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Vitamin C In Sepsis
3 Plays6 years ago
In this episode of Critical Matters, we will discuss the recently published CITRIS-ALI clinical trial evaluating the role of high dose Vitamin C in severe sepsis and ARDS.
Our guest is Dr. Emily Brant. Dr. Brant is a practicing intensivist and faculty at the University of Pittsburgh Medical Center. She was the lead author in the JAMA editorial entitled “Is High-Dose Vitamin C Beneficial for Patients with Sepsis?” which was published alongside the CITRIS-ALI Clinical Trial.
Additional Resources:
Is High-Dose Vitamin C Beneficial for Patients with Sepsis?: http://bit.ly/2nWKoDp
Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial: http://bit.ly/31s0QcD
Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study: http://bit.ly/2pBs433
Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis: http://bit.ly/2Bl523c
Books Mentioned in this Episode:
Becoming by Michelle Obama: https://amzn.to/2MvHRd3
Recommended
Transcript
Introduction to the Podcast
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.
Vitamin C and Sepsis: The Controversy Begins
00:00:32
Speaker
There has been a lot of excitement and controversy around the use of high dose vitamin C for sepsis and septic shock.
00:00:39
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Many have argued that because the potential benefits outweigh the cost and low harm risk, we should be using vitamin C in all our patients.
00:00:48
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Others, more cautionary, have argued that the data is insufficient and we should study its potential role with clinical trials and understand where it fits in our treatment schemes for sepsis.
Exploring the Citrus ALI Trial
00:01:00
Speaker
In today's episode of the podcast, we will discuss the recently published Citrus ALI clinical trial and the current evidence for high-dose vitamin C in sepsis.
00:01:10
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Our guest is Dr. Emily Brandt.
00:01:12
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Dr. Brandt is a practicing intensivist and faculty at the University of Pittsburgh Medical Center in Pittsburgh.
00:01:18
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She was the lead author in the JAMA editorial entitled, Is High-Dose Vitamin C Beneficial for Patients with Sepsis?
00:01:25
Speaker
which was published alongside with a Citrus ALI clinical trial.
00:01:29
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Emily, welcome to the podcast.
00:01:31
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Hi there.
00:01:32
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Thanks so much for having me.
00:01:33
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I'm excited.
00:01:34
Speaker
Excellent.
00:01:35
Speaker
So I think that maybe a good point to start would be if you could give us an idea of what are some of the reasons scientifically that have led to people have an interest in vitamin C and sepsis?
Potential of Vitamin C in Treating Sepsis
00:01:48
Speaker
Absolutely.
00:01:49
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Great question.
00:01:49
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So as you know, Sergio, sepsis is a huge problem across the nation and across the world.
00:01:55
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It affects over 2 million people every year, represents about 6% of all U.S. healthcare spending.
00:02:01
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Of every two to three patients in the hospital who die, unfortunately, one of those people will have sepsis.
00:02:05
Speaker
So number one, there is a huge amount of concern and a huge interest in finding a cure for sepsis.
00:02:12
Speaker
And that's sort of the number one thought in everybody's mind.
00:02:15
Speaker
I think the reason for the significant interest when it comes to vitamin C as a potential treatment for sepsis is sort of based on its pathophysiology and sort of the characteristics, the hallmark characteristics of sepsis.
00:02:27
Speaker
So thinking about it at the molecular level, sepsis is defined as a dysregulated host response to infection.
00:02:35
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This is associated with profound oxidative stress that's mediated by all of these inflammatory cytokines, things like PNF-alpha, all of these lipoproteins and lipoprotein saccharides.
00:02:44
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What this looks like at the cellular level then is some changes in the glycocalyx, some changes in the vascular integrity and vascular tone that at the clinical level looks like capillary leak with interstitial edema, profound hypotension, and multi-organ dysfunction.
00:03:00
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So I think the reason that vitamin C is so interesting as a potential source of help in this cause is that it's an antioxidant.
00:03:10
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So, number one, it binds to the adrenergic receptors and sort of improves the catecholamine response, therefore limiting the hypotension that's seen in sepsis.
00:03:20
Speaker
Secondarily, it's been noted to have some profound effects on endothelial dysfunction, so thought to eradicate sort of the leakiness associated with capillaries in the setting of sepsis and therefore decreasing the interstitial edema.
00:03:33
Speaker
And then there's also been some thoughts that it is bacteriostatic as well.
00:03:38
Speaker
So certainly if you think about it from the molecular level, it has a lot of promise.
00:03:41
Speaker
And I think that's sort of where the excitement is initially coming from.
00:03:44
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And Emily, could you tell me a little bit, what happens with vitamin C levels in patients who do have sepsis?
00:03:51
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Do we know that?
00:03:53
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Absolutely, we sure do.
00:03:55
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So humans and guinea pigs, which you might not have known, are incapable of synthesizing our own vitamin C. Therefore, we depend on exogenous sources.
00:04:03
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In healthy organisms, typically the amount of vitamin C that we get through our diet is sufficient.
00:04:08
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In critically ill patients, however, we do know that there is increased metabolic turnover from vitamin C, and therefore patients tend to be deficient.
00:04:16
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So if you think about our sailor friends way back in the 1700s, those folks were noted to have scurvy.
00:04:22
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Vitamin C levels in those folks are typically less than 11 micromoles per liter.
00:04:27
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In septic patients, we have seen that levels can be as low as the low to mid-teens.
00:04:32
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albeit not at scurvy levels, but in one observation cohort, patients with septic shock had levels as low as about 15 micromoles per liter.
00:04:41
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Other studies have seen about 40% of patients with sepsis might have plasma concentrations that are 23 micromoles or less.
00:04:48
Speaker
So certainly we do know that patients who are critically ill, particularly patients with sepsis, have increased demand and therefore have lower levels of vitamin C than you and I would who are otherwise healthy.
00:04:59
Speaker
Interesting.
00:05:00
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And I did not know that about the guinea pigs.
00:05:02
Speaker
I always felt like a guinea pig.
00:05:04
Speaker
And now I know why, maybe because we share that inability to synthesize our own vitamin C. Absolutely.
00:05:10
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You're welcome for that tidbit.
00:05:13
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So I think that it's very interesting, like you said, that there's clearly a deficiency in vitamin C in patients with sepsis.
00:05:20
Speaker
there is clearly mechanistically pathways that would be anti-inflammatory and as an antioxidant that would make sense would be helpful in sepsis.
00:05:31
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And I think that also very interesting for many, many years, I think our grandmothers have recognized that or thought that they recognize that drinking lemonade and orange juice when we have an infection or a flu seems to help.
00:05:45
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So maybe that is based on vitamin C, maybe not.
00:05:48
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But my question really is, how did vitamin C has been around for a long time, and all of a sudden, there's been a lot more interest in it within sepsis.
00:05:58
Speaker
What were the initial studies that maybe opened that can and really made people start thinking of vitamin C in a more serious way?
Merrick et al. Study and the HAT Protocol
00:06:06
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Yeah, absolutely.
00:06:07
Speaker
There's certainly been a couple relatively small trials and certainly a few observational studies that have been looking at vitamin C among sepsis patients.
00:06:15
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I think it's important to make a pretty significant distinction in that one of the protocols that often people think of, sort of the HAT protocol, which is hydrocortisone, ascorbic acid, or vitamin C and thiamine is what we sort of term the merit protocol is different than vitamin C alone.
00:06:31
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So just kind of important to make those two distinctions because mechanistically you could argue that there's a difference between the two different protocols, but nonetheless,
00:06:41
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The pretty major study that most people think about that really started to serve people's interest was the article that was published by Merrick et al.
00:06:50
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in CHEST.
00:06:51
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If you read the commentary really associated with this particular trial, it's really interesting to hear what Dr. Merrick says.
00:06:58
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Talks about 94 patients who had profound sepsis and profound septic shock.
00:07:02
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One patient in particular that he kind of thinks about, which was the impetus for the trial.
00:07:07
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pulled everything out of his pocket that he possibly could, which was the impetus for giving the HAT therapy.
00:07:13
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Nonetheless, this spurred the 94-patient trial that received the vitamin C, the thiamine, and the hydrocortisone.
00:07:20
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It was a before and after type of study design.
00:07:22
Speaker
It was single-center and certainly wasn't blind and so therefore has a few limitations, but this did show a pretty significant mortality reduction, which was the thought behind why we should be looking at vitamin C as a potential therapy in substance patients.
00:07:36
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This therefore stirred some more sort of randomized trial, a phase one trial that was done by Fowler and colleagues looking at the safety of giving patients ascorbic acid.
00:07:47
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And this was a three-armed randomized trial that was looking at high and low dose ascorbic acid and then versus placebo.
00:07:54
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And again, found some significant reductions in inflammatory biomarkers, including CRP and proclothetonin, and no significant increase in thrombomodulin, which is a biomarker that is seen and is thought to be associated with vascular injuries.
00:08:07
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The thought was that based on the findings that Dr. Merrick saw in his paper associated with his phase one trial that shows some improvement in inflammation, that that's sort of the basis for why Salern colleagues wanted to run a larger trial with sepsis and ARDS patients, which was citrus ALI.
00:08:24
Speaker
And it's very, very interesting also that there's been other small before and after studies that have been basically negative that did not reproduce the findings that Dr. Merrick did, which I think is a,
00:08:34
Speaker
not infrequent problem in medicine in general, but also in science, the inability to reproduce results of small trials.
00:08:41
Speaker
But one of the things that I wanted to get your thoughts on, Emily, was, and we were talking about this before we started recording, when I was in training, we didn't have social media, things did not travel as quickly, but it does seem that this particular vitamin C treatment and the original before and after trial with Dr. Merrick
00:09:04
Speaker
did all of a sudden go viral and was on many blogs, people talking about it, even got its way all the way to the national press and stories that were maybe a little bit over the top talking about a cure for sepsis and really generated a lot of noise that maybe 10 years or 20 years ago was not even possible for any type of therapy.
00:09:28
Speaker
Any comments from your perspective on that?
00:09:31
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Yeah.
00:09:32
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Absolutely.
00:09:32
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And to be honest with you, I think it all goes back to sort of the first thing that we talked about is sort of the how prevalent sepsis is and how deadly it is.
00:09:41
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So I think all of us, whether we be clinicians at the bedside or investigators or even sort of the lay folk hope that we can find a cure for this terrible illness.
00:09:51
Speaker
So I think at the base of everybody's heart, no matter it be Dr. Merrick, ourselves, anybody who's doing research, especially in sepsis, we're all hopeful that we are in fact going to find a cure for sepsis.
00:10:00
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So
00:10:01
Speaker
I think all of us thought back to our grandmothers who drank, in my case, mimosas whenever she was sick or lemonade or orange juice or whatever and thought, you know, we may have anecdotally felt that vitamin C was helpful in the case of our infection.
00:10:14
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So we all hoped that potentially it was the cure for sepsis.
00:10:18
Speaker
And I think that's where a lot of the social media interest came from, a lot of sort of the lay press interest came from is could this easy thing that we've been using for years potentially be the cure for sepsis?
00:10:28
Speaker
Though there could potentially be arguably an investigator bias and things of that sort, I think it was all based on the fact that we really want something to be effective.
00:10:38
Speaker
So it's been really interesting to read, especially in light of the editorial that I wrote about the trial, which we'll get into in a little bit.
00:10:45
Speaker
It's been really interesting to read people's thoughts about not only about the Citrus ALI trial, about my editorial and sort of about science around sepsis in general.
00:10:55
Speaker
And it's certainly very interesting to see what social media has done to us as investigators and research in general.
00:11:04
Speaker
Absolutely.
00:11:04
Speaker
And I think that what I always say is that it's fascinating to me that no matter what we talk about, what we're talking about, vitamin C and sepsis, or we're talking about ECMO and ARDS trials,
00:11:18
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regardless of the result, don't change the minds of those who are on one side or the other of the wall.
00:11:23
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And as physicians, I think that what we need to do is really get rid of that confirmation biases that we have and try to understand what really is the signal and what is out there.
00:11:35
Speaker
And I think that we all do this, but sometimes we apply a different ruler to the things that are aligned with what we believe in, right?
00:11:43
Speaker
That we don't believe.
00:11:44
Speaker
I think that the ruler should be the same for everything, which I think is
00:11:48
Speaker
a great segue into the citrus ALI study, which is what I wanted to talk about and being the first larger randomized study looking at this and in detail, maybe you could tell us what they did and what the study is about and we could start there.
Results of the Citrus ALI Trial
00:12:05
Speaker
Absolutely, absolutely.
00:12:07
Speaker
So as we talked a little bit about before, the pilot data that the folks used to design this trial was a phase one study that was looking at
00:12:17
Speaker
high versus low concentration or doses of ascorbic acid versus placebo.
00:12:24
Speaker
So what they were interested was, or what their hypothesis was, is that the administration of high dose vitamin C, which in this study was defined as 50 milligrams per kilogram every six hours for 96 hours, they hypothesized that this could potentially attenuate organ dysfunction, inflammation, and vascular injury.
00:12:40
Speaker
And this was all based on the findings of that phase one trial that showed
00:12:44
Speaker
decreases in CRP and procalcitonin and no significant increase in thrombomodulin among patients who had received vitamin C. So what they did is they enrolled 167 ICU patients who were receiving mechanical ventilation and developed ARDS within 24 hours of ICU admission.
00:13:00
Speaker
And this was based on the Berlin criteria that you and I used for the definition of ARDS in our clinical practice.
00:13:06
Speaker
Primary endpoints in this particular study
00:13:09
Speaker
Number one, they were looking at the change from baseline to 96 hours in a modified SOFA score.
00:13:15
Speaker
The modified SOFA score simply meant that not all patients had a bilirubin that was measured.
00:13:20
Speaker
So that was the only significant difference between the typical SOFA score that you and I might calculate.
00:13:26
Speaker
They also looked at a change from baseline of CRP, which was thought to be a marker of inflammation, and thrombomodulin, which represented a marker of vascular injury from baseline to 168 hours.
00:13:38
Speaker
They had quite a few secondary outcomes, 43 in fact.
00:13:41
Speaker
These included measures of inflammation and organ recovery, included vitamin C levels, as well as a whole bunch of other interesting secondary outcomes.
00:13:52
Speaker
A few of the results, thinking at baseline, patients were very well balanced.
00:13:56
Speaker
The most common sources of infection included pneumonia and intra-abdominal sepsis, so very generalizable to the population that you and I typically see in the intensive care units.
00:14:05
Speaker
Most of the patients that they enrolled were in shock at baseline.
00:14:10
Speaker
Upon enrollment, there was a significant vitamin C deficiency in both groups.
00:14:15
Speaker
Both groups' median levels are 22 micromoles or below.
00:14:18
Speaker
The administration of the vitamin C did seem to be effective.
00:14:26
Speaker
Patients who received the treatment did have significantly higher levels of vitamin C during the infusion and thereafter compared to those patients who received placebo.
00:14:35
Speaker
The intervention, as I mentioned, was the vitamin C 50 milligrams per kilogram Q6 hours for 96 hours.
00:14:41
Speaker
In terms of the primary outcomes, there were no significant differences between treatment groups.
00:14:47
Speaker
In terms of the modified SOFA score, it did decrease overall, but it was not significantly different between two groups, and the p-value between those two groups was 0.86.
00:14:57
Speaker
At 186 hours, the plasma levels of CRP and thrombomodulin were not significantly different between groups as well.
00:15:04
Speaker
If you think about it in the purest of sense, because the primary outcomes were not significant between the treatment and the placebo group, you could say that in the purest of sense, this was a negative trial.
00:15:16
Speaker
If we look at the secondary outcomes, however, when we look at the 28-day all-cause mortality rates, among those patients who received phallatom and C, it was 29.8%, and among the placebo group is 46.3%.
00:15:30
Speaker
This is a hazard ratio of 0.55 in favor of the treatment group with a p-value of 0.01.
00:15:37
Speaker
I will mention, as I mentioned in the editorial, however, this is without adjusting for multiple comparisons.
00:15:44
Speaker
Some other secondary outcomes that were relatively interesting, the patients in the vitamin C group did experience fewer ICU-free days and fewer hospital-free days.
00:15:53
Speaker
It's really important to mention and note, however, that this is largely driven by differences in mortality.
00:15:59
Speaker
So if you think about it, patients in the control group with zero hospital days and zero ICU-free days most likely represent those patients who died.
00:16:07
Speaker
So that difference in that secondary outcome could simply be secondary to the mortality difference.
00:16:13
Speaker
Which is interesting, right?
00:16:14
Speaker
It just can be linked to that mortality.
00:16:16
Speaker
But what happened?
00:16:18
Speaker
Were there any other of the secondary outcomes that went in the direction of mortality that would help, I mean, understand that?
00:16:25
Speaker
Yeah, the one thing that I think is relatively interesting to think about too is that though there was a significant mortality difference that you and I are very sort of interested and tantalized by, it's important to note that no other measures in the secondary outcomes were different.
00:16:39
Speaker
So no differences in the vasopressor amount that patients received, no difference really in measures of shock either.
00:16:46
Speaker
So those are a couple of other things that I think are really important to highlight.
00:16:52
Speaker
And I think that it's very interesting because I would like to, we'll have to see how this plays out, but when you read that, what they tried to do, and for me, the conclusion is that among the patients with sepsis and ARDS, high-dose vitamin C infusion compared with placebo did not significantly reduce organ failure scores at 96 hours or improve biomarkers at levels at 168 hours, period, full stop.
00:17:18
Speaker
And that's really what the trial
Scientific Rigor and Findings of the Trial
00:17:20
Speaker
showed.
00:17:20
Speaker
And I think historically, we've always argued that secondary outcomes might be hypothesis generating, but it's hard to say that you can make any clinical changes in your practice or big decisions based on those secondary outcomes because, I mean, they weren't designed to really, I mean, they weren't powered and you might have a statistical significance that could still be due to chance or for other reasons that we're not measuring.
00:17:47
Speaker
Yeah, absolutely.
00:17:47
Speaker
Totally agree with you.
00:17:49
Speaker
Yep.
00:17:50
Speaker
So what do you think from your perspective, and you do talk about it in the editorial, are some of the strengths and some of the weaknesses of this trial?
00:17:57
Speaker
Clearly, I mean, it was a well-designed trial.
00:17:59
Speaker
I mean, it was done, I mean, with a lot of scientific rigor.
00:18:01
Speaker
But maybe you could just walk us down, I mean, what you think would be on the strength side and what would be some of the weaknesses.
00:18:08
Speaker
Yeah, absolutely.
00:18:09
Speaker
So as you were getting at, definitely a very scientifically rigorous trial.
00:18:13
Speaker
It was a multi-center trial.
00:18:15
Speaker
Excellent protocol adherence.
00:18:17
Speaker
It was very generalizable.
00:18:18
Speaker
Many of the patients, if you kind of look at their table one, are patients that you and I see every day in the intensive care unit.
00:18:23
Speaker
So, many of the outcomes and things that they saw within their population, I think, can be generalized to a generalized population of patients with sepsis and ARDS.
00:18:32
Speaker
Furthermore, there was significant data collected.
00:18:34
Speaker
If you looked at many of the things that they looked at in terms of their secondary outcomes, tons of data collection performed, which
00:18:42
Speaker
I'm certainly not a co-PI or a PI on a randomized control trial, but the rigor through which they went to collect all this data is tremendously impressive and certainly will serve as a hypothesis for future trials, which will be really interesting and exciting to see.
00:18:57
Speaker
A couple of the weaknesses, however, could be related to the trial design itself.
00:19:02
Speaker
As I mentioned, this was based on pilot data that Fowler et al.
00:19:06
Speaker
looked at patients who had sepsis and were receiving vitamin C infusions.
00:19:10
Speaker
Given that the fact that the cohort in this case also had ARDS, one could argue that the timing of the administration of the vitamin C could have been delayed.
00:19:19
Speaker
If you think about the pathophysiology of vitamin C administration and sort of the way that we believe that it helps to curb the inflammatory process, you could argue that perhaps it was given a little bit too late, thinking about sort of the golden hour of resuscitation.
00:19:33
Speaker
Some of these folks were up to 48 hours after hospital admission, therefore,
00:19:38
Speaker
it's possible that they simply received the vitamin C too late.
00:19:42
Speaker
Secondarily, it's possible that they chose the wrong inflammatory biomarkers.
00:19:47
Speaker
As I mentioned before, this was delayed compared to the pilot data that they had.
00:19:51
Speaker
So perhaps the CRP and the thrombomodulin effects that they saw within their pilot data were different simply because this vitamin C administration was a little bit later.
00:20:00
Speaker
Third, was the dose correct?
00:20:03
Speaker
Certainly it appears that it was effective
00:20:06
Speaker
in that patients who receive vitamin C had supernormal plasma concentrations compared to the placebo group, but still one could argue that perhaps it just wasn't the right dose.
00:20:15
Speaker
So I think those are a couple of the weaknesses that I immediately thought about when I was reading the paper.
00:20:22
Speaker
Interesting, and I think that it's one of the limitations that we have with clinical trials.
00:20:27
Speaker
I mean, no matter how rigorous you are, there are always things that in retrospect, obviously, or that because of how we're trying to enroll these patients might become
00:20:36
Speaker
kind of limitations later
Future of Vitamin C in Sepsis Treatment
00:20:38
Speaker
on.
00:20:38
Speaker
Do you know, Emily, my understanding is that there's several other trials that are ongoing?
00:20:43
Speaker
Yeah, there are.
00:20:44
Speaker
There are.
00:20:45
Speaker
I actually just took a look at clinicaltrials.gov before we started just because I was curious.
00:20:50
Speaker
And there are currently two trials that are enrolling as we speak.
00:20:53
Speaker
I know the second of which is wrapping up.
00:20:56
Speaker
University of Pittsburgh is one of the sites for that.
00:20:59
Speaker
So
00:21:00
Speaker
I think though we all understand that we are taking care of very critically ill patients and we don't have a whole lot of time to wait in terms of if we find a therapy that potentially could be effective, is it worth it to our patients to try anything that will work just understanding that they're so sick and we simply don't have time to wait?
00:21:22
Speaker
But we are exceptionally lucky in the case of vitamin C in that we have two really large randomized control trials that are wrapping up
00:21:30
Speaker
recruitment right now.
00:21:31
Speaker
So I think we're going to have a lot more information and a lot more data very soon.
00:21:36
Speaker
So I think we're very lucky in this case that we might have an answer sooner rather than later when it comes to vitamin C. So if you had to take a stand right now in terms of how you as a clinician looks at this, where would you say we stand right now in terms of data with vitamin C?
00:21:55
Speaker
Absolutely.
00:21:57
Speaker
I think if you would ask me if I'm working at a bedside, if I had a patient who was in profound septic shock on multiple vasopressors, was on glucocorticoids and was simply not doing well, would I try vitamin C in that patient?
00:22:13
Speaker
If I'm honest with you, as a bedside clinician, I probably would.
00:22:17
Speaker
As a scientist, though I completely understand that it's probably not appropriate to differentiate myself as a clinician versus a scientist, being a purist at heart,
00:22:27
Speaker
I think that we need more data.
00:22:29
Speaker
So I simply believe that a tantalizing secondary outcome with a potential p-value that is suggestive of a signal, I think it's just simply not enough for us to make sort of wide sweeping changes to our standard of care.
00:22:46
Speaker
So I'm really excited and really interested to see what the new vitamin C trials have to say.
00:22:51
Speaker
But at this point, I think it's just simply too early to say that vitamin C is sort of the end-all be-all cure for sepsis.
00:22:57
Speaker
And I think that's an important distinction also in terms of I would go further, just not saying bedside clinician versus scientist.
00:23:05
Speaker
I would also talk about policy and being responsible for a lot of patients.
00:23:10
Speaker
I think that
00:23:11
Speaker
there are things that might be appropriate at an individual case by case to be evaluated at the bedside in which you would explain to the family and it might make sense in some situations, which is like you said, very different from making these blanket statements of everybody in the hospital should be getting vitamin C, everybody with sepsis should be getting vitamin C, which I think you could argue, well, the cost is low and the risk is not high, but everything we give has risks.
00:23:40
Speaker
I mean, there is no such thing as no risk.
00:23:42
Speaker
And I think that also, the other thing that I worry about, Emily, is that if we start doing things based on very little evidence and they become very prevalent, then you almost lose the equipoise needed to do the clinical trials.
00:23:56
Speaker
And it becomes very difficult to find more information or understand where things fall.
00:24:05
Speaker
So I presume that we would be on the same page.
00:24:08
Speaker
We would say that,
00:24:09
Speaker
for an individual patient, an individual clinician on a case-to-case basis, maybe.
00:24:16
Speaker
But definitely, I mean, it's something that everybody should be doing.
00:24:18
Speaker
Probably we have more information coming and we'll probably get more data.
00:24:24
Speaker
Well said.
00:24:24
Speaker
Couldn't have said it any better myself.
00:24:27
Speaker
Well, and I think that it's very interesting because I do agree.
00:24:30
Speaker
I mean, I think that we all are excited when there's something new we can provide our patients, especially patients with whom it's been very frustrating
00:24:38
Speaker
to really find, I mean, novel therapies.
00:24:42
Speaker
But I do think that the trial is a very, I think, a well-received piece of scientific information.
00:24:51
Speaker
I encourage everybody to read them alongside your editorial.
00:24:55
Speaker
All these trials that we mentioned will be linked in the show notes.
00:24:59
Speaker
So I hope that our readers take a look and hopefully we'll have new trials soon and we'll be able to bring you back to follow up on this discussion.
00:25:08
Speaker
But before I let you go, Emily, we'd like to close the podcast with some questions that tap into the wisdom of our guest and are unrelated to vitamin C or to
Recommended Reads and Personal Reflections
00:25:18
Speaker
sepsis.
00:25:18
Speaker
Would that be okay?
00:25:20
Speaker
I know nothing more than that, though, sir.
00:25:23
Speaker
Well, we'll try.
00:25:27
Speaker
So the first question is, what book of books have influenced you the most or what book have you gifted most often to others that's not related to vitamin C or sepsis?
00:25:38
Speaker
Absolutely.
00:25:38
Speaker
Well, I can tell you for one, I don't gift.
00:25:41
Speaker
You can ask my family this.
00:25:42
Speaker
I don't give gifts.
00:25:43
Speaker
But anyways, if I had to think about what book or books that's been most influential to me, I think I'm currently reading, I'm slow.
00:25:51
Speaker
I'm reading The Coming by Michelle Obama.
00:25:53
Speaker
I think that's been most influential to me.
00:25:55
Speaker
Kind of really speaks to my soul.
00:25:57
Speaker
I'm an extraordinarily blessed human being who grew up sort of among the lower middle class.
00:26:03
Speaker
Nobody in my family did medicine.
00:26:06
Speaker
Nobody really in my high school went to college for the most part.
00:26:09
Speaker
And I've been exceptionally blessed to have the opportunity to work in this field and work among patients and sort of work for patients.
00:26:17
Speaker
And every day for me is an honor and privilege.
00:26:19
Speaker
So I think I really think of Michelle Obama a lot and sort of where she came from.
00:26:23
Speaker
And this book has really been touching and influential to me.
00:26:28
Speaker
Okay.
00:26:28
Speaker
Well, definitely.
00:26:28
Speaker
I have not read it, but I have gifted that book to my wife.
00:26:31
Speaker
So she enjoyed it significantly.
00:26:34
Speaker
Nice.
00:26:35
Speaker
but I will link it and maybe I'll have to read it now.
00:26:38
Speaker
Yeah, you should.
00:26:41
Speaker
The second question, it relates to something that you believe to be true in medicine or in life that many other people don't seem to believe.
00:26:48
Speaker
Absolutely.
00:26:50
Speaker
I'm sure I'll be pegged as hashtag naive, but I think what I believe to be true is that if you believe it, you can do it.
00:26:58
Speaker
So as I said, I always wanted to be a doc and I believe that I could and people told me that I could and I did it.
00:27:03
Speaker
So I think
00:27:04
Speaker
Especially for younger docs and trainees who might be listening.
00:27:08
Speaker
Some days are rough, but if you believe that you can do it, you can get to be whatever you want to be.
00:27:14
Speaker
And I think that one of the things that I've always thought about when there were things that I was thinking in the future is you find people who are doing it who at one point were exactly where you were.
00:27:25
Speaker
Right.
00:27:25
Speaker
So what is different between me and that person?
00:27:28
Speaker
And I do agree.
00:27:29
Speaker
I mean, the grit to just move forward and move towards the things that you want is something that we should all believe in.
00:27:35
Speaker
And that's something that does not change throughout life.
00:27:37
Speaker
No matter where you are in your life, there's always opportunity to become something different.
00:27:41
Speaker
And I think that's important.
00:27:43
Speaker
So that's a great one.
The Essence of Compassion in Critical Care
00:27:45
Speaker
And the last one just relates to what would you want every intensivist who's listening to us to know?
00:27:50
Speaker
It could be a quote or a fact or just a thought.
00:27:54
Speaker
Absolutely.
00:27:55
Speaker
I had this mentor back in medical school and went to Jefferson.
00:27:57
Speaker
His name was Dr. Joe Maiden, and he always talked about how every day was an honor and privilege.
00:28:02
Speaker
The one thing that I've always tried to keep in mind when I'm rounding in the ICU is that for us, a day at work is but a day at work, but for our patients, it represents the first day for the rest of their lives, whether it be due to profound critical illness or post-ICU type of critical illness or post-sepsis recovery.
00:28:19
Speaker
Just try to keep in mind that, you know,
00:28:22
Speaker
we're caring for people and they're going through a rough time.
00:28:27
Speaker
And I think that's very important.
00:28:28
Speaker
And I think about this a lot also, Emily, and I have come to appreciate with years of practice now, what an immense privilege and honor it is to be at the bedside of a human being who dies.
00:28:41
Speaker
And I think that when you talk with people outside of medicine and even within medicine, outside of critical care, that is not something that everybody experiences.
00:28:50
Speaker
And I think that what
00:28:52
Speaker
what we do at those moments for the family and what we do at those moments for others, like you said, might go away at the end of the shift for us because we do it all the time, but it's something that is going to be in their memory for the rest of their life.
00:29:07
Speaker
And I think how we behave at those points has tremendous power in other people, and we should really honor that privilege and make sure that we're at our best in making a difference.
00:29:19
Speaker
Absolutely.
00:29:20
Speaker
So true.
00:29:21
Speaker
Emily, it was a real pleasure to talk with you about vitamin C. I definitely will try to get you back when we have more of these studies published and we'll hopefully have more answers.
00:29:33
Speaker
But again, thank you so much for your time.
00:29:37
Speaker
Absolutely.
00:29:37
Speaker
It was my pleasure.
00:29:40
Speaker
Thank you for listening to Critical Matters, a sound critical care podcast.
00:29:45
Speaker
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00:29:50
Speaker
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00:29:56
Speaker
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