PRIMEVIEW

SEPSIS AND SEPTIC SHOCK

For the Primer, visit doi:10.1038/nrdp.2016.45

Treatment
Sepsis has historically been difficult of sepsis needs MECHANISMS
MANAGEMENT to be early and
to define clinically. The condition is
characterized by a dysregulated systemic aggressive, and has
three main components Sepsis is a complex process that is not fully
inflammatory and immune response to
understood, although two broad phases have
infection that produces organ injury.
Broad-spectrum Fluidsare administered to been described: an inflammatory burst and
Septic shock is characterized by persistent
antimicrobial agents prevent organ injury and immune suppression. The inflammatory burst
hypotension and substantially increases
must be given to control shock; vasopressors are involves simultaneous recognition of infection-
the risk of death.
the infection; once the given to avoid prolonged derived microbial products and endogenous
infective culprit is hypotension. Ventilation to danger signals that trigger multiple converging
signalling cascades, leading to the expression of

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identified, de-escalate to prevent hypoxaemia might
EPIDEMIOLOGY genes encoding various inflammatory chemokines
a narrower-spectrum drug be needed in severe cases.

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and cytokines. Complement activation leads to

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Estimating the burden of sepsis is complicated vasodilation, tissue damage and multiple organ

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by the heterogeneous presentation of patients, failure. If patients survive this phase, they can

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controversy in clinical definitions, varying levels go on to exhibit chronic suppression of both the

ON
of awareness of sepsis as well as different coding

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innate and the adaptive immune systems in spite

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systems for sepsis in hospital databases. An

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of ongoing inflammation. This phase of sepsis is

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estimate in high-income countries suggests that

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characterized by profound leukocyte apoptosis.
31.5 million cases of sepsis occur annually, with

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EC

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potentially 5.3 million deaths. Data are scant INF Endothelial barrier dysfunction occurs

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on incidence and mortality in low-income and
early in sepsis and septic shock in
middle-income countries.

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particular, leading to hypotension and oedema

DIAGNOSIS
OUTLOOK
The symptoms of
sepsis are variable Defining the immunological state of the
and includemental MODULATION OF THE SEPTIC RESPONSE patient with sepsis or septic shock is of
alterations and particular interest to better understand the
difficulty breathing. syndrome, as well as to design and assess
Many biological agents to modify the early septic response have been assessed; these
Although infection is include antibodies that target various components of the signalling cascades in sepsis. immunotherapies. Indeed, immunophenotyping
the precipitating event However, none has proven effective to date, although several are still in trials. of patients with sepsis is being explored
in sepsis, a causative and includes quantification of monocyte
pathogen is not identified HLA-DR expression, loss of which has
in every patient. Rapid bedside assessment PREVENTION been implicated in sepsis. In addition,
of early organ dysfunction is crucial to drugs to reverse sepsis-induced
facilitate the diagnosis of sepsis. Septic shock Given that hospitalized patients warning systems that evaluate However, a considerable number immunosuppression are being designed
is characterized by severe hypotension (which are at high risk of developing haemodynamics, urine output, body of patients develop sepsis outside of and assessed. Continued development
requires vasopressor therapy to maintain a sepsis, clean care and minimization temperature and mental function the hospital setting. In this regard, of biomarkers that can distinguish
mean arterial blood pressure of >65mmHg) that of invasive procedures are in critically ill patients to prevent vaccination to reduce the burden sepsis from inflammation alone
is associated with an increased plasma lactate effective preventive strategies. sepsis and its progression to septic of infectious disease can reduce the also remains an area of
level of >2mmol per l. Hospitals should implement early shock and multiple organ failure. risk of sepsis. activeinvestigation.

Designed by Laura Marshall Article number: 16046; doi:10.1038/nrdp.2016.46; published online 30 June 2016

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