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    Nitric Oxide in Septic Shock: an experimental and clinical study

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    Sepsis and its sequelae are the leading cause of mortality in todays medical and surgical intensive care. The incidence of sepsis continues to increase. Mortality of septic shock ranges from 30 to 80% depending on the severity of disease and the presence of organ failure. Despite recent progress in antibiotic therapy and intensive care support mortality from septic shock has remained high over the last years. Sepsis can be defmed as the systemic response to severe infection.'" When certain micro-organisms or their toxic products invade the bloodstream, this may result in a wide variety of symptoms that are characteristic of sepsis and its sequelae (Table 1). When hypotension develops unresponsive to fluid therapy and signs of inadequate organ perfusion are present, the condition is often referred to as septic shock.s Shock develops in approximately 40 % of septic patients. The initial cardiovascular changes during hyperdynamic sepsis are characterized by massive vasodilatation with a normal to high cardiac output, low peripheral vascular resistance and severe hypotension.'" In a large number of patients the initial hypotension is unresponsive to treatment with fluid substitution or vasopressors. Umesponsive hypotension is present in 50% of patients that die of septic shock. In the first week unresponsive hypotension is the primary cause of mortality of septic patients. In the later stages of sepsis, the hyperdynamic circulatory state may turn into hypodynamic septic shock witl! failure to guarantee adequate oxygen supply to tissues and irreversible organ damage. In a retrospective study with one hundred intensive care patients with sepsis 80% of mortality in the first week was caused by severe hypotension