The 1991 ACCP/SCCM Consensus Conference established the Systemic Inflammatory Response Syndrome (SIRS) criteria as the basis for defining sepsis — any two of: temperature >38°C or <36°C, heart rate >90, respiratory rate >20, WBC >12,000 or <4,000. While groundbreaking for standardising sepsis definitions, SIRS proved overly sensitive and non-specific, capturing many non-infectious conditions.

ACCP/SCCM Consensus1992Landmark

Established SIRS criteria and sepsis definitions used for 25 years

Crit Care MedConsensus0

Proof

Landmark RCTs and pivotal trials that established the evidence base

Rivers' EGDT trial (2001) demonstrated that protocolised early goal-directed therapy — targeting specific haemodynamic endpoints within 6 hours — reduced septic shock mortality from 46.5% to 30.5%. This single-centre trial transformed sepsis management. However, the multi-centre ProCESS (2014, N=1,341), ARISE (2014, N=1,600), and ProMISe (2015, N=1,260) trials subsequently showed that protocolised EGDT provided no benefit over usual care, effectively dismantling the specific protocol while preserving the principle of early aggressive treatment.

Rivers EGDT2001Landmark

In-hospital mortality: 30.5% vs 46.5% (p=0.009) favouring EGDT

NEJMRCTN=263

ProCESS2014Landmark

60-day mortality: no significant difference between EGDT, protocol-based, and usual care

NEJMRCTN=1,341

ARISE2014Landmark

90-day mortality: 18.6% vs 18.8% (p=0.90), no benefit of EGDT

NEJMRCTN=1,600

ProMISe2015Landmark

90-day mortality: 29.5% vs 29.2% (p=0.90), no benefit of EGDT

Health technology assessment (Winchester, England)RCTN=1,260

Extension

Follow-up studies, subgroup analyses, and real-world validation

The Sepsis-3 Task Force (Singer/Seymour 2016) redefined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, replacing SIRS criteria with the SOFA score. The qSOFA bedside screen (≥2 of: RR ≥22, altered mentation, SBP ≤100) was proposed for rapid identification outside the ICU. This reconceptualisation shifted focus from the inflammatory response to organ dysfunction.

Sepsis-32016Landmark

Redefined sepsis using SOFA; introduced qSOFA for bedside screening

JAMAConsensus0

Now

Current standard of care and ongoing research directions

Sepsis management emphasises early recognition, rapid antibiotics, and individualised resuscitation rather than protocolised targets. The Surviving Sepsis Campaign Hour-1 bundle recommends lactate measurement, blood cultures, broad-spectrum antibiotics, and fluid resuscitation within 1 hour. Debate continues over qSOFA's sensitivity in the ED versus the older SIRS criteria, and lactate-guided resuscitation remains under investigation.

Landmark Trials in This Story

ACCP/SCCM Consensus1992Landmark

American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis

Established SIRS criteria and sepsis definitions used for 25 years

Crit Care MedConsensus0

Rivers EGDT2001Landmark

Early goal-directed therapy in the treatment of severe sepsis and septic shock

In-hospital mortality: 30.5% vs 46.5% (p=0.009) favouring EGDT

NEJMRCTN=263

ProCESS2014Landmark

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

60-day mortality: no significant difference between EGDT, protocol-based, and usual care

NEJMRCTN=1,341

ARISE2014Landmark

Goal-directed resuscitation for patients with early septic shock

90-day mortality: 18.6% vs 18.8% (p=0.90), no benefit of EGDT

NEJMRCTN=1,600

ProMISe2015Landmark

Protocolised Management In Sepsis (ProMISe): a multicentre randomised controlled trial of the clinical effectiveness and cost-effectiveness of early, goal-directed, protocolised resuscitation for emerging septic shock

90-day mortality: 29.5% vs 29.2% (p=0.90), no benefit of EGDT

Health technology assessment (Winchester, England)RCTN=1,260

Sepsis-32016Landmark

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

Redefined sepsis using SOFA; introduced qSOFA for bedside screening

JAMAConsensus0

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Frequently Asked Questions

What changed from SIRS to Sepsis-3?+

SIRS criteria (1991) defined sepsis based on inflammatory markers (temperature, heart rate, respiratory rate, WBC). Sepsis-3 (2016) redefined sepsis as life-threatening organ dysfunction, measured by the SOFA score, replacing the overly sensitive SIRS criteria with a focus on organ failure rather than inflammation.

What happened to early goal-directed therapy for sepsis?+

Rivers' EGDT trial (2001) showed mortality benefit from protocolised resuscitation. However, three large multi-centre trials (ProCESS, ARISE, ProMISe) found no benefit of EGDT over usual care. The principle of early, aggressive treatment was preserved but the specific protocol was abandoned.