Transcript
Speaker: Welcome to Critical Matters, a sound podcast covering a broad range of topics related to the practice of intensive care medicine.
Speaker: Sound provides comprehensive critical care programs to hospitals across the country.
Speaker: To learn more about our programs and career opportunities, visit www.soundphysicians.com.
Speaker: And now your host, Dr. Sergio Zanotti.
Speaker: Critical illness is frequently associated with neurological abnormalities.
Speaker: Acute metabolic encephalopathy is a commonly utilized diagnostic term in the ICU.
Speaker: What does it mean?
Speaker: How should we manage it?
Speaker: In today's episode of the podcast, we will discuss acute metabolic encephalopathies,
Speaker: Our guest is Dr. Elko Wittix, Professor of Neurology at Mayo Clinic College of Medicine and Science.
Speaker: He is also an attending neurointensivist in the Neurosciences Intensive Care Unit at the St.
Speaker: Mary's Hospital campus in Rochester, Minnesota, and serves as the chair in the Critical Care and Hospital Neurology Division, the Department of Neurology.
Speaker: Dr. Widix is also the founding editor in the journal Neurocritical Care, the official journal of the Neurocritical Care Society of which he is an honorary member.
Speaker: He is a recognized clinician, educator, and investigator with special interest in neurocritical care, emergency neurology, and neurological complications of critical illness.
Speaker: He has published extensively over 15 books, a single author and multiple collaborations with over 750 peer-reviewed articles and is about to relaunch a new edition of a book entitled Neurological Complications of Critical Illness, links of all of which will be in the show notes.
Speaker: It's a true honor to have him today to discuss this important topic.
Speaker: Elko, welcome to Critical Matters.
Speaker: Thank you so much.
Speaker: Thanks for asking.
Speaker: It's an interesting topic.
Speaker: Not easy, though.
Speaker: For sure.
Speaker: And I think that we might want to start just in terms of we were discussing before we started recording how metabolic encephalopathy is a very commonly diagnostic code used for billing and documenting purposes in the ICU, yet really means very different things
Speaker: for different patients, but also for different clinicians.
Speaker: And it's almost like a wastebasket term in some respects.
Speaker: And I wanted to know if you could just give us a little bit more your thoughts around the term and how we should be thinking about it.
Speaker: Yeah, absolutely.
Speaker: The problem is that, as we all know, if you would ask a neurologist to come into your intensive care unit to see a patient that you think is not
Speaker: recovering well after surgery or is not as bright and crisp after sepsis has been treated, you ask the neurologist to see the patient with the, often with the time of the consult is usually, please evaluate this patient for altered mental status.
Speaker: And for us,
Speaker: I think those are probably very common consults.
Speaker: As a sort of a backdrop, we at Mayo, and when I started at Mayo, we see all the neurointensivists see all the consults in all the ICUs, all the medical and surgical and transplant units.
Speaker: And we've been doing this for
Speaker: as long as been there for over 30 years.
Speaker: And so we see not only our own patients in our neurointensive care unit, but also do consults in other intensive care units.
Speaker: There's a number of reasons why we did that.
Speaker: I think it is important for neurologists when they come in is that they have a good grasp of what these patients are and what kind of surgeries they had, what kind of...
Speaker: concerns the intensivists had in treating these patients, what kind of medication they're using, how they'll have lives and how these, of these drugs, of the drugs that they are administered.
Speaker: So we've always been looking at those patients, always doing and on those consults.
Speaker: And again, altered mental status is the most, one of the most common reasons to see a patient.
Speaker: Now, over many years,
Speaker: if the CT scan is normal and there is no really clear focal findings, neurologists have the tendency to call it metabolic encyclopathy or even call it toxic metabolic encyclopathy and then go away and leave it at that.
Speaker: I felt that that's
Speaker: not the right way to do it.
Speaker: There may not be a good alternative to this term, and I'm not going to talk too much about symbiology, but just to explain that toxic metabolic encephalopathy is obviously not a diagnosis.
Speaker: We... If you have to go back to where this term came from,
Speaker: And metabolic encephalopathy came truly out of a classic book on coma by Fred Plum and Jerry Posner, where they tried to categorize patients who had an abnormal level of consciousness or comatose into structural lesions and non-structural lesions and decided that if it's non-structural, it has to be metabolic.
Speaker: And in that category,
Speaker: There are a large group of patients that you and I would not necessarily think is metabolic, including sub-regorn hemorrhage, including seizures, including any intoxication that would be listed on the metabolic encephalopathy or metabolic cause of coma.
Speaker: And that's why I think the idea was that, you know, there's something wrong with the metabolism of the brain and brain function.
Speaker: And therefore, we call it metabolic encephalopathy.
Speaker: So, the risk that you take is if you call it toxic metabolic encephalopathy, that you deny yourself looking into what it really means.
Speaker: What is toxic here?
Speaker: What is metabolic?
Speaker: And that you are not going to go through every step of the way trying to figure out
Speaker: what has really happened to the patient and why the patient is in the state that the patient is in, again with a normal CAT scan, obviously, or an even better, a normal MRI scan.
Speaker: So those are challenges for all of us and all this has been.
Speaker: I always tell my residents, if you go into an intensive care unit, the three most common causes of
Speaker: failure to awaken or not being alert is drugs, drugs, and drugs.
Speaker: We've, over the years and over many years, have been trying to cope with the number of drugs that were given to the patient, combinations of drugs that were given to the patient.
Speaker: That makes it almost impossible to have a reliable, unconfounded neurologic examination.
Speaker: We know that and we try to work our ways through it, but in many situations where we can be fooled, we think the patient is much worse, and then everything clears out of the system and the patient's much better, can be easily fooled by the medication that has been given to the patient.
Speaker: So the point here is that if you use the term metabolic encephalopathy,
Speaker: it's fine to use it, but it can only be used if you've looked carefully what you truly mean by that and what have you looked into to say that this is metabolic.
Speaker: It's probably better to say acute metabolic derangements, that there has been acute metabolic derangement in the patient is that way, rather than just say, I don't know what it is.
Speaker: It has to be metabolic because I can't find a structural lesion as far as I've been looking.
Speaker: and so it has to be metabolic.
Speaker: Obviously, I can talk about that.
Speaker: Obviously, you will miss a lot of disorders by just saying that.
Speaker: So there is a major concern using the term toxic metabolic.
Speaker: We know where it comes from.
Speaker: It's trying to put a lot of diagnoses into a categorization of abnormal consciousness, and it is...
Speaker: not right to do it that way, but there's not a good alternative term at the moment.
Speaker: And I think two things that come immediately to mind, Elko, is one is that the absence of a structural abnormality, the absence of identifying a structural abnormality just doesn't mean that it's not there.
Speaker: It might be that whatever we use is not sensitive enough, right?
Speaker: Because a lot of times... Yeah, and I think that's... Right, so first, I think...
Speaker: And these recommendations are quite obvious, but if I see a patient, it is not, it often is in a situation that I think needs to be remedied.
Speaker: A CAT scan might be a week old, an MRI scan has not been done,
Speaker: and some patients need a CT and CTA.
Speaker: To give an example, there are patients who have a— when a patient has an acute embolus to the basilar artery, the CT scan is normal, but you're in a lot of examination points to where it's an embolus to the basilar artery, and you need a CTA to figure out what is happening to the patient.
Speaker: It depends on how deep you look.
Speaker: I think MRI scans, although in the past it was more difficult to do, and it continues to be difficult to do in critical patients to move them out of the intensive care room, not so much because the movement is possible, or not so much because the patient is intubated, they need an additional anesthesiologist in the neuroimaging suite.
Speaker: But it is more that...
Speaker: these patients are outside your ICU and you don't want them to code in an MRI scanner.
Speaker: You want to be absolutely certain that the patient can undergo that one hour, sometimes two hour study, which will give you a significant amount of, potentially a significant amount of information.
Speaker: I mean, we've known that patients who have
Speaker: have an ongoing MRI scan, we find more abnormalities, and these abnormalities are obviously depending on what the underlying illness of the patient is, but you can find multiple infarcts, you can find, and certainly in a patient who has been resuscitated with a normal CT scan, you'll find an oxygen ischemic injury that can be profound, that is mostly missed on a regular CAT scan.
Speaker: And what is a,
Speaker: rapidly increasing and rapidly more recognized is that many patients have PRESS.
Speaker: Postereo-reversal encyclopathy syndrome, another term that we can talk about where that is coming from and how deceptive that term is.
Speaker: But what I'm talking about is edema in the occipital parietal lobes, often also in the thalamus.
Speaker: and other areas where that reduces your level of consciousness and can be seen in sepsis and in patients who are admitted with a hypertensive emergency or are hypertensive as a result of a certain drop that has been administered.
Speaker: And one of the other major causes of PRESS is obviously the immunosuppressive agents that are used in transplant patients.
Speaker: But besides that, the point to make here is that
Speaker: When you get a CAT scan, the CAT scan may be old, it may have changed the moment you see the patient, and MRI scans are more utilized now, and that probably will narrow down the group of patients that we now would classify as metabolic encephalopathy or toxic metabolic encephalopathies.
Speaker: And it's not uncommon that we find on MRI scan abnormalities that
Speaker: that even have EEGs that would suggest that this is a metabolic derangement, that there are abnormalities on the MRI scan.
Speaker: So if you don't understand or have a good grasp of what is happening to the patient, the MRI scan remains the go-to diagnostic test.
Speaker: Now, what we don't yet have discussed, probably the most important part of everything else is that
Speaker: what does your neurologic examination show?
Speaker: And a detailed neurologic examination will drive your test that you would order, obviously.
Speaker: So, and there are subtleties in your neurologic examination that would point you to a certain direction.
Speaker: So you always start with the neurologic examination, then you go from there.
Speaker: But again, when we say there is no structural injury, we may not necessarily know that all that well because our studies are not detailed enough.
Speaker: And the other aspect that I was thinking of as you were explaining this is that we also often
Speaker: we'll see that the derangements that we are blaming as the cause of the encephalopathy sometimes are corrected, yet the patient doesn't improve, which also makes you wonder what else is going on, right?
Speaker: Yeah, so that's another important thing to realize.
Speaker: So let's say you examine a patient and there's nothing really that strikes you, and that's, I think, 90% of the patient.
Speaker: where your examination reveals that the patient opens his eyes to a pain stimulus and there is a bit of a withdrawal response in both extremities and the eye movements do not show any pathological abnormalities and the brainstem reflexes are intact.
Speaker: The patient has been in that state for a while and has had no
Speaker: you know, for a week, no CNS-depressant drugs, that those patients, you're faced with a non-focal and non-localizing neurologic examination, and then you have to decide, well, what is causing it.
Speaker: Now, we often run into an argument, an argument may be a big word, but at least...
Speaker: disagreement, I would say, that a patient who has been uremic and is not uremic is not exactly the patient who was the patient before the patient became uremic.
Speaker: In other words, the moment that someone is uremic, it may take several days, even a week, before the patient starts improving.
Speaker: It's not that you can just dialyze the patient and the patient will be...
Speaker: much better the next day, it will take a long time.
Speaker: The same applies to patients who have had hyperaminemia in a setting of liver disease.
Speaker: Once you correct hyperaminemia after giving lactulose and rifaximide, for example, you will have to wait for many, many days for the patient to improve.
Speaker: I don't know.
Speaker: I think we do understand why there is such a delay, but the delay is often not appreciated, and we get into a discussion, well, this patient has all non-normal values, so it cannot be the case, and we need to look for something else.
Speaker: I think that's...
Speaker: Not always the case.
Speaker: I think once these abnormalities have occurred, the brain is not able to correct its function so quickly as we hope it would be.
Speaker: And in critical care, we have learned to think of organ failure in terms of syndromes.
Speaker: And I know that some people propose the term acute brain failure when we really don't know the cause.
Speaker: Any thoughts on that?
Speaker: Well, there is.
Speaker: There is brain failure, and you can call it acute brain failure, but that's just another term.
Speaker: I mean, a lot of patients have now been, are now, unfortunately, in my opinion, are labeled to hypoactive delirium.
Speaker: And then you get into a whole discussion, well, is hypoactive delirium different than encephalopathy?
Speaker: And I've seen patients diagnosed with hypoactive delirium and come in there and they're seizing.
Speaker: Or they have a marked abnormality, a new metabolic derangement, or they've been given medication that is still in their system that makes them hypoactive.
Speaker: Of course it does.
Speaker: So the terminology of that is,
Speaker: terminology is difficult and complicated and there's no I don't have a solution to it I don't there's not a magic term that would would solve all those problems but you got to be careful about
Speaker: labelling someone delirious, and then hyperactive delirium, while you then stop looking for alternative explanations.
Speaker: And that is, I think, what...
Speaker: is by being my experience and also experience with my colleagues, is that it's too easy to say, well, it's delirium or it's hyperactive delirium or it's an encephalopathy, and that's what it must be.
Speaker: Now, there are conditions in which we don't know what causes brain failure.
Speaker: It's not absolutely known that patients who have been septic
Speaker: I tend, the best way to say it's septic encephalopathy or encephalopathy of multi-organ failure.
Speaker: That leads to a marked brain dysfunction, and we don't know what it is.
Speaker: Is it the inflammatory markers or is there a reduced cerebral perfusion or is the brain just part of a...
Speaker: an innocent, not so innocent, but a bystander of all the organ function, and it is part of the organs that is hit by the primary process.
Speaker: We don't know what it is.
Speaker: If you do MRI scans, you rarely find an oxymic ischemic injury.
Speaker: You may find infarction there.
Speaker: You never find micro-absorces in the setting of an infection.
Speaker: So there is a dysfunction of which the patient can recover,
Speaker: over time.
Speaker: So, and we're gonna call it all acute brain failure, but that's again, you'll get back to your terminology that is insufficient and it's not going to be terribly helpful if you wanna look for the causes of it.
Speaker: And it seemed, Elko, that at the end of the day, obviously, we recognize that the terms sometimes are overlapping.
Speaker: They're not perfect and discriminating.
Speaker: But it's important to have this discussion because ultimately what we don't want is
Speaker: is for labeling patients and then maybe not pursuing a more thorough diagnostic approach or asking more questions of what else could it be, which might leave things that have very treatable interventions undiscovered.
Speaker: That's absolutely true.
Speaker: So if I see a patient, and let's assume the patient, you don't, I mean,
Speaker: many critical illness, many intensivists hope that there's a neurologist comes in and says, oh, have you thought about this?
Speaker: And then does a test, and it's completely different or a surprise to everyone.
Speaker: Well, that doesn't happen that often.
Speaker: In fact, it's rare that such a thing happens.
Speaker: We are...
Speaker: We're not magical, we often see the similar thing, but we can point out that in some patients you would need a new basic metabolic panel.
Speaker: It's good to get a new blood gas, and it's good to get a new serum ammonia and lactate.
Speaker: It's good at times to do a 24-hour EEG monitoring, do CESF if necessary, and obtain an MRI scan.
Speaker: And so,
Speaker: And then also look in certain situations if there is a toxic drug.
Speaker: And we've also come to appreciate over time that there are several antimicrobials, including cefepime, that have a neurologic
Speaker: syndrome with myoclonus and rigidity that can be recognized as such, and many of those patients have developed new renal failure while the doses remain the same or were just simply overdosed.
Speaker: So there's an
Speaker: a good initial approach to go stepwise through examination, trying to find if there's a localizing finding, then go and then do an extensive new metabolic panel and look and see their trends in certain directions, and ask for more laboratory work and more recent laboratory work to
Speaker: assure that nothing has changed.
Speaker: I mean, I've seen patients who, in which we asked for in serum pneumonia, that there was a surprise of the hyperhammonemia that nobody really understood why that would happen.
Speaker: For example, the best example are the patient with lung transplantation in which hyperhammonemia is detected
Speaker: and nobody thought about it, so that was the case.
Speaker: So new metabolic laboratory tests are necessary to potentially attribute it to the way the patient looks.
Speaker: It's also important to know, you know, if the liver has changed in its function, if the kidney has changed in its function, with all the drugs you're giving to the patient,
Speaker: are all changing in their clearance, and that has a major impact on how you examine the patient and how confounded the patient can be.
Speaker: And you mentioned cefepine and you also mentioned drugs, drugs and drugs as causes of altered mental status.
Speaker: Can we explore a little bit more on the confounding factors, which obviously is an important aspect of making sure that we eliminate them before we try to get to a diagnosis?
Speaker: One of the drugs that I wanted you to comment on from your perspective as a neurointensivist and neurologist is fentanyl.
Speaker: Very commonly utilized in general ICUs.
Speaker: I would subject that almost in every ICU there's fentanyl drips infusing, yet I don't think that a lot of clinicians appreciate the impact it can have on the brain.
Speaker: No, I think that's very poorly appreciated.
Speaker: And everyone who has had fentanyl for a procedure knows how down and out you can be afterwards.
Speaker: And it takes a little while for that to clear.
Speaker: And the half-life of these drugs are very much dependent how long the infusion has been given to the patient.
Speaker: If you're giving fentanyl 100 mics,
Speaker: daily for a week, don't expect that after 48 hours, the fentanyl is out of your patient's system.
Speaker: That's not the case.
Speaker: So we tend to underestimate that.
Speaker: I've seen, and I've probably been guilty myself too, is that,
Speaker: We thought that we think the patient is much worse and then clears after all the drugs have been discontinued or we just gave the patient a little bit more time.
Speaker: A typical example that I've seen where most mistakes are made are patients after cardiopulmonary resuscitation who have an osteoschemic injury and they're comatose and they're comatose for a reason.
Speaker: And if you are comatose following cardiopulmonary resuscitation,
Speaker: and you stay comatose, then you can, it's unmistakably so that all the other organs are also damaged.
Speaker: So your kidney has been, has had a big hit, your liver has had a big hit, and your initial studies look normal, but if you don't repeat them, you'll find that there's a significant injury to the liver and kidney that immediately makes it very difficult to clear the drugs that you've been giving to the patient,
Speaker: You want it to sedate the patient or whether the patient is in targeted temperature management makes it very difficult to get an unconfounded neurologic examination.
Speaker: So it's not only the drug or the time of administration of the drug that changes your half-life, which is so well known with midazolam and so well known with fentanyl,
Speaker: but it's also that there has been acute change in liver or kidney function, and also the combination that makes it very difficult to clear a drug.
Speaker: And then you're talking about elderly patients in which the clearance is not
Speaker: according to the half-life that has been listed.
Speaker: That's also changed.
Speaker: AIDS just simply does that.
Speaker: So an elderly patient who has been resuscitated and been given several days of fentanyl, your neural examination is extraordinary, and you gotta be very careful in determining
Speaker: whether what you see is what is truly the patient's functioning.
Speaker: And that's, I can...
Speaker: I can really attest to that, that's an important confounder.
Speaker: We often make a mistake by not accepting that and looking into it.
Speaker: Absolutely.
Speaker: What about, I wonder if you could comment, Elko, on electrolyte abnormalities of confounding factors, specifically glucose, sodium, and calcium.
Speaker: So many of them are not confounders.
Speaker: I think the only confounder is, I think the biggest confounder, of course glucose is, and of course if a hypoglycemic patient is, or a patient who has been hypoglycemic patient as a hypoglycemic injury will remain comatols with an MRI scan that can be completely normal or later become abnormal.
Speaker: A patient who has had significant changes in sodium, in sodium, either a significant hyponatremia or I think one far more common impact on your level of consciousness, a significant hypernatremia, are major confounders.
Speaker: And there is not an absolute cutout value
Speaker: But any patient who drops the sodium less than 125 or any patient who has a sodium more than 160, that will impact on their responsiveness and will have to be corrected before you can safely say that what you see on examination is what it truly is.
Speaker: So, but calcium and magnesium,
Speaker: These electrolytes in general do not impact on the brain.
Speaker: It may impact on your respiration and your peripheral nervous system, but not so much on the brain.
Speaker: Your major components, really, your major drugs or tests to do is a blood gas and your serum ammonia, and then look at...
Speaker: your BUN, creatinine and liver function tests and see if they haven't changed.
Speaker: Those are the tests that I think continue to be obligatory when you evaluate the patient.
Speaker: Now, vitamin deficiencies are often mentioned.
Speaker: I'm always continuing to be struck why we don't see Wernicke encephalopathy that often patients who have been critically ill are rapidly getting into a thiamine deficiency.
Speaker: But I think we administered them thiamine very rapidly in many patients.
Speaker: It's just almost an automatic thing to do in a patient who has malnourished or has an alcohol use disorder is that we
Speaker: and load them with thiamine very rapidly, and that might be the reason why we don't see it that often in a situation in which the thiamine stores are rapidly depleted as a result of their critical illness.
Speaker: And so we rarely see Wernicke encyclopathy, rarely see Wernicke-Korsakoff or any eye movement abnormalities in patients who are critically ill.
Speaker: Those are the ones to look at.
Speaker: Some vitamin deficiencies can
Speaker: can be seen at the best, the most important would be the B1 deficiency.
Speaker: Another, I think another interesting issue is what to do with EEG, how valuable is an EEG?
Speaker: And I can tell you from my own experience, we've done so many EEGs that are normal in a critical care unit.
Speaker: that we often wonder why are we even doing it and why are we even monitoring for 24 hours in those patients.
Speaker: And I can tell you from my own experience, the moment I think it's non-convulsive status, the EEG is normal.
Speaker: The moment I don't think of it, the EEG shows non-convulsive status.
Speaker: It is hard to see and many patients who have had seizures, you'll see it and many patients who have focal seizures or are in non-convulsive status and it's obvious,
Speaker: you'll see it and you don't need your EEG to tell you that the patient is seizing.
Speaker: So your EEG, the value of your EEG in a medical intensive care unit isn't all that great as we think it is.
Speaker: And there's often also a lot of misinterpretation that rhythmic triphasic waves that we've typically been associated with acute metabolic derangements
Speaker: should not be interpreted as non-convulsive status epilepticus, and these are often misinterpreted as non-convulsive status epilepticus, and then patient is overtreated, and the patient does not improve.
Speaker: So EEG monitoring is, I'm not arguing against it in certain patients and certain selected patients,
Speaker: But there's definitely, we're doing a lot of EEGs and a lot of EEGs return as non-contributory and non-diagnostic.
Speaker: And obviously, the EEG is not a one-time blood draw.
Speaker: It entails time and effort, and like you said, also subject to misinterpretation, and important for us to think about what we're ordering and how it can help us.
Speaker: One of the things I wanted to ask you very quickly, Elko, before we move on to the next topic, is relating glucose.
Speaker: Now, you obviously talked about the importance of the physical examination, but of some of these confounding factors, and especially of the metabolic abnormalities, glucose is the one that can give you focal findings when it's very high.
Speaker: Can you elaborate a little bit on that?
Speaker: Yeah, so I don't know what it is, but it's, but marked non-osmotic hyperglycemia is able to give focal findings.
Speaker: Hypoglycemia can also give focal findings.
Speaker: What do we mean by focal findings?
Speaker: It can be hemiparesis, it can be aphasia, but never specific abnormalities that pertain to abnormalities in the brainstem.
Speaker: Or, you know,
Speaker: loss of brainstem reflexes in those situations, except when it is extreme.
Speaker: But patients who have glucose in the 500 to 700 range can definitely have focal findings.
Speaker: And in some of those patients, and perhaps the majority of the patients that have been a prior stroke or an MRI abnormality that
Speaker: could indicate that some of the milder ectomages the patient might have are now exacerbated by significant hyperglycemia.
Speaker: In some of those situations, we thought that that would have been a mechanism, but it's not entirely clear why significant hyperglycemia or non-catholic hyperglycemia can cause these focal findings.
Speaker: but it does and it disappears when you correct it.
Speaker: So that's a known observation.
Speaker: Perfect.
Speaker: So we talked about organ failure being a common finding in the ICU and how different organ failures can impact the brain.
Speaker: I would like to just maybe review a little bit further on different organ failures and some characteristics or some important aspects that you consider for our clinicians to have in mind.
Speaker: And maybe we can start with acute respiratory failure.
Speaker: Yeah, so of acute respiratory failure, the question is what impacts on the brain?
Speaker: And I think one lesson to learn is that hypoxemia in general has to be extraordinarily profound to impact on the brain.
Speaker: And we actually have come to learn that most recently during the COVID pandemic in which patients were markedly hypoxemic.
Speaker: and still were alert.
Speaker: We call them the happy hypoxemics, but the basic physiology has always been that you need to be extraordinarily hypoxemic.
Speaker: before the brain loses its function.
Speaker: But what happens is that it's often, and that's why we call it an oxygen ischemic injury, is that the blood pressure may drop and then becomes a different issue.
Speaker: So hypoxemic, hypotensive patient is a different situation than purely hypoxemia.
Speaker: What changes your responsiveness is hypercarbia.
Speaker: And that is...
Speaker: definitely impacting on your level of consciousness.
Speaker: Of course, the more extreme, we've known them as CO2 narcosis, but patients who have a rise and sometimes not recognized rise, and that's one of the reasons why you need to do arterial blood gases, which there's not hypoxemia, but there is a rise in CO2.
Speaker: then that can definitely impact on the response of the patient, and the patient will improve if that's corrected.
Speaker: You did mention, Elko, a little bit about acute renal failure when we're talking about uremia.
Speaker: Any other comments regarding acute renal failure and acute encephalopathy?
Speaker: No, I think acute renal failure, I think urea or BUN remains in the best place
Speaker: I don't know how high it has to be, it's more trend.
Speaker: We have, I've convinced nephrologists who dialyzed a patient who wasn't convinced that that would make a difference and the patient improved.
Speaker: Not all the time, but there was a patient in which there's a significant trend upwards and it starts to cross the hundred number.
Speaker: I think a trial of dialysis did make a difference in
Speaker: in a considerable number of patients.
Speaker: So we try to do that and take the trend into account where someone who is suddenly got much worse is considering that as a possibility.
Speaker: If you would say, well, this patient had a high urea three months ago, and why do you think it is abnormal now?
Speaker: that is not always, it can always, not always can be said.
Speaker: It's more, why did this patient solidly had an extreme increase in urea?
Speaker: Could that impact on what you see?
Speaker: And some of these patients have clinical findings.
Speaker: I mean, they have astrolysis that aren't as new.
Speaker: or a multifocal myoclonus that is new.
Speaker: And if you find those abnormalities, it definitely would make sense to dialyze the patient and see if you could reduce that number.
Speaker: And I think, as you mentioned earlier, it might take a little bit of time for the symptoms to totally resolve.
Speaker: And the number itself might be different from patient to patient, right?
Speaker: Excellent.
Speaker: Yeah, what I said, there's no magic cutoff.
Speaker: Absolutely.
Speaker: Could you comment, Elko, on acute liver failure?
Speaker: And here it seems that, or liver failure, let's not call it acute, let's just say liver failure and cephalopathy, because there is quite a distinction in terms of what you need to do once you develop encephalopathy in the acute liver setting versus more chronic, acute on chronic liver setting.
Speaker: Yeah, that's a topic that we would think we would know everything about, but we don't.
Speaker: I think where we have the best understanding is acute feminine or feminine hepatic failure, in which the patient rapidly developed hepatic encephalopathy.
Speaker: And in that situation, we've now come to understand that there is, at some point, a transition from hepatic encephalopathy, which is basically a dysfunctional brain or brain failure as a result of hyperaminemia, that then becomes structural as a result of edema.
Speaker: And we think that hyperaminemia results in an increase in glutamine, which is in
Speaker: and osmolyte and causing brain edema.
Speaker: I think we still think that that's the main mechanism and that these patients' CT scans start to change.
Speaker: Interestingly, over time, transplant surgeons had to convince neurologists that that was the case.
Speaker: They always felt that, no, this is severe pavigan cephalopathy and nothing else.
Speaker: But repeated CTs can have shown that these patients can develop brain edema.
Speaker: And then with that brain edema, their intracranial pressure goes up.
Speaker: and the only way to treat that is liver transplantation.
Speaker: Treatment of increased intracranial pressure is difficult in those patients.
Speaker: You can definitely not use barbiturates in a patient who has no liver.
Speaker: The treatment is difficult to do, and liver transplantation is the only way to self.
Speaker: It's the patient.
Speaker: So there is a transition from severe hepatic encephalopathy, which
Speaker: may have very significant neurologic findings of increased rigidity and marked increase in your ocelocephalic response and even loss of Princeton reflexes that can be all attributed to severe hyperammonia.
Speaker: We're talking here very high ammonias that are seen in patients who have an acute liver failure.
Speaker: that that eventually lead to edema, and the edema needs to be treated aggressively, and the best way to treat it aggressively is a liver transplantation.
Speaker: Doesn't matter what the cause of a phalmitohepatic failure is, has no impact on it.
Speaker: Now, on the other hand, is it different in patients who have chronic liver failure and have acute hyperammonemia,
Speaker: as an acute on chronic.
Speaker: And that is an area that I think we start to recognize that it might be closer to the patient with thalmitabatic failure.
Speaker: And we now have data, and also we've seen that, and actually I've seen several cases recently, in which MRIs can show how toxic ammonia can be in a patient who has a chronic
Speaker: liver failure.
Speaker: You see cortical injury, you see injury that is profound in the cortex, often the insular cortex is involved, and patients may not necessarily improve after you've corrected the ammonia, for the simple reason that the ammonia has been significantly toxic in those patients.
Speaker: And that's a relatively new finding because in general, hepatologists,
Speaker: would not do MRI scans in those patients when they have acute or chronic renal failure or hepatic failure.
Speaker: They try to lower down the ammonia as best as they could or find a chance that can be repaired, but would not do MRI scans.
Speaker: They've now been able to see, not so much in a systemic way, and there's literature on the topic,
Speaker: that MRI scans can be abnormal and can show the significant toxic effect of ammonia.
Speaker: We had patients who were at a marked decline in their level of consciousness and state comatose and had progressive changes on their MRI scan and even progressive changes on their CT scan, of which we were not so sure if those patients will get better over time despite the correction of ammonia.
Speaker: So there is sort of a transition between something that is getting better if your ammonia is getting better to no, nothing will get better because the patient has had a toxic injury or has had brain edema as a result of hyperammonemia or prolonged hyperammonemia.
Speaker: And I don't know how long and prolonged and how high it can be,
Speaker: But every hepatologist knows that some patients it might be very difficult to bring the ammonia down.
Speaker: And sometimes MARS or even dialysis might be necessary in those patients, or aggressive search for a shunt might be necessary to reduce the ammonia that eventually could help the patient.
Speaker: So I think it's underestimated.
Speaker: And one of those, again, another example of something that we always felt was acute metabolic, or metabolic encyclopathy turns out to be a structural abnormality, now that we have MRI availability and that we have a better understanding what can happen to the brain, rather than just attributed to a metabolic dysfunction that, of which the brain will get better after we've corrected the metabolic dysfunction.
Speaker: It's very interesting.
Speaker: It just brings to mind, and I can't remember who said it, but a quote that says that the nature of disease doesn't change.
Speaker: It's we who change as we are able to now see what was imperceptible before, right?
Speaker: So we find more and more structural changes in what used to be considered metabolic.
Speaker: Yeah, you cannot say it any better than that.
Speaker: That's absolutely true.
Speaker: Very interesting.
Speaker: Any comments on thyroid failure?
Speaker: So obviously acute thyroid failure or myxedema coma is a classical presentation that's not very common.
Speaker: But I think from... No, and I do have to really have to think who was the last patient that I saw.
Speaker: But what I can recall is that a patient with myxedema is coma,
Speaker: looks like a hypothyroid.
Speaker: If you know how to recognize that, you will see that that's what it is.
Speaker: It's not out of the blue surprise if a patient has a severely hypothyroid.
Speaker: They have all the hallmarks of significant hypothyroidism while they are
Speaker: becoming comatose as a result of that.
Speaker: Some of them also will have specific MRI scan of the malitis, but most of them it's irreversible, fortunately, and we don't know about a really long-term effect of this.
Speaker: So they're recognizable.
Speaker: If you know how to recognize hypothyroidism, you'll be able to recognize mixed hypothyroid-associated coma.
Speaker: Perfect.
Speaker: That could not be the, it could be a problem.
Speaker: And we, we talked obviously that in the ICU, what's most common is multiple organ failure.
Speaker: Uh, any comments when we have multiple organs failing and we also have acute encephalopathy, any general comments?
Speaker: I mean, that's probably the most common patient.
Speaker: I think, I think, I think money of those pay.
Speaker: I think what, there's something happened to the brain.
Speaker: If, uh, if the patient is not awakening after there's multi-organ failure, but, um,
Speaker: Our observations there are extraordinary limit, and the reason is that patients don't survive multi-organ failure.
Speaker: So if you have patients who have survived, those patients have been treated for weeks often, and gradually the organs have improved, start to improve after many, many weeks in those survivors.
Speaker: And, and,
Speaker: I don't know how good we have examined them by neuroimaging.
Speaker: I don't think we have a good series of neuropathology in patients who did not survive, in which someone really carefully looked at the brain.
Speaker: So it's an area that surprisingly is poorly studied, although we see so many patients who died from sepsis, knowing what is happening to the brain in that circumstance, certainly if it leads to milder organ failure.
Speaker: It's an area that could be much better studied.
Speaker: Perfect.
Speaker: I think that one of the things that I really look forward when trying to understand syndromes or diseases is something like what people call first-order principles or fundamental precepts.
Speaker: And from reading many of your papers, it seems that when you think about metabolic encephalopathy, you think of three precepts that I just want to share with you and then get your comments answered.
Speaker: as we close on the topic.
Speaker: So number one is that the search for structural brain injury should continue despite what seems to be an obvious metabolic abnormality in that, like you said, to be careful with not falling prey of, oh, they have a metabolic problem and not really look for potential structural brain injury that might require intervention.
Speaker: Number two is that we must recognize the confounding conditions
Speaker: And eliminate them.
Speaker: And you said drugs, drugs and drugs.
Speaker: And two drugs that you talked about that I want to remind our listeners are cefepine and fentanyl, just because so many patients in the medical and surgical ICU are on those drugs that I think it's important to keep that in the back of our mind.
Speaker: And number three, which we talked a little bit about, Elko, is that the resolution of brain dysfunction may take a little bit longer despite what seems to be a normalized lab values, and that might be just part of the disease process that we don't fully understand.
Speaker: I couldn't have summarized it any better.
Speaker: That's exactly what it is.
Speaker: And finally, in terms of, you talked about the initial approach to encephalopathy, and you were very clear in terms of documenting and doing a good neurologic examination with the level of consciousness, obtaining new metabolic panel, and looking for trends and substantial changes.
Speaker: Always a good idea if you're evaluating a patient for acute encephalopathy to have a recent arterial blood class.
Speaker: You talked about
Speaker: the impact of oxygen, but more importantly, the impact of CO2.
Speaker: You said over and over again, ammonia and lactate.
Speaker: So make sure that we check a serum and ammonia, lactate that are recent.
Speaker: Imaging obviously is where we're gonna try to find these structural abnormalities, CT or MRI when appropriate.
Speaker: 24 hour EEG, you said something to consider, but you also mentioned that in the ICU, it may be not the highest yield in this general population.
Speaker: When did you obtain CSF, Elko?
Speaker: Yeah, I think we do that.
Speaker: It's almost obligatory in patients who are immunocompromised.
Speaker: I don't think we do it automatically in patients who are septic.
Speaker: Obviously, in patients who have a neurologic examination, it could suggest that there is an immunocompromised.
Speaker: and meningitis, but I think we have a low threshold in any immunocompromised patients who has a fever or even has no fever, to make sure that that's not more specifically looked at.
Speaker: Now, CSF is definitely obligatory in a patient who comes to an ICU and you don't know why the patient is comatose.
Speaker: That, of course, is in a different situation, but a patient in the setting of critical illness
Speaker: which in the overwhelming majority are patients who have had acute respiratory failure or sepsis, I think there is a low yield.
Speaker: I also don't think there's a high yield in patients who have endocarditis as a result of it, and it might even be dangerous to do a spinal fluid examination.
Speaker: in a patient who had endocarditis and may have epidural abscesses as a result of it.
Speaker: So CESF, mostly in patients who come into your medical ICU and you're working up the patient's coma in general, and definitely in patients who have been in a medical ICU who's immunocompromised or has had...
Speaker: chemotherapy or is the possibility of an opportunistic infection.
Speaker: Perfect.
Speaker: And you talked also about correcting all the potential confounders, whether it be replaced electrolytes, correct the vitamins.
Speaker: I think I want to reemphasize that there are antibiotics, and you talked a lot about cefepine, but others such as metronidazole can also have impact.
Speaker: And I don't think that non-neurologists are as aware and as aggressive and maybe evaluating and changing those when possible.
Speaker: We have
Speaker: multiple options usually, or we don't need antibiotics, which is usually the case, or something to think about.
Speaker: And the last aspect of the workup I wanted to ask you about are the approach to the encephalopathy is when do you consider these zebras?
Speaker: And you've written about like porphyria.
Speaker: We talked about Wernicke, which is not very common.
Speaker: Pelagra, some more rare congenital defects like melas.
Speaker: When do you even think of those, Elko?
Speaker: Rarely.
Speaker: Acute porphyria has occasionally come up.
Speaker: I listed them there because these are causes for unexplained cases, but I would think that in general practice, you probably almost never have to consider them.
Speaker: And they're called zebras for a reason.
Speaker: Excellent.
Speaker: Well, I definitely want to be respectful of your time, Elko, and I really appreciate you helping us understand this very commonly utilized concept of metabolic encephalopathy, but poorly understood and maybe poorly managed because we're not maybe approaching it in the right way a lot of times.
Speaker: So I really want to appreciate that.
Speaker: And we usually close the podcast with a couple of questions unrelated to the clinical topic.
Speaker: Would that be okay?
Speaker: Yeah, go ahead.
Speaker: What book or books have influenced you the most or what book have you gifted most often to others?
Speaker: Yeah, that's a difficult question for someone who has over a thousand books in his home.
Speaker: I think the books that I like most is obviously...
Speaker: Darwin's Origin of Species, but also the biography of Darwin by Jeanette Brown, a two-volume biography of Darwin, which I think is our greatest scientist ever.
Speaker: And so that's a book that I have reread multiple times.
Speaker: But of course, I like film, and as you probably mentioned, I...
Speaker: There are several books on film that I would recommend.
Speaker: I think if someone wants to really enjoy film and film criticism, virtually every book by David Thompson would be a good choice.
Speaker: He has a wonderful encyclopedia in which he discusses not only every actor, but also...
Speaker: a large number of films in short essays.
Speaker: And it's wonderful to read and highly novel and innovative.
Speaker: And I will also, I think one of the reasons why I ask these questions is because I'm a big believer in trying to really touch the humanistic part of medicine.
Speaker: And people are more than just their medical knowledge, which obviously in your case is
Speaker: quite vast and impressive but you have written about medicine and film and several books and neurology and film and I would definitely put the links to those in the show notes but when you said porphyria there's a famous movie that came to mind I think it was called
Speaker: the badness of King George, is that what drove him to go mad?
Speaker: Is that the right movie I'm thinking?
Speaker: Yeah, that's a good question, and the answer is no.
Speaker: He would never have acute porphyria, although everybody thought it is, and there's good arguments against it.
Speaker: That he had mental illness, I think, was right.
Speaker: But the problem we have, and I call that, and I have a chapter on that, it's called icono-diagnosis, means that
Speaker: physicians have the tendency to look at artwork and to try to figure out why, what kind of disorder the composer or the painter had.
Speaker: And sometimes it's well known what he has, and then it's interesting to see how an artist changes.
Speaker: But if you go...
Speaker: more deep into time, it's a lot of speculation and it's more entertainment than really science.
Speaker: So the same happened to
Speaker: King George that he was that there's no evidence to suggest he had acute porphyria it's a good movie though but no porphyria excellent the second question relates to beliefs what do you believe to be true in neurology or neurocritical care that most other intensivists outside of the neural world don't believe yeah
Speaker: I think there's one little, there's one major element actually.
Speaker: And the element is that patients who are neuro, have a neurocritical illness may not look so sick as many general intensivists know.
Speaker: So you can have a patient with a sub-record hemorrhage who is sitting in a chair and has a little bit of a headache
Speaker: who is critically ill, and critically ill meaning that a couple hours later the patient might be symptomatic from vasospasm.
Speaker: I think in general, and it applies to many neurocritical illnesses, is that patients have often such a high degree of secondary deterioration
Speaker: whether it's a, if it's a brain injury or if it's a peripheral nerve injury, myasthenia gravis, for example, is a good example, is that they look great and it is all not, and all the numbers look good, but why did this patient suddenly crash an hour or two later?
Speaker: And that's simply because it's not recognized or people don't,
Speaker: don't tend to think that they're that sick while they are extraordinary sick and are in the middle of a neurocritical, involving neurocritical illness.
Speaker: I think that's what I've seen over time is makes this specialty so difficult, is to judge who is going to deteriorate and how bad is this patient going to deteriorate.
Speaker: And I think it's a great teaching point for people who in our audience have a very broad practice in communities because you might be conditioned to really equate severity with how clinically the patient looks to you.
Speaker: And like you said, some of these neuro emergencies or neurocatastrophes might be impending on the border of the precipice and you just can't pick it up unless you really think about it and it can be deceiving.
Speaker: So I think it's a great point.
Speaker: Yeah, and I think it's important for us to understand what the trajectory of acute illness, acute neurology is.
Speaker: And knowing that trajectory would help us understanding what could happen in the next 24 hours or even hours in the emergency department or if the patient is in the emergency department.
Speaker: Perfect.
Speaker: And to close, Elko, I just wanted to ask, what would you want every intensivist who's listening to know could be a quote, a fact, or a thought?
Speaker: Say that again?
Speaker: What would you want every intensivist who's listening to know as a departing statement could be a quote or a fact or just a thought?
Speaker: Yeah, so I think what I...
Speaker: have noticed indefinitely over the last year is that, and certainly when we, after the pandemic, or during, still, we're still in the middle of the pandemic, but we're now in a period in which it's lightening up, but is that, and that's what I've been trying to do, is trying to continue to enjoy your work and understand
Speaker: that you're there for a reason and that you try to help patients as best as they can, help their families as best as they can.
Speaker: It's a lifestyle we've chosen to do.
Speaker: It's a difficult lifestyle we have.
Speaker: There's a lot of sacrifice for us and your own family involves, but we continue to think that we're trying to help the patient and their families.
Speaker: Absolutely.
Speaker: I think connecting with our purpose is something that we should do more frequently, especially like you said, after the pandemic.
Speaker: Well, Elko, I really want to thank you for being so generous with your time and also sharing your expertise with our listeners.
Speaker: I look forward to seeing you in an upcoming conference and saying hi, and also hopefully having you back on the podcast in the future.
Speaker: Thank you so much.
Speaker: Thank you so much for asking.
Speaker: Thank you for listening to Critical Matters, a sound podcast.
Speaker: Make sure to subscribe to Critical Matters on Apple or Google Podcasts and share with your network.
Speaker: Sound's transforming the way critical care is provided in hospitals across the country.
Speaker: To learn more, visit www.soundphysicians.com.
