Sepsis can be a difficult condition to diagnose thanks in part to non-specific criteria; the definitions of sepsis and septic shock were last revised in 2001. This February, the Journal of the American Medical Association (JAMA) published “The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)” to evaluate and update these definitions. (The definitions can be accessed at http://jama.jamanetwork.com/article.aspx?articleid=2492881.)

But how accurate are these definitions, and are they useful in clinical EM practice? ACEP Now medical editor-in-chief Dr. Kevin Klauer recently had a conversation with physicians who work with septic patients and are involved with sepsis survival care to get their opinions.

Moderator:

Kevin Klauer, DO, EJD, FACEP, chief medical officer–emergency medicine and chief risk officer for TeamHealth, executive director of the TeamHealth Patient Safety Organization, and medical editor-in-chief for ACEP Now

Participants:

Tiffany Osborn, MD, MPH, FACEP, serves on Centers for Disease Control and Prevention’s National Sepsis Task Force; member of National Quality Measures Technical Expert Panel for ACEP’s Clinical Emergency Data Registry and the ACEP EQUAL Network Sepsis Initiative; and representative for Surviving Sepsis Campaign

Donald M. Yealy, MD, FACEP, chair at Department of Emergency Medicine for the University of Pittsburgh/University of Pittsburgh Physicians; senior medical director, for Health Services Division of UPMC; and professor of emergency medicine for Clinical and Translational Sciences at University of Pittsburgh School of Medicine

John J. Rogers, MD, CPE, FACS, FACEP, vice president for ACEP; and co-ED medical director for Coliseum Northside Hospital, Macon, Georgia

Todd L. Slesinger, MD, FACEP, FCCM, FCCP, FAAEM, founding program director for the Emergency Medicine Residency at Aventura Hospital and Medical Center in Florida; and associate professor of emergency medicine and critical care at Florida International University

KK: We know that there were new sepsis definitions launched and published in February. What was the primary reason for drafting these new definitions?

DY: A group of experts primarily in critical care medicine from Europe and the United States had noted that it had been over a decade since the working definitions of sepsis in place had been evaluated. The experts found strengths and weaknesses with the previous definitions. It began not as a scheduled but as a not-surprising relook at a set of conditions.

KK: I appreciate that extra detail. Was there some critical event that happened, perhaps with the ProCESS [Protocolized Care for Early Septic Shock] trial? Do you think there was really something critical that happened that forced people to take a look and reevaluate?

DY: I do think that with all three trials [ProCESS, ProMISe [Protocolised Management in Sepsis trial] and ARISE [Australasian Resuscitation in Sepsis Evaluation trial] showing the overall improvement in sepsis care, there was a pocket of people who wondered whether it was all true or whether maybe the improvement is really a bit more muted than what was shown.

KK: Tiffany, given your work with the Surviving Sepsis Campaign, how do you see these definitions now being applied, and what are some of the potential obstacles to applying them to the Surviving Sepsis Campaign or guidelines?

TO: Part of the issue is that you have two ICU groups that came together and said, “We want to redefine what sepsis is.” There was a lot of consternation about the use of SIRS [systemic inflammatory response syndrome] as a definition because if you walked up the stairs too fast and had a cough, you could probably screen positive for SIRS. That, in essence, increases the number of patients you have in your denominator; if you’re looking for really sick patients, you have to get a lot more patients to find that subset you’re looking for.

It wasn’t until I went back and listened to Morgan on Scott Weingart’s podcast [EMTcrit.org] that I made this connection: These definitions were never intended to be used in the management of patients. A direct quote from the podcast is, “As discussed later, the SOFA [sequential organ failure assessment] score is not intended to be used as a tool for patient management, but as a means to clinically categorize a septic patient.” However, listed in their paper in big red letters is, “Screening for Patients Likely to Have Sepsis.”

TS: Maybe the terminology was bad, but Tiffany is right; qSOFA isn’t really a screening tool. It’s something you use once you already know someone has an infection. The definition authors propose it as a way to look at organ dysfunction, what we would call severe sepsis. You don’t apply qSOFA to every comer into the ED. First, you have to figure out if they’re infected, and then apply SOFA, which is a really complicated way to look at organ failure. SOFA was done in 1996. It’s barely younger than SIRS. They did this massive data crunch, and they came up with qSOFA as a way to say, “In my infected patient population, these are the people I should worry about more.” But you still have to find the infected population first.

KK: We’re still struggling to identify who actually has sepsis. The average reader and average emergency physician are at risk to interpret this new information to mean, “We’re moving away from SIRS, and instead we’re plugging in qSOFA as a screening tool,” even though a qSOFA was intended to be a risk stratification tool once you’ve identified those with sepsis.

DY: Kevin, I think you’ve hit the nail on the head. I don‘t think it’s a question of whether qSOFA is better or worse than SIRS; they’re intended for different purposes. qSOFA is new, and we don’t know how well it will stand up. They do different things.

JR: From the community physician perspective, the definitions aren’t particularly helpful. They seem to be more theoretical. I come away scratching my head thinking, “So, what am I supposed to do?” The answer is that you’re not supposed to do anything different than what you‘re already doing. I also worry about leaving out that severe sepsis group, those at high risk for deterioration, and identifying only those at a high risk of mortality (eg, septic shock).

KK: Maybe this whole change in definition is an academic discussion that has no applicability to the bedside. Does it move us any further along with our understanding of sepsis and our ability to diagnose it? I recall a quote by Niccolo Machiavelli in The Prince Book III, 1498: “Hectic fever [sepsis] at its inception is difficult to recognize, but easy to treat. Left untended, it becomes easy to recognize but difficult to treat.” I don’t think we’re much further along with identifying sepsis today than we were when he made this statement.

“At this time ACEP will reserve endorsement pending the response(s) to our feedback and suggestions. We also ask that moving forward that emergency physicians be included on this and future efforts given the high impact and frequency of sepsis, severe sepsis, and septic shock in the emergency department setting.”
—Michael J. Gerardi, MD, FAAP, FACEP, Past President, ACEP, letter to President of Society for Critical Care Medicine regarding release of consensus definitions for sepsis

TO: What the authors have done is very, very difficult, and I give them credit. But one of the problems is that they included only people who saw sepsis in one phase of the disease—the ICU guys. They basically said, “We’ll make the decisions and then send it out for you to comment on.” There was no North American EM group involved in creating or that has endorsed these definitions. There was no North American hospitalist group involved, and in fact, globally, there’s only one EM professional organization that endorsed the definitions. The people who see these patients at the most proximal stage of the disease weren’t included in the discussion. As Don points out, we’re in a business of sensitivity rather than specificity. Some think ACEP didn‘t endorse it because they weren’t part of the discussion. In my opinion, there are two reasons why ACEP didn’t give their endorsement: They don’t agree with the actual guidelines that are being drafted or the science behind it, and they don’t agree with the process.

KK: From the board’s perspective, John, was it political sour grapes? Why didn’t ACEP endorse the new definitions?

JR: The accusation that we were really just petulant children who were angry because we weren‘t invited to the party is not only dismissive, it’s patronizing and just frankly insulting. We didn’t agree with the process. We asked to be involved, and they said, “No, thank you,” which I think was a huge error on their part. More substantially, we don’t agree with their recommendations for a variety of reasons that were communicated to them. It was really disagreement on the substance.

DY: The failure in the process produced results that were incongruent with what an emergency physician thinks is most important. It isn’t the process; it’s the result that was created.

KK: The other issue we haven’t talked about is how the new definition of septic shock is exceptionally restrictive. It produces a group with a really high rate of mortality.

TS: If you look at the science critically, it looks like really good science. It looks like the authors did this amazing thing, and somehow, came up with qSOFA. But if you look at that final product, it doesn’t really work well for me as an emergency physician. The blood pressure part is simple, but they used a systolic of less than 100; we’re used to using less than 90. Their septic shock definition switched over to use mean arterial pressure (MAP), which makes it confusing. There are plenty of articles that show we’re really bad at agreeing on GCS [Glasgow Coma Scale] scores. How many of us who work in ERs know that everyone’s respiratory rate is 18? If you like historical quotes, in JAMA, 1957, Ross Kory wrote a cynical article about respiratory rate saying that it’s the biggest waste of time in medicine because everyone knows that those numbers aren’t accurate. Putting those three together may have seemed like it worked really well scientifically, but it makes for a really hard tool to use.

JR: When I first heard about qSOFA, I thought, “Great! This is going to make my life so much easier.” Then I looked at it and said, “You really did this by data mining. You haven’t studied it prospectively and validated it, and you want me to throw out SIRS.” Yes, I know SIRS isn’t the best thing since sliced bread, but I think at this point, it is premature to suggest that we should abandon SIRS for qSOFA.

KK: Clinical decision instruments based on associations—broad associations from large groups of patients, which are then extrapolated to one patient at the bedside—are frequently flawed.

DY: I think the Seymour paper [on the guidelines] comes right out and says, “Don’t use this now; it needs more testing prospectively.” I am certain we are going to see a deluge of papers in different settings looking at how this performs.

TO: This was based on retrospective EHR [electronic health record] data from more than 250,000 patients. However, there were some issues associated with that data that made them less than perfect. I want to make sure a couple of things are clear. The authors themselves say the definitions need prospective validation before being implemented. When we talk about qSOFA, we’re talking about a hypotensive, altered patient with tachypnea; it can be any two of those three things. You can take out tachypnea; we’ve already discussed the issues with respiratory rate. If you have an infected, hypotensive patient, or an infected, altered patient, that patient isn’t right; the janitor can tell you that the patient has a problem. When the authors say, “screening for patients likely to have sepsis,” they’re really defining sepsis as “people with infection or organ dysfunction.” qSOFA is easy to measure, doesn’t require labs, and is highly sensitive and highly specific for a bad outcome. But is this where we should start to risk stratify or where we should start our screening?”

KK: I want to hear from each of you about why you personally haven’t endorsed the definitions.

DY: It isn’t clear that this will improve care for patients in the early, undifferentiated phase of sepsis. It’s the front end not having a strong sensitivity value and, while being simpler, may have been too restrictive.

TS: For me, taking lactate and using it only in septic shock can confuse the general emergency physician, who can think, “Maybe lactate isn’t so important.” From a practical point of view, you cannot even use these “new definitions” to fulfill your SEP-1 (sepsis) quality measure or ICD10 coding requirements.

TO: Until this is prospectively validated, I think it has the potential to hurt patients; it definitely can hurt EM physicians and hospitals. National quality metrics often use mortality ratios, which equal observed mortality over expected mortality. Observed mortality is very easy; you can’t fake death. Expected mortality is based on diagnosis. So, if you’re using the new definition for sepsis, in which a hypotensive, septic patient would fit their definition of sepsis and not septic shock, and the government is using the previous definition for sepsis, your observed mortality is going to be much higher than expected.

KK: That’s a great lesson for avoiding the law of unintended consequences.

TO: These definitions are about measurement, not management. For emergency physicians, diagnosis tells us what to do; diagnosis equals decision. The next point has to ask, who we are missing? When you look at qSOFA, it’s easy to find what the consequences are for those whom we may not find. We use lactate as a screening tool. If you look at ProCESS, ProMISe, and ARISE, greater than 90 percent of those patients were screened with lactate and probably between 30 percent and almost 50 percent of patients were identified with lactate alone. If we don’t draw the lactate on patients who aren’t hypotensive, then how do we know how many we may miss?