Defining a disease which doesn’t exist?

Systemic Inflammatory Response Syndrome Criteria in Defining Severe Sepsis

By Dr Grace Nisbet

Can we do better than simply thinking that sepsis is one disease with one bundle of treatments? Not yet.

The current working definition of systemic inflammatory response syndrome (SIRS) underpins our diagnosis and thus subsequent management of septic patients. This definition was introduced by a North American consensus conference in 1991 and is based on four variables; temperature, heart rate, respiratory rate and white blood cell count, of which two must be met to be defined as ‘SIRS-positive’, and despite being re-examined in 2001, has mostly remained unchanged (LITFL).

However, the SIRS concept is something we have forced on a diverse range of diseases and syndromes for our convenience and perhaps because of our limited range of effective treatments. It is a fairly blunt tool, SIRS, as a basis of sepsis diagnosis, is sensitive but not specific: for example this study suggested that over 90% patients admitted to ICU meet the SIRS criteria. Moreover, other patients such as the elderly and those on medication affecting respiratory rate, heart rate, white cell count and temperature, may not become SIRS-positive despite having an infection with resultant organ failure and we see this frequently but label it “unable to mount a response” or some other get out clause, do they in fact have a different disease, or a different host response to the pathogen?

The paper (editorial in Nature Reviews Neurology, Medscape editorial) we are going to talk about this week by our friends at The Alfred ICU examines the validity the SIRS criteria in the diagnosis of severe sepsis. It is a retrospective study, looking at 13 years of data (which brings its own worries) from the Australian and New Zealand Intensive Care Society Adult Patient Database which contains details of over 1 million patients from 172 ICUs. The study compares SIRS-positive patients with proven or suspected infections (based on APACHE III score) with similar patients also with proven or suspected infection but who are SIRS-negative (ie meet fewer than 2 of the SIRS criteria).

Astonishingly, the authors find that using on the SIRS criteria misses one in eight patients with severe sepsis and that whilst these SIRS-negative patients have a lower mortality the rate of death in hospital is disturbingly high. Furthermore, the paper also shows a linear relationship between mortality and the number of SIRS criteria met, which of course beggars the question of why the arbitrary figure of two SIRS criteria was chosen as the magic number for a patient to be deemed ‘SIRS positive’?

A very important paper.

What are we to do with the results though, in Cambridge?

First we need to think about whether our definitions of sepsis are correct, if we are not going to use the SIRS criteria, what definition should we use?

The Global Sepsis Alliance recently wrote “sepsis is a life threatening condition that arises when the body’s response to an infection injures its own tissues and organs” but does that really take us forwards and help us treat our patients?

We routinely use C-reactive protein and procalcitonin (as suggested by the Surviving Sepsis Campaign) as an aid to clinical decision making, but are there other biomarkers, will they help?

If, as the paper suggests, we are really missing the diagnosis of sepsis in 1 in 8 patients as a result of them being SIRS negative are these people being harmed – or do they end up with antibiotics and organ support anyway?

With the ‘Sepsis Redefinition Task Force’ due to report this month, what might a new definition of sepsis be, if not based around the SIRS criteria?

Perhaps some more fundamental questions are forced out of the undergrowth by this study…

How do we measure the dose of sepsis?

Is the syndrome of sepsis definable?

If we could define it better would it alter treatment?

But the most important, and first question will be, as always:

Is the methodology of this paper robust?

Some interesting links:

Adelaide Emergency Physicians Journal Club.

EMCrit resources on sepsis.

Sample book chapter by JLV.

Editorial from 2013 which predicted the results of this study.