- Author: Klaus-Dieter Lessnau, MD, FCCP; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM more...
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 4 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) :
Core temperature of higher than 38°C (100.0°F) or lower than 36°C (96.8°F)
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/µL, less than 4,000/µL, or more than 10% immature (band) forms
The clinical suspicion of systemic inflammatory response syndrome by an experienced clinician is of utmost importance.
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.
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
Reactions to drugs or toxins
Heavy metal poisoning
All of these conditions share the common characteristic of hypotension due to decreased SVR and low effective circulating plasma volume.
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.
Systemic inflammatory response syndrome
Causes of SIRS include the following:
Fulminant hepatic failure
Toxic shock syndrome
TSS can result from infection with Streptococcus pyogenes (group A Streptococcus) or Staphylococcus aureus.
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
Metabolic failure in hormone production due to congenital conditions or drug-induced inhibition of synthetic enzymes (eg, metyrapone, ketoconazole)
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
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. From 1979-2000, the incidence of sepsis increased by 9% per year.
Sepsis is a common cause of death throughout the world and kills approximately 1,400 people worldwide every day.[6, 7]
Increased age correlates with increased risk of death from sepsis.
The mortality rate after development of septic shock is 20-80%. Data suggest that mortality due to septic shock has decreased slightly because of new therapeutic interventions. 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.
Higher mortality rates have also been associated with the following:
The finding of positive blood cultures
Infection with antibiotic-resistant organisms such as Pseudomonas aeruginosa
Elevated serum lactate levels
Impaired immune function
Poor functional status prior to the onset of sepsis.
Mortality rates associated with other forms of distributive shock are not well documented.
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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|Diagnosis||Pulmonary Capillary Wedge Pressure||Cardiac Output|
|Extracardiac obstructive shock
1. Pericardial tamponade†
2. Pulmonary embolism
Normal or decreased
1. Septic shock
2. Anaphylactic shock
|Normal or decreased
Normal or decreased
|Increased or normal
Increased or normal
|*In cardiogenic shock due to a mechanical defect, such as mitral regurgitation, forward cardiac output is reduced, although the measured cardiac output may be unreliable. Large V waves are commonly observed in the pulmonary capillary wedge tracing in mitral regurgitation.
†The hallmark finding is equalization of right atrial mean, right ventricular end-diastolic, pulmonary artery (PA) end-diastolic, and pulmonary capillary wedge pressures.
|Drug||Dose||Principal Mechanism||Cardiac Output||Blood Pressure||SVR|
|Dobutamine||2-20 mcg/kg/min||Beta 1||++||+||+|
|5-10 mcg/kg/min||Beta 1, dopamine||++||+||+|
|Epinephrine (low dose)||0.06-0.20 mcg/kg/min||Beta 1, beta 2 >alpha||++||+||+|
|Inotropic agents and vasoconstrictors|
|Dopamine (high dose)||>10 mcg/kg/min||Alpha, beta 1, dopamine||++||++||+|
|0.21-0.42 mcg/kg/min||Alpha >beta 1, beta 2||++||++||+|
|Norepinephrine||0.02-0.25 mcg/kg/min||Alpha >beta 1, beta 2||+||++||++|
|Vasopressin||0.10-0.40 U/min||V1 receptor||+||+||++|
(very low dose)
|Milrinone||0.4-0.6 mcg/kg/min after loading dose; 50 mcg/kg bolus over 5 min||Phosphodiesterase inhibitor||+||+/-||-|
|Alpha and beta refer to agonist activity at these adrenergic receptor sites.
Beta 1-adrenergic effects are inotropic and increase contractility.
Beta 2-adrenergic effects are chronotropic.
|Suspected Source||Recommended Antibiotic Therapy||Alternative Therapy|
|No source evident in a healthy host||Third-generation cephalosporin, eg, ceftriaxone 2 g IV q12h, ceftizoxime, ceftazidime||Nafcillin and aminoglycoside, imipenem, piperacillin/tazobactam|
|No source evident in an immunocompromised host||Ceftazidime 2 g IV q8h plus aminoglycoside||Imipenem or piperacillin/tazobactam plus aminoglycoside|
|No source evident in a user of intravenous drugs||Nafcillin 2 g IV q4h plus aminoglycoside||Vancomycin plus aminoglycoside, ceftazidime, imipenem, or piperacillin/tazobactam|
|Bacterial pneumonia, community acquired||Ceftriaxone 2 g IV q12-24 h plus macrolide||Levofloxacin 750mg IV q24h, cotrimoxazole or imipenem plus macrolide|
|Bacterial pneumonia, hospital acquired||Piperacillin/tazobactam 4.5 g IV q6h plus aminoglycoside, plus levofloxacin 750 mg IV q24h||Imipenem plus aminoglycoside, plus macrolide|
|Urinary tract infection||Ampicillin 2 g IV q4h plus aminoglycoside||Fluoroquinolone or third-generation cephalosporin plus aminoglycoside|
|Mixed aerobic and anaerobic abdominal sepsis, aspiration pneumonia, pelvic infection, and necrotizing cellulitis||Third-generation cephalosporin or ampicillin 2 g IV q4h plus aminoglycoside plus clindamycin 600 mg IV q8h or metronidazole 500 mg IV q6h||Fluoroquinolone plus clindamycin, imipenem, piperacillin/tazobactam|
|Meningitis||Ceftriaxone 2 g IV q12h plus vancomycin||Meropenem plus vancomycin, chloramphenicol plus cotrimoxazole plus vancomycin|
|Cellulitis/erysipelas||Nafcillin 2 g IV q4h||Cefazolin, vancomycin, clindamycin|
|Toxic shock syndrome (TSS) or streptococcal necrotizing fasciitis||Clindamycin 600 mg IV q8h||Cephalosporin, vancomycin, nafcillin|