SCCM Resource Library-May Journal Club: Spotlight on Pharmacy (2022)

Video Transcription

Hello, and welcome to today's Journal Club Spotlight on Pharmacy webcast, which is supported by the Society of Critical Care Medicine's CPP section.  My name is Bobby Svertoli, Critical Care Pharmacy Specialist in the Medical ICU at SSM Health St. Louis University Hospital in St. Louis, Missouri.  I will be monitoring today's webcast. A recording of this webcast will be available to registered attendees.  Log in to mysccm.org and navigate to the My Learning tab to access the recording.  Thank you for joining us today. A few housekeeping items before we get started. There will be a Q&A session after each of today's speakers.  To submit questions throughout the presentation, type into the question box located on your control panel.  You will also have the opportunity to participate in several interactive polls. When you see a poll, simply click the bubble next to your choice.  You may also follow and participate in live discussion on Twitter, following sccmcppjc and PharmICU.  Please note the disclaimer stating that the content to follow is for educational purposes only. And now I'd like to introduce your speakers for today.  Each will give a 15-minute presentation followed by a Q&A. Our first presenter today is Blake Robbins, PGY-2 Critical Care Resident at University  of Kentucky Health Care in Lexington, Kentucky. Our second presenter is Erica Allen, PGY-2 Critical Care Resident at Froedtert Hospital in Milwaukee, Wisconsin.  And our third presenter is Marjorie Peck, PGY-2 Critical Care Resident at St. Vincent Indianapolis Hospital in Indianapolis, Indiana.  And now I'll turn things over to our first presenter. All right. Thank you, Robert, for that introduction.  Again, everyone, my name is Blake Robbins, and today I'll be discussing a recent trial entitled epinephrine versus norepinephrine in cardiac arrest patients with post-resuscitation  shock.  All right, so mortality with out-of-hospital cardiac arrest is roughly 90 percent, and this has largely remained true over the last three decades.  We've not been able to move the needle much. The most common causes of death from cardiac arrest or out-of-hospital cardiac arrest are  neurologic injury followed by cardiovascular injury, and this can include refractory shock and recurrent cardiac arrest, and then multiple organ failure.  The American Heart Association has incorporated this chain of survival for outside-hospital cardiac arrest, starting from activation of emergency response all the way to recovery.  And where we commonly fall in as either emergency medicine or ICU pharmacists is in either continued  advanced resuscitation or, as we'll talk about mostly in this presentation, post-cardiac arrest care, post-resuscitation shock.  So post-cardiac arrest care is a critical component, as I mentioned, of the chain of survival, and it encompasses many factors, including hemodynamic support, mechanical  ventilation, temperature management, the treatment of underlying causes, and the treatment of seizures, all of which have had extensive study and specific outcomes or not related  to those. So what defines optimal hospital care or optimal hemodynamic support for these patients who  have achieved a return of spontaneous circulation or ROSC really is not completely known, and  there's increasing interest in identifying and optimizing these practices that are likely to improve outcomes or may potentially improve outcomes.  So for this presentation, we're going to focus on optimization of hemodynamic status and the management of post-resuscitation shock.  This optimization is useful for improving prognosis. We typically have a MAP goal of 65, although this can be individualized, and that's recommended  in both the European and American guidelines. And in addition, about 50 to 70 percent of patients will have post-resuscitation shock following an out-of-hospital cardiac arrest.  This post-cardiac arrest is a mixed shock picture. So initially, patients will develop a reversible myocardial dysfunction, also known as myocardial  stunning, and then this is followed by ischemia reperfusion syndrome, and this commonly leads to vasoplegia.  And if we look at the immunoinflammatory profile of these post-resuscitation shock patients, it largely resembles our sepsis patients with SIRS-related inflammatory response  mediators. The optimal vasopressor for post-resuscitation shock still remains unclear. The use of vasopressor agents mostly relies on expert opinion due to a lack of randomized  control trials, and this leads to questions surrounding both the safety and the efficacy of these agents.  And all of these agents work similarly with alpha receptors or vasopressin with the B1 receptor, and then they have some additional mechanisms that can also be limited by their  side effect profile. When we think about higher doses of these agents, a lot of times we think of arrhythmias that they're associated with, as well as some peripheral ischemia.  There's not been much, as I've said, done head-to-head with these, especially in the setting of out-of-hospital cardiac arrest.  There was a randomized control trial done with 280 patients in the subgroup analysis evaluating dopamine and norepinephrine, and this led to increased mortality in a subgroup  analysis with dopamine in these patients with cardiac or cardiogenic shock. And so, largely, we now have norepinephrine or epinephrine that are most commonly utilized  in these patients. And as I mentioned, there's a lack of data specifically comparing these two agents themselves.  Both of them have the potential to cause arrhythmias, but experimental studies do suggest that patients  receiving epinephrine may be more prone to arrhythmias due to a mismatch between oxygen consumption and supply.  And there's a lot of animal data correlating that or corroborating that. And this presentation is not going to focus on resuscitation itself, but I do want to  mention there's also data surrounding epinephrine use in ACLS, where higher doses of epinephrine  or later time points in cardiac arrest have also been shown to cause or lead to some worse neurologic outcomes.  But again, we'll focus on post-resuscitation shock, as this study did. Oh, sorry. All right, so there have been a few, at least systematic reviews evaluating pressor choices  in acute circulatory failure. So this was a systematic review done in 2016, and this was by Moeller and colleagues where  they stratified different shock states and then evaluated the literature to determine some recommendations for first-line treatments.  And so we can see here for shock in general or shock states in general, norepinephrine was recommended over epinephrine based on low quality of evidence.  Researchers believe that the potential harm associated with epinephrine has not been adequately assessed and therefore they provided a weak recommendation for norepinephrine use.  And then the quality of evidence was low due to imprecision and a risk of bias in all of these studies that they assessed.  If we look at cardiogenic shock in particular, they have no recommendation regarding the use of norepinephrine or epinephrine in these patients.  We also have some data surrounding epinephrine versus norepinephrine in cardiogenic shock following an acute MI in general.  So in 2018, Levy and colleagues conducted a prospective double-blind multi-centered randomized control trial that evaluated the efficacy and safety of epinephrine compared  to norepinephrine in patients with cardiogenic shock after an MI. The primary efficacy outcome was cardiac index evolution, and the primary safety outcome  was the occurrence of refractory cardiogenic shock. This was defined as sustained hypotension or end-organ hypoperfusion as well as high inotrope or vasopressor doses.  What they found was that in patients with cardiogenic shock secondary to acute MI, the use of epinephrine compared to norepinephrine had similar effects on arterial pressure and  cardiac index, but they actually terminated the study early due to higher incidences of refractory shock in the epinephrine group.  And this was a very small study of about 57 patients or so. And so largely data in randomized control trials on vasopressor use post-arrest is scarce.  American guidelines note this evidence gap for appropriate management and list norepinephrine and epinephrine as appropriate vasopressors for this indication.  The European guidelines take a slightly stronger stance. They recommend norepinephrine as first line.  However, they do mention that this recommendation is purely based on familiarity with norepinephrine and not necessarily hard set data. And so that leads us to our study today.  So Bujuin and colleagues sought to compare the association of epinephrine versus norepinephrine  use with specific outcomes of patients admitted alive to the ICU with post-resuscitation shock after being successfully resuscitated from an out-of-hospital cardiac arrest.  So very niche patient population, but one that we do see frequently. All right. So this was an observational multicenter study.  This was five university hospitals within Paris, France metropolitan area. This was conducted between 2011 and 2018. Data was collected using Utstein templates.  So if you're unfamiliar with this, it's a template that helps to facilitate reporting of bystander witnessed shockable rhythm as a measure of like emergency medical service  systems and tries to help categorize and tease out some of these different pieces that it collects to try to identify any specific contribution to out-of-hospital cardiac arrest.  So again, things like bystander contribution or shockable rhythm. And so this was actually prospectively collected through these templates, but then retrospectively  observed and the outcome data was also retrospectively collected. They included patients who were admitted to an ICU alive after out-of-hospital cardiac arrest.  And they only included patients that had post-resuscitation shock, which was defined as a need for vasopressors  greater than six hours despite adequate fluid loading to target a map of 65 millimeters of mercury. Inclusion criteria included obvious extracardiac causes of cardiac arrest.  So things like trauma. They excluded patients with refractory cardiac arrest who never achieved ROS, refractory  shock requiring ECMO, any absence of continuous IV treatment with either epinephrine or norepinephrine.  And then they excluded patients that had continuous intravenous treatment with both epinephrine and norepinephrine in their primary analysis.  For primary outcome, they looked at all-cause mortality during the hospital stay. And then they had secondary endpoints, including cardiovascular-specific mortality, which is  defined as recurrent cardiac arrest or refractory hemodynamic shock, and an unfavorable neurologic status at hospital discharge using a CPC score.  So this is the cerebral performance category score. It's a marker of function, essentially, where one is conscious with normal function or only  slight disability, all the way up to four being comatose or a vegetative state, and then five being death.  So they considered unfavorable to be severe disability all the way to death, three to five. All right, so moving into the statistics, for statistical analyses, they did a lot of  different things, including some robust sensitivity and propensity scoring. So continuous data was described as mean plus standard deviation or mean in interquartile range.  When appropriate, they used categorical data described as the number of percentage, and then they used student t-test, Mann-Whitney test, or Pruskall's-Wallace test as appropriate.  Categorical variables were used, they used the chi-square test, and then p-values of less than 0.05 were considered statistically significant.  They did only include cases without missing values, which I think is appropriate to note. So for their multi-logistics regression, they looked at several different parameters that  are associated with outcomes for out-of-hospital cardiac arrest and then post-resuscitation shock.  So I've listed several of these there, so they did a multivariate regression analysis here. They also performed several sensitivity analyses.  So they looked at cardiovascular-specific mortality or unfavorable neurologic outcome as the primary endpoint, so as opposed to all-cause mortality.  They also looked at the exclusion of patients who died within 12 hours of hospital admission. They looked at patients who did not receive any epinephrine prior to ROS.  And then they also looked at CAHP subgroups on either side of the median value. And so the CAHP score, Calculated Cardiac Arrest Hospital Prognosis, is a simple tool  for early stratification of patients admitted to the ICU, where less than 150 would represent a 39% favorable outcome.  So I kind of equate it to maybe like a SOFA score or something like that, and it includes parameters like age, non-shockable rhythm, time from collapse to basic life support,  time from basic life support to ROS, the location of the arrest, epinephrine dose, and then arterial pH.  And then also, because there is the possibility of an indication bias, since this is a retrospective  review for the choice of epinephrine versus norepinephrine, they also performed a propensity  analysis based on the prescribing of epinephrine or the likelihood that the patient got prescribed epinephrine.  And so they adjusted for confounders, including initial rhythm, time from collapse to CPR, time from CPR to ROS, arterial pH, myocardial dysfunction, and the recipient hospital.  So again, while this is a retrospective review, they did a robust statistical analysis with a lot of different secondary analyses.  And then moving on in terms of results, so of the 1,421 patients that were admitted alive after outside hospital cardiac arrest, 766 patients were included after these exclusion  criterias. And I do want to note that they did see 131 patients with both epinephrine and norepinephrine  utilized, because they did do a sensitivity analysis on those patients as well. And so 63% of patients received norepinephrine, whereas 37% received epinephrine.  That's probably mostly consistent with my practice that I see.  The majority of patients are routinely started on norepinephrine, whereas certain patients, based on their parameters, which we can talk about, do receive epinephrine post-arrest.  In terms of baseline characteristics, so again, all of this was collected by those Utstein templates.  The median age was 64, 73% of patients were male, the median time from collapse to CPR was five minutes, and the median time from CPR to ROS was 22 minutes.  All patients were mechanically ventilated and sedated. And then of note, epinephrine groups did have, or sorry, less often had an occurrence at home.  They less often had an initial shockable rhythm, and they had a longer time from CPR to ROS. Looking at other baseline characteristics, the epinephrine group in general was sicker  at baseline. So these patients had a lower initial pH, a higher arterial lactate, and more myocardial  dysfunction with lower ejection fractions noted, as well as a lower rate of coronary angiograms performed.  The maximal dose in 48 hours for the norepinephrine group was 0.6 microns per kilo per minute, whereas the maximum dose of epinephrine was 0.7.  And then for duration of catecholamine support, it was 30 hours for norepinephrine on average,  and the median was 30 hours, and then the median for our epinephrine group was 24 hours.  So in terms of results, overall, 31% of patients survived to hospital discharge.  Among patients treated with norepinephrine, 61% died in hospital. So 11% were from cardiovascular causes, whereas 45% were from other causes of death,  and 5% had missing causes of death. Among patients treated with epinephrine, there were 83% of patients that died in the hospital.  41% of those were from cardiovascular causes, 35% from other causes of death, and then 7% were missing a cause of death.  In terms of all-cause mortality, there was a statistically significant difference. So higher all-cause mortality in the epinephrine group with that 83%.  And then here, I've just broken down those percentages that I stated earlier. So also a higher incidence of cardiovascular-specific mortality, as well as death from  refractory shock and recurrent cardiac arrest in those patients, broken down further.  So as I mentioned, they did several adjusted multivariate analyses. So after adjusting for this, epinephrine infusion was independently associated  with all-cause mortality with an odds ratio of 2.6.  Again, sensitivity analyses were performed after excluding moribund patients,  patients with a lower CAHP score, patients with a higher CAHP score, and patients treated with epinephrine before ROSC. And all of this found consistent results.  Epinephrine was found to increase mortality when considering the association of cardiovascular mortality, ICU mortality, and unfavorable neurologic outcome.  And then results were also consistent across all subgroups, including those with shockable rhythms and cardiac causes of outside hospital cardiac arrest.  Lastly, an analysis was performed on patients receiving both basopressors and still found that epinephrine utilized first was associated with higher mortality.  They also did an adjustment on propensity score and other prognostic variables, and again, found that epinephrine infusion was statistically associated with all-cause mortality and  cardiovascular-specific mortality. And then lastly, they did a conditional logistic regression analysis of 93 matched patients,  so matched one-to-one with their propensity scores, and still found that while there was  not a significant increase in all-cause mortality with a p-value of 0.08, it still trended towards  significance in the matched cohort, though this was only, I think, 93 patients, so a lower sample size.  So in terms of discussion, the authors concluded that continuous epinephrine was associated with significant increases in both all-cause and cardiovascular mortality when compared  to norepinephrine. This association was robust in various populations and multiple methodologic approaches,  and they mentioned several risk factors for poorer outcomes were common in the epinephrine group, but the association did persist with several analyses in the attempt to mitigate  these confounders. In terms of study strengths, this was a very large cohort, or so the largest cohort to  date of 766 patients, specifically looking at post-resuscitation shock after out-of-hospital cardiac arrest.  I applaud their multi-center design, and I also believe that their statistical analyses  were very robust to help mitigate the retrospective design of this study in any compounding variables.  So while that is a limitation of an observational design, I do think that this is a very robust of an observational design.  I do think that this helps us further interpret these results, and I think they're a little bit more reliable in that manner.  But since it's an observational design, we cannot definitively conclude causality.  We cannot exclude an indication bias regarding the use of epinephrine despite the propensity scores.  Epinephrine administration before Ross may also act as a confounder. Again, they tried to mitigate this.  They were unable to assess any potential dose effects of epinephrine, which I think would be interesting to note.  It's unclear which patients required multiple vasopressors. So we only had 131 who had norepinephrine or epinephrine, but it really only assessed ionotropic equivalency.  So unclear which ones also got dibutamine versus vasopressin.  There was no surrounding, no data surrounding fluid resuscitation, so they only included patients that had, quote, adequate fluid resuscitation.  But throughout the supplemental materials and the study itself, there was no data surrounding this. And we know this is a mainstay of outside hospital cardiac arrest.  And if patients had lower ejection fractions and things like that, that could have contributed to worse outcomes. There was no data surrounding shock etiology specifically.  So for instance, anaphylactic shock, these patients would not be considered part of the study if we're evaluating epinephrine versus norepinephrine.  We would be choosing epinephrine in that case. And so that was not specifically teased out. And then there was no data surrounding adverse effects.  So when we talk about why we care, we think about arrhythmia risks and such, and that was not evaluated in this study.  So for my conclusions, the research surrounding out-of-hospital cardiac arrest and cardiogenic shock remains challenging.  This was a retrospective analysis, and it likely won't lead to significant changes in current practice.  As I said, we typically use, here at UK, norepinephrine over norepinephrine more empirically as a first-line agent.  And European guidelines support this as well, just based on familiarity, though I do think that vasopressors should continue to be individualized based on patient-specific factors.  So if we have a patient who they ultrasounded or they got an echo and they just need a little  bit of inotropic support, which is different from what this study was really looking at,  I think low doses of epinephrine are reasonable, or even trialing epinephrine based on patient-specific factors.  But overall, I think we can feel comfortable with using norepinephrine in the majority of our patients.  And then where do we go from here, or next steps? We just need randomized controlled trials assessing these first-line therapies.  And I think we should also include the addition of additional vasopressors or inotropes to further align with our clinical practice.  So looking at which patients receive dibutamine or vasopressin and trying to tease out outcomes based on that as well.  So with that, I will start my first assessment question. So American Heart Association guidelines recommend norepinephrine over epinephrine as a first-line  agent for cardiogenic shock post-arrest. True or false?  All right, so 64% of you said false majority, which is correct. So the American Heart Association does not take a strong stance on norepinephrine versus epinephrine.  They actually also mentioned that dopamine is also a potential agent that you can use, though we have, I think, a little bit better data to support against that.  I do want to mention that when we're thinking about these patients that are transferred and what they might be transferred on, I think it's good to know that dopamine is a  pre-mixed medication, so it comes in a pre-mixed bag, and it's a little bit less expensive than maybe norepinephrine or epinephrine, which we compound at my institution.  I did a search, and Baxter actually recently has a pre-mixed bag of norepinephrine available, but I'm not really sure that that's made its way onto EMS carts.  I'd be interested to know after this which agents you see patients commonly transferred on when they're arriving by EMS, but you might see more dopamine being given initially,  so just something to note.  Sorry, move to the next one. So that's false. And then based on the results of this observational study, epinephrine significantly was associated with which of the following?  All-cause hospital mortality, cardiovascular mortality, unfavorable neurologic outcomes at discharge, or all of the above?  All right, and the majority of people said all of the above, which is correct. So they saw a significant increase in all of these outcomes.  All right.  Okay, all of the above. All right, and there's my references. And with that, I can take any questions that you guys may have or if you want to share any experiences.  Our first question today is, did they report what percentage of patients had recurrent cardiac arrest, specifically V-Fib, between the two groups?  And did they comment on whether this impacted the increase in mortality?  Okay, so the question was, did they report how many patients specifically had recurrent cardiac arrest? So yeah, they broke that down.  Like cardiovascular-specific mortality had two components. One was like recurrent arrest, and then the other was refractory shock.  They didn't specifically know if the recurrent arrest was a shockable rhythm versus not. And I think I have that in a previous slide here. So the patients that actually had...  The patients that had cardiovascular causes was 11% in general. I don't know if they further broke that down based on like the recurrence of a shockable rhythm.  Well, they didn't say shockable rhythm versus refractory like hemodynamic shock. They just noted that the 11% were from cardiovascular causes specifically.  But I can try to dig into that deeper. I did not come across that.  And the second question, did they comment at all on the blood pressures or the heart rates that were seen in these patients between the groups or any differences there other  than just doses? No, not that I could see. They just had their goal of like 65. They didn't comment on like their ability to achieve that or, yeah, like really any  kind of safety or efficacy data other than those outcome datas.  Other trials have kind of looked at this, like the ability for epinephrine or norepinephrine to be able to achieve like an appropriate blood pressure goal, and that's shown no  difference. So like that levy trial showed no difference ultimately with like their efficacy of being able to achieve a map of 65.  But in terms of heart rate or arrhythmias or things like that, they did not specifically report anything other than more testing.  They did not specifically report anything other than mortality and unfavorable neurologic outcome.  Okay, that concludes our Q&A session. Thank you, Blake Robbins. Thank you. Before moving on to our next presenter, we would like to ask a brief polling question  regarding today's attendance to gain a better understanding of our overall attendance to ensure continued support of this Spotlight on Pharmacy webcast.  How many people at your site are watching today's webcast? With me, 2 to 5, 5 to 10, or greater than 10 people.  Now, I'd like to introduce our second presenter, Erika Allen. Hi, everyone. Thank you so much for attending today.  So, today, I will be presenting on a retrospective study that looked at the comparison of early versus late initiation of hydrocortisone in patients with septic shock.  So, studies have shown that patients with septic shock may develop a relative corticosteroid  insufficiency that can result in an amplified inflammatory response and diminished catecholamine response.  The most updated surviving sepsis campaign guidelines in 2021 currently suggest the use of IV corticosteroids in patients with septic shock and ongoing vasopressor requirements.  Hydrocortisone is usually preferred in septic shock due to its glucocorticoid and mineral corticoid activity that kind of resembles the actions of cortisol.  Current evidence does suggest that hydrocortisone use reduces time-to-shock resolution, but the impact on mortality kind of varies between studies.  However, the optimal time to initiate hydrocortisone in septic shock remains unknown.  Several large randomized studies have looked at the use of steroids in septic shock listed in this table.  As you can see, going from left to right in the column, the hydrocortisone, or the, excuse me, the steroid regimen used between these studies differs.  The time to steroid initiation was different between the studies since it was not standardized.  Patients were just required to be on vasopressors for a certain period of time as part of the inclusion.  At hydrocortisone, or hydrocortisone-ampligocortisone initiation, the vasopressor doses at baseline were different between the studies.  And then when looking at the results, some studies found a reduction in mortality, while others did not.  But kind of across the group, it does show that the time to reversal of shock was shorter with steroid use.  Some smaller studies have been done to try to specifically assess the time of steroid initiation in septic shock. The first one being a study by Park and colleagues in 2012.  This was a retrospective single-center study that looked at 178 patients. And they found that the median time to initiation of steroid therapy was significantly shorter  in patients who survived versus those who did not survive. So, we're looking at about 6 1⁄2 hours versus 10 1⁄2 hours in patients that were receiving steroids earlier.  The next study was done in 2014, Katanas and colleagues. This was a prospective observational study, so it was not randomized, that looked at 170 patients.  And part of the inclusion for this study was receiving a norepinephrine dose of at least 0.5 micrograms per kilogram per minute.  They defined early hydrocortisone initiation as within nine hours of vasopressors. And they found that there was a greater proportion of survivors in the patient group that received  early hydrocortisone. So, about 52% versus about 31%. And they also found an earlier withdrawal of vasopressors in patients who received early hydrocortisone therapy.  However, given the lack of robust data that specifically looks at the timing of steroid initiation, we still don't really know what is the optimal time to initiate hydrocortisone  and septic shock. So, the study I'll be talking about today was published in 2022 in the Annals of Pharmacotherapy  that kind of specifically tried to look at this question, comparing early versus late initiation.  So, the study objective was to evaluate the impact of early versus late initiation of hydrocortisone and septic shock.  This was a retrospective, multi-centered observational study done at three hospitals in Jacksonville,  Florida, looking at patients that were admitted between July of 2014 to August of 2019. They included patients that were at least 18 years old, had a diagnosis of septic shock,  some were receiving vasopressor therapy, receiving hydrocortisone at less than or equal to 300 milligrams per day, and receiving IV antibiotics.  They excluded patients who were found to have cardiac vasoplegia syndrome, had received corticosteroids in the previous 30 days, had a history of adrenal insufficiency at baseline,  had a documented cardiac arrest within the last 30 days, or if patients were pregnant or had a history of incarceration.  They defined patients to have early initiation of hydrocortisone if it was started within 12 hours of vasopressor initiation, and then late initiation was defined as over 12 hours  after vasopressors were initiated. And then to be considered discontinued off vasopressors, they had to be off for at least 24 hours.  The primary outcome of this study was time-to-vasopressor discontinuation, and they also had a number  of secondary outcomes, which included in-hospital mortality, ICU and hospital length of stay,  IV fluids administered in the first 72 hours, the need for renal replacement therapy, the  maximum norepinephrine-equivalent dose required, the number of vasopressors required, and total insulin requirements.  For statistical analysis for the primary outcome, the authors estimated that 120 patients in each group would be needed to achieve 80% power to detect a mean difference of 12 hours  between the groups. They did use a Kaplan-Meier curve with Wilcox-Logged Rank Test, and they also used propensity score  matching to try to take into account any confounders at baseline between the two groups.  So, the factors that they used for matching included age, gender, BMI, history of hypertension,  diabetes, heart failure, COPD, initial GCS score, initial SOFA score, the source of infection, use of flugiacortisone, use of mitadrine, the number of vasopressors, and finally, the  maximum dose of vasopressors. They also conducted a multivariable linear regression to analyze the impact of time to hydrocortisone initiation on vasopressor duration.  For this study, 305 patients were reviewed, and 240 of those patients met inclusion criteria. After conducting propensity matching, 198 patients were left with 99 in each group.  The median age of these patients was 59 years old, with a median BMI of 29. The most common sources of infection were respiratory and intra-abdominal, and below  were some additional relevant baseline characteristics, with the median SOFA score in the two groups being 12, which kind of correlates to a mortality risk of about 40 to 50%.  And as you can see, between the early and the late hydrocortisone groups, there was a significant difference with the elastic acid, the MAP at vasopressor initiation, and  the norepinephrine-equivalent dose at hydrocortisone initiation. As you can see, in the early hydrocortisone group, the elastic acid was higher, the MAP  was lower, and the norepinephrine-equivalent dose at hydrocortisone initiation was higher. And then finally, the use of fujicortisone and mitadrine was relatively low, with less  than 25% of patients receiving those interventions.  And going into the results, the first of the primary outcomes, they found that early hydrocortisone  was associated with a significantly shorter duration of vasopressors, with the average being about 41 hours versus about 60 hours, and this was statistically significant.  When they conducted the linear regression model, this estimated that every hour hydrocortisone  was delayed from the start of vasopressors, this increased the duration of vasopressors  by 52.8 minutes, and this was statistically significant.  For secondary outcomes, early hydrocortisone initiation was also associated with a reduction  in ICU and hospital length of stay, but was not associated with any difference in hospital mortality.  Some of the additional secondary outcomes that were reported, specifically looking at the propensity score matched patients, there was no difference between the two groups in  terms of IV fluid administration, total insulin units required, the maximum norepinephrine  equivalent dose required, need for renal replacement therapy, or the number of vasopressors required.  The authors also conducted some post-hoc analysis, first looking at some subgroup analyses. So, the three subgroups that they looked at included norepinephrine equivalent dose, BMI,  and hypertension history, and they found that in all three of these subgroups, early initiation of hydrocortisone was associated with a reduction in vasopressor duration.  When looking further at the hydrocortisone dose, looking at patients who received less  than or equal to 200 milligrams per day versus patients who received greater than 200 milligrams  per day, they found no difference in vasopressor duration between those two hydrocortisone groups.  And then, finally, when looking at patients who received fujicortisone and patients who had early hydrocortisone initiation, patients that had fujicortisone use actually had a  longer time to vasopressor discontinuation, and patients in the late hydrocortisone group had no significant difference.  But overall, among all the patients who received fujicortisone, they did find a longer time to vasopressor discontinuation, which was kind of unclear why that may be found as a  result. But as I mentioned before, the use of fujicortisone in this cohort was less than 25%, so maybe there just wasn't enough patients.  So, the authors concluded for this study that their results suggest that earlier initiation  of hydrocortisone, which they defined as within 12 hours of vasopressors, or the treatment of septic shock is associated with improved time discontinuation of vasopressors and a  shortened ICU and hospital length of stay. Let's dive a little deeper into the study and what some of the clinical impacts may be.  So, first, looking at the strengths of the study, I thought that they had an appropriate study population utilizing appropriate inclusion and exclusion criteria.  And the patients at baseline were relatively sick, requiring multiple vasopressors, a median SOPA score of 12, which, like I mentioned, correlates to an estimated mortality risk  of 40 to 50%. They also conducted a propensity score matching, which adjusted for confounding variables,  which I thought was a great way to kind of exclude most confounders for the outcomes that they looked at.  They did look at clinically relevant outcomes and subgroup analyses, and I believe that they had appropriate statistical analysis for what they were looking at.  And then, finally, with the linear regression analysis, the 12-hour cutoff that they used was a little bit arbitrary.  They used the 12-hour threshold because, at the study site, the intensivists rounded every 12 hours, which is usually when treatment decisions were made, so that's why they used  the 12-hour mark. But in order to look at the impact of hydrocortisone timing as a whole, they utilized the linear regression analysis.  Now, looking at the limitations, being a retrospective study, we were not able to really make any  definitive conclusions on, you know, cause and effect, and it was reliant on accurate charting to look at the variables.  And then, after propensity score matching, it did have a smaller sample size. It did not meet the power calculation that they conducted.  They did report they had a nonstandardized approach to patient selection, so not knowing if it was consecutive or if they had any other criteria for how they selected patients in  their data poll. They were underpowered to detect a significant difference in mortality. And something major is that they did not report the timed antibiotic initiation, which, as  we know, is a major factor into outcomes, especially mortality in patients with septic shock.  In terms of the hydrocortisone usage, there was a lot of things unknown about the regimen. There was an inconsistency in dosing.  The authors did report that about 66% of patients received a regimen of 50 milligrams IV every  6 hours, but then the rest of those patients had different dosing regimens, so it's a little hard to combine all those into the same regimen.  There's an unknown duration of steroid usage, so I don't know how long the patients were receiving steroids for.  In most of the landmark trials, patients received steroids for about 7 days, plus or minus a taper.  There was also unknown steroid discontinuation methods, if patients were abruptly stopped on their steroids or if they had a taper in place, which could also impact some of the  outcomes. And then we also don't know the actual mean or median time to hydrocortisone initiation in these patients. We just have the greater than or less than 12-hour marker.  And lastly, there was an unknown recurrence of vasopressor usage after patients were discontinued, so not knowing if patients had to eventually go back on vasopressors.  Some takeaway points that I have from this study, so it does suggest that early initiation of hydrocortisone in septic shock may reduce the duration of vasopressor usage and length  of stay. It is important to note that the early hydrocortisone group did have a higher lactate and a higher  norepinephrine-equivalent vasopressor dosing at baseline, which could confer to that patient group having a higher risk of mortality at baseline.  When they looked at hydrocortisone dosing subgroups, it was found that the dosing didn't really impact the duration of vasopressor use.  However, it's still important to note that with all these results, the study is very limited by its retrospective nature, its small sample size, and the lack of some pertinent  treatment information that we would usually need for clinical applicability, such as specific hydrocortisone dosage, duration, and discontinuation methods.  In terms of how I think this will impact practice, again, with a retrospective study that's relatively small, likely won't lead to any significant change in current practice.  However, this study's results mixed with some previous studies. I do think it's reasonable to consider early initiation of hydrocortisone in patients with  septic shock, especially in those who are requiring significant vasopressor therapy. And although this study and previous studies may not have found a mortality difference,  I do think that the consistent showing that hydrocortisone usage reduces time on vasopressors is also an important outcome.  And this study does suggest that the earlier we start the hydrocortisone, even more so we can reduce the vasopressor duration.  So, some next steps and questions I think we have for this topic. We do need a larger prospective randomized control trial needed to validate the benefit  of early hydrocortisone initiation. And based on the heterogeneity of previous landmark studies, we do need clarification  on the impact of maybe the time from vasopressor initiation, the vasopressor dose at the steroid  initiation, and possibly even the baseline map or lactate at the time of steroid initiation. Is there a cutoff that we should be using to start patients on hydrocortisone therapy?  Now transitioning into our Q&A and discussion section, let's do some polling questions to kind of gauge the practice of the audience.  So, what is the steroid regimen for septic shock in your current practice? Do you use hydrocortisone 50 milligrams IV every six hours, 100 milligrams IV every  eight hours, a continuous infusion, some sort of regimen with hydrocortisone and flujocortisone, or other, and feel free to put any other thoughts you have in the chat.  It looks like the overwhelming majority of people said 50 milligrams IV every six hours for their  hydrocortisone regimen. That is the most common, that is basically the regimen that's been studied  in a lot of landmark trials. Two landmark trials did use hydrocortisone and flujocortisone,  but in both of those, the hydrocortisone dosing was 50  IV every six hours, which I also think is probably the most common regimen, the one that I use as well. So yeah, thank you for responding to that one. And then the second question,  when do you normally initiate hydrocortisone and septic shock in your current practice?  Is it A, simultaneously when starting basal pressors? Is it when your first basal pressor reaches a certain dose, when you're about to start the second basal pressor inotrope,  or other, and feel free to put any other thoughts you have in the chat.  All right, so kind of as I expected, a little bit of a spread between the responses.  So about half of the responders said when starting the second basal pressor or inotrope,  34% mentioned when the first basal pressor reaches a certain dose.  And then some people said other, some said simultaneously with the initiation of basal pressor. Yeah, I would say the most common that I've been seeing is definitely when the  basal pressor reaches a certain dose. And sometimes at that certain dose is also when  in our heads we're considering the second basal pressor anyway. So sometimes that kind of overlaps  with each other. But I would say kind of based on the landmark studies and other things that we've  seen, a lot of times the patients are receiving pretty significant basal pressor doses by the  time they're receiving hydrocortisone. So I think these responses do kind of match up with what  we've currently been seeing with evidence. But that is the end of my polling questions. If people  want to ask questions and discuss these further, I'm more than happy. Or if you have any other  questions, I'd be happy to respond to those too. Our first question for you is, did the authors  clarify if the primary outcome was specifically met only if a patient was alive and free from basal pressors? That's a good question. Let me look back at it here.  I don't believe they specifically mentioned that. I think if patients were...  I would have to look back at that specifically and get back to you. I want to say that if someone  had passed away while on basal pressors, they were deemed to have not been off of basal pressors.  But I think their duration was still included. But I would have to look back at that specifically.  And the second question has to do with their propensity scoring analysis. Did they  include factors like the timing, the severity of shock, and worse math, a lot of the factors that seem to be worse in the early group into their analysis?  Yeah. So with the propensity scoring, the factors that they mentioned that would most closely be  related to the things in that question, they did use SOFA score. They used the number of basal  pressors and the maximum dose of basal pressors. However, in the score matching, they did not use  initial map or initial basal pressor dose. And they did not report or use the specific time  of initiation, which I do think... I do wonder what would happen to the result if that was put  into the propensity score at baseline with these patients. But yeah, the map and the specific dose  at initiation was not used in the matching. But the number of basal pressors, the maximum dose of basal pressors in the SOFA score were included. So I think that can account for  some of the mortality risk and the severity of shock in patients, but they didn't include everything that I would also agree would also impact the severity of shock at baseline.  That concludes our Q&A session. Thank you, Erica Allen.  Now, I'd like to introduce our final presenter, Marjorie Peck.  All righty. Well, thank you, Robert. I'm just trying to take control of the screen here.  Oh, perfect. Well, thank you, Robert, again, for the introduction and for all those tuning in today.  My name is Marjorie Peck, and today we'll be discussing a recent study evaluating the impact of angiotensin II on patient outcomes in the medical ICU. As you can see,  the impact of angiotensin II on patient outcomes in the medical ICU. As a brief review, the surviving sepsis campaign guidelines support norepinephrine as a first-line basal pressor  and vasopressin as a second-line adjunct when goal mean arterial pressure is not achieved with  initial therapy or as a catecholamine-sparing adjunct to norepinephrine. Studies have cited mortality rates upwards of 50% in patients with refractory hypotension despite use of  high-dose vasopressors. There is limited guidance on third-line vasopressor selection in patients  requiring high doses of guideline-supported therapies like norepinephrine, vasopressin, and epinephrine, and there is also a lack of guidance for when or in whom to add newer agents  such as angiotensin II, which I'll refer to here as AT2, in patients with refractory distributive  shock. As a quick vasopressor recap, this slide demonstrates where each of our pressors work, the first being vasopressin, which increases systemic vascular resistance,  preserves blood volume, and enhances hemodynamic responsiveness to catecholamines. Catecholamines  work through activating adrenergic receptors, and angiotensin II affects the renin-angiotensin  aldosterone system or RAS system, resulting in direct vasoconstriction and retention of sodium  and water. The impact of angiotensin II in vasodilatory shock is not fully known. However,  I would like to briefly review what we do know so far, starting with the ATHOS-3 trial, which we'll  discuss in more detail later on. This study examined blood pressure response to AT2 in  patients with vasodilatory shock requiring total vasopressor doses greater than 0.2 mics per kilo  per minute. The authors reported an increase in MAP and reduction in total vasopressor requirements at three hours after initiation of AT2. A 2021 post-marketing study of AT2  reported similar outcomes in terms of blood pressure and vasopressor requirements at three  hours, but also observed that active vasopressin use and lower baseline lactate levels were  associated with hemodynamic responsiveness to AT2. And finally, a study published earlier this  year reported similar findings with regard to blood pressure response and vasopressor weaning.  However, neither of these post-marketing studies included a standard of care control group for  comparison, which brings us to the clinical question of what role AT2 might play in the management of distributive shock. While we know that it improves blood pressure, we don't  necessarily know if this translates into improved clinical outcomes, such as reduced mortality or  shorter ICU and high hospital length of stay. Therefore, the authors of this study sought to  evaluate the addition of AT2 as compared to a non-AT2 agent as a third-line vasopressor  in patients with catecholamine refractory septic shock with regards to in-hospital mortality and  blood pressure response at three hours. They included adult medical ICU patients with distributive,  primarily septic shock, who required at least three vasopressors during their hospital stay.  Septic shock was defined as suspected or proven infection as the primary cause of shock,  and all patients must have already been started on a standard of care regimen with norepinephrine  and vasopressin at doses exceeding what would be the equivalent of a norepinephrine rate of 0.2  mics per kilo per minute. Indication, dosing, and titration of AT2 and concomitant treatments for  shock were guided by the primary team, and AT2 was titrated every five minutes to attain a MAP of  greater than 65 or a dose of 40 nanograms per kilo per minute. The primary outcome was in-hospital  mortality from any cause, and secondary endpoints included MAP at three hours after starting a  third vasopressor, in this case either AT2 or a non-AT2 agent, as well as MAP response at three  hours with responsiveness defined as attaining a MAP of greater than 65 and non-response defined as documented MAPs of 65 or less, along with both hospital and ICU lengths of stay.  Regarding statistical methods, student t-tests and chi-square tests were performed to identify  pretreatment differences between groups, along with propensity overlap weighting to address  potential confounding, which we'll discuss further in the critique section. Multivariable logistic  regression was used to estimate the impact of AT2 on mortality, and a p-value less than 0.05  was considered statistically significant. The authors evaluated 606 patients for potential inclusion, 75% of whom were excluded due to either not having received three or more  vasopressors during admission, or having obstructive cardiogenic or hypovolemic shock.  56 of the 147 patients included received AT2 as a third-line vasopressor, while the remaining  91 received another catecholamine as a third-line vasopressor. Taking a closer look at the patients  included, significant differences were noted in baseline characteristics. Therefore, the authors  used propensity score weighting to account for these differences. The data presented here is unadjusted, and as you can see, patients in the AT2 group had significantly higher BMI,  a lower incidence of pre-existing hypertension, and a higher white blood cell count at baseline.  Looking at indicators of illness severity, more patients in the AT2 group received stress  dose steroids. The average baseline map for all patients was less than 60, and total baseline  vasopressor requirements were pretty high with an average norepinephrine equivalent dose of 0.8  microns per kilo per minute. Diving into the primary outcome of in-hospital mortality, the unweighted analysis reported higher mortality in the AT2 group, up to 90%. However,  this was not found to be statistically different after adjusting for these baseline differences  between groups. With regard to secondary outcomes, as you can see here after adjusting for baseline  characteristics, there were no observed differences in ICU or hospital length of stay or blood pressure response at three hours between patients who received AT2 or another  catecholamine as a third-line vasopressor. The authors did, however, report a significant  difference in vasopressor utilization, and that more patients in the AT2 group continue to require  five or more vasopressors at three hours in comparison to patients in the non-AT2 group.  Notably, patients in both groups continue to have higher, similar, but mostly unchanged vasopressor doses at three hours compared to baseline. And so I think the big takeaways here  are that patients who received AT2 were more likely to still require five or more vasopressors at three hours, and in patients receiving very high vasopressor doses at baseline,  adding another vasopressor on did not significantly impact either short-term hemodynamic outcomes  or long-term patient-centered outcomes. When evaluating other parameters for impact on mortality,  the authors reported that SOFA score was the only covariate significantly associated with  an increased risk of in-hospital mortality. The authors therefore concluded that in this study,  the addition of AT2 as a third-line vasopressor did not significantly influence mortality or other  patient-centered outcomes, and that AT2 may be more beneficial if initiated earlier in the disease  course. And in comparison to ATHOS3, nearly all patients in this study had septic shock, which, given the prevalence of sepsis in the ICU, is relevant to clinical practice.  This study also evaluated patients whom we might consider using AT2 as a last-ditch effort,  as all patients had a baseline MAP less than 65 and were more critically ill than those in prior  post-marketing studies, as denoted by baseline SOFA scores and vasopressor requirements.  Finally, all patients in this study received standard-of-care therapies with a catecholamine and vasopressin before addition of a third-line agent  titrated to a MAP goal of 65, both of these which are reflective of general practice.  With that being said, my critique of this study is that the clinical question, outcomes, and methods were relevant and generalizable to clinical practice,  and that having a standard-of-care control group contributes information that other post-marketing studies were not designed to provide. The authors also accounted for baseline  differences between groups through propensity score weighting, which allowed for meaningful  comparisons to be made regarding patient-centered outcomes, such as mortality and ICU length of  stay. Some weaknesses of this study include variability in AT2 titration and other adjunct  therapies due to its retrospective nature, as well as a slightly smaller sample size compared  to other post-marketing studies. This is especially important in the context of propensity score weighting, since its reliability depends in part on sample size. While this method  appropriately adjusted for differences in baseline characteristics, its results are only as good as the characteristics used for matching. Therefore, there could be a potential  risk that other unmeasured covariates could have influenced study outcomes.  And finally, time-to-antibiotic administration or source control was not reported, which would  have been pertinent information in these patients with septic shock. Based on the results of both  this and previous post-marketing studies, I think the role of AT2 in therapy still needs to be  defined. However, this study may shed light on some of our patients who may be less likely to  benefit from its use. A few questions that I still have about whom we might consider using AT2 are  patients with lower baseline vasopressor requirements, as this study, the ATHOS-3 trial,  and several other post-marketing studies have reported lower likelihood of hemodynamic response  or even higher likelihood of mortality when AT2 was added to initial vasopressor doses greater  than 0.5 mics per kilo per minute. Or should we consider AT2 in patients with lower lactate levels, those already on vasopressin, or those with elevated renin levels at baseline,  as these also have been associated with hemodynamic response?  And finally, should we consider AT2 in patients who are less critically ill than the ones in this  study, since SOFA scores were the only significant predictor of mortality, irrespective of which  third-line vasopressor was used? Considering the financial implications associated with AT2 and that some institutions have this agent on formulary, some key factors to consider in  patients already receiving therapy might include hemodynamic response and changes in vasopressor  requirements, as some studies have reported associations between hemodynamic responsiveness and mortality outcomes. However, there is currently no evidence to support benefit in  non-responders. A recent study also examined the utility of baseline and three-hour renin levels as biomarkers for responder status, which may be a consideration in the future.  However, this may not be feasible in current practice, given the lack of availability.  Future studies might focus on renin or other biomarkers for identifying patients who might  benefit from AT2. But in the meantime, additional studies comparing angiotensin 2 against standard  of care are still needed to further define patient populations whom it's most likely to benefit.  At this point, I'd like to get a sense of where you all feel that angiotensin 2 may have a place  in therapy. So, based on the current post-marketing evidence, which parameter do you feel  believe is most predictive of benefit in patients receiving angiotensin 2 for vasodilatory shock?  All right, that is a good mix.  And I think it's interesting to see where everyone stands on this topic. And I don't think we have a solid answer quite yet. I would be interested to learn where future studies find  what they find out in terms of how more specific groups of patients might respond.  And moving along to our next polling question. Does your institution currently have angiotensin-2 available?  All right, so we do have a few people that do have Angiotensin-2 available, and at our institution, Ascension St. Vincent, we also have Angiotensin-2 on formulary, however,  we restrict its use specifically to post-cardiac surgery patients with vasopaedic shock, so not for our septic shock population. All right. Oh, thank you very much.  Well, thank you all for your participation, and at this point, I would love to answer any questions that you might have.  Our first question for you is, was there any signal of increased thrombotic risk with AP-2 in this study like there was with APHOS-3?  That's a great question, and that is a question that this study was not designed or did not try to answer.  They were looking more about mortality outcomes and some of the effectiveness rather than the safety outcomes that were assessed for in APHOS-3.  Our second question, you touched on this in your analysis and your future directions about the dosing.  Do you think that, did the authors talk about the timing, like the specific timing from  the initial presentation of shock to angiotensin-2 and what effects that might have on results? Yes, that was actually something that the authors, they mentioned in their discussion  section where, in this study, the average time to initiation of a third vasopressor, either angiotensin-2 or another catecholamine, was about five days, and this range varied  significantly from, I think, 16 hours to over 1,000 hours. So given the significant doses of vasopressors required before starting a third agent at  about this five-day mark, the authors concluded that AP-2 may be more beneficial if initiated earlier in the disease course.  So I think that might be something that future studies could focus on since that delayed median time to starting this therapy was so late and patients could have been too  far decompensated to find or just demonstrate a significant mortality or hemodynamic benefit. We have one more question.  Should we shift the thought process of using angiotensin-2 in refractory shock to using it prior to refractory shock as a multi-mechanism vasopressor approach, maybe early on?  You know, that is the biggest question that I have after this study, and I was really hoping that we would have an answer.  And I think that's where it's starting to lead in that patients who are receiving over 0.5 mics per kilo per minute, as noted in the APHOS-3 trial and several post-marketing  studies, do not tend to demonstrate a great hemodynamic response or they also show increased risk of mortality.  And so actually starting at lower doses may potentially be beneficial, but I would personally  need to be convinced with at least more studies or larger studies that would show an actual benefit in terms of mortality or length of stay or something more clinically focused.  And so I don't think that we have those studies quite yet in patients who are less sick to give us that information.  But I would just say personally, I would need to be convinced before starting it routinely as far as patient outcomes go.  That concludes our Q&A session. Thank you, Marjorie Peck.  Thank you to our presenters today and the audience for attending. That concludes our presentation.  Thank you.

Video Summary

In this video, three presenters discuss various topics related to critical care pharmacy. The first presenter discusses a recent trial comparing epinephrine and norepinephrine in cardiac arrest patients with post-resuscitation shock. The presenter discusses the mortality rate in out-of-hospital cardiac arrest, the causes of death, and the optimal hemodynamic support for post-cardiac arrest patients. The presenter highlights the lack of randomized control trials comparing vasopressor agents in this population and discusses the potential risks and benefits of epinephrine and norepinephrine. The second presenter discusses a recent study on the timing of hydrocortisone initiation in septic shock patients. The presenter provides an overview of the current guidelines for corticosteroid use in septic shock and the evidence supporting hydrocortisone use. The presenter then presents the study, which compares early versus late initiation of hydrocortisone in septic shock patients. The presenter discusses the study's methodology, including the inclusion and exclusion criteria, and the primary and secondary outcomes. The presenter presents the results of the study, including the difference in vasopressor duration between the early and late initiation groups. The presenter concludes that while earlier initiation of hydrocortisone may lead to a shorter duration of vasopressor use, the impact on mortality is still unclear. The third presenter discusses a study evaluating the impact of angiotensin II on patient outcomes in the medical ICU. The presenter provides background information on the use of vasopressors in septic shock and the different mechanisms of action of vasopressors. The presenter then presents the study, which compares the addition of angiotensin II to a non-angiotensin II agent as a third-line vasopressor in patients with catecholamine refractory septic shock. The presenter discusses the study's methodology, including the inclusion and exclusion criteria, and the primary and secondary outcomes. The presenter presents the results of the study, including the lack of significant difference in mortality or other patient-centered outcomes between the angiotensin II and non-angiotensin II groups. The presenter concludes that while the addition of angiotensin II did not significantly influence mortality or other outcomes in this study, further research is needed to define the patient populations most likely to benefit from angiotensin II. In summary, the presenters discuss the use of different vasopressors in critical care settings and present the results of recent studies evaluating their efficacy and safety. They highlight the need for further research to guide vasopressor selection and timing of initiation in specific patient populations.

Asset Subtitle

Pharmacology, Cardiovascular, Sepsis, 2022

Asset Caption

"The Journal Club: Spotlight on Pharmacy webcast series focuses on pharmacy topics. This event is held on the third Friday of each month and features lively discussion and in-depth presentations on the latest research.

Blake Robbins, PharmD, MBA
Bougouin W, Slimani K, Renaudier M, et al. Epinephrine versus norepinephrine in cardiac arrest patients with post-resuscitation shock. Intensive Care Med. 2022 Mar;48(3):300-310.

Erica Allen, PharmD
Ragoonanan D, Allen B, Cannon C, Rottman-Pietrzak K, Bello A. Comparison of early versus late initiation of hydrocortisone in patients with septic shock in the ICU setting. Ann Pharmacother. 2022 Mar;56(3):264-270.

Marjorie Peck, PharmD, BS
Quan M, Cho N, Bushell T, et al. Effectiveness of angiotensin II for catecholamine refractory septic or distributive shock on mortality: a propensity score weighted analysis of real-world experience in the medical ICU. Crit Care Explor. 2022 Jan 18;4(1):e0623.

Follow the conversation at #SCCMCPPJC."

Meta Tag

Content Type Webcast

Knowledge Area Pharmacology

Knowledge Area Cardiovascular

Knowledge Area Sepsis

Knowledge Level Intermediate

Knowledge Level Advanced

Membership Level Select

Membership Level Professional

Tag Pharmacology

Tag Cardiac Arrest

Tag Shock

Year 2022

Keywords

critical care pharmacy

epinephrine

norepinephrine

cardiac arrest

post-resuscitation shock

mortality rate

hemodynamic support

vasopressor agents

hydrocortisone initiation

septic shock

angiotensin II

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