Septic Shock


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.

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.

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 showing 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.

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).

With sepsis, 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] 0.21; overt pulmonary disease not the direct cause of hypoxemia)
  • Elevated plasma lactate level
  • Oliguria (urine output < 30 mL or 0.5 mL/kg for at least 1 h)


Severe sepsis is defined as sepsis complicated by end-organ dysfunction, as signaled by altered mental status, an episode of hypotension, elevated creatinine concentration, or evidence of disseminated intravascular coagulopathy (DIC).

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. Patients receiving inotropic or vasopressor agents may not be hypotensive by the time that they manifest hypoperfusion abnormalities or organ dysfunction.

BBacteremia is defined as the presence of viable bacteria within the liquid component of blood. It may be primary (without an identifiable focus of infection) or, more often, secondary (with an intravascular or extravascular focus of infection). Although sepsis is commonly associated with bacterial infection, bacteremia is not a necessary ingredient in the activation of the inflammatory response that results in severe sepsis. In fact, septic shock is associated with culture-positive bacteremia in only 30-50% of cases.

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.

The American-European Consensus Conference on ARDS agreed upon the following definitions of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).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, except that the PaO2/FiO2 ratio is 200 or less.


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