FEMALE SPEAKER: Welcome to Mayo Clinic COVID-19 Expert Insights and Strategies. The following activity is supported in part by an independent medical education grant from Pfizer Inc., And is in accordance with ACCME guidelines.

MODERATOR: All right. Thank you, everybody, for joining us today. I am pleased to be here as your host for the Metric 2020 session on hypotension. We are excited to have a really esteemed panel. So I'm going to start by introducing myself. I'm Erin Barreto. I am an Assistant Professor of Medicine and Pharmacy at Mayo Clinic in Rochester, Minnesota. And I am a practicing medical ICU clinical pharmacist.

And I'd like to have each of our panel representatives introduce themselves, and then we'll jump right into start talking about how each of these individuals manage hypotension in their practice. So let's get started. Dr. [INAUDIBLE], do you want to start?

MALE SPEAKER: Yup. So my name is [INAUDIBLE]. I work as an intensivist at Mayo Clinic Rochester. And most of my practice is involved with either the medical ICU or hematology, oncology ICU.

MODERATOR: Thank you. Dr. Littell, do you want to go next?

MALE SPEAKER: I'm John Littell. I'm an Assistant Professor of Emergency Medicine at the University of Minnesota, and I practice intensive care medicine at Abbott Northwestern hospital in a mixture of units. Medical, surgical, neurologic, and cardiovascular, including mechanical cardiac support. I also practice emergency medicine at [INAUDIBLE] Medical Center in Minneapolis.

MODERATOR: Great, thank you. Next up, I think, is Dr. Bauer.

MALE SPEAKER: Hi. Good afternoon. I'm [INAUDIBLE] Bauer. I am an intensivist at Mayo Clinic. I have a background of [INAUDIBLE] critical care. And then in this country, [INAUDIBLE] care. I do all kind of critical care.

MODERATOR: Wonderful, thank you. And Dr. Kashani?

MALE SPEAKER: Kianoush Kashani. Intensivist and nephrologist at Mayo Clinic. Working as nephrologist in ICU, and then medical ICU as intensivist. And [INAUDIBLE] research [INAUDIBLE] fluid management and septic management.

MODERATOR: Wonderful. And last but certainly not least, Dr. [INAUDIBLE].

FEMALE SPEAKER: Hi, I'm [INAUDIBLE]. I am an EM intensivist at Henry Ford Hospital, and I'm also a Clinical Assistant Professor at Wayne State University in Emergency Medicine. My practice areas at Henry Ford are emergency medicine and medical ICU. [INAUDIBLE] ECMO program, the medical ICU. And I also am part of the early interventions team, which provides critical care consultation at the ED.

MODERATOR: Fantastic. Well, I'm really excited. We have such a diverse panel of expertise from multiple institutions so I think this is going to be a really good conversation today. Maybe we can start with you, [INAUDIBLE], while we have you on the screen. Maybe you could start by talking to us about how, especially in the ED or the early intervention patients that you're seeing, [INAUDIBLE] hypotensive patient who makes their way through the first 30 cc's per kilo, what's next?

How do you go about trying to parse apart with the various diagnostic tests that you have available to you what the next step is in your treatment pathway?

FEMALE SPEAKER: Sure. So the emergency department is a bustling environment. And so I think it's sometimes time and crowding, and those other challenges that we don't necessarily face in the ICU, are really what influence a lot of what's immediately available. And I think after the first 30 cc's per kilo, the easiest and more accessible way for us to evaluate the patient in the ED ends up being some form of point-of-care ultrasound.

But as I tell my residents and fellows, and even colleagues, there is important limitations that you have to understand. And so I think with everything, it's using the trends of the data, understanding the physiology behind it. So often it comes down to a combination of point-of-care ultrasound, the impact on [INAUDIBLE] invasive monitoring devices are placed, then your ScvO2 combination with CVP. But not taking anything as a single point, or a single number or value, but really understanding the dynamic nature of it.

And being able to interpret it within the context of the physiology.

MODERATOR: That's great. Anybody else want to comment on the role of point-of-care ultrasounds in these situations?

MALE SPEAKER: Yeah. I would say the problem that I have with the point-of-care [INAUDIBLE] coming from the ED is excessive confidence in the finding. And this is particularly true in the context of either [INAUDIBLE] component. So I would just-- I think people rely too much on their finding on a point-of-care ultrasound, including the IVC collapsible or not.

So it needs to be interpreted with a grain of salt, and we need to do much more training in interpreting the point-of-care ultrasound before relying heavily on this finding.

MALE SPEAKER: Yeah, I kind of echo that. I kind of recognize my limitations as an ultrasonographer. When we have these hypotensive patients come in, there's a lot of things that a experienced echocardiographer could do. But my goal really is to see what is LV RV function, and do they have pulmonary edema based on thoracic ultrasound. And then beyond that is going to be kind of case by case, what information I take.

And I'm curious to kind of get other people's take in what all information that they used point-of-care ultrasound factor into the decision-making about volume versus pressor versus which pressor.

MALE SPEAKER: I think preload, and volume status, and point of care ultrasound is the area where we know the least and an area where, in general, we know relatively little. And it's also what's used most commonly. So it's a difficult place to be. I think the convention of measuring veca cava collapse is probably one of the things that's recognized most commonly as being a sonographic assessment for hemodynamics.

But the one that's probably the most problematic, or problematic enough that we shouldn't make, routine assessments of buying status based on vena cava ultrasound. It's one of the things I find the most challenging in teaching about the topic because it's cava collapse is index to the central venous pressure for the most part, and that's already a very problematic indicator. So I favor using a more global assessment.

These are all, I think, fairly complex ways of saying that we're left with basically clinical assessments for the most part, particularly in the time-compressed environment in the emergency department. And I think although there are problems with applying algorithmic approaches to these patients, I think in an environment like the ED where time, clinical data, and resources can all be limited, it's probably best to have a structured way of addressing those patients in the first hour or so.

And then teasing apart the nuance once they're either in the intensive care unit or if they're having a long length of stay in the ED during that phase of their care.

MODERATOR: Dr. Bauer, I just want to touch back on one thing that you had mentioned. While you offered up a primary concern about handling it, particularly in right ventricular failure, biventricular failure, can you talk through that just a little bit more for our listeners as to how that clinical decision-making can be flawed?

MALE SPEAKER: Well, every testing should be assessed in the context of pre-test probability and a post-test probability. And you need some basic skills to find some evidence of LV failure, RV failure. And since we talk about the IVC collapse, the collapsibility of the IVC in the site of the IVC. Take, for example, an RV failure, the IVC is dilated. That does not mean that the patient would not be responsible to a fluid channel, but we need to use extreme caution in this situation.

And you could have an IVC collapse [INAUDIBLE] patient [INAUDIBLE]. And well, [INAUDIBLE] the patient might be [INAUDIBLE] responsible [INAUDIBLE]. So I think people are too confident that the collapsibility of the IVC is the way to go. I think it needs to be put into context, and you need to have some kind of a sense whether or not your ultrasound change your clinical assessment.

So it does not replace the clinical assessment, and that's what's lacking most of the time. Oh, the IVC's collapsed [INAUDIBLE]. Wait a minute. You know? What's RV function, or previous RV function if you don't know. And we need to be a little bit more cautious to interpret [INAUDIBLE].

MODERATOR: Thank you.

MALE SPEAKER: Can I make a comment? So two points. One is that our colleagues in the emergency department have started using auto sonography way ahead of critical care, and they have implemented education and research in that very much ahead of us. And so gaining experience from them is an important factor, particularly for fluid therapy. Second is that at the upward trajectory of septic shock resuscitation particularly, I don't think there's a question that patients need fluid.

The question is, who should not receive fluids? So ultrasonography is used to assess the contraindications of fluid therapy. One in de-escalation phase [INAUDIBLE] use ultrasonography to identify the indications of fluid therapy because we don't want to give more fluid. Obviously, IVC and [INAUDIBLE] worthless as CVP. And so a combination of cardiac ultrasonography, [INAUDIBLE] ultrasonography, maybe [INAUDIBLE].

Flow rates or [INAUDIBLE], venous floor rates are important factors to identify congestion of organs rather than just looking into blood pressure and CVP or IVC. And so things are kind of moving targets. I hope that [INAUDIBLE], I understand that he's moving toward more advanced courses to add value to current tests that we are currently using for ultrasound. Hoping that our colleagues in the emergency department can teach us how they use it, outside of [INAUDIBLE], what other protocols they use to identify contraindications of fluid therapy.

The third point is that the 30 cc per kg is the median amount of fluid that [INAUDIBLE]. And so it was chosen by [INAUDIBLE] campaign as the target. However, some patients should not receive 30 cc per kg. Some patients should receive more. And this is another point that 30 cc per kg as becoming standard of care, but should not be a standard of care. It should be individualized for each patient.

MODERATOR: Those are all really great points. And I wanted to continue to build on this, Dr. Kashani since this is a really good transition to talk about, let's call it, fluid toxicity and when you reach for the vasopressors. So I think you all alluded to some risks associated with fluid therapy and using the diagnostic tools to guide when you would reach for vasopressors. And I know this is of particular interest to you, Dr. Kashani

What do you think of the emerging data with rifts or sensor with the fluid restrictive strategies in sepsis and septic shock, and earlier use of vasopressors?

MALE SPEAKER: So obviously it's a moving target. The amount of data to make us changing our practice is limited. However, they are consistent although a number of studies looking to that. So [INAUDIBLE] was a pilot study. [INAUDIBLE] different in outcome, but it showed some potential [INAUDIBLE] in comparison with those who received higher fluid in the first 72 hours. [INAUDIBLE], which is basically the resuscitation phase, the amount of fluids received in septic shock was less in intervention groups significantly, but they did better particularly from kidney standpoint.

For early vasopressors, again, I think the data is not sufficient. This is just-- a study came from [INAUDIBLE] certainly indicates that there is a signal, but I [INAUDIBLE] believe more studies on the topic.

MODERATOR: Anybody else want to comment on some of these fluid restrictive, early vasopressor studies that are coming out?

MALE SPEAKER: Well, I think it's probably time to introduce the concept of [INAUDIBLE] because I'm a true proponent that you have [INAUDIBLE] septic, one hour to stabilize your blood pressure. Now, I know that in ED it's very difficult because the waiting time, and the triaging area may go beyond one hour, and that's been a big debate following the proposal of the [INAUDIBLE]. And I cannot talk about the ED.

But I would say that if I get a patient in the ICU, and I think the patient is septic, and even if the patient has received some fluid prior to-- and I believe the fluid might be still needed, I make sure that between the time I see the patient, and in one hour from now, I want to make sure the [INAUDIBLE], let's says, 65. Because I think we need to have some guidelines. It can be tailored, but keep in mind a large number of patient, you have to have some simple attitude.

I find very often that people are [INAUDIBLE] because we don't think enough [INAUDIBLE] right away. And by the way, the guidelines say they can continue the fluid up to three hours, but you have to control your blood pressure. There's some good physiologic support, which is basically-- you need the [INAUDIBLE] the second [INAUDIBLE] or the fourth [INAUDIBLE]. I'm not going to go too much into the detail.

But I think stabilizing the blood pressure is, for me, the priority.

MODERATOR: Dr. Littell, interested in your thoughts. It looks like you have some.

MALE SPEAKER: Yeah. Can you hear me now?

MODERATOR: Now I can hear you, yes.

MALE SPEAKER: [INAUDIBLE]. Yeah, I'm sympathetic to the trend towards moving vasopressors earlier in the algorithm for a couple of reasons. One, because I think the opportunity to meet some of those early targets becomes more tangible. And because I think it's also an opportunity to limit some of the detrimental effects of volume overload that we see in the two, three, and four.

And so my goal is to try to find a way to be fluid sparing by thoughtfully using vasopressors early, granted in the absence of substantial data to support it. But with some data to indicate the downstream complications from overwatering patients. So I think relying on norepinephrine, for example, for both its after-load effects, but also it's venoconstrictive effects and contribution to preload, I think, is reasonable.

Especially in patients who don't seem overtly hypovolemic. Those who've kind of dwindled in a nursing home for several hours without access to food and water, for example. And using the vasopressor in conjunction with fluid therapy so that you can then potentially wean off of both earlier than you might later. Basically matching the intensity of the illness early on with the aggressiveness of the intervention.

Starting fluids, early vasopressors within reason. And then backing off on both, meeting some objective target as Dr. Bauer indicated. The map, for example.

MODERATOR: I think one thing I'd like to piggyback on here is a discussion about what happens when our resources might be a little bit more limited. So as an example, let's say we are keen to start vasopressors. Especially in the ED, or when you have multiple critically ill patients rolling around, Dr. [INAUDIBLE], do you have thoughts on peripheral administration of norepinephrine in those settings as you're kind of ramping up early in the hopes that you could peel back relatively quickly, and avoid that central access?

FEMALE SPEAKER: This is a hotly debated topic, I think. And I'll tell you at our institution, we have a tier-one policy against peripheral administration of vasopressors. So that makes it a challenge for us, certainly. I don't disagree with the statements that were made about targeting a map, and the importance of the organ perfusion pressure. But I think there are some pragmatic challenges depending on where you work.

And so, for example, certainly the policies and hospital policies against the administration of the vasopressors peripherally might be one of them. But also the challenges of if you've got an emergency department where you have crowding and boarding, you multiple resuscitations occurring at the same time, it's a little bit of a strain to have nurses running around and trying to administer vasopressors simultaneously to multiple patients.

So I think there is a pragmatic reason why sometimes fluids are the go-to. There is also, I think, a separation that needs to happen in our minds between that early phase of resuscitation versus the maintenance phase, or even the continued resuscitation phase as they are two different things. The 72 hours of fluid therapy that we looked at the [INAUDIBLE] trial, that's a lot longer than in what Dr. Littell and I are seeing in the emergency department.

And so there are two different phases of the illness. But I do think that having a goal in mind, and that goal being whether that's your map and your [INAUDIBLE], or a series of goals is really the key to the resuscitation. And when we talk about the evolution of EGDT, the goals that we had over 20 years ago are evolving. There's a little bit of picking into the details of is EGDT the right way or not, but not as much conversation around what are the new goals that we're looking for.

But it's really goal-directed resuscitation that we're all talking about.

MALE SPEAKER: Yeah. Can I make a comment on that? I think the early admission [INAUDIBLE] is even more true in people who are immunosuppressed. And so I think, and here we are lucky because our policy allow us to keep alive for up to 12 hours. [INAUDIBLE] Mayo in New York has been a strong advocate of peripheral IV. At the last [INAUDIBLE], there were people who were using [INAUDIBLE] for several days without too much complication.

And so I would say that if you start norepinephrine from [INAUDIBLE] in the ED, and I know that [INAUDIBLE] policy, but the triaging and the process, and the flow of the patient [INAUDIBLE] issue. But sepsis should be [INAUDIBLE] like a trauma. You have a trauma team. You should have a sepsis team, what is [INAUDIBLE] sepsis team concept. So basically, if you need norepinephrine, you should [INAUDIBLE] within the next six hours.

That would improve the flow. So it has to be a kind of a change in approach to the sepsis patient. The patient shouldn't be staying in the ED for more than six hours. I know that what I'm saying is difficult, and we are lucky here. But that should be the goal. So the director of ICU should basically have a sepsis bed like they have a trauma bed.

MALE SPEAKER: Dr. [INAUDIBLE] knows very well that the EGDT trial was run essentially by Dr. Rivers in a critical area of the emergency department, or at least initiated there. And so there are a number of creative solutions to solving this problem of busy EDs, and convincing the system of the time sensitivity of sepsis. It's a challenge. I wanted to make a couple of points on the access part of the equation. So I'm a believer in peripheral administration of vasopressors, at least for [INAUDIBLE] less than 12 to 24 hours through a reliably-placed large proximal antecubital IV.

And I think there's sufficient safety data to warrant that therapy. One of the challenges, though, with peripheral IV access in the emergency department is that sometimes the care-- sometimes those IVs are placed in the field, and may have been placed in a rolling ambulance under suboptimal conditions. And so the possibility of extravasation goes up somewhat under those circumstances.

So a peripheral IV, I think, is a reasonable access. But we have to make sure we're all on the same page about how reliable and how safe that IV is. And if a new one needs to be placed, fine. I think just taking kind of unfiltered peripheral IVs in the ED or the ICU, and administering vasopressors through them is risky. It just needs to be done with some caution.

MODERATOR: That's really helpful. Thank you for that clarification. I would like to bring in Dr. [INAUDIBLE] here. I have a question about individualizing map targets. Maybe not in the first three hours, but maybe in that 6 to 24 to 48-hour window. There's data now in elderly patients that suggests maybe we should be liberalizing a little bit here. Certainly in hypertensive patients, the opposite is true.

So interested in how you are applying these individualized map strategies to your practice as opposed to obviously the map of 65, which is especially in [INAUDIBLE] evidence-based.

MALE SPEAKER: Just to wrap up the comments from earlier, I kind of agree with the approach by kind of rest of the panel to kind of give concurrent pressure and volume just to try to limit some of that volume [INAUDIBLE]. And I know that one of the concerns is kind of the titratability of the vasopressors in a resource-limited ER setting, one of the options can be kind of just a fixed dose of low-dose norepinephrine, and then just volume to kind of supplement that.

And maybe Dr. Littell and Dr. [INAUDIBLE] can comment on that. Regarding individualized map targets, I'm kind of a simpleton, and so I kind of approach things in a simplistic manner. And I don't try to individualize map targets that much, and that's just really based on the fact that the vast majority of people, keeping things simple is adequate. Over time, you can kind of get a sense for where people belong, whether they belong higher or lower.

For the most part, I really don't individualize map targets too much.

MODERATOR: Dr. Kashani, I'd like to bring you in on that one. I think you maybe have thoughts, specifically from a renal perspective. I think you've muted yourself. On mute.

MALE SPEAKER: I'm sorry. I got distracted, my wife is on phone. So can you tell me the question?

MODERATOR: Yeah. Question is about individualizing map targets. Especially in, for example, we're seeing data in elderly patients, as well the opposite in hypertensive patients. How do you apply that [INAUDIBLE]?

MALE SPEAKER: So obviously, everybody knows about [INAUDIBLE] trial that showed those in higher target map [INAUDIBLE] hypertension, they did less acute kidney injury. So we looked into that. Among more than 1,000 patients who had baseline blood pressure measured prior to critical illness. And when they achieved their baseline blood pressure, or a little higher, they have significantly less mortality and less complications.

If they were less than their baseline blood pressure at the target, after six hours of resuscitation, they have significantly higher mortality and other poor outcomes related to ICU. So it's definitely important to identify what the map target is, and also indicate that map alone may not be sufficient to be able to be used as a target. I agree that map is important because it's available. Every single your institution can have a map available.

However, it may not be sufficient. We need not only indicators of organ congestion, you need indicators of fluid responsiveness. You also need indicators of fluid sufficiency. There are a lot of patients who we respond to, they do not need fluids. There are many, many other markers, both ultrasonography or other tests are being developed in order to help [INAUDIBLE] different information.

Hopefully map will become part of the panel of targets that we need to achieve. But at the moment, I think that map is the only thing that we have with lactate.

MODERATOR: Well, I think I want to keep us moving and talk about maybe some second-line strategies. So norepinephrine, probably we would agree. And I think has been invoked as the first-line go-to. When do you reach for the next line in your treatment algorithm? And what is it?

MALE SPEAKER: Vasopressin as a [INAUDIBLE]. Now?

MODERATOR: Yeah, there you go.

MALE SPEAKER: I still favor vasopressin as a second-line agent for a couple of reasons. But mostly because it makes sense to me to address the different receptors category rather than adding more beta agonists. I have a low threshold for using epinephrine in patients who might need inotropic support. And I tend to, just as a rule, avoid dopamine because of its association with malignant tachyarrythmias and dobutamine because you end up titrating up the vasopressin to manage the arterial dilation that you get as you come onto dobutamine.

Phenylephrine is commonly used peripherally. I think we've begun to see an argument that you don't have to use that as the exclusive peripheral vasopressor, which I appreciate because it's, I think, a drug not well matched to the pathophysiology of sepsis. And in terms of when I deploy vasopressin as my second-line agent, it calls to mind something Dr. Bauer once taught me which is that you need to look both at the status and the trajectory.

So if I find myself escalating the norepinephrine past sort of the moderate end of the range to meet the same map target, that suggests to me that I don't have sufficient control with that agent. And it's not logical to continue to add more norepinephrine, and that's a situation where I add a vasopressin.

MODERATOR: Dr. Littell, what does moderate mean to you?

MALE SPEAKER: I don't really have a number in mind. But probably once I've, practically speaking, once the dose of the norepinephrine has gone up two or three times, then I would add a different agent. It's really difficult to add an objective criterion to them.

MODERATOR: Yeah. I think we see that in a practice variability in really all the studies that are trying to use it, yeah.

MALE SPEAKER: It's more of the slope of the line than the position on the axis.

MODERATOR: Other people and their approaches to second-line interventions?

MALE SPEAKER: I use norepinephrine until I get to around 0.2 microgram per kg per minute. And if it goes beyond 0.2, or a patient remains on 0.2 for more than two or three hours, I add a second line. It's my personal [INAUDIBLE].

MODERATOR: How about looking at some of these other agents? So let's talk about angiotensin II, or the vitamins, steroids. Where do you kind of go for all of the, we'll call them all of the others? Do you think the vitamins trial, for example, put a nail in the coffin on that whole deal? Or are we still waiting [INAUDIBLE]?

MALE SPEAKER: [INAUDIBLE] there are [INAUDIBLE]. And I think right now maybe seven came out. I think the vitamin [INAUDIBLE] is to the septic shock what hydroxychloroquine is to COVID. [INAUDIBLE], and people like me who have used vitamin C before-- because vitamin C was very, very popular in the mid '80s where people were always reaching 3 gram vitamin C. And you knew it didn't work. OK?

So it just simply-- I [INAUDIBLE] the study going on. But I'm very, very surprised about the rush of doing excessive vitamin C without any substantiated fashion, and not a control, and I would say [INAUDIBLE]. As for the steroids, I think there's a good consensus right now that a refractory shock, which is defined the way you'd like. But usually [INAUDIBLE] station press [INAUDIBLE] one or two, depends on which country and continent you are.

After six hours, I think it's fair game to introduce some steroids. Keep in mind, for example, [INAUDIBLE] don't have vasopressin. So they go usually very easily to 0.5, 0.7. They don't like to go higher than that. And so they would start after six hours of [INAUDIBLE] at 0.5. We use [INAUDIBLE] vasopressin as a norepinephrine sparing agent. I would agree with Dr. Kashani that 0.2 is probably a good way to introduce the vasopressin as long as we confirm the patient is [INAUDIBLE].

And easy way to see [INAUDIBLE] blood pressure is low. And then maybe start steroids after six hours of fully inadequate resuscitation.

MALE SPEAKER: Can I add a comment about vitamin C? So some studies, it's been shown to decrease the shock or whatever benefit that's being shown. Whatever, I don't really care. The problem with all these studies is that they do not go beyond a certain amount of time of follow-up. We have measured oxide level among those patients who clinically receive therapeutic dose of vitamin C.

The majority of them have oxide level at the level that you expect from untreated [INAUDIBLE] patients. If patients do not become symptomatic, they do not develop acute kidney injury. However, these oxalates precipitate in conducting [INAUDIBLE]. It sits in the myocardium, it sits in the interstitium in the kidney. So if you look into these patients a year or two ahead, after that dose, then you will find some patients that they are dealing with chronic kidney disease, are dealing with other complications of these oxalate precipitation.

This is not [INAUDIBLE]. We had a few transplant patients who never recovered kidney function after receiving vitamin C. So I think it's a [INAUDIBLE] use of, even the research studies, use of vitamin C. All these studies that are published, and there are studies that are being conducted because it's one of them [INAUDIBLE]. But [INAUDIBLE] has another study ongoing for ARDS, and they're comparing [INAUDIBLE] and vitamin C in two-by-two factorial study.

They did a lot of due diligence to avoid toxicity of Tylenol, but they didn't do anything to make sure that there is no toxicity of biochemistry. So a lot of what we think are beneficial now, if we follow these patients a little longer, we may find the detrimental effect of those medications. So I would certainly against, [INAUDIBLE] against vitamin C. It makes us happy for half an hour, but doesn't make patient happy for long-term.

MODERATOR: I'd like to [INAUDIBLE] back on this conversation, and draw a distinction here between septic shock and post-op vasoplegia. I know we have a few people who come from the anesthesiology world as well as practice in CCU, or cardiovascular surgery. I wonder if we could just comment on the approach to refractory vasoplegia in the post-operative setting, and how that is distinct here.

MALE SPEAKER: Post-operative in general, or particularly postcardiotomy?

MODERATOR: Well, let's focus on postcardiotomy. But if you have specific distinctions you want to draw attention to there.

MALE SPEAKER: No. I just think that outside of the chest, we're typically talking about surgeries with some potential for gut flora translocation or stone extraction, and pyelonephritis. And things like that where there's a fairly stereotypical post-operative inflammatory state that I tend to treat much like [INAUDIBLE] from a non-operative source. Whereas postcardiotomy, there's all these dynamics of coming off of bypass, then ischemia reaper fusion.

Those patients tend to end up on a more complex mixture of hemodynamic support agents. Norepinephrine's still a mainstay. But typically, they end up on inotropic support as well. The practical consideration there is we're typically co-managing that with the operating surgeon who has their own set of insights given the fact that they've been in the chest, and seen the patient on and off pump. Seen what the response, grossly, from titration of support has been in the patient.

[INAUDIBLE] valve function, [INAUDIBLE] intraoperative TEE data, et cetera. And so all that input is valuable. There's typically also-- they bring along their experience and their training in terms of selecting agents, and so there can be some intercultural differences in how we manage certain aspects of the shock state. So none of this is a specific answer except that those patients typically end up on some combination of typically norepinephrine and [INAUDIBLE]. And then in some cases downstream, vasodilators.

MALE SPEAKER: And I would [INAUDIBLE] just to make a brief comment, there have been some-- I think [INAUDIBLE] benefit of the [INAUDIBLE] kit that we use in the smoke inhalation, those are still anecdotal. And I think there's at least one study going on that I'm aware. So I guess those are just Hail Mary type of resuscitation, and I would not recommend them on a regular basis.

MALE SPEAKER: Can I make a comment about vasoplegia in postcardiotomy? So I had the pleasure to go to post-cardiac surgery ICU and nephrology. So I see a lot of patients now are in trouble. Majority of them have vasoplegia as the driving factor for their kidney failure. I have seen such a variability in practice when it comes to management of these patients. Some receive cyanocobalamin, some receive vitamin C.

Some [INAUDIBLE]. Some go to [INAUDIBLE] too. And I think that it is very hard to make any sense of current data. If you look into it [INAUDIBLE] to see what can work. Indeed, we don't really have a good idea of what's causing it. I think it's a lot more complex than just activating outfall receptors. It probably has some pathophysiology behind it that we don't know what it is. We know there is some activation of [INAUDIBLE] factors, but what started it would be the key to provide some therapeutic option, not just temporizing measures until they get better.

And by the way, in [INAUDIBLE] trial, we recruited three patients. Two of them were vasoplegia after cardiotomy. And then these two patients were typical very sick patients. We started angiotensin II. Within 24 hours, they were off pressors and went to the floor. [INAUDIBLE]

MODERATOR: Is anybody else using angiotensin II in their practice?

MALE SPEAKER: No.

MALE SPEAKER: Using angiotensin II in severe [INAUDIBLE] septic shock, I think, the most recent was a typical [INAUDIBLE] reaction where huge [INAUDIBLE] procedure. And I think angiotensin II in those situations is good drug in combination with norepinephrine [INAUDIBLE], but those are exceptional cases. I think if you want to use it, you want to use it early. But this is really exceptional in practice, and we treat septic shock every day.

MALE SPEAKER: To call back Dr. [INAUDIBLE]'s comments from earlier, I think this is an area where we could desperately use some better tools to assess the patient's hemodynamics, organ system congestion, and whatnot because it tends to be an area where we use many complex drugs and devices in patients who we're monitoring with pulmonary artery catheters. And there's a mismatch between the data and the interventions.

MALE SPEAKER: And if I may add a comment. I [INAUDIBLE] earlier, and I think this is a very good concept [INAUDIBLE]. [INAUDIBLE] what create a sepsis initially, and then for longer hypertension which [INAUDIBLE]. Like we see with the [INAUDIBLE] circulation [INAUDIBLE]. Too much [INAUDIBLE]. And the [INAUDIBLE] when you dehydrate the patient too early. And I think it's really important to, once again, understand that the sooner you improve the [INAUDIBLE], it's not the blood pressure.

[INAUDIBLE] pressure that [INAUDIBLE], meaning that you [INAUDIBLE] not only your blood pressure, but your lactate, and the other [INAUDIBLE]. We didn't talk too much about the [INAUDIBLE], and the [INAUDIBLE] of CO2. Those are very marker of assessing at the bedside very easily the ongoing tissue [INAUDIBLE]. So the sooner you improve the [INAUDIBLE], and you improve the tissue [INAUDIBLE], the lesser you are in need to use those rescued medications.

MODERATOR: I want to kind of start looking to wrap up and put some of these comments in the context of the current pandemic. And Dr. [INAUDIBLE], I wanted to ask you where you see changes having to be made with respect to our standard strategies in light of the COVID-19 situation, specifically as it pertains to resources, shortages staff, whatever it happens to be for hypotension management?

MALE SPEAKER: I think that the experience from a lot of centers for COVID is that it at least appears to be primarily a respiratory problem. The shock is definitely there in it's upset, but not the predominant features we've seen in some other pandemics and other syndromes. And I think that going forward, resource allocation is going to be very much kind of individualized to the centers. The picture that we have here at Rochester, Minnesota is very, very different from what Dr. [INAUDIBLE] is describing at Henry Ford, for example.

It's two different settings, and it's very different from what my colleagues are experiencing in England, or in France and Italy. From a research standpoint, I think it's going to be important that there's a lot of speculation going on about what is potentially beneficial in the setting. And I think we just need to make sure that what we do is pretty standardized care with the exception of what it is within an IRB controlled trial.

I really don't think there's any scope for off-label use of medications outside of a research setting just based on the paucity of data right now.

MODERATOR: Other individuals want to comment on this? For example, I can't imagine we're going to be routinely sticking point-of-care ultrasounds on patients who are in deep isolation? Or in doing so, it's going to lead to some complexity for other patients. So just thinking about how this really would affect your standard approach to care.

MALE SPEAKER: I would push back a little bit against the restriction of ultrasounds since there are ways to either drape the equipment or to-- once there are a sufficient number of positive patients that their cohort [INAUDIBLE] one unit, then that allows you the opportunity of having equipment for multiple patients. I think this offers us an opportunity to provide excellent fundamental ARDS care in critical care, to standardize that across these patients.

And I agree to be very cautious about the degree to which we deploy off-label uses of therapeutics or novel therapeutics, or overhyped therapeutics in these patients. I think this is our opportunity to do what we do at a basic level very well, and to teach our non-intensivist colleagues who inevitably will be taking care of some of these patients, and sharing that burden to do the basics very well.

I think the success here will probably be largely borne on fundamentals of critical care and ARDS care, and fundamentals of hygiene. And then fundamentals of good clinical research in a fast-moving situation before we deploy any novel tools.

FEMALE SPEAKER: I just want to add on that because I agree with everything that's been said as having-- we're about 10 days into this, and we're certainly seeing it's predominantly a rapid-evolving ARDS. And so I think what Dr. Littell mentioned about focusing on delivering fundamentals of critical care is really what comes into the-- it should be the highest focus. In preparation, knowing each individual institution's capacities is really what we have found is the most important thing.

So the ultrasound, in particular, I think you can find areas where if you do have cohorted areas, you may deploy an ultrasound machine to that area. And then practicing infection control to clean that off. There are ways around it, but it's certainly thinking ahead of things. But really understanding what the capacities are currently so you can make contingency plans. And so we, at our institution, really have different levels and triage levels of at what threshold we move into different areas.

And so in the preparation of it, I think that's what everybody should be doing and thinking it through. We're already, within the first week, we have already moved to our plan of level 2 creating a COVID ED ICU within the ED because yes, we've got patients who are on aerosol-generating procedures and already vented. And they are holding and sitting in the emergency department, which is not unusual for our institution.

A very different process than in Rochester. But it is certainly a primarily respiratory illness. We are not seeing as much of that initial presentation of septic shock.

MODERATOR: Excellent. That's really good insight from the front lines. I know as a pharmacist, one thing I often get looked in on is drug shortages. So in the time that I have been in practice, one unfortunate time period, we did definitely have a norepinephrine shortage. And that was a complexity for a lot of patients. So let's just say, hypothetically, that were to happen. If you guys could offer your quick suggestions for what people do in that circumstance because that's the one that would probably take people out at the knees a little bit faster than some of the other rescue strategies.

MALE SPEAKER: Well, I would say, and based on the [INAUDIBLE] guideline on COVID published on Friday. And said by the others, we need to be very simple. We should stay away from we could do this, we could do that, we could place a line later on, let's see what happen, those kind of things. I think we need to get to the bottom of things. If you think you need to intubate, don't wait too much. Get your tubing.

If you do, get your lining. And since you have your line in, you get also ultrasound, and be very simple. And I would have no hesitation if we are running out of norepinephrine, to go to epinephrine. And if you are running out epinephrine, go back to dopamine. I mean, you need to be very flexible, but also very simple. I think the benefit will be not only for the patient, but for the majority, and needs to be simple.

As said earlier, you can consider a [INAUDIBLE] where you have [INAUDIBLE] for everybody. So even the limitation of masks [INAUDIBLE] where [INAUDIBLE] downfall for 4, 5, 6, 10 patients. And then you limit the change of masks. So there's a lot of things that can be-- I think simplification will be very helpful. You go for the goal, and I think the individualization in an institution may come afterwards, may come [INAUDIBLE].

That's basically what I would say based on the limited experience that you have.

FEMALE SPEAKER: Simple is also important for your entire nursing, techs. And there's a lot of changes that happen every day. There's a new protocol that will come out, it's overwhelming. And so keeping it simple, I think, keeps everybody on task. Because certainly the emotions around health care workers and their fears over transmission risks has been quite overwhelming. And so the simplicity of it is really important just to keep everybody on the same page moving forward.

MODERATOR: These are really great points. I think it's probably time for us to conclude does anybody have any parting thoughts that didn't come out in the discussion that they'd like to add?

MALE SPEAKER: Just one point to connect everything together is that the ARDS is obviously the most important organ failure. As part of management of fluids in order to avoid volume overload is important. In being in touch with our colleagues in China took care of 80,000 patients of COVID. RV failure apparently was very common secondary organ failure after ARDS.

So making sure these patients do not become volume overloaded is even more important than any other disease.

MODERATOR: Excellent. Thank you. All right. Well, I want to thank all of you for joining us today and spending an hour out of your very busy days to talk about hypotension management, especially in light of this pandemic. And I want to thank everybody for listening to another episode in our Metric 2020 series. And stay tuned for some additional ones on some exciting topics. Thanks, everybody.