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: Albumin is commonly used across a wide range of clinical settings and critical care practice.
Speaker: However, critical care clinicians vary widely in how and when they use it.
Speaker: In today's episode of the podcast, we will discuss the use of intravenous albumin in critical care.
Speaker: Our guest is Dr. Jeannie Callum, Director of Transfusion Medicine and Professor of Pathology and Molecular Medicine at Queen's University in Ontario, Canada.
Speaker: Dr. Callum's research focuses on blood utilization, hemostasis in the bleeding patient, and transfusion-related errors.
Speaker: She has received numerous awards and published extensively.
Speaker: Dr. Callum is the lead author of Use of Intravenous Albumin, a guideline from the International Collaboration for Transfusion Medicine Guidelines, published earlier this year in CHEST.
Speaker: Jeannie, welcome to Critical Matters.
Speaker: Thanks very much for having me.
Speaker: Albumin is one of my favorite topics, and I'm just really excited to get the guideline out to all the people in your critical care listener group.
Speaker: Absolutely.
Speaker: And I think it's like I mentioned in the introduction and we discussed in pre-recording conversations.
Speaker: It's something that is often utilized, so used, but often misused as well in the ICU and definitely worth taking a pause and reevaluating the guidelines and the available literature and having a conversation of where it really should be utilized and where maybe we should pause and think a little bit what we're doing.
Speaker: So as an introduction, could you tell us why you think intensivists should really care about this topic?
Speaker: So I think really until I started actually looking at the evidence for albumin, I didn't spend a lot of time worrying about albumin.
Speaker: I considered it was pretty inert.
Speaker: It was pretty safe.
Speaker: Perhaps we were overusing it, but it didn't cost as much money as maybe some of our other blood products.
Speaker: But then as I got more and more into depth when we were developing the guidelines, I actually think this is a really important topic that we need to address.
Speaker: So first of all, I think intensive issue care, because I think there's concerns about patient harm.
Speaker: The studies that are now more modern and they're better at tracking adverse events are seeing harm in the patients that are getting albumin compared to the patients that are getting placebo or normal saline or some other fluid.
Speaker: particularly transfusion associated circulatory overload.
Speaker: But also a really interesting finding that came out of the cardiac surgery literature with increased bleeding.
Speaker: And we'll talk about that later when we talk about, you know, potential harms.
Speaker: But that really had never been thought about prior to the cardiac surgery literature.
Speaker: There's also concerns not just about diluting your clotting factors causing bleeding, but also diluting your natural anticoagulants causing thrombobolic complications.
Speaker: And then as most intensiveists already know, there are concerns about giving albumin to patients with traumatic brain injury and increasing their mortality rate.
Speaker: And I think that's a pretty commonly known concern.
Speaker: What I think intensivists don't actually also think about is, well, where's it coming from and what is the harm to the donor when they donate the plasma that gets used to manufacture the albumin?
Speaker: And remember, donors, when they have an apheresis plasma run, can also have reactions that lead to the donor harm.
Speaker: And I think we need to consider about like the two patients, both the donor and the recipient.
Speaker: I think we need to care also about the cost of this product.
Speaker: at about $130 a bottle US.
Speaker: About the environment, if it's not really necessary, should we really be using all that plastic tubing and all the production costs and the transport of the album into the hospitals?
Speaker: I think I worry about the time that nurses spend infusing it.
Speaker: I'm sure they have something better that we could use their time for in terms of caring for the patient.
Speaker: And so I think there are a lot of reasons why we need to kind of step back and think about every time we prescribe albumin, do we really need it or are we doing sort of downstream harm to both the patient, the donor and the healthcare system?
Speaker: Excellent.
Speaker: And one of the things that we talked about before that was at least interesting for me as a different perspective is that there are some differences in the way albumin is managed and utilized across different countries.
Speaker: Could you mention a little bit of that?
Speaker: Yeah, so there's huge differences in the per capita use of albumin across countries.
Speaker: The United States is currently the gold medal user for albumin.
Speaker: And if my back of the envelope calculations are correct, you use about 600 grams per thousand population in the United States.
Speaker: And you're probably pretty similar to say Australia, they're running around 450.
Speaker: I'm not sure that's terribly different.
Speaker: Canada is about half of the U.S. and I think we use way too much and we're sitting around 250 grams per thousand population.
Speaker: But there are countries like New Zealand that use almost none and they're running around a hundred grams per thousand population.
Speaker: So it really shows why there's so much variability.
Speaker: It really calls for, you know,
Speaker: Perhaps New Zealand is slightly underusing, but certainly countries like Australia, Canada, and the U.S. are overusing it.
Speaker: There have been some papers looking at, you know, variability.
Speaker: We looked at the use of albumin in a clinical trial that we had done in cardiac surgery that related to fibrinogen replacement.
Speaker: But then we had collected, you know, how much albumin was given to patients, and the
Speaker: Difference were huge across the study sites, range from 5% to 100%.
Speaker: And there was no suggestion that the cardiac surgery patients getting a lot of albumin were doing better.
Speaker: If anything, it was suggesting they were doing worse.
Speaker: So I think there's variability between doctors, between hospital sites, between countries.
Speaker: And I don't think there's a really good reason to explain that variability other than just the culture of medicine.
Speaker: And I think like so many things in medicine, variability is a prime opportunity for improving outcomes and improving our processes and trying to understand how we can harmonize and maybe decrease that variation.
Speaker: So why don't we talk about the pharmacology of albumin like a one-on-one real quickly.
Speaker: And one of the things that I believe would be a good starting point would be what is albumin?
Speaker: Is it a drug or a blood product?
Speaker: I think that's really important.
Speaker: So it's a blood product.
Speaker: It's manufactured from plasma that's collected by apheresis from donors that come in several times a month and donate around 750 mils of plasma.
Speaker: And then that plasma gets taken to a manufacturing site and it's pooled and then manufactured into all of its constituents.
Speaker: And one of the things that's taken off during the manufacturing is albumin and it's bottled up.
Speaker: What's really interesting is many countries that supply through a blood bank because it's a blood product, but I think it's common in the United States, it comes through a pharmacy.
Speaker: And so that might also...
Speaker: You have the misperception that it's a pharmaceutical, but it's not made by recombinant DNA technology.
Speaker: It's a pretty big protein.
Speaker: It's about 70 kilodaltons.
Speaker: There is no recombinant albumin available for patient infusion.
Speaker: So because it's a blood product in every country, you need to get consent and you need to have a conversation with the patient about the risks, the benefits and the alternatives to albumin because it is a blood product.
Speaker: And I think that might be, like you mentioned, a big difference in terms of culture that most clinicians in the United States, as they just order it and get it from the pharmacy, are not thinking of it as a blood product.
Speaker: And that, I'm sure, has an influence in how you use it or misuse it.
Speaker: What about...
Speaker: What about the intravascular half-life and the oncotic effect?
Speaker: Those have always been proposed as big reasons why we should consider in some situations albumin.
Speaker: How much of that is truth or what is myth and what should we know as clinicians?
Speaker: Yeah, so I think if you gave up, albumin is perfect for like a normal volunteer because in a normal healthy person, an albumin infusion, the half-life is a couple of weeks.
Speaker: So it lasts like a really long time.
Speaker: But if you look at a patient that's in the intensive care unit, it only lasts for probably a couple of days, one day, two days, something like that, because albumin only stays in the intravascular space if the glycocalyx and endothelial cells are intact.
Speaker: Otherwise, it just sort of leaks out.
Speaker: And one of the reasons we know this must be true is because a trial was done in Australia called the SAFE study, where intensive care patients that were needing fluids were randomized to either normal saline versus getting albumin.
Speaker: So you would have expected some sort of a four to one ratio of the amount of albumin versus saline.
Speaker: saline that was given because you need a lot less of it to maintain the intravascular volume.
Speaker: But the ratio wasn't, you know, four to one.
Speaker: It was only 1.4 to one.
Speaker: So yeah, you used a little bit less fluid, but very little difference.
Speaker: And I think that that's because the albumin is leaking out of the intravascular space.
Speaker: So it's not actually staying where we want it in a sick patient.
Speaker: I think it probably does a bit better in the first six hours.
Speaker: But thereafter, I don't think there's a huge difference.
Speaker: There was a really good kind of almost like an investigative journalism piece that was written by a researcher in Canada called Donald Rettelmeyer.
Speaker: Because he wondered about, well, where's all the albumin going when we pump it into a sick patient?
Speaker: And, you know, he sort of went through, well, it doesn't come out in the urine because we've actually measured.
Speaker: It's obviously not coming out in the skin because we would see it.
Speaker: doesn't necessarily appear to be just going in the extra the extravascular space because you would expect it to become reabsorbed at some later point when they're back on the ward and we would see very high albumin levels when it got all reabsorbed but it doesn't it takes months and months for a sick patient to recover their albumin levels and so his hypothesis it must be leaking out into the gut
Speaker: and then it just out of the patient completely.
Speaker: So I think in a sick patient in the intensive care unit, albumin actually isn't that much better than some sort of a crystalloid alternative.
Speaker: And you did mention, Ginita, the SAFE trial, and we talked a little bit about the perceived safety of albumin by clinicians.
Speaker: And I think that that trial, that large clinical trial from Australia and New Zealand in a great way kind of left that message for a lot of intensivists that the outcomes might not be better, but hey, it's safe.
Speaker: But there are some dangers, right?
Speaker: Could you talk a little bit more in detail about the potential harms associated with albumin and what we've learned lately?
Speaker: Yeah, so because so many modern trials have been done in the last decade with albumin, they've collected the adverse events with much more scrutiny than we'd ever done before.
Speaker: So a bunch of trials were done in patients with cirrhosis.
Speaker: A group of trials were done in patients who were given albumin when they came in with an infection outside their peritoneal cavity.
Speaker: randomized to albumin versus, you know, just antibiotics with, you know, regular fluid responsiveness.
Speaker: And they found a fourfold increased risk in the rate of congestive heart failure for the patients that got albumin.
Speaker: And that was consistently seen across all the randomized trials and then summated into a systematic review.
Speaker: That same risk was seen in a very large trial that was published in the New England Journal of Medicine called the ATIRE trial that was led by Louise China.
Speaker: And in that trial, they gave albumin to target an albumin level of 30 in patients with decompensated cirrhosis that were in the hospital.
Speaker: and they managed to maintain the albumin level at 30.
Speaker: There was actually no difference in any outcome in that study, but there was an increase in serious adverse events, particularly the respiratory adverse events, because it was putting patients into heart failure.
Speaker: So there's no question that we need to be very careful about how we onboard it so that we don't put people into heart failure.
Speaker: And then,
Speaker: There was this concern about increased bleeding.
Speaker: So the Albix trial was a randomized trial in cardiac surgery patients that was conducted in Finland, where they randomized patients to getting all of their fluid as albumin for the pump prime and for fluid resuscitation post-cardiac surgery compared to just Ringer's lactate.
Speaker: And what was surprising in that study is patients that got albumin had higher rates of re-operation for bleeding and higher bleeding risk, which raised the hypothesis that maybe albumin dilutes your clotting factors.
Speaker: And in a bleeding patient, maybe we shouldn't be giving them so much albumin.
Speaker: What was interesting is actually when you go back to the SAFE study and you looked at red cell transfusion rates, it was actually higher...
Speaker: in the SAFE study in the albumin-treated patients.
Speaker: My interpretation of that when I read the SAFE study decades ago was it was just, it was hemodiluting patients.
Speaker: So they were more likely to fall below your transfusion trigger.
Speaker: So they were more likely to get a red cell transfusion.
Speaker: But we don't actually know if albumin makes you bleed more.
Speaker: And on the reverse, Dr. Ted Workington, who is a
Speaker: A clotting expert from McMaster University reported on a series of patients in the New England Journal of Medicine that developed peripheral gangrene after repeated albumin infusions.
Speaker: And he had samples on those patients so he could go back and show that the albumin was sequentially reducing the natural anticoagulants, and then the patients ended up with peripheral gangrene from thromboses.
Speaker: The only other kind of two things that we know is some patients get hypotension from albumin because albumin has some bradykinin, so it's particularly relevant if a patient is on an ACE inhibitor.
Speaker: And also, you can get full-blown anaphylaxis in patients that are missing certain proteins.
Speaker: And two really common proteins that humans are missing are IgA.
Speaker: So you can be IgA deficient with an anti-IgA, but also have toglobin deficiency.
Speaker: And so there have been case reports of fatalities
Speaker: from albumin transfusion in people with haptoglobin deficiency.
Speaker: In Canada, it's really important around this consent issue.
Speaker: In Canada, I don't know if it's true in the United States, but we are by regulations required to tell patients they had a blood product after they were admitted to hospital and we have to send them letters.
Speaker: So they often will get this letter after cardiac surgery to say, oh, you got out, you got a blood product.
Speaker: It doesn't say what kind of blood product.
Speaker: And there are patients always surprised because their surgeons told them, oh, we managed to get you through surgery without any blood products, forgetting about albumin is a blood product.
Speaker: And then we have an upset patient who retrospectively we have to talk through why they had to get albumin at the time of their cardiac surgery.
Speaker: Yes, I think albumin's pretty safe, but I think we need to be extremely cautious and really have a thoughtful conversation at the bedside with both the care team as well as the patient and their family about whether or not albumin's indicated in that particular patient.
Speaker: And I don't think that's the case in terms of the blood product consent or disclosure in the United States.
Speaker: I know that patients regularly get albumin, and I'm pretty sure that they don't get a letter or notified that they got a blood product.
Speaker: So that is an interesting difference.
Speaker: But again, another reason for us at least to pause and really think, okay, when is it the right time to give albumin and when it might not really be helpful but can also cause harm.
Speaker: So I would like to now jump, Jeannie, into the different categories of patients that you've discussed in the guidelines.
Speaker: Now, obviously, the guidelines discuss patients that don't relate to the ICU, like pediatric ICUs and pediatric patients, and we won't talk about them.
Speaker: But I would like to start with the general critically ill adult patients.
Speaker: And what's the recommendation or what were the findings of the group for the guidelines on the use of albumin as a first-line volume replacement in critically ill patients?
Speaker: So the guideline group recommended against the use of albumin as first-line treatments for fluid resuscitation in the critically ill adult patient.
Speaker: And that was based on a lot of evidence.
Speaker: So there are, I think we found about two dozen systematic reviews that had been done looking at, you know, different, you know,
Speaker: time periods looking at randomized control trials.
Speaker: So we're pretty certain as a frontline, it's not useful.
Speaker: There are two big studies that contribute the most evidence, the SAFE study that we talked about before, as well as a trial that was done in patients in ICU with infection called alveos.
Speaker: You know, both SAFE and alveos, the relative risk of death was pretty close to 1.0.
Speaker: And so as a
Speaker: Frontline, everybody, I don't think so.
Speaker: But for, you know, there might be some rescue use for a patient that's not responding well to a crystalloid frontline along with your inotropes and antibiotics or whatever else you're managing your patients with, that there might be some role as a rescue therapy.
Speaker: And that's also included in your surviving sepsis guidelines.
Speaker: But what's really clear is we don't have any studies for that.
Speaker: So we don't know what kind of albumin you should give.
Speaker: Should you give the 5% formulation or 25%?
Speaker: How much would you give?
Speaker: Or how long and when would you trigger it?
Speaker: Is it after three liters of crystalloid you should switch over to albumin?
Speaker: None of that's been flushed out in any kind of trials.
Speaker: And so certainly that calls for more trials evaluating albumin as a rescue therapy and patients just not responding to frontline crystalloid.
Speaker: So as first line, no evidence.
Speaker: As rescue, maybe, but we still don't have the details.
Speaker: And like you said, more studies would be needed.
Speaker: What about specific diseases or subcategories of critically ill patients, like patients with thermal injuries or patients with ARDS?
Speaker: Yeah, so fortunately, at least some trials have been done for ARDS.
Speaker: There are two small, both industry funded studies that use what we call in Canada, the albumin LASIK sandwich, where you kind of
Speaker: you know, merge both albumin and Lasix to try and get fluid off of patients.
Speaker: There's no question that by giving that combo to an ARDS patient, obviously that's highly selective, that doesn't have any hypotension because you can't take fluid off a hypotensive patient.
Speaker: It does take off weight off of patients, so they lose weight.
Speaker: But
Speaker: Patients losing the fluid weight, it doesn't translate into getting more patients off ventilators, getting patients out of the ICU faster.
Speaker: It appears to just have some sort of cosmetic effect.
Speaker: Yes, you're taking fluid off patients, but it's not translating into improved patient-important outcomes.
Speaker: In thermal injuries, there are actually four randomized controlled trials comparing crystalloids to albumin and burn patients.
Speaker: And those trials don't suggest that albumin is beneficial in burn patients.
Speaker: Most of the patients that were enrolled in those trials didn't have burns greater than 40% of their total body surface area, where you would probably use albumin.
Speaker: So I think there's...
Speaker: some equipoise for big burns after that first 24 hours and you have fluid creep and you just can't seem to maintain a good urine output and blood pressure that you might consider albumin.
Speaker: Because albumin didn't really pan out in those trials, there's some renewed interest in studying plasma as the rescue fluid when crystalloids aren't working properly.
Speaker: And so it's going to be interesting to see what those studies find.
Speaker: And now's a good time for the world to be looking at that because we now have safer plasmas, these pool of plasma products that have an 80% reduction in your risk of adverse events.
Speaker: Maybe you can get away with plasma, whereas before with our regular fresh rose and plasma, maybe you couldn't do that.
Speaker: So again, air gas, thermal injuries, doesn't look like it's a benefit across the board, maybe in highly selected patients.
Speaker: The other category I wanted to ask you about within the critically ill adult patient population is we all recognize that patients are critically ill who have lower albumin levels in their serum might have worse outcomes or be sicker.
Speaker: And I think intensivists love to normalize numbers.
Speaker: So is there any value in giving IV albumin in patients with low serum albumin?
Speaker: Yeah, so I think that this is where you can basically say you should never be treating an albumin level with albumin.
Speaker: That was historically tried in some pediatric trials.
Speaker: And then there was a study done in patients that were undergoing liver resection surgery.
Speaker: And of course, those patients, when they lose a lot of their liver, often have low albumin levels.
Speaker: Again, no benefit.
Speaker: And then most recently in the ATIRE study that we talked about earlier, where they were targeting this albumin level and decompensated cirrhosis patients to 30, there was absolutely no benefit.
Speaker: What's kind of like also interesting about that trial is when they looked at
Speaker: their sub-study of laboratory values in the patients that got alabamin versus not, looking at cytokines and markers of your fluid responsiveness and your glycocalyx, how intact it was, there was nothing.
Speaker: There was absolutely no difference between those two groups.
Speaker: So I really think, yes, people with low alabamin levels, they have worse outcomes in the ICU.
Speaker: It's the same.
Speaker: Patients in the ICU with lower hemoglobins, they have worse outcomes, but red cell transfusion doesn't change the fact that they have bad outcomes.
Speaker: I think we should think of albumin in that same way.
Speaker: So never ever give an albumin transfusion solely for the number.
Speaker: Perfect.
Speaker: I would like to transition to another category of patients that often present in the ICU, which are patients undergoing renal replacement therapy.
Speaker: And I think that the two areas where I've seen nephrologists recommend or utilize albumin and wanted to hear what the guidelines group found are
Speaker: was the use of albumin to prevent intradialytic hypotension, so hypotension during dialysis treatments, and the use of IV albumin to improve ultrafiltration during renal replacement therapy.
Speaker: Yeah, so I think that this is a really common practice that people are giving albumin for this.
Speaker: I think it's really common in some hospitals, and it's absolutely never done in other hospitals.
Speaker: And you have this divergent practice because of a kind of evidence-free zone.
Speaker: We have a total in a bunch of randomized trials in small numbers of patients, totaling around 100 patients for all four trials, where there's sort of a randomized crossover.
Speaker: So you would have a run with albumin and then a run with saline.
Speaker: And it's really, there's no definitive improvements in either the hypotension or the ability to achieve good ultrafiltration.
Speaker: Definitely nothing to say this should be standard of care in any kind of renal replacement therapy.
Speaker: Dr. Ted Clark from the University of Ottawa is doing an 800 plus patient randomized trial where patients will get randomized to albumin versus saline for their
Speaker: dialysis runs when they're admitted with new AKI to the intensive care unit.
Speaker: So hopefully that will at least give us a glimpse into, is there any flavor that people do better?
Speaker: Does it prevent them having renal failure on discharge from hospital and then permanently on dialysis?
Speaker: Does it get them out of ICU, shorten the number of dialysis days?
Speaker: Because every day that you're in the ICU is very expensive.
Speaker: dialysis is super expensive.
Speaker: So even if it saved you one day, it would be great.
Speaker: So wait for that study.
Speaker: It's called the Alter AKI study.
Speaker: So we're looking for that and maybe we can discuss it when it comes out again in the podcast.
Speaker: The other category of patients that we already talked about a little bit and you mentioned, which I think is a big area of utilization, at least in our practice in the United States, is the patients undergoing cardiovascular surgery.
Speaker: And I think there's two aspects of the use of albumin here that I wanted to ask you about and hear from you what the guidelines group found.
Speaker: First is albumin for priming the cardiopulmonary bypass circuit, which is something that intensivists might or might not be aware, but in many places has been proposed and practiced.
Speaker: And second, which is more in the realm of the ICU, is the use of albumin for post-op volume resuscitation in cardiac surgical patients.
Speaker: Yeah, so to inform the guideline, because no one had done a recent, really honestly, any systematic review of the evidence in cardiac surgery, we undertook that and we published that in the British Journal of Anesthesia.
Speaker: So it's basically a flop.
Speaker: So it doesn't do, albumin doesn't do anything for cardiac surgery.
Speaker: So we looked at all the trials that were done in pediatrics and adults and neonates where patients had been randomized to albumin for the pump prime or for volume resuscitation or for both.
Speaker: And we looked at every possible outcome that our systematic review group deemed was important.
Speaker: Things like mortality, length of stay, rate of renal failure,
Speaker: you know, any other kind of patient important outcome.
Speaker: And there was no benefit.
Speaker: The only change we saw is if you get albumin, your albumin levels are better, but that's just the laboratory test result.
Speaker: We don't really care about that.
Speaker: And then the biggest study that contributes to that was the alibic study out of Finland.
Speaker: And honestly, that one raised the concern for some harm.
Speaker: So I think if there's any place where we need to do a bit more aggressive deprescribing of albumin, it's in cardiac surgery, where maybe it's actually not just kind of neutral.
Speaker: It's actually harmful to patients.
Speaker: And certainly it's costing money.
Speaker: It's not doing anything.
Speaker: So we need to stop doing that.
Speaker: I think for a long time, nobody's been priming the bypass circuit with albumin.
Speaker: But now I really think you can't have a strong opinion that albumin should be a common thing that we do for cardiac surgery patients, adults or kids.
Speaker: In a lot of environments, I have seen that albumin might be a choice for the surgeons.
Speaker: They really seem to push it forward.
Speaker: And perhaps, I mean, socializing a little bit more, the potential effects on bleeding would be a way to dampen that enthusiasm because if there's something they don't like is bleeding after their surgeries.
Speaker: So definitely something that people should be aware of and just understand that the data doesn't really support it as being beneficial.
Speaker: And there is data that might indicate that it could cause harms for patients.
Speaker: Yeah, I don't think that message has been nicely knowledge-translated out, that not only is there no benefit, but maybe there might be harm.
Speaker: And the last group is patients with end-stage liver disease from cirrhosis.
Speaker: And I think that here we have a couple of areas where albumin has been utilized.
Speaker: And I definitely want to hear from you in terms of what the guidelines recommend.
Speaker: The first one that goes way back to my days as an internal medicine resident working on the liver wards was the use of albumin in patients with cirrhosis and ascites who undergo large volume paracentesis.
Speaker: What did the guidelines group find on this particular use?
Speaker: So we made a recommendation that gastroenterologists, hepatologists, and I guess sometimes this happens in the intensive care unit where they need a paracentesis when they're admitted to ICU, that we should continue using albumin, which is a pretty standard of care.
Speaker: But to recognize all we know right now, given the poor quality of the evidence, is that it improves your renin levels post large volume paracentesis.
Speaker: it changes your laboratory test results pretty substantially.
Speaker: So we think that large volume paracentesis without some sort of fluid replacement creates a major stress on your fluid status that potentially could lead to increased rates of hypertension, falls, renal failure.
Speaker: But we don't know because nobody's ever done a big enough study to know whether or not it changes patient important outcomes.
Speaker: We also don't know is, are there alternatives such as mitodrine or abegasaline that might be just as good as albumin?
Speaker: Because people haven't tested that very well, looking at patient important outcomes.
Speaker: And so, yes, we suggested doing it.
Speaker: Low certainty of evidence, weak recommendation, but a huge call.
Speaker: We need a trial because even that is pretty borderline.
Speaker: If you're doing a paracentesis and you take off less than five liters, you definitely don't need to do that.
Speaker: And I see that happening commonly, that people start their paracentesis, hang a bottle of albumin.
Speaker: Oh, I only took off a liter.
Speaker: You know, I won't give any more albumin, but they still gave albumin unnecessarily.
Speaker: So I think we can still somewhat optimize the use of it for large volume paracentesis.
Speaker: Perfect.
Speaker: What about the use of albumin in patients with cirrhosis and infections?
Speaker: And I think that here it's worth making the distinction of infections that are caused by spontaneous bacterial peritonitis, very common in this patient population, and something we commonly see in the ICU, versus infections that are extraperitoneal in origin, which are also common in the ICU.
Speaker: Okay.
Speaker: So this is where the evidence shows this conflicting outcome.
Speaker: So where it's beneficial for patients with infections from spontaneous bacterial peritonitis, but if you have pneumonia or you have urosepsis, it's possibly harmful.
Speaker: So in cirrhosis with spontaneous bacterial peritonitis,
Speaker: The trials are small, but they're consistent, and they consistently show a reduction in death and renal failure with the commonly used dose that was used in these trials of a big dose on day one and then a big dose on day three.
Speaker: No one's actually flushed out what the appropriate dose should be, but that was the dose that was used in the trials.
Speaker: One of the criticism of all of these trials in the SBP area is that nobody prescribed the fluid inotrope treatments for the control arm.
Speaker: They just got antibiotics and the doctor looked after the blood pressure.
Speaker: They didn't have a well-prescribed fluid resuscitation arm.
Speaker: And so people have criticized those studies where saying they're not valid because they weren't, you know, there were problems with the methodology.
Speaker: What was interesting on our guideline group is that many of the hepatologists said, oh, I don't use that day one, day three dose on most patients because I think it causes heart failure.
Speaker: So I spread it out over three days and that was the first time I'd heard of, oh, I don't actually follow the dose that was given in the trials.
Speaker: So...
Speaker: I tell my trainees, use this dose for the patients that aren't at risk of heart failure.
Speaker: But if you're concerned at all about heart failure, slow it down, give it over more days to minimize the risk of fluid overload.
Speaker: And again, this is a weak recommendation based on very small number of patients randomized into clinical trials.
Speaker: In contrast, in patients with infections someplace else,
Speaker: The systematic reviews of all the randomized trial suggest it's not beneficial in terms of mortality or renal failure or other important outcomes like length of stay, stay in the ICU, and it causes heart failure.
Speaker: And a lot of those studies are newer than the ones in SBP, which make me concerned enough that I really think we need another big trial, a definitive trial in patients with SBP to really confirm and
Speaker: you know, correct some of the methodologic concerns in those trials about no fluid resuscitation plan in the control patients.
Speaker: So in summary, obviously, even though it's a recommendation to do for the SPP, two things to note.
Speaker: One is that the way it's administered is still unclear, but it's not as fluid resuscitation, but more like a dose on day one and day three in the trials or over several days, like you mentioned, if you're concerned with heart failure at a smaller dose.
Speaker: And the second thing to also highlight is that we have not seen the same benefit in non-SPP infections, and that still needs to be understood a little bit better.
Speaker: Yeah, and I think a lot of my trainees, when they give 100 mils of 25% albumin, they don't really understand that that's a 500 mil intravascular volume resuscitation.
Speaker: So if you give
Speaker: three, four bottles.
Speaker: Four bottles is two liters of volume expansion in a short period of time.
Speaker: And so you can see that an older patient with heart failure who's already fluid overloaded might not tolerate that.
Speaker: And so just understanding the fluid shifts that happen after hyperonchotic albumin.
Speaker: And the last group of patients, which we talked in outside of cirrhosis, but is the use of albumin to treat, again, low serum albumin in patients who are hospitalized with decompensated cirrhosis.
Speaker: And some people have argued that it might help reduce kidney failure, rates of infection, and even improve mortality.
Speaker: What did the guidelines find in this particular subset of patients?
Speaker: Yeah, in this group of patients, we found a very large randomized trial called the ATIRE study.
Speaker: So this is pretty definitive, 777 patients to albumin to target to 30 versus just standard of care, let the albumin drip down.
Speaker: And there was no benefit in terms of their composite endpoint, which is a combination of new infection, renal failure, death.
Speaker: And there were more adverse events in the patients getting albumin.
Speaker: So there was no benefit and there was clear harm.
Speaker: And when they did sub-studies looking at
Speaker: markers of the clinical calyx, the cytokines, vasoactive proteins, and all that other kind of stuff in a subsidy, and they didn't find it did anything.
Speaker: So I think that, yeah, no, don't do that.
Speaker: I just think that's just wasting money, wasting albumin.
Speaker: As we wrap up the conversation on the guidelines, could you give us like an overall summary and some of the common pitfalls that clinicians should avoid based on the work that the guidelines group did in really evaluating the available literature that is currently available to us?
Speaker: So I think the first thing is I wouldn't be an albumin enthusiast.
Speaker: Even in the ones where we made recommendations that you should use it in large volume paracentesis and SVP, they're based on poor evidence, limited number of patients randomized into trial.
Speaker: So there just isn't the data there to support any evidence-based physician being an albumin enthusiast.
Speaker: And so be pretty cautious in your prescribing.
Speaker: And I think you need to now think about the risks before you prescribe.
Speaker: Whereas before you were just thinking about the benefits.
Speaker: Now I think we need to weigh the benefits and the risks nicely.
Speaker: So even if you give it, think thoughtfully about how are you gonna onboard it without causing CHF?
Speaker: Should you be avoiding it in the bleeding patient because of what was seen in the cardiac surgery trial?
Speaker: Avoiding it in patients with TBI that we've pretty much known for a long time that probably we should do that.
Speaker: And I don't think you should ever give it based on an albumin level.
Speaker: Hopefully nobody's doing that.
Speaker: And I really think we're at the point where albumin is really for a very niche population of patients rather than kind of a ubiquitous fluid that's used in the critical care population.
Speaker: One of the things that was clear to me after reading the guidelines is that there are still a lot of unanswered questions and that the available studies obviously are few and far apart and not the highest quality.
Speaker: Are there any ongoing studies that you think should be on our radar?
Speaker: You mentioned one earlier, but are there any other big studies with albumin that should be on people's radar and see what they teach us?
Speaker: Yeah, so I think probably the one that your listeners are going to be most interested in is there's a 1,600-patient septic shock albumin trial that's ongoing.
Speaker: So I think that that should help confirm the findings of albios and other trials that in septic shock patients, maybe it's not necessary.
Speaker: In addition, there's another smaller trial of 360 patients with community-acquired pneumonia.
Speaker: Again, looking at that kind of impact
Speaker: Infectious population that's in the intensive care and both septic shock and pneumonia are pretty common reasons for admission to critical care.
Speaker: We talked about the ultra AKI study that's being done in critical care patients with the new AKI, giving albium and versus saline for their dialysis runs.
Speaker: There's actually another cardiac surgery trial that's ongoing in Australia.
Speaker: It has the same name.
Speaker: It's ALBEX.
Speaker: I've been calling ALBEX Finland and ALBEX Australia, so nobody gets confused.
Speaker: It's in high-risk cardiac surgery patients versus the ALBEX trial that was in Finland, but it's more all comers.
Speaker: So it's just high risk.
Speaker: So hopefully that will reconfirm the findings of the ALBEX study.
Speaker: And then there's a last one, which is an outpatient trial, which you would think, oh, critical care physicians don't need to hear about this.
Speaker: But I think you need to be watching the results of this, because I think if it's a positive trial, it could have major impacts on your access to albumin in the critical care population.
Speaker: This is outpatients with bad cirrhosis that are doing badly as really a palliative care strategy.
Speaker: It's 400 patients.
Speaker: And the reason it's important is there were two randomized trials before COVID.
Speaker: called ANSWER and the VACS study.
Speaker: And one was positive and one was negative.
Speaker: And so people are doing it.
Speaker: But if this third trial is a positive trial, you will see hepatologists start using albumin in outpatients, and that's gonna put pressure on supply.
Speaker: And the second, you know, the biggest place we use it is critical care.
Speaker: And so I think we're gonna start having a little bit of fighting over the albumin if that cirrhotic trial in outpatients is positive.
Speaker: And the last trial actually reminds me of something I was thinking as you were talking at the beginning, is that when you don't think, when we think of blood products, we always think of it's not a limited resource, right?
Speaker: So we try to be more, better stewards of blood products because we know that
Speaker: They're not available in unlimited supplies to us.
Speaker: On the other hand, when clinicians think of albumin as just fluid, right, one type of fluidicitation, I don't think that same stewardish approach is in place.
Speaker: And they really believe that they can keep ordering as much as they want.
Speaker: But like you mentioned, if this is the case, we might start seeing that even if you order it, it might not be available for you.
Speaker: Yeah.
Speaker: So, so I think, watch that study.
Speaker: Um, uh, I think it's, uh, uh, it might, you know, cause a little bit of a scramble on albumin supplies during COVID.
Speaker: Um, there were shortages of, uh, albumin, uh, particularly 5% albumin.
Speaker: Um, and so I, I don't think we're,
Speaker: completely rock solid in our albumin supplies.
Speaker: The system must be pretty fragile if COVID can disrupt albumin.
Speaker: For sure.
Speaker: One of the things that we like to do as we wrap up the podcast, Ginny, is to ask you a couple of questions unrelated to the clinical topic, just to tap into the wisdom of our guests.
Speaker: Would that be okay with you and a good way to close?
Speaker: Oh, for sure.
Speaker: Go for it.
Speaker: So the first question relates to books.
Speaker: Is there any book that has influenced you significantly or a book that you have gifted other frequently to other people?
Speaker: Yeah, so I had to think a long time about this, about, you know, I read mostly fiction, but the book that I tend to give a lot of people is a book that was written by a hematologist at UCSF and an internist in Chicago called Ending Medical Reversal.
Speaker: And it's such a great book because it really talks about
Speaker: our approach in medicine is, oh, something's new.
Speaker: We start using it right away before we have any evidence.
Speaker: And then decades later, we do a trial and we find out usually it's harmful or no benefit.
Speaker: And we keep doing it.
Speaker: And, um,
Speaker: These two physicians detail this across like a whole bunch of stuff for transfusion medicine, like it's super common.
Speaker: Like we did this for recombinant factor 7a and then we found out it was harmful, but we keep doing it over and over again in medicine.
Speaker: So I think it's like for every doctor should be required reading.
Speaker: The two of them have a great analogy.
Speaker: It takes actually 20 years from when a trial shows that some treatment is not beneficial until it's still being recommended in review articles.
Speaker: Like, it takes us so long to adjust, and they...
Speaker: their analogy, it's like a high speed train.
Speaker: Instead of putting the brakes on, we just take the accelerator off and we just wait for it to gradually slow down.
Speaker: And so I think we need to really change our approach in medicine.
Speaker: We don't do new things until it's proven to make sure we're giving the safest possible care to patients.
Speaker: I think that's a great point and definitely we'll put that in the show notes.
Speaker: Now, I definitely am interested in hearing some fiction recommendations.
Speaker: A lot of authors have commented how fiction is the only truth of life.
Speaker: So any good fiction recommendations you could share?
Speaker: Yeah, the one that came to my mind was a book by H.G.
Speaker: Wells, which is The Time Machine.
Speaker: I don't know if you've read this, but it's about a guy that...
Speaker: goes forward and it's so optimistic.
Speaker: He goes forward 100,000 years and of course the world's a mess.
Speaker: And it's really about political things, which is so timely.
Speaker: We are in a bit of a political mess.
Speaker: But it's a really good read.
Speaker: It's a novella.
Speaker: It's not very long.
Speaker: It's really, really, it's a great read.
Speaker: It was like one of my summer readings this year.
Speaker: Awesome.
Speaker: We will definitely include that as well.
Speaker: I'm familiar with the book, but I have not read it, but definitely we'll pick up both of these and we'll let you know.
Speaker: Thank you so much.
Speaker: The second question, it relates to it for me.
Speaker: And I really believe that being able to change our mind on new evidence and new experience is the utmost sign of intelligence.
Speaker: So I would like for you to share with us something you changed your mind about in the last couple of years.
Speaker: Yeah, so the funniest first thing that came to my mind was like I switched from like a dedicated tea drinker to coffee and all it took was my research team to buy me an espresso machine and I was like, I can't stop drinking coffee now.
Speaker: But the second thing that came to my mind was I really changed my mind about the importance of
Speaker: patient, family members, on our guideline groups, on our clinical trial teams.
Speaker: The patient voice is so important.
Speaker: I'd had patients on prior
Speaker: you know, guidelines or approaches.
Speaker: And I wasn't really sure.
Speaker: I felt like their voices were never heard or they never spoke up.
Speaker: Uh, but most recently we've had some incredible benefit of the patient members on our guideline guideline team.
Speaker: We just did one recently on using the low volume tubes, the pediatric sample collection tubes for laboratory testing in the intensive care unit.
Speaker: And, uh,
Speaker: it was the patients that really convinced the intensivists that we needed to make a strong recommendation, um, that every patient in the ICU use the pediatric volumes.
Speaker: And, and I think we need to listen more to the patients and for us in transfusion medicine, we need to listen to the donors too.
Speaker: I think it's a great point.
Speaker: And I've been part of some guidelines committees, but also committees and societies, professional societies.
Speaker: And, uh,
Speaker: I can only recall one where there's a patient as a member and it made a huge difference, right?
Speaker: I mean, the perspective, but also I think it's being coherent with what we always say that what we do is patient-centered.
Speaker: Well, how can it be patient-centered if the people who are making decisions of how to best do it don't include the perspective and the experience of our patients and their families?
Speaker: So I think that is a phenomenal point.
Speaker: And
Speaker: To some extent, almost, I think you can make an analogy, as the presence of family members during rounds in the ICU or even during cardiac arrest in the ICU.
Speaker: That is an evolution that we've seen that maybe 10, 15 years ago was an absolute no way.
Speaker: And now it's more and more common done in the right setting.
Speaker: Yeah, and maybe we've gotten to the point where the patients and their families are ready to speak up.
Speaker: We've changed like our
Speaker: approach in medicine so patients feel like um we're not practicing in this paternalistic sphere anymore and now it's a conversation and so anyways the patients have been so brilliant on our more recent guidelines and so um yeah include them you know
Speaker: And many of them, not just one, you know, a couple of them.
Speaker: For sure.
Speaker: And the last question relates to what would you want every listener to know?
Speaker: Could be a quote, a fact, or just a departing thought.
Speaker: Yeah, I've tried to think of like what's going wrong in transfusion medicine that the critical care physicians could really help us with.
Speaker: And I think that it's about reporting transfusional reactions.
Speaker: So like no matter what country your listeners are in, you have to report all transfusional reactions, no matter how minor to your blood bank, including heart failure.
Speaker: In hemovigilance studies, about 150 adverse reactions to blood are being reported.
Speaker: That's like the statistics.
Speaker: So it looks like people never have transfusional reactions.
Speaker: But of course, when we do detailed chart reviews and active surveillance, we find it's 150 times more common.
Speaker: And for some things, it's so critical.
Speaker: Like if you have a transfusion-related acute lung injury,
Speaker: We need to find that donor and we need to get them to stop donating because they could kill somebody.
Speaker: So some of them are super important, but for the other stuff, we need to do research to figure out how do we stop those transfusional reactions to continuously make transfusion safer and safer for our recipients.
Speaker: So wherever you are, you must always report your transfusional reactions.
Speaker: I want to thank you first for all the work that you've done through the International Collaboration for Transfusion Medicine Guidelines, specifically, obviously, for the guidelines we discussed today.
Speaker: But I also want to thank you for sharing your expertise and your time with our audience.
Speaker: Hope to have you back maybe when some of these studies get published and we can discuss this topic again.
Speaker: Yeah, and just again, thank you so much for including the albumin guidelines from the ICATMG for your listeners.
Speaker: It's a great way to get new information out to the medical community.
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: Sounds transforming the way critical care is provided in hospitals across the country.
Speaker: To learn more, visit www.soundphysicians.com.
