Early Goal-Directed Therapy in Septic Shock
February 1, 2002 3 minutes read
Early Goal-Directed Therapy in Septic Shock
Abstract & Commentary
Synopsis: Patients treated to a normal SVO2 in addition to maintaining normal CVP, blood pressure, and urine output for the first 6 hours after presentation in septic shock in the emergency room experienced significantly lower mortality than those whose SVO2 was monitored but not treated.
Source: Rivers E, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-1377.
The debate over treatment of septic shock to hyperdynamic end points has been reopened with publication of this randomized, controlled study of 263 patients with severe sepsis and septic shock. Patients meeting the standard criteria for severe sepsis and septic shock were randomized to receive either conventional or goal-directed hemodynamic therapy for the first 6 hours of care, which was provided in the emergency department. Following this initial treatment period, care was continued in the ICU by intensivists blinded to the initial therapy the patients had received.
Of the 263 patients entered, 236 completed the study. In addition to routine monitors, all patients received central venous or pulmonary artery oxygen saturation monitoring. Standard therapy consisted of administering fluid boluses until the CVP was between 8 and 12 mm Hg and urine output > 0.5 mL/kg/h; vasopressors were administered if the mean blood pressure was less than 65 mm Hg. In the treatment arm, if mixed-venous oxygen saturation (SVO2) was less than 70%, additional fluids, vasopressors, and packed red blood cells were infused, keeping the hematocrit 30% or greater and achieving the saturation goal.
Mortality in the control group was 46.5% vs. only 30.5% in the treatment group (P = 0.009). In addition to the reduced mortality observed, at every measurement after the treatment interval the control patients had worse physiology scores, higher blood lactate concentrations, worse acid-base balance, and more evidence of organ failures. The survivors in the treatment group had a shorter duration of total hospital stay than the survivors in the control group. Duration of mechanical ventilation, ICU care, and vasopressor therapy were not different between the 2 groups.
Comment by Charles G. Durbin, Jr., MD
This is an important article as it supports the concept of early treatment and aggressive hemodynamic treatment of sepsis. Previous work has demonstrated that, once a patient arrives in the ICU with established sepsis, there is little benefit from aggressively pursuing hyperdynamic end points. In fact, a large multicenter study concluded that there was no benefit from this approach,1 and some clinicians have abandoned this treatment approach. However, doing so flies in the face of numerous studies that have demonstrated improved outcomes—including mortality—when patients are prospectively treated to hyperdynamic end points before undergoing major surgery. In fact, every prospective clinical study has shown that if patients achieve supranormal values, whether in the treatment or control group, their outcome is improved. This current report seems to bring these diverse opinions together. It establishes that early on in the septic patient, hyperdynamic end points make a huge difference in later outcomes. After the shock state is well established, no benefits accrue.
The study is limited by its experimental design. What it demonstrates is that a brief, early period of aggressive treatment improves outcome dramatically in septic shock. There are many questions that remain to be answered: For how long is it useful to attempt to reach hyperdynamic end points? Is there any additional benefit from continuing this treatment for a longer period of time? What hemodynamic goal should be chosen? Is SVO2 the most appropriate end point, and how should this goal be achieved? Even with the limitations inherent in this study, it is exciting to finally know that there is hope in improving outcome from this dreaded disease.
Dr. Durbin, Jr., MD, Professor of Anesthesiology, Medical Director of Respiratory Care, University of Virginia, is Associate Editor of Critical Care Alert.
Reference
1. Gattinoni L, et al. A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. N Engl J Med. 1995;333(16):1025-1032.
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