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

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

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

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

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.

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

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

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Current use of vasopressors in septic shock

Link to Abstract

Link to PDF

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.