ARISE study: EGDT no better than standard care

periph-vasoactive-iconThe second of three major trials assessing early goal directed therapy (EGDT) in sepsis – the Australasian ARISE Trial – has been published.

ARISE tested the hypothesis that EGDT, as compared with usual care, would decrease 90-day all-cause mortality among patients presenting to the emergency department with early septic shock in diverse health care settings.

There was no difference in all-cause mortality at 90 days between EGDT and standard care, in keeping with the results from ProCESS.

Why are the results so different from Rivers’ original EGDT study? The authors explain:


“although our results differ from those in the original trial, they are consistent with previous studies showing that bias in small, single-center trials may lead to inflated effect sizes”

This cautions us all against making major practice changes based on one single centre study. In critical care we’ve learned this before with subjects like tight glycaemic control and Activated Protein C. However I do believe that the things we know to be of benefit – early recognition, source control, antibiotics, and fluids – are effective in making ‘standard’ care “as good as” EGDT because of heightened awareness of the condition and its treatment, and Rivers’ initial study and the subsequent Surviving Sepsis Campaign Guidelines have played a major role in raising that awareness.

The ARISE study is appraised by Wessex’s The Bottom Line and discussed on the one and only EMCrit podcast.

The ARISE Investigators and the ANZICS Clinical Trials Group.
Goal-Directed Resuscitation for Patients with Early Septic Shock
N Engl J Med. 2014 Oct;:141001063014008.Full Text


Background
Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock. However, its effectiveness is uncertain.

Methods In this trial conducted at 51 centers (mostly in Australia or New Zealand), we randomly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care. The primary outcome was all-cause mortality within 90 days after randomization.

Results Of the 1600 enrolled patients, 796 were assigned to the EGDT group and 804 to the usual-care group. Primary outcome data were available for more than 99% of the patients. Patients in the EGDT group received a larger mean (±SD) volume of intravenous fluids in the first 6 hours after randomization than did those in the usual-care group (1964±1415 ml vs. 1713±1401 ml) and were more likely to receive vasopressor infusions (66.6% vs. 57.8%), red-cell transfusions (13.6% vs. 7.0%), and dobutamine (15.4% vs. 2.6%) (P<0.001 for all comparisons). At 90 days after randomization, 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group, for rates of death of 18.6% and 18.8%, respectively (absolute risk difference with EGDT vs. usual care, -0.3 percentage points; 95% confidence interval, -4.1 to 3.6; P=0.90). There was no significant difference in survival time, in-hospital mortality, duration of organ support, or length of hospital stay.

Conclusions In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days.