Sepsis 3.0 – No thank you

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.

Also, check out this post discussing the problems with the most recent surviving sepsis campaign targets.

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