So unlike some of the things you've heard about in the last few days, where many of you don't routinely care for brain death examinations, for example, which is something that I don't do, what I'm going to talk about now probably most of you are pretty comfortable with. So I'm going to, I think, run through this, because I think, again, most of you are pretty comfortable with the concepts of treating patients with life-threatening infections. And I'm happy to slow down if anybody disagrees with anything, but this is really, in most cases, a pretty straightforward talk. And the most challenging thing about treating somebody with sepsis is really making the diagnosis. And once you've done that, it's not complicated. So the only disclosure that I want to highlight is that, and I think I mentioned this at the beginning, is that I feel strongly that standardized care is better than random care for most patients. And so some of what I'm going to say is biased by that. So 30 years ago, before I was in practice, we had lots of terms to define severe infections. And roughly 25 years ago, people came up with a better but very flawed definition for sepsis that's listed up over here. I'm not going to go through it, because it's mostly flawed. The idea was that you could perhaps identify patients who were more likely to benefit from aggressive treatment. And again, the biggest challenge about treating somebody with sepsis is that we don't have a sepsis level. We're still stuck with lousy definitions and, from my own standpoint, lousy screening tools. And the most read paper in JAMA in the last decade was the new sepsis definitions, mostly because, one, they were new definitions. But the second is that, rather than getting a bunch of people in a room yelling at each other until you come up with a consensus, they actually use a new definition. And I think that's one of the reasons why, until you come up with a consensus, they actually use some data to derive and validate these definitions, which is wonderful. But the problem about these definitions is that they used them, they derived and validated them based on people with infections, whether or not they lived or died, not whether or not they had sepsis. And so that's been the biggest controversy about these new definitions. And towards that end, there is the non-lab value-based CLICSOFA score, which, again, allows you to triage between people who have mild infections and severe infections. My guess is, most of you, that it's not really helpful for, but for the frontline nurses and APPs and emergency room physicians and people who are just seeing these folks, they can sometimes help by looking at whether or not you've got organ failure. Again, it doesn't help in terms of whether or not you do or don't have sepsis. And for the past 20-something years, there's been ongoing iterations based on new evidence of the surviving sepsis guidelines to look at whether or not following standardized care improves outcomes. And generally, for groups of patients, they do. So I'm going to start out with a case, somebody who's got a bowel resection at another hospital and you don't have the medical records because care everywhere from Epic doesn't include the hospital that they send it to you. They show up. They're sick. They're hypotensive tachycardic febrile, have a high white count and an asthmatic leak on the CT scan. And they're given a couple liters of lactated ringers and started on vasopressors. And the reason that they have septic shock is that under the new definition now, in order to have septic shock, you've got to be hypotensive on vasopressors and have a high lactate. If you're just hypotensive and on vasopressors, you're sick. But you don't meet the new criteria for septic shock. And again, this is from that highly read JAMA paper. And I've went through, I think, most of the information here. So if you've just got an elevated lactate and you're septic, you've got a roughly one in four chance of dying. So you're pretty sick, right? There aren't many diseases. Mortality from acute MI is, what, 7%, 8% now. But if you show up with sepsis and have a high lactate, you've got a one in four chance of dying. If you're on vasopressors and hypotensive, you've got a 3 in 10 chance of dying. And if you've got a high lactate on vasopressors and you're hypotensive, then you've almost got a 50% chance of dying. So these folks are pretty sick. We don't have a biomarker. People have looking for years. People do a lot of things to try to diagnose sepsis. Procalcitonin doesn't work to diagnose sepsis, unfortunately. Be nice if it did, but it's not effective. And so really having a high index of suspicion for whoever shows up. If they're sick and you have no idea why they're sick, you probably ought to think about sepsis. So again, this is, you know sepsis is a medical emergency that it probably should be treated aggressively. In two of our nine hospitals, when somebody shows up to the emergency room, we will move them straight into the back if either the EMS person or the triage nurse thinks that they're sick. Or the triage nurse thinks that they're sepsis. So we're treating them the way many rivers suggested that we treat people, which is to treat them early and aggressively, which is the thing that probably helps with sepsis. Not so much goal-directed therapy, but rather early and aggressive treatment. And again, once you diagnose them, there's nothing here that is rocket science. You want to give some fluids. You want to give some antibiotics early. If they need source control, you want to do that. And you want to support them with a ventilator, with nutrition, with everything else. You want to prevent nosocomial complications. And then importantly, you want to look and see how you're doing. If you don't check and see how you personally or your hospital is doing, you likely will not be providing most of your patient's care. And I have to tell you that sometimes when I get our ICU's performance reports, some of us, including sometimes me, need to do a little bit better. And so feedback is extraordinarily important in making sure that you're treating patients well. So a second question that I suspect most of you will be pretty comfortable with, which of the following has been proven to improve outcomes in sepsis patients? Doing math in the morning, 30 cc's per kilogram, assuming that you can get an accurate weight on your patient, which I can't. Stressed-steroids, early goal-directed therapy, or sepsis performance improvement projects. It'd be nice if the first three were useful. Unfortunately, none of them have been proven in randomized controlled trials to improve outcomes. The only thing that's been proven in reasonably good trials is a sepsis performance improvement project. I should mention there is an ongoing trial looking at timing of antibiotics, comparing people to get it within the first hour and within the first three hours that hopefully will be done within the next couple of years. We'll have some more information about how aggressive you need to be in treating the folks who show up in your emergency room. So the surviving sepsis guidelines suggest that you screen patients and that you have some procedures to check and see how you're doing. Early antibiotics are important. There are a number of observational trials and a number of performance improvement trials, including the New York State experience when they instituted Ryan's regs. The mortality from sepsis went down and it was associated with the timing of antibiotics. So this is, I think, the third question. 67-year-old shows up with flank pain, fever, and dysuria. She gets a couple liters of fluids. She's started on peripheral vasopressors. She has a high lactate, high creatinine, and her urine looks messy. And she's got left-sided hydro. She's on vasopressors. And what this lady needs is source control. Antibiotics work in many patients. If you don't achieve source control, your patient's not going to get better. This used to be an article of faith. There was, a couple of years ago, the folks at UPMC looked at, for all their 40 or so hospitals, timing to source control and mortality. And if you got source control after six hours, your mortality was higher. It's an observational trial. There's all the biases of observational trials, both the ones in that you'll notice people who are sicker quicker, so you'll identify sepsis earlier on in the people who are really sick, but also the patients who you have to put the surgeon into an arm lock to get them to the OR because they're frail, they may take longer. The one thing I should notice is that most of the patients that I see who need source control have indwelling catheters that they're getting TPN or chemotherapy or other stuff, and they did not include those folks in this study. So you need to water patients. How you water them, whether most people think that you ought to give a balanced salt solution, you've heard about that before, it is probably better than normal saline, but you ought to water them a fair amount. You ought to give vasopressors when you need them. We have no new data past SOAP-2, which is now almost 20 years old, suggesting that norepinephrine is better and less risky than dopamine. Most people think that if you add vasopressin to norepinephrine, it's better than norepinephrine alone. This is mildly controversial, but there are a number of systematic reviews and meta-analysis that suggest that you'll do better with the two of them. And most people think that titrating to a mean arterial pressure of 65 is adequate. This is the sepsis PAM study from about a decade ago, suggesting that in all comers, aiming for a MAP of 80 is no better than aiming for a MAP of 65 in terms of mortality. More recently, Francois Lamontagne showed that giving lower doses of vasopressors to older patients, so aiming of a MAP between 60 and 65 is no worse, and maybe numerically, but not statistically better, than aiming for usual care. The difference between these two groups was about seven millimeters of mercury, of mean arterial pressure, and most people did not have a MAP of 60. They couldn't convince the nurses to turn down the MAP that low. This was greater than 65 patients, sorry, patients who were older than 65, so probably you can do this for younger patients, but they didn't test that in that study. So probably when I walk by many rooms in my ICU, sometimes somebody will have a MAP of 80 or 85, and it's always nice to say you might turn the dial down a little bit, and there are a couple of studies that suggest that. So how much do you volume resuscitate patients? My guess is if I were to poll everybody here, I would get 52 different answers. There are two recent trials, Clover's and Classic. Both of them enrolled sick patients. Both of them enrolled patients early, mostly in the emergency room, and both of them, before they randomized patients, gave them about two liters of fluids. So most people, and there'll be some new surviving sepsis guidelines coming out maybe early next year. My guess is the 30 cc's per kilogram is gonna go away, which is great, because I hate doing math when I'm standing up, and probably when I'm sitting down too. But you can, it is as safe to give a little bit of volume as it is to give a Costco-size amount of volume. None of these trials used what most of us do now, which is to put an ultrasound on somebody, or do a passive leg raise, or do something that measures dynamics. They all just gave prescriptions, so I don't think this is the final answer. But both of these studies show that you can, it is as safe, after you've given a couple liters of fluid, to start vasopressors. There's no data supporting one over the other. The other thing that I think made most people comfortable is that the majority of patients in the Clover's trial got peripheral vasopressors. And so, you don't have to, the first moment you meet the patient, ram a central line in them. If they're on high doses of vasopressors, you probably ought to think about doing it, but you don't have to do it first thing when you meet the patient. You can put in your A-line, you can give another liter of fluid, and then place in the central line. Again, I suspect this is what most of you do on a pretty regular basis, and you probably don't need me to tell you that. I think a lot of the benefit that we've gotten in the last couple of years is paying attention. Not giving too large tidal volumes, not giving too much oxygen, cutting down on sedation, mobilizing the patients, trying not to drool on your catheter when you're placing it, and other things that we should pay attention to. So again, sepsis is a medical emergency. You want to pay attention, make the diagnosis if they're sick, and give antibiotics early, get source control if you need to, and try not to do anything that will harm your patient. And that's sepsis in 13 or 14 minutes, I think. Does anyone have any questions?

sepsis

diagnosis

treatment

Sepsis-3 criteria

ICU performance