Sepsis

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Sepsis is a potentially life-threatening, systemic complication of an infection resulting from the spread of bacteria or their toxic products from a focus of infection. Pneumonia is the most common cause, followed by intraabdominal and urinary tract infections. No source is found in about one third of cases. The clinical presentation of sepsis is highly variable depending on the etiology.


Presentation

The clinical features of septicemia intensify over time from mild to severe.

The cardinal symptoms of sepsis include:

These features may be preceded by lethargy, headache and minor changes in consciousness.

In the elderly and immunocompromised patients, the clinical features may be quite subtle.

Workup

Early diagnosis and treatment of sepsis is the basic key in preventing the morbidity and mortality resulting from the sepsis.
Cardiac monitoring, blood pressure monitoring and pulse oxymetry are indicated in patients with septic shock. Once the patient is stabilized, the clinicians can move forward to the diagnostic workup. This involves the use of the following investigation to determine the cause and site of infection:

  • Blood CP
  • Blood culture
  • Chest radiography
  • Ultrasound abdomen and pelvis
  • Urea & creatinine levels
  • Liver function tests
  • Sputum culture
  • Urine culture
  • Arterial blood gases
  • Coagulation profile

Treatment

The following goals should be kept in mind while treating the patients with septic shock:

  • Adequate antibiotic therapy should be started as early as possible (within one hour of making the diagnosis in severe sepsis) [8].
  • In severe sepsis, resuscitation is performed during the first six hours to enhance the heart function in order to correct hypoxia, hypotension and hypoperfusion [9]. This is known as early goal directed therapy and effectively reduces mortality in these patients [10].
  • The source of infection should be identified identify and should be managed with anti-microbial therapy, surgery or both.
  • Adequate organ system function should be maintained.

Prognosis

The mortality resulting from sepsis is usually quoted to be in the range of 20-50% [7]. However, with the advances in the clinical trials in the past ten years, the mortality rate has been limited to 24 to 41%. The mortality greatly depends on the severity of illness.

The severity of the illness and the prognosis depend on the causative organism, site of infection, the strength of the patient’s immune system, the presence of any underlying disease and the developmet of septic shock.

Etiology

There are number of causes which lead to the development of sepsis. Most of these causes are bacterial in nature but viruses and fungi can also cause sepsis.

The common gram positive organisms that cause sepsis include Staphylocossus, Streptocossus and Enterococcus; whereas Proteus, Pseudomonas and Klebsiella are the common gram negative organisms.

In previously healthy adults, the most common sources of infection are intraabdominal infections, urinary tract infections and pneumonia. In many cases of septicemia, the focus of infection may not be apparent.

Few other rare causes include parasites, fungi, viruses and mycobacteria.

The common predisposing conditions for gram negative bacteremia include diabetes mellitus, lymphoproliferative disorders, cirrhosis of liver, burns, invasive procedures and neutropenia.

In contrast, intravenous drug abuse, vascular catheterization, the presence of indwelling mechanical devices and burns are the predisposing conditions for gram positive bacteremia.

Immunosuppression and broad-spectrum antimicrobial therapy predispose the patient to fungemia.

Epidemiology

In the United States, the per annum episodes of sepsis are 400,000 to 750,000. Sepsis is more common in the extremes of ages such as infancy or old age. Statistical data shows that the male gender more commonly develops sepsis; the sex ratio being 1.5:1.

The development of sepsis is favored by poor hygienic conditions and overcrowding. 5-10% of gram positive bacteremias and 50-60% of gram negative bacteremias are complicated by sepsis.

Sex distribution
Age distribution

Pathophysiology

The septic response results from the microbial signals or toxins coupled with the body response in the form of formation of cytokines, prostaglandins and the activation of complement C5a.

Microbial factors

Bacterial signals initiate the release of inflammaory mediators from leukocytes and endothelial cells. Exotoxins (such as peptoglycan and lipoteichoic acid produced by gram positive organisms) and endotoxins (such as lipopolysacchardie produced by gram negative organisms) are the important microbial factors in this regard.

Body response

There is convincing evidence to support the belief that sepsis develops from exaggerated systemic inflammatory response which is induced by infecting organisms. Some of the inflammatory mediators include TNF (tumor necrosis factor), cytokines, leukotrienes, interleukins, eicosanoids, interferon gamma, selectins and complement C5a [3][4][5].

The interaction of these mediators leads to an inflammatory cascade of reactions that causes widespread endothelial damage, hypotension, refractory shock and multiorgan failure.

Abnormalities of coagulation and fibrinolysis

As a result of endothelial damage, clotting factors and the extrinsic clotting cascade are activated. This leads to disseminated intra-vascular coagulation (DIC) and microvascular thrombosis which ultimately results in organ dysfunction and death [6].

Circulatory abnormalities

Distributive shock is characterized by the pathological vasodilatation and shunting of blood from vital to non-vital tissues and organs. Septic shock falls under this category. Disturbances in blood flow, micro-circulation and peripheral shunting of oxygen result in the deficiency of oxygen and accumulation of lactic acid.

Organ dysfunction and failure

As a result of the abnormalities in circulation, coagulation, peripheral shunting and chemical mediators, the main systems and organs of the body fail to function properly. The improper oxygenation that develops ultimately leads to organ failure and death.

Prevention

Promotion of the hygienic conditions and prevention of overcrowding greatly prevents sepsis. High risk individuals must be identified beforehand to ensure early diagnosis.

Summary

Sepsis can be defined as the systemic inflammatory response to microbial invasion. It is characterized by the presence of two or more of the following  four conditions [1].

  • Oral temperature greater than 38°C or less than 36°C
  • Heart rate more than 90 beats/minutes
  • Respiratory rate more than 20 breaths/minute; or less than 32 torr partial pressure of carbon dioxide.
  • Leukocyte count of more than 12,000 cells/mm3 or less than 4000 cells/mm3 or greater than 10% band forms

Dysfunction of major organs occurs in severe sepsis and may lead to septic shock. Septic shock can be defined as sepsis with hypotension that is unresponsive to fluid resuscitation with signs of organ dysfunction and perfusion abnormalities such as metabolic acidosis, acute alteration in mental status, oliguria or adult respiratory distress syndrome.

Early sepsis is usually reversible whereas patients with septic shock often die even if aggressive therapy is provided. For this reason, it is necessary to detect the cause of sepsis and treat it as early as possible. Sepsis causes millions of death each year [2].

Patient Information

Sepsis is a condition in which in which microorganisms or their toxins are present in the blood. It is characterized by fever, fast breathing and heart rate and an increase in white blood cell count. Individuals at the extremes of ages (old age or infancy) or those who have poor health, or unhygienic living conditions are more prone to the development of sepsis. Sepsis can be fatal if not diagnosed and managed promptly.

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References

  1. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Critical care medicine. Apr 2003;31(4):1250-1256.
  2. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Critical care medicine. Jan 2008;36(1):296-327.
  3. Salles MJ, Sprovieri SR, Bedrikow R, et al. [Systemic inflammatory response syndrome/sepsis--review and terminology and physiopathology study]. Revista da Associacao Medica Brasileira. Jan-Mar 1999;45(1):86-92.
  4. Avdeeva MG, Shubich MG. [Pathogenetic mechanisms of the initiation of systemic inflammatory response syndrome (a literature review)].
  5. Klinicheskaia laboratornaia diagnostika. Jun 2003(6):3-10.
    Jaffer U, Wade RG, Gourlay T. Cytokines in the systemic inflammatory response syndrome: a review. HSR proceedings in intensive care & cardiovascular anesthesia. 2010;2(3):161-175.
  6. Nimah M, Brilli RJ. Coagulation dysfunction in sepsis and multiple organ system failure. Critical care clinics. Jul 2003;19(3):441-458.
  7. Russel JA. The current management of septic shock. Minerva medica. Oct 2008;99(5):431-458.
  8. Soong J, Soni N. Sepsis: recognition and treatment. Clinical medicine. Jun 2012;12(3):276-280.
  9. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. The New England journal of medicine. Nov 8 2001;345(19):1368-1377.
  10. Jones AE, Brown MD, Trzeciak S, et al. The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: a meta-analysis. Critical care medicine. Oct 2008;36(10):2734-2739.

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