Why do we give Corticosteroids during Septic Shock?

Whether you're a med student, intern, resident, or nurse, you've wondered why in the world we give patients who are in septic shock stress dose steroids. This article breaks down in a not-so-easy to understand fashion of the nitty details that are too complex for my post-night shift brain to digest.

The powers that be in Critical Care, SCCM and ESICM, got together for this review with some big guns in the field to write this review discussing Critical Illness-related corticosteroid insufficiency.

Link to Abstract

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Annane D, Pastores SM, Arlt W, Balk RA, Beishuizen A, Briegel J, Carcillo J, Christ-Crain M, Cooper MS, Marik PE, et al.: Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM). Intensive Care Med 43(12):1781–1792, 2017.

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Cortisol Levels: Check prior to SDS in Septic Shock?

Your patient is in septic shock. They've gotten the correct source control, antibiotics, fluids, vasopressors. They remain hypotensive. Getting worse, actually. Could they have relative adrenal insufficiency or one of these fancy-termed conditions such as "critical illness-related corticosteroid insufficiency" (CIRCI)?

Should you check a cortisol level to find out or just start stress dose steroids?

In my practice, I do not check cortisol levels. No need to stick the patient for more blood. No need to waste any additional money for lab tests. No need to delay care in waiting for a lab result. Once the norepinephrine dose starts creeping up, I order stress dose steroids (as well as vitamin c and thiamine at the time of this writing). This is all my medical opinion and not advice, in case you didn't know.

The most recent trials on stress dose steroids do not check cortisol levels, so why should you? I tried to dig deeper into this point as I cannot get others to stop checking random cortisol levels on their critically ill patients. But why? There's no diagnostic consensus about the appropriate cortisol level for patients in septic shock. In addition to that, there's data that states that "both cortisol and synthetic ACTH challenge assays are unreliable in critically ill patients". So then why do we keep doing it?

Is there something out there that I don't know and you all can provide me with insight on? I'm looking for help on this.

A hat tip to the author. 

Reddy, Pramod. Diagnosis and Management of Adrenal Insufficiency in Hospitalized Patients. American Journal of Therapeutics, 2019. E-pub ahead of print.

Link to Article

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IV Vitamin C in Sepsis: It Should Help Decrease Vasopressor Doses and Duration

The VITAMINS trial didn’t pan out was not a positive study as it was conducted. I’ve already provided my take on that with my main argument being that they took too long to initiate the study drug (median time >25 hours, not including the time to arrive in the ICU). Sepsis management is expedient, you and I see it every day. Waiting over a day is not being expedient.

I’m seeing a benefit in my clinical practice, as admittedly worthless as my opinion is on the grand scheme of evidence. But when something doesn’t make sense from a results standpoint, you need to go back to the basics and wonder what happened.

Here are some things we absolutely know: 88% of patients in septic shock have hypovitaminosis C and 38% of septic shock patients have severe vitamin C deficiency. What many of you may not know, and I’m here to help you understand why I’m so surprised by the findings of the VITAMINS trial, is that vitamin c is a co-factor to the creation of endogenous catecholamines. That means that without vitamin c, your body isn’t going to produce the appropriate amounts of dopamine, norepinephrine, and epinephrine. It also is necessary for the production of vasopressin. It’s as simple as that. 38% of people will not produce appropriate endogenous catecholamines. The fact that administering exogenous vitamin c did not decrease time that the patients were receiving vasopressors in the study makes me wonder why. I am aware that there was a delay of >24 hours to start the therapies in the study but is there more I'm missing. Hopefully you can take some basic biochem away from this post as to why it should work (although it didn't in the study).

A 🎩 tip to the authors.

-EJ




Link to Article

Link to FULL FREE PDF

Carr, A.C.; Shaw, G.M.; Fowler, A.A.; Natarajan, R. Ascorbate-dependent vasopressor synthesis: A rationale for vitamin C administration in severe sepsis and septic shock? Crit. Care 2015, 19, e418.

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Thiamine, Ascorbic Acid and Corticosteroids: The Mechanisms by which they should help in Sepsis

Want some nerdy stuff? Well this is some nerdy stuff! I'm taking a nice deep look at this figure. I am not going to lie to you at this moment, October 19th, and tell you I know what all this means, because I don't. But people who are more intelligent that I am have suggested that these are the mechanisms by which thiamine, ascorbic acid, and corticosteroids should help in the treatment of septic patients. I have a lot to learn.

I hope I don't get dinged for copyright stuff but honestly if this offends you, let me know. I will take it down. I will likely go deeper into this article at a later time. Wanted to share this image with you right now, though.





Link to Abstract

Link to FREE FULL Article

Moskowitz, A.; Andersen, L.W.; Huang, D.T.; Berg, K.M.; Grossestreuer, A.V.; Marik, P.E.; Sherwin, R.L.; Hou, P.C.; Becker, L.B.; Cocchi, M.N.; et al. Ascorbic acid, corticosteroids, and thiamine in sepsis: A review of the biologic rationale and the present state of clinical evaluation. Crit. Care 2018, 22, 283.

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.

Ascorbic Acid, Thiamine, and Steroids in Septic Shock: Propensity Matched Analysis

Link to Article

Another day, another Vitamin C article. This one came out just two weeks ago, it’s not free, and the results are a bit strange. There are larger trials in the works. If I were part of the group of these authors, I’d be itchy to get my data out ASAP as well. Just 31 patients in each arm of this trial. Heck, even I could replicate this trial in my 20 bed MSICU if I wanted to over 1.5 years. The problem is that my bias admittedly is for the cocktail to work. I am wide openly admitting that, everyone. I have a bias. I want it to work bc I want my patients to live.  

There are numerous parts of this study that seem strange to me. 

1. the ICU mortality of the control arm is 42%. This number should not be quite as high based on the latest data. That could lead the p-value of 0.004 to be perhaps a bit too small. But considering that they used the same strategies to manage septic shock these pts in both arms, it’s still valid for that institution. 

2. The duration of the vasopressors were longer in the experimental arm. This makes NO sense as Vitamin C is a co-factor in the endogenous creation of catecholamines. Heck, even the authors admitted this was strange. 

3. There was no significant difference in hospital mortality. They probably needed a high n to get this to show a difference. The hospital medicine and palliative teams must be great at getting code status’ changed so that people don’t bounce back to the unit. 

4. Pts did not get off of the ventilator faster. Word on the street is that there’s preliminary data suggesting that it helps this process that just isn’t out yet. Stay tuned. 

Lastly, everyone is worried about renal failure. No difference in AKI here, folks. In fact, I am yet to see one report in any of these trials talking about renal calculi secondary to vitamin C in sepsis. 

What are your thoughts on the matter? Is your shop using this yet? Are you a believer or a skeptic?

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.

Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation

Link to Article

Direct download to full FREE PDF

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Marik Protocol for Septic Shock: Looking at Vitamin C

Hydrocortisone, Ascorbic Acid and Thiamine
(HAT Therapy) for the Treatment of Sepsis. Focus on Ascorbic Acid

Controversies. Controversies. Controversies. I tell you, the behaviors of Intensivists when it comes to king septic patients IV Vitamin C for sepsis are quite perplexing. We had a cheap drug, less than;$20 a day that MAY help treat sepsis and people don’t even bother to try it out. I know I use it because if it saves lives, why not try? Let’s say that the trials show a mortality benefit, two years have already passed since the first trial. Think of all the additional lives you could have saved but didn’t because your ego was in the damned way. If Marik is wrong, nothing bad happened. But if he’s right, you’re going to beat yourself up.

-EJ 



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.