Introduction

The ARISE (Australasian Resuscitation In Sepsis Evaluation) trial was a landmark study aimed at evaluating the effectiveness of early goal-directed therapy (EGDT) compared to usual care in patients with severe sepsis or septic shock. Conducted across multiple countries, the trial sought to determine if EGDT could reduce all-cause mortality at 90 days.

Study Design

• Type: Multicenter, randomized controlled trial
• Setting: 51 hospitals in Australia, New Zealand, Finland, Hong Kong, and Ireland
• Participants: 1600 adult patients presenting to emergency departments with severe sepsis or septic shock
• Randomization: 1:1 ratio to either EGDT or usual care
• Blinding: Unblinded

Eligibility Criteria

Inclusion:
– Suspected or confirmed infection
– ≥2 Systemic Inflammatory Response Syndrome (SIRS) criteria
– Evidence of refractory hypotension or hypoperfusion
Exclusion:
– Limitation of therapy order preventing implementation of the study protocol
– Inpatient transfer from another acute healthcare facility
– Confirmed or suspected pregnancy
– Inability to start EGDT within one hour of randomization or continue EGDT for 6 hours

Interventions

– EGDT Group:
– Protocol modeled after the Rivers trial
– Placement of an arterial line and central venous catheter (CVC)
– ScvO2 monitoring
– Standardized algorithm for fluids, blood products, and dobutamine administration
– Usual Care Group:
– Treatment decisions made by the treating team without a specific protocol
– ScvO2 measurement not allowed in the first 6 hours
– Antibiotic therapy at the discretion of the treating team

Primary Outcome

– All-cause mortality at 90 days:
– EGDT: 18.6%
– Usual care: 18.8%
– Relative Risk (RR): 0.98; 95% Confidence Interval (CI): 0.80-1.21; P=0.90

Secondary Outcomes

– Median Stay Durations:
– Emergency Department (ED): 1.4 vs. 2.0 hours (P<0.001)
– Intensive Care Unit (ICU): 2.8 vs. 2.8 days (P=0.81)
– Hospital: 8.2 vs. 8.5 days (P=0.89)
– Organ Support:
– Invasive Ventilation: 30.0% vs. 31.5% (RR 0.95; 95% CI 0.82-1.11; P=0.52)
– Duration of Invasive Ventilation: 62.2 vs. 65.5 hours (P=0.28)

Key Findings

Limitations

• Unblinded Design: Potential for bias due to lack of blinding
• Lower than Expected Mortality Rate: Resulted in underpowering of the study
• Generalizability: Conducted in a heterogeneous environment, which may affect applicability to other settings

Conclusions

Primary Conclusion:
– EGDT did not reduce all-cause mortality at 90 days compared to usual care in patients with severe sepsis or septic shock.
– Clinical Implications:
– The ARISE trial, along with the ProCESS and ProMISe trials, supports moving away from EGDT as the default therapy for severe sepsis and septic shock.
– Emphasis on early identification, antibiotic administration, and appropriate fluid resuscitation remains crucial.

Impact on Guidelines

• The findings from the ARISE trial have influenced sepsis management guidelines, leading to a shift away from strict adherence to EGDT protocols while still emphasizing the importance of early and appropriate treatment for sepsis.