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Critical Care of Patients with Cirrhosis
11 Plays6 years ago
In this episode of Critical Matters, we discuss the management of critically ill patients with cirrhosis. Our guest is Dr. Ram Subramanian, Medical Director of Liver Transplantation at the Emory School of Medicine in Atlanta. In his dual role as a transplant hepatologist and an intensivist, Dr. Subramanian is involved in the inpatient care of patients before and after liver transplantation and provides a unique perspective on caring for this complex patient population.
ADDITIONAL RESOURCES:
Management of critically ill cirrhotic patients: a multidisciplinary perspective: https://bit.ly/2Et9hN5
A detailed review on ACLF and the impact of scoring systems on prognosis: https://bit.ly/2AcTtev
A recent study evaluating the incidence and outcomes for patients with cirrhosis admitted to the ICU with an associated editorial by our guest: https://bit.ly/2BnQaAJ hhttps://bit.ly/2QzuPPc
BOOKS MENTIONED IN THIS EPISODE:
The McKinsey Edge: Success Principles from the World’s Most Powerful Consulting Firm by Shu Hattori: https://amzn.to/2QVVvZW
The McKinsey Mind: Understanding and Implementing the Problem-Solving Tools and Management Techniques of the World’s Top Strategic Consulting Firm by Ethan M. Rasiel and Paul N. Friga: https://amzn.to/2Glph6c
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Transcript
Introduction and Guest Introduction
00:00:09
Speaker
Welcome to Critical Matters, a sound critical care podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:17
Speaker
And now, your host, Dr. Sergio Zanotti.
00:00:22
Speaker
Patients with cirrhosis and chronic liver dysfunction from portal hypertension can develop complications that require admission to the intensive care unit.
00:00:30
Speaker
This is a complex and very sick patient population with a high morbidity and mortality.
00:00:34
Speaker
In this episode of Critical Matters, we will discuss some of the most common complications in these patients and their management in the intensive care unit.
Guest's Expertise and Role
00:00:42
Speaker
Our guest is Dr. Ramsu Bromanian.
00:00:45
Speaker
Dr. Subramanian completed his undergrad education, medical education, and residency training at the University of Chicago.
00:00:51
Speaker
He completed a hepatology fellowship at the University of Nebraska before returning to the University of Chicago for postgraduate training leading in gastroenterology, pulmonology, and intensive care.
00:01:02
Speaker
From early in his career, he has been interested in all aspects of studying and treating multi-organ failure in the context of portal hypertension and liver failure.
00:01:10
Speaker
Ultimately, he decided to pursue a career that combined both.
00:01:13
Speaker
Dr. Subramanian is Associate Professor of Medicine and Surgery and the Medical Director of Liver Transplantation at the Emory School of Medicine in Atlanta, Georgia.
00:01:21
Speaker
In his dual role as a transplant hepatologist and an intensivist, Dr. Subramanian is involved in the inpatient care of patients before and after liver transplantation.
00:01:31
Speaker
His clinical and research interests are focused on critical care issues related to hepatic failure and liver transplantation.
00:01:37
Speaker
He's a wonderful clinician, educator, and researcher, and I really can't think of a better person to discuss these topics with.
00:01:43
Speaker
Ram, welcome to Critical Matters.
00:01:46
Speaker
Thank you.
00:01:48
Speaker
So I think that... It's a pleasure to be here.
00:01:49
Speaker
Excellent.
Cirrhotic Patients in ICU
00:01:50
Speaker
I think a good place to start would be maybe giving us an overview of why do patients with cirrhosis come to the ICU in general?
00:01:59
Speaker
So the...
00:02:00
Speaker
A patient with cirrhosis can be admitted to the ICU for both hepatic and extra hepatic organ dysfunction.
00:02:07
Speaker
So if you just run the list of all the potential complications going from head to toe, they can have admission for worsening hepatic encephalopathy, worsening shock from a cardiovascular standpoint, which is typically a distributive shock.
00:02:24
Speaker
They can have unique lung derangements.
00:02:28
Speaker
such as hepatopulmonary syndrome that can cause hypoxemia, portopulmonary hypertension, that is a unique form of pulmonary arterial hypertension, and then they can have worsening in a hepatic hydrothorax that can cause issues in gas exchange.
00:02:46
Speaker
We go to, from a GI standpoint, they can have the very predictable catastrophic complication of massive variceal bleeding that can lead in hemorrhagic shock.
00:02:59
Speaker
And then another unique example from a renal standpoint would be worsening acute kidney injury in the form of hepatorenal syndrome.
00:03:07
Speaker
So that, in a nutshell, gives you an idea of how complex the cirrhotic patient is in the ICU and all the indications they can be admitted with that require critical care management.
00:03:24
Speaker
And I know that there are obviously not a large amount of studies that are focusing specifically on this cirrhotic population in the ICU, but I did come across a paper published earlier this year that you actually wrote an editorial for that came from the UK looking at what has happened in incidents and outcomes with these patients, and it seemed to suggest that
00:03:45
Speaker
even though the incidence of admission to the ICU, at least in the UK, is increasing, the mortality has seemed to improve but remains still high around 30%.
00:03:55
Speaker
And it brings up the concept of acute or chronic liver failure.
00:03:59
Speaker
Could you talk a little bit about that and explain what that concept means?
00:04:04
Speaker
Yeah.
00:04:05
Speaker
So just before we go into ACLF, just the point that you brought up, and this has been borne out in a couple of studies that over –
00:04:13
Speaker
the years, just with an improvement in critical care management of patients with cirrhosis, we have seen a steady improvement in outcomes in these patients admitted to the ICU.
00:04:26
Speaker
So I just wanted to reemphasize the point that he brought up that the application of good critical care makes a difference in these patients.
00:04:35
Speaker
So we should not be giving them a negative prognosis as they hit the ICU.
00:04:43
Speaker
Moving on to this concept of acute and chronic liver failure.
ACLF vs Decompensated Cirrhosis
00:04:48
Speaker
I must admit as an intensivist, I had a tough time wrapping my brain around the concept because as intensivists, we've been taking care of these patients with multi-organ failure in the setting of cirrhosis for a long time.
00:05:00
Speaker
But I think the one important distinction between ACLF and decompensated cirrhosis is as follows.
00:05:11
Speaker
When you think about decompensate cirrhosis, you typically imagine the patient with massive ascites, variceal bleeding, severe hepatic encephalopathy, with end-stage advanced portal hypertension.
00:05:22
Speaker
So that's decompensate cirrhosis.
00:05:25
Speaker
ACLF is a concept that has actually emerged from the hepatology literature where they suggest that folks
00:05:35
Speaker
with liver disease don't need to reach end-stage liver disease manifestations before they present to the ICU with multiragin failure.
00:05:43
Speaker
So you can have, for example, a 35-year-old with mild chronic liver disease who suddenly presents to the ICU in the absence of variceal bleeding, in the absence of severe hepatorenal syndrome with multiragin failure.
00:05:59
Speaker
So I think that is the important distinction
00:06:02
Speaker
that I think just for an intensive care audience is important to appreciate that you don't need a pre-existing history of end-stage liver disease manifestations to go into multirginal failure that is characterized, which is defined as ACLF with a high short-term mortality.
00:06:23
Speaker
So I think the big take-home point is as intensive care providers,
00:06:30
Speaker
we need to be aware that folks with mild chronic liver disease are also at risk for developing multirgon failure that requires aggressive management.
00:06:42
Speaker
So I hope that answers your question.
00:06:43
Speaker
Definitely.
00:06:43
Speaker
And I think, Ram, that based on at least my clinical experience in hospitals that are not dedicated transplant and pathology services, it would seem that
00:06:55
Speaker
probably the majority of our patients that we're admitting to the ICU are more of the ACLF or acute or chronic liver failure characteristic as opposed to true, true end-stage liver disease.
00:07:06
Speaker
And these are patients who either have a variceal bleed, a septic episode, or something else that triggers a decompensation.
00:07:13
Speaker
But I guess my question is, can you tell us a little bit more about these patients?
00:07:16
Speaker
I mean, I think that there seems to be a nihilistic approach to these patients, but the literature might suggest something a little bit different.
00:07:24
Speaker
Yeah, so going back to what we had spoken about before, I think we need to refocus our attention on applying good critical care principles to these patients.
00:07:38
Speaker
I think as opposed to the previous dogma that these patients have a truly negative outcome in the ICU and the fact that they've arrived in the ICU means that their risk of survival is low.
00:07:53
Speaker
We need to change that paradigm and re-strategize as far as offering them aggressive care with a goal to see if you can reverse the acute exacerbation so they can take them to a new steady state as a bridge to temporary stabilization with hopefully an eventual goal to bridge them to liver transplantation.
00:08:20
Speaker
A lot of these patients in ACLF can be in the younger size, and in my experience, age is a huge prognostic indicator as it applies to general critical care as well.
00:08:30
Speaker
But I think in particular in the ACLF patients, we need to be a bit more aggressive about offering them aggressive sort of all the strategies that we have in critical care in order to
00:08:49
Speaker
stabilize them to improve their short-term outcomes.
Managing GI Bleeding in Cirrhosis
00:08:53
Speaker
And I think that following that discussion, one of the most common reasons that I see in my practice, and I think a lot of our listeners see for these patients coming to the ICU, is acute gastrointestinal bleeding, presumed esophageal varices.
00:09:08
Speaker
Can we talk a little bit about how you approach the diagnostic phase first of somebody who comes in with a history maybe of alcohol-induced or underlying liver cirrhosis and now has a GI bleed?
00:09:22
Speaker
Yeah.
00:09:23
Speaker
So the first take-home message there, I think, is that location of the varus is important.
00:09:30
Speaker
So just before we even get into that, the usual things that need to be done for hemorrhagic shock, large-bore IV access, elective intubation for shock, and to facilitate endoscopy, especially if they have a compromised mental status.
00:09:45
Speaker
So those boxes need to be checked.
00:09:47
Speaker
Optimization of hematologic parameters with HDI and R, and the platelet count.
00:09:53
Speaker
And then moving on to treating the bleed itself.
00:09:59
Speaker
If assuming it's a variceal bleed, things that are important is location of the varics.
00:10:06
Speaker
So if it's a esophageal variceal bleeding, then that is more amenable to endoscopic hemostasis with endoscopic band ligation.
00:10:15
Speaker
If there is evidence, even if the patient is arriving from the outside, it's a gastric variceal bleed,
00:10:20
Speaker
Those varices are deeper in the mucosus or in the submucosus.
00:10:24
Speaker
They're typically in the fundus of the stomach, and therefore they're less amenable to endoscopic hemostasis.
00:10:30
Speaker
So in most centers, and especially if it's a sort of a non-academic center that does not have advanced endoscopic techniques, in my mind, a gastric variceal bleed should be an automatic indication to call interventional radiology for potential tips.
00:10:50
Speaker
So I think that's a big take-home message.
00:10:52
Speaker
Oesophageal varices, first try endoscopic band ligation.
00:10:56
Speaker
If it's a gastric varics, they should go straight to a TIPS procedure.
00:11:03
Speaker
The second sort of interventional radiology procedure is a BRTO, a balloon, which stands for balloon occluded transvenous, retrograde transvenous obliteration.
00:11:14
Speaker
That is a procedure where
00:11:19
Speaker
The interventional radiologist does not do a TIPS, so you don't go trans-repathic, but you actually access the, typically it's a gastric varics, directly using an inferior approach through the femoral vein.
00:11:34
Speaker
And you need to have the appropriate anatomy.
00:11:35
Speaker
You need to have a vessel that can be accessed into the gastric varics, but that includes direct coil embolization or ethanol embolization of the bleeding gastric varics.
00:11:46
Speaker
So the next question is when do you choose TIPS versus BRTO?
00:11:51
Speaker
So TIPS has to be used carefully, especially in the high MELD patient.
00:11:57
Speaker
So there are no magic numbers.
00:11:58
Speaker
But most centers, if MELD is greater than 20, or sometimes you wouldn't say 18, there is a risk of post TIPS hepatic decompensation, because you bypass the TIPS blood flow bypasses even those X number of functional hepatocytes.
00:12:13
Speaker
So there is a risk.
00:12:15
Speaker
of hepatic decompensation after tipsing a patient with a high MELSCO.
00:12:21
Speaker
So that is a prime example of where a BRTO may be helpful, where you do not put the patient through the risk of a TIPS in the setting of a high MELSCO, but then he's still able to achieve IR hemostasis with another approach using a BRTO.
00:12:39
Speaker
Another example of where tips may be contraindicated is somebody with right heart dysfunction from portable hypertension.
00:12:45
Speaker
So that is a classic example where if you know you're dealing with somebody with pulmonary artery hypertension with compromised RV function, there is a risk of putting them into acute right heart failure if you tips them and increase their venous return.
00:13:01
Speaker
And so there's another example where in order to prevent cardiac compromise after tips,
00:13:07
Speaker
BRTO may be a good idea instead of doing the TIPS procedure.
00:13:16
Speaker
Other therapies, and they should even precede endoscopy and IR interventions, is number one, octetide, which is a splatening vasoconstrictor, which can decrease splatening blood flow into the bleeding varics.
00:13:31
Speaker
Number two, PPI therapy.
00:13:36
Speaker
which at this moment in time we typically do drips but there's no great data on that.
00:13:41
Speaker
And number three, and which is important, is empiric antibiotics.
00:13:46
Speaker
And empiric antibiotics have been typically it's a choice of subtraction, it's a decent choice but that can be tailored depending on the site, has been shown to decrease the risk of re-bleeding and also improve
Hemostasis and Hemodynamics in Cirrhosis
00:14:01
Speaker
mortality.
00:14:01
Speaker
And the rationale for that is
00:14:03
Speaker
When somebody has a bleed, you increase the risk of bacterial translocation and therefore increase the risk of bacteremia and also the risk of SPP, which can then lead to a systemic cytokine storm.
00:14:16
Speaker
And so the rationale there is to blunt that cytokine storm with empiric antibiotics so that it can improve the portal hypertension and also improve mortality overall.
00:14:32
Speaker
So those are the big ones as far as interventions.
00:14:34
Speaker
The other thing I would add is, and this is a bit of a dying art within gastroenterology and intensive care, is balloon tamponade.
00:14:44
Speaker
I must confess that balloon tamponade has saved me many a time when you have bleeding that's refractory to endoscopic therapy as a bridge to TIPS procedure or to even transplantation.
00:15:01
Speaker
So just to go over the, it's called the Blakemore tube, if you will, or the Minnesota tube, it is basically inflating.
00:15:10
Speaker
It has the esophageal balloon and a gastric balloon, and you insert it in an intubated patient.
00:15:17
Speaker
And it's important to inflate the gastric balloon first,
00:15:22
Speaker
But you have to make sure that you do a test of 50 cc in the gastric balloon to make sure you're blowing the balloon up in the stomach and not in the esophagus.
00:15:32
Speaker
So once you've confirmed that the balloon is indeed in the stomach, then you blow it up to 400 cc with air, and then you pull on the end of the tube and it basically tamponizes the GE junction where the varicoseal supply is.
00:15:49
Speaker
And then the esophageal balloon, if you still have bleeding that's refractory to the gastric balloon insufflation, then you blow up the esophageal balloon with a manometer.
00:15:58
Speaker
But that, in a nutshell, is balloon tamponade therapy.
00:16:04
Speaker
But that is something that should always be considered, especially if you have lack of endoscopic hemostasis with the esophageal bleed or you have acute gastric virus for bleeding.
00:16:17
Speaker
as a bridge to TIPS procedure or a BRTL.
00:16:23
Speaker
And I think that something that is maybe important, I mean, and just get your opinion, obviously the balloon,
00:16:32
Speaker
esophageal or gastric balloon occlusion is really only in those who have confirmed diagnosis endoscopically, right?
00:16:39
Speaker
Because even though we always think that if a patient with cirrhosis is bleeding from the upper GI tract, it's an varices, there are a percent of cases in which it's not, and in those cases, it probably wouldn't help or could cause damage.
00:16:53
Speaker
Correct.
00:16:54
Speaker
So I think that's a good point.
00:16:55
Speaker
So I would always...
00:16:57
Speaker
Either you have outside hospital endoscopic data that documents a varicil bleed or they have been documented with varicil bleeding at your institution.
00:17:06
Speaker
So that's a good point.
00:17:07
Speaker
So I would just confirm that you're truly dealing with a portal hypertensive bleed before you go using a BlakeMall.
00:17:17
Speaker
And in terms of the expectations, what do you think is the current expectations for those who are maybe admitting these patients at night?
00:17:27
Speaker
I mean, endoscopic therapy, both diagnostic and therapeutic, should really be something that occurs within hours of the patient being stabilized, right?
00:17:36
Speaker
That is correct.
00:17:37
Speaker
That is correct.
00:17:37
Speaker
And so I think the call to the GI physician or provider should happen quick.
00:17:45
Speaker
as they hit the ICU, as the patient hits the ICU.
00:17:49
Speaker
I think that's a conversation that should be held early.
00:17:52
Speaker
These patients have a risk of rapidly progressing into hemorrhagic shock.
00:17:57
Speaker
And so I think if there's a suspected variceal bleed, time is of the essence to initiate that GI referral so that they can go on endoscopy sort of in an expedited fashion.
00:18:13
Speaker
Excellent.
00:18:13
Speaker
And I think that two aspects, Ram, that might be worth discussing now, which I think are related to treating especially those very severe or very refractory bleeds, are both the hemostatic aspects of treating cirrhotic patients and the hemodynamic aspects that also can be seen sometimes if patients develop infection or septic shock.
00:18:35
Speaker
So I think that why don't we start a little bit in terms of what are your parameters in terms of how you would support the hemostatic aspect and talk a little bit about what people think occurs in cirrhosis and what actually has occurred in terms of rebalancing.
00:18:50
Speaker
Yeah, so generally speaking, I think one take-home message in regard to the coagulopathy of liver disease is that an elevated INR
00:19:01
Speaker
does not necessarily translate to, in the absence of bleeding, does not relate to high risk of bleeding.
00:19:07
Speaker
Because it's important to note that when you have hepatic dysfunction, you lose both sides of the coagulation cascade.
00:19:14
Speaker
You lose, not only using factor V and VII, you're also losing protein C and protein S. So the net state of coagulation may be normal in these patients.
00:19:24
Speaker
In fact, folks can form DBTs with an INRF3.
00:19:27
Speaker
So that's sort of a question.
00:19:30
Speaker
comments just independent of variceal bleeding once they start bleeding I think all bets are off then you have to think about What is sort of optimal hemostatic hematologic parameters and again this?
00:19:44
Speaker
To my knowledge is no evidence-based data But one thing I would say is that the general consensus is that a political count greater than 50 can optimize
00:19:54
Speaker
thrombin generation and therefore the platelet plug.
00:19:56
Speaker
So that's something we shoot for, is at least keeping the platelet count greater than 50 in these patients.
00:20:02
Speaker
With regard to INR, I think, again, there's no evidence-based data supporting this.
00:20:10
Speaker
I think if you have an INR of 3 or 4 and you're bleeding, then I think it's reasonable to target an INR of sort of closer to 2.
00:20:18
Speaker
And INR FFP is about 1.6, so that's where you're going to get to.
00:20:21
Speaker
So I think that
00:20:23
Speaker
that level of correction is justified as far as using FFP and using platelets.
00:20:31
Speaker
The third would be cryoprecipitate, sort of targeting a fibrinogen.
00:20:36
Speaker
And I think in the setting of bleeding, a target fibrinogen greater than 100, I think is a reasonable goal.
00:20:44
Speaker
So I think those are rough parameters to think about, platelet count greater than 50, fibrinogen greater than 100,
00:20:51
Speaker
and INR is sort of in the range of 1.62 as far as correction of the INR.
00:20:58
Speaker
The other thing that we – again, there's no evidence on this, but if they are in renal dysfunction, and especially in sort of CKD, we do use DDAVP with a goal to improve the qualitative function of those few platelets that they have.
00:21:16
Speaker
So that's something that we do, especially if they have
00:21:20
Speaker
concomitant renal dysfunction.
00:21:25
Speaker
So I think that summarizes my thoughts on the hematologic management.
00:21:30
Speaker
One thing I would, again, as we do all kinds of other forms of hemorrhagic shock, is make sure that you monitor for cold coagulopathy, which can exacerbate the bleeding.
00:21:40
Speaker
So what that means using warmers, blood warmers, especially if you're doing a massive transfusion.
00:21:45
Speaker
Number two, I would make the point about watching serum calcium.
00:21:50
Speaker
as we do for other forms of resuscitation hemorrhagic shock is to monitor your calcium, especially if you're dealing with somebody who's hemodynamically unstable.
00:22:01
Speaker
So that was hematology.
00:22:02
Speaker
And then I think we briefly spoke about sort of cardiovascular ramifications.
00:22:07
Speaker
We can sort of go into that concept.
00:22:10
Speaker
And just to sort of share a few thoughts on that,
00:22:14
Speaker
The patient with cirrhosis who comes to the ICU is exquisitely sensitive to any hypotensive insults because they are living at a baseline decreased arterial blood volume.
00:22:30
Speaker
And that's why we have folks in the clinic or even on the non-ICU inpatient floors who are hanging out a map of 50-55 and they don't have any clinical signs of end-organ hypoperfusion.
00:22:40
Speaker
And that's because they have abnormal symptoms
00:22:44
Speaker
shunting of their cardiac output at a baseline level into the splatonic circulation because of splatonic visodilation.
00:22:50
Speaker
And so we've now come to appreciate that.
00:22:53
Speaker
And because of the splatonic shunt, they have a decreased effect of arterial blood volume.
00:22:58
Speaker
So when you superimpose a new hypotensive insult onto that physiology, whether it's variceal bleeding that causes hypovolemia, whether it's a large volume paracentesis that induces hypovolemia,
00:23:10
Speaker
when you have a septic trigger from a SPP or UTI, or if you have a new onset cardiac dysfunction, that gives you cardiogenic hypotension.
00:23:20
Speaker
All those incels can predictably further worsen the hemodynamic status and put them into a rapidly progressive shock.
00:23:32
Speaker
And so I think that is something for the intensive care provider.
00:23:34
Speaker
That is an important thing to appreciate.
00:23:37
Speaker
is how exquisitely sensitive these patients are to hemodynamic compromise.
00:23:42
Speaker
And then just extending that argument, and this is very predictable, especially in spontaneous bacterial peritonitis, is that you can anticipate or you need to be very vigilant for the development of acute kidney injury just because your hemodynamic collapse is going to cause renal hyperperfusion.
00:24:01
Speaker
And so you can sort of anticipate, you can see that AKI coming when you have
00:24:07
Speaker
a massive viracial bleed or a septic trigger.
00:24:11
Speaker
So just to sort of include hepatorenal syndrome in that context of superimposed shock of any etiology that we need to be aware of.
00:24:23
Speaker
Excellent.
00:24:24
Speaker
I think that one more question regarding the bleeding.
00:24:28
Speaker
So you talked about initial therapies with endoscopic therapies, adjuvant therapy, very important, like you said, to include the antibiotics.
00:24:37
Speaker
What about any role in the ICU or when should the intensivist start thinking about secondary prevention?
00:24:43
Speaker
Let's say we stabilize the patient to get their therapies.
00:24:46
Speaker
Is this something that happens in the ICU or something that happens later in terms of starting patients on
00:24:52
Speaker
potential agents that might prevent re-bleeding.
00:24:54
Speaker
That's a good point.
00:24:56
Speaker
So as you've already alluded to, something that we do routinely is initiate nonspecific beta-blocker therapy with natalol.
00:25:08
Speaker
Once the patient resolves his or her acute injury or acute bleed and stabilizes hemodynamically, then the data would support
00:25:18
Speaker
the initiation of nonspecific beta blockade, blocking both beta 1 and beta 2 receptors in order to decrease the risk of recurrent varicose bleeding.
00:25:28
Speaker
And so just to go with that rationale, beta 1 blockade is supposed to decrease the cardiac output, thereby decreasing splinting blood flow.
00:25:37
Speaker
And the second, the beta 2 blockade is actually to block the beta 2 receptors in the splinting circulation
00:25:45
Speaker
which can then lead to splantening vasoconstriction.
00:25:47
Speaker
So that is the rationale for using a nonspecific beta blocker as secondary prophylaxis for varicose bleeding.
00:25:59
Speaker
There is some data, and I think this is, I must admit, at our center we haven't fully subscribed to this.
00:26:05
Speaker
There is data from the Spanish literature, sort of, investigators in Spain
00:26:14
Speaker
published in the New England Journal about maybe three or four years ago that introduces the idea of an early tips, especially in somebody who has high risk for re-bleeding.
00:26:28
Speaker
It's almost like a prophylactic tips even after the cessation of the initial bleed.
00:26:34
Speaker
And that is something that I think is not universally applied, especially across the U.S. For the reasons that I mentioned, you have to watch
00:26:43
Speaker
You have to weigh the risks and benefits of the TIPS procedure, especially if you're dealing with somebody whose MELSCO is drifting and it may be high risk for post-TIPS decompensation from a hepatic standpoint.
00:26:55
Speaker
But that's more of a center-specific practice as to use TIPS prophylactically as secondary prophylaxis to prevent recurrent variceal bleeding.
00:27:08
Speaker
On that theme, and this is more of a...
00:27:12
Speaker
practice outside the ICU, but just to introduce the rest of the management, these patients should ideally undergo secondary prophylaxis with endoscopic banding as well, especially with esophageal variceal bleeding.
00:27:29
Speaker
They should be scheduled in a few weeks to repeat endoscopic evaluation and potential banding, and that can be repeated every four to six weeks.
00:27:41
Speaker
with a goal to eradicate the varices over time, and this will typically happen in the outpatient setting.
00:27:46
Speaker
So between the natal law and the endoscopic management, that is our sort of current strategy for segmented prophylaxis for variceal bleeding.
Encephalopathy in Liver Failure
00:27:57
Speaker
Excellent.
00:27:57
Speaker
And one of the things that we mentioned about selecting patients for tips is
00:28:02
Speaker
One of the potential complications is increased risk of hepatic encephalopathy.
00:28:06
Speaker
So I think that that might be a good lead way into talking about that other common complication that I think will land patients with cirrhosis in the intensive care unit.
00:28:15
Speaker
So maybe a good point to start, and I've heard you talk about this before, Ram, is making sure that we differentiate between what is
00:28:23
Speaker
the hepatic encephalopathy of acute liver failure or acute hepatic encephalopathy versus what we're talking about in this population with cirrhosis.
00:28:33
Speaker
Yes, I think that's an important point.
00:28:35
Speaker
So just to take a step back, we've been talking about cirrhotic patients, and we can, for the sake of this part of the conversation, couple ACLF with decompensated cirrhosis.
00:28:47
Speaker
So we're dealing with chronic liver disease.
00:28:49
Speaker
There's a whole other population of
00:28:52
Speaker
patients with liver failure that we term acute liver failure and that's a different disease process and just to define acute liver failure or ALF, ALF strictly defined is the onset of hepatic encephalopathy within six to eight weeks of first symptoms of hepatic dysfunction such as coagulopathy or jaundice and
00:29:19
Speaker
and this is the important part of the definition, in a patient without preexisting liver disease.
00:29:24
Speaker
So a classic example would be 28-year-old young person, no chronic liver disease, who takes a whole lot of Tylenol and comes with a Tylenol overdose.
00:29:33
Speaker
So that is the sort of the classic example of a patient with ALF, which is totally different from the rest of our conversation today.
00:29:44
Speaker
When you think about that ALF and think about that hepatic encephalopathy, that
00:29:50
Speaker
that phenotype of encephalopathy is very, very different from the hepatic encephalopathy of this erotic patient.
00:29:59
Speaker
And just to sort of cut to the chase, and then I'll dissect out the mechanistic rationale, when you see a patient with advanced encephalopathy who has achilleophilia, there is a risk of developing pathologic intracranial hypertension and cerebral herniation.
00:30:17
Speaker
So I think that's a big take-home message, and that's why it's so important
00:30:21
Speaker
to make sure you're dealing with ALF or ACLF.
00:30:25
Speaker
In ACLF, or sort of, and I'm using the term a bit loosely and I'm coupling decompensated cirrhosis into that, that hepatic encephalopathy has minimal to no risk of developing intracranial hypertension and therefore developing cerebral herniation.
00:30:46
Speaker
So why do we think this is the case?
00:30:49
Speaker
So just to go through that rationale,
00:30:52
Speaker
Ammonia is a player to some degree in the hepatic encephalopathy in both cases.
00:30:59
Speaker
It's not the whole story because especially in cirrhotic, you can have a stone cold normal ammonia level and they can be florally encephalopathic.
00:31:06
Speaker
So there are other mechanisms.
00:31:08
Speaker
But let's just for the sake of argument say there's some degree of hyperammonemia that contributes to both processes.
00:31:15
Speaker
Compare a 25-year-old tunnel overdose case
00:31:20
Speaker
with a 50-year-old hepatitis C cirrhotic case.
00:31:22
Speaker
So one is ALF and one is ACLF.
00:31:26
Speaker
Ammonia is getting metabolized in the urea cycle in the liver.
00:31:31
Speaker
When you have a hep C cirrhotic who's had the disease process for let's say 25 years, so the urea cycle in that context has been slowly dwindling away, but because of the chronicity of the disease process, you've had the time
00:31:49
Speaker
extrahepatic tissues to upregulate ammonia fixing mechanisms and the enzyme is good to mean synthetase and so for example muscle can upregulate glumensynthetase and so when you have an ammonia challenge where still bleeding for example even though the urea cycle in the liver is not working you've had time for extrahepatic tissues to create sinks for the ammonia and so you
00:32:16
Speaker
protect the brain from seeing an ammonia challenge when you have chronic liver disease.
00:32:23
Speaker
Contrast that scenario to the patient with ALF.
00:32:27
Speaker
25-year-old, perfectly normal, no chronic liver disease, decides to take a whole lot of Tylenol, acutely fries his or her urea cycle.
00:32:37
Speaker
Suddenly, you have a hyperammonemic milieu
00:32:41
Speaker
and you haven't had the luxury of time, as you saw in the cirrhotic, to fix ammonia extrahepatically.
00:32:47
Speaker
So suddenly, the CNS circulation sees this hyperammonic state and is not protected.
00:32:53
Speaker
And astrocytes, by the way, have gloomine synthetase.
00:32:56
Speaker
So then you have the risk of developing acute astrocyte swelling because the ammonia is fixed in the astrocytes.
00:33:05
Speaker
And that, I think, is a good mechanistic explanation for why
00:33:11
Speaker
the patient with ALF can develop cytotoxic edema and then develop intracranial hypertension versus the cirrhotic, which is the focus of our conversation today, who may develop hepatic encephalopathy but does not have the risk or has minimal risk of developing ICP elevations and cerebral herniation.
00:33:33
Speaker
So I think that's a very important take-home message where we need to make sure
00:33:40
Speaker
When we see a patient described as acute liver failure, then number one, we're truly dealing with acute liver failure.
00:33:48
Speaker
And the best way to tease that out, and the first question I ask somebody when they call me, they have a patient with acute liver failure because that term gets used very loosely, is what does the abdominal imaging show?
00:34:01
Speaker
If the CT or the MRI shows a shrunken liver, a big spleen, large varices, massive ascites,
00:34:09
Speaker
That, by definition, is not ALF.
00:34:12
Speaker
It's a ketone chronic liver disease.
00:34:15
Speaker
And so, abdominal imaging is the most practical and useful way to distinguish ALF and ACLF.
00:34:23
Speaker
And then you can triage.
00:34:24
Speaker
And then, if they say that I've got a patient with ALF who is encephalopathic, and they tell me, by the way, the abdominal imaging shows just a mild hepatic edema, the spleen size is normal,
00:34:36
Speaker
that really sends alarm bells off in my mind that this patient is truly ALF because they don't have radiographic signs of chronic portal hypertension and this patient is at risk for herniation.
00:34:46
Speaker
So that changes the whole equation as far as management and then we can get into management in our next conversation.
00:34:58
Speaker
But just to make the distinction regarding pathophysiology
00:35:02
Speaker
and distinguishing between the hepatic encephalopathy of ALF versus the physiology of hepatic encephalopathy of ACLF.
00:35:10
Speaker
I think it's very important and very useful to think about the mechanism because ultimately, like you said, patients with acute liver failure who die of hepatic encephalopathy die because they herniated it.
00:35:21
Speaker
And patients with chronic liver failure or acute and chronic liver failure don't herniate.
00:35:27
Speaker
And if they die, it's because of other issues related to their disease process.
00:35:31
Speaker
So let's dive into the hepatic encephalopathy of this erotic patient.
00:35:36
Speaker
And the first question I have is, I mean, I've always been taught and have thought of the diagnosis as being a clinical diagnosis, but there is obviously the pervasive ammonia level that is always present in the workups.
00:35:52
Speaker
Could you talk a little about the diagnosis and specifically the role of ammonia?
00:35:56
Speaker
Sure.
00:35:57
Speaker
So, um,
00:36:00
Speaker
As a practical point, when I have a cirrhotic who comes in with encephalopathy, I don't even check an ammonia level most of the time.
00:36:08
Speaker
If they are confused, they will see therapy with lactulose, rifaximin, zinc.
00:36:16
Speaker
So just from my decision algorithm regarding treatment, I don't use an ammonia level to guide my decision-making regarding starting therapy.
00:36:29
Speaker
So I think that's an important take-home message regarding for the ICU practitioner is that please don't use a normal ammonia level to rule out a diagnosis of hepatic encephalopathy as you decide to treat hepatic encephalopathy.
00:36:46
Speaker
Just a brief sort of sidebar note, in ALF, in acute liver failure, there's actually good data.
00:36:52
Speaker
that if you're stating the utility of using a serial ammonia level as a prognostic indicator for encyclopathy and intracrinal hypertension.
00:37:01
Speaker
And the data would suggest that if your serial ammonia levels are greater than 150 to 200, you actually have a higher risk of developing elevated ICP and all the negative effects of that.
00:37:14
Speaker
So there is diagnostic utility to serial ammonia levels in ALF.
00:37:18
Speaker
But going back to our population that we're talking about today,
00:37:22
Speaker
I don't routinely use serum ammonia levels to rule in a diagnosis of hepatic encephalopathy in these patients.
00:37:32
Speaker
And my decision regarding treatment is independent of the ammonia level.
00:37:35
Speaker
There is data suggesting, again, a couple of studies suggesting that serum ammonia levels may be useful to gauge response to therapy, especially if you don't have a patient waking up after two, three days of therapy.
00:37:52
Speaker
So there may be some utility with that.
00:37:54
Speaker
And just one other sort of comment in that context is if you have a cirrhotic who's densely encephalopathic, and they're coming in with a fourth admission for hepatic encephalopathy, one take-home message there is we should look carefully at the abdominal imaging, especially the abdominal vascular imaging, because some of these patients can develop spontaneous portosystemic shunts.
00:38:19
Speaker
And the classic example is a spenorenal shunt.
00:38:22
Speaker
It's basically a compulsory mechanism to deal with the portal hypertension to get the venous return back.
00:38:29
Speaker
The problem with some of these spontaneous shunts, especially if they get large, is that they bypass hepatic parenchymal flow.
00:38:37
Speaker
So the blood is not finding its way through the portal vein and totally bypassing the urea cycle, what's left of it.
00:38:42
Speaker
So these kind of patients can become florally encephalopathic even if they don't have a high mental score.
00:38:51
Speaker
and so there'll be a disconnect between the degree of liver disease severity as defined by the MEL score and the hepatic encephalopathy symptoms.
00:39:00
Speaker
So I think that's a useful practical point that if you have hepatic encephalopathy that's disproportionate to the MEL score or it just persists and is refractory to therapy, then you should make sure that you're not sitting on a spontaneous shunt.
00:39:17
Speaker
Now the next question is what do you do with a spontaneous shunt and there are actually
00:39:21
Speaker
case reports regarding embolizing that shunt with IR, but it's sort of a bit tricky.
00:39:27
Speaker
In our center, we have done it, anecdotally for persistence in the fifth admission for hepatic encephalopathy required intubation, but there is a risk of embolizing those shunts because then it can worsen the underlying portal of hypertension.
00:39:42
Speaker
Number two, in our cases, we have actually seen a higher risk of developing meseric vein thrombosis.
00:39:49
Speaker
which has implications regarding transplant candidacy.
00:39:52
Speaker
But just wanted to mention
00:39:54
Speaker
And I think that's a good tip, I mean, for those patients, like you said, that seem to be behaving in a way that goes out of the norm.
00:40:01
Speaker
Now, Ram, in terms of treatment, you mentioned lactulose and rifaximin.
00:40:07
Speaker
Why don't we start with, I mean, just in terms of your general approach.
00:40:11
Speaker
And one of the questions that always arises, or two questions that arise with lactulose is, are enemas a problem and should we avoid them?
00:40:19
Speaker
And two, how do I titrate my lactulose therapy in people in the ICU who might have a rectal tube?
00:40:27
Speaker
So, lactulose enemas, actually, personally, I think they're useful, especially if you have a compromised mental status or a tenuous airway.
00:40:37
Speaker
I think if you have somebody with sort of grade 2 encephalopathy, just to start with lactulose enemas, may be a good starting point to sort of improve the encephalopathy to a degree we can then switch to pure lactulose.
00:40:52
Speaker
So that's one strategy that we do use.
00:40:55
Speaker
A couple of caveats to lactulose in the ICU, and actually I'm almost tempted to say that we sometimes use refraxamine as first line.
00:41:06
Speaker
Number one is beware the risk of developing or exacerbating underlying ileus.
00:41:13
Speaker
Some of these folks may already have a septic ileus to begin with, and so lactulose can worsen that ileus, and we've had cases where
00:41:21
Speaker
folks have shown up to our ICU with nacecal perforation because they've been, I guess, sort of been very, had undergone aggressive lactulose, PO-lactulose therapy.
00:41:33
Speaker
Number two, I would caution against lactulose when you already have underlying metabolic acidosis, and that's typically a gap metabolic acidosis from hepatic failure coupled with renal failure.
00:41:48
Speaker
And then if you,
00:41:51
Speaker
exacerbate that metabolic acidosis with diarrhea, then you can add a component of non-capacidosis as well.
00:41:57
Speaker
So those are a couple of check boxes that I do for lactulose.
00:42:00
Speaker
Ileas and look at a KUB.
00:42:02
Speaker
And number two is watch your acid-base status.
00:42:05
Speaker
And those are, in my mind, a couple of contraindications to using PO lactulose in particular, which makes me actually go towards rifaximin as first line.
Advanced Treatments in Refractory Cases
00:42:16
Speaker
Rectal tubes is sort of a, it's an area of controversy.
00:42:21
Speaker
We've had some pretty significant lower rectal bleeds from chronic indwelling rectal tubes.
00:42:31
Speaker
And so we are still trying to come up with a protocol, and the latest is we deflate.
00:42:36
Speaker
If we put a rectal tube in with a goal to maintain hygiene and prevent circular D-cubes, especially the patient who's in the ICU for a while,
00:42:46
Speaker
We have to be very careful about how long we're keeping the balloon in because especially if there's a risk or the history of rectal varices I think it's definitely should be a contraindication of placing rectal tube number two we've had cases where they've had Stoker ulcers they've had pressure ulcers in the rectum that has caused massive hematochiesia that has been clinically significant so just a word of caution regarding rectal tubes in these patients
00:43:14
Speaker
and weighing the risks and benefits of it, especially when you're giving lactulose and inducing diarrhea.
00:43:20
Speaker
So you bring up a very good point that we have to be careful about the use of rectal tubes in these patients.
00:43:25
Speaker
And how do you titrate your lactulose therapy in general?
00:43:28
Speaker
Oh, yeah.
00:43:29
Speaker
So that part, yeah.
00:43:30
Speaker
So the rough rule of thumb, especially in the non-acute setting, is to titrate
00:43:38
Speaker
the three to four soft bowel movements per day.
00:43:41
Speaker
So that's the sort of the textbook description, especially in the outpatient setting when you're dealing with chronic hepatic encyclopathy.
00:43:48
Speaker
In the acute setting, I can extrapolate that data, but again, I would just watch your acid-base status and make sure you're not inducing a non-capacidosis, especially if you have normal bicarb to begin with, and then watch for the illness as well.
00:44:04
Speaker
So I think those are two issues, but the general
00:44:09
Speaker
The general practices are TID dosing, 30 cc TID, and see how they do, and just watch your bicarb and watch the number of bowel movements.
00:44:20
Speaker
You don't want to be inducing frank diarrhea in these patients.
00:44:24
Speaker
The other thing I should mention is the role of Miralax.
00:44:28
Speaker
As you may know, there's data now.
00:44:31
Speaker
suggesting the use of Miralax instead of lactulose for all the reasons, all the sort of the side effects of lactulose that I mentioned.
00:44:38
Speaker
And so that is something that is anecdotally gaining increasing use in our patients in the ICU, especially if you're having problems with lactulose.
00:44:53
Speaker
So just to mention that as well.
00:44:55
Speaker
And I also have two things.
00:44:57
Speaker
So one comment is that I've heard people talk about the three to four bowel movements being equivalent to like 500 mLs of stool.
00:45:05
Speaker
Is that true or appropriate at maybe indication?
00:45:09
Speaker
Yeah, so that's a rough, I think a decent estimate.
00:45:12
Speaker
I must say I haven't seen, again, I'm not aware of a great correlation with that volume, but I think that's a really
00:45:23
Speaker
reasonable, reasonable estimate, if you will.
00:45:26
Speaker
Something that's a reasonable, yeah.
00:45:30
Speaker
And you did mention the Miralax or the polyethylene glycol.
00:45:34
Speaker
There seems to be more talk about that in the literature.
00:45:37
Speaker
Any other comments you can make on, this I guess would be an alternative, not something you would add to lactulose, obviously, but any other comments on that use?
00:45:47
Speaker
Correct.
00:45:49
Speaker
No, it's just gaining increasing use.
00:45:53
Speaker
I'm not aware of at least the critical care setting a study that has addressed that question specifically, looking at lactulose versus Miralax and looking at sort of clinically important endpoints.
00:46:05
Speaker
But I would just mention that as something that we can use instead of lactulose in this patient population.
00:46:14
Speaker
One other thing that, and again, this is more...
00:46:18
Speaker
Our center specific is the use of albumin dialysis in these patients.
00:46:21
Speaker
So you may be familiar with the MARS system, which is an example of albumin dialysis that's the most used in the world.
00:46:30
Speaker
Very few centers in the US have adopted this strategy yet.
00:46:34
Speaker
But in my experience over the many years, this is the one indication which actually has randomized controlled trial level evidence
00:46:43
Speaker
that shows its efficacy in reversing refractory hepatic encephalopathy and cirrhosis.
00:46:50
Speaker
And our experience has been very supportive of that concept.
00:46:54
Speaker
We have folks, and we're just actually treating somebody now with a meld of 40 intubated, who has been refractory, has grade 4 dense encephalopathy on lactulose, rifaximin, zinc.
00:47:07
Speaker
We've also used IV metronidazole, which is a thing of the past, but we've added that as well.
00:47:14
Speaker
But the patient has refracted you to that, and we started albumin dialysis.
00:47:18
Speaker
And basically, just as a brief word on that, you're replacing the dialysate with a 16% albumin solution instead of an aqueous solution.
00:47:31
Speaker
And the rationale is you're extracting endogenous benzodiazepines, which are an example of a molecule that's specifically albumin-bound.
00:47:39
Speaker
that won't come off with the CRT circuit, but now will come off with the albumin analysis circuit.
00:47:45
Speaker
And in my experience, that has been a very valuable addition to hepatic encephalopathy treatment normatarium in those cases in which folks are refractory to conventional therapy.
00:47:56
Speaker
So this obviously would be something that you're using in refractory cases, but not as a first-line therapy.
00:48:03
Speaker
Correct.
00:48:04
Speaker
Correct.
00:48:05
Speaker
And so it has helped us
00:48:06
Speaker
Liberate folks in the ventilator has prevented us from intubating folks with worsening encephalopathy.
00:48:14
Speaker
So it's been a great addition to our options as far as the treatment of hepatic encephalopathy, especially as these patients are getting sicker and sicker awaiting transplant.
00:48:25
Speaker
Well, one of the things obviously that we've touched on through this conversation is that a
00:48:31
Speaker
You are in a very specialized tertiary, quaternary care center with a transplant service and a dedicated hepatic ICU.
00:48:40
Speaker
But what about in terms of most of our providers or most of our listeners probably are working in hospitals that don't have a transplant unit or don't have a transplant program for hepatic transplantation.
Liver Transplant Evaluation for ICU Patients
00:48:51
Speaker
When should these patients be referred for evaluation?
00:48:54
Speaker
When should we be reaching out to people who are doing transplants to try to get a gauge?
00:48:59
Speaker
Are these patients candidates for transplant or not?
00:49:02
Speaker
Yes, I think if a patient with cirrhosis shows up in the ICU, by definition they've had their first episode of decompensation.
00:49:10
Speaker
And I think in my opinion, if there are no significant psychosocial barriers, and I'll talk about that in a bit, to transplantation, then they should be considered for referral to a transplant center.
00:49:32
Speaker
From a biochemical standpoint, most liver transplant centers will start the ball rolling for transplant evaluation, especially in the outpatient setting, if the MELD score, which is for the audience, that's a score, and it's called a MELD sodium score now.
00:49:48
Speaker
It's basically a function of INR, bilirubin, creatinine, and the sodium, serum sodium.
00:49:55
Speaker
If that MELD score exceeds 15, and by the way, normal is about 6 to 7.
00:50:00
Speaker
The highest you can go is 40.
00:50:01
Speaker
But if it exceeds 15, that's a typical biochemical trigger to start a transplant evaluation.
00:50:09
Speaker
But from an ICU perspective, if they have their symptom of decompensation, variceal bleeding, hepatic encephalopathy, I think that should at least trigger a GI consultation.
00:50:23
Speaker
But the next step would be to think about referring, at least assessing that patient
00:50:31
Speaker
to see if there would be a suitable transplant candidate.
00:50:34
Speaker
So going into that scenario, things that could be potential barriers to transplant.
00:50:41
Speaker
So just to go over medical contraindications would be cardiac contraindications.
00:50:47
Speaker
They have severe three-vessel coronary artery disease or a compromised systolic function defined in the EF less than 40%.
00:50:59
Speaker
or they have severe portal pulmonary hypertension or any other form of pulmonary hypertension where their mean peer pressure is greater than 35.
00:51:07
Speaker
So those will be examples of where we will use those as contraindications to transplantation.
00:51:15
Speaker
Severe lung disease would be, and this is, we're talking about extremes, a severe chronic obstructive lung disease would be another potential, would be a contraindication.
00:51:25
Speaker
Psychosocially, and
00:51:27
Speaker
we can talk a little bit on this.
00:51:29
Speaker
Alcohol was, I'm using the word was, was a, active alcohol is a pretty hard stop for most transplant centers.
00:51:40
Speaker
And so the rough rule of thumb was they have to demonstrate six months of sobriety and be enrolled in a formal alcohol relapse prevention program before they would be considered for transplant evaluation.
00:51:54
Speaker
Now that paradigm is changing.
00:51:56
Speaker
across the country and across the world.
00:51:59
Speaker
And now, many of the centers, including ours, are actually on a case-by-case basis even considering transplant for acute alcoholic hepatitis.
00:52:10
Speaker
So this may be the 35-year-old with fresh binge alcohol, maybe the first attempt of alcohol, acute stressor,
00:52:20
Speaker
but they have a supportive family if they are, and again, this is always a controversial conversation in our selection meetings, but just to make the audience aware that the perspective on transplanting for alcoholic liver disease is undergoing an evolution.
00:52:37
Speaker
And so, you know, the active alcohol consumers that has precipitated the acute event,
00:52:45
Speaker
Depending on where you are in the country, it may be useful to touch base to the nearest transplant center to assess their policy regarding transplantation for alcoholic liver disease.
00:52:57
Speaker
And the other thing I would mention from a social standpoint is we are looking for a very sound family support system or social support system because transplant is putting the liver in just one piece of the whole puzzle.
00:53:13
Speaker
convince ourselves as transplant providers that the liver will be taken care of for a long period of time.
00:53:18
Speaker
So that's the other box we're trying to check is to make sure that there's enough of a family support and social support around to make sure that transplant is justifiable.
00:53:30
Speaker
And from a very practical standpoint, just a question regarding unfunded patients.
00:53:35
Speaker
I mean, most transplant centers probably can't afford to take patients who have no insurance or no funding.
00:53:40
Speaker
Is that correct?
00:53:41
Speaker
Or is that a misconception?
00:53:42
Speaker
That is correct.
00:53:43
Speaker
That is unfortunately, that is the current state of affairs.
00:53:47
Speaker
And we as a center do have on a case-by-case basis, we have X amount of charity care that we can offer.
00:53:56
Speaker
And we typically try to find the right
00:53:59
Speaker
patient for if it's a young patient with the right family support, maybe an acute liver failure from cryptogenic etiology, we do have the option to trigger that financial support, but that's an exception rather than the rule.
00:54:21
Speaker
Unfortunately, there are times when we are unable to
00:54:26
Speaker
offer transplantation as life-saving therapy because of financial issues.
00:54:32
Speaker
And in those candidates or in those patients who are not candidates for transplant, let's say, I think that from what we've discussed, Ram, it seems that these patients, every patient should deserve or deserves being evaluated by a transplant team.
00:54:46
Speaker
So I think that for those providers who are not transplant experts,
00:54:50
Speaker
we should not be making that decision.
00:54:52
Speaker
We should refer these patients early, hear from the transplant team, let them decide, tell us if it's a yay or a nay.
00:54:58
Speaker
But in those who are not candidates, can you talk about some aspects that might be prognostic in terms of very poor outcomes or when, I mean, appropriate goals of care discussions would be reasonable?
00:55:12
Speaker
I came across this paper and we talked about it a little bit before, I'm sorry, recording the podcast from the European Association of Study of Liver Disease and
00:55:20
Speaker
on the organ score and maybe the MELT, just your thoughts on how we could use those scores.
Prognostic Scores and Management Strategies
00:55:26
Speaker
Yeah, so the – especially when you talk about ACLF, I think the data would suggest – again, a few studies in Europe – but the data would suggest that when you're treating somebody with ACLF,
00:55:44
Speaker
you should continue aggressive therapy at least from days three to seven post the acute insult.
00:55:52
Speaker
And the prognostic scoring systems, depending on any of the scoring systems that we use in critical care, I think is applicable.
00:56:00
Speaker
But if the general trend shows an improvement by day seven of therapy, then it may be, especially in ACL, that may be grounds to continue aggressive management.
00:56:11
Speaker
So I think the important take-home message there is not to throw in the towel too fast as far as just offering them critical care support and not sort of drawing a line in the sand after day two or day three of aggressive management.
00:56:26
Speaker
So those would be some initial thoughts.
00:56:28
Speaker
I think there's still data emerging regarding, as you've mentioned, different prognostic scores being used, and the Europeans have really been active in this field.
00:56:37
Speaker
But I think it's important
00:56:39
Speaker
Going back to initial conversation regarding applying our established principles of critical care to this patient population to see if they will reverse their physiology before we deem them to be futile as far as therapeutic approaches.
00:57:00
Speaker
The one thing I would mention in this context is, and I think this question comes up a fair amount, is
00:57:07
Speaker
If a patient is deemed not a candidate at this time for whatever reason, and they are in acute kidney injury, some folks may, some nephrologists in particular may say that, oh, because they're not a transplant candidate, we're not going to support their acute kidney injury without due dialysis.
00:57:23
Speaker
And I would just, again, this is my personal bias, but I would make the argument that, especially a classic example would be alcoholic liver disease with HRS,
00:57:34
Speaker
is that if you stabilize them through the acute episode, and let's say they even transition to intermittent HD, you create a new baseline where you can stabilize them and maybe then create an opportunity for them to be reassessed for transplant in the future.
00:57:56
Speaker
So I think this conversation always seems to come up is,
00:57:59
Speaker
when is it futile to dialyze a patient with HRS, especially if you don't have transplant as an immediate backup.
00:58:05
Speaker
But I would make the argument that, especially with a young patient, to see if you can stabilize them in the short term with a goal to eventually see if they can be a transplant candidate in the future.
00:58:18
Speaker
And I think that that's also, I guess, an important reason why a very robust conversation with a transplant team is important because there's a difference between they're not a candidate now, but if A and B occur, they could be a candidate versus they're not a candidate full stop, right?
00:58:35
Speaker
Yeah, yeah, yeah.
00:58:37
Speaker
And especially in the younger patient, and I'm sort of bucketing younger age with an alcoholic liver disease, but we're seeing, again,
00:58:46
Speaker
We have a couple of patients right now in their 40s who are sick with alcoholic liver disease where we're trying to stabilize and severe multilagin failure where they're not transplant candidates right now.
00:58:55
Speaker
But we're rethinking how we define futility in these patients.
00:59:01
Speaker
Interesting.
00:59:02
Speaker
So I think that this has been a great conversation.
00:59:05
Speaker
There's a lot of topics that obviously we have not been able to dive into that maybe we could touch on on a future podcast.
00:59:12
Speaker
But one of the things that we like to do, Ram, at the end of the podcast is ask our guests a couple of questions not related to the topic just to kind of tap into their general wisdom and knowledge.
00:59:23
Speaker
Would that be OK?
00:59:25
Speaker
Oh, sure.
00:59:25
Speaker
Yeah.
00:59:26
Speaker
So the first question is, what books have influenced you the most or what book have you gifted most often to others?
00:59:35
Speaker
So I must admit I haven't done much reading outside of medicine in the past, but I did go through an MBA recently.
00:59:46
Speaker
And I share this in the context of actually ICU management.
00:59:51
Speaker
I think a lot of our intensive care colleagues are leaders in the ICU.
00:59:55
Speaker
And one book I came across, it's called The McKinsey Edge, and this is the McKinsey Consulting Company based on their context.
01:00:04
Speaker
But this book was written, I think, about a year ago, and I've read a few books on leadership, but this book in particular, I found it as a great read.
01:00:13
Speaker
I just couldn't put it down.
01:00:15
Speaker
And I think it's one of the things that appealed to me.
01:00:18
Speaker
It's very practical information.
01:00:21
Speaker
It's almost like a bullet point that the author expands on.
01:00:25
Speaker
but I think it gives some really useful insight into how a leader manages himself or herself, how he manages the folks that he leads, and how he or she grows in that role.
01:00:43
Speaker
And so I was reflecting on this book in the context of what we do in the ICU as physicians or as other providers, how we interact with our colleagues.
01:00:55
Speaker
Because at the end of the day, ICU is a team sport.
01:01:00
Speaker
And so I've been reflecting on that book and what I've learned from that book, which may be applicable to our ICU context.
01:01:09
Speaker
So that's one book in particular, The McKinsey Edge.
01:01:11
Speaker
And by the way, this is a series of books.
01:01:13
Speaker
There's a McKinsey mind.
01:01:14
Speaker
But it basically pulls those business concepts from that consulting firm and sees how we can apply it to other contexts, including medicine.
01:01:24
Speaker
And I think that a lot of it, a lot of what we need to learn is really universal, right?
01:01:29
Speaker
It's about managing people, managing teams, managing oneself.
01:01:33
Speaker
And like you said, I mean, where it's a context of a consulting firm or an intensive care unit, a lot of the behaviors that need to be managed are very similar.
01:01:41
Speaker
So we'll definitely put that book in the show notes.
01:01:43
Speaker
I mean, I have not read that book, but I definitely will pick it up.
01:01:46
Speaker
Sounds like a very interesting read.
01:01:48
Speaker
The second question, Ram, is what do you believe to be true in medicine or in life that most other people don't believe?
01:01:58
Speaker
So as I respond to this, I'm not sure whether I can say that other people don't believe, but I just want to say one philosophy that I have as I'm teaching medicine, especially to my trainees, is that
01:02:16
Speaker
Especially in ICU medicine, it's complex.
01:02:18
Speaker
We're dealing with a lot of data points.
01:02:20
Speaker
We're dealing with a lot of intricate physiology.
01:02:22
Speaker
But I always emphasize to them what I sort of term as first principles.
01:02:27
Speaker
Go back to your first principles.
01:02:29
Speaker
There are certain limited tenets of physiology, for example, that if you understand those basic building blocks, then you can use those building blocks to then connect the dots, however complex a system becomes.
01:02:47
Speaker
and I applied the same concept when I was teaching biochemistry, where you can, even though you've got
Shifting from Curative to Comfort Care
01:02:54
Speaker
so many biochemical reactions that deal with carbohydrate, fat, and protein metabolism, at the end of the day, you have seven reactions or eight reactions that underlie all those different biochemical pathways.
01:03:10
Speaker
So it's about getting those basics right and then connecting the dots.
01:03:16
Speaker
So I hope that
01:03:18
Speaker
that answer makes sense, but I just wanted to, I sometimes feel that we get so caught up in, especially as you're coming through the ranks of the complexity of medicine, especially in ICU medicine, that we sometimes forget the underlying foundation of it.
01:03:38
Speaker
So just a thought that I wanted to say with the audience is to really focus on the foundational blocks that then
01:03:48
Speaker
in many ways explains very complex systems.
01:03:51
Speaker
I love it.
01:03:52
Speaker
I think that getting back to first principles, it makes a lot of sense.
01:03:57
Speaker
I'm a big jazz fan, and Charles Mingus used to say that making the simple complex is commonplace, but making the complex exceedingly simple is creativity.
01:04:07
Speaker
And I think it applies also to the way you think at the bedside, right?
01:04:10
Speaker
There's a lot of clutter, but being able to go to those first principles, I think, is a great way to move forward and take good care of patients.
01:04:18
Speaker
And I would argue that whether people believe it or not, they don't behave in that way.
01:04:22
Speaker
Very often, I think they make things more complicated than they should.
01:04:25
Speaker
So I think it's a good reminder for the audience.
01:04:29
Speaker
And the last question, Ram, is what would you want every intensivist who's listening to our podcast today to know could be a fact or a quote or something specific about this population that we just discussed?
01:04:41
Speaker
Yeah, I'm reflecting on this question and maybe I'll just go back to what one of my mentors in critical care told me when I was in training.
01:04:54
Speaker
One thing I really appreciated him was his conversations with families regarding potential futility of care and sort of end of life discussions.
01:05:05
Speaker
This is something I still use to this day.
01:05:06
Speaker
I just channel his phrase.
01:05:10
Speaker
We do a lot of aggressive things in intensive care with a goal to reverse the process or the derangement.
01:05:20
Speaker
But one thing that he always said is, despite all the advancements in modern medicine, it has its limitations.
01:05:30
Speaker
And so as intensive care providers, we need to know
01:05:36
Speaker
when all interventions are potentially futile and whether we need to change our goals of care from one of cure to one of comfort.
01:05:47
Speaker
And the sort of that statement, although I learned this, I don't know, many years ago, it's still something that I use every time when I'm having that difficult conversation with the patient's family at the bedside.
01:06:04
Speaker
So I think just
01:06:06
Speaker
I just, as I was reflecting on this question, that's what came back to me as something that I wanted to share with the audience is to, we do a lot of high acuity procedures and interventions, but I think we just need to make sure that we check the box regarding the potential of
01:06:31
Speaker
futility of interventions, and how to have that conversation with the patient's loved one regarding making the transition from a curative process to a comfort process.
01:06:43
Speaker
And I think that this is a great place to stop.
01:06:46
Speaker
I really appreciate your time, Ram.
01:06:48
Speaker
Hope to have you back on the podcast soon and wish you a great end of the year.
01:06:53
Speaker
Thank you very much for your time.
01:06:55
Speaker
Thank you.
01:06:56
Speaker
Thanks a lot too.
01:06:57
Speaker
And thank you for having me.
01:06:59
Speaker
This was a great experience.
01:07:00
Speaker
Thank you.
01:07:03
Speaker
Thanks again for listening to Critical Matters.
01:07:06
Speaker
Make sure to subscribe to this podcast on iTunes or Google Play.