Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock
[Rivers E et al. NEJM 2001;345:1368]:
This is a report from the “Early Goal-Directed Therapy Collaborative Group” from the Emergency Medicine Department at Henry Ford Health Systems and Case Western to determine optimal methods to manage patients who arrive in the emergency department with severe sepsis or septic shock. The patients were randomized to receive either customary care or “early goal-directed therapy” for the first hours before admission to the ICU. Standard treatment consisted of arterial and central venous catheterization, critical-care consultation, submission of appropriate specimens for culture, antibiotics at the discretion of the clinician and hemodynamic support according to a published protocol (Crit Care Med 1999;27:639). The early goal-directed therapy included the following:
- Bolus 500 ml crystalloid q 30 min to achieve central venous pressure of 8–12 mm Hg.
- Vasopressors to maintain mean arterial pressure of at least 65 mm Hg; if mean arterial pressure exceeded 90 mm Hg, vasodilators were given until it was < or = 90 mm Hg.
- Red cell transfusion to a hematocrit of at least 30% if central venous oxygen saturation was less than 70%; if it persisted at less than 70%, dobutamine was given at 2.5 ug/kg/min and increased by 2.5 ug/kg/min q 30 min until venous oxygen saturation exceeded 70% or there was a maximum dose of 20 ug/kg/min.
- Patients who could not achieve hemodynamic goals received mechanical ventilation and sedatives.
There were 263 participants including 130 randomized to the early goal-directed therapy and 133 to standard therapy. There were no baseline differences between the two groups. In hospital mortality was significantly better with the early goal-directed therapy (30.5% vs. 46.5%;p = 0.009). Analysis of additional data showed the early goal-directed therapy was significantly better in achieving the goals of higher central venous oxygen saturation, lower lactate concentration, higher pH, and in mean APACHE II scores. The authors conclude that early goal-directed therapy provides significant benefit in outcome among patients with severe sepsis and septic shock who present to emergency rooms.
Studies of therapeutic intervention in patients with sepsis and septic shock have been studied extensively, but usually begin with admission to the intensive care unit. The emphasis here is on aggressive treatment in the earliest stages. A major goal is to prevent sudden cardiovascular collapse to avoid the need for vasopressors, mechanical ventilation, and catheterization of pulmonary arteries. Thus, the authors here showed nearly all patients in the early therapy group achieved the hemodynamic goals during the first 6 hours, and this was significantly better than those in the standard therapy group. In the editorial comment by Timothy Evans (NEJM 2001;345:1417) it is noted that the results here are substantially better than those achieved with activated protein C (NEJM 2001;344:699).