Narrator - Dr. Abel 00:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. This podcast Narrator - ? 00:11 is provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 This podcast contains general information for educational purposes only. This is not professional advice, and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - ? 00:27 And now on to the show. Dr. Sean Kane 00:31 Welcome to Episode 58 of HelixTalk. I'm your co host, Dr. Kane, and I'm Dr. Patel, and today's episode is entitled, Third time's the charm, redefining sepsis again, using sepsis three. So today we're talking about the relatively new sepsis criteria and guidelines for what exactly is sepsis. Dr. Khyati Patel 00:49 So Dr. Kane, I do not obviously practice in an acute care environment. So this idea and notion is very new to me, and I'm excited to talk about, you know, how the evolution of this definition has become and what it is now Great. Dr. Sean Kane 01:03 Well, why don't we start with a patient case? So let's say Dr. Patel that you were seeing a patient that presents to your clinic with shortness of breath, productive, cough, fever and chills, and we'll say that pneumonia is coming to acquire pneumonia is high up on your differential list. We'll say the patient has the typical past medical history of hypertension, hyperlipidemia, a diabetic, someone with end stage renal disease on hemodialysis, hasn't really been in the hospital, but certainly has some risk factors for getting sick and not having a great outcome from pneumonia. And you know, we'll say that their heart rate is a little tachycardic, 105 respiratory rate a little fast. At 25 they're saturating 92% on room air, and their blood pressure is on the lower side. So normally we'll say they run 130s 140s today, they're at 95 over 65 which is a mean arterial pressure of about 75 Do you have a chest X ray at your clinic that you work at? Dr. Khyati Patel 01:57 Oh yeah, we can put a stat one. So let's see what this patient has. All right, Dr. Sean Kane 02:01 so let's say you do your chest X ray, and it shows a likely right lower lobe pneumonia. And you know, the patient's not lightheaded, their blood pressure is low, but they're not confused. They're following commands mentally. They're completely alert and at their baseline. Dr. Khyati Patel 02:15 So chest X ray tells me it's a gold standard, so it tells me that patient has pneumonia, yeah. Dr. Sean Kane 02:21 And really the question that commonly comes up is, lots of people get pneumonia, but not everyone gets sepsis from their pneumonia. When we talk about sepsis, we're really referring to a disease state that isn't just from the infection, but it's kind of an exaggerated immune response to the infection. And really the question is, Does this patient have sepsis, or septic shock or severe sepsis, and if so, would we be more aggressive in their care in terms of going down a different treatment pathway than what we'd normally go with with just a normal patient? Dr. Khyati Patel 02:50 And I guess having tools to recognize the signs and symptoms and be able to define a patient would be very important, if I were to see this patient at a clinic, to triage them better whether they need to do walk in clinic or they need to be hospitalized, for that matter, and Dr. Sean Kane 03:05 for sure, you know, based on that patient's blood pressure, she probably needs to be evaluated for being in the hospital, right? And especially with her comorbidities like diabetes and end stage renal disease. But again, the question is, where does she end up in terms of, is it pneumonia, or is it pneumonia with sepsis or pneumonia with septic shock? Where does she stand? And that's really been a question that has been in flux for the last two and a half decades, in terms of what is sepsis and how to how do we define it and describe it and categorize patients? Right? So one thing that is Dr. Khyati Patel 03:37 clear is, what I know, with my limited knowledge of acute care management is that sepsis is different than bacteremia. Bacteremia is just the bacteria presence in the blood, right? Dr. Sean Kane 03:49 This is a huge misconception that sepsis means bacteremia. That's not true at all. So sepsis has nothing to do with bacteremia, although some patients who have sepsis will have bacteremia, bacteremia is not criteria to have sepsis. Dr. Khyati Patel 04:03 So like you said, Dr. Kane, we do have a new definition, but there has been some changes, you know, in history too. Can we give our listeners some idea of what was historically defined as sepsis? Dr. Sean Kane 04:15 So before 1991 there was no standard agreed upon definition of what was sepsis. So different people would call it different things, and that became really frustrating for researchers to do a study of septic patients, because no one agreed on what that meant. So in 1991 a publication was done where they finally defined and everyone agreed on what was sepsis. What they said was that sepsis was SIRS criteria, plus infection. And SIRS criteria is an acronym for systemic inflammatory response syndrome. There's basically four different criteria, either having a high or low temperature, most typically that you have a fever, your tachycardic heart rate above 90. You have a respiratory rate that is fast more than 20, or your PaCO2 is less than 32 so you're blowing off too much carbon dioxide. The fourth criteria is that you have an abnormal white blood cell count, either less than four or more, commonly, more than 12. Basically, they said that if you have two of these four things, so temperature, heart rate, respiratory rate, or white count, if you have two of the four that are abnormal, and we think you have an infection, we're going to call you as sepsis. Dr. Khyati Patel 05:18 And then there was a gradient of sepsis, right? So we had something called severe sepsis. What was that? Dr. Sean Kane 05:23 So? Severe sepsis was where you met the criteria for sepsis and you had some kind of organ dysfunction, hypoperfusion or hypotension, that could be anything from you meet the criteria for sepsis and you have altered mental status, you have a lactic acidosis, you have acute kidney injury, anything where you pick any tissue you want, if it's not working correctly because of low blood flow or hypoperfusion, then you count as having severe sepsis. Dr. Khyati Patel 05:48 And then I believe the septic shock was having the sepsis having some sort of organ dysfunction which was hypoperfusion related, and hypotension too. That was not corrected by just giving IVs to the point where patients now needed a medication, we call them pressors, to bring their blood pressures up. Dr. Sean Kane 06:07 Yeah. So really, what distinguishes a severe sepsis from a septic shock patient back in the 1991 criteria was basically, did you do okay if we gave you a big fluid bolus of normal saline or lactated ringers, or was your blood pressure bad, even after giving a lot of fluid, where you had to be started on norepinephrine, for example, or some other vasopressor? Dr. Khyati Patel 06:28 And so we practiced with that definition for about a decade, and then a decade later, we had a new definition. What was that? Dr. Sean Kane 06:35 Dr. Kane, yeah. So one of the frustrations that came out of the 1991 criteria is it was really easy to meet the criteria of sepsis. So for example, if I go out for a run, I'm going to be tachycardic, I'll have a high respiratory rate. And if I have a suspected infection of, let's say, a sinus infection, based on the criteria, I would theoretically meet that criteria for sepsis. But clearly, I'm not a septic patient in the sense of being at risk of dying from my infection. So based on that, they said, "You know what? Hold the phone — the SIRS criteria, two of the four SIRS criteria, are just too non‑specific." It does encompass almost all sepsis patients, but the problem is, it includes a bunch of other people who we don't really think meet our clinical criteria, clinical definition of sepsis. So what they did instead was they said, Okay, we still think that systemic infection is important. But instead of having a specific criteria of two of the four of whatever, we're going to leave it up to the clinicians, we're going to say, Okay, you get to use your clinical judgment, whether it's service criteria, white blood cell count, procalcitonin, CRP, altered mental status, some organ dysfunction, etc, the constellation of your clinical judgment. If you think that they have systemic inflammation based on your clinical judgment, and you think they have a suspected infection, we'll Dr. Khyati Patel 07:50 call that sepsis. Now. So let me guess, by putting the ball into the clinician's court, it was absolutely clear what sepsis needs, right? Dr. Sean Kane 07:58 Not at all, and that's really the problem. So it was really hard to classify these patients objectively, primarily for research and billing purposes, but just clinically to say yes or no they truly are septic or not. It wasn't objective enough, and that was by design, because we hated the SIRS criteria because they weren't specific enough. But then we end up on the other side of the spectrum, where it's really hard for everyone to agree, and that was the whole point of a definition in the first place. Dr. Khyati Patel 08:22 Yeah, you're creating a whole lot of gray situations over here when you say, well, we're going to leave it up to the clinicians to decide what it means. Dr. Sean Kane 08:29 And the good news, though, was, you know, back in 2001 we basically effectively had the same definition of severe sepsis and septic shock, so we kind of kept those things the same. It's just that we kind of redefined what sepsis meant at that point. Dr. Khyati Patel 08:43 So with this newer sepsis three definition, like we said, third time is a charm, and I am suspecting there are a lot of changes from former definitions. Dr. Sean Kane 08:51 Huge change here. So this was released in 2016 and the 2016 sepsis guidelines kind of endorsed, because it's actually endorsed by the same groups they endorsed the idea of what we could call now sepsis three, which was released in 2016 This is the third version of what is sepsis in terms of the definitions, and this was actually a pretty good change. So if you look at the guidelines, or look at the definition, the medical definition of sepsis is defined as a life threatening organ dysfunction due to a dysregulated host response to infection. Speaker 1 09:22 That's very straightforward, Dr. Patel, Dr. Sean Kane 09:25 so that's incredibly scientific. It's incredibly difficult to really discern that, especially if you're, you know, a pharmacy student trying to figure out, what does sepsis mean? Speaker 1 09:35 So let's break it down a little bit, shall we? Yeah. Dr. Sean Kane 09:38 So instead of that, I actually really prefer their version of a lay definition, which was a life threatening condition that arises when the body's response to an infection injures its own tissues and organs. Dr. Khyati Patel 09:49 So basically, what we used to call sepsis no longer is there. So patients are basically classified with sepsis only if they have organ dysfunction. Right? Dr. Sean Kane 10:00 So no longer do we have the criteria of some systemic inflammation, whether it's serious criteria or clinical judgment, plus infection. We kind of got rid of that. And our new terminology for sepsis is that you have to have some kind of organ dysfunction demonstrated, which was the older criteria for severe sepsis. But they kind of got rid of severe sepsis as a term. Now we just have sepsis, which is organ dysfunction caused by infection and septic shock. And I Dr. Khyati Patel 10:28 believe the septic shock essentially is still the same, where patients blood pressure is still not compensated with IV fluids, where they need Dr. Sean Kane 10:37 pressors. Exactly. So we still have the same concept with septic shock. It's just that we've redefined what sepsis means, and that's kind of the prerequisite of what is septic shock to understand what sepsis is in the first place. Dr. Khyati Patel 10:50 So I feel like the emphasis here is on the organ dysfunctions. Can we talk a little bit more about what they have defined and what all goes into calling it an organ dysfunction. Dr. Sean Kane 11:01 Yeah. So if we go back to our patient case, one of the problems in defining sepsis is we have a lot of treatments that are time sensitive. So starting antibiotics, giving IV fluids, reassessing the patient. These have to happen very quickly in septic patients to optimize the care of that sepsis patient. So in order to do that, you have to figure out who is septic and who is not septic. And sometimes it's very obvious, but really the tricky ones are the ones where it's not very obvious and you have to have a good clinical tool to help identify those patients, typically in the emergency room or in a clinic, that you can identify them quickly and start therapy quickly if it's not immediately obvious that they are a floridly septic patient. Dr. Khyati Patel 11:41 So I'm assuming the tools, or whatever criteria that we are going to discuss is more pertaining to something that is visibly evident, and not that we're waiting on labs to tell us whether this marker is up or down. Yeah, and Dr. Sean Kane 11:53 certainly we're still going to get the labs and we're going to use those to help with our differential diagnosis. But the best kinds of screening tools are the ones that don't require that you have lab values, like even SIRS criteria. You needed the white cell count to really see if they had that fourth criterion, and if they already met the first three, you didn't need it to say yes you have SIRS. But again, the SIRS criteria were really not specific. Dr. Khyati Patel 12:14 And the reason we are focused on identifying early on and starting treatment early on is because the evidence shows that treating patients with sepsis early on improves outcomes Absolutely. Dr. Sean Kane 12:26 So mortality is absolutely impacted by the timing of your antibiotics, the timing of your resuscitation efforts, which means giving fluids and potentially starting vasopressors. All of that matters. It's a very time sensitive process. Dr. Khyati Patel 12:39 So I know past weekend, we went out to a furniture store and got sofa, and then I saw that we're going to talk about qSOFA. That's one of the assessment scores. I believe the definition of qSOFA is different than my comfy sofa we got. Dr. Sean Kane 12:53 I would probably venture to guess so. qSOFA stands for quick Sepsis‑related Organ Failure Assessment. So there's qSOFA, and later we'll talk about SOFA. qSOFA is the quick version of SOFA. The sepsis‑3 recommendation is: first decide whether you suspect an infection; then use qSOFA as a rapid screen. qSOFA has three items (altered mentation, respiratory rate, systolic blood pressure). A GCS (Glasgow Coma Scale) less than 15 counts as altered mentation (not opening eyes to stimulation, not conversing normally, or not following commands). If any of those are abnormal, that is 1 point for qSOFA. Dr. Khyati Patel 14:07 And some of the previous markers, such as blood pressure and respiratory rates, do come as well, Dr. Sean Kane 14:13 correct. Absolutely. So the next thing in qSOFA is a fast respiratory rate. And unlike in SIRS, where they said the cutoff was 20, the new cutoff is 22 — so if you have a respiratory rate of 22 breaths per minute or higher, you count as having an abnormally high respiratory rate. And that would give you another point for qSOFA. Dr. Khyati Patel 14:34 And I believe another point is earn if the systolic blood pressure is equal to or lower than 100 millimeters of mercury, exactly. Dr. Sean Kane 14:41 And really, what qSOFA does is it's a very quick and easy screening tool that you can do during triage in an ER setting, where you don't have to get labs or anything crazy like that. And all you're doing is saying, 'Okay, this patient may or may not have sepsis, and I'm worried enough about it to do a qSOFA.' If the patient has two or three points (there are only three possible points), you have to do more workup to see: are they actually septic or not? Dr. Khyati Patel 15:09 And I guess that assessment is then done with not the quick qSOFA, but the actual SOFA, exactly. Dr. Sean Kane 15:15 So if you've earned two or three points from qSOFA, you progress on to do an actual SOFA. SOFA is a lengthier process in terms of giving points to the patient. It's based on your blood gas (ABG), your platelet count, bilirubin, blood pressure, GCS (Glasgow Coma Scale), serum creatinine and urine output. So clearly we have to draw blood and collect urine output for these patients — these are the components of the SOFA score. Dr. Khyati Patel 15:49 And so according to this SOFA score, what is considered sepsis then. Dr. Sean Kane 15:55 So what we're looking for is a change of two or more points in SOFA from your baseline. Typically, most patients with no significant past medical history will have a SOFA baseline of zero. If a patient's new SOFA score on presentation is two or more above baseline, that patient meets the objective definition of sepsis. Dr. Khyati Patel 16:29 And for example, let's say a patient comes with an organ failure already, for example, end stage renal disease. Then how do we view those patients? Dr. Sean Kane 16:38 So end stage renal disease is a really good example, because you get points for your urine output and your serum creatinine and SOFA. Exactly. So using that as an example, if I was an end stage renal disease patient with a very high serum creatinine and no urine output, my SOFA score would be at least four. That would be my baseline. So for that patient, like in our patient case example, she would have to have a sofa score of six or more to count as being septic because there would be two or more above her baseline. Dr. Khyati Patel 17:07 So so far, we define what an organ dysfunction means. Can we talk a little bit more about what a septic shock means according to this new definition? Yeah. Dr. Sean Kane 17:16 So unlike in 1991 and 2001 where basically septic shock had the same definition, they did update it for the sepsis‑3 criteria. So in this case, what they said is that you have to meet the sepsis definition — that means a change of SOFA score of two or more from your baseline — and you have to be hypotensive, requiring vasopressors, and you have to have a lactate greater than two despite getting adequate fluid resuscitation. Dr. Khyati Patel 17:41 Any particular reasons behind them focusing on lactate level with this new definition. Dr. Sean Kane 17:46 So you know, they went back and forth because some septic shock patients will and will not produce lactate. Most of the time they'll have a lactic acid level of two or more. Some of the older criteria and definitions and studies used lactate values of four or more, so it's a slightly more conservative value. But if they don't have an elevated lactate, it's possible other things are going on that may be clouding the picture. So they felt that having this lactate requirement would narrow down the kinds of patients that we're looking at a little bit more to the septic shock patient group, makes sense. And just for completeness, sake, IV fluids. In terms of what is inadequate resuscitation, we're talking about typically two to three liters of IV fluid, like normal saline. The actual dose is 30 milliliters per kilogram of body weight, given fairly quickly to the patient. But again, typically that's going to be about two to three liters of IV fluid. Dr. Khyati Patel 18:38 And so I'm assuming that the new definition has been adopted by some of the governing clinical organizations, absolutely. Dr. Sean Kane 18:47 So this new sepsis‑3 criteria was supported by the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM). Both organizations were involved in the development of the sepsis‑3 definition and in the Surviving Sepsis Campaign 2016 guidelines that adopted these definitions. Dr. Khyati Patel 19:16 So even after the adoption, maybe we should let our listeners know that you know, yes, these are the guidelines adopted by some of the well known or clinical organizations, but the fact that they go out and practice the hospitals might have their own guidelines, so make sure you focus on both, but be updated with the new changes Dr. Sean Kane 19:34 coming through. Yeah. I mean, keep in mind that these are relatively new definitions, criteria and things like that. So things like the US government are still making changes to adapt some of these billing and also research. So most of the previous research has used the older definitions, because these didn't exist yet. So the whole purpose of this is to make it easier to research this patient, group of sepsis patients, so that everyone is in agreement of objectively, how we define it. Things like. That. Dr. Khyati Patel 20:00 So maybe going back to our patient, if you all remember, it was a 65 year old patient with shortness of breath. The presentation was more pneumonia, like if we can then go by the definition, I think I'm going to jump at calculating the patient's cue so far. If you remember, the blood pressure was 95 over 65 (normal was ~130), and the respiratory rate was a little bit elevated at 25 — so here I think we have accumulated two points already, so I can say the patient's qSOFA score is two. Dr. Sean Kane 20:30 And remember, a qSOFA is our screening tool, so it doesn't mean she has sepsis. We have to proceed on to the SOFA. The purpose of qSOFA is to decide: is it worth doing a SOFA or not? Dr. Khyati Patel 20:41 And I think we kind of talked about the fact that because patient has an end stage renal disease, we will like to see a change in the baseline sofa score by either two or greater than two Exactly. Dr. Sean Kane 20:53 So her baseline will not be zero because of her end stage renal disease status. But if she has other organ dysfunction, this could be any of the organ systems that are included in SOFA — from ABG to platelets to blood pressure — all of these things are factored in. And if she gets at least two points on top of her baseline, then she would be classified as having sepsis. And this is clearly a very objective way to do it, to say yes or no, you either have it or you don't. You either have a change of two or more points or not. We've kind of gone away from the older 2001 definition of this clinical constellation of maybe you have these systemic signs of inflammation or not, right? Dr. Khyati Patel 21:34 So let's say, you know, we send bunch of labs over to the lab right now, and they're being calculated, and if she does have sepsis, can we clearly say, using the definition again, whether patient has septic shock or not? Dr. Sean Kane 21:46 So at this point, she does not have septic shock, but she certainly could, you know, be going in that direction. So in order for us to make that criteria of septic shock, she would have to be hypotensive with a mean arterial pressure less than 65 she would have to have a lactate level greater than two. But before we even look at those things, we have to give her some fluid. So the septic patients are going to get some amount of fluid. So 30 ml per kg, as I said, is a typical dose that we're going to give, if not more. So once we give her that minimum of, let's say, two to three liters of normal saline, typically, at that point we look at the MAP; if the mean arterial pressure is still low (less than 65) and her lactate is greater than two, At that point, that's when she would meet the definition of septic shock, and would consider things like vasopressors for her and many of the other adjunct therapies that we consider in a septic patient. Dr. Khyati Patel 22:37 Well, this is a very neat way to learn about what the new definition of sepsis involves, particularly focusing on the criteria for the organ dysfunctions and the quick scores that we can calculate to guide our clinical judgment better to kind of Dr. Sean Kane 22:53 summarize some of the content that we've talked about. So the sepsis criteria or definitions have changed now three times since 1991 the current definitions are called the sepsis three criteria, or definitions, and it describes sepsis and septic shock. And we no longer have the terminology of severe sepsis. Dr. Khyati Patel 23:12 And the qSOFA is a very quick screening tool to identify patients who may have sepsis. If the patient's qSOFA score is two or three, we do need to do more labs and get a confirmatory SOFA score to meet the definition of sepsis. Dr. Sean Kane 23:30 and that SOFA score is made up of many labs and vital signs that now objectively define sepsis, rather than relying solely on clinical judgment. We say a patient has sepsis if their SOFA score is two or more points above baseline (most patients have a baseline SOFA of zero). Dr. Khyati Patel 23:50 And like you alluded at the end, the septic shock is defined as meeting the sepsis definition, plus have hypotension that requires vasopressors. So again, in order to maintain that mean arterial pressure either equal to or greater than 65 and have lactate levels that are elevated greater than two despite having appropriate fluid resuscitation, great. Dr. Sean Kane 24:14 So I would encourage your listeners to check out our website, HelixTalk.com we have a couple references on there related to this episode, Episode 58 we'll have the actual document outlining the sepsis three definition, the 2016 surviving sepsis campaign, guidelines for sepsis. And also the authors of the qSOFA score made a website (qsofa.org) with an explanatory video outlining how they derived the criteria for qSOFA; they even provide an online calculator for the scoring system. We're also available at HelixTalk on Twitter. HelixTalk.com and we love the five star reviews and iTunes and emails with topic suggestions for future episodes. With that, I'm Dr. Kane, Dr. Khyati Patel 24:59 I'm Dr. Patel and as usual, study hard. Narrator - Dr. Abel 25:02 If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store. Search for HelixTalk and place your review there Narrator - ? 25:13 to suggest an episode or contact us. We're online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.