Metabolic theory of septic shock.

Septic shock is a life threatening condition that can develop subsequent to infection. Mortality can reach as high as 80% with over 150000 deaths yearly in the United States alone. Septic shock causes progressive failure of vital homeostatic mechanisms culminating in immunosuppression, coagulopathy and microvascular dysfunction which can lead to refractory hypotension, organ failure and death. The hypermetabolic response that accompanies a systemic inflammatory reaction places high demands upon stored nutritional resources. A crucial element that can become depleted early during the progression to septic shock is glutathione. Glutathione is chiefly responsible for supplying reducing equivalents to neutralize hydrogen peroxide, a toxic oxidizing agent that is produced during normal metabolism. Without glutathione, hydrogen peroxide can rise to toxic levels in tissues and blood where it can cause severe oxidative injury to organs and to the microvasculature. Continued exposure can result in microvascular dysfunction, capillary leakage and septic shock. It is the aim of this paper to present evidence that elevated systemic levels of hydrogen peroxide are present in septic shock victims and that it significantly contributes to the development and progression of this frequently lethal condition.