Septic shock

Septic shock is a potentially fatal

According to the earlier definitions of sepsis updated in 2001,[6] sepsis is a constellation of symptoms secondary to an infection that manifests as disruptions in heart rate, respiratory rate, temperature, and white blood cell count. If sepsis worsens to the point of end-organ dysfunction (kidney failure, liver dysfunction, altered mental status, or heart damage), then the condition is called severe sepsis. Once severe sepsis worsens to the point where blood pressure can no longer be maintained with intravenous fluids alone, then the criterion has been met for septic shock.^{[citation needed]}

Pathophysiology

The pathophysiology of septic shock is not entirely understood, but it is known that a key role in the development of severe sepsis is played by an immune and coagulation response to an infection. Both pro-inflammatory and anti-inflammatory responses play a role in septic shock.^[7] Septic shock involves a widespread inflammatory response that produces a hypermetabolic effect. This is manifested by increased cellular respiration, protein catabolism, and metabolic acidosis with a compensatory respiratory alkalosis.^[8]

Most cases of septic shock are caused by

In response to inflammation, a compensatory reaction of production of anti-inflammatory substances such as IL-4, IL-10 antagonists, IL-1 receptor, and cortisol occurs. This is called compensatory anti-inflammatory response syndrome (CARS).^[10] Both the inflammatory and anti-inflammatory reactions are responsible for the course of sepsis and are described as MARS (Mixed Antagonist Response Syndrome). The aim of these processes is to keep inflammation at an appropriate level. CARS often leads to suppression of the immune system, which leaves patients vulnerable to secondary infection.^[7] It was once thought that SIRS or CARS could predominate in a septic individual, and it was proposed that CARS follows SIRS in a two-wave process. It is now believed that the systemic inflammatory response and the compensatory anti-inflammatory response occur simultaneously.^[10]

At high levels of LPS, the syndrome of septic shock supervenes; the same cytokine and secondary mediators, now at high levels, result in systemic vasodilation (hypotension), diminished myocardial contractility, widespread endothelial injury, activation causing systemic leukocyte adhesion and diffuse alveolar capillary damage in the lung, and activation of the coagulation system culminating in disseminated intravascular coagulation (DIC).

The hypoperfusion from the combined effects of widespread vasodilation, myocardial pump failure, and DIC causes multiorgan system failure that affects the liver, kidneys, and central nervous system, among other organ systems. Recently, severe damage to liver ultrastructure has been noticed from treatment with cell-free toxins of Salmonella.^[11] Unless the underlying infection (and LPS overload) is rapidly brought under control, the patient usually dies.^{[citation needed]}

The ability of

According to current guidelines, requirements for diagnosis with sepsis are "the presence (probable or documented) of infection together with systemic manifestations of infection".[8] These manifestations may include:

• PaCO
  ₂
  less than 32 mm Hg, which signifies hyperventilation
• White blood cell count either significantly low (< 4000 cells/mm³), or elevated (> 12000 cells/mm³)
• Tachycardia (rapid heart rate), which in sepsis is defined as a rate greater than 90 beats per minute
• Altered body
  temperature: Fever
  > 38.0 °C (100.4 °F) or hypothermia < 36.0 °C (96.8 °F)

Documented evidence of infection may include positive blood culture, signs of pneumonia on chest x-ray, or other radiologic or laboratory evidence of infection. Signs of end-organ dysfunction are present in septic shock, including kidney failure, liver dysfunction, changes in mental status, or elevated serum lactate.

Septic shock is diagnosed if there is low blood pressure (BP) that does not respond to treatment. This means that intravenous fluid administration alone is not enough to maintain a patient's BP. Diagnosis of septic shock is made when

Septic shock may be regarded as a stage of SIRS (Systemic Inflammatory Response Syndrome), in which sepsis, severe sepsis and multiple organ dysfunction syndrome (MODS) represent different stages of a pathophysiological process. If an organism cannot cope with an infection, it may lead to a systemic response - sepsis, which may further progress to severe sepsis, septic shock, organ failure, and eventually, result in death.^{[citation needed]}

Treatment

Treatment primarily consists of the following:

1. Giving
   intravenous fluids^[13]
2. Early antibiotic administration [13]
3. Early goal directed therapy^[13]
4. Rapid source identification and control
5. Support of major organ dysfunction

Methylene blue has been found to be useful for this condition.^{[17][18][19][20]} Although use of methylene blue has mostly been in adults it has also been shown to work in children.^[21][22] Its mechanism of action is thought to be via the inhibition of the nitric oxide-cyclic guanosine monophosphate pathway.^[23] This pathway is excessively activated in septic shock. Methylene blue has been found to work in cases resistant to the usual agents.^[24] This effect was first reported in the early 1990s.^[25][26]

Other

While there is tentative evidence for β-Blocker therapy to help control heart rate, evidence is not significant enough for its routine use.^[27][28] There is tentative evidence that steroids may be useful in improving outcomes.^[29]

Tentative evidence exists that

Sepsis has a worldwide incidence of more than 20 million cases a year, with mortality due to septic shock reaching up to 50 percent even in industrialized countries.[33]

According to the U.S.

The mortality rate from sepsis, especially if it is not treated rapidly with the needed medications in a hospital, is approximately 40% in adults and 25% in children. It is significantly greater when sepsis is left untreated for more than seven days.[34]

References