symptoms.

Currently, sepsis and septic shock with subsequent multi-organ failure are the leading causes of death in adult intensive care units (ICUs), and most of the studies show a greater incidence of sepsis in male, ranging from 54% to 66% that may imply the effect of sex hormones on immunity, and the cardiovascular response.

According to the Third International Consensus Definitions for Sepsis and Septic Shock (2015), sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to increase mortality substantially.

A clinical construct of sepsis with persisting hypotension identifies patients’ with septic shock, which requires vasopressors to maintain mean arterial pressure (MAP ≥65 mm Hg) and to maintain serum lactate level at >2 mmol/L (18mg/dL) despite adequate volume resuscitation.

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