Septic shock

Overview
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 those of full-grown adults. The mortality rate from septic shock is approximately 50%.

Definition of septic shock
To diagnose septic shock the following two criteria must be met:
 * 1) Evidence of infection, through a positive blood culture.
 * 2) Refractory hypotension - hypotension despite adequate fluid resuscitation.
 * 3) * 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.
 * 4) * 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:
 * Heart rate > 90 beats per minute.
 * Body temperature 38°C.
 * Hyperventilation (high respiratory rate) > 20 breaths per minute or, on blood gas, a PaCO2 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.

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 Recombinant activated protein C (drotrecogin alpha) has been showen in large randomized clinical trials to be associated with reduced mortality (Number needed to treat (NNT) of 16) in patients with multi-organ failure If this is given, heparin should probably be continued. 