23/10/2017 Distributive Shock: Background, Pathophysiology, Etiology

Distributive Shock
Updated: Oct 08, 2015
Author: Klaus-Dieter Lessnau, MD, FCCP; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP,
MCCM more...

OVERVIEW

Background
Distributive shock results from excessive vasodilation and the impaired distribution of blood flow.
Septic shock is the most common form of distributive shock and is characterized by considerable
mortality (treated, around 30%; untreated, probably >80%). In the United States, this is the leading
cause of noncardiac death in intensive care units (ICUs). (See Pathophysiology, Etiology,
Epidemiology, and Prognosis.)

Other causes of distributive shock include systemic inflammatory response syndrome (SIRS) due to
noninfectious inflammatory conditions such as burns and pancreatitis; toxic shock syndrome (TSS);
anaphylaxis; reactions to drugs or toxins, including insect bites, transfusion reaction, and heavy metal
poisoning; addisonian crisis; hepatic insufficiency; and neurogenic shock due to brain or spinal cord
injury. (See Pathophysiology and Etiology.)

Types of shock
Shock is a clinical syndrome characterized by inadequate tissue perfusion that results in end-organ
dysfunction. It can be divided into the following four categories:

Distributive shock (vasodilation), which is a hyperdynamic process

Cardiogenic shock (pump failure)
Hypovolemic shock (intravascular volume loss)
Obstructive shock (physical obstruction of blood circulation and inadequate blood oxygenation)

Systemic inflammatory response syndrome

The American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM)

Consensus Conference Committee defined SIRS as the presence of at least 2 of the following 4
criteria (see Presentation) [1] :

Core temperature of higher than 38C (100.0F) or lower than 36C (96.8F)
Heart rate of more than 90 beats per minute
Respiratory rate of more than 20 breaths per minute or arterial carbon dioxide tension (PaCO 2)
less than 32mm Hg
White blood cell (WBC) count of more than 12,000/L, less than 4,000/L, or more than 10%
immature (band) forms

The clinical suspicion of systemic inflammatory response syndrome by an experienced clinician is of

utmost importance.

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Patient education

For patient education information, see Shock and Cardiopulmonary Resuscitation (CPR).

Pathophysiology
In distributive shock, the inadequate tissue perfusion is caused by loss of the normal responses of
vascular smooth muscle to vasoconstrictive agents coupled with a direct vasodilating effect. The net
result in a fluid-resuscitated patient is a hyperdynamic, hypotensive state associated with increased
mixed venous O2 saturation; however, evidence of tissue ischemia as manifest by an increased serum
lactate, presumably due to intraorgan functional shunts.

Early septic shock (warm or hyperdynamic) causes reduced diastolic blood pressure; widened pulse
pressure; flushed, warm extremities; and brisk capillary refill from peripheral vasodilation, with a
compensatory increase in cardiac output. In late septic shock (cold or hypodynamic), myocardial
contractility combines with peripheral vascular paralysis to induce a pressure-dependent reduction in
organ perfusion. The result is hypoperfusion of critical organs such as the heart, brain, and liver.

The hemodynamic derangements observed in septic shock and SIRS are due to a complicated
cascade of inflammatory mediators. Inflammatory mediators are released in response to any of a
number of factors, such as infection, inflammation, or tissue injury. For example, bacterial products
such as endotoxin activate the host inflammatory response, leading to increased pro-inflammatory
cytokines (eg, tumor necrosis factor (TNF), interleukin (IL) 1, and IL-6. Toll-like receptors are thought
to play a critical role in responding to pathogens as well as in the excessive inflammatory response
that characterizes distributive shock; these receptors are considered possible drug targets.

Cytokines and phospholipid-derived mediators act synergistically to produce the complex alterations in
vasculature (eg, increased microvascular permeability, impaired microvascular response to
endogenous vasoconstrictors such as norepinephrine) and myocardial function (direct inhibition of
myocyte function), which leads to maldistribution of blood flow and hypoxia. Hypoxia also induces the
upregulation of enzymes that create nitric oxide, a potent vasodilator, thereby further exacerbating
hypoperfusion.

The coagulation cascade is also affected in septic shock. Activated monocytes and endothelial cells
are sources of tissue factors that activate the coagulation cascade; cytokines, such as IL-6, also play
a role. The coagulation response is broadly disrupted, including impairment of antithrombin and
fibrinolysis. Thrombin generated as part of the inflammatory response can trigger disseminated
intravascular coagulation (DIC). DIC is found in 25-50% of patients with sepsis and is a significant risk
factor for mortality. [2, 3]

During distributive shock, patients are at risk for diverse organ system dysfunction that may progress
to multiple organ failure (MOF). Mortality from severe sepsis increases markedly with the duration of
sepsis and the number of organs failing.

In distributive shock due to anaphylaxis, decreased SVR is due primarily to massive histamine release
from mast cells after activation by antigen-bound immunoglobulin E (IgE), as well as increased
synthesis and release of prostaglandins.

Neurogenic shock is due to loss of sympathetic vascular tone from severe injury to the nervous
system.

Etiology
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The most common etiology of distributive shock is sepsis. Other causes include the following:

SIRS due to noninfectious conditions such as pancreatitis, burns, or trauma

TSS
Anaphylaxis
Adrenal insufficiency
Reactions to drugs or toxins
Heavy metal poisoning
Hepatic insufficiency
Neurogenic shock

All of these conditions share the common characteristic of hypotension due to decreased SVR and
low effective circulating plasma volume.

Septic shock
The most common sites of infection, in decreasing order of frequency, include the chest, abdomen,
and genitourinary tract.

Septic shock is commonly caused by bacteria, although viruses, fungi, and parasites are also
implicated. Gram-positive bacteria are being isolated more, with their numbers almost similar to those
of gram-negative bacteria, which in the past were considered to be the predominant organisms.
Multidrug-resistant organisms are increasingly common. [4]

Systemic inflammatory response syndrome

Causes of SIRS include the following:

Infection
Burns
Surgery
Trauma
Pancreatitis
Fulminant hepatic failure

Toxic shock syndrome

TSS can result from infection with Streptococcus pyogenes (group A Streptococcus) or
Staphylococcus aureus.

Adrenal insufficiency

Adrenal insufficiency can result from the following:

Destruction of adrenal glands due to autoimmune disease, infection (tuberculosis, fungal

infection, acquired immunodeficiency syndrome [AIDS]), hemorrhage, cancer, or surgical
removal
Suppression of hypothalamic-pituitary-adrenal axis by exogenous steroid, usually with doses at
20 mg daily or higher
Hypopituitarism
Metabolic failure in hormone production due to congenital conditions or drug-induced inhibition
of synthetic enzymes (eg, metyrapone, ketoconazole)

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Anaphylaxis

Anaphylaxis can develop as a result of the following:

Drugs such as penicillins and cephalosporins

Heterologous proteins such as Hymenoptera venom, foods, pollen, and blood serum products

Epidemiology
Occurrence in the United States

Sepsis develops in more than 750,000 patients per year in the United States. Angus and colleagues
estimated that, by 2010, 1 million people per year would be diagnosed with sepsis. [5] From 1979-
2000, the incidence of sepsis increased by 9% per year.

International occurrence

Sepsis is a common cause of death throughout the world and kills approximately 1,400 people
worldwide every day. [6, 7]

Age-related demographics

Increased age correlates with increased risk of death from sepsis.

Prognosis
The mortality rate after development of septic shock is 20-80%. [8] Data suggest that mortality due to
septic shock has decreased slightly because of new therapeutic interventions. [9] Early recognition and
appropriate therapy are central to maximizing good outcomes. Identifying patients with septic shock in
the emergency department, as opposed to identifying them outside of it, results in significantly
improved mortality. In one study, the mortality rate for emergency department-identified patients was
27.7%, compared with 41.1% for patients identified outside of the emergency department. [10]

Higher mortality rates have also been associated with the following:

Advanced age
The finding of positive blood cultures
Infection with antibiotic-resistant organisms such as Pseudomonas aeruginosa
Elevated serum lactate levels
Impaired immune function
Alcohol use
Poor functional status prior to the onset of sepsis.

Mortality rates associated with other forms of distributive shock are not well documented.

Complications
Duration of delirium is an independent predictor of long-term cognitive impairment. At 3-month and 12-
month follow-up, as many as 79% and 71% of patients have cognitive impairment. About one
third remain severely impaired. [11, 12, 13]
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Clinical Presentation

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