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World J Crit Care Med. May 4, 2014; 3(2): 45-54
Published online May 4, 2014. doi: 10.5492/wjccm.v3.i2.45
Metabolic theory of septic shock
Jay Pravda
Jay Pravda, Inflammatory Disease Research Centre, West Palm Beach, FL 33420, United States
Author contributions: Pravda J is the sole author of this manuscript and solely responsible for its content; Pravda J performed all the research, collected, analyzed and interpreted all the data; Pravda J conceived of and developed the Metabolic Theory of Septic Shock; Pravda J prepared and wrote the manuscript and performed all critical revisions; Pravda J certifies that the Metabolic Theory of Septic Shock is the product of his original research and Pravda J has overall responsibility for this manuscript.
Correspondence to: Jay Pravda, MD, MPH, Inflammatory Disease Research Centre, West Palm Beach, P.O. Box 32632, FL 33420, United States.
Telephone: +1-682-2513030 Fax: +1-888-7005813
Received: October 29, 2013
Revised: January 21, 2014
Accepted: March 3, 2014
Published online: May 4, 2014

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.

Keywords: Septic shock, Hydrogen peroxide, Hypermetabolic, Sepsis, Systemic inflammatory response syndrome

Core tip: For decades septic shock has been attributed to an over-active immune response. However, immune modulation has failed to reduce mortality, casting doubt on a direct causal role for the immune response in the development of septic shock. A closer look suggests that septic shock is the result of a generalized build-up of hydrogen peroxide, a toxic cellular by-product generated as a consequence of the hypermetabolic state that accompanies a systemic immune response. This finding points to the systemic accumulation of hydrogen peroxide as a significant risk factor for the development of septic and non-septic shock syndromes.