Tuesday, June 02, 2015

What is sepsis anyway?

A study recently published in NEJM evaluated SIRS criteria in severely ill patients with infection. The paper is confusing and its implications for present day practice are unclear, yet it is likely to garner considerable discussion.

From the abstract:


The consensus definition of severe sepsis requires suspected or proven infection, organ failure, and signs that meet two or more criteria for the systemic inflammatory response syndrome (SIRS). We aimed to test the sensitivity, face validity, and construct validity of this approach.


We studied data from patients from 172 intensive care units in Australia and New Zealand from 2000 through 2013. We identified patients with infection and organ failure and categorized them according to whether they had signs meeting two or more SIRS criteria (SIRS-positive severe sepsis) or less than two SIRS criteria (SIRS-negative severe sepsis). We compared their characteristics and outcomes and assessed them for the presence of a step increase in the risk of death at a threshold of two SIRS criteria.


Of 1,171,797 patients, a total of 109,663 had infection and organ failure. Among these, 96,385 patients (87.9%) had SIRS-positive severe sepsis and 13,278 (12.1%) had SIRS-negative severe sepsis.

Wait a minute. Here's where things get confusing. In the opening sentence the authors defined sepsis as having at least two SIRS criteria while in the results speak of “SIRS-negative severe sepsis.” Going on:

Over a period of 14 years, these groups had similar characteristics and changes in mortality (SIRS-positive group: from 36.1% [829 of 2296 patients] to 18.3% [2037 of 11,119], P less than 0.001; SIRS-negative group: from 27.7% [100 of 361] to 9.3% [122 of 1315], P less than 0.001). Moreover, this pattern remained similar after adjustment for baseline characteristics (odds ratio in the SIRS-positive group, 0.96; 95% confidence interval [CI], 0.96 to 0.97; odds ratio in the SIRS-negative group, 0.96; 95% CI, 0.94 to 0.98; P=0.12 for between-group difference). In the adjusted analysis, mortality increased linearly with each additional SIRS criterion (odds ratio for each additional criterion, 1.13; 95% CI, 1.11 to 1.15; P less than 0.001) without any transitional increase in risk at a threshold of two SIRS criteria.


The need for two or more SIRS criteria to define severe sepsis excluded one in eight otherwise similar patients with infection, organ failure, and substantial mortality and failed to define a transition point in the risk of death. (Funded by the Australian and New Zealand Intensive Care Research Centre.)

What do these findings mean? Anything new here? Here's what I get from the paper:

The mortality for critically ill patients with infection has been going down over the years. Well, nothing new there. We already knew that from ProCESS, ARISE and other studies.

Mortality risk increases with the number of SIRS criteria present but there is nothing particular about two criteria.

SIRS criteria do not capture all infected patients who need aggressive care. That may become important as sepsis care becomes increasingly performance driven and diagnostic criteria, used in a wooden literal sense become a substitute for thought.

The authors suggest that the definition of sepsis be broadened and not be restricted to patients with SIRS. Nothing new here either, because outside the performance and coding worlds that idea has already been implemented. As of 2012 the Surviving Sepsis guidelines no longer require SIRS criteria, instead defining sepsis as proven or suspected infection plus “some” of a long list of conditions including but not limited to SIRS.

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