article189

ARISE

"Early Goal-Directed Therapy in the Treatment of Septic Shock". The New England Journal of Medicine. 2014.

Clinical Question

Does early goal-directed therapy (EGDT) reduce all-cause mortality in patients with early septic shock presenting to the emergency department compared to usual care?

Bottom Line

In patients with early septic shock presenting to the emergency department, EGDT did not reduce all-cause mortality at 90 days when compared to usual care.

Major Points

Guidelines

At the time of the study publication, EGDT was included in international guidelines for the treatment of septic shock but this study suggests reconsidering its value as a standard of care.

Design

- Multicenter, randomized, parallel-group trial
- N=1,600 (EGDT group: n=796; usual care group: n=804)
- Setting: 51 centers in Australia, New Zealand, Finland, Hong Kong, and Ireland
- Enrollment: October 5, 2008 - April 23, 2014
- Follow-up: 90 days
- Analysis: Intention-to-treat
- Primary outcome: All-cause mortality within 90 days after randomization

Population

- Adult patients (≥18 years) with early septic shock (refractory hypotension or hypoperfusion) within 6 hours of emergency department presentation
- Interventions: EGDT group received specific protocol-based therapies for 6 hours; usual-care group treatments were determined by treating clinicians without a protocol
- Exclusion criteria: Significant limitations to treatment (e.g., DNR status), eligible life expectancy less than 90 days, pregnancy, transfer from another hospital with septic shock, acute cerebral vascular event, acute coronary syndrome, acute pulmonary edema, cardiac arrhythmias, status epilepticus, drug overdose, traumatic injury, burn injury, surgery or interventional radiology within the past 12 hours, contraindication to central venous catheterization, and enrollment in another interventional trial

Outcomes

- Primary: All-cause mortality at 90 days (EGDT: 18.6%, usual care: 18.8%; P=0.90)
- Secondary: No significant differences in survival time, in-hospital mortality, duration of organ support, or length of hospital stay

Criticisms

- The implementation of the EGDT and usual-care protocols might have differed across the diverse settings within multicenter trials, which may affect reproducibility of the study results.

Funding

National Health and Medical Research Council of Australia and the Alfred Foundation. ScvO2 monitors loaned by Edwards Lifesciences without further involvement.