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Management Of Acute - On - Chronic Liver Failure: Part 2
15 Plays5 years ago
In this episode of Critical Matters, we will continue our discussion on the management of acute-on-chronic liver failure (ACLF) in the ICU. Part 2 will cover pulmonary, rena,l and endocrine recommendations for ACLF patients. In a previous episode (Management of ACLF: Part 1) we covered an introduction to ACLF, cardiovascular, and hematology management recommendations.
Our guest is 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 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: journals.lww.com/ccmjournal/Fullt…cute_and.17.aspx
Guideline for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: journals.lww.com/ccmjournal/Fullt…cute_and.29.aspx
SCCM Liver Guidelines: www.sccm.org/getattachment/Rese…s-Table-Part-1.pdf
Books Mentioned in this Episode:
Thinking Fast and Slow by Daniel Kahneman: www.amazon.com/Thinking-Fast-Slow-Daniel-Kahneman
Recommended
Transcript
Introduction to Critical Matters Podcast
00:00:06
Speaker
Welcome to Critical Matters, a sound critical care podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:14
Speaker
Sound Critical Care provides comprehensive critical care programs to hospitals across the country.
00:00:20
Speaker
To learn more about our programs and career opportunities, visit www.soundphysicians.com.
Continuation of Liver Failure Discussion with Dr. Nanchal
00:00:27
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And now your host, Dr. Sergio Zanotti.
00:00:32
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Today we will continue our discussion on acute and chronic liver failure with Dr. Rahul Nanchal.
00:00:38
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This is a continuation of our previous episode where we discussed in detail guidelines related to the management of adult acute and acute and chronic liver failure in the ICU.
Pulmonary, Renal, and Endocrine Considerations in Liver Failure
00:00:48
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In the first part of our discussion, we talked about cardiovascular and hematologic considerations.
00:00:54
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Today, we're going to talk about pulmonary, renal, and endocrine considerations to finalize our discussion.
00:01:01
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related to this topic.
00:01:03
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Rahul, welcome back to Critical Matters.
00:01:06
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Thank you, Sergio.
00:01:07
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Happy to be here.
00:01:09
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Obviously a fascinating topic.
00:01:11
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We discussed a lot of issues related to acute and chronic liver failure in our previous episode.
00:01:17
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We delve in a bit more detail to the cardiovascular and hematology considerations.
00:01:22
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And today we're going to start with pulmonary.
00:01:25
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And there's a lot we can talk about, but I want to focus on three specific topics.
Portopulmonary Hypertension in Liver Transplant Candidates
00:01:30
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Portopulmonary hypertension,
00:01:31
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hepatopulmonary syndrome, and hepatic hydrothorax.
00:01:35
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So why don't we start with portopulmonary hypertension.
00:01:38
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Just tell us a little bit about what it is and what are the current recommendations for management.
00:01:43
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Sure.
00:01:43
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So portopulmonary hypertension is a specific type of pulmonary hypertension that occurs
00:01:51
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in uh you know specifically patients with chronic liver disease now i you know i i don't think we need to get in too much into the mechanisms you know the the mechanisms are complex and you know probably have to do with uh you know changes in the uh you know at the level of the pulmonary arterioles combined with the increased flow through the pulmonary system but just you know be that as it may just suffice it to say that
00:02:16
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you know, these people are at risk for, uh, or for pulmonary hypertension and especially the liver transplant candidates are being screened all the time because, uh, if you do develop pulmonary hypertension, uh, you know, about a certain level, it is actually a contraindication to liver transplant because, uh, people have acute right heart failure during the reperfusion phase once, uh, you know, and, you know, basically just very high incidence of mortality if, you know, of, uh, if that happens.
00:02:45
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And so people are always on the, at liver centers, people are always on the lookout for the development of pulmonary hypertension in the context of liver disease.
00:02:58
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And this is actually a arterial, this is not venous hypertension.
00:03:02
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This is actually pulmonary arterial hypertension.
00:03:06
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So unlike diastolic dysfunction where the pulmonary hypertension occurs because of pulmonary venous hypertension,
00:03:12
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this actually is truly a disease that is at the specific level of the, you know, sort of pulmonary arterioles.
00:03:23
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And again, Sergio, not a lot of data on what and how to treat this.
00:03:31
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What we do know is that, you know, if you do treat this and people are able to, and the pulmonary artery pressures are able to be reduced, people can get liver transplants.
00:03:42
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And so, you know, it's sort of an important entity to think about and, you know, and sort of start treatment if able.
00:03:49
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Now, the treatment is, you know, what to treat it with is sort of, you know, sort of controversial.
00:03:59
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The reason it is controversial, again, is because it is not high quality data.
00:04:03
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There is just one randomized controlled trial, which included
00:04:09
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exclusively, you know, portopulmonary hypertension patients, and which showed that Masitentan, which is, you know, one of the, you know, one of the drugs used for pulmonary hypertension, sort of improved hemodynamics and was safe in this population.
00:04:28
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Another drug, which is called Risaguat, was again, you know, one of the drugs used for pulmonary hypertension.
00:04:36
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They had about 13 patients with photopulmonary hypertension in that trial.
00:04:41
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And so much of the literature that is out there is extrapolated from the broader pulmonary hypertension literature.
00:04:53
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And although there are some small uncontrolled studies, some small observational studies of pulmonary hypertension-directed therapy, what we do know is that we should try and treat this
00:05:05
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and we should sort of try and bring the mean pulmonary artery pressure below 35, which is sort of the target for liver transplantation.
00:05:18
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And again, there was a conditional recommendation.
00:05:22
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There was low quality of evidence for all of the factors that I have described.
00:05:27
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But again, this is a unique and one of the very unique entities, this is very specific to liver disease.
00:05:33
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And I think treatment of this is probably necessary, not, obviously liver transplantation is sort of the ultimate goal, but even in terms of increasing exercise capacity, quality of life and things of that nature, I think something that should be considered for treatment.
00:05:55
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Excellent.
00:05:57
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And again, emphasizing that whole concept in clinicians who are not,
00:06:02
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working in transplant centers, they might overlook that even some situations like this when treated would make somebody eligible.
00:06:11
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So it's important to make sure that we have the right referrals and the right support to assure that we're providing the best options for our patients, regardless of what we can offer at our institution or not.
00:06:24
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Absolutely.
00:06:25
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I think if a person with liver disease gets diagnosed with pulmonary hypertension, that person should likely be referred to a liver transplant center because, again, they probably are the people who have the most experience with what to do and how to do this and how to best evaluate so that people become eligible for liver transplants.
00:06:48
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Yep.
00:06:49
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Excellent.
Hepatopulmonary Syndrome and Liver Transplantation
00:06:50
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The second topic I wanted to ask you about, Rahul, relates to hepatopulmonary syndrome.
00:06:55
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And I still remember how fascinated I was when I first understood and actually saw the bedside orthodioxia.
00:07:05
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And it just illustrates how pathophysiology sometimes can be so interesting from the clinical perspective.
00:07:12
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Yeah, this is, you know, again, this is one of the, so it is interesting, Sergio, that, you know, these are two opposite ends of the spectrum in terms of, you know, how the pulmonary vascular bed is affected in liver disease.
00:07:25
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You know, one is the development of photopulmonary hypertension, and, you know, the other is the development of these
00:07:31
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intravascular pulmonary, some IVPDs or intravascular pulmonary dilatations, which sort of lead to hypoxemia and sometimes refractory hypoxemia.
00:07:42
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But there is this phenomenon called orthodeoxia and proteptomia, which is just the opposite of what you find in heart failure.
00:07:49
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And so you lay down and you lay down flat and your shortness of breath gets better and your oxygen saturations actually get much better.
00:08:00
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And so it sort of behaves like a right to left intra-cardiac shunt at the level of the atrium.
00:08:09
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Just that it is not, these are pulmonary dilatations at the level of the arterioles and the capillaries.
00:08:18
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leading to severe hypoxemia.
00:08:21
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So again, the interesting thing about hepatopulmonary syndrome, Sergio, is that it is very responsive to liver transplantation.
00:08:32
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And people can be hypoxemic even after transplantation and hypoxemic for a few months.
00:08:39
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Some people just wonderfully get cured, and we don't know which
00:08:43
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who will and who won't, but there are some people that where the hypoxemia even persists, but over time it gets much, much better.
00:08:51
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And there is a exception to the liver transplant allocation score for hepatopulmonary syndrome, because if left alone, the people with hepatopulmonary syndrome actually do
00:09:03
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with exactly the same severity of disease, people with hepatopulmonary syndrome long-term tend to do worse than people who don't have hepatopulmonary syndrome and liver transplantation is actually a good cure.
00:09:13
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And so, you know, and so the people should be considered for this.
00:09:19
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There have been a variety of patients
00:09:26
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things tried for this.
00:09:28
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Ultimately, there was only one randomized control trial of garlic, which was done in India and showed some benefit in oxygenation, but it was a very small trial.
00:09:40
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So in the end, we just ended up saying, pending liver transplantation, we really don't know how to take care of this.
00:09:49
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This is just a best practice statement.
00:09:50
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So please give oxygen and provide supportive care.
00:09:54
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And the important aspect of not only recognizing the pathophysiology, which obviously is very interesting for us as clinicians, but the important message seems to be, Rahul, that this is something that is reversible with liver transplant and that supporting the patients as we get them ready for a liver transplant or as they get evaluated for a potential liver transplant is really what we should be focusing on at the bedside.
00:10:15
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Yes, that is true, sir.
Management of Hepatic Hydrothorax
00:10:17
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The last topic I wanted to talk within the pulmonary realm relates to hepatohydrothorax, which is
00:10:24
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a difficult clinical situation to manage sometimes and that is very usual or something that we see commonly in these patients as they have advanced disease that can cause a lot of symptoms.
00:10:37
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So what are the thoughts on, current thoughts and the recommendation on management of hepatic hydrothorax?
00:10:44
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Yeah, so there was a paucity of data on how to do this,
00:10:53
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As you have mentioned, this is the, so ascites, sort of you could, I think in my opinion ascites is probably more manageable than hepatic hydrothorax in terms of symptoms.
00:11:08
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Because once you develop hepatic hydrothorax, you get this, you get short of breath and you get this intense respiratory distress and things of that nature.
00:11:20
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it is a more difficult entity to manage, in my view, than just the societies.
00:11:29
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You know, obviously, TIPS, which decreases the portal pressures, is very helpful in both taking care of refractory acypies and hepatic hydrothorax.
00:11:44
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However, we do know that TIPS also increases the risk of hepatic encephalopathy.
00:11:47
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It may not be possible in all
00:11:50
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on all these patients.
00:11:51
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So if PIPS is not possible, we did say as a best practice statement that the tube thoracostomy with an attempt to cloridesis should be tried.
00:12:00
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Now there is a, there's sort of a misconception with, sort of a slight misconception with tube thoracostomy in these patients as well, that if you do tube thoracostomy, there will be continuous leakage of fluid, there'll be electrolyte loss and things of that nature, or there'll be infections.
00:12:17
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However, you know,
00:12:20
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most of the studies that have been out there have not really bored this out.
00:12:26
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And in systematic reviews of just, of, you know, tube therocostomies for non-malignant diffusions in general, rates of spontaneous pleurodesis have been very, very high, including the people with hepatic hydrothorax.
00:12:47
Speaker
and and so you know in an attempt to relieve symptoms in an attempt for paliation you know this can be tried uh with uh you know with either you know to either a palliative intent or you know spontaneous pleurodesis uh you know in fact in in people who were who got a there was a small series of patients uh in uh who had puped throcostomy as a bridge to liver transplant and
00:13:15
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there was spontaneous pleurodesis in about 50% of the patients.
00:13:19
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And so if you do this, you know, it is quite possible that there'll be pleurodesis and that, you know, that you might get rid of the problem.
00:13:28
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Excellent.
00:13:29
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And we did mention the last two that we discussed actually fall within a category that we didn't discuss at the beginning.
00:13:39
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I just wanted to make sure that we emphasize this to our
00:13:43
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listeners.
00:13:43
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We talked about strong recommendations as we recommend, we talked about what that implies.
00:13:48
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We talked about conditional recommendations as we suggest, and you also have a series of best practice statements.
00:13:55
Speaker
Could you just give us a short commentary, Rahul, on the best practice statement?
00:14:01
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Sure.
00:14:01
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So I think, you know, a best practice statement is a ungraded, strong recommendation.
00:14:13
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which are developed in, you know, in some, in very strict adherence to some guidelines.
00:14:25
Speaker
And the criteria for best practice statements, I think there are six criteria for best practice statements, okay?
00:14:32
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So one of the criteria is, is the statement actionable?
00:14:35
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So, you know, if you make a best practice statement, can an action be taken?
00:14:40
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The second criteria is, is the message necessary?
00:14:44
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The third criteria is, is the net benefit or harm unequivocal?
00:14:53
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The fourth criteria is, is the evidence difficult to connect and summarize?
00:14:58
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The fifth criteria is the rational explicit.
00:15:01
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And the sixth criteria is, can the grade be formally applied to it?
00:15:06
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where a grade cannot be formally applied and the evidence is really, you know, difficult to sort of collect, summarize and, you know, and use meta-analytic techniques.
00:15:15
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And there is a question that really needs a statement which is actionable.
00:15:19
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I think that is how we develop best practice statements.
00:15:22
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And so I think the panel thought that this was such a common problem that, you know, there, and there needed to be some guidance of, you know, what to do, but there was not enough evidence where we could,
00:15:36
Speaker
sort of summarize it and grade it formally, and so then therefore we issued a best practice statement, if that makes sense.
00:15:44
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It does, and it's a very important consideration because you're really identifying as a panel of experts a very relevant clinical issue that clinicians encounter on a regular basis and providing guidance in those instances obviously with actionable
00:16:05
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recommendations is also very valuable.
00:16:07
Speaker
And like you said, another big part of the effort that you've done with this document and with this whole process is identifying potential gaps in our knowledge that are worth investigating further with research in the future.
00:16:22
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Yes.
00:16:24
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Excellent.
00:16:25
Speaker
Well, we covered the three pulmonary topics that I think are most germane and relevant to acute and chronic liver failure.
00:16:32
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There's other things that you talk about in the document
00:16:35
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that will refer our audience to the document to read about that really relate to how we treat patients with respiratory failure in the ICU in general.
00:16:45
Speaker
But I wanted to move on to the renal considerations, Rahul.
Hepatorenal Syndrome: Diagnosis and Treatment Evolution
00:16:49
Speaker
And in the renal considerations, obviously, the one and foremost topic for acute and chronic liver failure, from my perspective at least, that I wanted to touch on is the hepatorenal syndrome.
00:17:03
Speaker
often encountered and often misunderstood.
00:17:07
Speaker
Yes.
00:17:08
Speaker
So, so can we maybe start with just discussing hepatorenal syndrome, you know, a little bit, I think the, you know, maybe the general audience may benefit from.
00:17:19
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Absolutely.
00:17:20
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Yeah.
00:17:21
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So, you know, traditionally hepatorenal syndrome, you know, hepatorenal syndrome very simply explained is a non-structural kidney injury
00:17:33
Speaker
that occurs because of the underlying pathophysiology of liver disease, which is splatonic vasodilation, but intense renal vasoconstriction because of arterial underfilling.
00:17:45
Speaker
So that is sort of, you know, in a very, very succinct way explaining, you know, the pathophysiology of, you know, of liver disease in general and what happens to the kidney.
00:17:55
Speaker
So that, you know, because if,
00:17:57
Speaker
arterial underfilling, there is intense retention of salt and water because the kidney thinks that it's being underfilled and that's the whole process of development of Xytes and things of that nature.
00:18:08
Speaker
And as the liver disease progresses, as vasodilation progresses, more of this sort of becomes a vicious cycle and the vasoconstriction in the kidney becomes even more intense.
00:18:21
Speaker
And then, you know, and finally the kidneys, you know, sort of fail, but really there is not a lot of structural damage to the kidneys.
00:18:31
Speaker
So it doesn't like, you know, you find tubular necrosis or things of that nature.
00:18:34
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If you look at the kidney, the kidney sort of, you know, appears to be structurally not normal.
00:18:42
Speaker
And the way we used to diagnose hepato-renal syndrome was that, you know, we would wait for a creatinine
00:18:50
Speaker
to go up to 2.5 in two weeks.
00:18:54
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And then, and this was, and I'm talking about like one hepatorenal syndrome and there were two types, and the definitions have changed.
00:19:01
Speaker
And then we would say, well, okay, now the creatinine is 2.5, it's been a couple of weeks.
00:19:06
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Let's try and give albumin to make sure that people are not hypovolemic.
00:19:10
Speaker
Let's stop the diuretics.
00:19:12
Speaker
Let's make sure that there is no shock.
00:19:14
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Let's make sure that it is actually in the context of cirrhosis and the cytis.
00:19:19
Speaker
which is liver disease, and then let's make sure that there is no structural kidney injury, which means they would say there is no other process going on, which would say, okay, there is no proteinuria, there are no red blood cell casts on your own microscopy, and the renal ultrasound is normal.
00:19:35
Speaker
So that was the definition that we used to use for hepatorenal syndrome, sort of acute kidney injury, very, very specific to patients with liver disease.
00:19:49
Speaker
And then we realized that, you know, when we were, you know, when we were doing this, A, we had all of these problems with creatinine because, you know, you wait for a creatinine to go up to 2.5.
00:19:59
Speaker
It may never go up to 2.5 because there's no muscle mass in many of these liver patients.
00:20:04
Speaker
And that we are, we were delaying therapy for too long.
00:20:06
Speaker
And if we delayed therapy for too long, you know, it was, people, you know, sort of had, you know, really worse, had bad outcomes.
00:20:15
Speaker
And so as our definitions of acute kidney injury in general evolved, the definitions of acute kidney injury for liver disease evolved as well.
00:20:26
Speaker
And hepatorenal syndrome type one became hepatorenal syndrome AKI or AKI hepatorenal syndrome.
00:20:32
Speaker
And the definition changed to say, well, if you have a increase of creatinine of 0.3 in 48 hours and you meet the rest of the criteria, that is hepatorenal syndrome.
00:20:44
Speaker
And so, and it was done in an effort so that, you know, we could recognize this, recognize this early.
00:20:52
Speaker
It took away some of the problems of, you know, of waiting for creatinine of 2.5 and we could start therapy.
00:20:58
Speaker
So, so, you know, I think, I think now what has happened, you know, due to that is that, you know, people are very much more attuned to the development of, you know, acute kidney injury in people who have liver disease
00:21:13
Speaker
and much more attuned to the development of hepato-renal syndrome in sort of people who have liver disease.
00:21:23
Speaker
Excellent overview.
00:21:24
Speaker
And with regards to the specific recommendation, it relates to vasopressors.
00:21:31
Speaker
What you'd explained in terms of the pathophysiology is we have severe vasodilation peripherally and severe vasoconstriction at the level of the liver.
00:21:39
Speaker
So I presume that what we're trying to do is
00:21:41
Speaker
increase the perfusion pressure that the kidney sees by raising the the pressure of the blood getting there is that correct yeah that's right so that's in essence what we are doing we are trying to control you know we are trying to construct these splatonic meso you know uh uh splatonic bed raise the mean arterial pressure and direct blood flow to the kidney so that is in essence what we are trying to do uh you know with these
00:22:05
Speaker
vasopressors, you know, obviously we are also trying to, you know, make sure that you have adequate circulating volume.
00:22:10
Speaker
So, you know, albumin has sort of become the sort of part of treatment of adrenal syndrome, but the specific use of vasoconstrictors in this context is exactly what you described is to divert blood flow to the kidney and to perfuse the kidney better.
00:22:25
Speaker
And the recommendation that the guidelines made was to recommend using vasopressors over no use, over not using vasopressors in critically ill patients
00:22:34
Speaker
with acute and chronic liver failure who developed hepatorenal syndrome.
00:22:37
Speaker
Any specific comments on the base of pressure that you would recommend?
00:22:44
Speaker
So, you know, and this is an area of where people have, you know, people have very strong opinions, I think.
00:22:55
Speaker
So teluripressin is not available in the U.S. And if you look at, you know, most of Europe, what is used there is teluripressin.
00:23:02
Speaker
However, if you look at, and granted there are not a lot of head to head comparisons, but if you do look at a systematic review, and now that has been, that was published in the Cochrane database, and I think just underwent a recent revision, they were not able to find any sort of, firstly, the evidence was very low quality, but they were not able to find evidence of any
00:23:31
Speaker
of benefit of one vasopressor over the other.
00:23:36
Speaker
So whether you use norepinephrine or you use vasopressin, or sorry, telvipressin, there was no difference in outcomes.
00:23:46
Speaker
Now, when you use mitodrine and octreotide, there was some suggestion that the reversal of hepatorenal syndrome may be a little delayed by using mitodrine and octreotide, which is what we use for splantic vasoconstriction.
00:24:01
Speaker
in the United States most often.
00:24:04
Speaker
But again, the quality of evidence was very low.
00:24:08
Speaker
And if you have to, so because telerepresent is not available in the US, if you have to use norepinephrine, that requires a central line in it.
00:24:15
Speaker
And in most places, I would presume admission to the intensive care unit.
00:24:19
Speaker
And mitodrine and octetide can just be given on the floor.
00:24:23
Speaker
And so one has to benefit, you know, sort of risks and benefits of, you know, doing either.
00:24:28
Speaker
And so therefore our recommendation was general that, you know, what if you diagnose vasopressor syndrome, please use, you know, a vasopressor agent and that vasopressor agent could be telrepresant, could be norepinephrine or mitodermal octetine.
00:24:42
Speaker
Excellent.
00:24:43
Speaker
Another important aspect of hepatoretinal syndrome relates to the fact that A, it's not reversed or cured with dialysis.
00:24:53
Speaker
but B, it is reversed and cured with a liver transplant.
00:24:57
Speaker
So identifying those patients who are truly candidates for liver transplantation is gonna be very important, and also how we would continue to support them if the renal failure deteriorates.
00:25:08
Speaker
Could you comment on that, Rahul, please?
Renal Replacement Therapy as a Bridge to Transplantation
00:25:10
Speaker
Yeah, sure.
00:25:11
Speaker
So, and that, and certainly you make a wonderful point, an excellent point, that if you develop an uric renal failure with hepatotype 1 hepatorenal syndrome,
00:25:24
Speaker
And you're sure it is hepatorenal.
00:25:25
Speaker
So it's not a reversible cause of acute kidney injury, but it is HRS, AKI, and you develop aneuretic renal failure to the point where you're requiring renal replacement therapy.
00:25:36
Speaker
So just placing people on renal replacement therapy does not recover with just renal replacement therapy.
00:25:47
Speaker
Liver transplantation is what is needed.
00:25:51
Speaker
And so the people who should get, you know, again, the people who should be put on renal replacement therapy are the people who are candidates for liver transplant.
00:26:03
Speaker
And, you know, and the renal replacement therapy should most often or most often, you know, there was strongly urge people to consider to use in hepatorenal syndrome to use renal replacement therapy as a bridge to liver transplantation.
00:26:22
Speaker
Excellent.
00:26:23
Speaker
The final topic I want to ask you about relates to endocrine and nutrition considerations.
Glucose Management in Liver Failure Patients
00:26:30
Speaker
And I would like to start with the ever ongoing discussion of glucose control.
00:26:37
Speaker
And the guidelines have a strong recommendation for serum glucose control.
00:26:42
Speaker
Could you tell us a little bit more about that, Rahul?
00:26:46
Speaker
Yeah.
00:26:46
Speaker
So, you know, so these are, so Sergio, these are,
00:26:52
Speaker
Again, it is difficult to find a randomized, or there is, I shouldn't say it's difficult, there is no randomized controlled trial of glucose control in people with liver failure.
00:27:08
Speaker
However, we do know generally that tight glucose control or very tight glucose control increases the risk of hypoglycemia.
00:27:17
Speaker
And this is probably
00:27:23
Speaker
way more applicable to people who have liver disease because they are prone to hypoglycemia for a variety of reasons that I think people are well aware of in any way.
00:27:36
Speaker
And so the consequences of hypoglycemia and first the occurrence or the chance of occurrence may be underestimated and the consequences of hypoglycemia
00:27:51
Speaker
may be underestimated as well.
00:27:52
Speaker
There was, you know, a few retrospective analyses have, you know, shown that people with decompensated cirrhosis, you know, had a much higher risk of mortality if they develop hypoglycemia.
00:28:10
Speaker
And so I think the, while we do not want, you know, blood sugars
00:28:15
Speaker
Yeah, I think we have moved away from the days where we want blood sugars running in the 300s and 400s from anyone.
00:28:21
Speaker
But I think the risk of hypoglycemia is real, especially for the liver disease population.
00:28:26
Speaker
And that, you know, our recommendation was founded on the basis that, you know, we should make a recommendation which sort of avoided the risk of hypoglycemia, but at the same time, you know, recognized that, you know, more than moderate hyperglycemia is
00:28:45
Speaker
uh yeah more than more than a little to moderate hypoglycemia is you know is probably not beneficial for patients and so you know so that so extrapolating from the other evidence and the wonderful uh meta-analyses several meta-analyses that you know that have been performed we sort of issued a strong recommendation on uh you know on keeping the blood sugar between 110 to 180
00:29:10
Speaker
which we felt would sort of balance both worlds, not induce the risk of hypoglycemia and not cause too much hypoglycemia as well.
00:29:20
Speaker
And this is actually a target that many ICUs have kind of fallen into in guidelines for most critically ill patients.
00:29:28
Speaker
But like you pointed out, in this particular population, hypoglycemia not only can be very recalcitrant to treatment,
00:29:36
Speaker
especially in the acute liver failure, but also is associated with high risk.
Dietary Protein Intake Considerations in Liver Dysfunction
00:29:43
Speaker
Correct.
00:29:45
Speaker
The next question relates to dietary protein load.
00:29:49
Speaker
Obviously, in patients who have chronic liver dysfunction, so that would include our patients with acute and chronic liver dysfunction, we're always worried about hepatic encephalopathy, and there's always been like a kind of a
00:30:01
Speaker
popular conception that if we give them too much protein, they won't be able to metabolize that and that could be a problem.
00:30:08
Speaker
What is the current thought and what is the recommendation along those lines?
00:30:11
Speaker
I think the current thoughts are that if you restrict protein and even in the patients of liver failure and cirrhotics, all you do is lead to amino acid breakdown, which causes metabolic derangements.
00:30:31
Speaker
there are reduced hypo-glycogen stores.
00:30:38
Speaker
Sorry, there are reduced glycogen stores in people with liver disease.
00:30:44
Speaker
And then when you become critically ill, there is a depletion of carbohydrate stores, and then there is amino acid breakdown.
00:30:52
Speaker
And if you don't feed someone protein, I think this response just gets
00:30:57
Speaker
exacerbated and it becomes a vicious cycle and it gets worse.
00:31:02
Speaker
These people more than others already have protein.
00:31:05
Speaker
Many of these people already with liver disease already have severe protein, calorie malnutrition, and they are not eating well before they become sick in general.
00:31:18
Speaker
And breakdown of amino acids and make breakdown of more muscle is probably not a good thing, probably exacerbates all of the metabolic arrangements, including hepatic and supply.
00:31:27
Speaker
Now there are not a lot of, there's not a lot of direct evidence, you know, for what happens, but there are some small trials and there is one small randomized control trial, which, you know, which sort of showed that protein restriction had no benefit on either hepatic encyclopathy or, you know, or mortality.
00:31:48
Speaker
And so, you know, we thought that, you know, restricting protein is probably, physiologically,
00:31:57
Speaker
Sure, there is a small randomized control trial, not a whole lot of other data, but this physiologically does not make sense to recommend restricting protein in these people.
00:32:06
Speaker
In fact, if enough protein is, the outcomes are probably likely to be better if people are fed and they are probably in better shape for liver transplantation and so on and so forth.
00:32:25
Speaker
the required protein that they need.
00:32:28
Speaker
Excellent.
00:32:29
Speaker
And the final considerations I would like to explore, Rahul, relate to medications in patients with acute or chronic liver failure.
Medication-Induced Liver Failure and Pharmacist Collaboration
00:32:37
Speaker
And there's two aspects that you've commented on the guidelines.
00:32:42
Speaker
One is looking for medication-induced liver failure in these patients, and the other one is to working with our pharmacy colleagues in dose adjusting.
00:32:52
Speaker
Could you make comments on both of those?
00:32:54
Speaker
Yeah, sure.
00:32:54
Speaker
So, you know, if you look at the United States, not worldwide, just, you know, just practicing and if you look at the United States and if you look at, you know, ALF, although it is rare or acute liver failure, there about 40 to 50% of, you know, acute liver failure is drug related.
00:33:23
Speaker
Obviously the most common cause is, as everyone knows is acetaminophen or Tylenol, but there are other idiosyncratic drug reactions, herbal medications, and a lot of other recreational drugs.
00:33:39
Speaker
There are a lot of other things which have been associated
00:33:42
Speaker
with liver injury.
00:33:46
Speaker
So anyone who comes in with ALF and ACLF, and what I forgot to mention, I'm sorry, when the first part of the talk when we were talking about ACLF is that at least in the European, the canonical study with the European study, for the first time described this entity, people were able to identify a cause in 60% of the patients.
00:34:10
Speaker
a cause of ACLF was not identified in 40%.
00:34:15
Speaker
And while people think that there could be sort of translocation across the gut of all of these bacterial products, which set up inflammatory response syndromes and things of that nature, it could easily be an overlooked medication that is causing some sort of drug-induced lung injury that has caused deterioration and acute on chronic liver failure or even
00:34:37
Speaker
acute liver failure.
00:34:40
Speaker
So I think it is really, really important that, and this is a highly overlooked, I think in clinical practice, and this is applicable to all of us, even at liver transplant centers that we tend to overlook the, or don't, or there is some sort of cognitive bias that makes us overlook drugs as an important cause of liver injury or acute on chronic liver failure.
00:35:04
Speaker
And I think a thorough assessment should be done
00:35:08
Speaker
once our patients present, especially in people where a cause is not easily identifiable.
00:35:19
Speaker
As to the dose adjustment of medications, I think this is very, the hepatic metabolism of drugs and what happens to the metabolism in acute liver failure or acute on chronic liver failure.
00:35:34
Speaker
especially if people are on ECMO or on RRT or have, you know, mass circuits, which a lot of liver transplant, transplantation centers use is really, really, really, you know, underestimated.
00:35:46
Speaker
And I think our pharmacists are the best people.
00:35:48
Speaker
It's a multi, it's a, always thought of critical care as a team sport.
00:35:52
Speaker
And, and, you know, our pharmacists are, are really, really important members of the team.
00:35:57
Speaker
And this is where they can be so helpful in those,
00:36:01
Speaker
in sort of pharmacological principles and dose adjustments in people who have chronic liver disease and sort of, because I can guarantee you the metabolism and the pharmacokinetics of many drugs are altered in people who have chronic liver disease or acute liver failure or acute on chronic liver failure.
00:36:18
Speaker
Excellent.
00:36:19
Speaker
So we discussed a breadth of topics related to this fascinating group of patients with acute on chronic liver failure.
Review of ICU Management Guidelines for Liver Failure
00:36:29
Speaker
I will put a lot of links in our show notes to the guidelines, which I encourage our listeners to read in more detail.
00:36:39
Speaker
Before we go to the closing part of our podcast, Rahul, I just want to kind of reemphasize the six strong recommendations that you've all made.
00:36:50
Speaker
Number one, recommending against the use of hydroxyethyl starch for initial resuscitation in patients with acute on chronic or acute liver failure.
00:36:59
Speaker
Number two, recommending using norepinephrine as a first-line basal suppressor in patients with ALF or ACLF who remain hypotensive despite flutal resuscitation.
00:37:10
Speaker
Number three, recommend viscoelastic testing, TEG or ROTM, over measuring INR, platelet, phrenogen, and critically ill patients with ALF or ACLF undergoing procedures.
00:37:22
Speaker
Number four, recommending against the use of electromalpav
00:37:27
Speaker
and acute chronic liver failure patients with thrombocytopenia prior to surgery or invasive procedures.
00:37:34
Speaker
Number five, recommending using vasopressors over not using vasopressors in critically ill patients with ACLF who develop hepatorenal syndrome.
00:37:44
Speaker
And number six, recommending targeting a serum glucose of 110 to 180 milligrams per deciliters in patients with acute liver failure or acute on chronic liver failure.
00:37:57
Speaker
Fascinating discussion, Rahul.
00:37:59
Speaker
Now let's move away from clinical medicine.
Dr. Nanchal's Influential Book and Decision-Making Insights
00:38:03
Speaker
And we'd like to finish the podcast with some questions that are unrelated to the clinical topic.
00:38:08
Speaker
Would that be okay?
00:38:10
Speaker
Absolutely, Sergio.
00:38:11
Speaker
The first question relates to books.
00:38:13
Speaker
What book or books have influenced you the most?
00:38:16
Speaker
Or what book have you gifted most often to others?
00:38:20
Speaker
I think the answer to both the questions is the same.
00:38:23
Speaker
So the book I think that has influenced me the most and I've gifted most often is by Daniel Kahneman called Thinking Fast and Slow.
00:38:35
Speaker
And just for those who are not aware, Daniel Kahneman is one of the fathers of behavioral economics, of cognitive theory.
00:38:44
Speaker
He obviously got a Nobel Prize for the work that is explained in that fabulous book.
00:38:49
Speaker
And it has tremendous implication
00:38:51
Speaker
to how we make decisions under uncertainty, which is every day in the ICU.
00:38:56
Speaker
So highly recommend it.
00:38:58
Speaker
We'll put a show link that is among my favorite books as well.
00:39:01
Speaker
And really a fascinating topic.
00:39:05
Speaker
It is, it is.
00:39:06
Speaker
It is.
00:39:07
Speaker
And maybe I shouldn't be saying this out aloud, but I have reread the book six times now.
00:39:13
Speaker
Well, there's nothing wrong with that.
00:39:18
Speaker
We read a lot, but sometimes people recommend that we should perhaps
00:39:22
Speaker
read less books and read the really good books more times.
00:39:25
Speaker
So you're right on track there, Rahul.
00:39:27
Speaker
Definitely a book worth rereading.
00:39:31
Speaker
The second question is, what do you believe to be true in medicine or in life that most other people don't believe, or at least they behave like they don't believe?
00:39:42
Speaker
Okay, I think, Sergio, the answer to the question is probably related to a lot of concepts.
00:39:52
Speaker
that are sort of so well elucidated in thinking fast and slow.
00:39:59
Speaker
So what I believe, I think, and perhaps, I don't know how many people believe this or not, maybe a lot of people do, but I think what I believe is that the greatest hoax of healthcare is that we convince ourselves that all of our actions benefit patients.
00:40:18
Speaker
And I don't think that is true.
00:40:21
Speaker
And I think that we take solace in all of these quality systems and our safety nets and things of that nature and believe that we are providing really good quality and great healthcare.
00:40:38
Speaker
And what we fail to realize is that these systems and the people who created them suffer from the same cognitive biases
00:40:47
Speaker
that lead to the errors in the first place.
00:40:50
Speaker
And the errors that occur are actually rare and one-off events.
00:40:56
Speaker
And we spend a lot of time sort of discussing those events and we don't ask the right questions.
00:41:02
Speaker
Our questions are, oh, what could be done better?
00:41:08
Speaker
Oh, what went wrong and what could be done better?
00:41:10
Speaker
And where the real question should be
00:41:12
Speaker
you know, given the exact same sense, you know, set of circumstances, what is the probability that a better decision could be made?
00:41:19
Speaker
And this iatrogenic harm is all around us.
00:41:22
Speaker
And you know, that we should be much more cognitively attuned to the amount of iatrogenic harm that, you know, that we cause patients.
00:41:29
Speaker
And that, you know, and one of the major iatrogenic harms is diagnostic error and suffers from, again, you know, it is all due to the same
00:41:38
Speaker
of cognitive biases that are explained and the behavioral aspects of cognitive decision-making theory that are explained in Daniel Kahneman's book.
00:41:50
Speaker
The other thing that's very fascinating about this issue that you mentioned, Rahul, is that two things I'll comment.
00:41:57
Speaker
One is that COVID has been an exponential lab test
00:42:05
Speaker
for seeing this every day in our behavior and the behavior of our colleagues.
00:42:09
Speaker
The prevalence of these cognitive biases and how they've led people to behave one way or the other is evident every day during this pandemic.
00:42:19
Speaker
And it's definitely worth reading and reconsidering how can we do a better job.
00:42:24
Speaker
And the second aspect that is very relevant, and I was thinking as you were sharing your thoughts, is this whole concept of resulting where we
00:42:35
Speaker
attach the quality of our decision-making to an outcome, yet we fail to recognize that in life in general, but definitely in medicine, luck is a huge component of that.
00:42:51
Speaker
And you can have perfect reasoning, make the right decision, the patient dies, and we may be thinking, what could we have done differently?
00:42:59
Speaker
What could we do better?
00:43:01
Speaker
Or on the other hand, what I see sometimes is we have horrible reasoning and the patient survives and we don't question anything because we think we did the right thing.
00:43:09
Speaker
And you were exactly mentioning that, and I believe it's a very powerful concept that all of us as clinicians should have the humility to really reflect on on a daily basis.
00:43:19
Speaker
Absolutely.
00:43:22
Speaker
The last question relates to what would you want every intensivist who's listening to us to know could be a quote, a fact, or something related to what we discussed today.
00:43:32
Speaker
So maybe, so, sorry, I'll leave you with a, something that has influenced me since I was a medical student and you know, in India, the, the book that we used for, to learn a physical examination was called Hutchinson's clinical methods.
00:43:52
Speaker
And, and you know, and he, the Hutchinson, you know, was a fabulous clinician from,
00:43:59
Speaker
Britain and the book's been around since the 1920s.
00:44:02
Speaker
But he had a few lines in there, a quote, which I will tell you.
00:44:08
Speaker
And I think that has influenced me and my practice all my life.
00:44:13
Speaker
So the lines of the quote is as follows.
00:44:18
Speaker
From inability to let well alone, from too much zeal for the new and contempt for what is old,
00:44:27
Speaker
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.
00:44:46
Speaker
That is a very powerful quote, a perfect place to stop Rahul.
00:44:52
Speaker
I do want to thank you first for the monumental effort that you and your
00:44:57
Speaker
panel did for such a wonderful document and such an important topic for our clinical practice.
00:45:03
Speaker
And second, for giving us the time to discuss these topics in more detail, I missed obviously a very difficult surge in Milwaukee and Wisconsin in general.
00:45:16
Speaker
Please take care.
00:45:18
Speaker
I look forward to seeing you soon again in person, but also having you back on the podcast.
00:45:22
Speaker
Thank you, my friend.
00:45:25
Speaker
Thank you for listening to Critical Matters, a Sound Critical Care podcast.
00:45:29
Speaker
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00:45:35
Speaker
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00:45:40
Speaker
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