icu

Early Goal-Directed Resuscitation Therapy in Sepsis

　　Emanuel Rivers, MD, MPH,[29] of Henry Ford Hospital, Franklin, Michigan, discussed his work on early goal-directed resuscitation therapy in sepsis.[30] When systemic inflammatory response syndrome is activated, it may progress to severe sepsis and septic shock. The patients admitted to the ICU for septic shock are already hypotensive and have evidence of tissue hypoperfusion and a high mortality. An imbalance between systemic oxygen delivery and oxygen demand may go unrecognized in the initial stages of shock when the patient is still hemodynamically stable, thus losing precious time as global tissue hypoxia precedes multiorgan failure and death.
　　A study was undertaken to test the hypothesis that early goal-directed therapy may affect the mortality of septic shock. A total of 263 patients with severe sepsis, septic shock, or the sepsis syndrome were enrolled in the study. Of these, 130 were randomly assigned to early goal-directed therapy and 133 to standard therapy. End points for the treatment group were normalized values for mixed venous oxygen saturation, arterial lactate concentration, base deficit, and pH. After insertion of a central venous catheter capable of measuring continuously central venous oxygen saturation and an arterial catheter, the patients were treated in the emergency department (ED) according to a protocol for early goal-directed therapy for at least 6 hours before being transferred to the ICU. The goals were central venous pressure (CVP) of 8 to 12 mm Hg, MAP of 65 to 90 mm Hg, and SvO2 of greater than 70%. These goals were achieved by the use of crystalloids, colloids, transfusion of red blood cells (to keep the hematocrit > 30%), inotropes, and dobutamine as appropriate.
　　When the goals were achieved and after 6 hours in the ED, the patient was admitted. After admission, the patient was managed by certified intensivists. Compared with previous optimization studies, the patients in this study were more hypovolemic, as indicated by the lower presenting CVP, cardiac index, SvO2, and the higher lactate. There were significant differences in mortality between the 2 groups: inhospital mortality was 30.5% in the early goal-directed therapy group, as compared with 46.5% in the group assigned to standard therapy (P = .009). The difference persisted after 60 days (44.3% vs 56.9%, P = .03). More dobutamine and more blood transfusions were administered to the treatment group. What is interesting is that despite the fact that the presenting CVP was similar between the 2 groups, more fluid was administered in the first 6 hours to the treatment group, probably reflecting decreased left ventricular compliance causing the elevated CVP. There were no differences between groups as far as total volume of administered fluid after 72 hours. The differences in mortality between groups were more pronounced in patients with a baseline MAP of more than 100 and lactate of more than 4 mM/L. The 28- and 60-day mortality difference between treated and untreated patients in this group was approximately 40% (P < .001). These patients did not necessarily have low CVPs on presentation, underlining the importance of decreased cardiac compliance in the initial stages of shock. The term "cryptic shock" is reserved for these patients. These are the patients with deceptively normal hemodynamic parameters, yet in high risk for complications and death because of global ischemia.
　　Dr. Rivers concluded that the role of early goal-directed therapy is to identify early high-risk patients, to prevent cardiovascular collapse, to treat hypovolemia and cryptic myocardial dysfunction, and thus decrease multiple organ failure and mortality.