SCCM Resource Library-Which Vasopressor Do I Pick From My Toolbox?

Video Transcription

Good morning, everyone. My name is Larry Busse, and I'm from Emory University. And I have the pleasure of moderating this session, which I think is going to be a great one.  It's nice that we're here in a nice, small, intimate hall to have some good discussion on shock and vasopressors. And so our first speaker is Dr. Jamie Gray, and she comes to us  from Hospital of the University of Pennsylvania. We'll be talking about blood pressure thresholds.  Thank you. Good morning. So this morning, I'll be talking about defining and defending a mean arterial pressure in vasodilatory shock. I have no conflicts of interest to disclose.  So the focus of this presentation will discuss the literature supporting a MAP target of 65 endorsed by the Surviving Sepsis Campaign, describe the effects  of different degrees of hypotension on outcomes in sepsis, as well as evaluate vasopressor strategies to optimize these outcomes.  Last month, the Global Burden of Disease Report was published with updates on the incidence of sepsis. One person dies from sepsis every 2.8 seconds.  In 2017, there were 48.9 million cases of sepsis worldwide, which attributed to 11 million deaths. These global deaths in 2017 attributed to almost one-fifth  of the deaths worldwide. So with these staggering statistics, we're constantly trying to optimize outcomes for our patients with sepsis and septic shock.  We're all familiar with the one-hour bundle with some of these initiatives that have shown improvements in outcomes including mortality in patients,  including early initiation of broad-spectrum antibiotics, optimization of IV fluid administration, as well as potentially vasopressor initiation and optimization of our MAP targets.  And that's what I want to focus on today. So if we think about our MAP goals and vasopressor titration, I think of it as a balance.  And so as we all know, sepsis is a complex pathophysiology. Autoregulation is lost during sepsis. And so with that, organ perfusion becomes dependent on blood flow.  And we utilize MAP as a surrogate of organ perfusion. And to do that and increase our MAP, we utilize vasopressors to implement vasoconstriction. And then with this,  the tissue perfusion would be increased. However, it's a balance. And so potentially with vasopressors, if we are using higher doses,  that vasoconstriction can sometimes cause decreased organ perfusion if we're overly vasoconstricting. And so it's with this balance that I think we need to evaluate  and assess our MAP targets, as well as how vasopressors help us achieve those while minimizing adverse effects. So first, we'll examine some studies  that evaluated high versus low MAP targets, sepsis-PAM and ovation. So sepsis-PAM was published in 2014 and was a slightly larger population of over 700 patients.  They enrolled patients within six hours of vasopressor initiation. Whereas ovation, published a few years later, was slightly smaller at 118 patients.  They enrolled patients within 24 hours of vasopressor initiation. And you can see that in the intervention of high versus low MAP, their targets were similar,  but shifted slightly as far as their high and low targets. When comparing the two groups, high versus low, there was no difference in mortality between these groups.  However, when considering special populations, sepsis-PAM found that in patients with chronic arterial hypertension, they did have a lower incidence of renal failure and the need  for renal replacement therapy in the high MAP group. In ovation, they did not have this finding. However, they did see that in patients older than 75,  there was a higher mortality in the patients in the high MAP group. As far as adverse outcomes, in both studies, they found that there was a higher incidence of arrhythmias  in the high MAP group, potentially due to the increased dose and duration of vasopressor use. In 2018, there was a individual patient data meta-analysis  that looked to determine if there are specific variables that potentially modify 28-day mortality at different MAP targets. This meta-analysis included primarily the ovation  and sepsis-PAM trials for a total patient population of almost 900. They also found that there was no difference in mortality between high and low MAP groups.  And they did not see a treatment effect in these special populations, including chronic hypertension, heart failure, or age. However, they did see that there was an increased risk  of mortality in the high MAP group when patients were on vasopressors for greater than six hours prior to randomization. They also found that arrhythmias were higher  in the high MAP group.  Another endpoint that we're often concerned about in patients with sepsis is sepsis-induced delirium and an altered mental status. And so there was a post-hoc analysis  of the sepsis-PAM trial published in 2019 that looked specifically at the subset of patients which were mechanically ventilated, sedated, and had available RAS scores.  The total number of patients was 532, and they looked at cerebral perfusion as an endpoint measured by RAS, as well as mortality. As far as baseline characteristics,  there was a higher incidence of renal failure in the low MAP group. Mortality between the two groups was not changed. And between the two groups, they did find  that there was a similar daily cumulative dosing of analgesic and sedative medications. And when looking at those groups based  on those similar comparison of analgesics and sedatives, they found that minimal and maximal RAS scores were significantly higher in the high target group.  Now this study did have some limitations in that this randomization from the original sepsis-PAM trial was broken. And patients in the low MAP group did have a higher  incidence of neuromuscular blockade which may have altered or significantly lowered their RAS scores. And so with that, sorry, and additionally,  it was hard to determine what this effect of the vasopressor and norepinephrine administration, if it was solely due to increased cerebral perfusion  or potentially increased perfusion to other vital organs that may have attributed to increased clearance of sedative and analgesic medications.  So the authors concluded that ventilated and sedated patients in the high MAP group did have faster improvement of arousal as measured by RAS scores.  And so this potentially is hypothesis generating and should be investigated further in larger trials. So kind of to summarize the data that we have so far,  it's somewhat inconclusive in definitive recommendations for our MAP targets. As for the surviving sepsis campaign, all patients should be targeted a MAP  of at least 65 in that first hour. Individualized targets, I think, still need to be examined a little bit further. But we could potentially consider it in these subsets  of patients that have chronic arterial hypertension and are potentially mechanically ventilated and sedated. But we need a little bit more data to elucidate that.  And I think additionally, it's important to examine our vasopressor effects on these MAP targets and outcomes. So first I want to talk about vasopressor initiation  and time to vasopressors. And so this was a retrospective cohort study published in 2014, and they found that the average time to norepinephrine administration was 3.1 hours.  And for every one hour delay in norepinephrine administration, mortality increased by 5.3%.  Additionally, last year, the SENSOR trial was published, which sought to evaluate shock control by six hours after diagnosis of sepsis. And so they included 310 patients  and evaluated early norepinephrine versus standard norepinephrine. They found that time to norepinephrine was shorter in the early group at 93 minutes.  Shock control rate was also higher in the early norepinephrine group at 76% versus the standard group at only 21%. There was no difference in mortality, however.  Additionally, the early norepinephrine group had a lower incidence of adverse effects, including pulmonary edema and arrhythmias.  And so with these two trials, I think it's safe to say that early initiation of vasopressors is important to quickly optimize our MAP targets and improve outcomes  in our patients with sepsis. So I think another important thing to consider is the duration of hypotension and how quickly we can get patients  to achieve their MAP as well as maintain it. And so in 2018, there was a retrospective analysis of electronic health records that looked for associations  between hypotension and in-hospital mortality, as well as acute kidney injury and myocardial injury. They used hypotension exposure definitions,  including a time-weighted average of MAP, and then the cumulative time below specific MAP thresholds. And they included over 8,000 patients. So the overall in-hospital mortality  in this study was around 15%, and they found that for every one unit increase in the time-weighted average MAP, increased hospital mortality,  acute kidney injury, and myocardial injury. So the risk for mortality, AKI, and myocardial injury were evident at MAP thresholds of 85.  However, that risk worsened at lower MAP thresholds. And so this study definitely supported the recommendation that maintaining a MAP well above 65  in a septic patient should be, at minimum, our target. In 2018, another study published was a retrospective analysis of the medical information mark for intensive care  from a hospital in Boston. They included over 5,000 patients, and they sought to describe the frequency and duration of hypotension in patients with septic shock.  They also wanted to determine if there were any associations with prolonged durations of hypotension and outcomes, including mortality.  The overall mortality was found to be 29.4% in these patients. And interestingly, 93.4% of patients had at least one documented MAP reading less than 65.  62% of patients had a MAP less than 65 for at least two hours. And so when we look at this effect on mortality, you can see that patients that had a MAP of less than 65  for less than two hours had a mortality of around 20%. However, when that increased to greater than two hours, mortality increased to 35%.  And when we look at the lower threshold of a MAP of 55, when that duration exceeded two hours, mortality increased to around 51%.  The study also sought to determine catecholamine dose and its effects on mortality, and they found that with higher norepinephrine dose equivalents greater than 1  but less than 1.5, the rate of mortality increased to around 54% versus those that had a lower norepinephrine dose requirement.  So in summary, they saw that prolonged episodes of hypotension are common, as well as these prolonged episodes increased the risk of mortality.  However, that potentially came at a cost of higher catecholamine dose, potentially affecting mortality as well. So in these patients where we've optimized fluid resuscitation  and have added our initial vasopressor, norepinephrine, and we're talking about duration of hypotension, it's important that patients may not respond to norepinephrine.  And so in these situations for refractory shock, I think it's important to consider what other agents we have available. And so we know that the surviving sepsis guidelines  recommend epinephrine or potentially vasopressin as second-line vasopressors, but there haven't been many studies evaluating those head-to-head.  And so first I want to talk about a study by McIntyre and colleagues that was published in 2018. They sought to describe whether the addition of vasopressin added  to catecholamine would decrease the incidence of adverse effects. And so when looking at the risk for mortality, there wasn't really a difference  in adding vasopressin to catecholamine. However, when looking at atrial fibrillation, there seemed to potentially be a benefit in decreasing the risk of atrial fibrillation  when vasopressin was added to catecholamines. That same effect was also seen in patients or in the risk for renal replacement therapy. However, that may have come at a slight cost  of a potential increased risk of digital ischemia in the patients that receive vasopressin plus catecholamine. So now I'd like to talk about two studies that are available  that did compare epinephrine versus vasopressin. And so this was an abstract that was presented at the CHEST annual meeting in 2017. It was a retrospective cohort study that looked  at three different groups. Group one was epinephrine plus norepinephrine. Group two was norepinephrine plus vasopressin. And group three was a combination of the three vasopressors.  They included 69 patients and looked at 28-day mortality. So in group one, which was the epinephrine plus norepinephrine patients, they did have a higher APACHE-2 score as well  as 100% mortality in that group and the highest incidence of arrhythmias at 71%. However, when adjusted for APACHE-2 score,  this effect on mortality and arrhythmias did not hold true, which leads us to believe that the patients in the epinephrine group were a sicker patient population.  Interestingly, vasopressin was most commonly added to norepinephrine in this patient population. A second study published last year also sought  to compare the addition of vasopressin or epinephrine to norepinephrine in refractory shock. They included 166 patients, of which propensity match scored 96, and they looked  at duration of shock-free survival. The mean epinephrine dose was 14.8 micrograms per minute, and vasopressin dose was not titrated at .03 units per minute.  And they found that between these two groups, the shock-free survival at seven days was similar between epinephrine and vasopressin groups,  as well as seven-day and 28-day mortality in the matched cohort. And so this study leads us to believe that potentially either agent is sufficient as a second-line vasopressor.  However, it doesn't specifically get into the subset of any specific patient populations with special characteristics that might benefit from one vasopressor over the other.  Lastly, Sheeran and colleagues published a study that was a web-based survey given to the European Society of Intensive Care Medicine,  seeking to understand current practice in vasopressor use, as well as MAP targets in sepsis. And so you can see that the main trigger  for vasopressor use was insufficient MAP response to initial fluid resuscitation. The first-line vasopressor was norepinephrine in 97% of respondents.  The MAP target was predominantly greater than 60 to 65, and higher MAP targets were used in patients with chronic arterial hypertension.  Additionally, they asked this group of experts to have consensus on 10 different recommendations, including vasopressor initiation as second-line therapy  when refractory to norepinephrine. And they came to a good degree of consensus with a strong recommendation that a second vasopressor should be added,  and that agent should be either vasopressin or terlopressin. Oops, sorry. So in conclusion, I think the literature supports that a MAP of 65 appears sufficient for most populations.  We should be initiating vasopressors early and avoiding prolonged periods of hypotension. Vasopressors should be used to optimize our MAPs in patients.  However, higher doses of catecholamines do appear to potentially increase mortality or have a higher incidence of adverse events. And so I think in summary,  before we can definitively say the MAP targets that we should be using in special populations, we also need to fully understand the effects of increasing our vasopressor doses  or potentially adding second vasopressors and how to optimize outcomes in our patients with septic shock. Thank you.  Thank you, Jamie. I think we'll save questions to the end so we can keep moving. And it's my great pleasure to introduce my friend and colleague, Dr. Ashish Khanna from Wake Forest,  who I've worked with on a number of occasions. And he's going to be talking to us about the evolution of vasopressors over the last two decades. Ashish?  Thank you, Larry. It's an honor and a pleasure to be here to talk about something that I'm very passionate about. Indeed, I've been involved in a little bit  of the vasopressor evolution. And so has Larry been over the last few years or so. So what's going to happen in my presentation is that I'm going  to take you guys back a few years and focus on some of the large landmark trials that have tried to develop evidence, specifically evidence for survival benefit of the vasopressors  that we commonly use today. And in the end, give you a sort of a summary of recommendations, which I'm sure all of you in the audience have several different ways  of using vasopressors. But hopefully, we have some messages that can be helpful for you all. My only disclosure is that my prior institution received funding  for the angiotensin II in high-output shock trial. So really, vasopressors, like I said, the old and the new. It's going to be a combination of some of the older ones  and the newer ones. And interestingly, some of the newer ones actually trace their roots back to about 60 years ago. I don't have the time or bandwidth to go back 60 years,  but I'm certainly happy to tell all of those stories afterwards. So my previous speaker did a fantastic job of telling us all about MAP thresholds.  But I'm going to bring you all back to this really, really quickly and sort of summarize and maybe touch on a few other areas of MAP thresholds that we did not talk about.  So point number one is that there's two sorts of studies we look at when we look at MAP thresholds and vasopressors. There's the randomized control trials,  definitely higher level evidence. And then there's large datasets. And essentially, to separate the two randomized control trials a few and far between.  The biggest work is the classic work done by Asphar and colleagues published in the New England, you know, in 2014. No difference in outcomes in two MAP targets, MAP 80 to 85  or 65 to 70, and then the side outcomes of chronic hypertension and more AKI in the low MAP target group. And all the way from then to two weeks ago until the 65 trial came out,  there wasn't really a large randomized trial of MAP thresholds. The 65 trial is interesting and it compared permissive hypertension in the ICU.  That's a MAP of 60 to 65 versus standard of care, which was MAP greater than 60. And I'll talk more about it in my slides, but they found no difference in mortality whatsoever.  It was also a trial of exposure to vasopressors. So more exposure to vasopressors to get to a MAP of 65 was probably not good for our patients  or the outcomes were just about as good in both groups. Now, in between all of this space is some of our personal work, which I've put up on the slide.  So we've talked about the work in intensive care medicine in 2018. We looked at 10,000 patients across ICUs from large data set in the United States.  And the biggest take-home message there was the earliest indicator of myocardial injury was at a MAP less than 85, which was definitely different from what a lot  of us would perceive as safe blood pressures. Now, I would like to highlight that myocardial injury is different from myocardial infarction.  And that difference we should keep clear. Pierre Asphar wrote an editorial for that and actually said MAP of 65 is probably a target of the past.  And clearly, there is probably a need for another sepsis BAM Part 2, which looks at slightly different outcomes. In the middle of all of this, we also published work  from a postoperative surgical ICU population, about 3,000 patients. And we saw similar results that the earliest indication of harm was around a median MAP of 80 to 87.  And that harm is myocardial injury. Plus, we've also seen delirium thresholds being increased at MAPs about 75 or so. And then, as highlighted in my previous speaker's talk,  post-hoc analysis from sepsis BAM has shown better arousal and RAS scores at the higher blood pressure target. So, I know I've confused you guys again  with what an appropriate MAP threshold is, but we'd like to understand that the debate is still not closed and probably still very much wide open.  So, we're going to use vasopressors, understand that, as I talk about the evolution of vasopressors, while we're all trying to drive high MAPs, what really matters is perfusion.  We don't have a great way to measure perfusion. These are our cytocam slides from the angiotensin 2 and high-output shock trial, which actually,  when I play this, this is a healthy patient. Look at the capillary density. Look at how the cells are crossing over at a fairly rapid speed.  And then, if I play the septic end-stage patient, look at the capillary dropout and how sluggish the blood flow is. Now, pushing blood pressure up might often get you  to this second image here and might not necessarily get you better perfusion. And that is the other part of this debate that is still wide open.  So, healthy and late sepsis, we still don't have a great way to see which is which, at least on an easily-available clinical or other point-of-care exam. What about vasopressors?  I'm here to talk about the evolution of vasopressors. And this slide here is probably common knowledge for most of you in the audience. We all know our common vasopressors.  We all know how they act. Effects on cardiac index, SVR, and heart rate. What I want to highlight here is the concept of norepinephrine equivalents that we've, you know,  talked about in several previous vasopressor trials. Understand that cumulative doses of vasopressins and catecholamines will add to norepinephrine equivalents.  So, it's not that you're on norepinephrine 20 mics per minute and vasopressin 0.02. That they're acting, they are acting through different mechanisms, but they're still acting  to increase norepinephrine equivalents. And that point should be kept in mind when we add on our vasopressors. So, I'm here to talk about the evolution.  And it goes back a few years where this work from John Myberg and colleagues from Australia looked at the comparison of epinephrine and norepinephrine.  Found no difference in the ability to get to a pre-specified MAP target. But did see that epinephrine was significantly associated with more lactic acidosis and a higher heart rate,  at least in the initial few hours of initiation. Norepinephrine does remain our drug of choice for septic shock and for good reason.  But epinephrine is still a very valid agent in case of the failing right ventricle or poor cardiac output situations. Understanding that we're looking  at the threat of lactic acidosis and increased tachycardia. Another classic trial, and most of the trials coming forth from here are comparisons of vasopressin and norepinephrine.  This is one of the classics. The VAST trial, Jim Russell and colleagues published this in New England 2008, compared vasopressin and norepinephrine in patients with septic shock.  These patients were initially all on norepinephrine and beyond a certain point, about five mics per minute in norepinephrine. They were then randomized  to either more norepinephrine or vasopressin. The Kaplan-Meier curves here show that there was no difference in a survival benefit at 20 or 90 days.  Now this interesting side light of this trial is that they did look at two strata. One was less severe septic shock. One was more severe septic shock.  Less severe septic shock being norepinephrine requirements between five to 14 mics per minute. And did interestingly show, if at least you look  at the p-values and the point estimates of absolute risk reduction, a better outcome in patients with less severe septic shock.  Though I would argue that it's almost statistical never, never land. You're about p-value of .04, .05. But then the physiological rationale would probably be  that early initiation of vasopressin, while your patient is still salvageable, is probably going to lead to better outcomes. This is my extrapolation of these results.  Clearly, the authors did not put this in their paper. But one way or the other, it does show some interesting side lights of a comparison of vasopressin and norepinephrine.  Another work at a very similar time, in the year 2010, Daniel DeBacker and colleagues published dopamine versus norepinephrine. Now, prior to this, dopamine, and all of us have,  some of us have lived in that era of renal dose dopamine. Dopamine being used for cardiogenic shock. This trial really was a nail in the coffin for dopamine, so to speak.  This trial compared dopamine and norepinephrine in a variety of shock states, found no difference in survival benefit. If anything, in a subset of patients with cardiogenic shock,  outcomes in the patients receiving dopamine were definitely inferior. More arrhythmias, increased mortality in subset of patients with cardiogenic shock.  So, where we were around the year 2010 was that dopamine was on its way out, based on evidence. And we were really left with norepinephrine, vasopressin.  And as I'm going to show you now, what we've done in the last 10 years or so, we've gone after comparing norepinephrine, vasopressin in different environments.  So, our vasopressor toolbox largely limited to catecholamines and vasopressin all the way up to the year 2018.  And as I'll talk about further, we did bring into play the renin-angiotensin system around that time, and that additional evidence would be interesting as we look at the evolution  of vasopressors. Is one better versus the other? I'll probably ask you guys when I finish my talk, but we'll see. All right.  So Anthony Gordon, in the year 2016, published this work in JAMA. Now the difference in this, the VANISH trial and VAST, is that this is early initiation of vasopressin.  So patients were put on vasopressin versus norepinephrine straightaway versus being on norepinephrine first and then being randomized. Outcomes were survival benefit.  There's no difference in survival benefit whatsoever. It was also a two-by-two factorial design where they compared with and without hydrocortisone  in both the groups, and primarily looked at renal outcomes and found no difference whatsoever in survival with or without renal failure, though the vasopressin group had less renal  replacement therapy. Certainly something to think about as all of us practice in various intensive care units all over the world.  A softer outcome, but something that does favor the use of vasopressin. Another subset of interesting patients is post-cardiopulmonary bypass, and this group  in Brazil, led by Hajar and colleagues, attempted to answer our questions, say, is vasopressin good for post-cardiopulmonary bypass vasoplegia?  We looked at a collapsed composite of a number of outcomes in these patients, and actually the event-free survival was better in vasopressin when looking at a collapsed composite of  outcomes and statistically significant. Although on a deeper dissection of this manuscript, you see that the biggest driver of these outcomes  is less atrial fibrillation, less renal failure in vasopressin. Clearly things that we know from our pharmacology, we know catecholamines tend to trigger more arrhythmias.  We know that vasopressin is probably better in setting of atrial fibrillation. So more evidence to suggest that vasopressin is probably a slightly safer agent in some  subsets of ICU populations. Going on further, and this agent sort of did not develop further, but did have significant  interest, telopressin is a V1-selective close cousin of vasopressin, tends to do away with the non-selective nature of vasopressin.  And at least in initial Phase IIb work that was published by Jim Russell, there was an ability to get to a MAP target, better fluid balances, less use of norepinephrine, faster  reading from norepinephrine. But as they went on to Phase III trials, the initial outcomes were not good, and most of those trials were stopped midway.  So this agent is not available for use in the United States of America as of now. Now our work, and Dr. Bussey was closely involved in this work as well, we looked at angiotensin  II in high-output shock or vasodilatory shock patients. And the renin-angiotensin system is certainly that unexplored frontier of management of hypotension in the ICU.  Our primary outcome being hemodynamic outcomes, being a MAP target of 75 or more, this being a Phase III pre-FDA clearance trial, we did achieve a significant difference in primary  outcomes with a large chunk of our patients, nearly 70%, getting to the primary MAP target. We did not see a difference in mortality or survival benefit one way or the other.  It was a small trial, about 300-odd patients, not powered for mortality, a pre-FDA approval trial.  But we have seen some interesting analyses on a number of post-hoc trials, which I'd like to briefly comment on as we look at evolution of vasopressors.  Importantly, we've seen better outcomes in patients with septic AKI. We've also looked at liberation from renal replacement therapy and seen definitely better  outcomes when we see faster liberation from renal replacement therapy. And most interestingly, we saw that patients who had low endogenous angiotensin-2, at least  a population median of angiotensin-2 to angiotensin-1 ratios, those who had low endogenous angiotensin-2, that was an independent predictor of mortality.  And when these patients were given exogenous angiotensin-2, they tended to do better.  Certainly a biological rationale why angiotensin-2 would seem to work specifically for some patient populations. And very finally, there were some super responders to angiotensin-2.  Patients who responded to less than 5 nanograms per kilo per minute in another pre-specified post-hoc analysis had did better afterwards.  So early days for angiotensin-2, still a lot needs to be done. But what I really want you guys to understand is that when we look at vasopressor evolution,  the big three, as I call it, SOP2, VAST, and now ATHOS3, the difference is that SOP2  and VAST were head-to-head vasopressor trials comparing specific vasopressors, where angiotensin-2 is trial is essentially angiotensin-2 versus standard of care.  So not a head-to-head comparison. But the point I want to convey with this slide is that one way or the other, if you look  at the odds and the p-values over in the end, vasopressors per day, per se, have not influenced mortality in the ICU.  They are an instrument to help us get hemodynamic stability, not necessarily drive mortality.  In fact, if you compare everything to norepinephrine, outside of a little bit of a harm that dopamine  showed in cardiogenic shock, comparing all other vasopressors to norepinephrine, there is no difference whatsoever.  Now this Cochrane review did not include the results of the VANISH trial. Might have influenced this Cochrane review a little bit. But again, I will bring back the same point.  Vasopressors in and of itself may not be the only reason for improved or poor survival in the ICU.  So as Bala Venkatesh, a close colleague and a friend who works with steroids and septic shock, and myself and Jeremy Cohen have just published, less is more.  Catecholamine sparing strategies, adjunctive strategies might be the way forward as we look at evolution of therapy in sepsis and septic shock.  And certainly, less is more brings me back to the 65 trial, which saw that permissive hypertension was probably as good as usual care.  I would encourage all of you to read the editorial by John Marshall. That's going to give you incredible insight into the real deal behind the trial and how  we should best interpret these results. Very finally, I love this slide. Every time I talk about vasopressors, I talk about the cogwheel, right?  So if you look at evolution of vasopressors, we've gone all the way from catecholamines, vasopressin, cellopressin, angiotensin II.  And all of these actually go all the way back to the 1950s and 1960s and moved all the way forward. But in and of itself, no one vasopressor is going to help you.  Probably early multimodal therapy is going to be most beneficial. And do not forget the others over here in the corner. Still don't forget the steroids.  Still don't forget the vitamins that most of us have adhered to recently. It's all going to come together. Only if you use it together, you use it in a multimodal fashion.  Thank you so much for your time. Open for questions afterwards. Thanks, Ashish. Two quick comments.  I think the cellopressin study was negative because they picked the wrong endpoint. And secondly, the VANK study, though positive, mortality was no different.  So there seems to be a very strong prevalence in all of these studies of organ sparing strategies, kidney sparing. But mortality has not moved at all.  Our last speaker, now for something totally different, Dr. Simon Lam, who comes to us from Cleveland Clinic.  And he's going to talk to us a little bit about cost-effectiveness analyses and how we practice this aspect of care with an economic perspective. Thank you for that introduction.  It's truly an honor to be here with all of you. So this talk is going to be quite different from the previous two talks.  I'm going to go ahead and tell you guys that I do not know the answer to this question. I'm also going to say that I'm not going to try really hard to convince you one way  or another which vasopressor is the most cost-effective. My overall goal for this talk is pretty much to increase exposure to cost-effectiveness  and to continue the conversations about how we could discuss cost and value within ICU. So the outline for today, I will primarily be talking within the context of septic shock,  but I'll provide an overview of cost-effectiveness and value assessment, and then discuss an  example of a cost-effectiveness analysis that was done by me and my colleagues to evaluate second-line vasopressors.  And my thought behind going through this example is so that we can demystify some of the methods and the ways that we can analyze cost-effectiveness data.  So to begin, what is cost-effectiveness, and why do I want to talk about this? It's because in my heart, I really believe that I'm a savvy shopper.  I'm the guy who gets a thrill buying something cheaper than my neighbor can buy it. I order a toilet paper by the pallets if I can save five cents per roll.  And I think in my case, you know, the stereotype of a frugal Asian father is 100% accurate. So I say the word frugal, but my kids just call me cheap all the time.  But oh, and by the way, I am in no way suggesting that the programming committee played into these stereotypes when they asked me to give this talk.  So as a savvy shopper, I use a lot of tools. I use all these tools to track prices, to get cash back, so I can get the best deals.  So just a show of hands, how many of you use any of these or use other tools to try to get the best deals? Pretty good.  So it seems like there's some savvy shoppers out there in the audience. And as a savvy shopper, I don't think I have to tell you how to spot a good deal. What is a good deal? Right?  You see a good deal, you do your own research, and you know it's a good deal. So case in point, let's say I'm trying to buy a certain item and the local boutique  shop has it for $150 a piece, but the mega shop has it for $100 a piece. Where would you guys buy it? No questions, right?  You would totally buy it at this mega shop because it's cheaper per item. But what if I told you that these items that I'm trying to buy are actually one ounce gold  bars that are worth $5,000 a piece? Does that change anything? Just doing some math, you'll see that if I buy all five from the mega shop, it'll cost  $500, but it'll net me a value of about $25,000. First if I buy it at this more expensive boutique store, I'm going to charge you $1,500, but it nets me a value of $50,000.  Doing this math a little bit further, if I shop at the more expensive store, it'll cost me an additional $1,000, but it'll net me an incremental benefit of $25,000.  In other words, I only have to spend four cents more for each dollar of benefit. So all you savvy shoppers out there that picked the cheaper store, now are going to  say, I'm going to buy it at the boutique shop. Maybe the more important question to ask, or the next question to ask, is when should you stop buying from more expensive stores?  Let's imagine that there's a third store, we'll call it the specialty shop, and it's 10 times more expensive than the boutique, $1,500 per item, but they have 20 gold bars.  Doing the same type of math, we'll see that if we shop at this specialty shop, it will cost $28,000, but it nets an additional benefit of $50,000.  And in other words, I would spend 57 cents more for each dollar of benefit. So I think all of you savvy shoppers can now realize, I will keep on shopping at more and  more expensive stores until my incremental cost is beyond what my incremental value is. So this is all pretty easy to understand, right, because we're talking about gold bars.  But what if we're talking about, from a different perspective, I'm going to change it now to clinical. So as a clinical savvy clinician, what is the value of a year of good life?  So that might be pretty easy to understand, too. I think most folks in this field would say somewhere in the one to three times GDP per capita range.  So for United States, it's about $50,000 to $150,000 for a year of good life. For Uganda, that's probably $500 to $1,500. But what if what I'm buying is not a year of good life?  What if what I'm buying is hemodynamic stability, time to map goals, lactate clearance? It's just really hard to put a dollar value to those outcomes that we care so much about  in the ICU. So if I were to sum up what is cost effectiveness and what is value, I would say more expensive does not equal no value.  We clearly demonstrate that with the previous example. That value comparison requires some sort of incremental assessment of both benefit and  cost, and it requires some sort of consistent unit of measure, whether that be gold bars or a year of good life.  And perhaps most importantly, the most cost effective option is just the most beneficial option that is below what you're willing to pay for it.  Just like you're more willing to shop at the more and more expensive store until the incremental cost outweighs the incremental value.  So just like I have tools to help me track prices and get cash back, the toolbox that we can use in economics is cost effective analysis to help us determine what is the  best bang for the buck for clinical care. Before we dive into cost effective analysis, I think we need to establish some common grounds first.  The first thing is human life is precious, and that pursuing additional benefit is valuable.  If we can't agree on this, then we would say that the most cost effective therapy is just to let the patients perish.  Pursuing additional benefit frequently costs more money, and innovation by itself is not an evil thing. Innovation is a good thing. We want more benefit.  And even expensive care is not a bad thing, as long as it's worth it, as long as it's worthwhile. And we're all functioning in a society with limited resources.  Once again, if we do not agree on this, then we would just pursue any care, regardless of how much it costs, even if it has an iota of additional marginal benefit.  So you would think because we function with limited resources, we have tons of cost effective analysis to guide our decisions. However, that's just categorically untrue.  This is a recent systematic review looking at cost effectiveness studies in the ICU. Over a 25-year period, they identified 97 studies, 97.  So I just went to PubMed and typed in these years and searched critical care, and I found 700,000 articles.  So this just shows how little cost effectiveness research is being done in the ICU. Out of these 97 studies, 20 of them were in sepsis, and zero of them were in vasopressor.  So how do we proceed from here? How do we talk about vasopressor costs without any data? So here we're going to transition into the work that me and my team did on second-line  vasopressors. And once again, it's more important to go through the thought process and the analyses than the actual results.  So why are we talking about second-line vasopressor in the first place? This is a survey that was already presented from the first presenter.  This is a survey done by over 800 physicians from 82 countries. When they surveyed on what was their first-line vasopressor to use, there was not a whole lot of controversy.  The majority of them said norepinephrine is first-line. However, when it comes to second-line, there was some differentiation.  Fourteen percent of them would say, I'm going to use norepinephrine until I reach some predefined maximum.  And 86% said, I'm going to use a second vasopressor before this pre-specified maximum. And the rationale behind doing that is they think norepinephrine might be ineffective,  and they want to limit side effects, want a second agent with independent mechanism or synergism.  I think you can group these last three together to say they want a second vasopressor that doesn't work similar to a catecholamine.  Our guidelines actually have recommendations on second-line vasopressor. It says to use either vasopressin or epinephrine as a second-line agent.  However, I demonstrated in the previous slide that 70% of physicians prefer an agent that's different, and epinephrine just doesn't fall within that category.  In a similar survey to clinical pharmacists, 70% of them responded that they prefer the use of vasopressin over epinephrine.  And as we all know, the most recent surviving substance campaign guidelines were published  prior to the availability of angiotensin-2. And any time we have some sort of innovative therapy, it's always good to evaluate whether  or not it's worthwhile, it's cost-effective or not. So for the purpose of this discussion, we're going to be talking about these second-line  vasopressors, increasing doses of norepinephrine, adjunctive vasopressin, or adjunctive angiotensin-2.  So whenever you do a cost-effective analysis, the first thing to determine is what is your outcome of measure? What is your consistent unit of measure to determine effectiveness?  And of course, you have to balance the availability of data with picking an outcome where you can actually put a cost value to it, a willingness-to-pay threshold to it.  It's really, once again, really difficult to put a willingness-to-pay threshold on map goals or reaching certain secondary outcomes.  It's important to look at it from various perspectives. If you're a bedside clinician or from an ICU or a hospital, you just might be caring about  ICU and hospital mortality or length of stay. And once again, I put these other outcomes here that we routinely capture in blue because it's hard to put a value to it.  However, if you're taking it from the patient or societal perspective, you are going to worry more about a long-term outcome, such as life years or quality-adjusted life years.  I think the interesting aspect of critical care is we can observe these outcomes quickly in the acute setting. However, these outcomes also affect the long-term outcomes.  For example, if someone survives their ICU episode, that could be many, many life years gained.  And similarly, if someone develops chronic sequelae from their ICU stay, that could affect the patient's quality of life for the rest of their life.  So going through some of the clinical data, I'm not going to belabor some of these because  we've already gone through a lot of the clinical data, but comparing vasopressin to catecholamines,  in the recent one to two years, there's been at least four meta-analyses comparing vasopressin  or vasopressin analogs compared to catecholamines for the treatment of distributive shock. So here's those four meta-analyses.  I would just say, numerically, all four meta-analyses found a mortality benefit in favor of vasopressin.  And three out of the four meta-analyses actually found a statistically significant improvement associated with vasopressin.  This last meta-analysis was done on an individual patient data level, and we're only able to get roughly half the patients from these other meta-analyses.  I only show this slide to suggest that there might be an outcome measure that we can put a value to that we can use for our cost-effectiveness model.  And this is the ATHOS-3 data that we already went over. This is angiotensin-2 adjunctive compared to norepinephrine.  And of course, we know that the primary outcome of MAP response at three hours was significantly different.  However, once again, it's hard to put a value to MAP response at three hours or even change in cardiac SOFA score.  However, we can see at least maybe a numeric difference in mortality that might be helpful for our cost-effectiveness model.  We can also evaluate these vasopressors based on their adverse effects profile, and this was already discussed with my previous two speakers.  This is from a narrative review from Jim Russell, and he basically suggests that various vasopressors will have different adverse effects.  And the other aspect I want to bring in here is these adverse effects from the ICU might actually be the other long-term sequelae.  For example, a patient who has AKI and survived their ICU episode may never recover their renal function, and that patient might develop the need for dialysis.  And that might affect the long-term care and the long-term cost of this patient. Changing gears to talking about how do we think about costs when we talk about vasopressors,  we can also think about it from various perspectives. From the ICU, we might care about length of stay, the use of devices like mechanical ventilation  or renal replacement therapy, adverse reactions, or the drug cost themselves. However, if you're taking it from the payer's perspective, of course they're going to care  about the cost from the ICU and the hospital, but they're also going to care about the cost for the whole patient for the duration of their care beyond the ICU for the rest of  their lives. And if you take it from the societal perspective, it's going to include both of these payer  and ICU perspectives, but it's also going to bring in the loss of productivity from the patient's perspective and their caregiver's perspectives.  So taking all of those costs and clinical parameters in mind, we designed a cost-effectiveness  analysis using a hypothetical cohort of patients with septic shock who are already receiving norepinephrine.  And once again, these are the three second-line vasopressors that we evaluated. And the outcomes that we came up with for a short-term outcome was ICU survival and  long-term outcome was quality gained. Once again, for our short-term survival, patients can receive any one of these second-line vasopressors.  And if you receive one of them, you have differing probabilities of developing these short-term adverse effects and also different rates of ICU survival.  For patients who actually survive their ICU length of stay, they might have developed additional long-term sequelae if they develop these short-term adverse effects.  And ultimately, that might affect the patient's quality of life and also cost of care. So we did a whole bunch of data collection, clinical data, including the probabilities  of all these adverse effects, ICU length of stay, effects based on these adverse effects, the probability of progressing to long-term sequelae, dosing and duration of vasopressors,  days of shock, ICU mortality, regular life expectancy after septic shock. In terms of costs, we evaluated drug costs, ADE costs, ICU costs, and also long-term sequelae.  We also looked at quality of life of septic shock survivors, regardless of whether they had or did not have long-term sequelae.  So all the clinical data that was used in this model was taken from RCTs. The cost data was taken from a payer's perspective, from various databases, publications, reimbursement  data, and they were all inflated to 2017 US dollars. We did a host of sensitivity analyses where we fluctuated all these parameters based on a pre-specified range.  And for this analysis, we set the willingness-to-pay threshold at $100,000 per outcome. So here's our base case results.  You can think of base case as if I did the analysis using all of those parameters that  I talk about with the most likely values. So don't think about any of the variants or uncertainty, just the most likely values.  So in the base case, we can see that adjunctive vasopressin was actually the least expensive, roughly $53,000, and it generated an ICU survival of 61%.  Norepinephrine was actually more expensive, roughly $5,000 more than vasopressin. However, it did not generate more ICU survival.  In economics terms, we'll say that norepinephrine is dominated by vasopressin. We can say the same thing for angiotensin 2, more expensive than vasopressin, but did  not generate more ICU survival. So it's also dominated by vasopressin. However, if you compare angiotensin 2 to norepinephrine, we see that it is slightly more expensive  than norepinephrine, and it does generate a little bit more ICU survival. And if you do this incremental cost-effectiveness ratio, or ICER, you'll see that it's $77,000,  which is less than our $100,000 threshold. In essence, we would deem this to be cost-effective if you were comparing ang-2 to norepinephrine.  This is what's called a tornado diagram. You can think of this as a univariable sensitivity analysis.  What it's basically asking is, if I fluctuated this parameter, ICU mortality risk between this pre-specified range of 56% to 39%, what would happen to my ICER if I kept everything  else as base case values? The couple of observations I want to give from this is our base case analysis was robust.  None of these parameters, no matter how much I fluctuated them, pushed the ICER above $100,000 per ICU survival.  The other thing that I want to point out, these are the top eight most important parameters, and it does not include drug costs.  Neither vasopressin costs or norepinephrine costs are included in the top eight most important. I only include the top eight because the graph becomes unreadable beyond that.  But basically, the ones below the eighth one is not important at all. The same things can be said when you compare ang-2 to vasopressin.  We have really robust base case data where fluctuations on these parameters, no matter how I fluctuate them, it never pushes the ICER above $100,000.  And similarly, drug costs, ang-2 drug costs or vasopressin drug costs was also not an important determinant of cost-effectiveness.  Looking at the base case evaluation of our long-term outcome, which is QALYs, in this analysis, escalating doses of norepinephrine was the cheapest, and it led to 3.78 QALY gained.  Adjunctive angiotensin-2 was slightly more expensive and led to more QALY gained. And if you do that calculation, this is the ICER, roughly $23,000.  Vasopressin compared to norepinephrine was more expensive but had dramatically more QALY gain. And here was the ICER, $19,000, which is, once again, below $100,000.  So we would call it cost-effective. The reason why ang-2 is considered extended-dominated is because this ICER, comparing vasopressin  to norepinephrine, was actually lower than this ICER. And it actually generated more QALYs. So in this analysis, we would also say vasopressin is the most cost-effective.  Similar trends, when we look at the one-way sensitivity analysis or univariable, none of the variations push the ICER above $100,000, and drug cost was not really a factor.  So I've been equating these tornado diagrams as univariable sensitivity analysis. You can think of this as a multivariable sensitivity analysis.  What we do here is we simulate 10,000 patients, and we select the parameters all at once based on their pre-specified ranges and the pre-specified distributions.  And then we simulate what would happen if we choose different willingness-to-pay thresholds. What is the probability of these simulations being cost-effective?  At our $100,000 per QALY gain, we can see that vasopressin is 87% of the time going to be cost-effective.  Even if we go down to a more reasonable willingness-to-pay threshold of 50,000, it's still at the 80% range.  So this, once again, suggests that vasopressin, in most of our simulations, is the most cost-effective.  So if I were to conclude based on the CEA, I would say vasopressin is the most cost-effective second-line vasopressor.  However, if vasopressin is not available, ANG2 would be a reasonable cost-effective second-line vasopressor.  And once again, vasopressor drug cost is just not a major parameter in the determination of cost-effectiveness.  And if I were to make conclusions about cost versus clinical in general, I think it's important to reiterate that health care is worthwhile. However, we have limited resources.  And currently, we make our value decisions largely based on gut feelings and largely based on silos.  For example, I'm from the pharmacy department, so I'm just going to care about drug costs. So I'm just going to pick the cheapest drug.  But as we can see, that's probably not the best approach when we think about cost in general. And we desperately just need more cost-effectiveness data in critical care.  Thank you for your time and attention.  Thanks very much to our panel of speakers. We'll open it up for questions. Come on up to the microphone if you'd like.  All right, well, I'll start with a question. Simon, that was a really interesting perspective. How would we go about looking at this as a more complex model,  not one-to-one, but rather bringing multiple agents into the equation? Is that possible to do that kind of analysis? It is, but it gets much, much more complicated.  If I were to print out this model right now, it would probably fit on this screen right here. There's just that many branches in the model.  And the more, any time you add a different parameter, you add an exponential amount of branches. So it could be done. Probably not by me, though.  Don't sell yourself short.  Other questions? Good morning, panel. Thank you very much. That was a great review and definitely some great ways to think about it. My name is Sonja.  I'm a critical care pharmacist out of Northwest Indiana. My question is, there was a paper maybe about a year or so ago that looked at the use of propofol  versus dexmedetomidine to help that switch over in order to help decrease catecholamine use. What are your thoughts?  Looks like we're passing this around. So short answer to your question is, use of sedation in the ICU is certainly a factor in determining  the amount of vasopressor needed to maintain a MAP. Personal practice, I don't feel that, as long as you're using your sedative agents in their usual doses, that should not  be the driver to change your vasopressor. There is a subset of patients that are going to need, for example, additional sedation to keep them appropriately sedated.  And there it certainly gets more challenging. I don't recommend switching from catecholamines to vasopressin just because you are on giant doses of sedation.  However, I do recommend early switch over if your patient is actually sick, if you have rip-roaring sepsis, if you don't have adequate source control, or your patient  has impending organ failure. And those are two slightly different clinical judgments that every intensivist has to make. Does that sort of answer your question?  So the article focused on patients who are on propofol. And then actually, because that subset required far more norepinephrine doses than the one that  was weight-based, switching them over to Depressidex or dexmedetomidine, does that actually help to decrease that norepinephrine drip rate? Sure. So the question is that, should we  switch over sedation as a mechanism to unload catecholamines? I mean, obviously, if your patient can tolerate it and the patient's not uncomfortable  and is still a good mechanism of sedation, that definitely we all know the value in keeping our patients slightly less sedated.  The whole perspective is not then just the catecholamine unloading. It's probably better outcomes for our patients one way or the other. All right. Craig. Why not use ketamine?  Yeah. Craig Weiner, University of Minnesota. Tell me if I'm wrong. My interpretation is that if you have any intervention in the ICU that is in a patient with a condition that's  going to have a long course, expensive hospitalization, a lot of post-ICU care, if there is any incremental benefit in terms of mortality, quality of life,  then the cost effectiveness, the cost of the intervention, whether we're talking about pressors, sedatives, anticoagulant reversals, ECMO, becomes very small  unless the intervention is extremely expensive. Is that true? That is categorically true. I would say we probably don't have a lot of cost effectiveness  data because we don't have a lot of interventions in the critical care setting that has that true mortality benefit. So I think in general, if you can  prove that your short-term care can lead to long-term outcomes, nine times out of 10, it will be cost effective.  Hi. Thank you, panel. Great presentations. I'm Karthik Jyothi. I'm an intensivist in Nashville, Tennessee. There's a subset of patients who are very difficult to wean off  of pressors. They're stuck on one to five mics of norepi, and that could be for a day or a few days, and they really increase length of stay. Do you think, in light of the 65 trial,  is that a group of patients you would lower their MAP cutoff, or would you consider other things, albumin, mitadrine, steroids, just things to try to wean them off pressors faster?  Yeah, I think that's a good question. I think those patients are always really difficult. There is some literature evaluating use of mitadrine to wean patients off vasopressors  when they're in that kind of post-sepsis resuscitation phase. And so I think there's ways to look at it. So I think definitely using other clinical endpoints,  as opposed to just MAP alone, to understand how you're optimizing outcomes in those patients is really important. And so if they are meeting those clinical endpoints, yes,  maybe potential alterations in their MAP target might be appropriate. But I also think once you're out of that post-resuscitation phase, using additional interventions,  such as mitadrine, could be a potential option in trying to wean those patients off these oppressors. Thank you. I just have a question, maybe? OK, I'm Shah from Allentown.  I'm in surgical critical care. Just a question. If your MAP is 60, and you already met your perfusion parameters, you know, base deficit and lactate, would you  change the MAP at that time? Sorry.  All right. Great question. And I get this question all the time. My patient's awake, alert, making urine. Everything looks good. Do you still want to drive the MAP up?  I think what we need to understand is that clinical judgment is one thing, and it certainly influences the ultimate decision making. But based on the data that we have published,  and those are, remember, retrospective large data sets, there is always an element of confounding. So we don't really know whether hypotension caused the organ  system injury, or whether hypotension was just a marker of organ system injury. But the key factor is things like myocardial injury,  which is just a troponin elevation in the absence of actual signs and symptoms of a heart attack, so to speak. And that part, I'm still skeptical about.  I do feel that there is strong association of myocardial injury after non-cardiac surgery with hypotension, even at MAPs of about 60. And those patients are dangerous,  because they're not going to have chest pain. They're not going to have EKG changes. All they'll have is a troponin elevation. You will argue that troponins can  be elevated in the ICU for a number of other reasons. But I will say that in the absence of evidence, it's probably better to be more vigilant with our blood  pressures, and still give them an appropriate MAP. What that MAP is, is probably still at least 65 for most of our patients. 10 years from now, if precision medicine tells us more,  I'm sure you and me are going to have different target MAPs than when we are patients in the ICU. Well, you also mentioned something about the steroids.  What is the status of the MAP protocol now? So I had the pleasure of moderating Bala Venkatesh's panel yesterday. And his recommendations were, he puts his patients  on hydrocortisone if they're mechanically ventilated, and septic shock on six hours of vasopressors. It doesn't have to be your second vasopressor.  It can just be your first vasopressor. He does not believe in the dose amount of vasopressor. Neither did the adrenal trial in roll patients  based on the dose amount of vasopressors. Mechanically ventilated septic shock on vasopressor, hydrocortisone does help. And that was shown in the adrenal trial. Thank you.  Hi, my name's Alyssa Holman. I'm from Raritan Bay in New Jersey. So one of my questions is, what is your thoughts on a higher  MAP target for patients who are on the targeted temperature therapy after a cardiac arrest? Like that period of time where they're like hypothermic,  is there a benefit to having a higher MAP goal, like 80 or such?  Thank you for the question. I didn't specifically look into that subset of patients. I'm not sure that I can 100% answer that for like the targeted temperature management patients.  What would be the rationale? Peripheral vasoconstriction? I think so. Because at our facility, we have this policy that states just universally target a higher MAP goal.  And I haven't yet found significant literature to support that. So I was just wondering if your expertise had found anything. Pardon me, is it OK if I interject? Please, go ahead.  Jake Jensen from Mayo Clinic. So the rationale for using a higher MAP goal in patients who have suffered cardiac arrest is the theory  that they lose cerebral autoregulation of blood flow. And they may not be able to maintain adequate cerebral perfusion at normal MAP.  The problem is that the studies have been predominantly observational and are highly confounded. There's a small randomized trial that did not  show a benefit in using a higher MAP goal for those patients. But it's an open question because the studies have been underpowered.  But it has to do with altered cerebral blood flow. Sorry to interrupt. Thank you.  Pablo Echeverria from O'Fallon, Illinois. I'm one of the intensivists. Working when we talk about quality in our ICU, we're very interested in moving away  from central catheters and central lines and use of pressors peripherally. Now we have more tools, ultrasound at the bedside, non-invasive cardiac output monitoring.  So I just want to know if there's any, there's no really data out there. But if there's any, you know, you have any experience developing protocols as far  as the use of the pressors. We're using up to 12 to 24 hours peripherally. And so far we get pretty good outcomes.  So I can just speak for my institution. We definitely preferentially want them to be administered via the central line. However, in emergency situations  we do allow the use in peripheral. We have not looked at our experience in terms of what, you know, do we have any adverse effects or anything like that.  But you know, that would actually be a pretty interesting cost-effectiveness model that we can run. So I have no idea. So I'll close out the session. I'm sorry we're out of time.  I want to thank our panelists again for their tremendous insight in the topic. And please enjoy the rest of the conference.

Video Summary

The video features discussions on shock and vasopressors by two doctors. Dr. Jamie Gray focuses on blood pressure thresholds and vasopressor use, highlighting the need to balance increasing mean arterial pressure (MAP) with minimizing adverse effects. She presents studies comparing high and low MAP targets and vasopressor strategies but finds inconclusive results, stressing the need for further data. Dr. Ashish Khanna discusses the evolution of vasopressors and landmark trials comparing different medications. He notes that while vasopressors can achieve hemodynamic stability, their direct impact on mortality in the ICU is uncertain. Dr. Khanna mentions the potential benefits of angiotensin II as a vasopressor and suggests that catecholamine-sparing strategies and adjunctive therapies may be the future of sepsis treatment. The transcript, on the other hand, focuses on the cost-effectiveness of vasopressor medications in septic shock treatment. The speaker emphasizes multimodal therapy and discusses the use of steroids and vitamins in combination with vasopressors. They introduce a cost-effectiveness analysis model that evaluates different vasopressors, with vasopressin deemed the most cost-effective. The importance of personalized medicine, maintaining adequate mean arterial pressure, and considering higher MAP goals in specific patient populations is also discussed. Ultimately, both the video and transcript stress the need for individualized care, further research, and cost-effectiveness considerations in using vasopressors.

Asset Subtitle

Pharmacology, Shock Non Sepsis, 2020

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2020 Critical Care Congress held February 16-19, 2020, in Orlando, Florida, USA.

Learning Objectives

Discuss the use of vasopressors in precise patient clinical scenarios during resuscitation in sepsis and septic shock
Explore new and novel vasopressors in comparison with older vasopressors as an evidence base to evaluate the role of each during evolution of therapy over the past two decades
Define and describe the effects of different degrees of hypotension in critically ill patients in the ICU
Analyze the effects of vasopressor costs with clinical outcomes during the course of patient treatment

Defining and Defending a Mean Arterial Pressure in Vasodilatory Shock

Jaime Robenolt Gray

Evolution of Vasopressors Over the Past Two Decades: Where Is the Evidence?

Ashish K. Khanna

Cost Effectiveness Versus Outcome Effectiveness: Is There a Right Balance?

Simon W. Lam

Meta Tag

Content Type Presentation

Knowledge Area Pharmacology

Knowledge Area Shock Non Sepsis

Knowledge Level Foundational

Membership Level Select

Membership Level Professional

Membership Level Associate

Tag Vasoactive Agents

Tag Economics

Tag Shock

Year 2020

Keywords

shock

vasopressors

mean arterial pressure

adverse effects

vasopressor strategies

landmark trials

sepsis treatment

cost-effectiveness

steroids

personalized medicine

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