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Corticosteroids in COVID-19 ARDS
6 Plays5 years ago
In this episode of Critical Matters, we will take a deep dive into the topic of corticosteroids in COVID-19 ARDS.
Our guest is Todd Rice, MD, an Associate Professor of Medicine in the Division of Allergy, Pulmonary and Critical Care Medicine at Vanderbilt University. Dr. Rice is an accomplished physician-scientist focused on research in patients with sepsis, ARDS, and acute respiratory failure. He recently co-authored an editorial published in JAMA; “Corticosteroids in COVID-19 ARDS: Evidence and Hope During the Pandemic.”
Additional Resources:
Corticosteroids in COVID-19 ARDS: https://bit.ly/3bFbFig
PROSPERO Meta Analysis: https://bit.ly/3m69rgD
RECOVERY Clinical Trial: https://bit.ly/35t59Ka
REMAP-CAP Clinical Trial: https://bit.ly/3m2Hkz3
CODEX Clinical Trial: https://bit.ly/3bJQdbU
CAPE-COVID Clinical Trial: https://bit.ly/3it8Xz7
Books Mentioned in this Episode:
When Breath Becomes Air by Paul Kalanithi: https://amzn.to/2ZlVZeX
Recommended
Transcript
Introduction and Guest Introduction
00:00:06
Speaker
Welcome to Critical Matters, a sound critical care podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:14
Speaker
Sound Critical Care provides comprehensive critical care programs to hospitals across the country.
00:00:20
Speaker
To learn more about our programs and career opportunities, visit www.soundphysicians.com.
00:00:27
Speaker
And now your host, Dr. Sergio Zanotti.
Dr. Rice's Research Overview
00:00:32
Speaker
Corticosteroids have been utilizing critical care for their anti-inflammatory and antifibrotic properties for decades.
00:00:39
Speaker
Both in sepsis and ARDS, debate over the role and efficacy of corticosteroids have lasted years.
00:00:45
Speaker
With the development of the COVID-19 pandemic, the potential role of corticosteroids once again became a topic of great interest and debate amongst intensivists.
00:00:53
Speaker
In today's episode of the podcast, we will take a deep dive into the topic of corticosteroids and COVID-19 ARDS.
00:01:01
Speaker
Our guest is Dr. Todd Rice.
00:01:02
Speaker
Dr. Rice is an associate professor of medicine in the Division of Allergy, Pulmonary and Critical Care Medicine at Vanderbilt University.
00:01:10
Speaker
He serves as the director of the medical ICU.
00:01:13
Speaker
As a physician scientist, he conducts clinical research in the ICU, specifically in patients with sepsis, ARDS, and acute respiratory failure.
00:01:21
Speaker
Dr. Rice's research has expanded in the last few years to using the ICU as a learning healthcare environment and conducting comparative effectiveness trials.
00:01:30
Speaker
In addition to having his own National Institute of Health NIH funding, Dr. Rice serves as the Vanderbilt PI for the prevention and early treatment of acute lung injury, the PETL network.
00:01:40
Speaker
Dr. Rice recently coauthored an editorial published in JAMA entitled Corticosteroids and COVID-19 ARDS, Evidence and Hope During the Pandemic.
00:01:50
Speaker
It is a true honor to have him on the podcast.
00:01:52
Speaker
Todd, welcome to Critical Matters.
Historical Context of Corticosteroids in Critical Care
00:01:54
Speaker
Thanks, Sergio.
00:01:57
Speaker
I would like to start with a
00:01:59
Speaker
brief historical context on the steroids and critical care, I mean, both in ARDS and in sepsis.
00:02:05
Speaker
Seems that we've been talking about them for decades now.
00:02:10
Speaker
I mean, I think it's been a little bit of a convoluted picture.
00:02:15
Speaker
And, you know, they, decades ago, were being used in these patients to decase the inflammatory cascade and try and, you know, overcome the body's inflammation to whatever the
00:02:27
Speaker
the etiology was of the ARDS or in septic shock, you know, the infection.
00:02:32
Speaker
And I think largely, as people know, there were lots of mixed results from those studies and a pretty convoluted picture that made it really hard to know what to do with steroids in patients that had either ARDS or septic shock.
00:02:50
Speaker
You know, then we had some
00:02:55
Speaker
reasonable randomized trials of high dose steroids that didn't seem to show a benefit.
00:03:00
Speaker
Some trials of late steroids in patients with ARDS where there may have been even potential neuromuscular weakness as a harm.
00:03:08
Speaker
And I think that for at least a significant proportion of the critical care world sort of turned people off to steroids and said, well, maybe they don't
Corticosteroids in Sepsis and ARDS
00:03:17
Speaker
work.
00:03:17
Speaker
They do have some side effects.
00:03:18
Speaker
Maybe we shouldn't be using them.
00:03:20
Speaker
But as many know, there's always been an interest.
00:03:24
Speaker
And from a biological plausibility and mechanistic standpoint, they've always seemed to make sense that they're anti-inflammatory and pretty nondescriptive anti-inflammatory, meaning they broadly cover a lot of inflammation and mechanisms of inflammation.
00:03:47
Speaker
And so the...
00:03:50
Speaker
the concept of this is an inflammatory condition and it seems like the body's inflammation is what's doing a lot of the damage in this situation, both in ARDS and septic shock.
00:04:00
Speaker
It seemed like biologically it would make sense that if we could turn that inflammation off or depress that inflammation, the patient should do better.
00:04:09
Speaker
So there's always been this interest in them because biologically they make a lot of sense.
00:04:15
Speaker
And then, as you know, in the last three or four years, there have been a number of studies that have been very provocative in saying maybe with the right approach and the right dose of steroids, maybe there is some benefit to them.
00:04:30
Speaker
And there's trials in septic shock, like approaches in adrenal, that say maybe they do get patients off of pressers faster and get people off the ventilator faster, and maybe
00:04:41
Speaker
I don't think it's definitive in septic shock, but maybe they even have a mortality benefit.
00:04:47
Speaker
And then in ARDS, DEX-ARDS came out a few months ago and had a positive signal for mortality.
00:04:55
Speaker
There are many people, me included, that think that that signal is so big that it's probably not really that big of a mortality signal, but have to admit that there's a mortality signal and that maybe in patients with ARDS, texamethasone may,
00:05:12
Speaker
may improve mortality, may improve outcomes.
COVID-19 Pandemic and Corticosteroid Usage
00:05:15
Speaker
I think part of the hard part, at least with ARDS, is that it's a very heterogeneous disease.
00:05:21
Speaker
And there's many, many, many different etiologies of it.
00:05:25
Speaker
And traditionally in the past, we've put all of those etiologies into the same bucket, called them ARDS.
00:05:31
Speaker
It's definitely a syndrome.
00:05:33
Speaker
It's a syndrome that can happen from many different diagnoses.
00:05:36
Speaker
And then we've tried to treat them all the same or try and study them all with the same potential intervention.
00:05:41
Speaker
And my suspicion is that that's what's contributed to the cloudiness and the muddling of this picture and made it harder for us to truly understand what the signal is of corticosteroids in patients with ARDS.
00:05:56
Speaker
It feels, Todd, that almost at the beginning of the year, like you said, DEXA-ARDS came out, but I think it was totally overrun by COVID and our focus on COVID, and we didn't really
00:06:09
Speaker
discuss it as much in many circles.
00:06:12
Speaker
But the feeling at the time was almost, steroids make sense.
00:06:17
Speaker
They probably work.
00:06:18
Speaker
We just haven't been able to figure out which are the exact patients that would benefit, right?
00:06:23
Speaker
Yeah, I think that's a big part of it.
00:06:26
Speaker
I think, you know, the other thing that trials like DEXA ARDS run up against is that there's some history with steroids.
00:06:34
Speaker
And so, you know, when a study like DEXA ARDS comes out and shows a
00:06:39
Speaker
what I consider to be a really big treatment effect, people say, well, if it's really that big, we should have, even if we had heterogeneity in the population and issues with trial design in the past, we should have been able to see something.
00:06:51
Speaker
There should have been something there.
00:06:52
Speaker
And if there wasn't anything there, then I don't know that there's any chance that the effect could be that big.
00:06:59
Speaker
And I think there may be some truth to that, but I also think that it's not
00:07:05
Speaker
it doesn't allow us to just dismiss the effect entirely and say, well, it can't be true because we haven't seen it in the past.
00:07:12
Speaker
And I think, you know, DEX-ARDS is swimming upstream a little bit from the past history of steroids and ARDS and, you know, no single study that showed a huge, huge effect.
00:07:27
Speaker
But I think that that's how progress is made and that's how we better understand treatments and diseases and,
00:07:35
Speaker
you know, as we're getting further and further into this and doing more and more steroids trials in ARDS, we're getting a better understanding.
00:07:42
Speaker
And DEXA ARDS is obviously the most recent part in non-COVID ARDS to give us information to kind of help clarify that better understanding.
00:07:52
Speaker
Before we started recording, we were just talking about the COVID pandemic.
00:07:56
Speaker
And one of the comments you made is that obviously as devastating as the pandemic has been for patients and as hard as it's been for healthcare providers,
00:08:04
Speaker
There's also always a several lining and one of them was the amount of effort that scientists around the world have put around trying to find answers.
00:08:14
Speaker
And specifically, we were just commenting on how much has been studied in steroids and ARDS due to COVID-19.
00:08:23
Speaker
So why don't we jump into COVID-19, ARDS and corticosteroids.
00:08:27
Speaker
And perhaps we could start Todd with a timeline that takes us back to February, March,
00:08:33
Speaker
when the initial recommendations from WHO and others were to not use corticosteroids in a widespread use, what the thought process was at that point?
Debate and Guidelines on Steroid Use in COVID-19
00:08:44
Speaker
Yeah, the World Health Organization, the CDC all had comments and recommendations not to use them, not to widespread use them for the treatment of COVID-19.
00:08:53
Speaker
Obviously in those statements, they always say that if a patient has a condition that would otherwise be treated with corticosteroids, so they have an asthma exacerbation or they have, you know,
00:09:04
Speaker
flare with lupus or another connective tissue disease that you would treat with steroids, then you should use steroids, but not to use them specifically for the treatment of COVID-19.
00:09:14
Speaker
And, you know, I'm not part of those organizations, so I can't necessarily tell you with confidence why they did that.
00:09:21
Speaker
But I do know that the data for other viral illnesses, especially flu, MERS, and SARS, suggested that steroids increased viral replication.
00:09:32
Speaker
you know, made it so that the virus replicated more readily and for a longer period of time.
00:09:38
Speaker
And I think that kind of preliminary data, not necessarily clinical with clinical outcomes, but preclinical in viral loads and viral replication, I think that data scared people about maybe steroids weren't going to be helpful because we've studied them in ARDS before and haven't found a huge signal, save DEXA ARDS, which was very recent.
00:10:03
Speaker
And there's a potential downside of if it makes the virus replicate, maybe it's going to make the disease even worse.
00:10:09
Speaker
And therefore, no strong recommendation.
00:10:12
Speaker
In fact, the recommendation to avoid steroids for the treatment of COVID-19 specifically from the World Health Organization and the CDC.
00:10:21
Speaker
Interestingly, the Surviving Sepsis Campaign actually had a weak recommendation.
00:10:24
Speaker
They said, we think you should use steroids in COVID-positive ARDS.
00:10:28
Speaker
And I think they were really kind of the ones that
00:10:31
Speaker
that went out on that limb and said, you know, with the DEXA ARDS data, we think that there may be a potential here for some benefit, and we, you know, recommend that maybe you should use them in that situation.
00:10:47
Speaker
And then the IDSA was sort of what I call the political response, which is use them in the context of clinical trials
00:11:00
Speaker
We need to study them, but we don't think they should be used in routine clinical practice at this point.
00:11:05
Speaker
And that's sort of the widespread recommendations and the diversity of recommendations across different groups.
Impact of COVID-19 on ICU Patients
00:11:15
Speaker
But I think you're right.
00:11:16
Speaker
In general, the most common recommendation was we don't recommend using these in patients that have COVID-19 for the treatment of COVID-19.
00:11:28
Speaker
And I think an important distinction for intensivists is that in our world, obviously a great number of patients that we're seeing in our ICU with COVID, especially in places where they have a high incidence, are going to be patients with ARDS.
00:11:42
Speaker
But the hundreds of patients that we see in our ICU with ARDS are just the tip of an iceberg of millions of patients with much milder COVID-19 symptoms.
00:11:52
Speaker
And that is probably also what people were alluding to in terms of making these recommendations.
00:11:57
Speaker
Yeah.
00:11:58
Speaker
Yeah, I completely agree.
00:12:01
Speaker
So let's talk a little bit about the trials.
00:12:04
Speaker
I think that there's a lot that came out in the last couple of months, which I think, like we mentioned earlier, is a silver lining and a great effort from the scientific community.
00:12:15
Speaker
But perhaps we could start with the early retrospective data out of China.
00:12:20
Speaker
And then if you could share with us the idea of the WHO Prospero meta-analysis
00:12:28
Speaker
in terms of how it was set up, and then we could probably go into the individual trials and put it all together later with the results of PROSPERO.
00:12:37
Speaker
Yeah, so the early retrospective data were data that, you know, as the word says, were retrospective.
00:12:47
Speaker
They went back and looked at patients that got steroids and compared them to patients who didn't get steroids and saw, you know, hey, it looks like the patients that were getting steroids may have done better.
00:12:57
Speaker
Everybody on this call probably, or everybody listening to this podcast probably understands that there are lots and lots of biases and confounders in retrospective data.
00:13:07
Speaker
And ensuring that the population of patients that got steroids is the same as the population you're comparing it to that didn't get steroids is really, really, really difficult.
00:13:18
Speaker
And we do a lot of statistical things like
00:13:23
Speaker
like propensity score analyses or adjustments for baseline variables and a lot of those to try and make those two populations that we're comparing as similar as possible.
00:13:34
Speaker
But there's always unknown confounders and there's always issues with things that aren't measured that you couldn't possibly have adjusted for or you couldn't even recognize that they were a potential confounder to even know to measure them to adjust for them.
00:13:49
Speaker
So there's always some issues with retrospective data.
00:13:52
Speaker
But retrospective data are sort of the first body of evidence and kind of give us an idea of, well, maybe this is something we should look at further and maybe this is something that we should examine in more detail in a prospective manner and maybe even in prospective randomized trials.
00:14:12
Speaker
The World Health Organization, you know, their job is to try and better the health of the global population and they,
00:14:20
Speaker
I think recognized along with a number of others, but they recognized that to get reliable and good information, we were likely going to have to combine efforts.
WHO and Global Data on Corticosteroids
00:14:32
Speaker
And during this pandemic, for a long time, there were lots and lots and lots of patients and places to study, but you got to get the trials up and running to do those studies if you're going to do prospective randomized trials.
00:14:47
Speaker
And there's always some
00:14:50
Speaker
lead time in that and some actual effort and infrastructure and time that has to be built and put into it in order to get the trial up and running.
00:15:00
Speaker
And the patients with COVID aren't waiting.
00:15:02
Speaker
They're continuing to just come into the institution.
00:15:05
Speaker
And so we heard pretty early on from colleagues in China that by the time they got their trials up and running and actually were starting to enroll, their cases were going away and they weren't completing their trials because they just didn't have enough patients anymore.
00:15:19
Speaker
which is a good thing from the population standpoint of COVID, but a bad thing because you need to have patients in order to run trials to get an answer as to treatments.
00:15:29
Speaker
And I think that signal coming from China and Italy and some of the early places really made it apparent that the best way we're going to get rigorous answers is to try and combine efforts.
00:15:41
Speaker
And that sounds like a no-duh, of course.
00:15:44
Speaker
I mean, that's how else would you do this?
00:15:47
Speaker
It sounds like the most
00:15:48
Speaker
obvious thing probably that'll be said in this podcast.
00:15:52
Speaker
But getting people to pull that off is hard.
00:15:55
Speaker
And getting people to networks, trialists, researchers to share their data, especially to share their data before they're already published, takes a lot of trust and takes a huge effort.
00:16:09
Speaker
Because, you know, we in the research world are always scared that we're going to get scooped on something or somebody is going to put our data out there before we publish it and then
00:16:17
Speaker
it'll make it non-publishable and we won't ever be able to publish it under our name.
00:16:21
Speaker
And so there was a lot of trust in the World Health Organization.
00:16:26
Speaker
The World Health Organization made a lot of promises and commitments to these networks to be very confidential with the data and to safeguard the data in a way that wouldn't inhibit or hurt
00:16:45
Speaker
potential future publication of individual trials and even worked with JAMA in making that so that they were all published together and so that there wasn't any scooping and there wasn't any pre-publication release of the data so that it would hinder the chance to publish it.
00:17:04
Speaker
So the concept of combining these trials, I mean, we've been doing meta-analyses, et cetera, forever, right?
00:17:11
Speaker
The concept is not new.
00:17:12
Speaker
The idea that we had to do this in order to get enough data to answer the question was readily apparent and apparent to a lot of people, but the machinery and the making it happen is where the World Health Organization really, really, really excelled and did a phenomenal job of getting large networks that were doing these trials to come together and say, yes, we will share our data with you so that we can have the most rigorous
00:17:40
Speaker
answer that we possibly can from all of the data that are potentially available to answer this question.
00:17:46
Speaker
And I think that also quite unique was, not for the first time, but not very common, the idea of doing this as the prospective meta-analysis, right?
00:17:54
Speaker
So getting everybody together on board from the get-go and moving forward, considering that time was a premium with the pandemic going on.
00:18:02
Speaker
Yeah.
00:18:02
Speaker
Yeah, I agree.
00:18:04
Speaker
That wasn't totally novel.
00:18:05
Speaker
It had been done a few times in the past.
00:18:09
Speaker
It certainly was in the early stages of things that have been done.
00:18:15
Speaker
And it increases the rigorousness of the meta-analysis because you know, prospectively, that you're getting these data.
00:18:21
Speaker
You can collect the data in a way that makes them a little bit more easily comparable and makes the analysis a little bit easier to understand and to do.
00:18:35
Speaker
Perhaps we could start with going through some of these trials in a brief description.
00:18:40
Speaker
I think that we'll put links to the trials for people to read in detail.
00:18:45
Speaker
And I think that ultimately it's the sum of this data and the meta-analysis that maybe guides us and gives us the final recommendations.
The Recovery Trial and Its Implications
00:18:55
Speaker
But it's almost, I think chronologically, the first one that we heard about and that really caused the most impact was recovery.
00:19:02
Speaker
Could you just tell us a little bit about recovery, please?
00:19:05
Speaker
Yeah, recovery was an open-label randomized trial done in the UK.
00:19:09
Speaker
The UK really got all of their kind of hospitals, their public hospitals together and said, we're going to do research on COVID.
00:19:17
Speaker
We're going to do it in a manner that even if you're not doing, not a hospital that's used to doing a ton of research, you're going to be able to do it.
00:19:25
Speaker
And we're going to do it in mass force.
00:19:27
Speaker
And in fact, I think during that time, one-sixth of the patients that were in the hospital with COVID
00:19:33
Speaker
were enrolled in a trial of some sort through the recovery is kind of the name of the platform.
00:19:40
Speaker
So there's recovery steroids, there's recovery plasma, there's recovery hydroxychloroquine.
00:19:45
Speaker
And recovery steroids enrolled a lot, a lot, a lot of patients in the range of 6,000 patients.
00:19:53
Speaker
It was open label, so patients and clinicians knew if they were randomized to steroids or if they were randomized to just standard of care.
00:20:01
Speaker
There was no placebo, it was just standard of care.
00:20:04
Speaker
And there are some issues with open label trials and there's some biases that can be introduced with open label trials, but it's also probably the quickest way to get a trial up and running and the way they did it in recovery, which was similar in REMAP-CAP, you'll hear about that also, allowed it to be done as just part of routine care.
00:20:25
Speaker
And there didn't have to be a lot of special research specific interventions or people or
00:20:32
Speaker
or blood draws in labs, et cetera, et cetera.
00:20:35
Speaker
You could just do it as sort of part of your routine care.
00:20:37
Speaker
It works really, really, really well for medications and therapies that are already approved and already in practice and that don't need a ton of safety studying and don't need a ton of regulatory monitoring to be done.
00:20:53
Speaker
And that obviously, corticosteroids fit that perfectly.
00:20:56
Speaker
So, and then people I think know that the results showed, you know, they were released first in a press release, which was very interesting for those of us on the front lines to say, what do you do with a press release?
00:21:06
Speaker
You know, it's one thing we were just starting to get used to what to do with preprints and understand sort of how we deal with those.
00:21:12
Speaker
And then recovery was released in a press release.
00:21:15
Speaker
There was a little bit of data in it, but not really the data that lets you analyze the trial results and understand them in depth at all in the press release.
00:21:25
Speaker
So it was released in a press release and the data showed, and I think people recognize this, that there was about a 30% reduction in the hospital mortality for patients in the ICU, or I'm sorry, patients on mechanical ventilation, and about a 20% reduction in mortality for patients that were on oxygen, but not mechanically ventilated.
00:21:46
Speaker
You know, it's just a huge effect, a huge, huge, huge effect.
00:21:49
Speaker
And I think maybe importantly also, there seemed to be no effect in patients that were not on oxygen when they were,
00:21:55
Speaker
started on their steroids.
00:21:57
Speaker
And so those were kind of the results that we had.
00:21:59
Speaker
Big, big, big trial, an effect that was really quite large and potentially differential effect depending on how sick the patient was.
00:22:10
Speaker
And this changed the whole landscape and also had a big impact on the trials that you wrote the editorial on that we'll discuss next.
00:22:19
Speaker
Could you just tell what the impact of this was on the trials and why ultimately
00:22:23
Speaker
the meta-analysis proved to be super valuable in this case.
00:22:29
Speaker
Yeah, I think the good and the bad of this is that there's a trial, it was done, it was big, it had an effect, and they're putting results out there.
00:22:41
Speaker
The bad side of this is that it made it really hard for other trials studying steroids to know what should we do with this.
00:22:47
Speaker
Is it ethical?
00:22:48
Speaker
Is it...
00:22:50
Speaker
okay to continue to enroll patients into a steroid trial where there's a placebo arm and patients aren't getting steroids?
00:22:56
Speaker
Are these data, these recovery data, good enough that everybody should just be getting steroids, that we should stop our trial?
00:23:02
Speaker
Is there this term equipoise?
00:23:05
Speaker
Do clinicians still have enough doubt on whether steroids work or not that they would even be willing to put their patients in these trials?
00:23:13
Speaker
Or
00:23:14
Speaker
Do patients have enough doubt as to whether or not these work or not, that they would be willing to say, yes, I'm willing to participate in a trial instead of just saying, I think it works, just give me the steroids.
00:23:24
Speaker
Those are tough, having gone through those a couple of times, those are tough decisions to make in a trial when new information comes out that makes it so that you need to consider changing your trial.
00:23:34
Speaker
And in this place, in this situation, not just changing your trial, but pretty much stopping your trial.
00:23:40
Speaker
And so every single one of them, I think independently,
00:23:43
Speaker
looked at the recovery results and said they're good enough results that we probably can't continue we can't continue to give people a placebo or a non-steroid harm in order to study this further and so they ended up stopping their trials when the recovery results were were released talk could we just recap the uh a
00:24:06
Speaker
three trials that ultimately were published together and are published alongside the meta-analysis that did include data from recovery as well.
Additional Trials and Meta-Analysis on Steroids
00:24:14
Speaker
But I think it's valuable for our audiences to know what these are.
00:24:17
Speaker
And you mentioned REMAP-CAP, and we can talk about that first.
00:24:22
Speaker
Yeah, REMAP-CAP is similar to recovery.
00:24:25
Speaker
It's an open-label trial, platform trial, so there are multiple actual interventions that you could get randomized to in REMAP-CAP, depending on which domain you fit into.
00:24:35
Speaker
So the remap cap steroids, corticosteroids, which is what was published in JAMA, randomized patients to their steroids or a standard of care in an open label fashion, again, without a blinded placebo to try and determine the effect.
00:24:49
Speaker
It was kind of in the US, kind of in the UK, kind of in Australia.
00:24:53
Speaker
So it's a multinational in Europe also.
00:24:56
Speaker
It's a multinational trial led by Derek Angus in Pittsburgh.
00:25:02
Speaker
It's kind of interesting to note that it was not a platform that was designed for COVID.
00:25:07
Speaker
It's actually an ongoing platform to study community-acquired pneumonia and treatments in community-acquired pneumonia.
00:25:13
Speaker
And then they essentially added a COVID domain when COVID was here.
00:25:17
Speaker
And so they sort of used already existing infrastructure in order to do this.
00:25:26
Speaker
And REMAP-CAP uses a Bayesian approach.
00:25:28
Speaker
So it's a little harder to understand because it's not a traditional frequent statistical approach.
00:25:34
Speaker
And the Bayesian approach just says sort of, it doesn't give you a p-value.
00:25:37
Speaker
Instead, it gives you an output that says, what's the probability that one arm is better than the other?
00:25:42
Speaker
And if we continue to go, what do we think the chance that one arm will be shown to be better than the other arm will be?
00:25:50
Speaker
And if you read the article, you can see that's how the outputs are from remap cap.
00:25:54
Speaker
There's a,
00:25:55
Speaker
a 90% chance, posterior probability, that steroids are better in patients that were randomized into, there's three arms in REMAP-CAP.
00:26:04
Speaker
There was a 90% chance they're better if they were randomized into the steroid arm.
00:26:07
Speaker
It's about an 82% chance they were better if they were randomized into the what's called shock-dependent or steroid shock-dependent arm.
00:26:15
Speaker
And in the steroid arm, the first arm of the 90%, they gave patients steroids.
00:26:21
Speaker
They gave,
00:26:24
Speaker
I'm going to forget actually what the actual steroid was.
00:26:28
Speaker
Sergei, you remember what the steroid was?
00:26:30
Speaker
They all ran together for me.
00:26:31
Speaker
Hydrocortisone.
00:26:32
Speaker
Yeah.
00:26:33
Speaker
Yeah.
00:26:34
Speaker
They and Cape COVID gave hydrocortisone.
00:26:36
Speaker
Kodak gave the dexamethasone.
00:26:37
Speaker
Yeah.
00:26:37
Speaker
So RemapCap gave hydrocortisone and they gave a fixed dose to patients in the steroid arm.
00:26:44
Speaker
They gave a fixed dose to patients in the steroid shock arm, but only when those patients were in shock.
00:26:50
Speaker
So
00:26:51
Speaker
Patients that were in shock at the beginning got randomized steroids, would get steroids, but patients who were not in shock, who got randomized in that arm, would only get steroids if they developed shock.
00:27:01
Speaker
So a little less than half of the patients in that arm actually got steroids.
00:27:05
Speaker
So it's a really complicated arm to understand.
00:27:07
Speaker
But even with that, it looked like steroids had a pretty high probability, a really high probability actually, of being better than the standard of care group.
00:27:17
Speaker
And this study, as the other ones,
00:27:21
Speaker
showed this probability based on the base and approach like you explained of 90% in the patients who got the steroids regardless and 83% of being better than those who got it in the shock mode but did not reach its primary threshold to call it a positive trial, correct?
00:27:39
Speaker
Correct.
00:27:40
Speaker
Yeah, correct.
00:27:42
Speaker
A big part of that, you'll hear that in all three of these trials, a big part of that is that
00:27:47
Speaker
they were all stopped early.
00:27:48
Speaker
They were stopped when the recovery results came out.
00:27:50
Speaker
So they have fewer patients enrolled in them than they had hoped they were going to have or that they were planning to try and enroll.
00:27:57
Speaker
And because of that, they don't have quite the confidence in their answers that they were hoping to have gotten had they been completed with enrollment to the planned numbers.
00:28:08
Speaker
The second trial is the CODEX trial, which is the one that gave dexamethasone, and I think it was conducted principally in Brazil.
00:28:16
Speaker
Could you give us a synopsis of that trial, Todd?
00:28:20
Speaker
Yeah, so the CODEX trial was in Brazil, another open label trial, and used dexamethasone, so very similar to recovery.
00:28:30
Speaker
Actually used a little bit of higher dose, 20 milligrams instead of six milligrams for the first, I think, five days, and then 10 milligrams for the second five days, if I remember correctly.
00:28:41
Speaker
So a little bit of a higher dose of dexamethasone in Brazil.
00:28:45
Speaker
And, again, didn't meet statistical significance for its outcome, but showed in general benefit to, I think their primary endpoint was ventilator-free days, which is days alive and off of the ventilator, and showed improvement in those that did not reach statistical significance.
00:29:02
Speaker
Also looked at mortality and showed a mortality signal that was, again, not statistically significant, but very, very, very consistent with what the recovery results showed.
00:29:14
Speaker
I mean, all three of these trials, REMAP-CAP codex and the next one we'll talk about, CAPE-COVID, have signals that are remarkably similar to the recovery signal.
00:29:25
Speaker
And that's, I think, where the value in the meta-analysis comes into is that it shows you how consistent the signal seems to be across all these trials, even if some of them, REMAP-CAP codex, for example, don't have enough power to reach statistical significance because they were stopped early.
00:29:43
Speaker
And the last one you mentioned is CAPE COVID, which I think had the particular aspect that was the only one that utilized placebo.
00:29:51
Speaker
Yeah.
00:29:52
Speaker
Yeah, CAPE COVID was a French trial.
00:29:55
Speaker
It uses hydrocortisone, just like RemapCap did, but it's the only one of the group, even including recovery, that's blinded and used an actual placebo-controlled arm.
00:30:07
Speaker
So its endpoint was this funny endpoint of death or death.
00:30:13
Speaker
respiratory failure, persistent respiratory failure at 21 days, or the opposite of that, which is getting over survival and getting over respiratory failure at 21 days.
00:30:24
Speaker
And essentially that is, it's a little bit complicated, but essentially that is coming off of the ventilator at 21 days and being alive.
00:30:32
Speaker
So it's a little bit akin to ventilator-free days.
00:30:35
Speaker
And, you know, it again got stopped early, but it actually had a signal in some of its outputs
00:30:42
Speaker
that was statistically significant and showed benefit of hydrocortisone in patients that had COVID and severe respiratory failure.
00:30:53
Speaker
And it's very interesting that these trials, if were to be published independently or different time spans, would all probably still add to the confusion because we would say that they technically show a signal, but they're not positive per se.
00:31:11
Speaker
And I think that that's where probably the value of this prospective meta-analysis by the WHO comes into play and giving us a little bit more confidence of what to do with these patients.
00:31:22
Speaker
So could you tell us what ultimately the Prospero meta-analysis showed and who did it include?
00:31:27
Speaker
Yeah, so the Prospero, I think, included the four trials we talked about, Recovery, Remap, GAP, Codex, and CapeCOVID.
00:31:37
Speaker
It also included three other trials.
00:31:39
Speaker
that I don't think are published yet, but are smaller and were also stopped because of recovery of steroids.
00:31:48
Speaker
One of those trials actually looked at methylprednisolone.
00:31:50
Speaker
So there's a couple nice things about Prospero.
00:31:54
Speaker
One is that it allows us to sort of look at the effect of different steroids, both hydrocortisone and dexamethasone, which are used in multiple trials, and then even one trial with methylprednisolone.
00:32:05
Speaker
and look at those steroids and kind of see is the effect consistent?
00:32:07
Speaker
Are we seeing anything that's different among the different specific steroids?
00:32:13
Speaker
The other thing I think that it kind of did was it just gave the full picture.
00:32:18
Speaker
What is the real consistency among these trials?
00:32:21
Speaker
And if we put them all together and get huge, huge, huge numbers, what does the effect size look like?
Impact of Steroids on COVID-19 Outcomes
00:32:26
Speaker
And so in Prospero, they found that mortality went from 40%, and this is in mechanically ventilated,
00:32:34
Speaker
patients, so the patients with severe COVID-19, mortality went from 40% to 32% compared to from the standard of care arm to the steroid arm.
00:32:44
Speaker
So an 8% reduction, absolute reduction in mortality, which is a 20% relative reduction for the 40% in the standard of care arm.
00:32:51
Speaker
8% is a pretty big reduction.
00:32:53
Speaker
That means that if you treat 12 and a half, so call it 13 patients with steroids, you'll save one life.
00:32:59
Speaker
One patient will
00:33:02
Speaker
survive that would have otherwise died if you treat 13 patients with steroids.
00:33:07
Speaker
So that's a pretty good effect.
00:33:08
Speaker
We don't see that effect very much in critical care medicine.
00:33:12
Speaker
And it's an effect size that is tangible and palpable and not such that you have to treat 100 patients in order to see one positive outcome.
00:33:24
Speaker
And considering the numbers that we're seeing, I think that we can all do the math real quickly.
00:33:29
Speaker
And it does add up to a lot of saved lives in this pandemic.
00:33:32
Speaker
Yeah, absolutely.
00:33:34
Speaker
Absolutely.
00:33:37
Speaker
Another aspect of Prosperol that you mentioned that I think is worth reemphasizing is that because it included all these studies with different steroids, that effect that you're quoting is on the use of steroids and includes dexamethasone, methylprednisolone, there's only one study, and hydrocortisone, correct?
00:33:57
Speaker
Correct.
00:33:58
Speaker
Yep.
00:33:58
Speaker
Yeah, I think it suggests pretty strongly that it's a class effect, that this is a steroid class effect, and that there's nothing specific about texamethasone from the recovery trial, that it's the only one that will benefit people, and that it's corticosteroids in general.
00:34:14
Speaker
And I think that also helps us with the mechanism that suggests that all of these are similar in that they're anti-inflammatory, and it's decreasing the inflammatory response from the body and the damage that's done from that inflammatory response.
00:34:27
Speaker
that's providing the benefit to these patients.
00:34:30
Speaker
One thing that Prospero looked at, sorry, Sergio, the other thing that Prospero looked at is dose and couldn't actually see a difference in dose either.
00:34:38
Speaker
High dose like was done in Codex versus a lower dose that was recovery and the other trials.
00:34:45
Speaker
So, you know, the hypothesis at least, maybe strong hypothesis from that is that you don't need a high dose and that low dose may actually be as beneficial as a high dose.
00:34:57
Speaker
I think there may still be a little bit of a lingering in that question, but at least for now, I think the data suggests that low dose is as good as high dose and you don't have to use high doses in these patients.
00:35:08
Speaker
Which I think is important in terms of side effects, which was going to be my next question.
00:35:12
Speaker
One of the aspects that perhaps we didn't get as much information as we would want because of the design of recovery and some of the other trials was what's the impact on side effects or potential complications from steroids?
00:35:26
Speaker
Yeah, I completely agree.
00:35:29
Speaker
Some of that you can read out of the editorial that the way these trials were done in an open label and in the middle of a pandemic, collection of side effects in a rigorous way was just not a high priority.
00:35:41
Speaker
And we still have a little bit of a void on truly understanding what might be the side effects in these patients.
00:35:49
Speaker
Many of you listening to this podcast probably are using steroids in your patients, so you'll relate a little bit to when I've used them
00:35:56
Speaker
I've found that there's obvious hyperglycemia.
00:35:59
Speaker
It's not a huge side effect because we usually can treat it with some insulin and treat it pretty well.
00:36:04
Speaker
But the bigger side effect that we've seen that we've really struggled with is this delirium and almost like a psychosis.
00:36:10
Speaker
It appears, at least to me anecdotally, it appears to be worse in elderly patients.
00:36:16
Speaker
And unfortunately, the elderly patients appear to be more affected by COVID and tend to get more severe disease.
00:36:22
Speaker
So we're seeing those in our ICUs and in our hospitals more.
00:36:26
Speaker
And the delirium is, at times, treatment limiting.
00:36:31
Speaker
And what I mean by that is, is that it's so bad that, you know, you struggle to keep the patient safe because they really are so confused and they're all over and they're trying to climb out of bed and they're pulling at things.
00:36:42
Speaker
And those, I think, are hard because we have,
00:36:45
Speaker
in-depth discussions at the patient's bedside on rounds about, you know, do we need to stop the steroids?
00:36:50
Speaker
Do we need to, is this side effect so bad that we can't continue this treatment, which we now have data suggest is really beneficial for the patients because we're hurting them with the steroids.
00:37:02
Speaker
And I think those are the hard things to understand and the hard, the data that we need, the question that we need more data on to truly kind of understand, you know, what to do in that situation.
00:37:16
Speaker
As the pandemic evolved, there was a big debate amongst people who were recommending all sorts of therapies with the argument that better to do something than nothing and with the argument that if we wait for the trials, we're never going to get the answer and people are going to die.
00:37:31
Speaker
I think that the steroid story is a great story to illustrate that when people get together and we have the numbers, that is the right time to do these trials so that we can get some answers.
Corticosteroids in Non-COVID ARDS
00:37:43
Speaker
And I think that's a story that is worth also
00:37:47
Speaker
underlying because it's been a constant, I think, discussion amongst clinicians lately.
00:37:53
Speaker
In order to bring things together, Todd, based on all that we discussed, where do you think today the use of corticosteroids stands for COVID-19 ARDS, and what's the impact of these studies in COVID on other patients with ARDS?
00:38:10
Speaker
Yeah, I think in non-COVID ARDS, there are still some questions about what is the effect of steroids.
00:38:17
Speaker
DEXA-RDS gives us some data, but, you know, it's not like we have in COVID where we have thousands and thousands of patients in multiple trials that we put together and have a similar signal.
00:38:27
Speaker
So I think there may still be some randomized trials in patients with non-COVID ARDS to better understand the effect of steroids in that group.
00:38:37
Speaker
But I think it's becoming harder and harder because I think as the data are starting to come together and come out and we're gathering more and more of it, more and more of the data, I think the tide is kind of swinging to steroids may truly be a treatment of choice in patients with non-COVID ARDS.
00:38:57
Speaker
It's an easier question for me in patients with COVID ARDS.
00:39:00
Speaker
And, you know, you could tell from the editorial that Holly Prescott and I wrote,
00:39:06
Speaker
that both of us feel pretty strongly that steroids should be the standard of care for patients with severe COVID-19.
00:39:13
Speaker
Patients in the ICU with respiratory failure from COVID should get steroids unless there's just a huge, big contraindication and a reason they can't get it.
00:39:22
Speaker
I think the data are pretty convincing that they improve outcomes and you can pick some outcomes, come off the ventilator, keeping you off the ventilator, saving your life, getting you out of the hospital,
00:39:34
Speaker
I think it has a positive effect on all of those.
00:39:37
Speaker
And so I think steroids are the, I agree with the World Health Organization, I think they're the kind of new standard of care for critically ill patients with COVID.
00:39:49
Speaker
I do think that there are still a lot of unanswered questions.
00:39:53
Speaker
The question of, that we talked about earlier, what do you do when you start a patient on steroids and then they have such bad delirium that you have a hard time keeping them safe from themselves?
00:40:03
Speaker
I think that's one question.
00:40:05
Speaker
I think dose is a little bit of a question.
00:40:07
Speaker
Maybe that our preliminary data suggests dose doesn't matter, but I think we need more better data in that realm.
00:40:14
Speaker
And I think the population for steroids is another big question.
00:40:19
Speaker
It's pretty easy.
00:40:20
Speaker
We're in a good spot for the intensivist because I think it's pretty easy that the patient that's sick with respiratory failure from COVID, that population I think is pretty clearly defined that we should probably give steroids to.
00:40:32
Speaker
But we're starting to see articles that there's different phenotypes of those patients.
00:40:36
Speaker
And maybe steroids work for a predominant phenotype, but not for a less predominant phenotype, a phenotype that maybe is more vascular coagulopathy type than a inflammatory phenotype, for example.
00:40:50
Speaker
And it's never, a bunch of us have talked about this, it's never really made sense to me that the marker of will steroids work or not is whether or not somebody puts you on oxygen.
00:40:58
Speaker
That just doesn't seem to make a ton of sense to me.
00:41:01
Speaker
And I think work needs to be done to figure out better markers and better indicators of which patients truly benefit from, which patients with COVID truly benefit from corticosteroids and which patients with COVID either don't benefit or maybe even potentially get harmed by corticosteroids.
00:41:20
Speaker
Those biomarkers may be inflammatory biomarkers.
00:41:22
Speaker
They may be something we've never actually studied before, but I think there needs to be work in that
Unresolved Questions on Steroid Therapy
00:41:28
Speaker
area.
00:41:28
Speaker
And then the last kind of question to me, people have asked me, well, can you use it with remdesivir?
00:41:34
Speaker
Can you use it with antivirals?
00:41:36
Speaker
And that to me, isn't even a question.
00:41:37
Speaker
I think it's pretty clear that they work in different manners.
00:41:41
Speaker
The mechanisms of action is entirely different between remdesivir, which is an antiviral and steroids, which is an anti-inflammatory.
00:41:48
Speaker
And I think you both can use them together and maybe are helped by using them together.
00:41:53
Speaker
Maybe that's even better to use them together.
00:41:55
Speaker
So I think using them together is the right approach.
00:41:58
Speaker
The real unanswered question to me is duration of therapy.
00:42:02
Speaker
And some of this will resonate with, I think, on the podcast.
00:42:05
Speaker
We have a number of patients that we see that after 10 days of steroids that we've been using from the recovery trial, day 11 and day 12, the patient seems to be doing worse.
00:42:15
Speaker
Their inflammatory markers, like their CRP or their ferritin or their LDH or ASD or pick an inflammatory marker, are increasing.
00:42:23
Speaker
And they almost look like they got rebound inflammation from us stopping their steroids.
00:42:28
Speaker
In that population, should we give them their steroids back?
00:42:31
Speaker
Should we restart it?
00:42:32
Speaker
Did we just go too short?
00:42:34
Speaker
Do they need a longer course?
00:42:36
Speaker
Should we taper it?
00:42:37
Speaker
I think those are all questions that need to be answered.
00:42:40
Speaker
And I think they're questions that could have significant contribution to improving the care of these patients and improving the outcomes of patients that we're treating already with steroids, because we know that's the right thing to do, but we don't really know how to implement that in practice and get out of treating them with steroids.
00:42:59
Speaker
The patient who you treat with steroids, who got better, who is already out of the ICU and on their way home, that patient stopping the steroids, I think seems to be a reasonable thing to do.
00:43:11
Speaker
But that patient who's still critically ill and or getting worse, I think we still have that question to answer.
00:43:16
Speaker
And I think that, like you mentioned, these are very important questions that hopefully we will be able to continue to study and understand.
00:43:24
Speaker
But I think it's worth emphasizing once again
00:43:27
Speaker
the success story of really getting data in the midst of a pandemic and finding a therapy that seems to have an impact on important patient outcomes such as mortality and getting off the ventilator as a big win and I think a lesson for future pandemics if they were to come that the sooner we start organizing in terms of collaborating scientifically, the more likely we are to find answers that ultimately will help our patients.
Collaboration and Future Research
00:43:55
Speaker
Yeah, absolutely.
00:43:56
Speaker
And I think I would take it even a step further, Sergio.
00:43:58
Speaker
I would say, and we say this, I think, in the editorial, that this may set the stage and the standard for collaboration even outside of pandemics.
00:44:08
Speaker
You know, there are multiple groups that have questions about the same things in critical care.
00:44:13
Speaker
You know, there's some big high-level topics that we'd like answers on that have multiple large networks doing studies on them.
00:44:21
Speaker
And although there have been preliminary talks between some of those networks that I know about, for example, in general, those networks work in an isolated fashion to try and answer that question.
00:44:30
Speaker
And I think, you know, the World Health Organization has shown us a path forward of a way of being more efficient and answering these questions in a faster manner and a more efficient manner for the benefit of our patients, honestly.
00:44:42
Speaker
And hopefully that'll carry over even, that'll be one of those silver linings, as you said,
00:44:46
Speaker
from the pandemic that will carry over even into non-pandemic research that we can be collaborative in that way.
00:44:52
Speaker
Absolutely.
00:44:54
Speaker
Todd, I really appreciate your expertise on this
Personal Insights and Reflections from Dr. Rice
00:44:57
Speaker
topic.
00:44:57
Speaker
We customarily will end the podcast with a couple of questions that are outside of the context of the clinical topic.
00:45:04
Speaker
And if that would be okay, I would like to go that direction.
00:45:08
Speaker
Yeah, that'd be great.
00:45:09
Speaker
So the first question, Todd, relates to books.
00:45:12
Speaker
Are there any book or books that have influenced you the most or that you have gifted more often to others?
00:45:18
Speaker
Yeah, you know, I'm not a huge book reader, so this is a little bit of a hard question for me.
00:45:24
Speaker
I read a lot of medical literature and not as much book reading, but one book that sort of has meant a lot to me and has sort of stood out to me is a book called When Breath Becomes Air that many of you, I'm sure, have potentially read by Paul Kalanithi.
00:45:41
Speaker
And Paul was actually a neurosurgeon who, during residency, developed EGFR-positive lung cancer and ultimately passed away from his lung cancer, but writes this autobiography.
00:45:53
Speaker
And there are a number of sort of stories in the autobiography that hit home with me.
00:45:58
Speaker
One is that, you know, we're on one side of this patient-doctor relationship, but we are not immune from becoming the other side, where we're the patient.
00:46:07
Speaker
And it only takes a few minutes
00:46:09
Speaker
few times of becoming the patient to re-examine and look at that relationship differently when you're on the doctor side.
00:46:16
Speaker
I think many of us have experienced that and sort of can relate to that.
00:46:20
Speaker
The other thing that this book sort of sits with me well is that probably the biggest achievement, sounds kind of funny, maybe it's not the right way to say it, the highlight of my medical career so far is that
00:46:37
Speaker
my mentor came down with pancreatic cancer and asked me to take care of him and provide care at the end of his life.
00:46:43
Speaker
And although that was hard to do, it resonates with me that it was a very, very, very special thing.
00:46:52
Speaker
And it opened up so many additional thoughts about medicine and that it isn't just about care that's provided, it's about compassion and it's about empathy.
00:47:03
Speaker
And, you know, Paul says a lot in his book, it's about morals.
00:47:06
Speaker
and doing the right things.
00:47:07
Speaker
And I think that resonates a lot.
00:47:09
Speaker
The book came out shortly after I had cared for my mentor.
00:47:13
Speaker
And so I think it was sort of an open nerve that it kind of touched and really kind of rested and sat well there.
00:47:22
Speaker
So I think that's probably the big book that I like to talk about.
00:47:26
Speaker
It's an excellent read and we'll definitely link it in the show notes.
00:47:30
Speaker
The second question relates to something that you believe to be true in medicine or in life.
00:47:35
Speaker
that most people don't believe or act as they don't believe?
00:47:39
Speaker
Yeah, this one's a little nihilistic maybe.
00:47:44
Speaker
I think we in medicine want to do stuff and we like doing stuff.
00:47:51
Speaker
And sometimes doing things is not necessarily the right thing.
00:47:54
Speaker
So that's part of it.
00:47:56
Speaker
The other part of it is that in critical care, and this is specifically
00:48:04
Speaker
true for critical care, unfortunately.
00:48:06
Speaker
We've learned a ton of physiology, and then when we've taken that physiology and tried to apply it to the bedside, we've often been wrong in what we've been doing.
00:48:14
Speaker
And when we study things like higher tidal volumes, which improve oxygenation, but then when we studied it, it showed that it actually reduced mortality, or, you know, DVT, not DVT, sorry, GI prophylaxis,
00:48:30
Speaker
This seems to make sense, but when we study it says, well, it may not be saving lives and it could be harmful to people.
00:48:35
Speaker
And so in the ICU specifically, sometimes doing stuff, even doing stuff that physiologically is sound, may not be beneficial for our patients.
00:48:45
Speaker
And so, you know, I'm very much an evidence-based guy, and I think you got to have the evidence because the physiology all makes sense.
00:48:55
Speaker
And then when we apply it, it often doesn't happen in vivo like we think it's supposed to.
00:49:01
Speaker
So I think one of the, you know, it's a funny question, funny answer to a question, what do you believe to be a truth in medicine or life?
00:49:08
Speaker
Most people, other people don't believe.
00:49:10
Speaker
And I think the answer to me is that just doing something isn't necessarily good for our patients.
00:49:19
Speaker
It's something that I think was also highlighted during this pandemic and the discussions and the behavior of many clinicians and emphasizes the reasons why we need to really try to get the data
00:49:29
Speaker
and use the best available evidence always to try to answer those questions.
00:49:34
Speaker
Yeah, I don't know if everybody else ran into this like I did.
00:49:37
Speaker
At my institution, what happened at the beginning of this pandemic was that lots of non-intensivists became involved in intensive care.
00:49:46
Speaker
And what I mean by that was, is I had daily talks with rheumatologists and daily talks with my hematologists, and they were trying to relate things that they saw and recognized in their field to the ICU.
00:49:59
Speaker
And oftentimes, I knew they were wrong.
00:50:03
Speaker
So they'd say, this is an inflammatory process, right?
00:50:05
Speaker
We have to give an IL-6 receptor antagonist because IL-6 levels are high and we have to do that.
00:50:10
Speaker
And while I don't know if IL-6 receptor antagonists are good or bad in this disease, I was fairly confident that just giving them because IL-6 levels were high, we had tried that before in critical illness and it hadn't gone that well for us and that we shouldn't just
00:50:25
Speaker
say if A is abnormal, we should do something to make A normal again, because that's been shown numerous times that that's not what's beneficial for our patients.
00:50:35
Speaker
Not to mention, I think, the lack of perspective on time, and especially with IL-6 antagonists, remembering that they came to rheumatology after failing in critical care.
00:50:48
Speaker
Yeah, absolutely.
00:50:49
Speaker
And that's how they became big in rheumatology.
00:50:51
Speaker
Somebody salvaged them in another field.
00:50:55
Speaker
The last question, and I know that you have to go to take care of patients, have a clinical meeting, is what would you want every intensivist that's listening to know could be a quote or a fact to close?
00:51:08
Speaker
Yeah, I think the quote that was taught to me as I was growing up in my medical life was, don't just do something, sometimes just stand there.
00:51:19
Speaker
And, you know, that goes to what we talked about before, which is that just doing something isn't necessarily beneficial for the patients.
00:51:25
Speaker
And sometimes just giving the patient time and letting what you're already doing work is the answer to these problems.
00:51:36
Speaker
And sometimes not doing something but being with the family and being with the patient and being present there is the right answer, too.
00:51:44
Speaker
So that quote runs through my head a lot.
00:51:47
Speaker
And when I'm sitting there thinking, oh my gosh, I don't know what to do.
00:51:49
Speaker
What should I do?
00:51:51
Speaker
And then that thought comes through of, well, maybe the thing is don't do something, just stand here and let things develop and try and take in the picture and see what happens.
00:52:00
Speaker
So I think that's the quote that I would relay is don't just do something, sometimes just stand there.
Conclusion and Farewell
00:52:06
Speaker
That's a perfect place to stop.
00:52:08
Speaker
Todd, I really want to thank you for your time and sharing your expertise with our audience.
00:52:12
Speaker
I look forward to talking with you about other topics related to critical care.
00:52:17
Speaker
in the future.
00:52:18
Speaker
Thank you very much.
00:52:19
Speaker
Sounds great.
00:52:20
Speaker
Thanks, Sergio.
00:52:20
Speaker
Thanks for the time.
00:52:22
Speaker
Thank you for listening to Critical Matters, a Sound Critical Care podcast.
00:52:27
Speaker
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00:52:33
Speaker
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00:52:38
Speaker
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