Should stress-dose steroids be given?

Welcome back to Depth of Anesthesia. This is a podcast that critically explores our clinical practices. I'm David Hao and I'm an anesthesia resident at the Massachusetts General Hospital. This week's episode will be available on Anesthesiology News. You can check out their new podcasts through the Anesthesiology News Presents channel wherever you get your podcasts.

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Now let's get going with a very exciting show that we have for you today. Our first guest is Dr. Jonathan Charnin, who our listeners may recall from episode 19, is hydrocortisone, asorbic acid, and thymine therapy effective for treatment of sepsis. Dr. Charnin is an assistant professor of anesthesiology in the divisions of multi-specialty anesthesia and critical care medicine at the Mayo Clinic. Dr. Charnin, welcome back to the show. Hey David, it's great to be back.

Thanks for having me. And our second guest is Dr. Daniel Saddawi-Konefka, who our listeners will recall is a recurring guest on our episodes. Dan is the residency program director here at Massachusetts General Hospital. Dan, welcome back to the show. Thanks, David.

Good to be on with you and good to be on with John as well. Good seeing you, Dan. I'm definitely looking forward to the conversation with you guys. So our case today is that of a 40-year-old woman who's presenting for a laparoscopic liver resection. She has a history of recently diagnosed rheumatoid arthritis, and her symptoms have been reasonably well controlled on a regimen of fifteen milligrams of prednisone daily for the past two months.

After induction of general anesthesia, the attending notices that the resident is about to administer a hundred milligrams of hydrocortisone. The attending inquires about the reasoning, and the resident reports that the patient needs stress dose steroids. A claim, as our listeners will recall, is a practice decision that we either believe is true or something that we default to. Dan, what are some of the claims in this case? All right, so we have a young lady going for liver dissection who's uh been on prednisone for a while.

And it sounds it sounds to me like the the highest level claim is that the resident says that they need stress dose steroids Uh some of the claims that might be buried in there are one that she's not going to mount the stress response with endogenous corticosteroids effectively. So I guess there's a claim that maybe she's adrenally suppressed. A second claim might be that if she is adrenally suppressed, the stress of surgery sort of mandates that she get additional steroids. And that if she doesn't, something untoward will come to her. Excellent.

Here now are two questions for our listeners to consider. What is the level of your agreement with the claims that Dan has laid out, with the highest level claim being that this patient needs strestosteroids? And what is the level of evidence for what you believe? Dr. Charnin, I think it'd be worthwhile for us to start with a bit of a review of the different types of adrenal insufficiency. and various diagnostic strategies. Yeah, so the adrenal system has been known for to be uh an important part of homeostasis. for a long time and there definitely are several diseases that uh can cause uh primary adrenal insufficiency You can have a a primary adrenal insufficiency from a pituitary disease or from adrenal disease.

Some patients have uh absence of both adrenal glands. uh for surgical reasons like multiple endocrine neoplasia. And those people will have a primary adrenal insufficiency where they just can't mount any form of adrenal response Secondary adrenal insufficiency uh is certainly seen, but is less common and Unlike primary adrenal insufficiency, it's typically that the adrenal system is suppressed because of exogenous steroid use. We believe that in most of these cases the renin angiotensin aldosterone system remains intact. Uh and so there's not necessarily a mineralocorticoid deficiency Uh but there is a deficiency in the body's ability to make glucocorticoids. Measuring how much glucocorticoids are made uh can be done, uh, but it's a laborious process and it's fraught with measurement error.

A the most common test is the Cosentropin stimulation test, where uh Cosentropin is given It's essentially exogenous ACTH to cause the adrenals to dump out hydrocortisone. And then you measure the hydrocortisone uh before stimulation 30 minutes and 60 minutes thereafter. And so we can get a sense if we have a clinical curiosity about whether somebody does have secondary adrenal insufficiency. For people who have a primary adrenal insufficiency or potentially a secondary adrenal insufficiency, they may not be able to respond to stress the way they should Keep in mind for patients with primary adrenal insufficiency, there is a rate of what was we call adrenal crisis, which is typically related to illness or infection or some other stressor.

And about six percent of people with primary adrenal insufficiency will have an adrenal crisis each year, and it will often manifest with hypotension. And adrenal crisis has a mortality that is close to six percent per episode. So, adrenal insufficiency is certainly a real thing for some patients, but it's harder to tease out who in the perioperative period is at risk and how much risk they're at, and what that risk means. Going on for just a second about the physiology of cortisol, you'll recall that uh the hypothalamus is always scanning for needs for uh anti-inflammatory effect It's also on the diurnal cycle of cortisol production. The hypothalamus sends corticotropin releasing hormone, or CRH, to the pituitary gland, and the pituitary then sends adrenocorticotropic hormone, ACTH, to the adrenal glands, which then make cortisol.

We know that cortisol has a half-life of about 90 minutes, and During its short half-life, it does a lot of fantastic things. Recall that cortisol binds to several different receptors in the nucleus of cells. that drives production of different proteins in the cells, leading to specific effects. But we've learned in the last 30 years that there are also Steroid receptors throughout the body, often on the plasma membrane of cells, especially on cells on the endothelium, smooth muscle, and heart. These plasma membrane receptors often influence ion flows with ions like calcium. And so when people have hypotension that relates to cortisol deficiency, it often responds very quickly to a supplementation of cortisol due to the fact that all the cortisol needs to do is bind to these receptors on the heart and the vascular tree.

So it sounds like cortisol has a number of important physiologic functions, including interaction with steroid receptors. As you mentioned, in patients with primary adrenal insufficiency, the rate of adrenal crisis is actually about 6%. And the mortality corresponding to each event is also fairly significant at 6%. Dan, can you touch on when we first started to raise concerns about chronic steroid therapy and potential secondary adrenal insufficiency, especially in the perioperative space? Yeah, so i it was noticed um that giving extract from animal adrenals could uh counteract the adrenal insufficiency in humans in the early 1930s And there were a number of steroids that were then characterized, mostly actually out of, you know, where where Jana is now, Mayo Clinic, uh Kendall's lab, and another lab in Zurich. scientist by the name of Reichstein.

And they uh isolated cortisone that started being used in nineteen forty eight. Actually they both got the Nobel Prize for it in nineteen fifty. But 1948 is sort of when it started being used. Actually rheumatoid arthritis, like the patient in our in our case, was what it was initially used for. And there were two case reports from the early 1950s of patients who came in for surgeries and ended up having profound hypotension and died.

Um two separate case reports. In both cases, autopsy revealed that the adrenals were atrophic So this led the authors to conclude that the patients had died from adrenal cortical insufficiency that they said was secondary to adrenal suppression from the cortisone that they were receiving Now obviously these case reports have been criticized for all the confounding factors and the fact that they had no biochemical proof of adrenal insufficiency. But that's kind of where it all started. So, Dan, carrying on with this topic of chronic steroids and potential complications relating to steroid administration, if you are on chronic steroids, do you then have adrenal insufficiency? That's a really good question.

And it's sort of central to the claim that we're looking at here is, okay, if you're on a chronic steroids, can we call you adrenally suppressed? Well, if you if you look at up to date, it says, and I'll quote this, any patient who is currently taking more than 20 milligrams per day of prednisone, or its equivalent. for more than three weeks should be assumed to have functional suppression of hypothalamic pituitary adrenal function. 20 milligrams of prednisone a day is a good amount. Physiologic prednisone is probably on the order of 5 to 10, or maybe a little bit on the south side of that range. So 20 milligrams of prednisone per day, two to three times normal amount.

But that's, you know, that you can assume that they have it, but do they actually have it is kind of another question. There was a meta-analysis that was published in the Journal of Clinical Endocrinology and Metabolism in 2015 In this meta-analysis, they looked at 74 studies. Now the authors themselves are very forthright in saying that there's a high likelihood of bias in most of these studies because the studies just aren't very large and they don't control for a lot of different things. So in all of these studies that they looked at, patients were on steroids for some period of time through some route of administration. And I'll sort of jump to the punchline , and that is that the percentage of adrenally insufficient patients uh in patients who were taking, I'll say, oral corticosteroids was 48.7 %.

So it's about a flip of the coin uh in terms of oral corticosteroids. They also looked at other forms of administration such as inhalation, topical administration, and intranasal administration. All of those were lower in terms of the incidence of adrenal insufficiency. Secondary adrenal insufficiency. Interestingly, those that got intra-articular corticosteroids, that was also around 50% Some secondary things they looked at was does treatment duration matter?

And they broadly categorized patients into less than one month of use, one month to one year, or one year or more And yeah, it made a difference. For the short-term use, less than one month, the all-comer incidence was 1.4 %. For medium term, it was close to 12%. And for long term 27.4%. That's lower than the flip of the coin we looked at before because that's all forms of administration of steroids.

They also looked at does the dose make a difference? And they classify them as low, medium, and high dose. Now every study that they included has slightly different route of administration, different drug. So it's a little bit hard to say exactly how they classified it. Um you can look at exactly how they classified each study in their supplement.

But broadly speaking it looks like if they had less than ten milligrams per day of prednisone, they consider that low dose. 10 to 20 uh was equivalent to medium and greater than 20 was high dose. Almost all the studies that they included had supra physiologic doses, just to point that out. And there was a dose response here as well. So low dose was the chance of adrenal insufficiency was 2.4%, medium dose 8.5 %, and high dose 21.5%, respectively. So, you know, the to go back to your question, David, if you're on chronic steroids, do you have adrenal insufficiency?

I think broadly speaking, the answer is there is some chance that you do. In folks who are on oral steroids, all comers , it's about a flip of the coin. And if you're on higher dose and for longer periods of time, it's higher. Now, Dr. Charnin, taking what Dan's now talked about and applying it into the perioperative space, does surgery require an adrenal response? I think the answer is uh surgery is a fantastic opportunity to encounter stress and inflammation.

And not all operations induce the same amount of stress or inflammation in every patient, and not all operations are the same Part of how the body responds to stress is with an adrenal response and it's important to have cortisol as part of the natural response to stress and inflammation. If the body is unable to make a sufficient stress response, you can certainly have hypotension or other symptoms like abdominal pain, fever, malaise , or postural hypotension. I think one of the things that is commonly repeated in the dogma is that there are different requirements for mild, moderate, and major surgery And there are different lists that have been created for what is likely to produce a low, medium, or high inflammatory response what may be required for a low, medium, or high dose of glucocorticoid replacement for somebody that you think is at risk for adrenal insufficiency But keep in mind there's always a wild card in that we know what the operation is, but we don't always know the patient's stress response, which is in some part genetic And the stress response may mean that even for a smaller operation, maybe they have a moderate response or or more exuberant response uh patients are able to uh throw their own genetic factors in uh that differ sometimes from the expected size of the operation.

And Dr. Charnin, touching a little bit on what you talked about in terms of how the stress response can differ between patients, I understand we have a systematic review and meta-analysis actually looking at the cortisol stress response that's induced by surgery. Yes, going along with the idea that different operations induce a different inflammatory response and will have a different stress hormone requirement. Uh Preet and others in the Journal of Endocronology from 2018 did a nice meta-analysis of studies primarily in the recent literature from 1990 onwards. And they found 71 smaller trials and that measured cortisol and the stress of surgery. They were able to collect almost 3,000 patients.

And interestingly, they found that uh as you would expect, the bigger the operation, the bigger the cortisol leak or the the greater the body's re requirement to combat stress with more cortisol. However, they also found something that I think would be intuitive to a lot of anesthesiologists, that minimally invasive surgery didn't require as much cortisol production to offset the effects of the inflammatory response of surgery. And this goes along with, I think, what many of us have seen in the operating room for years, that minimally invasive surgery, for whatever reason, doesn't induce the profound stress response that an open operation does. Hey John, in that study, how did they measure what stress response was quote unquote required?

This was primarily a look back on studies that had recorded the cortisol level in the patients. Independent variable is the cortisol, and the dependent variable is the size of the operation. So it sounds like overall the perioperative cortisol stress response is quite dynamic, and as the meta-analysis alluded to, it can be influenced by a couple of things that are patient-specific, surgical, or anesthesia related. So the big question then is what's the evidence that bad things happen if steroids aren't given to patients who are otherwise on chronic steroids? Yeah, you know, one of the things that uh one study I wanted to bring up just because I think it's I think there's a place for using it in making decisions is actually an animal study Um and I don't know that we've spent a lot of time talking about animal studies on depth of anesthesia.

We usually are looking for things that are closer to clinical care that we might see. And the troublesome thing that we'll come to learn with these folks who are on chronic steroids is that most of the studies we have are little and and pretty confounded. So sometimes it's nice to to make sure we have a good it stands to reason or we've got some closer to closer to really controlled settings to to make sure that, you know, um if we can't see an effect there, then gosh, maybe there's nothing to to search for. So there's a study by Udlsman and colleagues, and um what they did was they took primates uh and uh there weren't very many I want to say a fewer than 10 primates And they randomized them, uh, so first I'm sorry, first they removed all of their adrenal glands.

So these are very, very adrenally insufficient monkeys And then they randomize them to receive supraphysiologic uh doses of steroids, so 10 times normal dose. Physiologic doses of steroids or subphysiologic, so one-tenth the normal dose. And they did open cholosystectomies on all these funkies. And what they found was that the animals who are treated with sub-physiologic doses, so those one -tenth the normal dose of steroid They had markedly lower blood pressures and higher incidence of electrolyte abnormalities and increased mortality as compared with the controls. Importantly, or sort of notably, there was no difference in those outcomes when they looked at the monkeys who are either treated with physiologic doses of steroids. and then got their open colees, uh, or those treated with supraphysiologic steroids and then got their uh open colees.

And those were compared to the control of the the monkeys who did not have adrenalctomies Now, for sure there's a difference between uh having an adrenalctomy and being potentially adrenally insufficient after being on chronic steroids But um put it this way, if we didn't see any difference in these uh in this sort of a study, uh assuming it was properly powered, it would sort of question whether or not we should we should go further to even uh consider looking at anything uh more clinically uh approximate. So just kind of an interesting animal study there, David Yeah, and I'm glad you mentioned this study because I do agree that it affords us an opportunity to observe physiology in conditions that we would have a real difficulty replicating as cleanly in humans.

Heading now to some of the clinical evidence on possible bad things that might happen if steroids aren't given, I'll start with a paper that was published in the British Journal of Anesthesia back in nineteen seventy three by Kellett and colleagues. This is actually a fairly often quoted study in the literature on this topic, and it's called Adrenocortical Function and Clinical Course During and After Surgery in Unsupplemented Glucocorticoid-Treated Patients. This was a prospective cohort study of 74 patients undergoing, quote, major operations and 30 patients undergoing, quote, minor operations All the patients had to have been taking at least 5 mg of prednisone a day for a minimum of 15 days. Interestingly, only the minor operation group had a control group, which consisted of 14 patients with no endocrine abnormalities and who were never treated with glucocorticoids.

Everyone had their exogenous glucocorticoids discontinued 36 hours pre-operatively. For the minor group, they restarted steroids 24 hours post-op. and for the major group they restarted steroids 72 hours post op. For the minor surgery group, symptoms and signs of adrenal cortical insufficiency were only observed in one patient and in the major surgery group, hypotension was seen in 18 of 74 patients. When they explored these hypotensive events further, they were able to attribute eleven out of the eighteen to bleeding, sepsis, or anaphylactic reactions. Of the seven remaining cases, only three of the patients had low cortisol levels, which was defined as less than fifteen micrograms per a hundred milliliters.

And in all seven of these patients the hypotension either resolved spontaneously or with treatment of possible hypovolemia. David, just to summarize what I hear you saying some some what I think are some important points. And maybe you can tell me if I've got this right In minor surgery, really there was one patient who showed signs of adrenal insufficiency. In major surgery, there were some hypotensive folks, as we might expect with major surgery. But of those patients, so 74 patients total in the major surgery group, three had both unexplained hypotension and low cortisol levels.

Uh that may or may not be causally linked, but at least we're correlated. Is that is that am I understanding correctly? Yep, you got it spot on This was one of the first and larger studies to question the frequency of stress-induced adrenocortical insufficiency, even when steroids are withheld in a population that had otherwise been receiving them. A couple of limitations to observe, though. The method used to measure cortisol levels in this study was a fluorometric assay, which is something that's rarely used today.

And in addition, there is no agreed upon definition of what exactly constitutes a low cortisol level in physiologically stressed individuals. So the 15 micrograms per 100 mil cutoff was somewhat arbitrary. Moving on to some other evidence, what study do you have for us, Dr. Charnin? was a small trial, but a good size number for 1997. This study took eighteen patients, uh, all of whom had reason to have secondary adrenal insufficiency, it divided them into two groups A six persid group that received steroid supplementation at the time of their operation with 100 milligrams of cortisol and a twelve person group that only received normal saline at the time of their operation as a placebo instead of stresto steroids.

In the posto-operative period, they did not determine that there was any difference between the groups in hypotension or other symptoms of adrenal insufficiency. Even though the majority of the subjects were not given supplemental steroids. So it sounds like all of the patients had confirmed adrenal insufficiency by preoperative ACTH stimulation. And these patients were subsequently randomized to either stress dose steroids or their usual daily dose with placebo. And it appears that the study was unable to find any major differences with respect to blood pressure.

Is that correct? That's right. Perfect. And Dan, I know you have a study now looking at renal transplant patients. What can you tell us about this?

Yeah, so this is a study of 52 uh kidney transplant recipients published in the Journal of the American College of Surgeons by Bromberg and colleagues. in 1995. And what they did was uh they took 52 uh renal allograph patients who uh uh were undergoing 58 procedures And none of them received stress dose steroids. That was the design, was just let's see how they do if we only give them their baseline immunosuppressive doses of corticosteroids. So there's really no comparator group here. But then they followed uh clinical and laboratory evidence of um adrenocortical insufficiency, things like hypotension, myalgias, artralgias.

Serum sodium, acinophyll count, uh 24-hour urinary-free cortisol. And all comers, for those 58, they found no evidence for agrinocortical insufficiency in any of the patients. Now that's that's a relatively small study, as we're seeing with a lot of these. And uh it wasn't as though they got no steroids. They got their baseline immunosuppressive doses.

So it's hard to know exactly what to conclude from this study. The authors actually called the title Stress steroids are not required for patients receiving a renal allograft and undergoing operation. Which might be a bold claim based on only 52 patients, but that said it's one of the larger trials that we that we have. And uh it does at least make us think about whether we need to do supplemental supra-physiologic doses of uh steroids As compared to whatever the baseline amount of steroid is that they are receiving. And Dr. Charnin, I know you have one final paper that we'll discuss, and this was actually a relatively recent paper done in only 2014 compared to some of the other papers we've been discussing today.

Uh and this looks at patients in major colorectal surgery. What can you tell us about how this study was designed? Yeah, absolutely. This is a a genius uh group to do a study in because a lot of patients with inflammatory bowel disease do undergo major colorectal surgery and are treated with steroids uh to modify the course of their disease. And so I'm glad they looked at this Uh Dr. Karen Zagilian and others looked at 92 steroid-treated patients with inflammatory bowel disease undergoing major colorectal surgery And they divided him into two groups.

One group received what would commonly be considered uh a good dose of stress dose steroids, including a hundred milligrams of hydrocornisone, uh, three times daily, followed by taper. And the other group had their usual steroid dose divided into three and given throughout the day intravenously as a replacement of their usual steroid dose. So the two arms are high-dose stress dose steroids versus continue to give the patient intravenously what they usually take by pill. And they were looking not just for hypotensive episodes that would lead to ICU admission. They were looking for things like postural hypotension or hemodynamic instability that uh required fluid boluses.

Interestingly, they found in both of these groups very similar rates of hypotension and other side effects This was designed as a non-inferiority trial, and they found their primary endpoint in that replacing the usual dose of corticosteroids intravenously was non-inferior to high doses of steroids And I think it supports the idea that even for somebody having a major colon operation, providing a certain quote-unquote stress dosteroid may not be critically important. But keep in mind, when you only have 50 or 60 patients in each group, there's a chance that it's an insufficient sample to generalize to all the patients in America. And so there may be some other patients who would have showed a difference uh if there had been more patients enrolled.

I think that's a great point and something to definitely think about because as we've seen with some of the literature we've discussed up until this point, the studies are heterogeneous, the results are often Tough to interpret. And I think the story is further complicated by the fact that a Cochrane review on this subject published back in 2013 was actually retracted. It was based in part on articles such as the Glauniac article that Dr. Charnin reviewed. And what they actually concluded was There's currently inadequate evidence to support the use of supplemental peroperative steroids in patients with adrenal insufficiency It is likely that in the majority of adrenally suppressed patients undergoing surgery, administration of the patient's daily maintenance dose may be sufficient and that supplemental doses are not required.

It was after comments were received via direct correspondence, which have challenged the eligibility criteria and interpretation of the evidence. summarized in this review that the Kaukhan review was actually retracted and so it's no longer uh accessible. One of the questions I have and I think that our listeners might have is What's the harm to steroid supplementation? Why not just give every patient hydrocortisone in the hopes that you cover any potential issues? Yeah, that's a really good question, David. I'll just take a brief stab at it to say that there are a lot of things that are implicated in the in the administration of perioperative steroids, such as impaired wound healing immunosuppression um interactions with anesthetic agents, uh psychiatric disturbances, and so forth.

That said, I'm not sure how significant those are, you know, as John and I were talking about this uh podcast episode in general. We reflected on how how it's actually fairly common practice for each of us to administer dexamethasone, uh which which is quite potent as a glucocorticoid to our patients um for either um anti -emetic or analgesic effect. Uh John, I think you looked up a little bit of the uh Of the conversion there, is that right? That's right, Dan. I've looked up at the conversion and I keep looking it up about every couple of years because I never want to believe the numbers that I come up with.

I almost always treat uh postoperative nausea and vomiting with four milligrams of dexamethasone, and as it turns out four milligrams of dexamethasone converts to just over a hundred milligrams of hydrocortisone. And if you were to happen to give 10 milligrams of dexamethasone, as I sometimes do for my ENT cases, that converts to more than 260 milligrams of hydrocortisone. So a lot of my patients are receiving more than stress dose steroids in a long-acting form because dexamethasone has a long half-life, even when I'm not giving hydrocortisone. Yeah, same same here. So David, you know, do they have uh do steroid supplementation is that does that cause problems for our patients?

I think that might be a great starter piece for a separate Depth of Anesthesia podcast episode. Yeah, I'm glad you guys brought that up Because I'd say that a fair number of clinicians are administering at least four milligrams of dexamethasone in adult patients, which as Dr. Charnin mentioned is equivalent to about 100 milligrams of hydrocortisone Which is a pretty fascinating conversion when you think about it in the context of this discussion. Dan, any other thoughts? Yeah, I really like the exploring this particular claim because One of the things, David, you and I had talked about before you even recorded the first episode of uh Depth of Anesthesia was how important it was to know what the evidence was underneath each of your practice habits.

And just because there wasn't robust evidence to support a practice habit doesn't mean necessarily that you ought not to do it. It doesn't mean that you should either. But one of the things I think you and I both felt strongly about was that as as uh clinicians who who take pride in their work, it's important to know what is substantiated by what levels of evidence So I think this falls squarely into that area. Whether or not you give stress dose steroids or just call it covered by your dexamethasone, uh I think it's still important to to not sort of just rely on luck or or uh habit, but instead to really understand what uh the evidence is underneath it all.

Yeah, I couldn't agree more, Dan. All right, Dan, I know this is probably gonna be pretty tough because we've been all over the place with this episode, but could you try to summarize some of the evidence that we've discussed for our listeners today? Let's give it a shot. So I think we started out with this case of the uh 40-year-old who is on steroids. And uh initially John talked a little bit about the physiology. of uh the HPA axis and adrenal insufficiency.

We then talked about the two case reports from the early 1950s that showed uh the two folks who the two patients who had died with adrenal atrophy on autopsy. We talked then about a meta-analysis that showed that it was kind of a flip of a coin as far as folks on chronic steroids, whether or not they are adrenally insufficient. Doctor Jarnan then covered the physiologic stress of different surgeries and what normal cortisol responses were, to sort of get a sense of how much of a response might be needed. And then we turned our attention to talking about what bad things might happen if steroids are withheld for patients who are either adrenally suppressed or on chronic steroids.

We talked about one animal study where they did the adrenalctomies on uh primates and those primates that received sub-physiologic doses of steroids. uh did not do well um in terms of all the markers, blood pressure, electrolyte abnormalities, and uh mortality as compared to the other monkeys, those that either didn't have adrenolectomies or got physiologic doses or supraphysiologic doses. David, you talked a little bit about the Kellett study, which looked at patients undergoing major operations and minor operations. Who had been on steroids and what the incidence of hypotension was and how that hypotension correlated with adrenaline sufficiency And from that we we extracted that it looks like maybe 5% of a little less than 5% of patients with major surgery had hypotension that was correlated with adrenal insufficiency.

John then talked about the Glauniac study, which was the VA study where they randomized patients to getting either saline or their home dose. Small, small study, but no differences between uh outcomes in terms of hypotension uh or other signs of adrenal insufficiency. Uh we mentioned the Bromberg trial, which was the kidney donor, the kidney transplant recipients. uh where patients just all got their normal daily immunosuppressives as opposed to supraphysiologic steroids and they did not in those patients small sample uh notice any deleterious consequences We then talked about the Zagian trial , which was a prospective randomized trial where they randomized folks to essentially home dose. uh versus supraphysiologic doses and found no difference in outcomes after matrix colorectose surgery.

David talked a little bit about the withdrawn Cochrane review. And then we hinted at what, if any, might be risks of giving high-dose steroids, but uh talked a little bit about how our common practice with uh administration of dexamethasone might make a lot of this moot. Uh David, does that sound like a reasonable summary of all that we covered? Reasonable and very helpful to to hear it all back. Dr. Charnin, any concluding thoughts?

Yeah, just one thought. Uh I know a lot of anesthesiologists uh went into anesthesia so that they would never have to use a steroid calculator. But sometimes it's fun to look up how powerful dexamethasone is, because it's a really strong drug If you find yourself unexpectedly sending a patient who you think may have secondary adrenal insufficiency to the ICU, that's usually my cue to ask myself again whether I think they've had adequate steroid replacement. And if I've given them four of Dexamethazone, I'm usually happy that they have. Thank you both for joining me on the show today.

It was an absolute pleasure to have you guys back to share some of your expertise with our listeners. Thanks for inviting me, David. This has been great. Pleasure to be with you, David. Thanks for joining us on the show today, and a special shout-out to everyone who's been submitting new episode ideas.

We're hard at work researching many of them, so I hope to have some of these new episodes out for you soon. If you enjoyed this episode, please leave us a five-star review on Apple Podcasts and consider writing a review. If you didn't enjoy this episode, you're Probably gone by now. Stay hungry and keep asking questions.