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Evevident
Original paper
2014NEJMPulmonary/Critical Care

ProCESS

A randomized trial of protocol-based care for early septic shock

RCTSepsis

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Overview

In modern early septic shock care, protocol-based EGDT did not improve mortality versus usual care.

Clinical takeaway

ProCESS showed that the invasive EGDT protocol from Rivers was not required when contemporary sepsis recognition and treatment were already strong.

Key result

60-day mortality was similar across EGDT (21.0%), protocol-based standard care (18.2%), and usual care (18.9%).

Practice impact

Supports timely sepsis care without mandatory central venous oxygen saturation targets.

Evidence

Study design

Multicenter, three-arm randomized controlled trial.

Enrollment

1,341

Follow-up

60-day in-hospital mortality (primary); mortality also reported at 90 days and 1 year.

Geography

United States

Clinical question

Does protocol-based EGDT or protocol-based standard therapy improve outcomes compared with usual care in early septic shock?

Population

  • Emergency-department patients with septic shock at 31 contemporary US academic hospitals.

Intervention

Protocol-based EGDT (Rivers-style, with ScvO2 targets) or protocol-based standard therapy (no mandatory central line).

Comparator

Usual care directed by the treating team.

Primary outcome

60-day in-hospital mortality.

Protocol-based resuscitation, including the invasive EGDT bundle, did not improve survival over usual care in contemporary septic shock.

Relative risk (EGDT vs usual care) / 1.04 / CI 95% CI 0.82-1.31 / p=0.83

Key results

  • 60-day in-hospital mortality: 21.0% (protocol-based EGDT), 18.2% (protocol-based standard therapy), and 18.9% (usual care), with no significant differences.
  • EGDT vs usual care: relative risk 1.04 (95% CI 0.82-1.31; p=0.83).
  • Usual care already included prompt antibiotics and substantial early fluid resuscitation.

Harms

  • The EGDT arm required central venous catheterization and used more dobutamine and blood transfusion.
  • Renal-replacement therapy was used more often in the protocol-based standard-therapy group (6.0%) than usual care (3.1%).

Clinical Use

When to cite

  • When explaining modern sepsis resuscitation as early recognition, antibiotics, fluids, and vasopressors rather than mandatory central-line targets.

Practice impact

  • Supports timely sepsis care without mandatory central venous oxygen saturation targets.

Applicability

  • Most applicable to emergency-department patients with septic shock treated in contemporary systems with early antibiotics and fluids.

Limitations

  • Conducted after sepsis quality initiatives had already raised the standard of usual care.
  • Does not argue against early antibiotics, fluids, vasopressors, or source control.
  • Findings were concordant with the ARISE and ProMISe trials.

Common misinterpretations

  • ProCESS refutes the mandatory Rivers EGDT bundle, not the value of early recognition and resuscitation.
  • A negative result reflects that usual care had improved to match protocolized care, not that resuscitation is unimportant.

Related evidence

Rivers EGDT - Earlier Trial

Citation

ProCESS Investigators, Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370(18):1683-1693. doi:10.1056/NEJMoa1401602

In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes.