Septic Shock

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Septic Shock
Chief Editor: Michael R Pinsky, MD, CM, FCCP, FCCM more... Updated: Aug 13, 2012

In 1914, Schottmueller wrote, “Septicemia is a state of microbial invasion from a portal of entry into the blood stream which causes sign of illness.” The definition did not change much over the years, because the terms sepsis and septicemia referred to several ill-defined clinical conditions present in a patient with bacteremia. In practice, the terms often were used interchangeably; however, fewer than half the patients with signs and symptoms of sepsis have positive results on blood culture. Furthermore, not all patients with bacteremia have signs of sepsis; therefore, sepsis and septicemia are not identical. In the past few decades, the discovery of endogenous mediators of the host response has led to the recognition that the clinical syndrome of sepsis is the result of excessive activation of host defense mechanisms rather than the direct effect of microorganisms. Sepsis and its sequelae represent a continuum of clinical and pathophysiologic severity. Serious bacterial infections at any body site, with or without bacteremia, are usually associated with important changes in the function of every organ system in the body. These changes are mediated mostly by elements of the host immune system against infection. Shock is deemed present when volume replacement fails to increase blood pressure to acceptable levels and associated clinical evidence indicates inadequate perfusion of major organ systems, with progressive failure of organ system functions. Multiple organ dysfunctions, the extreme end of the continuum, are incremental degrees of physiologic derangements in individual organs (ie, processes rather than events). Alteration in organ function can vary widely from a mild degree of organ dysfunction to frank organ failure. This article does not cover sepsis of the neonate or infant. Special consideration must be given to neonates, infants, and small children with regard to fluid resuscitation, appropriate antibiotic coverage, intravenous (IV) access, and vasopressor therapy. See Neonatal Sepsis for complete information on this topic.

Classification of shock
Shock is identified in most patients by hypotension and inadequate organ perfusion, which may be caused by either low cardiac output or low systemic vascular resistance. Circulatory shock can be subdivided into 4 distinct classes on the basis of underlying mechanism and characteristic hemodynamics, as follows: Hypovolemic shock Obstructive shock Distributive shock Cardiogenic shock These classes of shock should be considered and systemically differentiated before establishing a definitive diagnosis of septic shock . Hypovolemic shock results from the loss of blood volume caused by such conditions as gastrointestinal (GI) bleeding, extravasation of plasma, major surgery, trauma, and severe burns. The patient demonstrates tachycardia, cool clammy extremities, hypotension, dry skin and mucus membranes, and poor turgor.
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Septic Shock

Obstructive shock results from impedance of circulation by an intrinsic or extrinsic obstruction. Pulmonary embolism and pericardial tamponade both result in obstructive shock. Distributive shock is caused by such conditions as direct arteriovenous shunting and is characterized by decreased resistance or increased venous capacity from the vasomotor dysfunction. These patients have high cardiac output, hypotension, large pulse pressure, a low diastolic pressure, and warm extremities with a good capillary refill. These findings on physical examination strongly suggest a working diagnosis of septic shock. Cardiogenic shock is characterized by primary myocardial dysfunction, resulting in the inability of the heart to maintain adequate cardiac output. These patients demonstrate clinical signs of low cardiac output, while evidence exists of adequate intravascular volume. The patients have cool clammy extremities, poor capillary refill, tachycardia, narrow pulse pressure, and a low urine output.

Definitions of key terms
The basis of sepsis is the presence of infection associated with a systemic inflammatory response that results in physiologic alterations at the capillary endothelial level. The difficulty in diagnosis comes in knowing when a localized infection has become systemic and requires more aggressive hemodynamic support. No criterion standard exists for the diagnosis of endothelial dysfunction, and patients with sepsis may not initially present with frank hypotension and overt shock. Clinicians often use the terms sepsis, severe sepsis, and septic shock without a commonly understood definition. In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a consensus conference to establish definitions of these and related terms.[1, 2] Systemic inflammatory response syndrome (SIRS) is a term that was developed in an attempt to describe the clinical manifestations that result from the systemic response to infection. Criteria for SIRS are considered to be met if at least 2 of the following 4 clinical findings are present: Temperature greater than 38°C (100.4°F) or less than 36°C (96.8°F) Heart rate (HR) greater than 90 beats per minute (bpm) Respiratory rate (RR) greater than 20 breaths per minute or arterial carbon dioxide tension (PaCO2) lower than 32 mm Hg White blood cell (WBC) count higher than 12,000/µL or lower than 4000/µL, or 10% immature (band) forms Of course, a patient can have either severe sepsis or septic shock without meeting SIRS criteria, and conversely, SIRS criteria may be present in the setting of many other illnesses (see the image below).

Venn diagram show ing the overlap of infection, bacteremia, sepsis, systemic inflammatory response syndrome (SIRS), and multiorgan dysfunction.

In 2001, as a follow-up to the original ACCP/SCCM conference, an International Sepsis Definitions Conference was convened, with representation not only from the ACCP and the SCCM but also from the European Society of Intensive Care Medicine (ESICM), the American Thoracic Society (ATS), and the Surgical Infection Society (SIS). The following definitions of sepsis syndromes were published in order to clarify the terminology used to describe the spectrum of disease that results from severe infection.[3] Sepsis is defined as the presence of infection in association with SIRS. The presence of SIRS is, of course, not limited to sepsis, but in the presence of infection, an increase in the number of SIRS criteria observed should alert the clinician to the possibility of endothelial dysfunction, developing organ dysfunction, and the need for aggressive therapy. Certain biomarkers have been associated with the endothelial dysfunction of sepsis; however, the use of sepsis-specific biomarkers has not yet translated to establishing a clinical diagnosis of sepsis in the emergency department (ED).
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7] Multiple organ dysfunction syndrome (MODS) is defined as the presence of altered organ function in a patient who is acutely ill and in whom homeostasis cannot be maintained without intervention. It may be primary (without an identifiable focus of infection) or. leading to diffuse endothelial disruption. Mediator-induced cellular injury The evidence that sepsis results from an exaggerated systemic inflammatory response induced by infecting organisms is compelling. 5. more often. and leading to further endothelial and end-organ damage. overt pulmonary disease not the direct cause of hypoxemia) Elevated plasma lactate level Oliguria (urine output < 30 mL or 0. increased endothelial permeability. and activation of coagulation pathways.5 mL/kg for at least 1 h) Severe sepsis is defined as sepsis complicated by end-organ dysfunction. elevated creatinine concentration. Bacteremia is defined as the presence of viable bacteria within the liquid component of blood. or evidence of disseminated intravascular coagulopathy (DIC).21. but on a systemic scale. inflammatory mediators are the key players in the pathogenesis (see the table below). an episode of hypotension. and thrombosis of end-organ capillaries.11/11/13 Septic Shock With sepsis. Patients receiving inotropic or vasopressor agents may not be hypotensive by the time that they manifest hypoperfusion abnormalities or organ dysfunction. secondary (with an intravascular or extravascular focus of infection). Septic shock is defined as a state of acute circulatory failure characterized by persistent arterial hypotension despite adequate fluid resuscitation or by tissue hypoperfusion (manifested by a lactate concentration greater than 4 mg/dL) unexplained by other causes. See the following articles for more information: Pediatric Sepsis Bacterial Sepsis Toxic Shock Syndrome Pediatric Toxic Shock Syndrome Pathophysiology The pathophysiology of septic shock is not precisely understood. vascular permeability. Although sepsis is commonly associated with bacterial infection. local vasodilation. In fact. as signaled by altered mental status. septic shock is associated with culture-positive bacteremia in only 30-50% of cases. except that the PaO2/FiO2 ratio is 200 or less. bacteremia is not a necessary ingredient in the activation of the inflammatory response that results in severe sepsis. Endothelial damage itself can further activate inflammatory and coagulation cascades. Table 1. the release of inflammatory mediators. but it involves a complex interaction between the pathogen and the host’s immune system. at least 1 of the following manifestations of inadequate organ function/perfusion is typically included: Alteration in mental state Hypoxemia (arterial oxygen tension [PaO2] < 72 mm Hg at fraction of inspired oxygen [FiO2] 0.medscape. creating in effect a positive feedback loop. The American-European Consensus Conference on ARDS agreed upon the following definitions of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).[8] The criteria for ALI include the following: An oxygenation abnormality with a PaO2/FiO2 ratio less than 300 Bilateral opacities on chest radiograph compatible with pulmonary edema Pulmonary artery occlusion pressure less than 18 mm Hg or no clinical evidence of left atrial hypertension if PaO2 is not available ARDS is a more severe form of ALI and is defined similarly. Mediators of Sepsis (Open Table in a new window) emedicine. vasodilation. The normal physiologic response to localized infection includes the activation of host defense mechanisms that result in the influx of activated neutrophils and monocytes. 6. These mechanisms are in play during septic shock.[4.com/article/168402-overview 3/22 .

stimulates B and T lymphocyte proliferation. other proinflammatory effects Complement Nitric oxide Lipid mediators Enhance vascular permeability and contributes to lung injury Phospholipase A2 Enhance neutrophil-endothelial cell interaction.com/article/168402-overview 4/22 . platelets.11/11/13 Septic Shock Type Cellular mediators Mediator Activity Lipopolysaccharide Activation of macrophages. regulate leukocyte migration and adhesion. platelet activation and chemotaxis. neutrophils. and play a role in pathogenesis of sepsis PAF Eicosanoids Arachidonic acid metabolites Adhesion molecules emedicine. and endothelium releases various cytokines and other mediators Lipoteichoic acid Peptidoglycan Superantigens Endotoxin Humoral mediators Cytokines TNF-alpha and IL1β Potent proinflammatory effect Neutrophil chemotactic factor IL-8 Acts as pyrogen.medscape. inhibits cytokine production. contributes to shock MIF Involved in hemodynamic alterations of septic shock G-CSF Promote neutrophil and macrophage. induces immunosuppression IL-6 Activation and degranulation of neutrophils IL-10 Cytotoxic. augments vascular permeability.

but their contributions to the sepsis syndrome remain to be established. The most toxic component of the gram-negative bacteria is the lipid A moiety of lipopolysaccharide. and phospholipase A2 are generated during sepsis. leading to massive cytokine production. The other cytokines that have a supposed role in sepsis are IL-10. but its role in pathogenesis is not clear. peptidoglycan (grampositive and gram-negative bacteria).medscape. consequently. The gram-positive bacteria cell wall leads to cytokine induction via lipoteichoic acid. Various bacterial cell wall components are known to release the cytokines. Additionally. which play a pivotal role in initiating sepsis and shock. IL = interleukin. High levels of IL-6 are associated with mortality. The complement system is activated and contributes to the clearance of the infecting microorganisms but probably also enhances the tissue damage. interferon gamma. Several cytokines are induced.[12] Inflammatory mediators instigate direct injury to the vascular endothelium. 10. platelet-activating factor (PAF). causing organ dysfunction and death. they are necessary for defense against microorganisms but also may become toxic inflammatory mediators contributing to tissue damage and organ dysfunction. including tumor necrosis factor (TNF) and interleukins (ILs). Circulating levels of IL-6 correlate well with outcome. granulocyte colony-stimulating factor (G-CSF). TNF = tumor necrosis factor. IL-8 contributes to the lung injury and dysfunction of other organs. PAF = platelet-activating factor. and granulocyte macrophage colony-stimulating factor (GM-CSF).com/article/168402-overview 5/22 . macrophage migration inhibition factor. including the cytokines just mentioned. NO plays a major role in the hemodynamic alterations of septic shock. Hypotension. but. that induce protean manifestations on most cell types. MIF = macrophage inhibitory factor. and lipoteichoic acid (gram-positive bacteria). gram-positive bacteria may secrete the superantigen cytotoxins that bind directly to the major histocompatibility complex (MHC) molecules and T-cell receptors. cytokines activate the coagulation pathway. Plasma levels of endothelial activation biomarkers are higher in emedicine. The contact systems become activated. especially IL-1. triggering the extrinsic coagulation cascade and accelerating production of thrombin.[9. A dual role exists for neutrophils. resulting in capillary microthrombi and end-organ ischemia. from immune effector cells to vascular smooth muscle and parenchymal cells. Several of the harmful effects of bacteria are mediated by proinflammatory cytokines induced in host cells (macrophages/monocytes and neutrophils) by the bacterial cell wall component.11/11/13 Septic Shock Selectins Leukocyte integrins G-CSF = Granulocyte colony-stimulating factor. once the infection becomes systemic. bradykinin is generated. 11] (See Abnormalities of coagulation and fibrinolysis.) Gram-positive and gram-negative bacteria induce a variety of proinflammatory mediators. which is a hyperdynamic form of shock. IL12. called cytokines. An initial step in the activation of innate immunity is the synthesis de novo of small polypeptides. IL-8 is an important regulator of neutrophil function. Both of these factors also help to keep infections localized. In addition. The chemokines (monocyte chemoattractant protein–1) orchestrate the migration of leukocytes during endotoxemia and sepsis. synthesized and released in significant amounts during sepsis. occurs via induction of nitric oxide (NO). including lipopolysaccharide (gram-negative bacteria). The lipid mediators (eicosanoids). the cardinal manifestation of sepsis. Abnormalities of coagulation and fibrinolysis An imbalance of homeostatic mechanisms leads to disseminated intravascular coagulopathy (DIC) and microvascular thrombosis. the effects can also be detrimental. the endothelial cells release tissue factor (TF).

usually is depressed. inhibition of calcium influx. IL-1β. norepinephrine and epinephrine) that are released during shock. a natural fibrinolytic. coagulation. and vascular smooth muscle relaxation. NO. and phospholipid. This disparity is termed maldistribution of blood flow. with a resultant defect in emedicine. 15] Tissue plasminogen activator (t-PA) facilitates conversion of plasminogen to plasmin. and TNF-alpha. TF interacts with factor VIIa to form factor VIIa-TF complex. factor VIII. Factors responsible for myocardial depression of sepsis are myocardial depressant substances. indicating activation of the clotting system and fibrinolysis.medscape.[17] The resulting vasodilation can be refractory to endogenous vasoactive hormones (eg. forms intravascular clots. which is characterized by pathologic vasodilation and shunting of blood from vital organ to nonvital tissues such as skin. the cardiac output usually is elevated (the hyperdynamic phase of sepsis and shock). In addition. and adipose. The insoluble fibrin. mitochondria can become dysfunctional. the rise in cardiac output often is limited by hypovolemia and a fall in preload because of low cardiac filling pressures.[13] The coagulation factors are activated as a result of endothelial damage.com/article/168402-overview 6/22 . Potassium efflux from cells results in hyperpolarization. but the primary factors are thought to be (1) activation of adenosine triphosphate (ATP)-sensitive potassium channels in vascular smooth muscle cells and (2) activation of NO synthase. Although an elevation of cardiac output occurs. Early in septic shock. The process is initiated via binding of factor XII to the subendothelial surface. pulmonary hypertension. The predominant hemodynamic feature of septic shock is arterial vasodilation.[16] Circulatory abnormalities As noted (see Background). the performance of the heart. NO also activates potassium channels. The levels of protein C and endogenous activated protein C (APC) are also decreased in sepsis. thus compromising oxygen utilization at the tissue level.11/11/13 Septic Shock patients whose hypotension is the result of sepsis than in patients with hypotension of other causes. septic shock falls under the category of distributive shock. Activation of coagulation in sepsis has been confirmed by marked increases in thrombin-antithrombin complex and the presence of D-dimer in plasma. When intravascular volume is augmented. This implies that low global tissue oxygen extraction is the mechanism that may limit total body oxygen uptake in septic shock. The final product of the coagulation pathway is the production of thrombin. initiate coagulation by activating TF. The basic pathophysiologic problem seems to be a disparity between the uptake and oxygen demand in the tissues. which converts soluble fibrinogen to fibrin. skeletal muscle. either between or within organs. plasminogen activator inhibitor (PAI-1) and thrombin activatable fibrinolysis inhibitor (TAFI). coronary blood flow abnormalities. the arterial-mixed venous oxygen difference usually is narrow. such as IL-1α. Even though cardiac output is elevated.[14. The imbalance among inflammation. and beta-receptor down-regulation. and fibrinolysis results in widespread coagulopathy and microvascular thrombosis and suppressed fibrinolysis. which activates factors X and IX. which may be more pronounced in some areas than in others. Inflammatory cytokines. This activates factor XII. and then factor XI and eventually factor X are activated by a complex of factor IX. The insidious nature of sepsis is such that microcirculatory dysfunction can occur while global hemodynamic parameters such as blood pressure may remain normal. various cytokines. Thrombin. calcium. The mechanisms implicated in this pathologic vasodilation are multifactorial. Diminished peripheral arterial vascular tone may result in dependency of blood pressure on cardiac output. Endogenous APC is an important proteolytic inhibitor of coagulation cofactors Va and VIIa. activates protein C. causing vasodilation to result in hypotension and shock if insufficiently compensated by a rise in cardiac output. The potassium-ATP channels are directly activated by lactic acidosis. via thrombomodulin. and the blood lactate level is elevated. which then functions as an antithrombotic in the microvasculature. reflected by stroke work as calculated from stroke volume and blood pressure. along with aggregated platelets. Endotoxins increase the activity of inhibitors of fibrinolysis—namely. The endothelial dysfunction and vascular maldistribution characteristic of distributive shock result in global tissue hypoxia or inadequate delivery of oxygen to vital tissues. ultimately leading to multiple organ dysfunction and death. Endogenous APC also enhances fibrinolysis by neutralizing PAI-1 and by accelerating t-PA–dependent clot lysis.

medscape. derangement of apoptosis plays a critical role in tissue injury in patients with sepsis. which is compounded by the inability of the erythrocytes to navigate the septic microcirculation. and contributes to organ dysfunction. MODS is associated with widespread endothelial and parenchymal cell injury because of the following proposed mechanisms: Hypoxic hypoxia . Reactive oxygen species. Therefore. This is called cytopathic or histotoxic anoxia—that is. including protein C. such as the heart and brain. and NO may cause damage to mitochondrial electron transport.The septic circulatory lesion disrupts tissue oxygenation. and contributes to edema of various organs. but other tissues. sepsis leads to regional changes in oxygen demand and regional alteration in blood flow of various organs. Therefore. and lactate acidemia in patients experiencing septic shock. Microvascular and endothelial abnormalities contribute to the septic microcirculatory defect in sepsis. because other investigators argue that supply dependence is artifactual rather than a real phenomenon. Cardiovascular dysfunction Significant derangement in the autoregulation of the circulatory system is typical in patients with sepsis. In patients experiencing septic shock. the autonomic nervous system).This is the principal mechanism by which dysfunctional cells normally are eliminated. NO). and. but the global oxygen extraction ratio is relatively low. an inability to use oxygen even when it is present. consequently. alters the metabolic regulation of tissue oxygen delivery. During a fall in oxygen supply. The precise mechanisms of cell injury and resulting organ dysfunction in patients with sepsis are not fully understood.Subclinical coagulopathy signified by mild elevation of the thrombin time or activated partial thromboplastin time or by a moderate reduction in platelet count is extremely common.com/article/168402-overview 7/22 . However. NO. oxygen uptake depends on oxygen supply over a much wider range than normal. cardiac output becomes distributed so that most vital organs. remote from the infectious focus. and to the development of ARDS. and no organ system is immune to the consequences of the inflammatory excesses of sepsis. Maldistribution of blood flow. prostacyclin) and vasoconstricting substances (eg. Impaired secretion of vasopressin also may occur.11/11/13 Septic Shock capacity to extract oxygen locally. resulting in multiple organ dysfunction syndrome. Direct cytotoxicity .Endotoxin. Vasoactive mediators cause vasodilatation and increase the microvascular permeability at the site of infection. or both may occur. endothelin) affect regional blood flow. peripheral shunting of oxygen are responsible for diminished oxygen extraction and uptake. oxygen extraction may be too low for tissue needs at a given oxygen supply. The regional regulation and the release of vasodilating substances (eg. Coagulopathy . disturbances in the microcirculation. vasoactive substances (eg. The peripheral blood flow abnormalities result from the balance between local regulation of arterial tone and the activity of central mechanisms (eg. TNF-alpha. remain relatively better perfused than nonvital organs are. such as the gut epithelium. Mechanisms of organ dysfunction Sepsis is described as an autodestructive process that permits the extension of the normal pathophysiologic response to infection (involving otherwise normal tissues). and endothelial growth factors lead to microcirculatory injury. NO plays a central role in the vasodilatation of septic shock. leading to disordered energy metabolism. Increased systemic microvascular permeability also develops. particularly the lung microcirculation. and oxygen uptake may increase with a boost in oxygen supply—a phenomenon termed oxygen uptake supply dependence or pathologic supply dependence. but overt DIC is rare. the delivery of oxygen is relatively high. Immunosuppression . Organ dysfunction or organ failure may be the first clinical sign of sepsis. this concept is controversial. may undergo accelerated apoptosis. Coagulopathy is caused by deficiencies of coagulation system proteins. pathologic supply dependency of oxygen. However. The oxygen uptake increases with a rise in body temperature despite a fall in oxygen extraction. The proinflammatory cytokines may delay apoptosis in activated macrophages and neutrophils.The interaction between proinflammatory and anti-inflammatory mediators may lead to an imbalance and an inflammatory reaction. In patients with sepsis who have low oxygen extraction and elevated arterial blood lactate levels. which emedicine. antithrombin III. and TF inhibitors. lytic enzymes. Apoptosis (programmed cell death) . or immunodeficiency may predominate.

diminished venous return from venous dilation. Following initial extravasation of intravascular fluid. The exudative phase occurs in the first week and is dominated by alveolar edema and hemorrhage. Neutrophil entrapment within the pulmonary microcirculation initiates and amplifies the injury to alveolar capillary membrane. and ALI progresses to ARDS. emedicine.com/article/168402-overview 8/22 . 1986): (1) the exudative phase of edema and hemorrhage.75-1. furthermore. in whom the ratio is less than 0. is involved in this process. Migration of macrophages and neutrophils into the interstitium and alveoli produces many different mediators. Patients with preexisting cardiac disease are unable to increase their cardiac output appropriately. termed diffuse alveolar damage (DAD). The clinical and pathological evolution can be categorized into the following 3 overlapping phases (Katzenstein. along with leukoagglutination and deposition of platelet fibrin thrombi. Pulmonary dysfunction The pathogenesis of sepsis-induced ARDS is a pulmonary manifestation of SIRS. An alveolar inflammatory exudate persists. lymphocytes.medscape. Through the use of the Frank-Starling mechanism. this inability is caused by intrinsic and extrinsic compression of capillaries and plugging of the capillary lumen by blood cells. cardiac output is often increased to maintain BP in the presence of systemic vasodilatation. If addressed at an early stage. ARDS is a frequent manifestation of these effects. an acute inflammatory response through all the phases of injury. causing ensuing alveolar edema. Continued infiltration occurs with neutrophils and mononuclear cells. (2) the proliferative phase of organization and repair. The microcirculation is the key target organ for injury in patients with sepsis syndrome. A decrease in the number of functional capillaries leads to an inability to extract oxygen maximally.11/11/13 Septic Shock may permit the persistence of vasodilatation. As many as 40% of patients with severe sepsis develop ALI. These enhance the surface tension at the air-fluid interfaces. core organs may not receive appropriate oxygen delivery. but in many cases. complete resolution may occur. In other patients. ALI may be reversible. and repair and hyperplasia of type II pneumocytes. The edema fluid is protein rich. A complex interaction between humoral and cellular mediators. and (3) the fibrotic phase of end stage fibrosis. producing diffuse microatelectasis. and fibroblasts. the host response is uncontrolled. and release of myocardial depressant substances. a progressive respiratory failure and pulmonary fibrosis develop. A direct or indirect injury to the endothelial and epithelial cells of the lung increases alveolar capillary permeability.0. If this process can be halted. Increased endothelial permeability leads to widespread tissue edema involving protein-rich fluid. the ratio of alveolar fluid edema to plasma is 0. which contribute to the alveolar and epithelial cell damage. Necrosis of endothelial cells and type I pneumocytes occur. inflammatory cytokines and chemokines. therefore.65. Hypotension is caused by the redistribution of intravascular fluid volume resulting from reduced arterial vascular tone. ALI is a type of pulmonary dysfunction secondary to parenchymal cellular damage that is characterized by endothelial cell injury and destruction. destruction of type I alveolar pneumocytes. Injury to type II pneumocytes decreases surfactant production. The central pathologic finding in ARDS is severe injury to the alveolocapillary unit. and type II pneumocyte proliferation is evident. deposition of platelet and leukocyte aggregates. the plasma proteins in alveolar fluid inactivate the surfactant previously manufactured. compared with patients with hydrostatic cardiogenic pulmonary edema. Changes in both systolic and diastolic ventricular performance occur in patients with sepsis. The other histological features include dense eosinophilic hyaline membranes and disruption of the capillary membranes. Sepsis interferes with the normal distribution of systemic blood flow to organ systems. inflammation and fibrosis of pulmonary parenchyma develops into a morphologic picture.

Acute respiratory distress syndrome (ARDS). The proliferative phase is prominent in the second and third week following onset of ARDS but may begin as early as the third day. This is a high-pow ered photomicrograph of an early stage (exudative stage) of DAD. Organization of the intra-alveolar and interstitial exudate. parenchymal necrosis. w hich may develop into the fibrotic stage of DAD. though the process may begin in the first week. Lung collagen deposition increases. excessive collagen deposition. and interstitial myofibroblast reaction occur. Overgrowth of bacteria in the upper GI tract may aspirate emedicine.com/article/168402-overview 9/22 . occurs. This photomicrograph show s a delayed stage (proliferative or organizing stage) of diffuse alveolar damage (DAD). is pathologically diffuse alveolar damage (DAD). The fibrotic phase occurs by the third or fourth week of the onset.11/11/13 Septic Shock Acute respiratory distress syndrome (ARDS). Gastrointestinal dysfunction The GI tract may help to propagate the injury of sepsis. infiltration with chronic inflammatory cells. This photomicrograph show s an early stage (exudative stage) of DAD. which convert the exudate to cellular granulation tissue. The fibrin stain show ing collagenous tissue. occurs. Proliferation of type II cells and fibroblasts. transforming into fibrous tissue. commonly observed in septic shock as a part of multiorgan failure syndrome. is pathologically diffuse alveolar damage (DAD). the air spaces are irregularly enlarged. hyaline membranes are present. The collagenous fibrosis completely remodels the lung.medscape. and collagen and fibroblasts are present. This photomicrograph show s a delayed stage (proliferative or organizing stage) of diffuse alveolar damage (DAD). and alveolar duct fibrosis is apparent. commonly observed in septic shock as a part of multiorgan failure syndrome. microcystic honeycomb formation. Proliferation of type II pneumocytes has occurred. and traction bronchiectasis follows.

Its absence in commercial total parenteral nutrition (TPN) formulations leads to a breakdown of the intestinal barrier and to translocation of the gut flora into the circulation. and extensive burns. The mechanism involves systemic hypotension. Fungal infections are the cause of sepsis in 0. Causative microorganisms Before the introduction of antibiotics in clinical practice. emedicine. the abnormal synthetic functions caused by liver dysfunction can contribute to both the initiation and progression of sepsis. Glutamine is necessary for normal enterocyte functioning. Anaerobic pathogens are becoming less important as a cause of sepsis. The pathogenesis is poorly defined. In addition to inadequate glutamine levels. The most common disease states predisposing to sepsis are malignancies.11/11/13 Septic Shock into the lungs and produce nosocomial pneumonia. Renal dysfunction Acute renal failure (ARF) caused by acute tubular necrosis often accompanies sepsis. In one institution. the incidence of anaerobic bacteremia declined by 45% over a 15-year period.810. thereby allowing translocation of bacteria and endotoxin into the systemic circulation and extending the septic response. The optimal level of nutritional intake is interfered with in the face of high protein and energy requirements. Patients with indwelling catheters or devices are also at high risk. gram-negative bacteria have become the key pathogens causing severe sepsis and septic shock. which contribute to renal injury. In most patients with sepsis. liver dysfunction leads to a spillover of these products into the systemic circulation. trauma. and activation of neutrophils by endotoxins and other peptides. gram-positive bacteria were the principal organisms causing sepsis. with the exception of patients who are immunocompromised with neutropenia. Septic shock usually causes ileus.[18] Hepatic dysfunction By virtue of the liver’s role in host defense.2% of patients with sepsis. release of cytokines (eg. direct renal vasoconstriction.medscape. The gut’s normal barrier function may be affected. as well as total B-cell and Tcell counts. chronic liver disease. where an obvious source often is not found. a source of infection can be identified. sepsis also is a common complication after major surgery.com/article/168402-overview 10/22 . Sepsis is seen most frequently in elderly persons and in those with comorbid conditions that predispose to infection. chronic renal failure. This may be one of the factors that drives sepsis. Etiology Most patients who develop sepsis and septic shock have underlying circumstances that interfere with the local or systemic host defense mechanisms. Central nervous system dysfunction Central nervous system (CNS) involvement in sepsis produces encephalopathy and peripheral neuropathy. TNF). The reticuloendothelial system of the liver acts as a first line of defense in clearing bacteria and their products. and the use of narcotics and sedatives delays the institution of enteral feeding. and their incidence appears to be increasing (see the image below). Multiple sites of infection may occur in 6-15% of patients. In addition. such as diabetes or any immunocompromising disease. More recently. diabetes mellitus. this may lessen the immune response by decreasing leukocyte and natural killer cell counts. and the use of immunosuppressive agents.

medscape. and the following are the common pathogens: E coli Streptococcus faecalis Bacteroides fragilis Acinetobacter species Pseudomonas species Enterobacter species Salmonella species Infections of the male and female reproductive systems are the cause of septic shock in 10% of patients. Fungal infections are a rare cause of septic shock. Lower respiratory tract infections are the cause of septic shock in 25% of patients. and the following are the common pathogens: Streptococcus pneumoniae Klebsiella pneumoniae Staphylococcus aureus Escherichia coli Legionella species Haemophilus species Anaerobes Gram-negative bacteria Fungi Urinary tract infections are the cause of septic shock in 25% of patients. and the following are the common pathogens: E coli Proteus species Klebsiella species Pseudomonas species Enterobacter species Serratia species Soft tissue infections are the cause of septic shock in 15% of patients.11/11/13 Septic Shock An 8-year-old boy developed septic shock secondary to Blastomycosis pneumonia. followed by abdominal and soft tissue infections. and the following are the common pathogens: S aureus Staphylococcus epidermidis Streptococci Clostridia Gram-negative bacteria Anaerobes GI tract infections are the cause of septic shock in 15% all patients.com/article/168402-overview 11/22 . Each organ system tends to be infected by a particular set of pathogens (see below). and the emedicine. Respiratory tract infection and urinary tract infection are the most frequent causes of sepsis.

diabetes mellitus. prosthetic devices. liver cirrhosis. solid malignancy. trauma. hemodialysis and peritoneal dialysis catheters. In the United States. asplenia) Major surgery. and Neisseria meningitidis is the most common cause of such infections (see the image below). such as childbirth. intravascular devices. cardiopulmonary diseases. alcoholism. Gram stain of blood show ing the presence of Neisseria meningitidis. In 1 study. Epidemiology United States statistics Since the 1930s. complement deficiencies.com/article/168402-overview 12/22 . studies have shown an increasing incidence of sepsis. and S aureus. Miscellaneous infections are the cause of septic shock in 5% of patients. S epidermidis. abortion. Candida species) are the common pathogens. Risk factors Risk factors for severe sepsis and septic shock include the following: Extremes of age ( < 10 y and >70 y) Primary diseases (eg.000 cases of septic shock and 100. IV drug abuse [see the image below]. immunosuppressive therapy. the incidence of bacteremic sepsis (both gram-positive and gram-negative) increased from 3. corticosteroid therapy. endotracheal tubes) Previous antibiotic treatment Prolonged hospitalization Other factors.8 cases emedicine. neutropenia. and malnutrition A 28-year-old w oman w ho w as a previous intravenous drug user (human immunodeficiency virus [HIV] status: negative) developed septic shock secondary to bilateral pneumococcal pneumonia.000 deaths per year occur from this disease.medscape. catheters. hematologic malignancy) Immunosuppression (eg. burns Invasive procedures (eg.11/11/13 Septic Shock following are the common pathogens: Neisseria gonorrhoeae Gram-negative bacteria Streptococci Anaerobes Foreign bodies leading to infections are the cause of septic shock in 5% of patients. and fungi/yeasts (eg. 200.

6 and 4.3% of hospital discharges.[19] The National Center for Health Statistics published a large retrospective analysis using the National Hospital Discharge Survey of 500 nonfederal US hospitals. and the incidence of sepsis increased 3-fold between 1979 and 2000. Incidence ranged from 0. International statistics A Dutch surveillance study examined the incidence.000. and outcome of sepsis in patients admitted to a university hospital. and outcome of severe sepsis in the United States.000 such visits annually (0.[21] ARDS has a reported incidence ranging from 1. Out of these cases.[19] A more recent large survey of ED visits showed that severe sepsis accounts for more than 500.[22] Subsequent studies report a higher incidence: 12. and an additional 17. However.4 per 1000. with a sharp increase in the number of cases in patients older than 50 years. In addition. most sepsis episodes are observed in patients older than 60 years. The mortality rate was 28. which included more than 10 million cases of sepsis over a 22year period.2 cases per 1000 admissions in children to 26.medscape. increased use of immunosuppressive agents and chemotherapy. Sex distribution for septic shock Epidemiologic data have shown that the age-adjusted incidence and mortality of septic shock are consistently greater in men. Compared with younger patients. This method yielded 300 annual cases per 100. elderly patients are more likely to have atypical or nonspecific presentations with sepsis.[19.[19] Hospital billing codes were used to identify patients with infection and organ dysfunction consistent with the definition of severe sepsis.000 population per year for ARDS and 18.5-8. or an estimated 750.7 billion nationally. and are more likely to have underlying diseases.6 cases per 1000 persons.000 population per year.4% in elderly people. and that the mean length of stay in the ED is approximately 5 hours.1% were admitted to an intensive care unit (ICU). increased recognition of disease. 13.6% and ranged from 10% in children to 38. A 2001 article reported the incidence. Septicemia accounted for 1. gram-positive organisms surpassed gram-negative organisms as the most common cause of sepsis.11/11/13 Septic Shock per 1000 admissions in 1970 to 8.6 cases per 100.26 cases per 100 hospital discharges. with an annual total cost of $16.000 population per year for acute lung injury.7 cases per 1000 discharges to 18.com/article/168402-overview 13/22 .3% were cared for in an intermediate care or coronary care unit. that the majority of patients presented to EDs without an academic affiliation.3% of all hospitalizations.4 cases per 100. all of these factors adversely affect survival. The percentage of male patients varies from 52% to 66%. elderly patients are more susceptible to sepsis. Severe sepsis resulted in an average cost of $2200 per case. Between 1980 and 1992. 24] At present.000 population. the incidence of nosocomial blood stream infection in 1 institution increased from 6. a higher incidence of lung emedicine. cost.[23] Age distribution for septic shock Sepsis and septic shock occur at all ages.7% of total visits). a position they still hold today. in 1987. Of note.[19] Analysis of a large sample from the major centers reported the incidence of severe sepsis as 3 cases per 1000 population and 2. respectively. causes.000 population per year to 240 per 100. have less physiologic reserve to tolerate the insult from infection.000 cases annually in the United States.2 per 1000 in individuals older than 85 years.However. 51. it is not clear whether this difference can be attributed to an underlying higher prevalence of comorbid conditions. from 83 cases per 100. increased use of indwelling lines and devices. a strong correlation exists between advanced age and the incidence of septic shock.9 cases per 100. and increase in chronic diseases such as end-stage renal disease and HIV.[20] The reasons for this growing incidence likely include an increasingly elderly population.[20] Angus et al published linked data from several sources related to hospital discharge from all hospitals from 7 large states. The increase in the number of patients who are immunocompromised and an increasing use of invasive diagnostic and therapeutic devices predisposing to infection are major reasons for the increase in incidences of sepsis. The mortality rate from ARDS has been documented at approximately 50% in most studies.7 per 1000 in 1987. increased performance of invasive procedures and organ transplantation. The investigators reported that the incidences of sepsis syndrome and septic shock were. 2. Advanced age is a risk factor for acquiring nosocomial blood stream infection in the development of severe forms of sepsis.

[19] Given that there is a spectrum of disease from sepsis to severe sepsis to septic shock. The mortality rates were 7% with SIRS. impaired host immune status. and 46% with septic shock. The study by Angus et al. 24] One study found that in the setting of suspected infection. there is evidence to suggest that meeting increasing numbers of SIRS criteria is associated with increased mortality. or whether women are inherently protected against the inflammatory injury that occurs in severe sepsis. mortality rates seem to have decreased.[27] A link between impaired adrenal function and higher septic shock mortality has been suggested. the mortality rate specifically caused by the septic episode itself is specified and is 14. black patients with septic shock had a higher incidence of underlying diabetes and renal disease. The poor prognostic factors are advanced age.3-20%. and clinical evidence of organ dysfunction. poor prior functional status. Development of sequential organ failure. The adrenal gland is enlarged in patients with septic shock compared with controls. and continued need for vasopressors past 24 hours. 16% with sepsis. The following clinical characteristics are related to the severity of sepsis: An abnormal host response to infection Site and type of infection Timing and type of antimicrobial therapy Offending organism Development of shock Any underlying disease Patient’s long-term health condition Location of the patient at the time of septic shock Factors consistently associated with increased mortality in sepsis include advanced age. The risk factors for early mortality in this study were higher severity of illness score.11/11/13 Septic Shock infection in men. emedicine. However. Prognosis The mortality rate of severe sepsis and septic shock is frequently quoted as anywhere from 20% to 50%.[28] In 1995. mortality varies depending on the degree of illness. the incidence of septic shock and severe invasive infection was higher in the young. a multicenter prospective study published by Brun-Buisson (1995) reported a mortality rate of 56% during ICU stays and 59% during hospital stays.[26] In patients with septic shock. was associated with increased 28-day mortality in patients with septic shock. comorbid conditions.[24] However. In recent years. which suggests a possible genetic predisposition to developing septic shock. In some studies.com/article/168402-overview 14/22 . infection with a resistant organism. Potential reasons for this include issues relating to decreased access to health care and increased prevalence of underlying medical conditions. 20% with severe sepsis. A study by Jung et al found that an absence of this enlargement. The National Center for Health Statistics study showed a reduction in hospital mortality rates from 28% to 18% for septicemia over the years. which might explain the higher rates of infection.[20] A more recent large epidemiologic study tied the increased incidence of septic shock in the black population to increased rates of infection necessitating hospitalization and increased development of organ dysfunction.[25] In this study. several clinical trials have documented a mortality rate of 40-75%. more overall deaths occurred due to the increased incidence of sepsis. is a harbinger of poor outcome. indicated by total adrenal volume of less than10 cm3 . Furthermore. this emphasizes the importance of identifying organ dysfunction over the presence of SIRS criteria.medscape. and 77% of all deaths occurred within the first 14 days.[20. 19] Incidence of septic shock by race One large epidemiologic study showed that the risk of septicemia in the nonwhite population is almost twice that in the white population. with the highest risk accruing to black men. development of acute organ dysfunction was independent of comorbidities. healthy black population. the presence of 2 or more acute organ failures at the time of sepsis. however. reported a mortality rate of about 30%. despite adequate supportive measures and antimicrobial therapy.[19. which likely more accurately reflects the incidence of severe sepsis and septic shock.[4] Twenty-seven percent of all deaths occurred within 2 days of the onset of severe sepsis. just meeting SIRS criteria without evidence of organ dysfunction did not predict increased mortality.

Blood and Lymphatic System Center. Most patients who showed improvement achieved maximal recovery by 6 months. Professor of Medicine. Site Director. Canada Steven Mink. St Boniface General Hospital Sat Sharma. antibiotics that are effective against the organism that is ultimately identified) has a significant influence on mortality. There have been no studies to date that have prospectively evaluated the effect of single-dose etomidate on the mortality of septic shock. initiating broad-spectrum coverage until the specific organism is cultured and antibiotic sensitivities are determined is important. Sat Sharma. The complications with the greatest adverse effect on survival are ARDS. MD. Contributor Information and Disclosures Coauthor(s) Steven Mink. Chief Editor Michael R Pinsky. Studies have shown that appropriate antibiotic administration (ie. Department of Critical Care Medicine. FCCP. American College of Chest Physicians. Canadian Medical Association. its effect on the quality of life of survivors was previously not well characterized. University of Pittsburgh Medical Center. Controversy exists over the use of etomidate as an induction agent for patients with sepsis. Sprung et al. FRCPC Professor and Head. (See Clinical Presentation.com/article/168402-overview 15/22 . and need for chronic nursing home or institutionalized care. with the lung function improving to 80-90% of predicted values. with debate centered on its association with adrenal insufficiency. as well as Shock. Vice-Chair of Academic Affairs. Respiratory Medicine. University of Manitoba. Sepsis (Blood Infection). Although sepsis mortality is known to be high. CM. University of Manitoba.11/11/13 Septic Shock shock. bacteremia. reliance on family support. the highest with gram-negative sepsis. New evidence shows that septic shock in elderly persons leads to significant long-term cognitive and functional disability compared with those hospitalized with nonsepsis conditions.[30] However.3). St Boniface Hospital. and Cardiopulmonary Resuscitation (CPR). the authors did not address the fact that those patients receiving etomidate required orotracheal intubation and thus were a sicker subset. Royal College of Physicians and Surgeons of Canada. and pneumonia.medscape. Section of Pulmonary Medicine. Bioengineering. The long-term use of statins appears to have a significant protective effect on sepsis. Approximately 16% of patients with ARDS died from irreversible respiratory failure. and Public Health Center. Royal Society of Medicine.[29] End-organ failure is a major contributor to mortality in sepsis and septic shock. DIC. Cardiovascular Disease and Anesthesiology.) The frequency of ARDS in sepsis has been reported from 18-38%. in the CORTICUS study. Society of Critical Care Medicine. American Thoracic Society. see the Shock Center. University of Pittsburgh School of Medicine emedicine. and World Medical Association Disclosure: Nothing to disclose. MD. and ARF. Division of Pulmonary Medicine. MD Head. American College of Physicians-American Society of Internal Medicine. and a low blood pH (< 7. FCCM Professor of Critical Care Medicine. Sepsis and multiorgan failure are the most common cause of death in ARDS patients. reported that patients who received etomidate had a significantly higher mortality rate than those who did not receive etomidate. ranging from 18-25%.[31] Patient Education For patient education information. MD is a member of the following medical societies: Alpha Omega Alpha Disclosure: Nothing to disclose. Department of Internal Medicine. MD. For this reason. Septic shock is often a major sentinel event that has lasting effects on the patient’s independence. FRCPC is a member of the following medical societies: American Academy of Sleep Medicine. Department of Internal Medicine.

Division of Critical Care Medicine. Program Director. Cooper Hospital University Medical Center Disclosure: Nothing to disclose. MD.medscape. Clara-Dina Cokonis. R Phillip Dellinger. Consulting Staff. FCCP. American College of Chest Physicians. FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America Disclosure: Nothing to disclose. Critical Care Medicine Fellowship Program. American Academy of Emergency Medicine. Case Western Reserve University School of Medicine Barry E Brenner. Harvard Medical School. and Association of Military Surgeons of the US Disclosure: Nothing to disclose. MD is a member of the following medical societies: American Academy of Dermatology emedicine. FACEP. New York Dirk M Elston. European Society of Intensive Care Medicine. Medical Director. American College of Emergency Physicians. PhD. MD. University of Texas Health Sciences Center San Antonio Daniel J Dire. American Academy of Emergency Medicine. American College of Physicians. FAAP. University of Texas Medical School at Houston. University of Medicine and Dentistry of New Jersey. MD. American College of Critical Care Medicine. University of Medicine and Dentistry of New Jersey Disclosure: Nothing to disclose. Head. and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. American Heart Association. Division of Critical Care Medicine. MD. American Academy of Pediatrics. Division of Dermatology. PhD Visiting Associate Professor. FACEP.com/article/168402-overview 16/22 . and Society of Critical Care Medicine Disclosure: LiDCO Ltd Honoraria Consulting. New York Academy of Medicine. American Thoracic Society. American College of Emergency Physicians. Artisan Grant/research funds Other Clinical Trial. Medical/Surgical/Cardiovascular Surgical Intensive Care Unit. Cheetah Medical Consulting fee Consulting Additional Contributors Fatima Al Faresi. Agenix Grant/research funds Other Clinical Trial Daniel J Dire. UAE Disclosure: Nothing to disclose. Department of Medicine. FAAP. Department of Medicine and Infectious Disease Service.11/11/13 Septic Shock Michael R Pinsky. FACP Assistant Professor of Medicine. MD. Clinical Professor. Robert Wood Johnson School of Medicine. American Thoracic Society. PhD. Al Ain. iNTELOMED Intellectual property rights Board membership. Shock Society. MD Dermatologist. FACEP Professor of Emergency Medicine. MD. Edwards Lifesciences Honoraria Consulting. Robert Wood Johnson Medical School. Department of Emergency Medicine. John L Brusch. Applied Physiology. MD. Case Medical Center. Ackerman Academy of Dermatopathology. BRAHMS Grant/research funds Other Clinical Trial. FCCM is a member of the following medical societies: American College of Chest Physicians. Tawam Hospital. Arkansas Medical Society. MD. Cooper University Hospital Disclosure: Wyeth Consulting fee Consulting. University Hospitals. MD Director. New York Academy of Sciences. American Heart Association. FAAEM Clinical Professor. MD Staff Physician. Professor of Internal Medicine. FACEP is a member of the following medical societies: Alpha Omega Alpha. Emergency Medicine. Association of University Anesthetists. Program Director. Cambridge Health Alliance John L Brusch. Ltd Honoraria Consulting. Department of Pediatrics. Dirk M Elston. MD Professor of Medicine. CM. FAAEM is a member of the following medical societies: American Academy of Clinical Toxicology. Barry E Brenner. Ismail Cinel.

New York Methodist Hospital. FACEP Clinical Associate Professor. American College of Emergency Physicians. JD is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians Disclosure: M L Plaster Publishing Co LLC Ownership interest Management position emedicine. Fletcher Allen Health Care. MD. Department of Emergency Medicine. Rosalind Franklin University of Medicine and Science. and Society for Investigative Dermatology Disclosure: Nothing to disclose. University of Pennsylvania. DO. Department of Dermatology. MD is a member of the following medical societies: New York Academy of Sciences and Society of Critical Care Medicine Disclosure: Nothing to disclose.11/11/13 Septic Shock Disclosure: Nothing to disclose. Professor. Department of Medicine. and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. Department of Internal Medicine. Clerkship Directors in Emergency Medicine. Steven M Manders. St George's University School of Medicine Theodore J Gaeta. Department of Internal Medicine. University of Vermont College of Medicine Paul Krusinski. Department of Emergency Medicine. Department of Emergency Medicine. and American Society for Dermatologic Surgery Disclosure: Nothing to disclose. American Medical Association. MD is a member of the following medical societies: American College of Emergency Physicians. Council of Emergency Medicine Residency Directors. Franklin Flowers. Faculty of Medicine and Health Sciences. Director. DO. American Medical Student Association/Foundation. Michael R Filbin. Cook County Hospital Cory Franklin. Division of Dermatology. MPH. University of Florida College of Medicine Franklin Flowers. New York Academy of Medicine. Department of Medicine and Otolaryngology. Emergency Physicians Monthly Mark L Plaster. MD is a member of the following medical societies: American Academy of Dermatology. Massachusetts Medical Society. MD Chief. MD Assistant Professor of Dermatology. Weill Cornell Medical College. Division of Dermatology. and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. Department of Emergency Medicine. Adjunct Professor. Affiliate Associate Professor of Pediatrics and Pathology. MPH. MD Director of Dermatology. Mark L Plaster. is a member of the following medical societies: American College of Mohs Micrographic Surgery and Cutaneous Oncology Disclosure: Nothing to disclose. MD. Cory Franklin. MD. MD Professor. United Arab Emirates University Hassan I Galadari. Vice Chairman and Program Director of Emergency Medicine Residency Program. American College of Physicians. Associate Professor. FACEP is a member of the following medical societies: Alliance for Clinical Education. MD Clinical Instructor. Theodore J Gaeta. MD Clinical Assistant Professor. Massachusetts General Hospital Michael R Filbin. Hassan I Galadari.com/article/168402-overview 17/22 . Division of Critical Care Medicine. Academic Chair.medscape. Paul Krusinski. Professor. JD Executive Editor. University of Medicine and Dentistry of New Jersey Disclosure: Nothing to disclose. MD is a member of the following medical societies: American Academy of Dermatology.

[Medline]. Hibberd PL. Brun-Buisson C. et al. [Medline]. PharmD. Crit Care Med.11/11/13 Septic Shock Francisco Talavera. Epidemiology of sepsis syndrome in 8 academic medical centers. Sharma S. Jun 1992. Jun 2006. Apr 2003. Bone RC. et al. Eric L Weiss. JAMA. Artigas A. University of Nebraska Medical Center College of Pharmacy. Mar 8 2001. Cook D. Jul 16 1997. MD. Crit Care Med. Kumar A. Office of Service Continuity and Disaster Planning. LaRosa SP.com/article/168402-overview 18/22 . Dhainaut JF.20(6):864-74. [Medline]. and Texas Medical Association Disclosure: Nothing to disclose. Paul L Foster School of Medicine. Levy MM. Hudson L. Case Medical Center Vicken Y Totten. 8. Department of Dermatology. Carlet J. Clinical Associate Progressor. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Director of Research. et al. Physicians for Social Responsibility. Bernard GR. risk factors. Chairman. A multicenter prospective study in intensive care units. Roberts D. [Medline]. Angus D. MS. Texas Tech University Health Sciences Center. The ACCP/SCCM Consensus Conference Committee. The American-European emedicine. MD Assistant Clinical Professor. University Hospitals. Falke K.278(3):234-40. References 1. MS. et al. 6. [Medline]. French ICU Group for Severe Sepsis. Lanken PN. MD is a member of the following medical societies: American Academy of Dermatology. Marshall JC. Light B. DTM&H is a member of the following medical societies: American College of Emergency Physicians. SUMC and LPCH Bioterrorism and Emergency Preparedness Task Force. Consulting Staff. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. [Medline]. Southern Association for Oncology. FAAFP Assistant Professor.34(6):1589-96. Doyon F. Mountain View Dermatology. et al. DTM&H Medical Director. Kahn KL. N Engl J Med. and outcome of severe sepsis and septic shock in adults. Texas Dermatological Society. American College of Occupational and Environmental Medicine. Southeastern Surgical Congress. [Best Evidence] American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Vincent JL. Cerra FB. Sep 27 1995. MD. Jun 1992. American Medical Association.31(4):1250-6. Wood KE. PhD Adjunct Assistant Professor. American Society of Tropical Medicine and Hygiene. Parrillo JE. Bernard GR. 2. American College of Chest Physicians/Society of Critical Care Medicine.101(6):1644-55. et al. Case Western Reserve University School of Medicine.344(10):699-709. Sands KE. Abraham E. Efficacy and safety of recombinant human activated protein C for severe sepsis. Medscape Drug Reference Disclosure: Medscape Salary Employment Vicken Y Totten. 5. Richard P Vinson. Southern Clinical Neurological Society. Incidence. 4. FACEP. Carlet J. Department of Emergency Medicine. 7. Department of Surgery (Emergency Medicine). Fellowship Director. 3. [Medline]. JAMA. Bates DW. Chest. FACEP. Editor-in-Chief. Association of Military Dermatologists. Graman PS.274(12):968-74. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Laterre PF. Balk RA. MD. MD. Stanford University Medical Center Disaster Medicine Fellowship. Brigham KL. Fink MP. and Wilderness Medical Society Disclosure: Nothing to disclose. Lopez-Rodriguez A. FAAFP is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. et al. Crit Care Med. Stanford University Medical Center Eric L Weiss.medscape. PA Richard P Vinson.

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