Episode 21- Updates and Controversies in the Early Management of Sepsis and Septic Shock

Disclaimer: This is the unedited transcript of the podcast. Please excuse any typos. Jeff:  Welcome back to Emplify, the podcast corollary to EB Medicine’s Emergency Medicine Practice. I’m Jeff Nusbaum, and I’m back with my co-host, Nachi Gupta. This month, we’ll be talking Updates and Controversies in the Early Management of Sepsis and Septic Shock. We have a special  episode for you this month… We’ve brought Dr. Jeremy Rose, one of the peer reviewers, and a sepsis expert, on with us to talk through the content this month. Jeremy: Dr. Jeremy Rose here. Thanks for having me in on this conversation.  I’m always happy to talk about this topic because it’s clearly important.  There’s a great deal of confusion around sepsis and I hope that in the next couple minutes we can clarify things in a way that really help your average front line doc trying to get it right. Nachi: So Dr. Rose, before we get started, tell us a bit about your background and your interest in sepsis… Jeremy: I’m the Assistant Medical Director and Sepsis Chair at Mount Sinai Beth Israel in Manhattan.  For those listening, my hospital probably looks a little bit like yours.  We’re busy, interesting, and just a little rough around the edges.  We like it that way.  More importantly, though, we mirror the national averages regarding sepsis.  Roughly half of in-hospital mortality is associated with septic  in some fashion.  Pretty incredible when you think about it.  Half. Jeff:  Sepsis chair... clearly this is an important topic if it warrants it’s own chair at a major hospital in NYC. But getting back to the article this month. This month’s issue was authored by Faheem Guirgis, Laurent Page Black, and Elizabeth DeVos of the University of Florida, Department of Emergency Medicine. Nachi: And it was peer reviewed by Michael Allison, Assistant Director of the Adult ICU at Saint Agnes Hospital, and Jeremy Rose and Eric Steinberg of Mount Sinai Beth Israel. Jeff: So as well all know Sepsis is bread and butter emergency medicine, but, what is sepsis?  It seems that every month or so we have a new guideline, bundle, definition, or whatever… I think it’s best to start with the basics -  At its core, sepsis is a dysregulated response to infection that can be life-threatening. Nachi: Right and it’s the combined inflammatory with immunosuppressive features of sepsis that lead to the devastating organ dysfunction and even death. Optimal management of septic patients has been a source of intense research, stemming from the landmark study by Rivers in 2001. Jeremy, can you give us a little historical context there? Jeremy: Rivers was a real pioneer.  He found a 16% mortality reduction with randomization to an early aggressive care bundle.  Amazing work.  That being said, many components of that bundle have since been disregarded.  For example, Manny Rivers would measure CVP in all of his patients, something we rarely do. Nachi: Not to cut you off and steal your thunder there, but we’ll get to the most recent updates in management shortly. Let’s first talk definitions and terminology, and specifically, diagnosis, which is definitely a big elephant in the room. As Jeff mentioned a few minutes ago, diagnostic criteria have undergone so so so many changes. Jeff: Yes it has! 1991 marked the first standardized definition.  Then in 2001, sepsis-2 was introduced.  In 2014, the Society of Critical Care Medicine and the European Society of Intensive Care Medicine started a task force, and by 2016, updated definitions were out again! Sepsis-3!! A lot of this came after the realization that SIRS was just too broad and was overly sensitive and non-specific. Jeremy, why don’t you take us through Sepsis 3. Jeremy: So just to back up a little and frame this: Here’s the fundamental problem:  As we likes to say, “there’s no troponin for sepsis.”  And if you look at our patients, we tend not to miss the hypotensive, tachycardic, febrile patient.  We know they’re septic.  But how do we find the ones who don’t look as sick.  Frequently elderly, possibly with normal-ish vitals and no fever.  Those can be a lot harder to spot, but they may indeed be septic.  Also, for research purposes we have to have a common definition, so Sepsis 3 came up with something called the SOFA score. The problem with the SOFA score is that its difficult to perform in the ED.  It has parameters like bilirubin that often aren’t available when we want to screen out very sick patients.  Fortunately there is the abridged version qSOFA, which identifies non-icu patients who are at high risk of inpatient mortality. So here it is, and if you get one thing from this episode, this is it: There are ONLY 3 criteria to the qSOFA.  3 Criteria. RR > 22; AMS; SBP <= 100. That’s it. If you have two of these criteria, you are up to 14 times more likely to die of sepsis during a hospital admission. That’s pretty profound; these patients are very sick.  This is meant to replace SIRS.  It also captures  a much sicker population than the patients included in the Medicare definition. Jeff: So why do you think these parameters turn out to be so useful? Jeremy:  Drilling down into these criteria you can see the pathophysiology at work. Obviously, SBP < 100 means sick.  Interestingly, an elevated RR also turns out to be prognostic, because you’re seeing the compensation for an underlying acidosis.  WHen you see a patient breathing quickly, it’s either from a primary respiratory problem or them trying to relieve an underlying acidosis. The caveat here is that you have to check it. At our hospital in southern Manhattan, patients tend to breathe around 16.  At our hospital in northern Manhattan they like to breath around 18. It’s probably because the air is thinner.  Seriously though, you have to actually measure RR for this to work. Temp is not in QSOFA but we should be checking that too. And I mean checking it by putting something that measures temperature inside the patient. We’ve looked at the forehead and tympanic thermometers and in real world conditions, they tend to underestimate by a degree or more. Think about that. A patient with a headache and a temperature of 99.5 is a very different patient than one with a temp of 100.5.  Make sure you measure temperature. Nachi: Very true and these two patients can definitely go down very different management pathways! Rounding out our discussion on sepsis-3. We should note that severe sepsis is now a term of the past under Sepsis-3. And sepsis-3 redefined septic shock as “hypotension not responsive to fluid resuscitation” with the added requirement of vasopressors to maintain a MAP greater than or equal to 65 and with a lactate > 2. So quite a few changes! Jeff: And Jeremy, sticky topic coming up here. Center for Medicare and Medicaid Services (or CMS) quality measures - They haven’t really caught on to and adapted to Sepsis-3 yet, have they? Jeremy:  The CMS mandate is based on the presence of SIRS criteria. Sepsis 3 is based on SOFA.  This is definitely confusing.  Part of the challenge in discussing this topic is separating out the QI guidelines from what is actually relevant to patient care based on the latest evidence-based medicine. Nachi: That seems fair.  We’re really going to put you in an uncomfortable spot for a second and push you here Jeremy. Do you have any insight into why CMS isn’t interested in following the mountains of research that have led to sepsis-3? Is there a reason they are sticking to their current criteria? Jeremy:  I think some of it is the slow pace of bureaucracy and the time that it takes to develop a consensus on management.  Even if we can agree on who is septic, it’s really hard, if not impossible to link the care to a pay-for-performance metric which is what CMS ultimately would like to see.  That’s not how Sepsis-3, or for that matter, SIRS, was designed to be used.  You’re trying to take a tool which was originally designed for research and mold them into a tool used for pay for performance. Nachi: What a struggle. The CMS metrics are slightly different from the 2001 sepsis guidelines also. Take a look at Table 2 of the article for a quick comparison of sepsis-3, 2001 sepsis, and cms side-by-side. And for those on twitter, we’ll be sure to tweet this table out too for your review. Jeff: With so many different scores and definitions, I think that adequately sets the stage for the challenge this month’s authors faced coming up with real evidenced based guidelines. Nachi: Oh absolutely.  And to make matters worse - this is a HUGE problem. We’re talking up to 850,000 ED visits annually in the US, and 19 million cases worldwide. Compounding this, sepsis results in death in approximately 1 out of 4 cases. Not only is it lethal, it is also very costly -- 17 billion dollars per year in the US alone! Jeff: And don’t forget importantly the 30-day hospital readmission rate. Sepsis is coming in at a higher readmission rate and cost per admission than acute MI, CHF, COPD, and PNA. Nachi: Let’s speak briefly on the etiology and pathophysiology of sepsis: we all know that sepsis is due to local infections that then become systemic. Previously, it was believed that the bacterial infection itself was the cause of the clinical syndrome of sepsis. However, we now know now that the syndrome of sepsis is due to the inflammatory and immunosuppressive mediators that were triggered by the infection. Normal immune regulatory safeguards fail and this leads to the syndrome. And interestingly, several studies have shown that critically ill septic patients experience reactivations of specific viruses that were previously limited to patients with severe immunosuppression. Jeff: Definitely something to look out for in your criticall...