Norepinephrine versus Epinephrine for Cardiogenic Shock caused by a Myocardial Infarction

This is one sexy pilot study. The authors here decided to take a look at norepinephrine (NE) versus epinephrine in patients with cardiogenic shock s/p MI. They didn't use dopamine as they had noted an article that I have reference here where I discussed how dopamine actually increases mortality in cardiogenic shock compared to NE. 

The rationale why the authors went to NE was because data has shown that the myocardium may have a more favorable effect on myocardial O2 consumption. Epi was believed to cause more deleterious effects. Ultimately, though, none of this had been proven in a trial. Well, here is the trial. 

Over the course of 5 years they included 57 patients. See why I have such respect for these folks who do trials? I have no idea where I am going to be in 5 weeks, let alone 5 years. They measures a ton of parameters and did their statistical jumping jacks that I will not bore you with (but the article is entirely free for those curious minds out there). 

Ultimately, what we are about is how the patients did. With regards to their MAP, CI, and SVI, they were the same. As one would expect, the HR for the patients on epi was higher. Also expected, as epi hits more of the beta receptors, there was an increase in lactate in these patients (which doesn't mean they need more fluids).  

There was an early termination of the study, though, as 37% of the patients on epi went into refractory shock while just 7% of the patients on NE did the same (p=0.008). 

The authors acknowledge that it is a small trial but they were able to see a clear difference between the two groups. There are numerous other limitations to the study as well that they acknowledged.

When your patients are in cardiogenic shock, how do you all use your vasopressors/inotropes?

-EJ

Levy BC, Clere-Jehl R, Legras A, et al. Epinephrine versus norepinephrine in cardiogenic shock after acute myocardial infarction. J Am Coll Cardiol. 2018;72:173–82.

Link to Abstract

Link to FULL FREE Article



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Renal dose Dopamine, taking down a myth.

When one looks at the dates where the publications disproved "renal dose dopamine", you see three articles published in 2000, 2003, and 2004. It's 2020 and this has not yet been put to bed. Now, I’m all worked up about this because I’ve had clinicians tell me that it absolutely works. I saw it in residency, fellowship, and now in private practice. I’m sure some of you see it at your institutions, too.
There’s data that it improves urine output transiently but no data that it improves renal outcomes in critically ill patients. No changes in creatinine. No changes in renal replacement therapy rates. In fact, that whole discussion has been put to bed so much that there haven’t been any comments made on it over the last 15 years. No further trials attempting to prove it works. Is that why we’re still seeing it? Well, it’s time to bring the arguments against renal dose dopamine, or even using dopamine altogether back into the fray.
The data about it being beneficial was from the 60’s in animal and healthy human studies. The latest studies, however, say it doesn’t work and in fact may be harmful. I have attached some of my preliminary slides from my Vasopressors in 2020 lecture. These are some of my preliminary slides. More info will come from me directly as I present these but it should provide you with an idea of why we should rarely see dopamine in our ICU's anymore. 
Do you still all use dopamine? If so, what for?
I used to use it during codes as it was already packaged in the code carts. We have since gotten rid of these and my badass pharmacy colleagues prep me levophed drips within seconds. 

Debaveye, Y., and Van den Berghe, G.: “Is There Still a Place for Dopamine in the Modern Intensive Care Unit?” Anesthesia and Analgesia. 98(2):461–468, February 2004.

Link to FREE PDF

Holmes, C., and Walley, K.: “Bad Medicine: Low-Dose Dopamine in the ICU,” Chest. 123(4):1266–1275, April 2003.

Link to CHEST Article

Bellomo R, Chapman M, Finfer S, et al. Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial: Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 2000; 356: 2139–2143

Link to NOT FREE Lancet Article

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Early Vasopressors in Septic Shock?

This is a question that is often asked. Do we give fluids until the patient no longer "responds to fluids" or start vasopressors early?

Here's my bias: I dislike arbitrarily pounding patients with fluids. It causes harm. We know this.

I don't know what people who aren't doing advanced hemodynamic monitoring of some sort mean when they say "they respond to fluids". "I gave a liter of fluids and the BP got better" for 30 minutes is not a determinant of fluid responsiveness. Remember, I've cited here before that critically ill patients extravasate 80% of that liter of fluids within one hour. What did you really do outside of feeling like you did something? The authors used PPV, SVV, echo with VTI combined with PLR, end-expiratory occlusion maneuvers, and capillary refill time. Did I mention that these authors are legends in the field? Well, they are.

In my opinion, providing pressors early provides a safety net of sorts to the organs to make sure they're being perfused. You've seen it often in your ED and ICU. Patient comes in sick. They're hypotensive, they get their 30cc/kg and their BP gets "better". The cuff cycles again 15 minutes later and their BP is now 60/30. How long did those organs go under-perfused? Minutes matter. We NEED to get better at this. After all, we are supposed to be the biggest badasses in medicine, yet we often shrug our shoulders and react when it's ugly instead of preemptively fixing the issues.

Turns out that very early vasopressors were beneficial to the patients. The definitions of the two groups are defined on my slides. The outcomes are also defined there for the sake of not taking up too much space.

This could be practice changing data. I personally start vasopressors really early in my practice. Some may say, let's wait for a prospective randomized clinical trial before putting this into practice. To those people I say, there's no harm in this. Also, you can't blind the physicians so when that study comes out positive some will say "oh but the physicians weren't blinded". Research. Sigh.

A hat tip to the authors. This article was published yesterday. How's that for cutting edge?

-EJ

Ospina-Tascón, G.A., Hernandez, G., Alvarez, I. et al. Effects of very early start of norepinephrine in patients with septic shock: a propensity score-based analysis. Crit Care 24, 52 (2020).



Link to Abstract

Link to FULL FREE PDF



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Weaning Order of Norepinephrine and Vasopressin in Septic Shock Patients

This is a post for all my Critical Care Nurses out there! Please tag and share with your friends and colleagues. When you have a patient in shock on norepinephrine and vasopressin and has turned the corner, which vasopressor do you turn off first: norepinephrine or vasopressin? From my hard digging through the internets I have only found three studies which touch on this topic. Also, this seems like a pretty simple RCT that I could actually do at my shop. Anyone interested in joining in on the fun to make it multi-centered? These slides to some extent will be featured in my Hawaii and Portland lectures later this year. Seems like I'll be heading to Brooklyn and Indian Wells, CA in 2021.

Here's what the data says. Spoiler alert: there's no 100% correct answer.

2010: Bauer, et al. did a retrospective study where the team found that patients did better if the NE was weaned first and the vasopressin was weaned second.

2017: Hammond, et al. also performed a retrospective study which found similar results: patients did better if they weaned off the NE first. So far so good for weaning off NE first.

2018: Jeon, et al. just had to throw a wrench into everything. This was a prospective randomized trial where the results were the exact opposite of the other two. Ugh. Those of you who have been hanging out with me long enough may recognize that I covered this study in March of 2019 when the page was just getting ramped up.

Well what's the right answer? I guess we just don't know. Dealers choice. The randomized trial should hold more of an answer due to it being higher on the scale of evidence. The studies are small, hence me considering on doing a trial on this since ultimately it's not going to cause any harm and I really don't have a bias. What do you think?

-EJ

Link to Article (not free)

Bauer S, Aloi J, Ahrens C, Yeh J, Culver D, Reddy A. Discontinuation of vasopressin before norepinephrine increases the incidence of hypotension in patients recovering from septic shock: a retrospective cohort study. J Crit Care. 2010;25(2):362.e7-362. e11.

Link to Article (not free)

Hammond DA, McCain K, Painter JT, Clem OA, Cullen J, Brotherton AL, Chopra D, Meena N. Discontinuation of vasopressin before norepinephrine in the recovery phase of septic shock. J Intensive Care Med. 2017:885066617714209

Link to Full FREE PDF

Jeon K, Song JU, Chung CR, Yang JH, Suh GY (2018) Incidence of hypotension according to the discontinuation order of vasopressors in the management of septic shock: a prospective randomized trial (DOVSS). Crit Care 22(1):131

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Vasopressors have immunologic activity

This is a post I’m 90% sure you’re going to learn something from because I had NO IDEA this was a thing until I was doing all my research on vasopressors. I’m sure it’s not going to get many likes nor any shares, but it’s cool stuff like this that really gets me excited. Not many know what tumor necrosis factor is and what interleukins are, but they all play a huge role in inflammation and the overresponse of the body in sepsis. I’m going to stay far away from the specifics on this one. We give catecholamines and Vasopressin to our patients almost daily, might as well know the intricacies of these treatments. Cool stuff, right? A 🎩 tip to the authors.

Thanks for following along in my insanity.

-EJ




Link to Abstract

Link to FULL FREE ARTICLE (maybe)

Stolk RF, van der Poll T, Angus DC, van der Hoeven JG, Pickkers P, Kox M (2016) Potentially inadvertent immunomodulation: norepinephrine use in sepsis. Am J Respir Crit Care Med 194(5):550–558

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Vasopressin: Titratable Doses? Monotherapy in Septic shock?

This is what I love about the community in social media. We all just push each other to be better. Rishi posted today about titratable Vasopressin and, me being the data junky that I am wanting to know every study I could possibly know under the sun, had two studies in my back pocket ready to share with everyone. I was planning on sharing this study with you all further down the road but, Rishi indirectly pushed me so here I am sharing this article with you all rather than going out for a run. No, there's no one study where they just looked at titrating vasopressin. What this study does show us, though, is that the authors used vasopressin as a titratable medication as well as a mono therapy medication (that means not just adding it to norephinephrine when it reaches X dose. Studies like this indirectly guide us to what can and can't be done moving forward in medicine. If you get into trouble with a patient, one can justify it by saying "the VANISH study showed that it's safe to use it in this manner". I'm always worried about the lawyers, I'm not going to lie.

The goodies in this article and what I want you to focus on today is not necessarily the conclusions of the article nor all the subgroup analysis, but rather I want you to look at the methods on how they performed the study.

Patients were able to receive titratable doses of vasopressin up to 0.06U/min. That means that they were able to exceed the 0.04U/min you and I use every day.

They also titrated to a MAP of 65 or 75. Note that they did not use a systolic blood pressure. I have covered why you shouldn't do that unless you have an arterial line on youtube and here in the past.

The MAP of 75 is also important because there's data that higher MAP's in patients with chronic hypertension is better for them. I see shops where the MAP goal is 60 and that's just plain stupid and only acceptable on a case by case scenario.

Patients in this study received vasopressin as monotherapy for septic shock and it did not cause issues.

There is much to be said about the methodology of this trial which I am not going to get into today. I'll be here forever. Instead, you can hear me take it apart live in Hawaii in May 2020.

A hat tip to the authors.

- EJ





Link to Abstract

Link to FREE PDF

Gordon AC, Mason AJ, Thirunavukkarasu N, et al. Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. JAMA 2016; 316: 509.

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Enteral Nutrition Can Be Given to Patients on Vasopressors

Link to Article (Not Free)

I have always been interested in the nutritional status of our patients in the ICU and I don't quite have my mind made up regarding a lot of things. Actually, within the next few months I am going to be asking my registered dietician colleagues here for help with a number of clinical questions.
Truth is that there is a void of solid data regarding nutrition, when to start, how much, how much protein, etc. I understand the ASPEN guidelines have provided some consensus, but much of it is expert opinion rather than actual data. I digress. A topic for another day.
Regarding this article that was published yesterday, the author detailed the vasopressors doses at which one should start feeds (or not start, norepinephrine > 0.3-0.5mcg/kg/min is a no-no), resuscitation markers that should make us feel more comfortable with starting feeds such as decreasing downtrending vasopressor doses.  He also describes the feeding strategy of starting with tropic feeds at 10-20cc/hr.  Lastly, he describes signs of intolerance including residuals > 500cc, note, not 250, not 300... 500.
I have some honest questions for which I personally do not know the answer, though. I need help with this if someone knows the answer. From an evolutionary standpoint, we do not eat when we are ill. Just remember your appetite for a big delicious meal when you last had a significant viral illness. Should we really start to immediately feed these patients? Also, I do not feel that our bodies are accustomed to this whole continuous feeds phenomenon. We normally bolus feed ourselves. Are we shocking the system by doing continuous feeds? See? This is why I need help from some badass registered dietitians.
A 🎩 tip to the author!

-EJ

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Optimal norepinephrine-equivalent dose to initiate epinephrine in patients with septic shock

Link to Abstract

I am quite confused by this article. I was hoping for some answers on how to manage norepinephrine and epinephrine in septic shock but instead I am left scratching my head wondering what in the world happened here. If you're on my page and following along in on this journey, then you know a thing or two about septic shock patients. This article was supposed to provide us with some data regarding when to start epinephrine on these patients once levophed was already running. Instead, you find a retrospective observational study with a statistically significant difference between the optimal dose group and the non-optimal dose group. Within the subgroup analysis, though, you can find that 83.3% of the optimal dose group was also on vasopressin while 62.3% of the non-optimal group was on vasopressin (p=0.001). Does this mean that there's a dose to start epinephrine when a patient is on norepinephrine, or does this mean that before starting epi, you should have vasopressin on board? 

-EJ

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Current use of vasopressors in septic shock

Link to Abstract

Link to PDF

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