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Management of Acute-on-Chronic Liver Failure in the ICU
13 Plays2 years ago
In this episode, Dr. Zanotti discusses the management of acute-on-chronic liver failure (ACLF) in the ICU. He is joined by Dr. Nanchal, a practicing critical care physician with an interest in liver disease. He is a Professor in the Division of Pulmonary and Critical Care Medicine, at the Medical College of Wisconsin, in Milwaukee. Dr. Nanchal is also the lead author of the Society of Critical Care Medicine’s Guideline for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU.
Additional Resources
Executive Summary for Guideline for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Neurology, Peri-transplant Medicine, Infectious Disease, and Gastroenterology Considerations: https://journals.lww.com/ccmjournal/pages/articleviewer.aspx?year=2023&issue=05000&article=00010&type=Fulltext
Guideline for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Neurology, Peri-transplant Medicine, Infectious Disease, and Gastroenterology Considerations: https://journals.lww.com/ccmjournal/pages/articleviewer.aspx?year=2023&issue=05000&article=00011&type=Fulltext
Guideline for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Cardiovascular, Endocrine, Hematologic, Pulmonary, and Renal Considerations: https://journals.lww.com/ccmjournal/Fulltext/2020/03000/Guidelines_for_the_Management_of_Adult_Acute_and.29.aspx
Previous Episodes of Critical Matters on the Topic of Acute-on-Chronic Liver Failure:
https://soundphysicians.com/podcast-episode/?podcast_id=342&track_id=953807698
https://soundphysicians.com/podcast-episode/?podcast_id=342&track_id=965563996
Books Mentioned in this Episode:
Noise: A Flaw in Human Judgement. By Daniel Kahneman, et al: https://bit.ly/3sqfRin
Seven Brief Lessons on Physics. By Carlo Rovelli: https://bit.ly/45jv82N
Anaximander: And the Birth of Science. By Carlo Rovelli: https://bit.ly/3sqgqbZ
Recommended
Transcript
Introduction to Critical Matters Podcast
00:00:06
Speaker
Welcome to Critical Matters, a sound podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:14
Speaker
Sound provides comprehensive critical care programs to hospitals across the country.
00:00:19
Speaker
To learn more about our programs and career opportunities, visit www.soundphysicians.com.
00:00:26
Speaker
And now, your host, Dr. Sergio Zanotti.
Understanding Liver Failure in ICU - Guidelines Overview
00:00:32
Speaker
Patients with acute and acute on chronic liver failure are at high risk of developing critical illness.
00:00:38
Speaker
The unique pathophysiology of liver disease related to critical illness presents a series of challenges to clinicians.
00:00:43
Speaker
In today's episode of the podcast, we will discuss highlights of the guidelines for the management of adult acute and acute on chronic liver failure in the ICU, neurology, peritransplant medicine, infectious disease, gastroenterology considerations.
00:00:58
Speaker
This guideline was released earlier this year and was produced by a panel of 29 members with expertise in aspects of care of the critically ill patient with liver failure and or the methodology of EBM guideline development.
00:01:10
Speaker
We will focus on recommendations for managing of acute and chronic liver failure patients in the general ICU setting.
Expert Introduction: Dr. Rahul Nanshaw
00:01:18
Speaker
Our guest today is Dr. Rahul Nanshaw.
00:01:20
Speaker
Dr. Nanshaw is a practicing critical care physician with an interest in liver disease.
00:01:24
Speaker
He is a professor in the Division of Pulmonary and Critical Care Medicine at the Medical College of Wisconsin in Milwaukee.
00:01:30
Speaker
Dr. Nanshaw is a recognized clinician, educator, and has a long list of publications.
00:01:34
Speaker
He is the lead author and co-chair of the guideline for the management of adult acute and acute on chronic liver failure in the ICU that we will discuss today.
00:01:43
Speaker
In the previous episode of the podcast, we discussed the first part of these guidelines, which focused on the management of cardiovascular, endocrine, hematologic, pulmonary, and renal considerations.
00:01:54
Speaker
That podcast and the paper will be referenced in the show notes.
00:01:59
Speaker
Rahul, welcome back to Critical Matters.
00:02:02
Speaker
Thanks, Sergio.
00:02:03
Speaker
Thanks for having me.
Defining Liver Failure Types
00:02:05
Speaker
Well, as you were saying, acute and chronic liver failure, a very important aspect of daily practice in ICUs all over the country and the world, very common presentation.
00:02:16
Speaker
And we were talking that you had embarked on these guidelines some time ago.
00:02:21
Speaker
We had an opportunity to discuss the first part of the guidelines, and today we're going to discuss the second part of the guidelines that were recently published in Critical Care Medicine.
00:02:30
Speaker
So as a starting point, maybe we can refresh our audience's memory on some of the important definitions.
00:02:36
Speaker
And I wanted you to define acute liver failure, chronic liver failure, and then acute on chronic liver failure.
00:02:45
Speaker
Sure.
00:02:45
Speaker
And again, thanks for having me, Sergio.
00:02:49
Speaker
For the purposes of the guideline, I think we defined acute liver failure.
00:02:54
Speaker
So the definition of acute liver failure was sort of a traditional definition, the onset of synthetic liver dysfunction and hepatic encephalopathy within 26 weeks.
00:03:06
Speaker
weeks of an acute insult to a previously healthy liver.
00:03:09
Speaker
So, you know, that's an important distinction point, I think, between acute liver failure and the and chronic liver failure and acute and chronic liver failure, that acute liver failure refers to an insult and liver dysfunction and hepatic encyclopathy occurring in a previously healthy liver.
00:03:26
Speaker
Now, chronic
00:03:27
Speaker
The chronic liver failure is, and this is something that I think most of us recognize as cirrhosis, if you really have to define it, it's just probably progressive liver dysfunction that lasts more than six months.
00:03:42
Speaker
And acute and chronic liver failure, which is sort of a newer entity and a lot's been sort of...
00:03:49
Speaker
recognized about this entity over the past decade.
00:03:53
Speaker
The definition of acute on chronic liver failure is something acute that happens on acutely decompensated chronic liver disease associated with organ failure, which has a very high short-term mortality.
00:04:07
Speaker
So I think, you know, it's good you ask this question because, you know, there's very distinct entities and, you know, very distinct pathophysiology and some of the management aspects may overlap, but, you know, definitions are important.
00:04:20
Speaker
I agree, and I think it's always a good starting point.
Misconceptions in Liver Failure Management
00:04:23
Speaker
Now, you did mention, Rahul, that acute and chronic liver failure is a more novel concept that we're recognizing, yet it has probably been around in our ICUs for some time, and I would say...
00:04:37
Speaker
For most intensivists in general medical and medical surgical ICUs, it might be the more common presentation that we deal with, right, in the ICU at least.
00:04:45
Speaker
Could you give us a little bit more insight into some of the epidemiology and some of the problems that might lead acute and chronic liver failure patients to the ICU?
00:04:55
Speaker
And also if you could comment on some of the misconceptions that intensivists might have about these patients.
00:05:01
Speaker
Yeah, sure, you know, and you're exactly right, Sergio.
00:05:04
Speaker
I think acute and chronic liver failure has been around for as long as intensive care units have been around.
00:05:11
Speaker
I think we've known about this entity, you know, for a long, long time or, you know, or dealt with it in one way, shape, form or the other, but recognizing it and defining it and, you know, and sort of putting definitions around it and some structure around it has occurred previously.
00:05:28
Speaker
And believe it or not, there are three major definitions for acute and chronic liver failure.
00:05:34
Speaker
It's not important to get into what the nuances of the definitions are, but there is an Asia-Pacific definition, there is a European definition, and then there is a North American definition, and they are slightly different.
00:05:46
Speaker
But I think organ failure is what is common amongst all of these definitions.
00:05:55
Speaker
Normally we think of cirrhosis as decompensated cirrhosis in terms of someone has a varicial bleed or someone has large ascites or someone has hepatic encephalopathy.
00:06:04
Speaker
Now you start putting organ failure on top of it, kidney failure and respiratory failure and shock.
00:06:10
Speaker
Those are sort of the hallmarks of acute and chronic liver failure.
00:06:17
Speaker
And so this is a syndrome which is sort of associated with very, very high mortality.
00:06:25
Speaker
The causes of acute and chronic liver failure are many fold.
00:06:30
Speaker
The most common cause of acute and chronic liver failure is an infection that develops in the background of cirrhosis or chronic liver disease.
00:06:38
Speaker
The second most common cause is alcoholic hepatitis or alcohol intake.
00:06:44
Speaker
Probably in the East, viral infections or reactivation of hepatitis B is important.
00:06:50
Speaker
Vericeal bleed is another trigger.
00:06:51
Speaker
So there is some inciting event that leads to acute deterioration of liver function and then organ failure.
00:07:00
Speaker
What is important to note is that I think in about 30% of cases, the cause is never recognized.
00:07:06
Speaker
People just have deterioration of liver function, deterioration of their chronic liver disease, and associated organ failures.
00:07:18
Speaker
I think the misconceptions surrounding acute and chronic liver failure is that I think a lot of intensivists, you know, sort of give up and say that these things have very poor prognosis.
00:07:31
Speaker
Well, that is true.
00:07:32
Speaker
What is also true is that if appropriately managed and given the appropriate ICU support,
00:07:38
Speaker
Up to 20% of people with ACLF-3, that's acute and chronic liver failure, grade 3, which is the severest form of acute and chronic liver failure, can actually reverse their grade or even completely resolve their acute and chronic liver failure.
00:07:51
Speaker
So it's really important that people recognize these early, people recognize the organ failures early, and they support these patients in an appropriate fashion.
00:08:02
Speaker
What is also true is that if you look at one of the most recent studies, controlled for severity of illness, people with acute and chronic liver failure had no worse outcomes than just general ICU patients.
00:08:15
Speaker
And I think the third thing is that I think people should be thinking about referral to a liver transplant center early because these people actually have very high outcomes.
00:08:24
Speaker
mortality within 30 days, especially if you're ACLF grade 2 or ACLF grade 3.
00:08:29
Speaker
And with liver transplantation, you know, people actually do pretty well, but the sort of window for liver transplantation is very, very short and very, very narrow, very high weightless mortality.
00:08:41
Speaker
And so people, you know, should A, recognize this entity early and B, think about, you know, sort of referring to a liver transplantation soon.
00:08:53
Speaker
Center for Liver Transplantation.
00:08:54
Speaker
So I hope that answers your question, Sergio.
00:08:56
Speaker
Absolutely.
00:08:57
Speaker
And I think that these are all important aspects because like you said, the recognition of patients with cirrhosis who are admitted to the ICU with some decompensation or acute problem is very common.
00:09:10
Speaker
And I think the recognition of organ failure in any form would put them in that acute on chronic liver failure category.
00:09:17
Speaker
And like you said, understanding that these patients have a very high mortality, yet it's not futile to care for them.
00:09:24
Speaker
And if we can get them for the proper candidates early to a transplant center, that might actually be not only a life-saving, but might change their trajectory in a very dramatic way.
00:09:36
Speaker
So important for all of us, even when we don't have a transplant,
00:09:40
Speaker
program in our hospital to refer them to the right place.
00:09:43
Speaker
So those, I think, are excellent points for our audience to keep in mind.
Guideline Development Process
00:09:48
Speaker
Now, the genesis, Rahul, for our conversation today, obviously, is the topic of acute and chronic liver failure, and it's really going to be developed around the context of the guidelines that you helped develop.
00:09:58
Speaker
Could you just tell us at a very high level the overview of this guideline process?
00:10:04
Speaker
Yeah, sure.
00:10:04
Speaker
So I think the, you know, firstly, the Society of Critical Care Medicine was kind enough to think that this topic was, you know, was relevant and allowed us to develop these guidelines.
00:10:17
Speaker
So the co-chairs were, which were me and Ram, were actually chosen by the society.
00:10:23
Speaker
After that, we chose panel members that had expertise in a variety of areas, including cardiovascular disease, and each of them had a specific interest in liver disease.
00:10:35
Speaker
And so we had a dietician, we had an APP, we chose people with expertise in ID, with gastroenterology, hepatology, and so on and so forth.
00:10:45
Speaker
And then we divided these experts into various groups for the purposes of this part of the guidelines, which we had four groups.
00:10:54
Speaker
And then in conjunction with the, and each group had a group leader, and in conjunction with the group leader, we formulated questions that we thought would be important to clinicians as well as patients, prioritized some outcomes, and then did a review of the literature.
00:11:10
Speaker
systematic review of the literature and then use the grade process to sort of formulate recommendations and then finally used, you know, the evidence to decision framework to sort of finalize these recommendations for, you know, for the audiences.
00:11:27
Speaker
Perfect.
00:11:28
Speaker
And obviously, there's a lot of recommendations that have come up from the guidelines published in the two separate papers.
00:11:33
Speaker
And we'll have links to all of these in the show notes.
00:11:36
Speaker
But one of the things that I wanted you to explain a little bit is the implications of the strength of recommendation, right?
00:11:43
Speaker
So,
00:11:45
Speaker
There are some that have strong and some that are conditional recommendations.
00:11:48
Speaker
And I think that is worded with a we recommend versus we suggest.
00:11:52
Speaker
What does that mean at the patient, the clinician, and maybe even at more of a society level?
00:12:00
Speaker
Yes, a great question, Sergio.
00:12:04
Speaker
As I mentioned, these recommendations were keeping in line with the grade methodology and the language that is suggested by grades.
00:12:14
Speaker
If something is a strong recommendation, we use the language we recommend.
00:12:19
Speaker
If something is a conditional recommendation, we use the language we suggest.
00:12:23
Speaker
Of course, strong recommendations,
00:12:29
Speaker
I think it has three components to it.
00:12:31
Speaker
It has a patient component, it has a clinician component, and it has, like you said, a society or a policymaker component.
00:12:37
Speaker
And the patient component is that if we recommend, if you are recommending something, then most patients in this situation, in that particular situation, would want what we recommended.
00:12:50
Speaker
And it doesn't mean that all of them would, but the people who would not would be actually a very, very small proportion.
00:12:57
Speaker
From a clinician perspective, when we make a strong recommendation, we are saying that most clinicians would agree that patients should receive what we have recommended.
00:13:10
Speaker
Adherence to this recommendation could be used as a performance, as a quality criterion, or as a performance indicator.
00:13:18
Speaker
And from a policymaker perspective or from a societal perspective, the recommendation could be adapted as a policy in most situations, including the use of performance indicators and so on and so forth.
00:13:32
Speaker
And for very strong recommendations, clearly the benefits outweigh whatever little risks the recommendation has.
00:13:42
Speaker
For a conditional recommendation, it is not as clear.
00:13:45
Speaker
So for a conditional recommendation, I think for patients, a majority of people would probably want the recommendation, but it is possible that quite a few don't.
00:13:58
Speaker
From a clinician perspective, clinicians are, you know, many clinicians would agree that, you know, this is the course of action, but the different choices are likely for different circumstances, and they would say that this recommendation should, you know, be tailored to the individual patient circumstance or perspective, and this should include patient preferences, perhaps not that, you know,
00:14:20
Speaker
recommendations should ever not include patient and, you know, and family values.
00:14:25
Speaker
But I think in conditional recommendations, it's a little more that, you know, we take into account what the patient says, what the family says, and whatnot.
00:14:31
Speaker
And, you know, and we are a little bit more, how should I put it?
00:14:35
Speaker
We are a little bit more iffy about, you know, about it.
00:14:38
Speaker
And from a policymaker perspective, you know, it is hard to make, you know, sort of a performance indicator or it is hard, you know, it is
00:14:46
Speaker
Making a performance indicator surrounding the recommendation would require considerable debate from a variety of stakeholders.
00:14:53
Speaker
And in this sort of conditional recommendation, the clinicians and everyone sort of agrees that perhaps although the benefits may outweigh the benefits, but it is less clearer than a strong recommendation.
00:15:13
Speaker
Perfect.
00:15:14
Speaker
So let's dive into the actual recommendations and talk about how to treat
Antibiotic Prophylaxis in Liver Failure
00:15:18
Speaker
these patients.
00:15:18
Speaker
And I want to start with infectious diseases.
00:15:22
Speaker
So this is one of the most common reasons why patients with acute and chronic liver failure may end up in the ICU or a common occurrence.
00:15:31
Speaker
But another common cause that brings patients to the ICU in this subset is gastrointestinal bleeding or bleeding associated with portal hypertension complications.
00:15:45
Speaker
Could you tell us about the use of antibiotic prophylaxis in these patients?
00:15:50
Speaker
Yeah, I think this is, you know, just to take a step back, Sergio, a lot of recommendations in this guideline were conditional just because, or, you know, there were several areas where we couldn't make recommendations because either the data was indirect or we just didn't have recommendations
00:16:06
Speaker
you know, enough good quality data, you know, for, as you very well know that patients with liver disease are, or at least advanced liver disease are frequently excluded from randomized controlled trials of critically ill patients.
00:16:20
Speaker
So, you know, it is sort of hard to find good quality data in people with
00:16:25
Speaker
with acute liver failure or acute on chronic liver failure, but this was one of the areas where we were able to issue a strong recommendation for antibiotic prophylaxis after gastrointestinal bleeding.
00:16:37
Speaker
And I think, like many of our audience knows, it's common practice to give
00:16:42
Speaker
give antibiotic prophylaxis after GI bleeding.
00:16:45
Speaker
And the reason is that in large meta-analysis, and even when we looked at all of the evidence and did our own meta-analysis, not only was
00:16:58
Speaker
not only was the occurrence of infection, the occurrence of SPP, the occurrence of bacteremia reduced, but even mortality was reduced when you gave antibiotic prophylaxis after GI bleed.
00:17:09
Speaker
The mortality was likely reduced because of the reduction of infections.
00:17:14
Speaker
But we found pretty strong evidence and pretty good evidence that this is one of the things that should always be done.
00:17:25
Speaker
And like you mentioned, this is one of the strong recommendations based on the available evidence.
00:17:30
Speaker
So important for our clinicians to remember, if you admit somebody with an upper GI bleed and they're a chronic liver failure, acute on chronic liver failure, you should start prophylactic antibiotics.
00:17:41
Speaker
And would ceftriaxone be appropriate?
00:17:43
Speaker
Is that kind of what we recommend these days?
00:17:45
Speaker
Perfect.
00:17:45
Speaker
Yeah, yeah, so I think, you know, for prophylaxis of a GI bleed, I think a third generation cephalosporin, cephtriazin would absolutely be appropriate.
00:17:55
Speaker
Cephalopaxime, I think, would be an equally good choice.
00:17:58
Speaker
Perfect.
00:17:59
Speaker
So the other topic that I believe is important in infectious disease in the context of our discussion is obviously SPP, spontaneous bacterial peritonitis, another common reason why patients might end up under our care in acute and chronic liver failure.
00:18:16
Speaker
Before we go into some of the recommendations, Rahul, could you just give us a little bit more of a general overview of SPP, kind of how does it usually present, when we should suspect it, and how do you confirm the diagnosis?
00:18:28
Speaker
You know, obviously, Sergio, if, you know, someone comes in and say, someone with liver disease, and ascites comes in and says, I have abdominal pain and I have a fever and, you know, and things of that nature, it is sort of, yes, you know, they likely have SPP.
00:18:44
Speaker
But in my practice, at least what I have found is that
00:18:48
Speaker
The presentation of SPP is actually so varied that it is probably just, you know, a person comes in sick and they have ascites, it is, you know, probably just very wise to at least get a diagnostic tab and rule out SPP.
00:19:02
Speaker
So the way to, you know, do this is just, you know, send a few cc's of
00:19:07
Speaker
And it does not have to be a therapeutic tap.
00:19:09
Speaker
It's very easily done at the bedside, just a few cc's of fluid sent for cell count and culture.
00:19:16
Speaker
And obviously the diagnosis of SPP rests on finding more than 250 neutrophils.
00:19:24
Speaker
in a sample of the acetic fluid and at the same time starting sort of broad spectrum antibiotics.
00:19:33
Speaker
And so this is such a, I think it is so common and so commonly missed and the presentations are so varied that it can be easily missed.
00:19:42
Speaker
I think it probably behooves us, especially if people are ill and require admission to the ICU, that a diagnostic sort of DAP be done when you don't know what's going on or presentations are less clear or someone presents with confusion or hepatic encyclopathy or things of that nature and you're looking for a trigger, a diagnostic paracentia should be performed.
00:20:05
Speaker
Yeah, I think that's a great point, Rahul, that really very insidious in his presentation and that we should have a super high index of suspicion.
00:20:13
Speaker
Anybody who's presenting with history of chronic liver disease who is critically ill, maybe there's unclear or non-characteristic symptoms, but also important to mention like you mentioned
00:20:24
Speaker
you were talking earlier that somebody might present with a GI bleed and then develop SPP within the hospital.
00:20:30
Speaker
So again, to maintain that level of vigilance, we, we talked, we'll talk about, about, about therapy, but the first recommendation that I think is based really on data that is mostly obtained from non-cirrhotic and non-acute and chronic liver failure patients relates to the timing of antibiotics for SPP and for SPP and septic shock.
00:20:52
Speaker
Any comments there?
00:20:52
Speaker
Yeah.
00:20:53
Speaker
Yeah, I think, you know, again, as you mentioned, there is actually not a whole lot of data that pertains specifically to, at least not prospective randomized control data that, you know, prospective, there have been some retrospective observational studies, but there is nothing that actually pertains specifically to acute liver disease.
00:21:14
Speaker
However, there is so much data from, you know, just general septic shock, general sepsis, and things of that nature, and also knowing that,
00:21:24
Speaker
you know, the patients with liver disease, they have a unique pathophysiology, they are vasodilated at baseline and probably have limited cardiopulmonary reserve, and infections are the major cause of acute on chronic liver failure, and that, you know, as organ failure progresses, like with any other critical illness, you know, short-term mortality actually rises exponentially, so as you go from grade 1 to grade 2 to grade 3 ACLF,
SBP Management Strategies
00:21:50
Speaker
there is exponential rise in mortality.
00:21:53
Speaker
I think the timing of antibiotics and the control of infection is so important.
00:21:58
Speaker
And that's why we sort of suggested, of course, the recommendation was
00:22:04
Speaker
conditional and the quality of evidence was low because of a variety of reasons.
00:22:09
Speaker
A, there is no direct evidence.
00:22:11
Speaker
B, the evidence that is there is all retrospective.
00:22:15
Speaker
We had to issue a conditional recommendation.
00:22:17
Speaker
So we did suggest that the appropriate antibiotics are started as soon as possible after recognition and ideally within one hour of onset of shock in critically ill ACLF patients with SVP.
00:22:34
Speaker
And I also think that this also pertains probably, most of the data is for SVP, but we have probably for other infections as well that if you recognize an infection, start antibiotics as soon as possible.
00:22:48
Speaker
And if you have shock, absolutely within one hour.
00:22:52
Speaker
If starting antibiotics as soon as possible, probably, you know, in a lot of cases will prevent either ACLF or the progression of ACLF if you're in ACLF grade one or so on and so forth.
00:23:02
Speaker
And so those are some of the recommendations for, you know, the timing of antibiotics and SVP and septic shock.
00:23:07
Speaker
Perfect.
00:23:08
Speaker
Now, in terms of the timing, obviously, sooner is always better, and that is going to be even more important for critically ill patients in septic shock.
00:23:19
Speaker
What about the choice of antibiotics?
00:23:21
Speaker
So we talked about ceftriaxone as a good prophylactic, and that historically was a starting point for SBP, but my understanding, I'm reading the guidelines, is that maybe we need to think a little bit broader.
00:23:33
Speaker
Can you tell us what the recommendation is today?
00:23:37
Speaker
Yeah, I think we did recommend that we use broad-spectrum antibiotics for the initial management of SVP and that ceftriaxone or a third-generation cephalosporin be reserved for low-risk community-acquired SVP.
00:23:54
Speaker
And so, you know, as you very well know, Sergio, the epidemiology of infections in general have changed with the, you know, use, misuse, overuse of antibiotics and a variety of other factors.
00:24:07
Speaker
And that we more and more, we are dealing with resistant infections, not only in, you know,
00:24:14
Speaker
especially if they are nosocomial healthcare associated or healthcare acquired.
00:24:18
Speaker
But also now in the community, we have been more and more, we have been dealing with resistant infections.
00:24:23
Speaker
And so, you know, our recommendation is probably to, you know, take into account risk factors for resistant infections, A, B, where you acquired the infection, you know, whether you acquired it in the hospital or you acquired it in the community, whether you've been exposed to antibiotics before or not, whether you have other risk factors for multidrug resistant pathogens,
00:24:44
Speaker
and what your local sort of antibiogram, especially if you're in the hospital, what your local microbiological structure looks like before you decide on the choice of antibiotics.
00:24:59
Speaker
And people should be cognizant that there are the prevalence of ESBLs in organisms like MRSA or BRE,
00:25:06
Speaker
is growing in prevalence.
00:25:08
Speaker
And again, like I had mentioned before, these people have little reserve, and infections are the main cause of, and especially SPP, the main cause of one of the main causes of ACLF and progression of ACLF.
00:25:22
Speaker
I think all of these factors should be taken into account.
00:25:26
Speaker
When initiating antibiotic therapy, the choice of third-generation cephalosporin should be reserved for absolutely low-risk patients.
00:25:36
Speaker
Perfect.
00:25:38
Speaker
Another area that applies directly to SPP is the use of albumin.
00:25:43
Speaker
So albumin obviously has been studied and debated as a fluid recitation for sepsis and currently is not part of the standard just based on the available evidence.
00:25:56
Speaker
But your recommendations in the guideline do suggest that or recommend that the use of albumin in SPP specifically has value.
00:26:05
Speaker
Could you tell us a little bit more about that, Rahul, please?
00:26:09
Speaker
Yeah, sure.
00:26:09
Speaker
So, you know, there is a inherent vasodilated and, you know, sort of immune dysfunctional state of cirrhosis.
00:26:19
Speaker
And other than acting as a volume expander, I think albumin has a lot of other immunomodulatory, you know, sort of, and a lot of other effects that are probably beneficial for patients in cirrhosis.
00:26:33
Speaker
And, you
00:26:34
Speaker
And when we looked at the data from, you know, I think there were four randomized controlled trials, of course, you know, the largest of them was published in the New England Journal of Medicine, I think in 1998 now.
00:26:47
Speaker
And all of these four trials, when people were given albumin, you know, it was associated with a reduction in the odds of mortality, in the reduction of renal failure, and, you know, in general, it was found to be very, very beneficial.
00:27:04
Speaker
And we did even in our rationales, we went as far as to say that if once a diagnosis of SPP has been established, you should probably just give albumin just because of the inherent vasodilacted state of liver disease, even if the need for volume resuscitation is not obvious.
00:27:30
Speaker
just to increase the circulating, you know, all of these people have decreased effective arterial circulating volume just to increase that and maybe perhaps even to stave off or prevent people going into acute and chronic liver failure.
00:27:42
Speaker
So again, you know, very important.
00:27:44
Speaker
I think clinicians should recognize, you know, that they should give, as soon as, you know, they diagnose SPP, albumin should be given.
00:27:53
Speaker
What's the recommendation in terms of dosing?
00:27:56
Speaker
So I think the first dose, typical initial dose is one and a half grams.
00:28:02
Speaker
And the first day is one and a half grams per kg of 25% albumin.
00:28:05
Speaker
And that, I think, important to emphasize, Rahul, is not necessarily for flu resuscitation.
00:28:12
Speaker
It's just basically we're treating the SBP with that dose of albumin regardless.
00:28:17
Speaker
Exactly.
00:28:19
Speaker
And would you be more inclined to use albumin as you resuscitate patients with SBP later as well?
00:28:25
Speaker
Yeah, I think, you know, my practice is to give albumin for resuscitation.
00:28:32
Speaker
This is one of the, I think, one of the very few disease states that, you know, I prefer to give 25% albumin for resuscitation.
00:28:42
Speaker
Perfect.
00:28:43
Speaker
What about, you mentioned earlier, the diagnostic parasyntesis to make the diagnosis of SPP.
00:28:51
Speaker
What's the role of a large volume parasyntesis in SPP?
00:28:55
Speaker
And if you could define what a large volume parasyntesis is considered.
00:28:59
Speaker
Sure.
00:29:00
Speaker
I think, so, Sergio, the definition of a large volume SPP is removal of more than four liters of acetic fluid.
00:29:10
Speaker
And, you know, although there is...
00:29:17
Speaker
There is a lot of debate over whether a large volume paracentesis should be performed or should not be performed in people with SPP.
00:29:28
Speaker
As you very well know, large volume paracentesis can induce paracentesis-associated circulatory dysfunction, low blood pressure, shock, and things of that nature, which can eventually lead to renal impairment and worsening of acute and chronic liver failure.
00:29:46
Speaker
we did not actually find any evidence to suggest that this should be performed.
00:29:52
Speaker
So we recommended that it is okay not to perform large-volume paracentesis in patients with SVP unless there was an absolutely compelling reason for it, like intra-abdominal hypertension or things of that nature, but rather to just do a diagnostic paracentesis.
00:30:14
Speaker
And I think that's an important distinction, right?
00:30:17
Speaker
If you have an indication such as you have a documented intra-abdominal hypertension, removing a situs will be therapeutic or will help treat that intra-abdominal hypertension that can also potentiate organ failure such as renal failure.
00:30:34
Speaker
Exactly, Sergeant.
00:30:35
Speaker
Perfect.
00:30:36
Speaker
And the last question or topic that I want to discuss within the SPP category was the use of metodrine and telepresin for SPP.
00:30:46
Speaker
These medications have been utilized for patorenal syndrome, but is this something you would start early or what is the role for metodrine and telepresin in SPP?
00:30:58
Speaker
So Sergio, you know, in short, I think we did not actually find any evidence that in the absence of hepatorenal syndrome, that these medications would, you know, would be helpful.
00:31:17
Speaker
So we actually recommended not to use these medications, either mitodrine or telorepresin, for critically ill patients with ACLF.
00:31:26
Speaker
Now, if people have hepato-renal syndrome, you know, I think that's a different entity and it's a different, you know, that's a totally different sort of animal.
00:31:36
Speaker
And, you know, as you very well know, these vasoconstrictors are sort of the cornerstone of treatment, you know, of that entity.
00:31:44
Speaker
But in the absence of that, they should not be used.
00:31:48
Speaker
Perfect.
00:31:49
Speaker
So let's switch gears and talk about gastroenterology topics.
Managing Portal Hypertensive Bleeding
00:31:53
Speaker
And obviously, these are very relevant to these patients.
00:31:58
Speaker
A lot of admissions to the ICU are related along GI problems in patients with chronic liver disease, developing acute and chronic liver failure.
00:32:08
Speaker
So the first recommendation that I wanted you to give us a little bit more insight is the timing of endoscopy for acute and chronic liver failure ICU patients with known or suspected portal hypertensive bleeding.
00:32:22
Speaker
Yeah, sure.
00:32:22
Speaker
So, you know, interestingly enough, Sergio, there is actually very little data that, you know, guides this recommendation.
00:32:29
Speaker
The American Association for the Study of Liver Diseases recommends that endoscopic evaluation occur no later than 12 hours, you know, of presentation of an acute variceal bleed.
00:32:42
Speaker
And there is a meta-analysis, which is, you know, basically retrospective observational studies and at very high risk of selection bias.
00:32:51
Speaker
But
00:32:52
Speaker
Physiologically, I think early endoscopy, especially in portal hypertensive bleeding, makes a lot of sense, right?
00:33:00
Speaker
So, as you very well know, variceal bleeding is one of the triggers of acute and chronic liver failure.
00:33:08
Speaker
And if you delay endoscopy, you risk hemodynamic instability, more blood transfusions, more portal hypertension, more bleeding.
00:33:18
Speaker
And considering all of these things, considering the physiological effects of early endoscopy and what we would be preventing, we actually said that we recommended that, and this was a best practice statement,
00:33:32
Speaker
And not a, you know, not a strong or conditional recommendation because of, you know, because of what I have told you.
00:33:38
Speaker
And so we recommended that, you know, EGD or endoscopy be performed no later than 12 hours in critically ill patients with ACLF and, you know, who have portal hypertensive bleeding.
00:33:48
Speaker
And like you mentioned, this is a best practice statement, mostly because there was a strong sentiment on the guideline panel that this is important, yet obviously it's something that has not been or may be hard to study in randomized trials, correct?
00:34:03
Speaker
Exactly, exactly, Sergeant.
00:34:05
Speaker
And I think it's an important recommendation because for most of our audience, the intensivists are not doing the endoscopy.
00:34:14
Speaker
So making sure that we're all on the same page in terms of what would be considered a best practice window for these patients to have an intervention, I think 12 hours is obviously valuable, right?
00:34:26
Speaker
You don't have to come right now, but within 12 hours, this patient should be evaluated with endoscopy.
00:34:32
Speaker
Exactly, and especially given the fact that general GI bleeding, most people will say, well, within the first 24 hours is okay, but this is a little different than just general GI bleeds or general upper GI bleeds, where a lot of bleeding, say it's after you give them a proton pump inhibitor, this is not the case with acute portal hypertension, hyperdense like bleeding.
00:34:57
Speaker
Perfect.
00:34:57
Speaker
And you mentioned the PPI, and we obviously use this a lot in non- and liver patients for upper GI bleeds, and there's been demonstrated beneficial effects of using PPIs and decreasing re-bleeding.
00:35:11
Speaker
What's the role of proton inhibitors in portal hypertensive bleeding?
00:35:15
Speaker
You know, again, this was a recommendation where we did have some data, but, you know, at least in liver disease, as you very well know, again, you know, PPIs can have some adverse effects as well, especially dysbiosis, effects on the microbiome, increased risk of SVP and, you know, and sort of hepatic encyclopathy.
00:35:36
Speaker
But we felt that
00:35:38
Speaker
when people had, you know, bleeding, acid suppression was really, really important, especially in any kind, even with portal hypertensive bleeding, because once you, you know, treat portal hypertensive bleeding, you know, creating that, you know, suppressing acid in terms of healing and in terms of, you know, other beneficial effects that were extrapolated from, you know, non-
00:36:02
Speaker
sort of liver disease patient trials were important enough for us to issue a strong recommendation to say that, you know, we should use proton pump inhibitors in patients with portal hypertensive bleeding.
00:36:15
Speaker
Perfect.
00:36:16
Speaker
And what about the use of other medications such as Oxetide or Somatostin analogs in portal hypertensive bleeding?
00:36:23
Speaker
Yeah, again, that's, you know, that's, so there's, so somatostatin and this thing was, you know, this is where we have data with liver disease.
00:36:35
Speaker
You know, obviously, you can use a somatostatin analog or telrepresin.
00:36:40
Speaker
Until recently, telrepresin was not available in the United States.
00:36:43
Speaker
It's just become available.
00:36:45
Speaker
But the, not only, you know,
00:36:51
Speaker
Although the effect on the re-bleeding is a little unclear, but the use of octreotide or somatostatin analogs is actually associated with a mortality benefit in portal hypertensive bleeding after someone has performed banding or sclerotherapy, and this is one of the pharmacological agents which is helpful and should be used, and this is one of the strong recommendations in the document.
00:37:15
Speaker
I'm a big believer in making sure that patients always get treatments that we consider to be standard of care, best practice, or based on evidence.
00:37:27
Speaker
And I always say that for many diseases, the first three or four steps should be the same for everybody.
00:37:31
Speaker
And then you start looking, okay, how do they respond?
00:37:34
Speaker
What's different about this patient?
00:37:35
Speaker
And maybe...
00:37:36
Speaker
go a little bit deeper or do different things.
00:37:39
Speaker
But it sounds from our discussion so far, for the common presentation of a GI bleed in a patient with acute and chronic liver failure, which we presume has a portal hypertensive origin, they should get...
00:37:54
Speaker
prophylactic antibiotic.
00:37:56
Speaker
They should get an endoscopy within the 12 hours of arrival.
00:38:00
Speaker
They should get a PPI and they should probably be treated with octetide or telepression if you have that available.
00:38:07
Speaker
Would that be fair?
00:38:08
Speaker
Yes, that is absolutely true, Sergio.
00:38:10
Speaker
And you've hit the nail on the head.
00:38:11
Speaker
You know, that is exactly like you said, you know, these are standard of care things.
00:38:16
Speaker
And this is something that I do for every patient that presents with a portal hypertensive pain.
00:38:23
Speaker
So once you've implemented all of those and the patient has a re-bleed, what's the next step?
00:38:30
Speaker
Do you re-endoscope or do you talk about tips?
00:38:36
Speaker
I think, you know, practices, so to tell you the truth, real-world practices likely differ from, you know, from place to place.
00:38:44
Speaker
But there is, I think there is, you know, sort of,
00:38:49
Speaker
Pretty good evidence that re-bleeding, if patients re-bleed despite their initial attempt at banding and sclerotherapy and they have received all of the things that we talked about, that strong consideration should be given to TIPS.
00:39:07
Speaker
And, in fact, there is a trial where, although it is very small, that if you do tips early, one-year outcomes in terms of mortality and in terms of recurrence of re-bleeding are much better.
00:39:24
Speaker
than TIPS.
00:39:25
Speaker
So in centers that have the expertise and there are experienced operators, obviously the performance of TIPS requires access to an experienced operator and a center with expertise.
00:39:37
Speaker
If you have those, strong consideration should be given to TIPS.
00:39:42
Speaker
Obviously there are contraindications associated with TIPS, so those have to be kept in mind.
00:39:47
Speaker
However, in cases of re-bleeding, after a good-faith attempt at all of the initial things we talked about to control bleeding, strong consideration should be given to the performance of tips.
00:39:59
Speaker
Perfect.
00:40:01
Speaker
And the last topic I wanted to talk about was neurology.
00:40:05
Speaker
And there's a lot of recommendations regarding hepatic encephalopathy, but what I wanted to start with was if you could differentiate for our clinicians the differences between
00:40:17
Speaker
in broad terms, between hepatic encephalopathy in a patient with acute liver failure and hepatic encephalopathy in patients with acute on chronic liver failure.
Hepatic Encephalopathy: Acute vs Chronic
00:40:27
Speaker
Yeah, sure.
00:40:28
Speaker
Certainly a very important question and I think very important for the audiences to know.
00:40:32
Speaker
So, you know, as we had mentioned in the, you know, at the start of this podcast, the definitions of acute liver failure.
00:40:40
Speaker
So the acute liver failure, so liver insult occurring in a previously healthy or a normal liver.
00:40:46
Speaker
And, you know, ammonia is central to the development of hepatic encyclopathy.
00:40:51
Speaker
And, you know, so the brain has not, acute liver failure, is not used to elevated ammonia levels.
00:40:57
Speaker
And so, you know, what happens is that, you know, people get encephalopathic very quickly, and they might even develop cerebral edema associated with the encephalopathy because of these high ammonia levels.
00:41:13
Speaker
This does not occur in ACLF.
00:41:14
Speaker
So the entity of hepatic encyclopathy is very different in acute on chronic liver failure as it is in ALF.
00:41:24
Speaker
Secondly, all of the therapies that we use for hepatic encyclopathy and control of hepatic encyclopathy in chronic liver disease or ACLF do not work
00:41:38
Speaker
for ALF.
00:41:40
Speaker
And so the way to control hyperammonemia and ALF is to do plasmapheresis or, you know, or do continuous renal replacement therapy.
00:41:47
Speaker
While, you know, the, while usually the hyper, the hepatic encyclopathy and acute on chronic liver failure is, you know, sort of treated with lactulose and rifaximin and so on and so forth.
00:42:00
Speaker
Hopefully I sort of answer your question about the sort of differences.
00:42:04
Speaker
So the brain, because acute and chronic liver failure develops on pre-existing chronic liver disease, the hepatic encyclopathy is less associated with cerebral edema, usually does not develop, and probably develops less slowly and progresses rather than patients who have acute liver failure.
00:42:25
Speaker
Oh, absolutely.
00:42:26
Speaker
And I think you also mentioned some of the therapeutic differences because the underlying pathophysiology is quite different.
00:42:33
Speaker
So even though we're calling both clinical syndromes, hepatic encephalopathy, the process is very different and what kills patients might be very different.
00:42:43
Speaker
So without going too deep into the acute liver failure, hepatic encephalopathy, two recommendations that I noted that perhaps a little bit different of what was done some time ago, where the one for measuring intracerebral pressure, ICPs, and the use of targeted hypothermia to lower ICP, those seem to be much more...
00:43:15
Speaker
or people were more enthusiastic about them before.
00:43:18
Speaker
But from what I understood, Rahul, the evidence that you looked at doesn't really support any of those.
00:43:24
Speaker
That is exactly right.
00:43:27
Speaker
You know, the evidence doesn't support either the use of ICP monitors or of hypothermia in acute liver failure.
00:43:38
Speaker
And what is very interesting is that as our
00:43:42
Speaker
knowledge of pathophysiology has grown and as our general management of ICU patients has gotten better, the incidence of cerebral edema has actually markedly declined in patients with acute liver failure.
00:43:55
Speaker
So hardly anyone, very few patients actually develop, people might develop hepatic encyclopathy to some degree, but they rarely develop cerebral edema these days.
00:44:04
Speaker
And on the other hand, what was recommended as potential useful therapeutic interventions was, like you mentioned already, the use of plasmapheresis, the use of continuous renal replacement, and also the use of hypertonic saline, correct?
00:44:21
Speaker
Exactly, exactly, Sergeant.
00:44:23
Speaker
So now that we, a little bit more about hepatic encephalopathy and acute and chronic liver failure, if you could just give us kind of like an overview of how to suspect it and some tips and pearls and first-line therapies on this topic, which is very common in the ICU.
00:44:42
Speaker
Yeah, I mean, you know, so...
00:44:44
Speaker
As you said, exceedingly common, Sergio.
00:44:46
Speaker
And, you know, what I say is always look for a trigger for hepatic encyclopathy.
00:44:53
Speaker
Lots of times, as we have talked about before, it is SPP and it can be very subtle.
00:44:57
Speaker
And so, you know, a person presents with SPP and has ascites, you know, make sure you get the diagnostic tap.
00:45:03
Speaker
Make sure you're looking for hypovolemia, make sure you're looking for drugs, make sure you're looking for other things that have happened to cause hypokalemia and whatnot, other things that have precipitated hepatic encyclopathy.
00:45:19
Speaker
The presentation is, again, variable.
00:45:22
Speaker
People can present from anywhere to deep stuporous comas that require intubation and mechanical ventilation because they can't protect their airways.
00:45:30
Speaker
So just mild confusion and a little bit of asterisks.
00:45:33
Speaker
And the classification is actually called West Haven's classification.
00:45:37
Speaker
And what is important for our audience is to count as an organ failure across definitions, whether it is the North American definition or whether it is the European definition.
00:45:51
Speaker
One has to have grade three to grade four values.
00:45:54
Speaker
hepatic encyclopathy.
00:45:56
Speaker
And so one of the most common presentations in people with acute and chronic liver failure or even just decompensated cirrhosis and I think looking for a precipitant, extremely important, removing or treating the precipitant, very important, and again treating the hepatic encyclopathy, very important.
00:46:18
Speaker
Any other comments?
00:46:20
Speaker
I know that there were some recommendations on the use of rifaxamine and polyethylene glycol.
00:46:26
Speaker
Yeah, sure.
00:46:26
Speaker
So I think the cornerstone of management is still non-absorbable disaccharides, and so lactulose remains the cornerstone of management for...
00:46:42
Speaker
for hepatic encephalopathy.
00:46:44
Speaker
I think the addition of rifaximin as an adjunct to lactolose is very important, especially if the hepatic encephalopathy is not resolving.
00:46:56
Speaker
The combination of lactolose and rifaximin seems to work much better and may even have a mortality benefit.
00:47:05
Speaker
Now, the addition of polyethylene glycol, there are, I think, two trials which use polyethylene glycol in place of lactolose.
00:47:15
Speaker
But I would reserve it for people who do not tolerate lactolose or develop some bowel distension or things of that nature.
00:47:21
Speaker
Those are the people I think to give polyethylene glycol to.
00:47:24
Speaker
Remember that we are giving large volumes of polyethylene glycol in people who can't.
00:47:29
Speaker
There's always a risk of aspiration with this, but again, a useful adjunctive therapy if lactose is either not working or people are not tolerating lactose.
00:47:41
Speaker
Perfect.
00:47:43
Speaker
Rahul, first I just want to thank you for spearheading this massive undertaking of really putting together these guidelines.
00:47:52
Speaker
We'll have references to all the papers.
00:47:54
Speaker
I really encourage our audience to read the papers because the...
00:47:59
Speaker
Not only the recommendations are important, but also the discussion of the why and the literature behind them, which also for me was a reminder of how hard it is to perform large randomized trials in a subpopulation on chronic liver failure and acute liver failure patients and how much they're still to be studied in terms of managing these patients, right?
00:48:25
Speaker
You're exactly right, Sergio.
00:48:26
Speaker
I think, and it's surprising, right?
00:48:30
Speaker
We see it so commonly, yet there are so few randomized controlled trials, and there is a lot to be done and a lot to be studied.
00:48:38
Speaker
Is there anything else you want to add to the clinical topic before we move on to the closing part of the podcast, Rahul?
Early Recognition and Transplant Referral
00:48:44
Speaker
Yeah, I think I would just, you know, probably for the audiences, just...
00:48:49
Speaker
maybe remind people that there is, it is always, you know, please be cognizant.
00:48:56
Speaker
Recognition is really important.
00:48:58
Speaker
And then, you know, refer to a center that has transplant capabilities at the right time is really important.
00:49:05
Speaker
Perfect.
00:49:06
Speaker
And you've been on the podcast before, so you know that we like to ask a couple of questions unrelated to the clinical topic to just learn a little bit from the wisdom of our guest.
00:49:16
Speaker
Would that be okay?
00:49:18
Speaker
Of course.
Recommended Readings by Dr. Nanshaw
00:49:19
Speaker
So the first question relates to books.
00:49:21
Speaker
Are there any books that have influenced you or struck you recently or gifts or books that you have gifted often to other people?
00:49:31
Speaker
Yeah, so, you know, great question, Sergio.
00:49:33
Speaker
So, you know, I'm a big fan of Daniel Kahneman.
00:49:36
Speaker
And so I think the last time we talked, you know, I said thinking fast and slow has really, you know, had really influenced me.
00:49:45
Speaker
There's a new book of his called Noise.
00:49:47
Speaker
And, you know, which is about why...
00:49:51
Speaker
the same people make different decisions given exactly the same circumstances and what we can do to avoid that.
00:49:58
Speaker
And especially important, for example, in our judiciary systems and especially important in medicine and whatnot.
00:50:05
Speaker
So I think I have found his books to be particularly insightful and particularly very enlightening.
00:50:14
Speaker
And the books that I have gifted the most, and I'm sort of an armchair
00:50:18
Speaker
quantum physicist.
00:50:19
Speaker
And so the book that there is a book by Carlo Rovelli called the seven brief lessons of physics.
00:50:24
Speaker
You know, that's another book that has really influenced me a lot.
00:50:27
Speaker
And that is that is a book that I've gifted the most.
00:50:30
Speaker
And the nice thing of the Reveille book is that it's a short read.
00:50:32
Speaker
So it's a perfect gift.
00:50:35
Speaker
And yeah, we talked about this last time on thinking fast and slow, but I agree.
00:50:40
Speaker
I think Daniel Kahneman, for those who don't know, a Nobel laureate, father of behavioral economics and really of studying how we think, right?
00:50:51
Speaker
And noise is a wonderful read.
00:50:53
Speaker
And like you said, very, very applicable to what we do in medicine on a daily basis.
00:50:59
Speaker
So we will...
00:51:00
Speaker
Definitely link both of these books.
00:51:01
Speaker
I highly recommend it.
00:51:03
Speaker
I've enjoyed both of them and have also gifted Carlo Rovelli books to others.
00:51:09
Speaker
Great.
00:51:09
Speaker
So the second... What's that?
00:51:11
Speaker
You like quantum physics as well, I guess.
00:51:13
Speaker
I do.
00:51:14
Speaker
Okay, very nice.
00:51:16
Speaker
So the other book that I really enjoyed from Carlo Rovelli that's very new is his last, I don't know if it's his last book, but it's a book called Anaximander and really talks about the first great scientist in Greek history.
00:51:28
Speaker
Yeah.
00:51:29
Speaker
And it just shows you, I mean, how much people have evolved in the way they think and just a fascinating, fascinating read.
00:51:40
Speaker
So we'll reference all these in the show notes.
00:51:42
Speaker
Thanks for those recommendations.
00:51:46
Speaker
What do you believe to be true, Rahul, in medicine or life that most other people don't believe or don't behave like they believe?
The Role of Randomness in Medicine
00:51:55
Speaker
I don't know whether other people don't believe or don't behave like they believe, but I think I...
00:52:01
Speaker
One of the things that, you know, again, it's influenced a lot by Daniel Kahneman and, you know, and people like him is the role of randomness in life and chance in life.
00:52:10
Speaker
I think we discount the role of, you know, randomness in life.
00:52:14
Speaker
And, you know, people sort of tend to think that, you know,
00:52:17
Speaker
there is something special about, you know, a situation when it is all very random.
00:52:21
Speaker
And, you know, as an example, if you take a thousand people and give them a coin and, you know, ask them to toss a coin, you'll probably find one person who tosses 10 heads in a row or 10 tails in a row for that matter of fact.
00:52:34
Speaker
And, you know, that person was like, oh, wow, you know, there is something special when it's just, you know, you're liable to find one person who
00:52:42
Speaker
who sort of, you know, just by chance alone, who tosses 10 heads in a row or 10 tails in a row.
00:52:49
Speaker
And I think it's a great point also to bring back to medicine, right?
00:52:53
Speaker
So especially when you're looking at small numbers, people try to put an explanation to everything.
00:52:58
Speaker
So if all of a sudden they're measuring the ratio to mechanical ventilation, compliance with sepsis bundles, mortality, whatever you want to call it in your ICU, and it goes up,
00:53:10
Speaker
The first thought, or it goes down, the first thought is people attach all sorts of explanations to why that happened.
00:53:16
Speaker
And the most likely reason is that it's just a random finding, right?
00:53:19
Speaker
Yeah, exactly.
00:53:21
Speaker
And so, you know, Sergio, it is so great that you, it's so important that you brought this up.
00:53:26
Speaker
So this reminds me of the...
00:53:29
Speaker
of Tversky and you know, thought about the airline pilots in Israel.
00:53:35
Speaker
I don't know if you sort of read that or not.
00:53:38
Speaker
The regression to the mean, absolutely.
00:53:40
Speaker
Yes, exactly.
00:53:44
Speaker
So what it says, and I always remind people because of the law of small numbers, that if your sepsis numbers look really bad this month, I almost always guarantee that without doing anything, they will look better next month.
00:53:58
Speaker
Exactly.
00:53:58
Speaker
And if they looked very good this month, I can guarantee almost that they will look a little bit worse next month, right?
00:54:05
Speaker
Yes, exactly.
00:54:06
Speaker
Exactly.
00:54:08
Speaker
Perfect.
00:54:09
Speaker
And the last question is just related to what would you want every person listening to our podcast today to know?
Final Reflections on Liver Failure Management
00:54:17
Speaker
Do you mind if I read out a quote that I actually read in a...
00:54:27
Speaker
in a book of physical exams.
00:54:28
Speaker
So we used the book of, you know, I trained in India, I went to medical school in India, and we had used a book called Hutchinson's Clinical Methods.
00:54:37
Speaker
And, you know, and this was, this was, the book was, I think it was first published, you know, 100 years ago or so, and has now, and several editions later, you know, it's continued.
00:54:48
Speaker
But,
00:54:49
Speaker
There was a quote in the book by Lord Hutchinson himself, which, you know, has influenced me quite a bit.
00:54:55
Speaker
And so I would like to read that out if that's okay.
00:54:57
Speaker
Please, please.
00:54:58
Speaker
Okay, so the quote said, it's called the Physician's Prayer, and it goes as follows.
00:55:04
Speaker
From inability to let well alone, from too much zeal for the new and contempt for what is old, from putting knowledge before wisdom, science before art, and cleverness before common sense, from treating patients as cases, and from making the cure of the disease more grievous than endurance of the same, good Lord deliver us.
00:55:27
Speaker
I think it's a perfect place to stop.
00:55:29
Speaker
I think very wise words, and I'm a big fan of old books, Rahul.
00:55:32
Speaker
My grandfather used to tell me that old books are always great because only the good ones become old, right?
00:55:39
Speaker
Yeah, exactly.
00:55:41
Speaker
Well, Rahul, always a pleasure to have you back to discuss topics that I know you're very passionate about, but also, like in this case, acute and chronic liver failure, a very relevant topic to our audience and to our practices.
00:55:54
Speaker
I look forward to having you back, and thank you so much for sharing your expertise and your time with us today.
00:56:00
Speaker
Thanks, Rory.
00:56:01
Speaker
Thanks for having me.
00:56:01
Speaker
I really appreciate it.
00:56:05
Speaker
Thank you for listening to Critical Matters, a sound podcast.
00:56:09
Speaker
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00:56:15
Speaker
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00:56:19
Speaker
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