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PCT Reassessed
10 Plays3 months ago
In this episode, Dr. Zanotti discusses the role of Procalcitonin in the ICU.
He is joined by Dr. Simran Gupta, an infectious disease specialist at Brigham & Women's Hospital in Boston. Dr. Gupta has additional training in Clinical Research, Transplant, and Infectious Disease. She recently published an article on reassessing the role of Procalcitonin in critically ill patients with sepsis.
Additional resources:
Reassessing Procalcitonin-Guided Antibiotic Therapy in Critically Ill Patients with Sepsis: Lessons from the ADAPT-Sepsis Trial. S. Gupta, et al. Clinical Infectious Disease 2025: https://pubmed.ncbi.nlm.nih.gov/40579227/
Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis: The ADAPT-Sepsis Randomized Clinical Trial. JAMA 2025: https://pubmed.ncbi.nlm.nih.gov/39652885/
Procalcitonin-guided antibiotic therapy may shorten the length of treatment and may improve survival- a systematic review and meta-analysis. M Papp, et al. Crit Care 2023: https://pubmed.ncbi.nlm.nih.gov/37833778/
Books and entertainment mentioned in this episode:
Shantaram: A Novel. By Gregory David Roberts: https://bit.ly/4ovVHKX
SHANTARAM – Apple TV series: https://tv.apple.com/us/show/shantaram/umc.cmc.atxsrive40xli3zh3uxjimut
Recommended
Transcript
Introduction to Critical Matters Podcast
00:00:06
Speaker
Welcome to Critical Matters, a sound podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:14
Speaker
Sound provides comprehensive critical care programs to hospitals across the country.
00:00:19
Speaker
To learn more about our programs and career opportunities, visit www.soundphysicians.com.
00:00:26
Speaker
And now your host, Dr. Sergio Zanotti.
Understanding Procalcitonin's Role
00:00:32
Speaker
Procalcitonin, a peptide precursor of the hormone calcitonin, is often elevated in response to bacterial infections.
00:00:39
Speaker
This characteristic, as an acute phase reactant, has attracted interest in its clinical use at the bedside to enhance decision-making regarding antimicrobial therapy.
00:00:49
Speaker
In today's podcast, we will discuss the role of procalcitonin in the ICU.
00:00:53
Speaker
Our guest is Dr. Simran Gupta, an infectious disease specialist at Brigham's and Women's Hospital in Boston.
00:00:59
Speaker
Dr. Gupta has additional training in clinical research, transplant, and oncology infectious disease.
00:01:04
Speaker
She recently published an article on reassessing the role of procalcitonin in critically ill patients with sepsis, and we will base our discussion on this article and some recent clinical trials.
00:01:16
Speaker
Simran, welcome to Critical Matters.
00:01:19
Speaker
Thank you for having me.
00:01:20
Speaker
I'm excited to be here.
00:01:22
Speaker
So we're gonna talk about procalcitonin in the ICU.
00:01:25
Speaker
And my first question is why should intensivists care about this topic?
00:01:31
Speaker
Well, it's a hot topic.
00:01:32
Speaker
We don't have a lot of markers to guide our treatment of patients with infection, namely to know when to stop antibiotics in patients in whom infectious source is not necessarily found or who look like they have an infection, but we don't really know what's going on.
00:01:49
Speaker
And with antimicrobial resistance, emergence of multidrug-resistant organisms,
00:01:55
Speaker
antimicrobial stewardship is really, really important.
00:01:58
Speaker
And so, you know, potentially procalcitonin can help us guide that.
00:02:03
Speaker
Excellent.
00:02:04
Speaker
I would like to start with some procalcitonin basics and just give us a little bit of
Procalcitonin and Bacterial Infections
00:02:10
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the description.
00:02:10
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It's kinetics, what can cause false positives or false negatives.
00:02:14
Speaker
So we just can have a level setting for all our listeners.
00:02:19
Speaker
Absolutely.
00:02:20
Speaker
So as you said before, it's a calcitonin precursor hormone.
00:02:25
Speaker
It's produced by the C cells of the thyroid, and it's generally upregulated in response to cytokines that are triggered by systemic bacterial infections.
00:02:35
Speaker
And it's thought to be downregulated by intravirone gamma stimulated by viral infections.
00:02:41
Speaker
But that being said, there's been a ton of research that has shown that SARS-CoV-2 infection can highlight PCT levels.
00:02:49
Speaker
So that's a situation in which you just want to be sure that you're really looking at a bacterial infection and not a SARS-CoV-2 infection.
00:02:58
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It's pretty sensitive and specific for bacterial sepsis, probably around 77% to 79% sensitive and about the same for specificity for sepsis.
00:03:09
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And it really is better than some of those other biomarkers that we've studied like CRP,
00:03:15
Speaker
white blood cell, ESR, et cetera.
00:03:19
Speaker
The false negative and false positive rates are a bit less.
00:03:23
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And the kinetics make it really favorable to study.
00:03:26
Speaker
It rises within two to four hours of a bacterial infection onset, peaks within 24 hours, and then it really declines pretty rapidly as the infection resolves.
00:03:36
Speaker
So it's pretty potentially useful to inform antibiotic discontinuation.
00:03:41
Speaker
So as you explain, my understanding is that compared to other biomarkers, like you mentioned CRP and even white count, the kinetics are favorable and also it seems to have better specificity and sensitivity.
00:03:55
Speaker
Is that correct?
00:03:56
Speaker
Yeah, that's correct.
00:03:57
Speaker
It really rises pretty quickly after bacterial infection onset.
00:04:03
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It peaks quickly and then it comes down as the bacterial infection resolves.
00:04:06
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So it's very favorable for study.
00:04:10
Speaker
What are some potential uses at the bedside for procalcitonin in the ICU?
00:04:14
Speaker
If you were to think as an obviously ID specialist, but what are the buckets where you would consider or where PCT has been studied as potentially useful?
00:04:26
Speaker
Yeah, well, there have been a lot of randomized clinical trials.
00:04:30
Speaker
Some of the trials have looked at whether it's helpful in initiation of antibiotics, but the majority of trials have looked at whether it is useful in discontinuation of antibiotics.
00:04:43
Speaker
And as an ID doctor, that's really where I see the most use for it right now.
00:04:48
Speaker
In patients who come in, it doesn't really tell me who looks sick, who looks septic.
00:04:53
Speaker
It doesn't tell me whether or not I should start antibiotics.
00:04:55
Speaker
That's really a clinical judgment for me based on, you know, other lab tests as well and radiographic findings.
00:05:02
Speaker
But for example, in a patient in the ICU who's had sort of these
00:05:06
Speaker
non-specific favors, fevers, and may look inflammatory, may be infected, but I just don't really know.
00:05:13
Speaker
That's when I really use the propalcitonin to decide, you know, can I stop antibiotics or do you think I need to continue them?
Guiding Antibiotic Use with Procalcitonin
00:05:21
Speaker
Would it be fair to say that the overuse of antibiotics, probably at least in the ICU arena, is not so much a function of starting empiric antibiotics in critically ill patients, but not stopping them when we have good evidence that we're probably not treating an infection or the infection has improved significantly?
00:05:44
Speaker
You know, interestingly, I think it's a function of both.
00:05:47
Speaker
We definitely tend to allow antibiotics to be on longer than are probably necessary, just because that white blood cell count might still be a little bit elevated or, you know, maybe they look a little bit off their baseline when we go to see them in person.
00:06:02
Speaker
But definitely, you know, we've done a lot of work to see these broad spectrum antibiotics starts in the ED, for example.
00:06:09
Speaker
Patients get vancomycin and cephepine, you know, almost for just for a white blood cell count of 11 with no other symptoms when they walk in the door.
00:06:18
Speaker
And there's a lot of syndromes that mimic sepsis, that mimic infection.
00:06:21
Speaker
And so I actually think it's a function of both.
00:06:24
Speaker
starting antibiotics when maybe they aren't needed and also starting broad spectrum antibiotics and then sort of our reluctancy to discontinue antibiotics in patients who are otherwise stable, but maybe we have this inkling about
00:06:41
Speaker
Perfect.
00:06:42
Speaker
And I was really looking at this through the prism of really critically ill patients.
00:06:48
Speaker
So from my perspective as an intensivist, if I have somebody who is on a vasopressor, hemodynamic unstable, somebody who has organ failure or is on a mechanical ventilation coming to my ICU,
00:07:00
Speaker
I feel much more comfortable starting periodic antibiotics and then figuring out what to do as opposed to maybe some of the patients that you mentioned are patients who are not as sick in which we have a little bit more time to figure things out.
00:07:14
Speaker
But I hear you both are important.
00:07:16
Speaker
And obviously, the interest on procalcitonin has really centered around how can we tailor our antibiotics for shorter therapy durations, but also for people who really need them as opposed to just treating everybody with broad-spectrum antibiotics and increasing resistance.
00:07:35
Speaker
Yeah, absolutely agree.
00:07:37
Speaker
And definitely some of the studies that have been done in randomized control trials have looked at whether it's helpful with the initiation and really it's helpful with discontinuation of antibiotics.
00:07:47
Speaker
And I think that's where, you know, most of the research has gone into and where it can be helpful really clinically in decreasing our antibiotic use and sort of our antibiotic stewardship practices.
00:08:00
Speaker
I would like to talk about some of the evidence-based or some of the studies in more detail that help us with PCT-guided therapy in critically ill patients.
00:08:11
Speaker
We're going to probably focus on the discontinuation, as you mentioned.
00:08:15
Speaker
But before we go into that area, is there any evidence or any important studies that you want to mention regarding initiation of empiric antibiotics?
00:08:25
Speaker
You did mention something in the ED, but specifically for critically ill patients, anything you can add there?
00:08:32
Speaker
You know, there's only been one randomized control trial that I can think of that looked at using procalcitonin for initiation of antibiotics in these critically ill patients.
00:08:44
Speaker
There have been a couple randomized control trials in the ED, but they've been focusing just on respiratory tract infections.
00:08:51
Speaker
And so the one that I can think of was from, I think, 2010, and it looked at both patients
00:08:58
Speaker
you know, can you withhold initial antibiotic therapy if your procalcitonin is low, and then also discontinuation of antibiotic therapy when procalcitonin declines.
00:09:09
Speaker
And really, it was only found that that's sort of where the future studies picked up off in terms of discontinuation of antibiotics.
00:09:18
Speaker
But really, the withholding initial antibiotic therapy was hard to study.
00:09:22
Speaker
I think a lot of clinicians were pretty reluctant to do that.
00:09:25
Speaker
And so there was not significant
00:09:28
Speaker
protocol adherence.
00:09:29
Speaker
And then that study itself didn't find any different in mortality rate, though there was a difference in duration of antibiotics in that study.
00:09:41
Speaker
You also mentioned that even though we think of procalcitonin as linked to bacterial infections, with SARS-CoV-2, it can go up.
00:09:52
Speaker
So I remember during COVID, one of our big concerns was, do we add antibiotics?
00:09:58
Speaker
And some people are saying, well, the procalcitonin is elevated.
00:10:01
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You should.
00:10:01
Speaker
But then again, I mean, that just might be because of the COVID itself, right?
00:10:07
Speaker
Yeah, absolutely.
00:10:08
Speaker
That can definitely be from the COVID itself.
00:10:10
Speaker
And so I think that's a situation in where, you know, the rest of how the patient looks, their oxygen requirement may be, or their white blood cell count, all of those in conjunction with their radiographic findings and their other clinical symptoms and vital signs are really important to decide whether or not you think there is also superimposed bacterial infection.
Clinical Trials on Procalcitonin
00:10:29
Speaker
Because, you know, because as we know, some patients with COVID do have that.
00:10:32
Speaker
But I think the majority of patients with COVID did not have superimposed bacterial infection as well.
00:10:39
Speaker
When we talk about PCT-guided antibiotic therapy discontinuation, there's been a larger number of clinical trials, and the article, the viewpoint you wrote in clinical infectious disease obviously reassesses this body of literature, but also focuses on a more recent trial that we'll get into detail.
00:10:59
Speaker
But could you tell us about the early studies in critically ill patients?
00:11:03
Speaker
I think it was Prorata, SOPS, ProGuard, Progress, etc.?
00:11:08
Speaker
Yes, definitely.
00:11:09
Speaker
So Prorata was the one that looked at both initially withholding antibiotics as well as declining.
00:11:15
Speaker
And from that is where some of the other RCTs were born.
00:11:20
Speaker
And they all really focused on withholding or discontinuing antibiotics, not withholding antibiotics.
00:11:27
Speaker
Um, when propalcitonin falls from a certain level to their, to their baseline.
00:11:32
Speaker
So there was pro guard, uh, that happened around 2014, I believe.
00:11:36
Speaker
And it was done in Australia.
00:11:39
Speaker
These were also critically ill patients and they had a pretty, um,
00:11:43
Speaker
a pretty rigid threshold for discontinuing antibiotics.
00:11:47
Speaker
So they said if the procalcitonin was less than 0.1 or declined 90% from the baseline on daily procalcitonin measurements, then you could stop the antibiotics.
00:11:59
Speaker
And that study actually did not find any difference in the median duration of antibiotics.
00:12:06
Speaker
You know, it was nine versus 11 days, but ultimately it wasn't statistically significant and also no difference in 90 day mortality.
00:12:14
Speaker
It's interesting, maybe one of the reasons that they didn't find any significant difference was because it was a very conservative procalcitonin cutoff, really rigid.
00:12:23
Speaker
And so there have been a couple of other trials since then as well.
00:12:26
Speaker
There was SAPS, as you mentioned, in 2016 that occurred in the Netherlands, again, in critically ill ICU patients.
00:12:36
Speaker
a little bit less conservative of a procalcitonin threshold.
00:12:40
Speaker
So they did the same threshold as was done in prorata.
00:12:44
Speaker
So you could discontinue antibiotics
00:12:46
Speaker
If your procalcitonin decreased to over 80% of the peak or if it was less than 0.5, so significantly higher than the 0.1 for ProGuard.
00:12:57
Speaker
And that one did show a median duration difference of antibiotics in five days in the procalcitonin group versus seven days in the non-procalcitonin group.
00:13:08
Speaker
as well as a decreased 28-day mortality rate and a one-year mortality rate.
00:13:14
Speaker
So that was pretty exciting.
00:13:18
Speaker
But overall, the algorithm adherence was low, and it was an open-label study.
00:13:22
Speaker
And so that garnered some critiques about how that study was conducted.
00:13:30
Speaker
And then lastly, there was, as you mentioned before we talk about the most recent one, it was PROGRESS, which was in 2021.
00:13:37
Speaker
And this one wasn't conducted only in ICUs.
00:13:41
Speaker
It was conducted in ICUs and non-ICU settings, but it was all patients who met sepsis criteria, so sepsis-3 criteria.
00:13:48
Speaker
And again, they used sort of a very similar procalcitonin threshold to SAPS and PRORADA, and
00:13:57
Speaker
And they also found a median duration of antibiotics that was less than the procalcitonin group.
00:14:03
Speaker
So five days in the procalcitonin group and 10 days in the sort of non-procalcitonin control group.
00:14:13
Speaker
There was also fewer infections associated to adverse events like C. diff, multidrug-resistant organisms, as well as lower 28-day mortality.
00:14:24
Speaker
So I think those are the big four RCTs that have happened in sort of the last 15 to 20 years before, as you mentioned, that we're going to talk about next, the ADAPT sepsis trial.
00:14:36
Speaker
And in terms of challenges, you mentioned it with some of these studies, I guess, adherence to the protocol, procalcitonin cutoffs in terms of being too rigid.
00:14:46
Speaker
Was there anything else that you would consider a concern or that informs how people were thinking clinically at that point?
00:14:57
Speaker
Yeah, I think, you know, the other really big sort of point of discourse from all those randomized control trials, excuse me, were that they were all open evidence, or sorry, open label.
00:15:09
Speaker
And so the procalcitonin results were shared with all the physicians and
00:15:14
Speaker
Which patient was in the intervention arm, which patient was in the control arm.
00:15:18
Speaker
And so that really, obviously, as you know, creates a risk of bias.
00:15:21
Speaker
And so I think that was one of the biggest critiques of those trials.
00:15:24
Speaker
And then, of course, the low algorithm adherence as well was a critique of the trials.
00:15:30
Speaker
And I think finally, one of the things that came up was, for example, we said that in progress, the standard of care arm had sort of a 10 day median duration of antibiotics.
00:15:43
Speaker
And that's actually like kind of long if you think about it.
00:15:46
Speaker
You know, we've had a lot of research lately, for example, the balance trial that got published in the New England Journal of Medicine recently showing that seven days of antibiotic therapy is plenty for
00:15:58
Speaker
for gram-negative, strep, enterococcus, bacteremia infections in patients who are very ill.
00:16:04
Speaker
So 10 is quite long.
00:16:06
Speaker
And so that really makes you wonder, like, what was the nature of the antibiotic stewardship programs in these control arms?
00:16:13
Speaker
You know, like maybe the durations would have been even shorter in the control arms if there was just antibiotic stewardship.
00:16:20
Speaker
You don't even need the procalcitonin.
00:16:22
Speaker
So those are some of the points that have come up about these trials.
00:16:29
Speaker
And more recently, the ADAPT sepsis trial, obviously, was trying to further define the role of procalcitonin.
00:16:38
Speaker
Can we talk in more detail about that trial?
00:16:41
Speaker
Oh, yeah, absolutely.
00:16:42
Speaker
So ADAPT sepsis is the newest sort of kit on the block, and it's the largest sort of randomized control trial to study procalcitonin.
00:16:51
Speaker
And actually, interestingly, it studied both procalcitonin and CRP, even though we know we've talked about why procalcitonin is probably a better biomarker to study.
00:17:02
Speaker
The, you know, spoiler alert with the CRP is that it really didn't show any sort of help in terms of antibiotic stewardship.
00:17:09
Speaker
But they did a lot of really good things with the ADAPT sepsis trial.
00:17:14
Speaker
So they really saw that there was a lot of critiques about, you know, the open label nature of the study, of the prior studies, the algorithm adherence, et cetera.
00:17:26
Speaker
And so the investigators in ADAPT sepsis really addressed the blinding concerns.
00:17:31
Speaker
So they had a concealed intervention protocol.
00:17:34
Speaker
And then they also addressed the concerns about, you know, antibiotic stewardship and the control arms of the prior studies.
00:17:40
Speaker
And they made sure that their standard of care arm received, you know, regular antibiotic stewardship guidance, 72-hour stewardship reviews, et cetera.
00:17:52
Speaker
So it really tried to address some of those, those things that were thought to be faults of the prior studies.
00:17:57
Speaker
But in this particular one, ADAPT sepsis, it was done in the UK and I think 40, 41 ICUs.
00:18:05
Speaker
And they studied procalcitonin, CRP, and then standard of care, sort of a one-to-one-to-one try study design.
00:18:15
Speaker
They, they,
00:18:16
Speaker
Of course, you know, excluded patients similarly to the prior trials, like patients who were severely immunocompromised, patients who were at high risk of death, etc.,
00:18:28
Speaker
And then their protocol was pretty interesting.
00:18:31
Speaker
So what they did is instead of telling the physicians taking care of the patients what the actual procalcitonin level was, which is what they did in the prior studies, they would have an investigator review the procalcitonin results every day and then give a specific piece of advice to the clinical team.
00:18:50
Speaker
And so that piece of advice was either protocol strongly supports stopping antibiotics or
00:18:57
Speaker
And that was based on a procalcitonin level of less than 2.5.
00:19:00
Speaker
The second piece of advice they could give was protocol support stopping antibiotics.
00:19:07
Speaker
And that was either based on a procalcitonin between 0.25 and 0.5 or greater than 80% fall from baseline.
00:19:16
Speaker
And then the last piece of advice they could give was protocol support standard care where your procalcitonin didn't meet sort of any of the criteria we've talked about before.
00:19:27
Speaker
And that's how they conducted their study.
00:19:29
Speaker
And they found a significantly reduced duration of antibiotic therapy within 28 days of randomization in the procalcitonin group compared to the standard of care.
00:19:39
Speaker
So procalcitonin group, 9.8 days, standard of care, 10.7 days.
00:19:44
Speaker
And they also found a non-inferior 28-day mortality rate.
00:19:54
Speaker
And then with the CRP, as we talked about before, there really was no significant difference in median duration of antibiotics or mortality rate.
00:20:03
Speaker
Were there any particular aspects of ADAPT sepsis that you find insightful for applying this at the bedside or anything special about this study other than the results and that obviously the scale?
Guidelines and Evidence for PCT Use
00:20:20
Speaker
Well, I think it's probably just our best trial to date that the most well done probably to show that it's, you know, we can potentially use this biomarker to help us decrease antibiotics.
00:20:35
Speaker
You know, I thought it was great that both groups got sort of the same.
00:20:41
Speaker
strategies and teaching and review.
00:20:43
Speaker
And so really the outcome was very much so, um, very much so based on the procalcitonin guided therapy.
00:20:52
Speaker
So I thought that was interesting and I thought it was probably our best data, um, to date.
00:20:59
Speaker
Excellent.
00:21:00
Speaker
I'd like to talk about practical considerations.
00:21:02
Speaker
And the first topic I wanted to ask you, you mentioned a little bit earlier, is there's been a flurry of studies demonstrating that short durations of antibiotic therapy for a list of different infections has no impact on outcomes.
00:21:22
Speaker
So you can get...
00:21:24
Speaker
Basically, same mortality, same results with less antibiotics.
00:21:29
Speaker
Do you think that this makes procalcitonin less relevant in the ICU?
00:21:34
Speaker
Yeah, you know, that's a great question.
00:21:37
Speaker
And I do think that that is something that really needs to be thought of, you know, really strongly.
00:21:44
Speaker
So,
00:21:45
Speaker
you know, again, the patients, there was sort of a median duration of 10 days of antibiotics in these patients.
00:21:53
Speaker
And like we said, the recent balance trial demonstrates that seven days of antibiotic therapy is safe.
00:21:59
Speaker
So if we sort of already know that in our patients,
00:22:02
Speaker
What are we using the procalcitonin for and why are we still treating for a median duration of 10 days anyways?
00:22:09
Speaker
You know, we really should be focusing on antimicrobial stewardship in these patients and treating for what we think is the appropriate amount of time based on really strong research.
00:22:20
Speaker
It seems that we're anchored on longer durations in critically ill patients, and perhaps a better approach would be to anchor ourselves on much shorter durations and then try to figure out what procalcitonin, do we need to continue the antibiotic beyond that, right?
00:22:34
Speaker
It seems that for so many patients, five days might be all they need, right?
00:22:38
Speaker
Yeah.
00:22:39
Speaker
Yeah, I think there's plenty of research, you know, that shows that seven days is really sufficient and whether or not less than seven days is sufficient hasn't necessarily been studied in RCTs.
00:22:50
Speaker
I think, you know, any infectious disease doctor or even intensivist can maybe tell you their anecdotal experience.
00:22:57
Speaker
And mine is usually that I do seven days of therapy for this sort of unexplained sepsis picture.
00:23:04
Speaker
And so I think if we really focus our strategies on
00:23:08
Speaker
like antimicrobial stewardship in that sense.
00:23:11
Speaker
We probably don't even need procalcitonin in these situations.
00:23:15
Speaker
In terms of other challenges, I also recognize that often critical care clinicians are very reluctant to stop antibiotics in their patients.
00:23:29
Speaker
It's almost like they want to keep pushing.
00:23:32
Speaker
Any thoughts?
00:23:33
Speaker
I mean, there or maybe for that at least a biomarker can be helpful.
00:23:38
Speaker
But how do you deal with that when you're the one trying to convince people to stop antibiotics?
00:23:45
Speaker
Well, that's definitely a struggle that, you know, we face.
00:23:48
Speaker
And it's understandable, too.
00:23:50
Speaker
You know, it's really hard to stop antibiotics in a patient that you're looking at and you're thinking, like, this patient just doesn't look good.
00:23:58
Speaker
In those situations, you know, I think based on the evidence, probably, and the fact that it's really made its way to the intensivist literature, procalcitonin, I think it could be helpful for intensivists who maybe don't have as much
00:24:15
Speaker
uh, experiences, ID physicians, for example, with treating these sort of unspecified sepsis type syndromes.
00:24:21
Speaker
But I think also just keeping in mind that, um, sepsis like syndromes, there's a ton of non-infectious mimics of sepsis like syndromes, especially in immunocompromised patients.
00:24:33
Speaker
And that's, you know, that's who I typically see.
00:24:35
Speaker
I'm one of the trans-like immunocompromised host ID, um,
00:24:40
Speaker
providers at Brigham and the non-infectious mimics of sepsis are vast.
00:24:48
Speaker
And so I think if we keep that in mind, that really helps us with our diagnostic strategies and thinking about, you know, is it really infection and does this patient really need to be on antibiotics for this long or is there something else going on?
00:25:03
Speaker
How does cost factor into the use of procalcitonin?
00:25:09
Speaker
You know, I don't think procalcitonin is that expensive.
00:25:13
Speaker
You know, I think it's somewhere between, depending on which hospital you're at, what lab you're sending your tests to, I think it's somewhere between $20 to maybe $80 a test.
00:25:25
Speaker
So, you know, in the big scheme of things, not the most expensive test that we could send, but
00:25:33
Speaker
But there have been some studies in the literature talking about, you know, procalcitonin's cost effectiveness and the real world experiences.
00:25:42
Speaker
And it's really just yielded kind of mixed results.
00:25:44
Speaker
There haven't been a lot of strong yeses or strong no's overall in terms of using it.
00:25:51
Speaker
And so I think, you know, the question really is, do you want to put your money into procalcitonin testing and then the cost that it takes to sort of implement that?
00:26:03
Speaker
management and monitoring of the procalcitonin, or would you rather put your money on effective antibiotic stewardship strategies?
00:26:13
Speaker
Fair.
00:26:14
Speaker
In terms of guidelines, any comments on where procalcitonin falls on sepsis guidelines, recent pneumonia guidelines, or other guidelines related to critically ill patients and infection?
00:26:28
Speaker
Yeah, well, actually, it is in the sepsis guidelines, but it's in the 2021 Surviving Sepsis Campaign Guidelines.
00:26:36
Speaker
They call it weak and low-quality evidence, but their recommendation is that it can be used as an adjunct to clinical evaluation to decide when to discontinue antimicrobial therapies and
00:26:51
Speaker
in patients who had like an initial diagnosis of sepsis and it's sort of unclear what the optimal duration of therapy is.
00:27:00
Speaker
You know, to note, these guidelines came out before the ADAPT sepsis trial.
00:27:04
Speaker
So it will be interesting to see if there's any thought about changing the quality of evidence behind those guidelines, you know, whenever they're revisited in the future.
00:27:15
Speaker
But they did grade that recommendation as sort of weak and low quality, given sort of all of the key limitations we talked about of the original randomized control trials.
00:27:27
Speaker
In terms of practical use, how would you recommend PCT be or not be utilized in clinical practice by intensivists today?
00:27:38
Speaker
Well, if you're going to use it, I think, you know, the only place to use it right now, the only data that we have to support its use is in discontinuation of antibiotics.
00:27:51
Speaker
Definitely, I would not use it in the initial evaluation to decide whether or not to initiate antibiotics.
00:27:58
Speaker
I think that is really a different clinical decision.
00:28:03
Speaker
But overall, I'm still sort of unclear if it should be routinely adopted in ICUs, just sort of given all of the things that we've talked about with the prior studies.
00:28:15
Speaker
But I think, yeah, if we're going to implement it at all, we should probably use it in antibiotic discontinuation and then use algorithms sort of like ADAPT sepsis or SAPS where they use a cutoff threshold of like 0.5 for the procalcitonin or a decrease of about 80% from the peak value to decide whether or not to stop antibiotics.
00:28:40
Speaker
So those would be appropriate thresholds if you implement it.
00:28:43
Speaker
But if you're going to measure 80%, you probably need to have a baseline, right?
00:28:48
Speaker
So you've got to get procalcitonin, which a lot of patients get regardless in the ED, and then use that to measure that progression.
00:28:55
Speaker
So use either a decrease of 80% from the peak or a level that's below 0.5.
00:29:03
Speaker
Is that correct?
00:29:04
Speaker
Yeah.
00:29:06
Speaker
Yeah, I think, you know, that's where SAPS and ADAPT-seps is, which are the largest trials.
00:29:10
Speaker
Those are the cutoffs they use.
00:29:12
Speaker
And I think that would be potentially appropriate if you're going to use procalcitonin.
00:29:17
Speaker
But you brought up a good point, which is then you have to have sort of serial measurements.
00:29:23
Speaker
And the algorithms use, I think, daily procalcitonin measurements in all of their studies.
00:29:29
Speaker
And
00:29:30
Speaker
In real-world practice, we use it maybe a little bit more sporadically, but that's maybe where some of the cost limitation comes in is if you're really using it daily for a patient with a 10-day ICU stay, then that could be an issue with cost.
00:29:46
Speaker
Fair.
00:29:47
Speaker
In terms of other common pitfalls or any pros for success that you want to add for those who might be inclined to use the procalcitonin?
00:29:58
Speaker
Um, yeah, I, I think, you know, sometimes I see, uh, the house staff or, or anyone look at the procalcitonin and say, um, it's negative.
00:30:11
Speaker
The patient is coming in their febrile, their tachycardic, but it's negative.
00:30:14
Speaker
So, you know, let's hold off on it on starting antibiotics.
00:30:18
Speaker
As we talked about, I think that's probably not the best use of it.
00:30:22
Speaker
And in a patient like that, where I'd be concerned about sepsis, I would start antibiotics.
00:30:26
Speaker
Um,
00:30:27
Speaker
And then I've seen some, you know, some folks want to wait for a couple of days after the procalcitonin has really become negative to stop antibiotics.
00:30:37
Speaker
And I'd encourage you to stop antibiotics a little bit earlier in those situations.
00:30:42
Speaker
So in summary, really, it shouldn't be used to decide initial yes or no.
00:30:49
Speaker
If we utilize it, we should, based on the evidence, use it to determine if it's okay to stop.
00:30:56
Speaker
And that would require a protocol.
00:30:58
Speaker
And we're looking at either an 80% decline from the peak or a level below 0.5.
00:31:03
Speaker
Would that be fair?
00:31:05
Speaker
Summary?
00:31:06
Speaker
Yeah, yeah, that's absolutely correct.
00:31:08
Speaker
You know, I would not use it to start antibiotics.
00:31:12
Speaker
I think it's possible to use it to stop antibiotics.
00:31:15
Speaker
That's where all the data is.
00:31:18
Speaker
But I actually think just antibiotic stewardship in general, looking at some of these other big randomized control trials that have come out, like the balance trial that we've talked about a couple of times, I think that's really where the money is in terms of antibiotics.
00:31:37
Speaker
such as those that we're learning from those trials, procalcitonin may actually not be needed.
00:31:43
Speaker
Without making this an antibiotic stewardship episode, what would you want our intensivist listeners to understand or any advice on how to best interact with our stewardship programs at our local hospitals and ICUs, which is usually going to be driven by our infectious disease colleagues?
00:32:06
Speaker
How can we make the most out of that relationship that really help our patients?
00:32:12
Speaker
Um, that's a great question.
00:32:14
Speaker
I feel like there's always a little tug and pull there between, you know, our stewardship teams and the teams that are at the bedside.
00:32:20
Speaker
And it's tough when you're not seeing the patient to, to, um, be able to give maybe the best robust advice.
00:32:26
Speaker
But I think,
00:32:27
Speaker
you know, have an open mind when you're talking to the stewardship team.
00:32:30
Speaker
It's usually our, our antibiotic stewardship, you know, doctors and nurses and our pharmacists.
00:32:37
Speaker
And so have an open mind when you're talking to them, have an open discussion, understand where everybody's coming from.
00:32:43
Speaker
And it can often be a pull and tug sort of conversation, but ultimately we all just want what's best for that patient.
00:32:50
Speaker
And so, you know, we don't want to give them any antimicrobial side effects.
00:32:54
Speaker
And we also, you know,
00:32:55
Speaker
don't want to, don't want to not treat them.
00:32:59
Speaker
Anything coming down the pipe pipeline in terms of research that you're excited about, or do you think that we're kind of finding that Procrastone has its niche, has its value, but there are other aspects of care that probably are more relevant and that can get us to the same place?
Future Directions for Procalcitonin Research
00:33:21
Speaker
Well, I think, you know, one thing that this, when we were writing this viewpoint, me and my co-authors, something that it really spurred in us was thinking about, okay, well, technically the data doesn't show that we can use it to initiate antibiotics, but can it be used in the initial evaluation of patients, which is a little bit different, but
00:33:43
Speaker
of a question and, you know, instead of using it in the ICU setting where we could just, again, you know, do antimicrobial stewardship, can we actually use it in the ED, but in a different way, not necessarily to start antibiotics, but maybe to help with our diagnostic reasoning.
00:34:03
Speaker
So maybe, you know, a low procalcitonin in the ED supports
00:34:10
Speaker
diagnostic reasoning and risk stratification in a patient who presents with like a non-infectious mimicker of sepsis.
00:34:17
Speaker
So maybe that prompts the clinician in the ED to pursue sort of a more aggressive evaluation for non-infectious etiologies.
00:34:24
Speaker
And they can still give the antibiotics and that's fine because we know it can't be used in that setting to decide whether or not to give the antibiotics.
00:34:31
Speaker
But maybe it gives that clinician a little bit more of that push that, okay, I need to find what else might be the etiology here.
00:34:40
Speaker
So that's something that we thought a lot about when we were writing this, this viewpoint.
00:34:44
Speaker
And that's something we're looking at ourselves is just, you know, how many of these patients that show up to the ED looking like they're septic are actually having bacterial infections.
00:34:56
Speaker
And that really, I know this is not a podcast about antimicrobial stewardship, but all of it sort of comes back to that.
00:35:02
Speaker
And so that's the research that we're sort of looking into now.
00:35:04
Speaker
And I think where maybe some of the, some of the excitement is going to be.
00:35:10
Speaker
Yeah, I agree.
00:35:11
Speaker
And we always want like definite answers.
00:35:13
Speaker
But the reality is that these are just elements that we try to put together based on each individual patient and try to decide what's best for that patient.
00:35:23
Speaker
But based on the literature that you reviewed and what you've shared with us, the place of procrastination, I believe, is a little bit more detailed now.
00:35:34
Speaker
And we understand it better, its limitations, but also its potential use.
00:35:38
Speaker
But again, it doesn't seem like this is the wonder biomarker that will give us all the answers that we need for this very difficult patient population.
00:35:49
Speaker
Yeah, I think you said that absolutely correctly.
00:35:51
Speaker
You know, it's good.
00:35:53
Speaker
It's got some use.
00:35:55
Speaker
It's not a bad test by any means, but it's not sort of the cure-all for stopping antibiotics or working up for other causes of sepsis.
00:36:06
Speaker
Simran, we'd like to finish the podcast additionally with a couple of questions that are unrelated to the clinical topic.
00:36:11
Speaker
Would that be okay?
00:36:13
Speaker
Oh, sure.
Personal Recommendations and Insights
00:36:15
Speaker
The first question relates to books.
00:36:17
Speaker
Is there a book that has influenced you significantly or a book that you have gifted to others often?
00:36:24
Speaker
Oh, interesting.
00:36:25
Speaker
So I think there's one book that I always tell everybody is my favorite.
00:36:29
Speaker
I don't I don't know if I've convinced anybody to read it because it's almost a thousand pages long.
00:36:35
Speaker
But it's called I don't know if you've ever heard of it.
00:36:36
Speaker
It's called Shantaram.
00:36:38
Speaker
It was written in early 2000s.
00:36:41
Speaker
And it's sort of loosely based on the author's real life, but it's about a guy who was in a high security prison in Australia and he ends up escaping this prison and then finds himself sort of in the heart of Bombay in the 1980s.
00:36:56
Speaker
And it's just, it's intensely immersive.
00:36:59
Speaker
It's amazing.
00:37:00
Speaker
You really feel sort of everything that the author feels living in sort of the Bombay slums, but also seeing the juxtaposition with the rich Bombay life as well.
00:37:13
Speaker
The characters are really sort of unforgettable.
00:37:15
Speaker
You don't ever forget what you're hearing and reading about them.
00:37:21
Speaker
And it's kind of philosophical, and there's a whole...
00:37:25
Speaker
uh, a whole idea about redemption and morality in the book.
00:37:29
Speaker
And so it's really just, it's just an amazing, um, book to read.
00:37:33
Speaker
And then it's very interesting because the author, um, actually works as a doctor for some of the poor in the slums when he lands in India.
00:37:42
Speaker
And so just hearing about those experiences as well, it's a, it's a really amazing book and I highly recommend anybody to read it, but it's definitely a commitment.
00:37:50
Speaker
It's nearly a thousand pages.
00:37:52
Speaker
I had not heard about it, but it sounds fascinating and really interesting.
00:37:57
Speaker
And we'll link it in the show notes.
00:37:59
Speaker
And I would definitely give it a try.
00:38:01
Speaker
Maybe in small bites.
00:38:02
Speaker
But yeah, I know that it's like, oh, my God, would you see the size probably, right?
00:38:07
Speaker
Yeah.
00:38:08
Speaker
In between shifts, maybe.
00:38:10
Speaker
There you go.
00:38:12
Speaker
The second question relates to, could you share something that you changed your mind about over the last couple of years?
00:38:20
Speaker
Yeah.
00:38:22
Speaker
Okay, well, I think actually that in the last maybe, I think this has even really been in the last three years, I've changed my mind about how I define success.
00:38:35
Speaker
So, you know, in medicine, I was taught, you know, med school, residency, fellowship, attending, aim for the next thing, publish the next paper, you know, get your next promotion.
00:38:46
Speaker
And for a long time, I think I measured success on that.
00:38:51
Speaker
And I think I've come to a point in my life now where all of that is amazing and that makes me very happy.
00:38:57
Speaker
But I measure my success in almost like
00:39:00
Speaker
how happy I feel in life, you know, with my, in my personal life with my dogs and my partner, for example, or how I feel with like my patients, you know, I just, I love taking care of my patients.
00:39:12
Speaker
They, you know, enjoy having me as their doctor.
00:39:14
Speaker
And if my patients are happy, I'm happy.
00:39:17
Speaker
If my family is happy, I'm happy.
00:39:19
Speaker
And so I think that's really my definition of success now.
00:39:22
Speaker
And I think that's changed over the last few years.
00:39:25
Speaker
Yeah.
00:39:26
Speaker
And it's interesting, right?
00:39:27
Speaker
Because you can always go back to old philosophy, whether Western or Eastern philosophy, and you'll find truths that have perjured through time.
00:39:39
Speaker
And usually when different people around different eras and different places of the world came up with similar conclusions, I tend to believe that there has to be something valid there.
00:39:49
Speaker
And this whole concept that you're describing really is what the Greeks call eudaimonia, right?
00:39:55
Speaker
The contentment of making a difference, the contentment of having an impact on others and that tranquility and peace, which is very different to some of the external proxies of success that society keeps pushing on us, right?
00:40:09
Speaker
Absolutely.
00:40:10
Speaker
Oh, absolutely.
00:40:11
Speaker
And I do believe that especially in medicine, there's nothing wrong with taking care of patients.
00:40:18
Speaker
And that can be your main aspiration is to take good care of patients.
00:40:24
Speaker
And that's why we went to med school.
00:40:26
Speaker
So I do believe that worth evaluating.
00:40:30
Speaker
And ultimately, what I really take from what you shared is that we have to be
00:40:37
Speaker
truthful to ourselves and figure out what success means for us and that is different for each person or should be different for each person and uh yeah go ahead sorry just saying that i i think that's really been the opening the eye-opening thing is that success is different for each person and it's not not necessarily measured by what somebody else thinks of you or what you feel like you have to a
00:41:10
Speaker
show yourself to other people.
00:41:12
Speaker
It's really about finding, like you said, that contentment within yourself and what makes you happy and what makes your patients happy.
00:41:19
Speaker
Absolutely.
00:41:21
Speaker
And the final question is, what would you want every listener intensivist or ICU clinician that's listening to know?
00:41:29
Speaker
Could be a quote, a fact or a departing thought.
00:41:33
Speaker
Oh, you know, I think it's less so like a fact, but maybe just something to remember.
00:41:40
Speaker
And I know I'm sure, you know, most intensivists remember this, but we see in the ICU, you see patients in probably their worst stage of life, you know, incredibly, incredibly sick.
00:41:54
Speaker
And you're not just taking care of the patient, but you're honestly also taking care of the family.
00:41:59
Speaker
And you're seeing them in some of their worst times of their life because they're seeing their loved one in just, you know, a horrible position.
00:42:07
Speaker
And things get busy, things get tiring, we can get frustrated with whatever may happen in the hospital.
00:42:16
Speaker
But just remember that this might be like an okay day for you, even if it's a poor day in comparison, but this is probably the worst day for your patients and their families.
00:42:27
Speaker
So have that compassion, have that humility and really remember that.
00:42:32
Speaker
That's a perfect place to stop.
00:42:33
Speaker
Simran, thank you so much for sharing your time and your expertise.
00:42:37
Speaker
I look forward to having you back on the podcast to talk about other critical care related topics and infectious disease.
00:42:45
Speaker
And I look forward to seeing you in person soon.
00:42:48
Speaker
Absolutely.
00:42:49
Speaker
Thank you so much for having me today.
00:42:53
Speaker
Thank you for listening to Critical Matters, a sound podcast.
00:42:57
Speaker
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00:43:03
Speaker
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00:43:07
Speaker
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