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: We accept many interventions and beliefs in critical care at face value, not because they are rooted in strong evidence, but because they have been passed down through training and tradition.
Speaker: We do things a certain way because that's how it has always been done.
Speaker: This type of ingrained knowledge is often referred to as dogma.
Speaker: In a previous episode, we explored the importance of challenging dogma, particularly when the supporting evidence is weak or absent.
Speaker: Today, we continue that discussion by examining critical care practices that persist despite a lack of strong scientific validation.
Speaker: Our guest for this episode is Dr. Mervyn Singer, an internationally recognized leader in critical care medicine.
Speaker: Dr. Singer is a professor of intensive care medicine at University College London and distinguished clinician, researcher, and educator.
Speaker: His groundbreaking work has influenced how we think about sepsis, hemodynamic monitoring, the rural mitochondrial septic shock, and many other aspects of critical illness.
Speaker: Through his research, publications, and dynamic presentations, he has inspired me and countless intensivists worldwide to think critically, challenge conventions, and push the boundaries of our field.
Speaker: It's a true honor to have Dr. Singer back on the podcast.
Speaker: Let's dive into our conversation.
Speaker: Mervyn, welcome back to Critical Matters.
Speaker: Sergio, thank you very much for the A for the introduction and B for the repeat invitation.
Speaker: Absolutely.
Speaker: So the genesis of this conversation was a follow-up article you published in Intensive Care Medicine, Challenging Management Dogma Where Evidence is Non-Existent, Weak or Outdated, Part 2.
Speaker: And unlike most movie sequels, I guess we're after the Oscars, this article actually was as good as Part 1.
Speaker: Yeah.
Speaker: It's a lot like Godfather 2.
Speaker: Yes.
Speaker: There you go.
Speaker: Godfather 2.
Speaker: And I think as an introduction, maybe you could tell us why you think this is an important topic for clinicians at the bedside.
Speaker: Yeah.
Speaker: Yeah.
Speaker: I think it actually is crucial because I think, unfortunately, we're not brought up to challenge.
Speaker: The way, certainly, medicine's taught in Europe and I guess in the United States as well and in other countries is just to learn things by rote, just accept things that the boss told you or the textbook told you, and then you just regurgitate the facts afterwards without actually challenging
Speaker: the accuracy or the history of where these so-called facts came from.
Speaker: So I think it's good to have an open mind, even when things are just done because they were pushed on from our mother's knee and this is how you do things.
Speaker: Well, perhaps we ought to be smarter.
Speaker: Excellent.
Speaker: And as we start talking about the topic, what do you consider to be a definition or how would you explain to somebody what dogma is?
Speaker: yeah well dogma comes from the greek and it means that which one thinks is true um and so this becomes an ingrained belief that unfortunately uh certainly in medicine um becomes repeated over time and then the spoken fact and the written fact become um interpreted as truth and fact uh when perhaps uh
Speaker: Going back to the original word, that which one thinks is true gets replaced by that which we think is true.
Speaker: And I think truth is a heavy word probably for the bedside, right?
Speaker: Because there's so much that we don't know or that changes as we go along.
Speaker: But we've tried to move forward over the last several decades, the concept of evidence-based medicine.
Speaker: In your practice, what does that really look like, Mervyn?
Speaker: Well, I have...
Speaker: Problems with evidence-based medicine.
Speaker: So on the one hand, we need to understand how best to treat our patients.
Speaker: That's a given.
Speaker: And clearly we can't ignore the literature.
Speaker: My worry or qualm about evidence-based medicine is, especially the large multicenter randomized trial,
Speaker: is predicated around a response of a population rather than an individual response.
Speaker: And so it may be a positive trial, so some people benefit more than some people who are harmed and therefore the overall effect is benefit.
Speaker: Yes, he may be helping some, but actually harming others.
Speaker: So wouldn't it be nice to actually try and target the patients who will benefit from an intervention?
Speaker: And then moving on from that, a lot of the trials are one size fits all.
Speaker: So we need to be able to tailor when to start, how much to give, when to stop to that individual patient.
Speaker: So yes, I'm a believer in evidence.
Speaker: cognizant of the problems in the way we currently interpret it and apply it.
Speaker: And I think it's important, obviously, to also question the way we conduct these trials and what the evidence really means.
Speaker: Like you said, not only question dogma, just because there's a trial doesn't mean that that's the right intervention for my patient.
Speaker: And I think another aspect that we don't have to dive into deep, but that is real, is that over the years, not only in medicine, but in other scientific disciplines,
Speaker: We have seen that it's very difficult sometimes to reproduce the results of a positive trial.
Speaker: It's not a given, right?
Speaker: Which makes you wonder, is this real or just a fluke?
Speaker: Yeah, or different populations respond differently.
Speaker: And so by the time one group's actually enrolled into the trial or there may be racial, cultural differences, comorbidities, all of these things imply that actually one size, again, doesn't fit all.
Speaker: And this problem of reproducibility, I think in many, many areas of medicine, not just critical care, the same thing has been shown over and over again.
Speaker: And I believe that dogma, like many other things in life, evolve or become present in our lives because they have a benefit.
Speaker: And even though today we're talking about how to question dogma, maybe we'll focus on some of the dangerous aspects of dogma.
Speaker: Could you tell us how dogma could be valuable in clinical practice?
Speaker: Well, I think it's that comfort blanket.
Speaker: This is the way we've been doing it for years.
Speaker: And also we can hide behind established practice, good or bad.
Speaker: this is the way certainly I don't know in the United States but in the UK if there's a medical legal case if there's a reasonable body of medical opinion who would agree with a certain way of managing it that basically gives support to the defendant clinician that what they did was reasonable and so we often hide behind dogma because this is the way things were done so
Speaker: I think there's a general assumption that patients benefit from things being done in a certain way, even though there's not the hard and fast evidence that this is beneficial overall, number one, but also number two, it's beneficial to individual patients.
Speaker: Again, this argument I was making that some may benefit, some may potentially not benefit at all or even be harmed, but at least we've got comfort in knowing there's precedent.
Speaker: And the last thing I want to talk about before we jump into some of the actual discussions of fighting specific dogmatic concepts is the idea of confirmation bias and how it plays into perpetuating behaviors at the bedside.
Speaker: I think a lot of clinicians, a lot of colleagues see themselves as scientists.
Speaker: I usually tell people that we're not scientists, we're clinicians.
Speaker: And the reason we're not scientists is because we don't behave like scientists, right?
Speaker: We believe what we would like to believe and we justify it.
Speaker: Any thoughts on that, Mervyn?
Speaker: Yeah, I 100% agree.
Speaker: I love because hopefully good scientific discipline means you go back to first principles, you look at all the data there is and then work out what is hopefully accurate and what isn't, what supposition and what hard fact and then...
Speaker: Clearly in medicine, you know, which populations should we apply it to?
Speaker: Often, again, trials only look at a certain population and we have this nasty habit of extrapolating it because it suits our beliefs, comfort blankets, whatever.
Speaker: And so...
Speaker: you know this perpetuation of hope expectation belief often pushes the hard fact into the background or under the swamp
Speaker: Excellent.
Speaker: So let's dive into fighting the actual dogma when evidence is weak, non-existent, or outdated.
Speaker: And in the paper that we'll reference in the show notes, you discuss four very common situations in practice.
Speaker: I mean, there are things that for most critical care patients,
Speaker: clinicians probably occur on a daily, if not weekly basis.
Speaker: And frequently, I mean, are part of our practice.
Speaker: And I think it's great sometimes to stop and think about it.
Speaker: Why do we do this the way we do it and what's out there?
Speaker: So why don't we start with the first one, which is give a week's course of antibiotic treatment and tell us kind of how you thought about that and what you found in the evidence and what do you recommend?
Speaker: Well,
Speaker: I suppose traditionally been a bit of an antibiotic nihilist.
Speaker: Again, when you delve into the literature, yes, antibiotics are without doubt useful, but they're often sort of thrown around willy-nilly, often inappropriately, often to excess.
Speaker: And increasingly, I think people are beginning to recognise that there are lots of harms associated with
Speaker: giving antibiotics either inappropriately, excessively or for too long.
Speaker: And, you know, we're obviously aware of the rash or the renal dysfunction, etc.
Speaker: But there's a whole load of other things that cause problems.
Speaker: You know, they affect immune functionality, mitochondrial functionality.
Speaker: Obviously, the microbiome has gained a lot of attention in recent years and how antibiotics can very quickly disrupt
Speaker: and normal microbiota so i think there's an increasing awareness that perhaps we need to be more careful and clearly antimicrobial stewardship has come to the fore because of increasing issues with resistance and obviously you get overgrowth of fungi and resistant organisms if you throw antibiotics around for too long or inappropriately so
Speaker: Again, when I was brought up as a junior doctor, it was, well, the patient's really sick, we need to go for longer and, you know, add in two or three antibiotics.
Speaker: And that's become sort of established dogma based on, sadly,
Speaker: very, very little evidence.
Speaker: And the number of prospective randomized trials of, for example, antibiotic duration or comparing combination therapy against monotherapy in critically ill patients, vanishingly small.
Speaker: So there's been, thankfully, some improvement over the last few years, but there's often been this preset idea that, oh, give a week's treatment, or if they're really all give them two weeks,
Speaker: or even longer, because that's got lodged in our mind as a decent course.
Speaker: When you look at the literature, most bugs, unless they're very deep-seated, for example, an osteomyelitis or an endocarditis, most infections are treated literally effectively within one or two doses, let alone days.
Speaker: And yet,
Speaker: the patient's given a week and again there was the uh the dogma certainly in the uk that the patient was really encouraged to finish a course and not stop early so all of these things were perpetuated
Speaker: and then why did we pick seven days in the first place why a week well it's convenient to just do things in terms of one week's course two week course etc and if you look drug companies tend to package courses of antibiotics as 7 14 28 days in the package and so that dogma has been perpetuated by how we actually
Speaker: conduct the prescription and the treatment.
Speaker: And just laughingly in the article, I highlighted the fact that Emperor Constantine in, I think it was 321 AD, decreed a seven-day week.
Speaker: And the Romans beforehand had been using eight-day weeks.
Speaker: The Egyptians had been using 10-day cycles.
Speaker: And so, you know, had we stuck with an eight-day week, we'd be giving eight-day courses of therapy or 16 or 24.
Speaker: a completely arbitrary choice that we've alighted on seven days and again perhaps can blame Emperor Constantine for coming up with a seven-day week.
Speaker: It's fascinating.
Speaker: I was reading the article and I read that piece and I never thought about it but Constantine really has had a tremendous impact on my life.
Speaker: I mean so many things in my upbringing I think are just because
Speaker: Constantine decided that's the way it would be from antibiotics to me doing my first communion, I guess, right?
Speaker: All those things.
Speaker: I mean, thanks to Constantine, the unintended consequences of decisions.
Speaker: Exactly.
Speaker: And I'm sure he wouldn't have predicted how he would influence antibiotic prescribing.
Speaker: Now, one of the things that you talk about also is obviously that we talked about pros and cons for everything, right?
Speaker: Now, this in particular seems to be a situation where the pros are...
Speaker: very clear, but very, very few.
Speaker: And there's a lot of cons that people, I think, don't appreciate.
Speaker: And I think this is a common mistake from clinicians, right?
Speaker: Not really appreciating the potential negatives of continuing ongoing antibiotics that are unneeded, especially when it's one after another in the ICU, it can cause compound problems.
Speaker: So I guess the positive of giving antibiotics is that, like you said, it reduces the risk of undertreatment, right?
Speaker: Like I gave only one dose and that was not enough.
Speaker: But the data suggests that probably seven days for most uncomplicated cases or not deep-seated cases is probably overkill.
Speaker: What are some of the cons of continuing that extra day, two days, three days or more of antibiotics?
Speaker: I think...
Speaker: Probably it's hard at the individual patient level to actually work that out because clearly we may not see that in single patients.
Speaker: But clearly there are, potentially at a population level there's a harm.
Speaker: Again, the influence on encouraging resistance, fungal overgrowth, keeping patients in hospital an extra day or whatever.
Speaker: Let's just finish the course.
Speaker: So it's too much of a faff to put them on oral or send them home and arrange intravenous so they're kept in hospital so that they could finish the course.
Speaker: So there are lots of
Speaker: potential downsides and often in medicine what we do is convenient for us and we then assume it's convenient for the patient but hey wouldn't it be nice to get out of hospital earlier if they don't need the treatment let them escape sooner and and often you know i do wonder you know how often patients are kept in just to finish off the course
Speaker: And also, I mean, the message we give to patients, I mean, that if they miss one dose, right, I mean, sometimes, I mean, patients will freak out, right?
Speaker: Like that's going to cause a tremendous impact on their infection.
Speaker: And trying to explain that sometimes to patients is quite interesting.
Speaker: But you're right.
Speaker: I think that this is an area where we are moving the needle slowly.
Speaker: I don't think that we walked away from the seven-day kind of cycle, but we are moving towards less antibiotics, right?
Speaker: I mean, you mentioned in the paper, and now it's published, the ADAPT trial, large sepsis randomized clinical trial, looking at the use of biomarkers.
Speaker: to reduce safely the use of antibiotics.
Speaker: And also at the same time, a couple of months ago, a large paper looking at the comparison of seven days versus 14 days for bacteremia that, I mean, has obviously certain criteria, but that was also one of those that, oh, you have bacteremia, you need now 14 or 21 days of IV antibiotics, right?
Speaker: So I think that slowly figuring out that we can do shorter, shorter courses.
Speaker: Do you think that the route for that is going to be through biomarkers initially?
Speaker: I think, well, my view of biomarkers, I think they're a comfort blanket again.
Speaker: It just gives the clinician added confidence to think about stopping.
Speaker: And I think,
Speaker: unfortunately you know the traditionally c-reactive proteins being used as a biomarker for stopping but we know the lag time for that to normalize is often a day or two behind the patient's clinical improvement but the clinician feels oh we've got to wait till that crp approaches normal before we feel confident that we've treated the infection
Speaker: But the point, I think, to stress here is that these inflammatory markers, CRP, procalcitonin, the white count, etc., are markers of inflammation, which has been triggered by the infection rather than ongoing infection.
Speaker: My question,
Speaker: again going back to this personalizing care yes i think biomarkers help in that sense as the comfort blanket but my clinical practice was very much predicated on how does the individual respond so if they're improving clinically better uh after you know
Speaker: three days treatment, whatever, I might give another 24, 36 hours of treatment and then stop.
Speaker: So in some patients, I'll use three or four days of treatment.
Speaker: Other patients, you know, may need longer.
Speaker: But the fact that, you know, if a patient's going to respond to an antibiotic, by and large, it happens pretty quickly.
Speaker: If they haven't responded in three, four, five days, and they're still as ill, if not deteriorating, then you've got to think,
Speaker: is the bug sensitive to the antibiotic?
Speaker: Often we can't find a bug.
Speaker: Secondly, is it deep-seated?
Speaker: Is there an abscess somewhere that the antibiotics actually can't get to and penetrate?
Speaker: Or is there an infection in the first place?
Speaker: And often there's so-called sepsis mimics, where it's an inflammatory or an autoimmune condition, which is actually nothing to do with infection or
Speaker: It may be a viral, virally-driven cause, et cetera.
Speaker: And so we're just continuing with the antibiotics just on the off chance they've got a bacterial infection when actually it might be something completely different, non-bacterial or non-infectious.
Speaker: Perfect.
Speaker: Any recommendations from your part in terms of other things that we should be thinking about in this particular topic before we move on to the next clinical scenario?
Speaker: I think the other thing I'd just like to stress here is that we put a lot of stock on bacteremia.
Speaker: And I think partly, again, the dogma there is we get very excited that we've grown something or the lab has grown something in the blood.
Speaker: However, actually, again, if you look at the data, and this is data going back,
Speaker: 30 40 50 years and acknowledged by microbiologists but generally clinicians aren't aware of it but the number of circulating bacteria in a bacteremia are vanishingly small so my way of explaining it is that we have in every mill of blood you know it's
Speaker: Sorry, a liter of blood, 10 to the, sorry, start with a mill of blood.
Speaker: So we have 10 to the sixth white cells.
Speaker: So we've got a huge number of white cells in a mill of blood, but actually for a bacteremia, the usual number of bacteria, colony forming units in that mill of blood is below 10.
Speaker: So even with an endocarditis where the infection is in contact with the bloodstream directly, you then might get into the hundreds or maybe even to the thousands.
Speaker: But that's still way, way, way below the millions of white cells that are actually present in that mill of blood.
Speaker: And so I would argue that bacteremia is actually more a biomarker of an infection rather than something to get het up about.
Speaker: Because, again, when we come to studies looking at gram-negative sepsis or whatever, or even gram-positive, the number of distant embolic phenomena related to that infection are vanishingly small.
Speaker: You know, we very rarely see, even with staph, we very rarely see somebody with a staph infection getting a staph endocarditis or a staph osteomyelitis.
Speaker: It does happen from time to time, but it's very rare that these things actually occur, you know, especially as a secondary phenomenon.
Speaker: So, you know, I think I'd like to stress the fact that, yes, staph,
Speaker: you know, bacteremia is comforting because we've grown something, but there's a huge amount of importance attached to bacteremia in terms of, oh, we need to treat for longer because it's in the blood, when actually it's probably, as I mentioned earlier, an absence of adequate immune surveillance, allowing those few bacteria to carry on circulating.
Speaker: Yeah, I think that's a great point.
Speaker: And I have to say that for the next topic, I've been quite dogmatic about this when I feel guilty now.
Speaker: So I've definitely questioned seven days and 14 days of antibiotics.
Speaker: But standardized management protocols for diabetic ketoacidosis, boy, have I taught that and done that in a dogmatic way.
Speaker: So this is something very common and we just do whatever the textbook told us, right?
Speaker: And we kind of do the same thing over and over again and apply the same ruler to all sorts of different patients.
Speaker: Can you talk a little bit more about this one, Mervin?
Speaker: Yeah.
Speaker: Again, it's going back to that one size fits all.
Speaker: And it just seemed, well, it's always seemed a bit crazy to me that we apply exactly the same rules, regardless of whether the patient comes in, you know, dry as a bone or actually reasonably well hydrated, but, you know, because they've been drinking well, etc.
Speaker: So we do the same thing.
Speaker: Some people are established diabetics on diabetes.
Speaker: 100 units of insulin a day.
Speaker: Some people are de novo discovered as being diabetic.
Speaker: And so generally their insulin requirements will be much lower.
Speaker: Yet we give a fixed dose of insulin to everyone regardless.
Speaker: So there are all these things that we do that you think, well, hang on, why don't we personalize to what the patient needs rather than just give this fixed dose to everyone?
Speaker: And the second problem is that a lot of the
Speaker: complications of sequelae of how we treat the patient are well recognized.
Speaker: So it's well recognized that hypokalemia is a common problem because we've given a load of insulin, which has driven the blood potassium level down.
Speaker: Not so bright.
Speaker: Hypoglycemia is well recognized because, again, too much insulin is given to some patients.
Speaker: Their glucose levels plummet.
Speaker: And as a consequence, you know, the patient becomes hypoglycemic and then there's got to be a response.
Speaker: Likewise, this rigid fixed amount of fluid loading, some patients, especially if they've got, for example, chronic heart disease, do they need?
Speaker: you know, 8, 10, 12 liters given over a relatively short period of time.
Speaker: And so it seems a bit crazy that we've adopted this fixed protocol.
Speaker: Again, based on no literature, there's no evidence, there's been randomized trials to actually show that this is the best way of treating everybody in diabetes.
Speaker: So it gives this general rule
Speaker: but then we hide behind or junior doctors then in the middle of the night can use this.
Speaker: But at the same time, when something goes wrong with the patient, how often is it that the patient's blamed rather than the management protocol?
Speaker: And when you reviewed this, it doesn't seem like you found a lot of good evidence to support many of these practices.
Speaker: Yeah, ironically, actually, just literally, in last year, at the end of last year, a consensus conference of diabetic societies from America, Europe, UK, etc.
Speaker: come out with a consensus report.
Speaker: which essentially agrees with what I've been saying.
Speaker: So I prejudged a recommendation, and now they're saying, well, perhaps we ought to be a bit more aware of not drowning the patient with too much fluid, not drowning the patient with saline and causing a hypochloremic acidosis, etc.
Speaker: So essentially, all the messages I was preaching in this article, apart from...
Speaker: they still maintain giving a fixed dose of insulin is a good idea, which I've just previously argued against.
Speaker: Titrate to the patient and look for a
Speaker: a drop a gradual drop in the glucose level rather than giving everyone a similar dose but essentially they've moved across to uh the singer way of uh um treating it i'm not saying uh i was a direct influence but you know there's this been this belated recognition that what they've been preaching for years perhaps is a little bit outdated and likewise there was
Speaker: in previous guidelines and iterations, a big push towards using blood ketone levels as the way to manage the patient as a primary goal rather than the glucose.
Speaker: And now, interestingly, based on no data, I should hasten to add, and now that's been dropped from this consensus report.
Speaker: So this report came out in diabetes care in 2024.
Speaker: And generally, I think it's a much, much better idea
Speaker: article and a much more considered approach to managing hyperglycemic crises.
Speaker: Excellent.
Speaker: And I think that, like you mentioned, it's important, right, for us to question what we're doing and to question where this evidence comes.
Speaker: And I think that's important today, not only in medicine, but everywhere when somebody says something.
Speaker: Where did you get that, right?
Speaker: Where does this come from?
Speaker: Try to find the source.
Speaker: And sometimes what we'll find is that there is no source.
Speaker: And then we should really be thinking might there be a better way of doing this.
Speaker: So I have to say, though, Mervyn, that you did suggest in the paper that maybe society should get together and come up with a consensus.
Speaker: So maybe they did listen.
Speaker: Maybe they did read the paper and said, let's do it.
Speaker: As a gentle criticism, these were only diabetologists.
Speaker: So there wasn't any involvement, as far as I'm aware, from emergency medicine, doctors.
Speaker: intensive care medicine, internal medicine, etc.
Speaker: And, you know, I would argue politely that, again, I don't know in the States, but we certainly in the UK, we don't generally have diabetologists as a frontline service.
Speaker: They tend to come after the event once the patient's been stabilized.
Speaker: Yes, it's interesting how we have this tendency, I think, as human beings to believe that we're the experts and forget the people who actually do the work.
Speaker: And we all do it, right?
Speaker: But that's a great example.
Speaker: I mean, I can't remember the last time an endocrinologist specializing in diabetes took care initially of a patient who came in with a hyperglycemic emergency to the ICU.
Speaker: Indeed.
Speaker: Indeed.
Speaker: So we share a common experience.
Speaker: For sure.
Speaker: So the next topic is one that is extremely common.
Speaker: I think it happens every day in every ICU.
Speaker: And that's bicarbonate improves ventricular contractility and severe metabolic acidosis.
Speaker: So as we learned that giving a push of bicarbonate doesn't really fix certain things, we still seem to be holding to this idea well, but to help the heart pump a little bit more efficiently in this severely acidotic and shock patient, it does make a difference.
Speaker: So tell us a little bit about what you found there, Mervin.
Speaker: Yeah.
Speaker: So...
Speaker: As you say, Sergio, this has become established dogma.
Speaker: Oh, the patient's sick, they have a severe acidosis, and that is a reason why the heart's not pumping, rather than, well, what's the cause of the severe metabolic acidosis that perhaps might be more relevant and pertinent?
Speaker: When we do a blood gas, you know, to measure the bicarbonate, what we're measuring is a sort of extracellular measurement, and...
Speaker: it's the intracellular pH that's probably more relevant because most of the enzyme activities and so forth are occurring within the cell and there the pH actually is often a lot, well it is a lot lower compared to what we're measuring in a blood gas sample.
Speaker: So it varies from organ to organ but it's probably somewhere around the 6.8 to 7, 7.1 range
Speaker: and it's been shown again this is more sort of ex vivo type studies that in different organelles there can be this huge variation in pH some are very acidic going down to like four or five and some actually normally live in a more alkalotic environment you know going up to eight so we're making an assumption about what's going on inside the cell um with what we are measuring in the bloodstream and
Speaker: There's some animal data from, oh, you know, 50, 100 years ago, suggesting that bicarbonate is good.
Speaker: Often these studies have actually failed to use equimolar concentrations of bicarbonate.
Speaker: non-bicarbonate fluid.
Speaker: So is it the bicarbonate that's making the difference?
Speaker: Or is it the fact that the animal is just being fluid resuscitated?
Speaker: There were some very small studies 30, 40 years ago where in patients where they did look at patients with a metabolic acidosis and compared
Speaker: getting bicarbonate, I think from memory it was 8.4%, with an equimolar saline solution, which was about 5 molar, and essentially found no difference.
Speaker: So these patients were often volume deplete.
Speaker: So I think this belief that, oh, the heart will suddenly pump better purely because I've corrected the pH, a difference
Speaker: doesn't address the problem I was mentioning, that it's actually the cause of the low pH that we need to be addressing rather than just manipulating numbers so that the patient died, but they had normal pH.
Speaker: And then there are all of these different arguments against giving lots of bicarbonate for the sake of giving it.
Speaker: Shift of the oxyhemoglobin curve, perhaps if you're not blowing off the CO2, if you're giving bicarbonate quickly,
Speaker: You know, the carbon dioxide basically can't be washed out, and then it diffuses into the cell, actually paradoxically making intracellular acidosis worse.
Speaker: So again, these are more in vitro experiments, but extrapolated to patients.
Speaker: So there are potential downsides to giving the bicarbonate.
Speaker: um but also you know you're giving a high prosmolar fluid a lot of saline load etc so the you know so i think bicarbonate in the right patient is a great drug to use um there was a nice trial done in france it's being repeated at the moment it was the bicar study where
Speaker: a lot of the time people are put on renal replacement therapy because they're acidotic, and the premise of this multicenter trial from France, Samir Jabea was the main author, and it came out in The Lancet, I can't remember, a few years ago, but the argument there was, well, actually, if we...
Speaker: get on top of the acidosis so that the patient doesn't need to go on a filter, will that benefit them?
Speaker: And they actually found that there was a significant reduction in need for renal replacement therapy and a signal towards an improved outcome.
Speaker: Now, clearly, that needs to be repeated and it is being repeated as we speak.
Speaker: But I'm not completely dismissing the role of bicarbonate.
Speaker: In the right patient, it's a very appropriate treatment.
Speaker: But just to give it without actually thinking, well, what's the underlying cause of the problem?
Speaker: And that's what I should be doing.
Speaker: I'd move away from that.
Speaker: And it seems that we definitely, I mean, used to use a lot of bicarb historically, and we would use it to treat metabolic acidosis.
Speaker: And then eventually we figured out, okay, it doesn't actually treat anything for the acidosis.
Speaker: You want to treat the underlying cause.
Speaker: But this seems to be kind of the area where we kept holding on, right?
Speaker: Okay, well, but...
Speaker: When somebody is in shock and their heart's not working, that's when it really makes a difference.
Speaker: And it's one of those drugs that almost like there's a couple in critical care that are almost like last rites, right?
Speaker: Nobody dies without getting bicarb in the ICU.
Speaker: And steroids.
Speaker: And steroids, yeah.
Speaker: But thinking about it, I think, and questioning and trying again, I think it ultimately leads back to what you were saying about the renal patients is that for every therapy, it's about finding the appropriate patient.
Speaker: Right.
Speaker: And when we when we the bigger the group, the more likely is that we might be giving it to people in whom it could cause harm or not help.
Speaker: So so I think that's something that hopefully we keep talking about the promise of personalized medicine.
Speaker: But but I think at least we have to start thinking a little bit more about do I do I really need to do this or what could be the potential consequences like you mentioned.
Speaker: There are a good list of physiologic reasons that you mentioned that you could argue that maybe giving somebody in shock who's crashing bicarbonate is not going to help them but could harm them.
Speaker: Yeah.
Speaker: And when I was a lad many, many years ago, it was de rigueur to give bicarbonate in cardiac arrest.
Speaker: And just over each iteration of cardiac arrest guidelines, bicarbonate suddenly dropped down the list, list, list, and now it's fallen off.
Speaker: the list of recommendations.
Speaker: I think partly because they haven't actually done the trials, but I think people have recognised that this is something that we were just doing by rote without any decent evidence base.
Speaker: Absolutely.
Speaker: And the last topic that you talked about has to do with our, I think, our obsession with making things normal, super normal, our obsession with making things, quote unquote, right as soon as possible.
Speaker: And I guess our inability to sometimes restrain ourselves and feeling that we have to do something, right?
Speaker: And that is a hypophastotemia needs correction.
Speaker: And can you talk a little bit about this and what you found?
Speaker: Yeah, again, it's, as you say, this obsession with making numbers look normal.
Speaker: So if the patient dies or deteriorates, then we've done everything we could to achieve homeostasis or normality.
Speaker: And we've learned over the years that, well, actually, we don't have to ventilate as hard to get the carbon dioxide levels in the normal range or gas.
Speaker: ventilate hard to get the oxygen levels up or give as much oxygen, etc.
Speaker: So we can tolerate permissive hypoxemia, permissive hypercapnia, blood pressure.
Speaker: We don't have to drive the blood pressure up to the patient's pre-morbid level, etc., etc., etc.
Speaker: So I think there's been this realisation that this fixation with normality
Speaker: often doesn't help and actually may cause harm.
Speaker: And so with phosphate, yes, it's relatively cheap giving phosphate.
Speaker: Although there was interestingly a paper from Australia recently where they looked at the cost, the green cost of giving phosphate, not just the cost of the bag, but the plastic ware, et cetera, et cetera.
Speaker: And it was considerable.
Speaker: Again, when you go back to the literature and say, well, what's it based on?
Speaker: Again, there's this belief that low phosphate equals muscle weakness and other problems.
Speaker: But based on very, very, very little data, if at all, there's a few animal models where an acute drop in phosphate may potentially have been related to that, but arguably other things, other factors may have been involved themselves.
Speaker: And I'd also stress that circulating phosphate accounts for less than 1% of total body phosphate.
Speaker: We've got loads in our cells, in our bones, etc.
Speaker: So just an acute drop.
Speaker: which you see with critical illness.
Speaker: You see giving insulin will bring phosphate intracellularly.
Speaker: So, you know, basically it's a fairly starvation drops of phosphate.
Speaker: So there's very, very many causes of why phosphate should drop.
Speaker: And arguably the body's smarter than we give it credit for.
Speaker: So who knows, it may even be part of an adaptive process process.
Speaker: the phosphate drops maybe to go intracellularly because you're not suddenly excreting huge amounts of phosphate.
Speaker: So we've got this fixation with giving things.
Speaker: And my argument is, well, do we need to?
Speaker: Yes, it's a few hundred mils of fluid in a bag.
Speaker: It's relatively cheap, but it's again, one of these things that, well, if we don't need to, why do it in the first place?
Speaker: And
Speaker: A lot of people walk around chronically with very, very low phosphate levels.
Speaker: Alcoholics are a good example.
Speaker: And my pet story is I had a patient once or a number of years back who was an alcoholic, chronic alcoholic.
Speaker: And I can't remember why they came into intensive care, but essentially they were sitting out of bed eating breakfast.
Speaker: They'd improved.
Speaker: And the phosphate at the time was 0.01 millimoles per litre.
Speaker: So the normal range is 0.7 to 1.4.
Speaker: And the guy's value was 0.01, so virtually unrecordable in the blood.
Speaker: And yet he was sitting out of bed eating breakfast normally and chatting away.
Speaker: And so it made me realize that, hmm, are we just chasing numbers for the sake of chasing numbers?
Speaker: Lack of trial data again, where's the evidence?
Speaker: Actually making the numbers look normal make a blind bit of difference.
Speaker: There isn't any.
Speaker: There's a lot, again, refeeding syndrome.
Speaker: I'll probably get howls of abuse from people interested in nutrition.
Speaker: But, you know, a lot of refeeding syndromes,
Speaker: based on the phosphate dropping, but the phosphate will drop when you give insulin.
Speaker: It will drop when you start feeding, but just leave the patient alone and it'll come up in the next day or two.
Speaker: So where's the evidence that, oh, you've got to cut down the amount of food just because the phosphate has dropped because you're worried about refeeding syndrome, which I would argue is way overblown in the average critical care patient.
Speaker: There are lots of inflammatory comments from me, Sergio.
Speaker: No, but I think it's good for us to think about this, right?
Speaker: Because I think a very similar story that we're learning with some data recently is potassium and cardiac patients.
Speaker: There was a very nice study last year.
Speaker: I think it came out in JAMA in CT surgery patients.
Speaker: I think it's the hyper-K study or something like that.
Speaker: That's right.
Speaker: They just randomize patients post-cabbage to keep their potassium above like the 4.5 or 4 that everybody recommends in the cardiology world versus just, okay, if it's really low, replace it, right?
Speaker: And again, no difference, right?
Speaker: So I think that...
Speaker: We don't think of the unintended cost of this, but you talked about, and it's not only the number that we spend on a medication, the medication itself, but everything else that's associated with using things that we don't need, I think add up, right?
Speaker: And I think it's a lot of good food for thought since we're talking about refeeding syndrome, I think for us to ponder for sure.
Speaker: Yeah, 100.
Speaker: I think that's another great example of how things become established in our mind and then it becomes automatic rather than considered.
Speaker: So as we move, moving forward, obviously you gave us four great examples of what I would say are true dogmas in our practice.
Speaker: I'm sure that a lot of our listeners encounter these situations on a regular basis.
Speaker: They're very common.
Speaker: As you pointed out in the article in our discussion today, the existing evidence is either outdated or non-existent.
Speaker: So maybe there's evolving evidence that might suggest that maybe we should be a little bit more open to try to do what's best for the patient that we are treating at that given time.
Speaker: Do you have any recommendations in terms of how the individual clinician should focus moving forward?
Speaker: What are things that they can do?
Speaker: What would you recommend your trainees and the people who you're mentoring?
Speaker: I think actually I'd go even earlier.
Speaker: I think what we've got to do is reevaluate medical education as a whole.
Speaker: Increasingly, there's less reliance on thinking.
Speaker: or guidelines, and that encourages a sort of brainstem approach to treating the patient rather than looking at the patient in front of you at that point of time and trying to work out what is the best course of treatment.
Speaker: So, yes, you have to be informed by the literature.
Speaker: 100%, but that still shouldn't prevent you from actually modulating, tweaking your response to that patient.
Speaker: And obviously, rather than just doing something and walking away, it's doing something and looking at the response and then working out, is this beneficial, harmful, harmful,
Speaker: no effect, do I need to do more or less?
Speaker: So you're titrating to effect rather than just giving a standard therapy just because that's the way we're brought up.
Speaker: So I think it's very much a case of
Speaker: the way we approach teaching to encourage trainee doctors nurses etc to challenge in a polite way obviously but to actually say well what's this based on or you know go to the literature and say well is there any evidence for this or perhaps are we potentially in some patients or a lot of patients unwittingly causing harm so so i think it's just the broader
Speaker: a view of how we approach medicine.
Speaker: You know, I think, unfortunately, and I see this, you know, when I go around to get talks around the world, you know, physiology is a dying thing.
Speaker: art stroke science and that people nowadays don't rely on an understanding and appreciation of physiology to manage patients.
Speaker: It will give them fluid and at a certain point put on a vasopressor.
Speaker: We should be smarter than that, I think.
Speaker: So I think education is key.
Speaker: And I think it points out also to a paradox, which is never have we've had so much information at the tip of our fingertips yet.
Speaker: So what we need to do is not there's no value in knowing things if you can't apply them.
Speaker: And I still remember, Mervyn, when
Speaker: there was value in remembering by memory the doses of certain medications.
Speaker: This w as a long time ago.
Speaker: Now that's like superfluous information.
Speaker: You can find it out in a second, right?
Speaker: And more important is, I mean, like you said, to be more critical in applying, okay, what's best for this individual patient?
Speaker: What am I seeing?
Speaker: What can we do to help this patient move forward?
Speaker: So I think that's a great, great take-home message.
Speaker: Well, you've been on the... Go ahead.
Speaker: Sorry, no, no, I'm just literally going to congratulate you on your summing up.
Speaker: Well, you've been on the podcast before, Mervyn, so you know that we like to finish with some questions that are unrelated to the clinical topic.
Speaker: Hopefully they're not very dogmatic, but I definitely want to talk about a couple of things.
Speaker: Would that be okay?
Speaker: Yep, far away.
Speaker: So we like to talk about books.
Speaker: Last time you mentioned Factfulness from Hans Rosling.
Speaker: Since we last talked, is there any book that has really struck you or made you think recently?
Speaker: Yeah, actually, I enjoyed a book on the influenza pandemic of 1918-ish.
Speaker: It was called Influenza by a doctor called Jeremy Brown.
Speaker: And I enjoyed that because, again, there was a lot of...
Speaker: sort of resonance with how we manage or mismanage COVID as a global community.
Speaker: And I think, again, time and again, we don't learn the lessons from the past.
Speaker: And it just brought home to me, you know, perhaps a lack of awareness and appreciation.
Speaker: And we unfortunately keep on reinventing the wheel when the wheel has already existed.
Speaker: And I think, I don't know if I read that specific book, but I definitely read a book on the 1918 influenza pandemic.
Speaker: And I agree, it was very, very insightful.
Speaker: And the Spanish flu that started in Kansas, right?
Speaker: Always interesting to know, I mean, how things really happen.
Speaker: But like you said, I think our problem is that we're prisoners of our own perspective and our perspective is very limited in time, right?
Speaker: And if you go a little bit farther,
Speaker: behind in time usually find very similar situations to what you're finding at the present moment, whether it be a pandemic, a political situation.
Speaker: And I think that we could be a little bit better in trying to learn from those experiences.
Speaker: I think that we'll definitely put that in the show notes.
Speaker: Yeah, and also from others' experiences, I think, again, using COVID as an example, obviously it happened in China and then hit Italy, France, etc.
Speaker: And we could have learned, you know, the UK, US, etc.
Speaker: We could have learned from the experiences a lot more of how the Italians were coping and what they were doing rather than, you know, making up our own rules.
Speaker: And certainly the inconsistencies, and I'm not just talking about the UK, I know in America too, you know, there were government recommendations that often got changed quite rapidly.
Speaker: But at the same time, different hospitals were applying different criteria, rules, regulations, again, often based on no good data.
Speaker: And it just struck me that, especially now with a globally well-connected community, the ability to actually pass reliable information on should have been a lot better.
Speaker: Absolutely.
Speaker: So the next question, Mervyn, is about music.
Speaker: Is there like a music album or particular piece of music that you would want to have with you if you were stuck on an island or maybe since we're talking about pandemics, isolated in a new pandemic?
Speaker: Hopefully not.
Speaker: I'd probably go for something classical because the beauty of those is, you know, like a boxed collection, you know, be open symphonies or something.
Speaker: So you've got the quiet periods and you've got the, you know, the loud, noisy, dramatic bits.
Speaker: And so depending on your mood, you can pick the pastoral symphony and you can have when you're feeling a bit more energetic or want to be woken up, you can go into...
Speaker: Beethoven's 5th or 9th, you know, the bits of it.
Speaker: So, you know, so it's very much a case of dipping into what mood you're in at the time and pick the music to soothe that mood.
Speaker: Perfect.
Speaker: Is there something you've changed your mind about recently?
Speaker: Good question.
Speaker: I think...
Speaker: I think AI in the sense that there's like a lot of things in medicine, there's been, you know, in the world in general, there's huge amounts of hype.
Speaker: And...
Speaker: I'm encouraged by the progress of AI, yet I'm still very, very cautious that, you know, and you can just see over the years how AI, you know, whether it's Google Maps or whatever, you know, how it's changing our lives without us necessarily appreciating or realizing it.
Speaker: I think the application to medicine I'm still a little bit cautious about, especially I think as a prop in terms of helping the clinician.
Speaker: But I think in terms of AI actually dictating therapy, I still think we're quite a way beyond that.
Speaker: I think the way obviously technology is evolving,
Speaker: it might be sooner than I think.
Speaker: But I think in the first instance, I'd very much use it as a prop to aid the clinician rather than to replace the clinician with a machine because I think medicine is still an art as well as a science.
Speaker: For sure.
Speaker: And finally, to close, is there something you want everybody who's listening to know?
Speaker: Could be just a parting thought, a quote, or a fact.
Speaker: Yeah.
Speaker: Don't forget physiology.
Speaker: I think that's the perfect place to stop.
Speaker: I think it's a very important message.
Speaker: And I want to thank you again, Mervyn, for your expertise, sharing your expertise with us, your time, and always for making us think a little bit outside of the box and question what we're told to be true at the bedside.
Speaker: Love it.
Speaker: It's very kind of you to invite me and thank you very much and hope that your listeners also get a few nuggets from this hour or so.
Speaker: Thank you.
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.
