Septic shock

Septic shock is a serious medical condition caused by decreased tissue perfusion and oxygen delivery as a result of infection and sepsis. It can cause multiple organ failure and death. Its most common victims are children, immunocompromised individuals, and the elderly, as their immune systems cannot cope with the infection as well as healthy adults are able. The mortality rate from septic shock is approximately 50%.

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Definition of septic shock

To diagnose septic shock^[1] the following two criteria must be met:

1. Refractory hypotension - hypotension despite adequate fluid resuscitation.
   • In adults it is defined as a systolic blood pressure < 90 mmHg, or a MAP < 60 mmHg, without the requirement for inotropic support, or a reduction of 40 mmHg in the systolic blood pressure from baseline.
   • In children it is BP < 2 SD of the normal blood pressure.

In addition to the two criteria above, two or more of the following must be present:

• Hyperventilation (high respiratory rate) > 20 breaths per minute or, on blood gas, a P_aCO₂ less than 32 mmHg.
• White blood cell count < 4000 cells/mm³ or > 12000 cells/mm³ (< 4 x 10⁹ or > 12 x 10⁹ cells/L).

Types

A subclass of distributive shock, shock refers specifically to decreased tissue perfusion resulting in end-organ dysfunction. Cytokines TNFα, IL-1β, IL-6 released in a large scale inflammatory response results in massive vasodilation, increased capillary permeability, decreased systemic vascular resistance, and hypotension. Hypotension reduces tissue perfusion pressure and thus tissue hypoxia ensues. Finally, in an attempt to offset decreased blood pressure, ventricular dilatation and myocardial dysfunction will occur.

Causes

The process of infection by bacteria or fungi can result in systemic signs and symptoms that are variously described. In rough order of severity, these are bacteremia or fungemia; septicemia; sepsis, severe sepsis or sepsis syndrome; septic shock; refractory septic shock; multiple organ dysfunction syndrome, and death.

The condition develops as a response to certain microbial molecules which trigger the production and release of cellular mediators, such as tumor necrosis factors (TNF); these act to stimulate immune response. Besides TNFα, other cytokines involved in the development of septic shock include interleukin-1β, and interferon γ.

Treatment

Treatment primarily consists of 1) Volume resuscitation 2) Early antibiotic administration 3) Rapid source identification and control and 4) Support of major organ dysfunction.

Among the choices for pressors, a randomized controlled trial concluded that there was no difference between norepinephrine (plus dobutamine as needed for cardiac output) versus epinephrine.^[2]

Antimediator agents may be of some limited use in severe clinical situations:

• Corticosteroids, especially if combined with a mineralocorticoid, can reduce mortality among patients who have relative adrenal insufficiency^[3]
• Recombinant activated protein C (drotrecogin alpha) has been shown in large randomized clinical trials to be associated with reduced mortality (Number needed to treat (NNT) of 16) in patients with multi-organ failure^[4] If this is given, heparin should probably be continued.^[5]

References

1. ^ Tslotou AG, Sakorafas GH, Anagnostopoulos G, Bramis J. Septic shock; current pathogenetic concepts from a clinical perspective. Med Sci Monit. 2005 Mar;11(3):RA76-85. PMID 15735579 Full Text.
2. ^ Annane D, Vignon P, Renault A, et al (2007). "Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial". Lancet 370 (9588): 676-84. doi:10.1016/S0140-6736(07)61344-0. PMID 17720019.
3. ^ Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellissant E. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002 Aug 21;288(7):862-71. PMID 12186604
4. ^ Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr; Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001 Mar 8;344(10):699-709. PMID 11236773
5. ^ Levi M, Levy M, Williams MD, et al (2007). "Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa (activated)". Am. J. Respir. Crit. Care Med. 176 (5): 483–90. doi:10.1164/rccm.200612-1803OC. PMID 17556722.

See also

• Anaphylactic shock
• Cardiogenic shock
• Neurogenic shock
• Sepsis
• Shock
• Systemic inflammatory response syndrome (SIRS)