Reducing Mortality in Severe Sepsis and Septic Shock

Andrew T. Levinson, M.D., M.P.H.; Brian P. Casserly, M.D.; Mitchell M. Levy, M.D.


Semin Respir Crit Care Med. 2011;32(2):195-205. 

In This Article

Early Goal-directed Therapy

In a landmark 2001 study by Rivers and colleagues, an absolute mortality reduction of 16% was found in patients treated with this early gold-directed therapy (EGDT) protocol when compared with patients who received standard care. A total of 263 patients with severe sepsis and septic shock presenting to a large urban academic medical center emergency department were randomized to a protocol of 6 hours of EGDT based on central venous pressure (CVP) and central venous oxygen saturation (ScvO2). Those enrolled in the comparison group also had CVP monitoring. Patients in the EGDT group got significantly more fluids in the first 6 hours (5 L on average) compared with those in the control group (average 3.5 L). Total hospital stay mortality was 30.5% in the EGDT group compared with 46.5% in the comparison group, a very significant difference.[35] Several observational studies have validated the effectiveness of protocol-directed resuscitation.[36–40] EGDT has become one of the cornerstones of the SSC guidelines. Despite, accumulating clinical evidence of the value of EGDT these interventions remain underutilized and controversial.[8,9,41] One major criticism of this study was that there was much higher mortality in the control group than might have been expected.[42] The design of the study did not allow assessment of the relative contribution of individual components of the protocol. Several large RCTs are under way to resolve this ongoing controversy.


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