Until recently, the hospital mortality of patients with severe sepsis and septic shock was 50%. In 2001, a single-center ED study found that mortality in patients with severe sepsis or septic shock was significantly lower among those treated according to a 6-hour protocol of early goal-directed therapy (EGDT) than for those receiving standard therapy. That study involved a specific protocol in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets.
“Many wondered if all the EGDT steps were needed and if changes in critical illness care have since altered the impact of the catheter-guided sepsis care,” says Donald M. Yealy, MD. To address this question, Dr. Yealy and colleagues designed a multicenter trial comparing alternative resuscitation strategies in patients with septic shock. Published in the New England Journal of Medicine, the study tested whether protocol-based resuscitation was superior to usual care. They also tested whether a protocol with central hemodynamic monitoring to guide treatments was superior to a simpler protocol that used bedside exams to trigger care. “We wanted to see if we could achieve better outcomes by simply recognizing septic shock early and treating it aggressively with fluids and vasopressors absent a catheter-based algorithm,” says Dr. Yealy.
Conducted in 31 U.S. EDs and in 1,351 enrollees, Dr. Yealy and colleagues randomly assigned patients with septic shock to one of three groups for 6 hours of resuscitation:
1. Protocol-based EGDT given by a dedicated two-person team.
2. Protocol-based standard therapy by the same team that did not require the placement of a central venous catheter, administration ofninotropes, or blood transfusions.
3. Usual care titrated by the bedside physiciannwithout aids.
“Our goal was to examine different aggressive approaches after early recognition, not study delayed care or to disprove previous findings,” Dr. Yealy says.
The final results showed no difference in 60-day hospital mortality across treatment groups, ranging from about 18% (simple protocol) to 21% (EGDT). Longer-term mortality and hospital care also did not differ among the groups. Each group had high rates of early antibiotic use (97%).
“Care is getting better, but we still have room for improvement, since 20% of patients with sepsis and septic shock still died in the short-term,” says Dr. Yealy. “Our findings demonstrate that mastering the basics of sepsis care improves outcomes, and there is no single ‘best’ approach. The key is to recognize shock early, treat it aggressively, and continue to monitor responses to care. The ‘how’ of resuscitation is less important than recognizing the need to look and treat early and often.”
ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683-1693. Available at: http://www.nejm.org/doi/full/10.1056/NEJMoa1401602.
Casserly B, Baram M, Walsh P, et al. Implementing a collaborative protocol in a sepsis intervention program: lessons learned. Lung. 2011;189:11-19.
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Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008; 36:296-327.
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