A hepatology question

[Solidsnake]

I'm not sure if this is the right forum section

45 years old male patient , cirrhotic, His condition rapidly deteriorated without obvious precipitating factors

What do u think are the causes of this deterioration ?
What investigations do u order ?

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[Dimoak]

I'm not sure if this is the right forum section

45 years old male patient , cirrhotic, His condition rapidly deteriorated without obvious precipitating factors

One of the most important things is to get Hx of illness.

What do u think are the causes of this deterioration ?

Portal hypertensive bleeding ddx ascites, CBDobs

What investigations do u order ?

Prothrombin INR, bilirubin, multiview liver, shunt consult (depending on acuteness).

Hopefully that helps somewhat. 🙂

 

[Solidsnake]

Ok the question lacks some information , the patient has ascites and the rapid deterioration concerns his mental functions

should that give suspicion of development of post cirrhotic hepatitis and then Hepatoma ..... and maybe spontaneous bacterial peritonitis ?

Thanks Dimoak for help

 

[Dimoak]

Based on the information you've provided, IMHO the likeliest pathology would be PSE. What precipitating factors have been ruled out?

 

[Scaredshizzles]

Ok the question lacks some information , the patient has ascites and the rapid deterioration concerns his mental functions

should that give suspicion of development of post cirrhotic hepatitis and then Hepatoma ..... and maybe spontaneous bacterial peritonitis ?

Thanks Dimoak for help

If AMS is all you're going on as far as deterioration, then you're mainly considering just hepatic encephalopathy (ammonia levels may be a marker to follow up, physical exam signs like asterixis.) Variceal bleeding leading to shock and serious SBP may of course lead to AMS, but you don't mention GIB nor fever/acute abdomen.

You always follow up LFTs on cirrhotic patients. (contrary to popular belief, LFTs generally remain somewhat elevated until the very bitter end, but as mentioned bilirubin/coags may be better at identifying exacerbations.) Reasons for exacerbations may include hepatitis, hepatoma, SBP and increased functional load relating to diet/meds/substance. You look at electrolytes; and if you really suspect something is up, you tap the ascites.

If you're still grasping for a diagnosis, if the patient was hepatitis - before. you would consider serology. The tap probably isn't very reliable for detecting malignancy if the patient had underlying cirrhosis, but AFP and imaging.


As far as what I've seen, usually elevated ammonia levels are a prereq for lactulose treatment for cirrhotic patients with AMS, but I don't know if the actual guidelines require that---but remember it isn't the most pleasant of treatments unless you're massively constipated.

 

[Solidsnake]

What precipitating factors have been ruled out?

I guess ingestion of proteins, drugs, tapping, trauma, surgery,

You look at electrolytes; and if you really suspect something is up, you tap the ascites.

could tapping the ascites cause further encephalopathy ?

my professor says

"Keep the patient wet and wise better than dry and demented"

 

[Scaredshizzles]

I guess ingestion of proteins, drugs, tapping, trauma, surgery,



could tapping the ascites cause further encephalopathy ?

my professor says

"Keep the patient wet and wise better than dry and demented"

If you think there is an infection you don't have much of a choice, you need the diagnosis. And sometimes you need large volume paracentesis to relieve syptoms from massive ascites when nothing else works. Of course you risk introducing infection w/ this...And it is hard to clear infections with ascites as their focus (it is like trying to sweep a pond clean, not so easy for your immune system.)

 

[Dimoak]

I guess ingestion of proteins, drugs, tapping, trauma, surgery,

In this case, the precipitates you should be watching are serum levels of potassium, sodium, glucose, water, and renal insufficiency. Low enough levels of the aforementioned combined with high basicity would rule in PSE.

I definitely agree with ammonia markers as well, as high levels would necessitate ICP monitoring.

 

[Scaredshizzles]

In this case, the precipitates you should be watching are serum levels of potassium, sodium, glucose, water, and renal insufficiency. Low enough levels of the aforementioned combined with high basicity would rule in PSE.

I definitely agree with ammonia markers as well, as high levels would necessitate ICP monitoring.

The only problem with this is where do you set the cut offs for electrolyte imbalance to think it is contributory? Patient's with ESLD just aren't going to have normal electrolyte levels. Terminal or near terminal patient's in general regardless of cause usually don't have normal electrolyte levels; in addition edema certainly tends to cause hyponatremia by dilution effect; and the presence of ascites tends to give degrees of kidney dysfunction and poor adrenal output. If you've been trending the BMP for a while you might be able to note an acute change.

 

[Dimoak]

I'm not sure if the values are set in stone, but I'd say <125mmol Na, <2.75 K, and <3.0 sugar would be clinically significant for non-infection PSE, especially if drug ingestion isn't a culprit.

I believe there's literature that demonstrated certain types of encephalopathy responded to lactulose even in the absence of CSE of Ammonia, although even then those levels improved. In the event of infection, you may not need lactulose as the encephalopathy will in many cases respond to neomycin.

 

[Scaredshizzles]

I'm not sure if the values are set in stone, but I'd say <125mmol Na, <2.75 K, and <3.0 sugar would be clinically significant for non-infection PSE, especially if drug ingestion isn't a culprit.

I believe there's literature that demonstrated certain types of encephalopathy responded to lactulose even in the absence of CSE of Ammonia, although even then those levels improved. In the event of infection, you may not need lactulose as the encephalopathy will in many cases respond to neomycin.

It's pretty much been shown that ammonia is not likely the direct cause of hepatic encephalopathy, it's just a good marker, like urea for kidney failure/uremia. The one problem with ammonia of course is that you're dealing with a volatile gas, which can give very variable test results. You draw bloods a few minutes from each other and you'll have the same urea level, but the value of your ammonia test is not so precise, just like an ABG can be pretty variabe.

 

[Dimoak]

My point was that if you have a confirmed case of MHE or PSE, you need ammonia markers to determine whether ICP monitoring would be required. Ammonia doesn't cause encephalopathy, but encephalopathy generally includes elevated ammonia levels, which can increase ICP to the point of herniation risk. I'm not sure if the literature has concluded on a specific value, but the general consensus is that if any of the draws show high levels of ammonia, ICP becomes a concern even if later draws don't show a value as high.

 

[Scaredshizzles]

My point was that if you have a confirmed case of MHE or PSE, you need ammonia markers to determine whether ICP monitoring would be required. Ammonia doesn't cause encephalopathy, but encephalopathy causes elevated ammonia levels, which can increase ICP to the point of herniation risk. I'm not sure if the literature has concluded on a specific value, but the general consensus is that if any of the draws show high levels of ammonia, ICP becomes a concern even if later draws don't show a value as high.

I don't think I've ever seen elevated ICP in cirrhotic encephalopathy. Severe acute hepatic encephalopathy (poisoning usually) is said to lead to brain herniation (like Reye's syndrome.) But I haven't seen enough of those cases to know the utility of ammonia levels in deciding when to monitor ICP. (I'd imagine it would be better to play it safe a monitor ICP in severe acute liver failure than to wait for neurological signs or papilledema to develop.)

But I've never read nor can I think of a mechanism by which encephalopathy itself can raise ammonia levels, in the latter case it would be the severe acute hepatic failure that would raise ammonia levels. In a sense some of the vascular changes related to cirrhosis and portal hypertension might actually protect the body from the release of toxins more systemically (i.e. trapping in ascites.)

p.s. I just searched for it, and I do see some cases of elevated ICP in cirrhosis related encephalopathy. I can't really comment on that, but I've seen a fair number of inpatients with a working diagnosis of hepatic encephalopathy and elevated ammonia levels who were not in an ICU receiving ICP monitoring nor receiving measures to manage possible elevated ICP.

 

[Dimoak]

I don't think I've ever seen elevated ICP in cirrhotic encephalopathy. Severe acute hepatic encephalopathy (poisoning usually) is said to lead to brain herniation (like Reye's syndrome.)

n=? (I'm not trying to be abrasive, I'm just curious).
Encephalopathy can sometimes be misdxed in a cirrhotic patients with AMS due to their treatment. Real PSE most often occurs in ESLD with a fairly lengthy hx of cirrhosis. Encephalopathy doesn't actually cause brain herniation; they can just both occur simultaneously because the buildup of toxins in the brain due to a heavily scarred liver can cause both AMS (encephalopathy) as well as astrocytitis (increased ICP, which can lead to herniation).

But I've never read nor can I think of a mechanism by which encephalopathy itself can raise ammonia levels, in the latter case it would be the severe acute hepatic failure that would raise ammonia levels.

As I mentioned above, encephalopathy does not raise ammonia levels. I just realized that in my previous post I wrote "causes" instead of "includes". Sorry about the confusion. 🙂

In a sense some of the vascular changes related to cirrhosis and portal hypertension might actually protect the body from the release of toxins more systemically (i.e. trapping in ascites.)

That would actually be like emptying cotton balls into a stream. Sure some of it would be seeped up, but in the case of hepatic shunting, most of those toxins would get passed (or around) the liver, and at that point, they're going to endup right back in the heart. Since ammonia penetrates the blood brain barrier pretty easily, it causes astrocyte inflammation, which swells the brain. The reason(s) lactulose is given is/are

1.) it inhibits the conversion of protein into ammonia in the bowel,

2.) the associated lumenal pH drop helps convert ammonia into ammonium, which then gets absorbed into the lumen (some literature suggests this, but I'm not sure if it's been proven).

 

[Scaredshizzles]

n=? (I'm not trying to be abrasive, I'm just curious).
Encephalopathy can sometimes be misdxed in a cirrhotic patients with AMS due to their treatment. Real PSE most often occurs in ESLD with a fairly lengthy hx of cirrhosis. Encephalopathy doesn't actually cause brain herniation; they can just both occur simultaneously because the buildup of toxins in the brain due to a heavily scarred liver can cause both AMS (encephalopathy) as well as astrocytitis (increased ICP, which can lead to herniation).


Not abrasive, just a good discussion. I imagine that perhaps you have spent more time in an ICU than I have. But being at a center with plenty of ICU beds, I can tell you the vast majority of classic hepatic encephalopathy is managed with inpatient beds. You certainly might have cerebral edema as part of your pathophysiology, but herniation really isn't the concern with your classic encephalopathy in your cirrhotic patient. As such, ICP monitoring just isn't done often from a practical standpoint, you monitor ICP when you're concerned about actual herniation. With toxic ingestion hepatic encephalopathy, that is a different story, you do get patients herniating. What the difference is in terms of pathophysiology, I don't know?...perhaps in chronic liver disease the brain adapts to being exposed to increasing levels of toxin over time...as opposed to the mechanism I suggested before, that portal hypertension slows down toxin deliver to the systemic circulation. The why I suggest that theory is the observation in the past that shunting (especially before TIPS procedure was implemented) can precipitate hepatic encephalopathy.

Now you might have more of a surgical or ICU background and perhaps you have seen the other side of it, those few cases where ICP rises significantly enough that you wish to monitor it. But from a general prospective, it is not common. Now if you're not certain it is directly related to the cirrhosis---which of course does happen, or if the patient is suffering other sequelae--bleeding, renal insufficiency, etc., the patient may be in a more monitored setting at first.

 

[Dimoak]

Not abrasive, just a good discussion. I imagine that perhaps you have spent more time in an ICU than I have. But being at a center with plenty of ICU beds, I can tell you the vast majority of classic hepatic encephalopathy is managed with inpatient beds. You certainly might have cerebral edema as part of your pathophysiology, but herniation really isn't the concern with your classic encephalopathy in your cirrhotic patient. As such, ICP monitoring just isn't done often from a practical standpoint, you monitor ICP when you're concerned about actual herniation. With toxic ingestion hepatic encephalopathy, that is a different story, you do get patients herniating. What the difference is in terms of pathophysiology, I don't know?...perhaps in chronic liver disease the brain adapts to being exposed to increasing levels of toxin over time...as opposed to the mechanism I suggested before, that portal hypertension slows down toxin deliver to the systemic circulation. The why I suggest that theory is the observation in the past that shunting (especially before TIPS procedure was implemented) can precipitate hepatic encephalopathy.

Now you might have more of a surgical or ICU background and perhaps you have seen the other side of it, those few cases where ICP rises significantly enough that you wish to monitor it. But from a general prospective, it is not common. Now if you're not certain it is directly related to the cirrhosis---which of course does happen, or if the patient is suffering other sequelae--bleeding, renal insufficiency, etc., the patient may be in a more monitored setting at first.

Perhaps in a classic case where infection brought on the hepatic encephalopathy and is actively being treated with abx or the pt was put on lactulose at the onset of encephalopathy, it's going to reverse before it becomes a threat to the brain. It seems that a lot of the literature that advocates ICP monitoring in hepatic encephalopathy has it secondary to FHF, which wouldn't apply to a cirrhotic. I was referring to a case where an endstage cirrhotic could have had toxins building up in the brain for weeks before finally presenting with encephalopathy. In this case, the increased ICP wouldn't be due to fluid in the extravascular compartment, but rather inflammation of astrocytes. I think at that point, you'd want to know ICP for multiple reasons, if at least to see whether the pt would qualify for a transplant.

 

[Scaredshizzles]

Perhaps in a classic case where infection brought on the hepatic encephalopathy and is actively being treated with abx or the pt was put on lactulose at the onset of encephalopathy, it's going to reverse before it becomes a threat to the brain. It seems that a lot of the literature that advocates ICP monitoring in hepatic encephalopathy has it secondary to FHF, which wouldn't apply to a cirrhotic. I was referring to a case where an endstage cirrhotic could have had toxins building up in the brain for weeks before finally presenting with encephalopathy. In this case, the increased ICP wouldn't be due to fluid in the extravascular compartment, but rather inflammation of astrocytes. I think at that point, you'd want to know ICP for multiple reasons, if at least to see whether the pt would qualify for a transplant.

Right, I mean there is a fair amount of research I'm sure on acute liver failure, like there is probably close to as much research on DM1 as there is on DM2. In acute liver failure, there is more hope for recovery or at the least more success with transplant compared to the cirrhotic who already has damage to various other organs. No one ever knows how much the information can be usefully adapted to chronic disease with likely different pathophysiology (i.e. does the somogyi effect really apply in type 2 DM or are you just harming the patient by pulling back on the insulin. Or how directly does tightening glucose control prevent macrovascular adverse outcomes in DM2...that is of course being hotly contested in NEJM and JAMA on nearly a weekly basis.) I think it is probably safe to say that in cirrhosis related hepatic encephalopthy you do get brain edema (edema is common to the pathophysiology of most encephalopathy, viral or toxic). But the edema alone just isn't usually the cause of death if there is death.

 

[Dimoak]

Right, I mean there is a fair amount of research I'm sure on acute liver failure, like there is probably close to as much research on DM1 as there is on DM2. In acute liver failure, there is more hope for recovery or at the least more success with transplant compared to the cirrhotic who already has damage to various other organs. No one ever knows how much the information can be usefully adapted to chronic disease with likely different pathophysiology (i.e. does the somogyi effect really apply in type 2 DM or are you just harming the patient by pulling back on the insulin. Or how directly does tightening glucose control prevent macrovascular adverse outcomes in DM2...that is of course being hotly contested in NEJM and JAMA on nearly a weekly basis.) I think it is probably safe to say that in cirrhosis related hepatic encephalopthy you do get brain edema (edema is common to the pathophysiology of most encephalopathy, viral or toxic). But the edema alone just isn't usually the cause of death if there is death.

So we're in agreement, that in a straightforward hepatic encephalopathy case that's responding well to treatment (neomycin, lactulose, or rifaximin if available and indicated) ICP issues really aren't a concern. But in a more complicated case with advanced cirrhosis, unclear tests or hx, ammonia and ICP monitoring would be indicated.

 

[Scaredshizzles]

So we're in agreement, that in a straightforward hepatic encephalopathy case that's responding well to treatment (neomycin, lactulose, or rifaximin if available and indicated) ICP issues really aren't a concern. But in a more complicated case with advanced cirrhosis, unclear tests or hx, ammonia and ICP monitoring would be indicated.

Generally I would say not advanced cirrhosis...cirrhosis is end stage liver disease from a chronic process. What is referred to as fulminant liver failure is where you're more concerned as ICP. (I hate the term fulminant because I don't think it is a good descriptive word in this case.)

 

[Solidsnake]

thanks Dimoak & Scaredshizzles for your participation .

 

[Dimoak]

Generally I would say not advanced cirrhosis...cirrhosis is end stage liver disease from a chronic process. What is referred to as fulminant liver failure is where you're more concerned as ICP. (I hate the term fulminant because I don't think it is a good descriptive word in this case.)

Well it's really not my place to convince you of otherwise in the absence of conclusive literature. But yeah, I agree that acute hepatic failure may be a better descriptive word. I think the "fulminant" part describes the tendency of the hepatic failure to rapidly "fulminate out" and affect other organ systems. I never disputed that ICP is more relevant in an acute case, but I still hold that when a cirrhotic presents, there is still relevance to knowing ICP, for reasons I noted in previous posts.

 

[ArcherM2]

I've taken care of a good number of severely decompensated cirrhotics with associated encephalopathy and those with fulminant liver failure on my months in the ICU and I have never seen anyone get a bolt or herniate. Is this standard of care at your institutions?

 

[souljah1]

I'm a third year resident who is going into pulmonary/critical care. I've never ever seen ICP monitoring for a cirrhotic with hepatic encephalopathy.

Cirrhotics don't usually have acute changes that lead to cerebral edema and subsequent herniation. ICP monitoring is rarely, if ever, used to monitor ICP in cirrhotics. Cirrhosis is a chronic process and the brain has time to upregulate amino acids and osmols to offset toxin build up - which prevents cerebral edema. In fulminant hepatic failure, there is no time to do this and cerebral edema is a serious concern. I agree with scaredshizzles.

There is no evidence that trending NH3 has clinical utility.

The AASLD guidelines do not recommend ICP monitoring for encephalopathy that occurs in cirrhotics. Even in fulminant hepatic failure, ICP monitoring is often no utilized. These patients are coagulopathic and putting a bolt in their head is not benign. It's actually very institution dependent.

As far as the original post: a cirrhotic with "rapid deterioration" could be from a whole host of things.

 

[maxheadroom]

I'm not sure where this ICP monitoring idea is coming from. I've spent a fair amount of time on the surgical side of a liver service (ugh) and I've NEVER seen an ICP monitor placed. I'm pretty sure that the Neurosurgeons would laugh their *****es off when you called and asked for one.

 

[Winged Scapula]

ICP monitoring is not indicated for hepatic encephalopathy. It is a metabolic problem, not structural and a bolt or ventric will not help.

 

[Dimoak]

Thanks to everyone for the learning opportunity!