Oxygen and nitric oxide metabolism in sepsis.

ALVAREZ, SILVIA; EVELSON, PABLO; CIMOLAI, MARIA CECILIA

Free Radical Pathophysiology

Research Signpost

Lugar: Kerala, India; Año: 2008; p. 223 - 236

Sepsis is the most common cause of death among hospitalized patients in non-coronary intensive care units. It is a paradigm of acute whole body inflammation, with massive increases of NO and inflammatory cytokines in the biological fluids, systemic damage to vascular endothelium, and impaired tissue and whole body respiration despite adequate oxygen supply. As mitochondria utilize 90% of total body oxygen consumption to generate ATP, organ dysfunction could be a consequence of impaired bioenergetic process. Thus, mitochondria play a central role in the intracellular events associated with inflammation and septic shock, as active sources and sensitive targets of NO. The pathogenic role of NO in sepsis and septic shock can, in fact, encompass both vascular alterations and the direct cellular toxic effects of NO, peroxynitrite and other NO-derived products. Treatment of septic shock usually includes respiratory support to optimize tissue oxygenation, intravenous fluid administration, broad-spectrum antimicrobial therapy and anti-inflammatory agents (glucocorticoids and non-steroidal anti-inflammatory drugs), and vasopresor support; all of which are limited in their effectiveness. Despite the utilization of increasingly sophisticated and potent antibiotic and adjunctive therapies, sepsis remains a leading cause of death.