Transcript
Speaker: Welcome to Critical Matters, a sound podcast covering a broad range of topics related to the practice of intensive care medicine.
Speaker: Sound provides comprehensive critical care programs to hospitals across the country.
Speaker: To learn more about our programs and career opportunities, visit www.soundphysicians.com.
Speaker: And now your host, Dr. Sergio Zanotti.
Speaker: Procalcitonin, a peptide precursor of the hormone calcitonin, is often elevated in response to bacterial infections.
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.
Speaker: In today's podcast, we will discuss the role of procalcitonin in the ICU.
Speaker: Our guest is Dr. Simran Gupta, an infectious disease specialist at Brigham's and Women's Hospital in Boston.
Speaker: Dr. Gupta has additional training in clinical research, transplant, and oncology infectious disease.
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.
Speaker: Simran, welcome to Critical Matters.
Speaker: Thank you for having me.
Speaker: I'm excited to be here.
Speaker: So we're gonna talk about procalcitonin in the ICU.
Speaker: And my first question is why should intensivists care about this topic?
Speaker: Well, it's a hot topic.
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.
Speaker: And with antimicrobial resistance, emergence of multidrug-resistant organisms,
Speaker: antimicrobial stewardship is really, really important.
Speaker: And so, you know, potentially procalcitonin can help us guide that.
Speaker: Excellent.
Speaker: I would like to start with some procalcitonin basics and just give us a little bit of the description.
Speaker: It's kinetics, what can cause false positives or false negatives.
Speaker: So we just can have a level setting for all our listeners.
Speaker: Absolutely.
Speaker: So as you said before, it's a calcitonin precursor hormone.
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.
Speaker: And it's thought to be downregulated by intravirone gamma stimulated by viral infections.
Speaker: But that being said, there's been a ton of research that has shown that SARS-CoV-2 infection can highlight PCT levels.
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.
Speaker: It's pretty sensitive and specific for bacterial sepsis, probably around 77% to 79% sensitive and about the same for specificity for sepsis.
Speaker: And it really is better than some of those other biomarkers that we've studied like CRP,
Speaker: white blood cell, ESR, et cetera.
Speaker: The false negative and false positive rates are a bit less.
Speaker: And the kinetics make it really favorable to study.
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.
Speaker: So it's pretty potentially useful to inform antibiotic discontinuation.
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.
Speaker: Is that correct?
Speaker: Yeah, that's correct.
Speaker: It really rises pretty quickly after bacterial infection onset.
Speaker: It peaks quickly and then it comes down as the bacterial infection resolves.
Speaker: So it's very favorable for study.
Speaker: What are some potential uses at the bedside for procalcitonin in the ICU?
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?
Speaker: Yeah, well, there have been a lot of randomized clinical trials.
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.
Speaker: And as an ID doctor, that's really where I see the most use for it right now.
Speaker: In patients who come in, it doesn't really tell me who looks sick, who looks septic.
Speaker: It doesn't tell me whether or not I should start antibiotics.
Speaker: That's really a clinical judgment for me based on, you know, other lab tests as well and radiographic findings.
Speaker: But for example, in a patient in the ICU who's had sort of these
Speaker: non-specific favors, fevers, and may look inflammatory, may be infected, but I just don't really know.
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?
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?
Speaker: You know, interestingly, I think it's a function of both.
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.
Speaker: But definitely, you know, we've done a lot of work to see these broad spectrum antibiotics starts in the ED, for example.
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.
Speaker: And there's a lot of syndromes that mimic sepsis, that mimic infection.
Speaker: And so I actually think it's a function of both.
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
Speaker: Perfect.
Speaker: And I was really looking at this through the prism of really critically ill patients.
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,
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.
Speaker: But I hear you both are important.
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.
Speaker: Yeah, absolutely agree.
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.
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.
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.
Speaker: We're going to probably focus on the discontinuation, as you mentioned.
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?
Speaker: You did mention something in the ED, but specifically for critically ill patients, anything you can add there?
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.
Speaker: There have been a couple randomized control trials in the ED, but they've been focusing just on respiratory tract infections.
Speaker: And so the one that I can think of was from, I think, 2010, and it looked at both patients
Speaker: you know, can you withhold initial antibiotic therapy if your procalcitonin is low, and then also discontinuation of antibiotic therapy when procalcitonin declines.
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.
Speaker: But really, the withholding initial antibiotic therapy was hard to study.
Speaker: I think a lot of clinicians were pretty reluctant to do that.
Speaker: And so there was not significant
Speaker: protocol adherence.
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.
Speaker: You also mentioned that even though we think of procalcitonin as linked to bacterial infections, with SARS-CoV-2, it can go up.
Speaker: So I remember during COVID, one of our big concerns was, do we add antibiotics?
Speaker: And some people are saying, well, the procalcitonin is elevated.
Speaker: You should.
Speaker: But then again, I mean, that just might be because of the COVID itself, right?
Speaker: Yeah, absolutely.
Speaker: That can definitely be from the COVID itself.
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.
Speaker: Because, you know, because as we know, some patients with COVID do have that.
Speaker: But I think the majority of patients with COVID did not have superimposed bacterial infection as well.
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.
Speaker: But could you tell us about the early studies in critically ill patients?
Speaker: I think it was Prorata, SOPS, ProGuard, Progress, etc.?
Speaker: Yes, definitely.
Speaker: So Prorata was the one that looked at both initially withholding antibiotics as well as declining.
Speaker: And from that is where some of the other RCTs were born.
Speaker: And they all really focused on withholding or discontinuing antibiotics, not withholding antibiotics.
Speaker: Um, when propalcitonin falls from a certain level to their, to their baseline.
Speaker: So there was pro guard, uh, that happened around 2014, I believe.
Speaker: And it was done in Australia.
Speaker: These were also critically ill patients and they had a pretty, um,
Speaker: a pretty rigid threshold for discontinuing antibiotics.
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.
Speaker: And that study actually did not find any difference in the median duration of antibiotics.
Speaker: You know, it was nine versus 11 days, but ultimately it wasn't statistically significant and also no difference in 90 day mortality.
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.
Speaker: And so there have been a couple of other trials since then as well.
Speaker: There was SAPS, as you mentioned, in 2016 that occurred in the Netherlands, again, in critically ill ICU patients.
Speaker: a little bit less conservative of a procalcitonin threshold.
Speaker: So they did the same threshold as was done in prorata.
Speaker: So you could discontinue antibiotics
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.
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.
Speaker: as well as a decreased 28-day mortality rate and a one-year mortality rate.
Speaker: So that was pretty exciting.
Speaker: But overall, the algorithm adherence was low, and it was an open-label study.
Speaker: And so that garnered some critiques about how that study was conducted.
Speaker: And then lastly, there was, as you mentioned before we talk about the most recent one, it was PROGRESS, which was in 2021.
Speaker: And this one wasn't conducted only in ICUs.
Speaker: It was conducted in ICUs and non-ICU settings, but it was all patients who met sepsis criteria, so sepsis-3 criteria.
Speaker: And again, they used sort of a very similar procalcitonin threshold to SAPS and PRORADA, and
Speaker: And they also found a median duration of antibiotics that was less than the procalcitonin group.
Speaker: So five days in the procalcitonin group and 10 days in the sort of non-procalcitonin control group.
Speaker: There was also fewer infections associated to adverse events like C. diff, multidrug-resistant organisms, as well as lower 28-day mortality.
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.
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.
Speaker: Was there anything else that you would consider a concern or that informs how people were thinking clinically at that point?
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.
Speaker: And so the procalcitonin results were shared with all the physicians and
Speaker: Which patient was in the intervention arm, which patient was in the control arm.
Speaker: And so that really, obviously, as you know, creates a risk of bias.
Speaker: And so I think that was one of the biggest critiques of those trials.
Speaker: And then, of course, the low algorithm adherence as well was a critique of the trials.
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.
Speaker: And that's actually like kind of long if you think about it.
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
Speaker: for gram-negative, strep, enterococcus, bacteremia infections in patients who are very ill.
Speaker: So 10 is quite long.
Speaker: And so that really makes you wonder, like, what was the nature of the antibiotic stewardship programs in these control arms?
Speaker: You know, like maybe the durations would have been even shorter in the control arms if there was just antibiotic stewardship.
Speaker: You don't even need the procalcitonin.
Speaker: So those are some of the points that have come up about these trials.
Speaker: And more recently, the ADAPT sepsis trial, obviously, was trying to further define the role of procalcitonin.
Speaker: Can we talk in more detail about that trial?
Speaker: Oh, yeah, absolutely.
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.
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.
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.
Speaker: But they did a lot of really good things with the ADAPT sepsis trial.
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.
Speaker: And so the investigators in ADAPT sepsis really addressed the blinding concerns.
Speaker: So they had a concealed intervention protocol.
Speaker: And then they also addressed the concerns about, you know, antibiotic stewardship and the control arms of the prior studies.
Speaker: And they made sure that their standard of care arm received, you know, regular antibiotic stewardship guidance, 72-hour stewardship reviews, et cetera.
Speaker: So it really tried to address some of those, those things that were thought to be faults of the prior studies.
Speaker: But in this particular one, ADAPT sepsis, it was done in the UK and I think 40, 41 ICUs.
Speaker: And they studied procalcitonin, CRP, and then standard of care, sort of a one-to-one-to-one try study design.
Speaker: They, they,
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.,
Speaker: And then their protocol was pretty interesting.
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.
Speaker: And so that piece of advice was either protocol strongly supports stopping antibiotics or
Speaker: And that was based on a procalcitonin level of less than 2.5.
Speaker: The second piece of advice they could give was protocol support stopping antibiotics.
Speaker: And that was either based on a procalcitonin between 0.25 and 0.5 or greater than 80% fall from baseline.
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.
Speaker: And that's how they conducted their study.
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.
Speaker: So procalcitonin group, 9.8 days, standard of care, 10.7 days.
Speaker: And they also found a non-inferior 28-day mortality rate.
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.
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?
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.
Speaker: You know, I thought it was great that both groups got sort of the same.
Speaker: strategies and teaching and review.
Speaker: And so really the outcome was very much so, um, very much so based on the procalcitonin guided therapy.
Speaker: So I thought that was interesting and I thought it was probably our best data, um, to date.
Speaker: Excellent.
Speaker: I'd like to talk about practical considerations.
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.
Speaker: So you can get...
Speaker: Basically, same mortality, same results with less antibiotics.
Speaker: Do you think that this makes procalcitonin less relevant in the ICU?
Speaker: Yeah, you know, that's a great question.
Speaker: And I do think that that is something that really needs to be thought of, you know, really strongly.
Speaker: So,
Speaker: you know, again, the patients, there was sort of a median duration of 10 days of antibiotics in these patients.
Speaker: And like we said, the recent balance trial demonstrates that seven days of antibiotic therapy is safe.
Speaker: So if we sort of already know that in our patients,
Speaker: What are we using the procalcitonin for and why are we still treating for a median duration of 10 days anyways?
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.
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?
Speaker: It seems that for so many patients, five days might be all they need, right?
Speaker: Yeah.
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.
Speaker: I think, you know, any infectious disease doctor or even intensivist can maybe tell you their anecdotal experience.
Speaker: And mine is usually that I do seven days of therapy for this sort of unexplained sepsis picture.
Speaker: And so I think if we really focus our strategies on
Speaker: like antimicrobial stewardship in that sense.
Speaker: We probably don't even need procalcitonin in these situations.
Speaker: In terms of other challenges, I also recognize that often critical care clinicians are very reluctant to stop antibiotics in their patients.
Speaker: It's almost like they want to keep pushing.
Speaker: Any thoughts?
Speaker: I mean, there or maybe for that at least a biomarker can be helpful.
Speaker: But how do you deal with that when you're the one trying to convince people to stop antibiotics?
Speaker: Well, that's definitely a struggle that, you know, we face.
Speaker: And it's understandable, too.
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.
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
Speaker: uh, experiences, ID physicians, for example, with treating these sort of unspecified sepsis type syndromes.
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.
Speaker: And that's, you know, that's who I typically see.
Speaker: I'm one of the trans-like immunocompromised host ID, um,
Speaker: providers at Brigham and the non-infectious mimics of sepsis are vast.
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?
Speaker: How does cost factor into the use of procalcitonin?
Speaker: You know, I don't think procalcitonin is that expensive.
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.
Speaker: So, you know, in the big scheme of things, not the most expensive test that we could send, but
Speaker: But there have been some studies in the literature talking about, you know, procalcitonin's cost effectiveness and the real world experiences.
Speaker: And it's really just yielded kind of mixed results.
Speaker: There haven't been a lot of strong yeses or strong no's overall in terms of using it.
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?
Speaker: management and monitoring of the procalcitonin, or would you rather put your money on effective antibiotic stewardship strategies?
Speaker: Fair.
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?
Speaker: Yeah, well, actually, it is in the sepsis guidelines, but it's in the 2021 Surviving Sepsis Campaign Guidelines.
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
Speaker: in patients who had like an initial diagnosis of sepsis and it's sort of unclear what the optimal duration of therapy is.
Speaker: You know, to note, these guidelines came out before the ADAPT sepsis trial.
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.
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.
Speaker: In terms of practical use, how would you recommend PCT be or not be utilized in clinical practice by intensivists today?
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.
Speaker: Definitely, I would not use it in the initial evaluation to decide whether or not to initiate antibiotics.
Speaker: I think that is really a different clinical decision.
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.
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.
Speaker: So those would be appropriate thresholds if you implement it.
Speaker: But if you're going to measure 80%, you probably need to have a baseline, right?
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.
Speaker: So use either a decrease of 80% from the peak or a level that's below 0.5.
Speaker: Is that correct?
Speaker: Yeah.
Speaker: Yeah, I think, you know, that's where SAPS and ADAPT-seps is, which are the largest trials.
Speaker: Those are the cutoffs they use.
Speaker: And I think that would be potentially appropriate if you're going to use procalcitonin.
Speaker: But you brought up a good point, which is then you have to have sort of serial measurements.
Speaker: And the algorithms use, I think, daily procalcitonin measurements in all of their studies.
Speaker: And
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.
Speaker: Fair.
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?
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.
Speaker: The patient is coming in their febrile, their tachycardic, but it's negative.
Speaker: So, you know, let's hold off on it on starting antibiotics.
Speaker: As we talked about, I think that's probably not the best use of it.
Speaker: And in a patient like that, where I'd be concerned about sepsis, I would start antibiotics.
Speaker: Um,
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.
Speaker: And I'd encourage you to stop antibiotics a little bit earlier in those situations.
Speaker: So in summary, really, it shouldn't be used to decide initial yes or no.
Speaker: If we utilize it, we should, based on the evidence, use it to determine if it's okay to stop.
Speaker: And that would require a protocol.
Speaker: And we're looking at either an 80% decline from the peak or a level below 0.5.
Speaker: Would that be fair?
Speaker: Summary?
Speaker: Yeah, yeah, that's absolutely correct.
Speaker: You know, I would not use it to start antibiotics.
Speaker: I think it's possible to use it to stop antibiotics.
Speaker: That's where all the data is.
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.
Speaker: such as those that we're learning from those trials, procalcitonin may actually not be needed.
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?
Speaker: How can we make the most out of that relationship that really help our patients?
Speaker: Um, that's a great question.
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.
Speaker: And it's tough when you're not seeing the patient to, to, um, be able to give maybe the best robust advice.
Speaker: But I think,
Speaker: you know, have an open mind when you're talking to the stewardship team.
Speaker: It's usually our, our antibiotic stewardship, you know, doctors and nurses and our pharmacists.
Speaker: And so have an open mind when you're talking to them, have an open discussion, understand where everybody's coming from.
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.
Speaker: And so, you know, we don't want to give them any antimicrobial side effects.
Speaker: And we also, you know,
Speaker: don't want to, don't want to not treat them.
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?
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
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.
Speaker: So maybe, you know, a low procalcitonin in the ED supports
Speaker: diagnostic reasoning and risk stratification in a patient who presents with like a non-infectious mimicker of sepsis.
Speaker: So maybe that prompts the clinician in the ED to pursue sort of a more aggressive evaluation for non-infectious etiologies.
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.
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.
Speaker: So that's something that we thought a lot about when we were writing this, this viewpoint.
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.
Speaker: And that really, I know this is not a podcast about antimicrobial stewardship, but all of it sort of comes back to that.
Speaker: And so that's the research that we're sort of looking into now.
Speaker: And I think where maybe some of the, some of the excitement is going to be.
Speaker: Yeah, I agree.
Speaker: And we always want like definite answers.
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.
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.
Speaker: And we understand it better, its limitations, but also its potential use.
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.
Speaker: Yeah, I think you said that absolutely correctly.
Speaker: You know, it's good.
Speaker: It's got some use.
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.
Speaker: Simran, we'd like to finish the podcast additionally with a couple of questions that are unrelated to the clinical topic.
Speaker: Would that be okay?
Speaker: Oh, sure.
Speaker: The first question relates to books.
Speaker: Is there a book that has influenced you significantly or a book that you have gifted to others often?
Speaker: Oh, interesting.
Speaker: So I think there's one book that I always tell everybody is my favorite.
Speaker: I don't I don't know if I've convinced anybody to read it because it's almost a thousand pages long.
Speaker: But it's called I don't know if you've ever heard of it.
Speaker: It's called Shantaram.
Speaker: It was written in early 2000s.
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.
Speaker: And it's just, it's intensely immersive.
Speaker: It's amazing.
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.
Speaker: The characters are really sort of unforgettable.
Speaker: You don't ever forget what you're hearing and reading about them.
Speaker: And it's kind of philosophical, and there's a whole...
Speaker: uh, a whole idea about redemption and morality in the book.
Speaker: And so it's really just, it's just an amazing, um, book to read.
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.
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.
Speaker: It's nearly a thousand pages.
Speaker: I had not heard about it, but it sounds fascinating and really interesting.
Speaker: And we'll link it in the show notes.
Speaker: And I would definitely give it a try.
Speaker: Maybe in small bites.
Speaker: But yeah, I know that it's like, oh, my God, would you see the size probably, right?
Speaker: Yeah.
Speaker: In between shifts, maybe.
Speaker: There you go.
Speaker: The second question relates to, could you share something that you changed your mind about over the last couple of years?
Speaker: Yeah.
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.
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.
Speaker: And for a long time, I think I measured success on that.
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.
Speaker: But I measure my success in almost like
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.
Speaker: They, you know, enjoy having me as their doctor.
Speaker: And if my patients are happy, I'm happy.
Speaker: If my family is happy, I'm happy.
Speaker: And so I think that's really my definition of success now.
Speaker: And I think that's changed over the last few years.
Speaker: Yeah.
Speaker: And it's interesting, right?
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.
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.
Speaker: And this whole concept that you're describing really is what the Greeks call eudaimonia, right?
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?
Speaker: Absolutely.
Speaker: Oh, absolutely.
Speaker: And I do believe that especially in medicine, there's nothing wrong with taking care of patients.
Speaker: And that can be your main aspiration is to take good care of patients.
Speaker: And that's why we went to med school.
Speaker: So I do believe that worth evaluating.
Speaker: And ultimately, what I really take from what you shared is that we have to be
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
Speaker: show yourself to other people.
Speaker: It's really about finding, like you said, that contentment within yourself and what makes you happy and what makes your patients happy.
Speaker: Absolutely.
Speaker: And the final question is, what would you want every listener intensivist or ICU clinician that's listening to know?
Speaker: Could be a quote, a fact or a departing thought.
Speaker: Oh, you know, I think it's less so like a fact, but maybe just something to remember.
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.
Speaker: And you're not just taking care of the patient, but you're honestly also taking care of the family.
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.
Speaker: And things get busy, things get tiring, we can get frustrated with whatever may happen in the hospital.
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.
Speaker: So have that compassion, have that humility and really remember that.
Speaker: That's a perfect place to stop.
Speaker: Simran, thank you so much for sharing your time and your expertise.
Speaker: I look forward to having you back on the podcast to talk about other critical care related topics and infectious disease.
Speaker: And I look forward to seeing you in person soon.
Speaker: Absolutely.
Speaker: Thank you so much for having me today.
Speaker: Thank you for listening to Critical Matters, a sound podcast.
Speaker: Make sure to subscribe to Critical Matters on Apple or Google Podcasts and share with your network.
Speaker: Sound's transforming the way critical care is provided in hospitals across the country.
Speaker: To learn more, visit www.soundphysicians.com.
