Official reprint from UpToDate®

www.uptodate.com ©2019 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Definition, classification, etiology, and pathophysiology of shock in adults

Authors: David F Gaieski, MD, Mark E Mikkelsen, MD, MSCE

Section Editor: Polly E Parsons, MD
Deputy Editor: Geraldine Finlay, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2018. | This topic last updated: Feb 18, 2018.

INTRODUCTION — Shock is a life-threatening condition of circulatory failure. The effects of shock are
initially reversible, but rapidly become irreversible, resulting in multiorgan failure (MOF) and death. When a
patient presents with undifferentiated shock, it is important that the clinician immediately initiate therapy while
rapidly identifying the etiology so that definitive therapy can be administered to reverse shock and prevent
MOF and death.

The definition, classification, etiology, and pathophysiology of shock are discussed in this review. The clinical
presentation and diagnostic evaluation of undifferentiated shock and the evaluation of patients with specific
forms of shock are discussed separately. (See "Evaluation of and initial approach to the adult patient with
undifferentiated hypotension and shock" and "Evaluation and management of suspected sepsis and septic
shock in adults" and "Clinical manifestations and diagnosis of cardiogenic shock in acute myocardial
infarction" and "Etiology, clinical manifestations, and diagnosis of volume depletion in adults" and "Initial
evaluation of shock in the adult trauma patient and management of NON-hemorrhagic shock" and "Clinical
presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary
embolism".)

DEFINITION — Shock is defined as a state of cellular and tissue hypoxia due to reduced oxygen delivery
and/or increased oxygen consumption or inadequate oxygen utilization. This most commonly occurs when
there is circulatory failure manifested as hypotension (ie, reduced tissue perfusion). Shock is initially
reversible, but must be recognized and treated immediately to prevent progression to irreversible organ
dysfunction. "Undifferentiated shock" refers to the situation where shock is recognized but the cause is
unclear.

CLASSIFICATION AND ETIOLOGY — Four types of shock are recognized: distributive, cardiogenic,
hypovolemic, and obstructive. However, these are not exclusive, and many patients with circulatory failure
have a combination of more than one form of shock (multifactorial shock) (table 1). There are many etiologies
within each class, all of which are discussed in detail in the sections below. (See 'Distributive' below and
'Cardiogenic' below and 'Hypovolemic' below and 'Obstructive' below and 'Combined' below.)

Septic shock, a form of distributive shock, is the most common form of shock among patients admitted to the
intensive care unit, followed by cardiogenic and hypovolemic shock; obstructive shock is rare [1,2]. As an
example, in a trial of 1600 patients with undifferentiated shock, septic shock occurred in 62 percent,
cardiogenic shock in 16 percent, hypovolemic shock in 16 percent, other types of distributive shock in 4
percent (eg, neurogenic shock, anaphylaxis), and obstructive shock in 2 percent [2].

In the emergency department (ED), the percentage of each type of shock seen depends upon the population
served by the ED [3,4]. As an example, busy, urban, level-I trauma centers will see a higher percentage of
hemorrhagic shock. In one study of 103 patients with undifferentiated shock presenting to a busy, urban ED,
36 percent of patients had hypovolemic shock, 33 percent had septic shock, 29 percent had cardiogenic, and
2 percent had other forms of shock [3].

Distributive — Distributive shock is characterized by severe peripheral vasodilatation (vasodilatory shock).

Molecules that mediate vasodilatation vary among the etiologies discussed in the sections below.

Septic shock — Sepsis, defined as a dysregulated host response to infection resulting in life-threatening
organ dysfunction [5], is the most common cause of distributive shock. Septic shock is a subset of sepsis
associated with mortality in the 40 to 50 percent range that can be identified [6] by the use of vasopressor
therapy and the presence of elevated lactate levels (>2 mmol/L) despite adequate fluid resuscitation. The
type of pathogen causing sepsis varies with the population studied. In the United States, gram-positive
bacteria (eg, Pneumococcus, Enterococcus) are the most common pathogens responsible for severe sepsis
and septic shock. However, antibiotic-resistant organisms (eg, methicillin-resistant staphylococcus), gram-
negative organisms (eg, Pseudomonas, Klebsiella, Enterobacter), and fungi (eg, Candida) are more
commonly encountered in those with shock from sepsis, when compared with patients who have sepsis
without the features of shock. The definition, epidemiology, prognosis, and evaluation of patients with
suspected sepsis and septic shock are discussed separately. (See "Sepsis syndromes in adults:
Epidemiology, definitions, clinical presentation, diagnosis, and prognosis" and "Evaluation and management
of suspected sepsis and septic shock in adults".)

Systemic inflammatory response syndrome (SIRS) — SIRS is a clinical syndrome that is characterized
by a robust inflammatory response, usually induced by a major body insult that can be infectious (see above)
and noninfectious (list below). (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical
presentation, diagnosis, and prognosis", section on 'Definitions'.)

Examples of noninfectious conditions that can be complicated by SIRS include the following:

● Pancreatitis (see "Clinical manifestations and diagnosis of acute pancreatitis", section on 'Natural history
and complications')

● Burns (see "Complications of severe burn injury")

● Hypoperfusion caused by trauma (see "Initial evaluation of shock in the adult trauma patient and
management of NON-hemorrhagic shock")

● Significant blunt trauma and crush injury (see "Initial evaluation of shock in the adult trauma patient and
management of NON-hemorrhagic shock")

● Amniotic fluid embolism (see "Amniotic fluid embolism syndrome")

● Air embolism (see "Air embolism")

● Fat embolism (see "Fat embolism syndrome")

● Idiopathic systemic capillary leak syndrome (see "Idiopathic systemic capillary leak syndrome")

● Post-successful return of spontaneous circulation after a cardiac arrest [7], myocardial infarction, or
cardio-pulmonary bypass (see "Sepsis syndromes in adults: Epidemiology, definitions, clinical
presentation, diagnosis, and prognosis")

Neurogenic shock — Hypotension and, in some cases, overt shock are common in patients with severe
traumatic brain injury and spinal cord injury. Interruption of autonomic pathways, causing decreased vascular
resistance and altered vagal tone, is thought to be responsible for distributive shock in patients with spinal
cord injury. However, hypovolemia from blood loss and myocardial depression may also contribute to shock
in this population. (See "Acute traumatic spinal cord injury", section on 'Cardiovascular complications' and
"Management of acute severe traumatic brain injury", section on 'Initial evaluation and treatment'.)
 Anaphylactic shock — Shock from anaphylaxis is most commonly encountered in patients with severe,
immunoglobulin-E (Ig-E) mediated, allergic reactions to insect stings, food, and drugs. In addition to
hemodynamic collapse, bronchospasm and increased airway resistance are cardinal features of anaphylaxis.
However, it can also be seen in patients with allergies to natural rubber latex, and clinically similar but
physiologically different anaphylactoid reactions are seen in patients with allergies to iodinated contrast (table
2). (See "Anaphylaxis: Acute diagnosis", section on 'Causes and mechanisms'.)

Drug and toxin-induced shock — Drug or toxin reactions that can be associated with shock or SIRS-like
syndromes include those associated with drug overdoses (eg, long-acting narcotics); snake bites; insect bites
including scorpion envenomation and various spider bites; transfusion reactions; heavy-metal poisoning
including arsenic, iron, and thallium; and infections associated with toxic shock syndrome (eg, Streptococcus
and Escherichia spp). (See "Use of blood products in the critically ill" and "Invasive group A streptococcal
infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis".)

Cyanide and carbon monoxide cause shock from mitochondrial dysfunction. (See "Cyanide poisoning" and
"Carbon monoxide poisoning" and "Inhalation injury from heat, smoke, or chemical irritants".)

Endocrine shock — Addisonian crisis (adrenal failure due to mineralocorticoid deficiency) and
myxedema can be associated with hypotension and states of shock. In states of mineralocorticoid deficiency,
vasodilatation can occur due to altered vascular tone and aldosterone-deficiency-mediated hypovolemia.
Although thyroid hormone plays a role in blood pressure homeostasis, the exact mechanism of vasodilation
in patients with myxedema is unclear; concurrent myocardial depression or pericardial effusions likely
contribute to hypotension and shock in this population. (See "Clinical manifestations of adrenal insufficiency
in adults", section on 'Hypotension' and "Myxedema coma", section on 'Cardiovascular abnormalities' and
"Cardiovascular effects of hypothyroidism".)

Patients with thyrotoxicosis can develop high-output cardiac failure and do not develop shock per se.
However, with progression, these patients can develop left ventricular systolic dysfunction and/or
tachyarrhythmia, leading to hypotension. (See "Cardiovascular effects of hyperthyroidism", section on 'Heart
failure' and "Overview of the clinical manifestations of hyperthyroidism in adults", section on 'Cardiovascular'.)

Cardiogenic — Cardiogenic shock is due to intracardiac causes of cardiac pump failure that result in
reduced cardiac output (CO). Causes of cardiac pump failure are diverse, but can be divided into the
following three categories listed in the sections below (table 1).

Cardiomyopathic — Cardiomyopathic causes of shock include myocardial infarction involving greater

than 40 percent of the left ventricular myocardium, myocardial infarction of any size if accompanied by severe
extensive ischemia due to multivessel coronary artery disease, severe right ventricular infarction, acute
exacerbation of heart failure in patients with severe underlying dilated cardiomyopathy, stunned myocardium
following cardiac arrest, prolonged ischemia or cardiopulmonary bypass, myocardial depression due to
advanced septic or neurogenic shock, and myocarditis. (See "Clinical manifestations and diagnosis of
cardiogenic shock in acute myocardial infarction", section on 'Pathophysiology' and "Clinical manifestations
and diagnosis of cardiogenic shock in acute myocardial infarction", section on 'Etiology' and "Right ventricular
myocardial infarction" and "Coronary artery bypass graft surgery in patients with acute ST-elevation
myocardial infarction", section on 'Cardiogenic shock' and "Clinical manifestations and diagnosis of
myocarditis in adults".)

Patients with hypertrophic cardiomyopathy or severe diastolic heart failure rarely present with cardiogenic
shock, but these underlying conditions may contribute to hypotension and shock from other causes (eg,
sepsis, hypovolemia). (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation"
and "Clinical manifestations and diagnosis of heart failure with preserved ejection fraction".)

Arrhythmic — Both atrial and ventricular tachyarrhythmias and bradyarrhythmias may induce
hypotension, often contributing to states of shock. However, when CO is severely compromised by significant
rhythm disturbances (eg, sustained ventricular tachycardia, complete heart block), patients can present with
cardiogenic shock. If CO is absent because of the underlying rhythm (eg, pulseless ventricular tachycardia,
ventricular fibrillation), patients can present in cardiac arrest. (See "Overview of atrial fibrillation" and "Wide
QRS complex tachycardias: Approach to the diagnosis" and "Ventricular arrhythmias during acute myocardial
infarction: Incidence, mechanisms, and clinical features" and "Third degree (complete) atrioventricular
block".)

Mechanical — Mechanical causes of cardiogenic shock include severe aortic or mitral valve insufficiency,
and acute valvular defects due to rupture of a papillary muscle or chordae tendineae (mitral valve defect) or
retrograde dissection of the ascending aorta into the aortic valve ring or an abscess of the aortic ring (aortic
insufficiency). Additional causes include severe ventricular septal defects or acute rupture of the
intraventricular septum, atrial myxomas, and a ruptured ventricular free wall aneurysm. While a ruptured
ventricular aneurysm can cause cardiogenic shock due to reduced output from the left ventricle, it can also
present with the features of obstructive shock, when bleeding is contained by the pericardial sac, or
catastrophic hemorrhagic shock, when the pericardial sac is breached and hemorrhage is ongoing. (See
"Acute mitral regurgitation in adults" and "Acute aortic regurgitation in adults" and "Clinical manifestations and
diagnosis of ventricular septal defect in adults" and "Mechanical complications of acute myocardial infarction"
and "Cardiac tumors".)

Critical aortic stenosis or mitral stenosis rarely present with cardiogenic shock, but often contribute to
hypotension and shock from other causes (eg, sepsis, hypovolemia). (See "Clinical manifestations and
diagnosis of aortic stenosis in adults" and "Clinical manifestations and diagnosis of rheumatic mitral
stenosis".)

Hypovolemic — Hypovolemic shock is due to reduced intravascular volume (ie, reduced preload), which, in
turn, reduces CO. Hypovolemic shock can be divided into two categories: hemorrhagic and nonhemorrhagic
(table 1).

Hemorrhagic — Reduced intravascular volume from blood loss can result in shock. There are multiple
causes of hemorrhagic shock, of which blunt or penetrating trauma (includes multiple fractures without vessel
injury) is the most common, followed by upper (eg, variceal hemorrhage, peptic ulcer) or lower (eg,
diverticular, arteriovenous malformation) gastrointestinal bleeding. (See "Initial evaluation of shock in the
adult trauma patient and management of NON-hemorrhagic shock", section on 'Pathophysiology' and
"Causes of upper gastrointestinal bleeding in adults" and "Etiology of lower gastrointestinal bleeding in
adults" and "Initial management of moderate to severe hemorrhage in the adult trauma patient", section on
'Classification of hemorrhage'.)

Less common causes include intraoperative and postoperative bleeding, ruptured abdominal aortic or left
ventricle aneurysm, aortic–enteric fistula, hemorrhagic pancreatitis, iatrogenic (eg, inadvertent biopsy of
arteriovenous malformation, severed artery), tumors or abscess erosion into major vessels, postpartum
hemorrhage, uterine or vaginal hemorrhage from other causes (eg, infection, tumors, lacerations),
spontaneous peritoneal hemorrhage from bleeding diathesis, and ruptured hematoma. (See "Management of
symptomatic (non-ruptured) and ruptured abdominal aortic aneurysm", section on 'Ruptured AAA' and "Left
ventricular aneurysm and pseudoaneurysm following acute myocardial infarction" and "Clinical manifestations
and diagnosis of acute pancreatitis" and "Overview of the complications of peptic ulcer disease", section on
'Penetration' and "Overview of postpartum hemorrhage" and "Managing an episode of severe or prolonged
uterine bleeding", section on 'Etiology'.)

Nonhemorrhagic — Reduced intravascular volume from fluid loss other than blood can cause shock.
Volume depletion from loss of sodium and water can occur from a number of anatomic sites (see "Etiology,
clinical manifestations, and diagnosis of volume depletion in adults", section on 'Etiology'):

● Gastrointestinal losses (eg, diarrhea, vomiting, external drainage)

● Skin losses (eg, heat stroke, burns, severe dermatologic conditions including Stevens-Johnson
syndrome)
 ● Renal losses (eg, excessive drug-induced or osmotic diuresis, salt-wasting nephropathies,
hypoaldosteronism)

● Third space losses into the extravascular space or body cavities (eg, postoperative and trauma,
intestinal obstruction, crush injury, pancreatitis, cirrhosis)

Obstructive — Obstructive shock is mostly due to extracardiac causes of cardiac pump failure and often
associated with poor right ventricle output. The causes of obstructive shock can be divided into the following
two categories, listed in the sections below (pulmonary vascular and mechanical) (table 1).

Pulmonary vascular — Most cases of obstructive shock are due to right ventricular failure from
hemodynamically significant pulmonary embolism (PE) or severe pulmonary hypertension (PH). In these
cases, the right ventricle fails because it is unable to generate enough pressure to overcome the high
pulmonary vascular resistance associated with PE or PH. While hemodynamic collapse in the setting of PE is
traditionally attributed to mechanical obstruction, pulmonary vasoconstriction mediated by vasoactive
mediators such as serotonin and thromboxane also contribute to the observed pathophysiology [8]. Patients
with severe stenosis or with acute obstruction of the pulmonary or tricuspid valve may also fall into this
category. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected
acute pulmonary embolism", section on 'Hemodynamically unstable patients' and "Classification and
prognosis of pulmonary hypertension in adults", section on 'Classification'.)

Acute right heart syndrome can, given ventricular interdependence, mimic left ventricular dysfunction
resulting in cardiogenic shock. Acute right heart syndrome is associated with myocardial infarction localizing
to the right ventricle, massive volume overload, hypoxemic vasoconstriction resulting in acute pulmonary
hypertension, and pulmonary embolism. In patients with pre-existing pulmonary hypertension and right
ventricular dysfunction, ischemia, volume overload, or hypoxemia should be avoided as these insults can
result in acute-on-chronic right ventricular dysfunction resulting in cardiovascular collapse. (See 'Cardiogenic'
above.)

Mechanical — Patients in this category present clinically as hypovolemic shock because their primary
physiologic disturbance is decreased preload, rather than pump failure (eg, reduced venous return to the
right atrium or inadequate right ventricle filling). Mechanical causes of obstructive shock include the following:

● Tension pneumothorax (see "Primary spontaneous pneumothorax in adults", section on 'Clinical

presentation')

● Pericardial tamponade (see "Cardiac tamponade", section on 'Physiology' and "Cardiac tamponade",
section on 'Etiology')

● Constrictive pericarditis (see "Constrictive pericarditis", section on 'Physiology' and "Constrictive

pericarditis", section on 'Etiology')

● Restrictive cardiomyopathy (see "Definition and classification of the cardiomyopathies", section on

'Restrictive cardiomyopathy')

Abdominal compartment syndrome (ACS), defined as sustained intra-abdominal hypertension associated

with organ dysfunction can exacerbate shock. Primary ACS develops in patients with an intra-abdominal
injury, whereas secondary ACS is frequently the result of massive volume resuscitation. ACS impairs
cardiovascular function by both reducing venous return and by impairing myocardial contractility. (see
"Abdominal compartment syndrome in adults")

Combined — Patients often present with combined forms of shock. Examples include:

● Patients with shock from sepsis or pancreatitis primarily have distributive shock (due to the effects of
inflammatory and anti-inflammatory cascades on vascular permeability and peripheral vasodilation);
however, they also often have a hypovolemic component (due to decreased oral intake, insensible
 losses, vomiting, diarrhea) and a cardiogenic component (due to inflammation-related myocardial
depression).

● Patients with underlying cardiomyopathy may present with hypovolemic shock (from over-diuresis) and
cardiogenic shock (from inadequate compensatory tachycardia and/or stroke volume).

● Patients with severe traumatic injury may have hemorrhagic shock from blood loss as well as distributive
shock from SIRS or, less commonly, fat embolism.

● Patients with trauma to the spinal cord can have distributive shock from injury-related autonomic
dysfunction and cardiogenic shock from myocardial depression.

● Patients with a ruptured left ventricular free wall aneurysm can have cardiogenic shock from primary
pump failure, obstructive shock from cardiac tamponade when blood loss is contained by the pericardial
sac, and hemorrhagic shock when blood loss is not contained by the pericardial sac.

● Patients with septic shock may transition from a distributive (low systemic vascular resistance [SVR])
shock state to multifactorial shock state after massive volume resuscitation that results in abdominal
compartment syndrome and/or acute right heart syndrome.

PATHOGENESIS AND PATHOPHYSIOLOGY — The general mechanisms, physiology, and stages of shock
are discussed in the sections below (see 'Mechanisms of shock' below and 'Physiology' below and 'Stages of
shock' below). The pathogenesis and physiology of specific forms of shock are discussed separately:

● Septic shock (see "Pathophysiology of sepsis")

● Burns (see "Burn wound infection and sepsis", section on 'Pathogenesis')

● Amniotic fluid embolism (see "Amniotic fluid embolism syndrome", section on 'Pathophysiology')

● Air embolism syndrome (see "Air embolism", section on 'Terminology and pathophysiology')

● Fat embolism syndrome (see "Fat embolism syndrome", section on 'Pathogenesis')

● Idiopathic systemic capillary leak syndrome (see "Idiopathic systemic capillary leak syndrome", section
on 'Pathogenesis')

● Spinal cord injury (see "Acute traumatic spinal cord injury", section on 'Pathophysiology')

● Anaphylactic shock (see "Pathophysiology of anaphylaxis")

● Toxic shock syndrome (see "Staphylococcal toxic shock syndrome", section on 'Microbiology and
pathogenesis')

● Myxedema coma (see "Myxedema coma", section on 'Epidemiology and risk factors' and "Myxedema
coma", section on 'Cardiovascular abnormalities')

● Cardiogenic shock (see "Pathophysiology of cardiogenic pulmonary edema")

● Pulmonary embolism (PE) (see "Overview of acute pulmonary embolism in adults", section on
'Pathogenesis and pathophysiology')

● Pericardial tamponade (see "Cardiac tamponade", section on 'Physiology')

● Constrictive pericarditis and restrictive cardiomyopathy (see "Differentiating constrictive pericarditis and
restrictive cardiomyopathy")

Mechanisms of shock — Cellular hypoxia occurs as a result of reduced tissue perfusion/oxygen delivery
and/or increased oxygen consumption or from inadequate oxygen utilization [9-11]. Cellular hypoxia, in turn,
causes cell membrane ion pump dysfunction, intracellular edema, leakage of intracellular contents into the
extracellular space, and inadequate regulation of intracellular pH. These biochemical processes, when
unchecked, progress to the systemic level, resulting in acidosis, and endothelial dysfunction, as well as
further stimulation of inflammatory and anti-inflammatory cascades. Compounding this process is a further
reduction in tissue perfusion from complex humoral and microcirculatory processes that impair regional blood
flow [11,12].

Serum lactate levels, when elevated, have traditionally been used as surrogates for hypoperfusion and tissue
hypoxia. Admittedly, lactate flux is more complex than the tissue hypoxia hypothesis suggests, as
epinephrine-mediated aerobic glycolysis in skeletal muscle contributes to hyperlactatemia [13] as well,
elevations in serum lactate level are useful risk-stratification tools in undifferentiated shock.

Physiology — The major physiologic determinants of tissue perfusion (and systemic blood pressure [BP])
are cardiac output (CO) and systemic vascular resistance (SVR):

BP = CO X SVR

CO is the product of heart rate (HR) and stroke volume (SV):

CO = HR X SV

The stroke volume is determined by:

● Preload

● Myocardial contractility

● Afterload

SVR is governed by:

● Vessel length

● Blood viscosity

● Vessel diameter (ie, vessel tone)

Thus, biologic processes that change any one of these physiologic parameters can result in hypotension
and shock.

The hemodynamic profiles measured on pulmonary artery catheterization that distinguish each class of shock
are shown in the tables (table 3 and table 4). Common to most forms of shock is diminished CO and/or SVR.
Occasionally, the SVR is low relative to a high CO (eg, thyrotoxicosis), which can result in poor tissue
perfusion. In general, severe hypovolemia, cardiogenic shock, and late-stage obstructive shock are
characterized by a low CO and compensatory increase in the SVR to maintain perfusion to vital organs,
whereas distributive shock is classically associated with reduced SVR and compensatory increase in the CO.
However, the CO may be normal in the early phases of hypovolemic and obstructive shock. Similarly, in some
cases of severe distributive shock (eg, sepsis and neurogenic shock) or combined shock, both CO and SVR
may be reduced.

Some forms of shock have normal CO and SVR. As an example, patients with profound mitochondrial
dysfunction (eg, inheritable mitochondrial disease, carbon monoxide, and cyanide poisoning) are shock
states that occur despite normal CO, SVR, and tissue perfusion because they are due to inadequate oxygen
utilization. (See "Mitochondrial myopathies: Clinical features and diagnosis" and "Carbon monoxide
poisoning" and "Cyanide poisoning" and "Inhalation injury from heat, smoke, or chemical irritants".)

Stages of shock — Shock is a physiologic continuum [10,14]. It begins with an inciting event, such as a
focus of infection (eg, abscess) or an injury (eg, gunshot wound), which can progress through several stages.
The early stages of shock (pre-shock, shock) are more amenable to therapy and are more likely to be
reversible, compared with end-stage shock, which is associated with irreversible end-organ damage and
death.

● Pre-shock – Pre-shock is also known as compensated shock, or cryptic shock. It is characterized by

compensatory responses to diminished tissue perfusion [15]. As an example, in early hypovolemic pre-
shock, a compensatory tachycardia and peripheral vasoconstriction may allow an otherwise healthy
adult to be asymptomatic and preserve a normal blood pressure despite a 10 percent reduction in total
effective arterial blood volume. Thus, tachycardia, a modest change in systemic blood pressure
(increase or decrease), or mild to moderate hyperlactatemia, may be the only clinical signs of early
shock [16]. Potentially, with timely and appropriate management, deterioration can be prevented and
signs of impending deterioration can be reversed (eg, normalization of serum lactate levels).

● Shock – During shock, the compensatory mechanisms become overwhelmed, and signs and symptoms
of organ dysfunction appear including symptomatic tachycardia, dyspnea, restlessness, diaphoresis,
metabolic acidosis, hypotension, oliguria, and cool, clammy skin.

The signs and symptoms of organ dysfunction typically correspond to a significant pathophysiologic
perturbation [17-19]. As examples, in hypovolemic shock, clinical signs and symptoms are associated
with a 20 to 25 percent reduction in arterial blood volume, and, in cardiogenic shock, a fall in the cardiac
index to less than 2.5 L/min/m2 is required before signs and symptoms appear [19].

● End-organ dysfunction – Progressive shock leads to irreversible organ damage, multiorgan failure
(MOF), and death. During this stage, anuria and acute renal failure develop, acidemia further depresses
CO, hypotension becomes severe and recalcitrant to therapy, hyperlactatemia often worsens, and
restlessness evolves into obtundation and coma. Death is common in this phase of shock.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics"
and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer short, easy-to-
read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail
these topics to your patients. (You can also locate patient education articles on a variety of subjects by
searching on "patient info" and the keyword(s) of interest.)

● Basics topic (see "Patient education: Shock (The Basics)")

SUMMARY AND RECOMMENDATIONS

● Shock is defined as a state of cellular and tissue hypoxia due to reduced oxygen delivery and/or
increased oxygen consumption or inadequate oxygen utilization. "Undifferentiated shock" refers to the
situation where shock is recognized but the cause is unclear. (See 'Definition' above.)

● Four types of shock are recognized. However, many patients have a combination of more than one form
of shock listed below (table 1):

• Distributive shock has many causes, including septic shock, systemic inflammatory response
syndrome (SIRS; eg, pancreatitis), neurogenic shock, anaphylactic shock, toxin-related shock, and
endocrine shock (eg, addisonian crisis).

• Cardiogenic shock may be cardiomyopathic (eg, myocardial infarction), or due to an arrhythmia (eg,
sustained ventricular tachycardia) or a mechanical abnormality (eg, acute valvular rupture).
 • Hypovolemic shock may be due to hemorrhagic (eg, trauma) or nonhemorrhagic fluid losses (eg,
vomiting).

• Obstructive shock may be pulmonary vascular related (eg, pulmonary embolism [PE]) or due to a
mechanical cause of reduced preload (eg, tension pneumothorax, pericardial tamponade).

● Cellular hypoxia results in cell membrane ion pump dysfunction, intracellular edema, leakage of
intracellular contents into the extracellular space, and inadequate regulation of intracellular pH. These
biochemical processes, in turn, progress to acidosis, endothelial dysfunction, and further stimulation of
inflammatory and anti-inflammatory cascades. (See 'Mechanisms of shock' above.)

● Common to most forms of shock is diminished cardiac output (CO) and/or systemic vascular resistance
(SVR). In general, severe hypovolemia, cardiogenic shock, and late-stage obstructive shock are
characterized by a low CO and compensatory increase in the SVR to maintain perfusion to vital organs,
whereas distributive shock is classically associated with reduced SVR and compensatory increase in the
CO. Shock due to disorders of mitochondrial function (eg, carbon monoxide poisoning) have normal CO
and SVR. (See 'Physiology' above.)

● Shock begins with an inciting event that may progress through several stages: pre-shock, shock, and
end-organ dysfunction. The progression can culminate in irreversible end-organ damage and death.
(See 'Stages of shock' above.)

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

1. Vincent JL, De Backer D. Circulatory shock. N Engl J Med 2013; 369:1726.

2. De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment
of shock. N Engl J Med 2010; 362:779.
3. Kheng CP, Rahman NH. The use of end-tidal carbon dioxide monitoring in patients with hypotension in
the emergency department. Int J Emerg Med 2012; 5:31.
4. Jones AE, Craddock PA, Tayal VS, Kline JA. Diagnostic accuracy of left ventricular function for
identifying sepsis among emergency department patients with nontraumatic symptomatic
undifferentiated hypotension. Shock 2005; 24:513.
5. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for
Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315:801.
6. Shankar-Hari M, Phillips GS, Levy ML, et al. Developing a New Definition and Assessing New Clinical
Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock
(Sepsis-3). JAMA 2016; 315:775.
7. Adrie C, Laurent I, Monchi M, et al. Postresuscitation disease after cardiac arrest: a sepsis-like
syndrome? Curr Opin Crit Care 2004; 10:208.
8. Smulders YM. Pathophysiology and treatment of haemodynamic instability in acute pulmonary
embolism: the pivotal role of pulmonary vasoconstriction. Cardiovasc Res 2000; 48:23.
9. Barber AE, Shires GT. Cell damage after shock. New Horiz 1996; 4:161.
10. Kristensen SR. Mechanisms of cell damage and enzyme release. Dan Med Bull 1994; 41:423.
11. Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013; 369:840.
12. Hinshaw LB. Sepsis/septic shock: participation of the microcirculation: an abbreviated review. Crit Care
Med 1996; 24:1072.
 13. James JH, Luchette FA, McCarter FD, Fischer JE. Lactate is an unreliable indicator of tissue hypoxia in
injury or sepsis. Lancet 1999; 354:505.
14. Abboud, FM. Pathophysiology of hypotension and shock. In: The Heart, Hurst, JW (Eds), McGraw-Hill,
New York 1982. p.452.
15. Shoemaker WC. Temporal physiologic patterns of shock and circulatory dysfunction based on early
descriptions by invasive and noninvasive monitoring. New Horiz 1996; 4:300.
16. Chien S. Role of the sympathetic nervous system in hemorrhage. Physiol Rev 1967; 47:214.
17. Tuchschmidt JA, Mecher CE. Predictors of outcome from critical illness. Shock and cardiopulmonary
resuscitation. Crit Care Clin 1994; 10:179.
18. Casey LC, Balk RA, Bone RC. Plasma cytokine and endotoxin levels correlate with survival in patients
with the sepsis syndrome. Ann Intern Med 1993; 119:771.
19. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis
Definitions Conference. Crit Care Med 2003; 31:1250.

Topic 1594 Version 17.0

GRAPHICS

Classification of shock

Septic Gram positive (Pneumococcus, Staphylococcus, Streptococcus,

Enterococcus, Legionella, Listeria)
Gram negative (Klebsiella, Pseudomonas, Escherichia,
Haemophilus, Neisseria, Moraxella, Rickettsia, Francisella
[tularemia])
Fungal (Candida, Aspergillus)
Viral (influenza, cytomegalovirus, Ebola, varicella)
Parasitic (Plasmodium, Ascaris, Babesia)
Mycobacterium (Mycobacterium tuberculosis, Mycobacterium
abscessus)

Non-septic Inflammatory shock (systemic inflammatory response syndrome)

Distributive – Burns, trauma, pancreatitis, postmyocardial infarction, post
coronary bypass, post cardiac arrest, viscus perforation, amniotic
fluid embolism, fat embolism, idiopathic systemic capillary leak
syndrome
Neurogenic shock – Traumatic brain injury, spinal cord injury
(quadriparesis with bradycardia or paraplegia with tachycardia),
neuraxial anesthesia
Anaphylactic shock – IgE-mediated (eg, foods, medications, insect
bites or stings), IgE-independent (eg, iron dextran),
nonimmumnologic (eg, exercise or heat-induced), idiopathic
Other – Liver failure, transfusion reactions, vasoplegia (eg,
vasodilatory agents, cardiopulmonary bypass), toxic shock
syndrome, toxicologic (eg, heavy metals), beriberi

Cardiomyopathic Myocardial infarction (involving >40% of the left ventricle or with

extensive ischemia)
Severe right ventricle infarction
Acute exacerbation of severe heart failure from dilated
cardiomyopathy
Stunned myocardium from prolonged ischemia (eg, cardiac arrest,
hypotension, cardiopulmonary bypass)
Advanced septic shock
Myocarditis
Myocardial contusion
Cardiogenic
Drug-induced (eg, beta blockers)

Arrhythmogenic Tachyarrhythmia – Atrial tachycardias (fibrillation, flutter, reentrant

tachycardia), ventricular tachycardia and fibrillation
Bradyarrhythmia – Complete heart block, Mobitz type II second
degree heart block

Mechanical Severe valvular insufficiency, acute valvular rupture (papillary or

chordae tendineae rupture, valvular abscess), critical valvular
stenosis, acute or severe ventricular septal wall defect, ruptured
ventricular wall aneurysm, atrial myxoma

Hypovolemic Hemorrhagic Trauma, gastrointestinal bleeding (eg, varices, peptic ulcer),

intraoperative and postoperative bleeding, retroperitoneal bleeding
(eg, ruptured aortic aneurysm), aortic-enteric fistula, hemorrhagic
pancreatitis, iatrogenic (eg, inadvertent biopsy of arteriovenous
malformation, or left ventricle), tumor or abscess erosion into
major vessels, ruptured ectopic pregnancy, postpartum
hemorrhage, uterine or vaginal hemorrhage (eg, infection, tumors,
lacerations), spontaneous peritoneal hemorrhage from bleeding
diathesis

Non- Gastrointestinal losses (eg, diarrhea, vomiting, external drainage);

 hemorrhagic skin losses (eg, heat stroke, burns, dermatologic conditions); renal
losses (eg, excessive drug-induced or osmotic diuresis, salt-
wasting nephropathies, hypoaldosteronism); third space losses
into the extravascular space or body cavities (eg, postoperative
and trauma, intestinal obstruction, crush injury, pancreatitis,
cirrhosis)

Pulmonary Hemodynamically significant pulmonary embolus, severe

vascular pulmonary hypertension, severe or acute obstruction of the
pulmonic or tricuspid valve, venous air embolus

Mechanical Tension pneumothorax or hemothorax (eg, trauma, iatrogenic),

Obstructive pericardial tamponade, constrictive pericarditis, restrictive
cardiomyopathy, severe dynamic hyperinflation (eg, elevated
intrinsic PEEP), left or right ventricular outflow tract obstruction,
abdominal compartment syndrome, aorto-caval compression (eg,
positioning, surgical retraction)

Endocrine (eg, adrenal insufficiency, thyrotoxicosis, myxedema

coma)
Metabolic (eg, acidosis, hypothermia)
Mixed/unknown
Other – Polytrauma with more than one shock category, acute
shock etiology with pre-existing cardiac disease, late under-
resuscitated shock, miscellaneous poisonings

Aortic dissection causes shock when retrograde dissection results in cardiac tamponade, acute aortic insufficiency,
and myocardial infarction; please refer to the UpToDate topic text for details.

PEEP: positive end-expiratory pressure.

Graphic 99574 Version 5.0

Causes of anaphylaxis

Allergens (IgE-dependent immunologic mechanism)

Foods, especially peanut, tree nut, crustacean shellfish, finned fish, milk, egg

Insect stings (eg, Hymenoptera venom) and insect bites (eg, kissing bugs)

Medications (eg, antibiotics, NSAIDs)

Biologic materials, including allergen immunotherapy, monoclonal antibodies, chemotherapy agents, and
vaccines*

Natural rubber latex

Food additives, including spices, insect-derived colorants (eg, carmine), and vegetable gums

Inhalants (rare) (eg, horse dander, cat dander, grass pollen)

Human seminal fluid (rare trigger of anaphylaxis in women)

Occupational allergens (eg, stinging insects, natural rubber latex)

Immunologic triggers (IgE-independent mechanism)

IgG-dependent (rare) (eg, to high-molecular weight dextran, infliximab)

Coagulation system activation (eg, heparin contaminated with oversulfated chondroitin sulfate)

Idiopathic anaphylaxis
Consider the possibility of a hidden or previously unrecognized trigger

Consider the possibility of a mast cell activation syndrome, including systemic mastocytosis

Nonimmunologic triggers (direct activation of mast cells and basophils)

Physical factors (eg, exercise ¶, cold, heat)

Medications (eg, opioids, NSAIDs)

Radiocontrast agents

Alcohol (ethanol) (may augment, rarely induces)

Any food, insect sting or bite, or medication or biologic can potentially trigger anaphylaxis. Novel or unusual
allergen triggers include storage mite-contaminated flour and saliva from kissing bugs. They also
include mosquitoes, pigeon ticks, green ants, and pharaoh ants and venoms from jellyfish, scorpions, and snakes.
Medications include taxanes, platins, and other chemotherapy drugs, biologic agents, including monoclonal
antibodies, such as rituximab, cetuximab, infliximab, and uncommonly, omalizumab. Some triggers, such as
radiocontrast media, insect venoms, and medications (such as NSAIDs) can act through more than one
mechanism.

IgE: immunoglobulin E; NSAIDs: nonsteroidal anti-inflammatory drugs; IgG: immunoglobulin G.

* Reactions to vaccines are rare and typically involve an excipient, such as gelatin, rather than microbial content.
¶ Often involves a cofactor, such as a food, medication (eg, an NSAID), or exposure to cold air or water.

Graphic 70667 Version 22.0

Hemodynamic values of normal recumbent adults

Mean Range

Cardiac index (L/min/m 2) 3.4 2.8 to 4.2

Stroke volume index (mL/m 2/beat) 47 30 to 65

Arteriovenous oxygen difference (mL per liter of blood) 38 30 to 48

Arterial saturation (%) 98 94 to 100

Pressure* (mmHg)

Left ventricle
Systolic 130 90 to 140
End-diastolic 7 4 to 12

Left atrium
Maximum 13 6 to 20
Minimum 3 –2 to +9
Mean 7 4 to 12

Pulmonary artery wedge ("PC")

Maximum 16 9 to 23
Minimum 6 1 to 12
Mean 9 6 to 15

Pulmonary artery
Systolic 24 15 to 28
Diastolic 10 5 to 16
Mean 16 10 to 22

Right ventricle
Systolic 24 15 to 28
End-diastolic 4 0 to 8

Right atrium
Maximum 7 2 to 14
Minimum 2 –2 to +6
Mean 4 –1 to +8

Venae cavae
Maximum 7 2 to 14
Minimum 5 0 to 8
Mean 6 1 to 10

End-diastolic volume index

Left ventricular (mL/m 2) 70 50 to 90

Resistance (dyn×s/cm 5)
Total systemic 1150 900 to 1400
Systemic arteriolar 850 600 to 900
Total pulmonary 200 150 to 250
Pulmonary arteriolar 70 45 to 120

* Baseline for pressure measurements one-half of anteroposterior chest diameter. 1 mmHg = 133.332 Pascal (PA) =
0.133 kPa.

Reproduced with permission from: Hurst JW, Rackley CE, Sonnenblick EH, Wenger NK. The Heart: Arteries and veins. 7th
ed. McGraw-Hill, Inc, New York 1990. Copyright © 1990 McGraw-Hill Companies, Inc.

Graphic 70326 Version 19.0

Hemodynamic profiles of shock on pulmonary artery catheter in adults

Physiologic Tissue
Preload Pump function Afterload
variable perfusion

Pulmonary Mixed venous

Clinical Systemic vascular
capillary wedge Cardiac output* oxyhemoglobin
measurement resistance
pressure saturation ¶

Hypovolemic ↔ (early) or ↓ (late) ↔ (early) or ↓ (late) ↑ >65% (early) or

<65% (late)

Cardiogenic ↑ ↓ ↑ <65%

Distributive ↔ (early) or ↓ (late) ↑ or ↓ (occasionally) ↓ >65%

Obstructive

PE, PH, ↔ (early) or ↓ (late) ↔ (early) or ↓ (late) ↑ >65%

tension
pneumothorax

Pericardial ↑ ↓ ↑ <65%
tamponade Δ

PE: pulmonary embolus; PH: pulmonary hypertension; PAC: pulmonary artery catheter.
* Cardiac output is generally measured using the cardiac index.
¶ Mixed venous oxyhemoglobin saturation cutoff measured on PAC is 65%, but on triple lumen catheter is 70%.
Δ Equalization of right atrial, right ventricular end-diastolic and pulmonary artery wedge pressures is classic in pericardial
tamponade and distinguishes it from primary cardiogenic shock.

Graphic 99516 Version 3.0

Contributor Disclosures
David F Gaieski, MD Nothing to disclose Mark E Mikkelsen, MD, MSCE Nothing to disclose Polly E
Parsons, MD Nothing to disclose Geraldine Finlay, MD Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform
to UpToDate standards of evidence.

Conflict of interest policy