Early Goal-directed Therapy and Myocardial Dysfunction

The cardiovascular system plays a central role in the pathophysiology and prognosis of sepsis, yet the correct hemodynamic management of septic patients is still vigorously debated. Despite guidelines, the use of CVP and PAOP is seriously criticized for inaccurate prediction of fluid requirement. Recently studies showed that early goal-directed therapy (EGDT) aimed at achieving a ScvO2 of ≥70% significantly improved survival of septic shock patients, yet EGDT has not been adopted by all intensivists. The investigators have recently found using 2D echocardiography in 262 patients with severe sepsis or septic shock and treated by the conventional guidelines (without ScvO2) that diastolic dysfunction and reduced stroke volume index are strong independent predictors of mortality. In the present study the investigators intend to test the effect of EGDT on resuscitation, on long term myocardial function and left ventricular volumes and on survival in ICU patients with severe sepsis and septic shock. Patients will be randomized to EGDT (resuscitation directed by ScvO2) or standard of therapy for the first six hours after diagnosis of severe sepsis or septic shock and admission to the ICU. After six hours patients in septic shock will be further monitored with non invasive cardiac output (PiCCO, Pulsion Technologies). All patients will be followed daily by 2D \& 3D transthoracic echocardiography with detailed measurements of systolic and diastolic left and right ventricular volumes and functions. Patients in the EGDT group will be compared to the control group for parameters of initial resuscitation (fluid volumes, ScvO2 achieved, inotrope use), initial values from non invasive cardiac output at six hours, interventions required from institution of non invasive cardiac output, early and long term effects on cardiac function and volumes from echo measurements, and mortality. The effectiveness of EGDT will thus be examined in the short and long terms.