Facebook
Twitter
LinkedIn
Email
 |
Checking for direct PDF access through Ovid | |
Excerpt
Synopsis: Early goal-directed therapy with aggressive fluid replacement, guided by central venous pressure and venous oxygen saturation measurements, significantly improves outcome in patients with severe sepsis and septic shock.
Source: Emanuel Rivers, Bryant Nguyen, Suzanne Havstad, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368–1377.
Sepsis and septic shock are significant causes of morbidity and mortality. In the United States, it has been estimated that there are approximately 751,000 cases (3.0 cases per 1000 population) of sepsis and septic shock each year, leading to 215,000 deaths. Among hospitalized patients in noncoronary intensive care units (ICUs), sepsis is the most common cause of death. Several studies suggest that the incidence of sepsis is increasing, likely as a result of increasing use of immunosuppressive therapies and invasive devices. In the elderly, the incidence of sepsis and septic shock and related mortality rates are significantly higher. With the projected growth of the elderly population, the incidence of sepsis is bound to increase additionally. The financial impact of managing patients with sepsis is enormous: the present economic burden is estimated to be $16.7 billion per year.
The mortality rate associated with sepsis has previously been variably estimated to be between 20% and 50%. One of the major reasons for such a variation in previous estimates of morbidity and mortality has been a lack of consistent criteria for defining the so-called sepsis syndrome. In 1992, American College of Chest Physicians-Society of Critical Care Medicine consensus conference developed specific criteria for defining sepsis and organ failure. Four specific terms were used: systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock. The term SIRS was used to describe a clinical response arising from a nonspecific insult and was defined as the presence of two or more of the following: temperature >38°C or <36°C, heart rate > 90 beats per minute, respiratory rate >20 breaths per minute or Pco2 <32 mm Hg, and white blood cell count >12.9 ×109/L or <4.0 ×109/L or the presence of > 10% band forms. Sepsis was defined as the presence of SIRS associated with a confirmed infectious process. Disregarding the term sepsis syndrome, members of the consensus conference defined severe sepsis as the presence of sepsis with either hypotension or systemic manifestations of hypoperfusion (lactic acidosis, oliguria, or altered mental status). Finally, septic shock was defined as sepsis with hypotension despite adequate fluid resuscitation, associated with hypoperfusion abnormalities that included, but were not limited to, lactic acidosis, oliguria, or alteration in mental status. Septic shock leads to multiorgan dysfunction syndrome, which is the final complication of a critical illness, with mortality rates well over 50%. The transition from SIRS to severe sepsis and septic shock involves a cascade of pathologic changes induced by circulatory abnormalities resulting in global tissue hypoxia, which activates the coagulation cascade, complement system and the fibrinolytic system. The peak effect of these changes occurs within 3 to 5 days.
Even though the care of critically ill patients has progressed significantly during the last 50 years, the mortality rate of severe sepsis and septic shock has not improved. A major reason for the lack of benefit from therapeutic interventions has been the lack of early detection and intervention before the spiraling cascade of complement activation and coagulation abnormalities begins. The authors of the present study argue that whether a person with sepsis will recover depends not only on the severity of illness and the underlying organ reserve but also on the speed and adequacy of the therapy instituted.
