Sepsis 3.0 – No thank you

First10EM sepsis 3.0 no thank you sofa

Thought you had sepsis all figured out? Not so fast. The Third International Consensus Definitions for Sepsis and Septic Shock were just released, and can be read here for free.

The new sepsis definitions:

  • Sepsis: Life-threatening organ dysfunction caused by a dysregulated host response to infection
    • This definition requires you have a way to identify organ dysfunction:
  • Organ dysfunction: an acute change in total SOFA score ≥2 points consequent to the infection
  • The SOFA score? Actually, the sequential organ failure assessment score. You can check it out on MDCalc. To measure this, you need a bunch of laboratory and clinical variables:  PaO2, FiO2, platelet count, glasgow coma scale, bilirubin, blood pressure and creatinine.
  • qSOFA: SOFA has too many variables, so they give us a screening tool: hypotension (SBP ≤ 100mmHg), altered mental status (GCS ≤ 13), and tachypnea (resp rate ≥ 22)
  • Septic shock: Sepsis with persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and having a serum lactate level >2 mmol/L (18 mg/dL) despite adequate volume resuscitation

My first question: Why do we need these new definitions?

Sepsis is a broad, syndromic term that is difficult to define. Distinguishing sepsis from uncomplicated infection, which is a primary goal here, is a very reasonable thing to do. Clearly there are patients that meet the current definition of “sepsis” who we don’t worry about (think flu season), whereas we have all seen sick patients that don’t meet SIRS criteria. No one loves SIRS.

However, I question the clinical need for a new definition. (Refining research definitions is a different topic.) I have not seen confusion about sepsis leading to bad clinical outcomes.

The authors of this paper make two arguments for the need for these new definitions. First, they state that public awareness of sepsis is poor. Although the public may not understand our complicated sepsis terminology (most medical students don’t), the number of patients who come to the emergency department because they are worried about an infection clearly indicates that the public is aware of serious infectious diseases. Furthermore, making the definition highly technical and based on laboratory findings will do nothing to help the public understand sepsis.

The second argument these authors put forth is that “health care practitioners require improved clinical prompts and diagnostic approaches to facilitate earlier identification and an accurate quantification of the burden of sepsis”. I am not sure where the evidence is that we need more prompts. I do know that every sepsis expert has argued that ProCESS, ARISE, and ProMISe all failed to show a benefit to protocolized care because we are getting so good at treating sepsis. So if we are so good at treating sepsis, and sepsis outcomes are improving under the current definitions, what is the urgent need for a new definition?

How good are these new definitions?

So how good is this new SOFA score? Well, in a large retrospective database review, SOFA had a higher association with mortality than SIRS in ICU patients (area under the curve 0.74; 95% CI, 0.73-0.76 versus  0.64; 95% CI, 0.62-0.66). However, this was not compared to what we actually use: clinical judgement. More importantly, outside of the ICU, SOFA and SIRS were the same! (Area under the curve 0.79; 95% CI, 0.78-0.80 versus 0.76; 95% CI, 0.75-0.77.) So for our emergency department patients, there is no difference between this new, more complicated system and what we are already using.

What about the value of the qSOFA score? It does have similar predictive value to the SOFA score (although it hasn’t been prospectively validated) and I like that it is fully clinical.  But does it really help us? How many hypotensive patients with altered mental status were you missing the diagnosis of sepsis in? I think this is just taking the most obvious aspects of our clinical judgment and repackaging it as a score. I can’t imagine that qSOFA will be beat physician judgement in a prospective trial.

How bad is SIRS?

Is SIRS helpful? I have never been a huge fan of SIRS, but this is a quote from the paper: “the current use of 2 or more SIRS criteria to identify sepsis was unanimously considered by the task force to be unhelpful.” This is an interesting statement. I agree that SIRS criteria are neither sensitive nor specific. However, if they are truly unhelpful, how exactly have we been identifying sepsis for the last decade? I have diagnosed and treated hundreds of patients with sepsis using the SIRS criteria. How could they possibly be completely unhelpful? I admit that I use clinical judgment in addition to the SIRS criteria. The heart rate of 115 in a 25 year old with an obvious influenza picture worries me less than the heart rate of 90 in the 80 year old with fever and some mild abdominal pain. However, I am sure the same clinical judgement will apply when interpreting the SOFA score.

Funny enough, for all that they hate SIRS, the new definition of sepsis still includes SIRS. In order to have sepsis you have to have a SOFA score ≥ 2, but you also need an infection. How do you diagnose infection? Changes in temperature, white blood cell count, heart rate, and respiratory rate. In other words, the SIRS criteria.

Is it worth the work?

I don’t think that the current definition of sepsis is ideal. However, there is nothing in this paper to convince me that the new definitions are any better. Changing the definition of sepsis is not a trivial matter. A lot of money has been spent developing sepsis protocols around the world. All of our current research uses the old definitions. Without evidence that these new definitions result in patient oriented clinical benefit, I see no reason to adopt these definitions into daily emergency medicine practice.

Discussion

I don’t completely disagree with these authors. They recognize that “there are inherent challenges in defining sepsis and septic shock”. Sepsis is a very broad term, applied to a heterogenous, incompletely understood condition. However, I am not sure that these new definitions will help my patients. I want definitions that change my management. At this point, the definitions that guide management should still be those used in the clinical trials. (This is the root of the whole lactate 2 versus 4 debate. It’s all well and good to change the definition to 2, but when the trials used 4, that is obviously the number we should be using to guide our clinical management.)

The authors also state that “neither qSOFA nor SOFA is intended to be a stand-alone definition of sepsis”, which given the reported test characteristics is probably a good thing, but it also makes these “definitions” a lot less defining.

Bottom line

Without prospective evidence that new definitions will help my patients, I will not be adopting these new definitions into practice.

Could they be helpful? Sure – but prove it to me. Sepsis is currently very well treated. New definitions could help, but they could also harm. We should not be in any rush to change.

I will continue using clinical judgement, which include SIRS, to diagnose sepsis. I will continue to provide early, empiric antibiotics. I will continue to resuscitate my patients. For now, these new definitions can stay where they belong: amongst the academics reclining on their office SOFAs.

Other Sepsis 3.0 opinions:

Josh Farkas goes over his top 10 problems with the new sepsis definitions on PulmCrit (and its really good) (added Feb 29, 2016)

I also briefly review one of the papers that is used to criticize SIRS in my post: Is SIRS really that bad? (added Mar 4,2016)

Salim covered these new definitions on REBEL EM

There is also an excellent post on St. Emlyn’s

Lauren Westafer and Jeremy Faust somehow released a FOAMcast before the paper was even released

May 1, 2016 Update: Some more posts that have covered sepsis 3.0:

Sepsis is not a disease on intensive care network

EMCrit #169: Sepsis 3.0 with Merv Singer and EMCrit Wee: Cliff Deutschman with additional thoughts on sepsis 3.0

References

Shapiro N, Howell MD, Bates DW, Angus DC, Ngo L, Talmor D. The association of sepsis syndrome and organ dysfunction with mortality in emergency department patients with suspected infection. Annals of emergency medicine. 48(5):583-90, 590.e1. 2006. PMID: 17052559

Singer M, Deutschman CS, Seymour CW. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 315(8):801-10. 2016. PMID: 26903338 [free full text]

ProCESS: Yealy DM, Kellum JA et al. A randomized trial of protocol-based care for early septic shock. The New England journal of medicine. 370(18):1683-93. 2014. PMID: 24635773

ARISE: ARISE investigators. Goal-directed resuscitation for patients with early septic shock. The New England journal of medicine. 371(16):1496-506. 2014. PMID: 25272316

ProMISe: Mouncey PR, Osborn TM, Power GS. Protocolised Management In Sepsis (ProMISe): a multicentre randomised controlled trial of the clinical effectiveness and cost-effectiveness of early, goal-directed, protocolised resuscitation for emerging septic shock. Health technology assessment (Winchester, England). 19(97):1-150. 2015. PMID: 26597979

Author: Justin Morgenstern

Community emerg doc, FOAM enthusiast, evidence junkie “One special advantage of the skeptical attitude of mind is that a man is never vexed to find that after all he has been in the wrong.” - William Osler

14 thoughts on “Sepsis 3.0 – No thank you”

  1. Thanks for the post Justin

    Agree – “same shit, different shovel!”

    We do need a robust, common language to ensure we are on the same page when communicating about these patients.

    In a small hospital with variable skill, knowledge etc I think a simple “score” may help to clarify issues
    Less useful in big units with lots of smart teams
    C

    Like

    1. Thanks Casey
      I agree – and I don’t think that the current sepsis definitions are ideal.

      This post is mostly a response to the excitement I have seen about this, perhaps bolstered by our FOAM community. To me, this is the kind of paper that should be presented at a conference that only the sepsis research geeks attend. And no one should even hear about it until it has actually been integrated into studies.

      Could these new definitions be better – sure. But there is no reason to be jumping on these outside of clinical research at this point. I worry that our enthusiasm could get away from us, and we will see sepsis protocols changing around the world before there is really any evidence.

      Like

  2. great post. I share the same concerns, and see some issues with the new definitions & where we go from here. I can not help but wonder if this is a response to the newly minted & watered down sepsis definitions by CMS and a way to keep the pendulum swinging.

    There is still significant mortality with a score of one for qSOFA, and in a “zero miss” societal mindset, I can not possibly see this being broadly rolled out until more solid data comes out. On one hand, if the willingness to less aggressively treat everyone slows, mortality will slowly creep back up as some sickies will sneak up on us. On the other, our current state of every elevated INR with a fever & tachycardia being considered severe sepsis and needing aggressive resuscitation will increase cost on multiple fronts and provide unnecessary care.

    So, understanding that we live in an imperfect society, what is the lesser evil?

    To me, when you have a significant mortality associated with a disease entity (say, transient hypotension in the setting of pyelo), I’d rather have over evaluation than undertreatment. The current CMS measures are for admitted patients, and allows some wiggle room to think – in theory, if you say in the chart “I don’t think this INR bump is from sepsis” – the patient should not get counted toward your severe sepsis numbers anyway.

    Make no mistake, I applaud the authors for fighting overdiagnosis and overtreatment, but I think there are more productive ways to do it without affecting patients that would otherwise slip under the radar using qSOFA: Off the top of my head, the use of POCUS-guided resuscitation, early pressor usage, perhaps looking at short stay / obs units for “weak” sepsis admits (& associated outcomes), discouraging the use of vanco/zosyn as front line anti-microbial activity, and early transition to PO antibiotics (perhaps even in the ED). There are other ways to work within the confines of the current system other than going completely against the grain on this one.

    /end rant.

    Like

  3. Metabolic Theory of Septic Shock
    Please do a search for the above

    Core tip: For decades septic shock has been attributed to an over-active immune response. However, immune modulation has failed to reduce mortality, casting doubt on a direct causal role for the immune response in the development of septic shock. A closer look suggests that septic shock is the result of a generalized build-up of hydrogen peroxide, a toxic cellular by-product generated as a consequence of the hypermetabolic state that accompanies a systemic immune response. This finding points to the systemic accumulation of hydrogen peroxide as a significant risk factor for the development of septic and non-septic shock syndromes.

    Like

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