A Randomized Trial of Protocol-Based Care for Early Septic Shock (ProCESS)

Rivers et al. (2001) showed that Early Goal-Directed Therapy (EGDT) — a protocolized resuscitation targeting specific hemodynamic endpoints (CVP 8–12, ScvO₂ ≥70%, MAP ≥65) — reduced sepsis mortality by 16%. This became standard of care. ProCESS was the first of three trials to challenge this.

Multicenter RCT (31 US EDs, n=1,341) comparing three strategies: protocol-based EGDT, protocol-based standard therapy, and usual care in patients with septic shock presenting to the ED.

60-day in-hospital mortality was similar across all three groups: EGDT 21.0%, protocol-based standard 18.2%, usual care 18.9% (p=0.83). EGDT patients received more IV fluids, blood transfusions, and vasopressors.

Protocolized EGDT (with ScvO₂ monitoring, CVP targets, and blood transfusions) is not superior to usual care in septic shock. The key elements that matter are: early recognition, prompt antibiotics, and adequate resuscitation — not the specific protocol endpoints.

Usual care had improved significantly since 2001 (Hawthorne effect). ED-based trial may not apply to all settings. Concurrent ARISE and ProMISe trials confirmed these findings.