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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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

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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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Keep the Dopamine at the bottom of the shelf

Does your friendly neighborhood cardiologist or intensivist start your Cardiogenic Shock patient on dopamine? Do you ever ask them when was the last time they read a study? I don’t mean to be harsh but this data is now almost a decade old.

This study placed dopamine far down on the vasopressor selection totem pole. They looked at patients who were in all types of shock, hypovolemic, septic, and cardiogenic on norepinephrine or dopamine and checked a bunch of outcomes.

What did they find? Well, no difference in mortality EXCEPT in those patients in Cardiogenic Shock. (p=0.03). Also, dopamine caused more severe arrhythmias than norepinephrine: 6.1% vs. 1.6%.

24.1% of the dopamine patients had arrhythmias and 12.4% in the norepinephrine group. That’s a lot of time managing side effects. No thank you.

Also, I need to find more data on this “renal dose dopamine” nonsense. This study showed an increase in urine output in the first 24 hours but then it evened out. They had an equal fluid balance when all was said and done. Although there was no statistically significant difference (p=0.07) in renal function and the norepinephrine group trended towards having better renal function. I know seeing urine makes us feel all warm and fuzzy inside but if it’s providing false reassurance than what is it worth?

Still want to use dopamine? I hope not.

-EJ

Link to Article

De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010;362(9):779–789. doi:10.1056/NEJMoa0907118

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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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