Monday, June 01, 2015

The ProMISe trial in perspective

I'm a little late with this. This is the third of the three new randomized trials of early goal directed therapy (EGDT) for septic shock. From the NEJM article:


We enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01; 95% confidence interval [CI], 0.85 to 1.20; P=0.90), for an absolute risk reduction in the EGDT group of −0.3 percentage points (95% CI, −5.4 to 4.7). Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit. There were no significant differences in any other secondary outcomes, including health-related quality of life, or in rates of serious adverse events. On average, EGDT increased costs, and the probability that it was cost-effective was below 20%.


In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome.

These trials, the other two being ProCESS and ARISE, have stirred some over reaction. Instead of hyping the issue with statements like “EGDT is dead” a more nuanced approach might be more informative. As I pointed out in my recent reaction to the ARISE results:

What was actually being compared in this study? To me it was strictly protocolized EGDT versus EGDT minus the SVO2 monitor with more room for clinical judgment.

In perspective

What do the Rivers study, ProCESS and ARISE tell us? Here's my take:

Volume assessment remains important but the best way to do so is unknown. Do it via CVP, physical exam or other means, however you will.

Assessment of tissue perfusion is important but the best method is unknown, whether via SVO2, lactate monitoring or bedside clinical examination.

Lower transfusion targets can be applied to septic shock just as in other conditions.

Since publication of the Rivers study “usual care” has risen to the standard of EGDT due to uptake of the Surviving Sepsis guidelines.

Guidelines and pathways must leave room for clinical judgment if evidence is to be applied for all it's worth.

EGDT is not dead. The notion is sound. How best to set resuscitation goals and monitor their achievement is not as simple as some have thought.

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