What is sepsis?

In recognition of Sepsis Awareness Month in September, Dr Gando, Editor-in-Chief of Journal of Intensive Care, tells more about the syndrome in this blog. Although old, sepsis is not yet fully characterized and this deregulated inflammation, which occurs with severe infection, affects millions of people worldwide.

The research behind sepsis
Find out more about the research behind sepsis
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Defining sepsis

Sepsis has been accepted as a syndrome of systemic inflammation that occurs in response to infection. In addition, another important concept recognized worldwide is that the presence of viable pathologic organisms in the blood is unnecessary for the diagnosis of sepsis.

The 2001 International Sepsis Definitions conference followed the initial 1991 definitions, which was the real start of the new period of sepsis.

Inflammation is a non-specific response against diverse infectious- (sepsis) and non-infectious (trauma) insults that delimits and repairs the tissue damage caused by the insults. Local inflammation is recognized as rubor (redness), tumor (swelling), calor (heat) and dolor (pain), and when a systemic response is elicited, it is called SIRS (Systemic Inflammatory Response Syndrome), which consists of tachypnea, tachycardia, hyperpyrexia and leukocytosis.

Advancing our understanding of innate immunity

Recent advances in immunology have led to the recognition of common ligands involved in SIRS, and to the understanding that the processes of SIRS are involved in innate immunity.

Pathogen-associated molecular patterns (PAMPs) are derived from microorganisms, while damage-associated molecular patterns (DAMPs) are molecules produced in stressed or damaged tissues in connection with sepsis itself.

The innate immune responses are triggered by the sensing of PAMPs or DAMPs by pattern-recognition receptors, such as the toll-like receptors expressed on the immunocompetent cells. The sensed danger signals activate both intracellular signal transduction pathways and plasma cascades, which together produce pro-inflammatory cytokines, further stimulating the production of inflammatory biomarkers.

Innate immune responses originally protect the host from insults; however, if the insults are sufficiently severe, physiological immune inflammatory responses change into pathological reactions, leading to organ dysfunction and deeply affecting the patient’s outcome. In fact, sepsis was the 11th leading cause of death in the United States in 2010.

A recent publication indicated that septic patients remained at an increased risk of death after hospital discharge, despite the fact that the mortality has declined from 80% 30 years ago to 20-30% at present. Sepsis seriously accelerates physical and neurocognitive decline and leads to a low quality of life for patients.

Improving prognosis

It is clear that early recognition and diagnosis of sepsis and an early start of evidence-based treatment strategies can improve the prognosis of sepsis. The Declaration of Barcelona in 2002 aimed to raise public and professional awareness of sepsis and its treatment, to foster the development of practice guidelines, and to implement worldwide standards of care through the development of global protocols.

During the same period, the Institute of Healthcare Improvement (IHI) began the 100,000 lives campaign, which established treatment bundles, a group of interventions that, when practiced together, lead to better outcomes than when implemented individually.

Early identification of sepsis and implementation of early guideline-based therapies by physicians have been documented to improve the outcomes for patients and to decrease sepsis-related mortality.

The latter aim of the declaration was achieved in partnership with the IHI as sepsis resuscitation and management bundles, while three Surviving Sepsis Campaign Guidelines published in 2004, 2008, and 2012 have realized the first two missions.

In fact the early identification of sepsis and implementation of early guideline-based therapies by physicians have been documented to improve the outcomes for patients and to decrease sepsis-related mortality.

The 2012 Guideline further strengthened the idea that performance improvement should be used to improve the outcomes of patients with sepsis. It should be kept in mind that protocol implementation associated with education and performance feedback has been shown to change clinician behavior and is associated with improved outcomes and cost-effectiveness in sepsis.

The next groups that should be targeted to improve the outcomes of sepsis are the lay public and healthcare practitioners. Surprisingly, or as a matter of course, 88% of the general public interviewed had never heard of the term ‘sepsis’ and the people who had heard of it it didn’t recognize that it is a leading cause of death.

To raise the awareness of sepsis by educating patients, families and healthcare professionals to ensure that they treat sepsis as a medical emergency, a voluntary health organization, the Global Sepsis Alliance (GSA), was founded in 2004.

The GSA supports the efforts of over one million caregivers in more than 70 countries as they seek to better understand and combat what many experts believe to be the leading cause of death worldwide.

The GSA began World Sepsis Day, September 13, in 2012 with the motto “Stop Sepsis, Save Lives”. The World Sepsis Declaration pronounced five global goals with key targets to be achieved by 2020.

They say that by 2020, sepsis will have become a household word synonymous with the need for emergency intervention. Lay people will better understand the early warning signs of sepsis. In addition, families’ expectations of the delivery of care will have risen such that delays will be routinely questioned.

I strongly believe in this goal.

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