“Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock” – Emanuel Rivers et al., The New England Journal of Medicine, November 8, 2001
Sepsis and septic shock are common conditions associated with high mortality, and the incidence and mortality continue to rise [1,2]. Sepsis is defined as a systemic inflammatory response with deteriorating hemodynamic parameters, most often due to disseminated infection, and septic shock occurs when the blood, oxygen and nutrient supply is so compromised that it causes multi-organ failure. Sepsis is an acute problem, characterized by rapid onset and deterioration, and treatment is time sensitive. Antibiotics are the mainstay of therapy, as they will eliminate the offending microbes, but supportive care to maintain organ function is crucial in reducing mortality.
The investigators of this study proposed an early (within the first 72 hrs) goal-directed treatment schedule for this supportive care. They outlined parameters to measure organ perfusion with goals for therapy – central venous pressures (goal 8-12 mmHg), central venous oxygen content (goal > 70%) and arterial pressures (goal 65-90 mmHg). To meet these goals, they administered fluids, blood, vasopressors, vasodilators and inotropes. This therapy regimen was compared with standard therapy at clinicians’ discretion. The outcomes measured were organ dysfunction by APACHEII scores, MODS scores,arterial pH and serum lactate levels and 28 and 60-day all cause mortality.
During the first 72 hours, central venous oxygen saturation goals were achieved in ~60% of standard therapy patients and ~95% of goal directed therapy patients. Hemodynamic parameters (arterial pressures, central venous pressures) were at goal in 86% of standard therapy patients and 99% of goal directed therapy patients. Patients in the goal directed arm had higher blood pressures and higher central venous oxygen saturations during the entire 72 hours. Goal directed therapy patients received more fluids, more blood and more inotropes within the first 6 hours of therapy, but required less fluids, less blood and less vasopressors after that (hours 7-72).
APACHE II and MODS scores of organ dysfunction were lower in patients in the goal directed group during hours 7-72. Base deficit was lower, serum lactate was lower and arterial pH was higher during the same time period. Twenty-eight day and 60-day mortality figures were lower in the goal directed group, which was mainly the result of in-hospital mortality.
Why We Do What We Do
Treatment and management of sepsis is highly dependent on early therapy. As illustrated in this trial, aggressive fluid, blood and inotropic resuscitation in the first 6 hours can have profound impact on further treatment requirements and organ dysfunction in the following 3 days, as well as in-hospital mortality. Early recognition is also key to initiating therapy during the period where it is most helpful. Increased volume and blood administration outside the first 6 hours did not result in improved organ function or mortality. Directing therapy towards specific hemodynamic goals standardizes practice and gives clinicians strong guidelines to treat towards. Therefore, the benefits of placing invasive central venous and arterial lines outweigh the complications of these procedures.
Organ perfusion in septic shock is a simple physiologic system that must be aggressively managed early on to improve patient outcomes. Even though cardiac output and vascular permeability might be severely limited, administration of fluid and blood to carry oxygen and nutrients can support the body during the critical period of the disease. As clinicians, we must all learn to recognize sepsis early and target therapy to hemodynamic goals to provide the best outcome for our patients in such a dangerous and common disease.
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Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early
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