Welcome back everyone to Plumb Peeps.

Ferf and I are so excited to be back together.

We're kind of right now in the middle of summer, so hope everyone's enjoying their time.

I think it's such a special time in the hospital.

There's new residents.

There's new fellows.

So much excitement.

So excited to bring you, though, a new case today and get back with things.

Yeah.

I love this time of year.

New interns, new residents, new fellows.

I feel like everyone has really great questions.

And then the questions often let you teach about some core physiology or core topic, which is great.

But they also then sometimes for topics that are a little more nebulous, make you really go back and say, what do I understand about this, and what don't I understand?

And and so, actually, we're gonna talk today about a topic that is one that I think is pretty poorly understood, but also extremely, important and basically ubiquitous in any ICU where you're gonna be practicing.

So we're gonna be talking about ICU acquired weakness today and hopefully drill through some of the uncertainty and get down to some of the misconceptions and some of the facts that we can understand about this to help take care of patients.

Yeah.

And we're very excited to welcome our special guests.

We have one returning, and then we have a pump peeps first today.

We're thrilled to welcome our first physiatrist.

And for those of you who may be asking what a physiatrist is, that's a health care provider specializing in physical medicine and rehabilitation.

But our first to the show and honored to welcome doctor Jim DeVaney, who's a physiatrist who just completed a neurocritical care fellowship at BIDMC.

He's currently transitioning to a clinical associate position at the University Health Network, University of Toronto, where he'll be working as a PM and R consultant within the ICU.

Jim, such a pleasure to have you on.

Welcome to POMP peeps.

Thank you, Christina.

It's a pleasure to be here.

Yeah, thanks, Jim.

We're equally thrilled to welcome back doctor Kalila Paez.

Kalila works at Beth Israel Deaconess.

She's now a third year senior medical resident, interested in pulmonary and critical care and medical education.

She's done some great episodes with us in the past, and, we're thrilled to have you back.

Thanks for having me.

It's always great to be back.

Absolutely.

And just as our standard disclaimer, as a reminder, this podcast is not meant to be used for specific medical advice.

The views we expressed today may not reflect those of our respective employers.

And the case we will present today is HIPAA compliant.

Any details or patient identify, facts may have been changed to protect the privacy of our patient.

Thanks, Verve.

And, Klayla, welcome back.

As as Dave mentioned, I feel like you're, yeah, almost a Plum Pipes veteran.

I love doing some partnering with you of some recent Core I Am projects.

So really love the collaboration, that we've had with you so far.

Excited you're a senior resident now.

I feel like the leader of the team, the know all.

So excited for your year and your growth.

And you actually brought this case to Dave and I to discuss.

So thank you for this opportunity, and we're hoping that you can start out today by just describing, how the patient presented to you.

Yeah, of course.

It's it's great to be here.

Thanks guys So let's start with the case.

We have this 65 year old male patient He has a history of hypertension and type two diabetes And he's initially admitted to the icu because of severe sepsis secondary to a pneumonia.

So he was mechanically ventilated.

He was placed on vasopressor support, and he even got Cape Cod dose steroids.

And then after about two weeks in the ICU, even though his septic shock had improved with IV antibiotics, he was still having this profound generalized weakness, particularly in his proximal proximal muscles.

And we were having a hard time weaning him off of the ventilator, and it was already day 14.

His vital signs were otherwise stable.

He was breathing at a 100% on the vent.

And his physical exam was most significant for this profound symmetric limb weakness, more so in his lower extremities.

His deep tendon reflexes were intact.

He had preserved cranial nerve function, and we didn't see any sensory deficits.

So this patient came in for sepsis, has gotten better for a set from a sepsis point of view, and now his primary issue is more so weakness.

So, Christina, when you're taking care of these patients, what are you usually thinking about?

How are you usually approaching it?

Great.

Thanks, Kyle.

And thank you so much for the question.

And and you brought up some great things already that we should be thinking about.

Just duration of hospital admission.

So you mentioned two weeks.

Other comorbidities you mentioned as well as coming in with sepsis and getting steroid dosing, as you said, kind of the Cape Cod protocol.

So some things that we should be considering.

But when you're thinking about, an approach to weakness in the ICU, I know there's many frameworks that you can think about, but one that I like is really going from brain to muscle.

So neuroanatomical and system based framework for thinking about weakness in the ICU.

And as I said, the idea is to work from central to peripheral, so brain to muscle, to systematically consider where along the motor pathway the problem could be because it could be so many different places.

And I think one thing when when you start to have a a broad differential, you're gonna start just naming potential etiologies.

And sometimes for myself, if I do that, I get a little bit disorganized and may miss something.

So I really try to do systems based.

So this could be starting with the brain and spinal cord, then moving to the anterior horn cells, the peripheral nerves, the neuromuscular junction, and finally, the muscle itself.

So as I said, I think it breaks down things in a way that's organized and practical.

So you're not just listing diagnosis, but really thinking about them on the level of dysfunction.

And I'm sure we'll get to hear from you and and Jim and and Dave in a bit just on other ways to think about this and really important tests and diagnostics that we should consider.

But to think about this more broadly going through the the system from a CNS standpoint, I think some etiologies that probably those listening today are already considering, right, is any trauma that may, the patient may have experienced, any recent hemorrhage or infarction that could have, could have occurred, as well as potential infection.

And this is going to be broad, but such as encephalitis, potentially new abscess formation.

This is where we can think about myelopathies as well.

Subclinical seizures is also very important.

And then a topic I'm sure will get you is just always having delirium as part of this etiology for the overall brain and CNS.

So after I think about the CNS and think of those etiologies, I really then move to more of the anterior horn cells where this could be more motor neuron disease, poliomyelitis or West Nile virus could be considered in this.

Moving from anterior horn cells into peripheral nerves, thinking about Guillain Barre syndrome, as well as several neuropathies.

And this could be more from a vasculitic component, a perineoplastic component, or really critical illness polyneuropathy that you should be considering.

Moving from peripheral nerves, I then go to neuromuscular junction.

So, thinking about myasthenia gravis.

I work with a lot of oncology ICU patients who may be on checkpoint inhibitors.

So, sometimes you can get a myasthenia gravis like effect from checkpoint inhibitors to have on your differential.

But also thinking about Lambert Eaton syndrome, botulism or any neuromuscular blocking drugs.

And then from neuromuscular junction, as I said, going to muscle last.

So, So, thinking about etiology such as inflammatory myopathies, such as polymyositis as well as dermatomyositis.

Rhabdo definitely should be considered.

More rare cases, rare cases we should still have on the differential could be some mitochondrial myopathies.

More common cases to think about in someone who's been hospitalized for two weeks, you know, drug induced or toxic myopathies.

And then we always have to think about critical illness myopathy.

So, I know a lot of things are just said.

But, again, I think if you could remember and take away from today, just go from brain to muscle and be system based.

I think that could at least help you think of a, of good differentials.

But based on the differential, right, lots of things to talk about today.

But what kind of patterns do you associate these with, and what could we be looking for?

Yeah.

So I think weakness is such a a broad term, and then we're starting to try to hone down on it.

And and you don't have to know and be an expert on all these things, but it really does help you to have a framework to think through it.

It also helps you frame a good question for your consultants, which will include everybody from neurology to your physical therapist, to your physiatrist like Jim, who are gonna come in and give an evaluation.

And if you can really have a a picture that's well described, that can help everybody.

And so I I also take that same anatomic approach.

And then Kyla already did a really great job of adding some of the things that we are gonna be asking asking about.

So the first is, is this symmetric or asymmetric weakness, right, asymmetric weakness, I really start thinking about central nervous system problems, upper meridional problems because everything else should likely affect the nerves, the neuromuscular junctions, the muscles in a similar way.

And so asymmetric really gets my warning signs coming up about whether or not I have some acute CNS process that might need to be an evaluation.

So some patient tells me that all of a sudden can't move their arm, Obviously, it could be a peripheral nerve compression, but my first question is, do I need some head imaging for a central stroke going on?

The next thing that I think about is the pattern of it.

Is this sort of proximal versus distal?

Now this I always find frustrating personally because everything has an atypical presentation.

Right?

So even the things that we think about as being really like a distal where it's a bit like Guillain Barre syndrome has this sort of ascending distal weakness that comes up.

You know, you'll have that atypical case that comes in where somebody just starts with a respiratory failure phenotype.

And so I do like the patterns, but and I do gather that information.

But obviously, you have to keep in mind that it can be atypical or common presentations of common diseases.

But some things are like really textbook.

So like, ascites is really are gonna be a weakness in the proximal muscles, the deltoids, biceps, triceps, the quadriceps, hamstrings, and the lower extremities.

And so the worst thing is usually follow that typical pattern.

So I wanna get a sense of that.

Sensory loss, really, a lot of these conditions distal, to the anterior horn cells really shouldn't have sensory involvement unless you have remote neuropathy.

So that always raises something in my head about, okay, I'm not really thinking about neuromuscular junction or the myocyte itself if I have combined sensory loss.

It's gotta be the mixed nerves or above that are carrying this.

And then I I care about reflexes as well is that a little bit of that same distinction.

Anything that's a neuromuscular blockade or below neuromuscular muscle should have that preserved circuit even if any if something centrally is going on.

And so if I have preserved reflexes, I'm really thinking more distal in that central nervous system down to myocyte distribution.

And if it's got a change in reflexes, hypo, hyper, areflexic, then I'm thinking, more proximal to that.

So these are the types of info I get.

I am gonna we're gonna post a graphic and an image to show some of this so you can see where all of these conditions lay out along that spectrum and we'll talk through each of them right now because that would be a pretty boring podcast.

But that but Kalaia has already given us some interesting information that this is a patient who has this going on.

It is symmetrical.

It's in the limbs, more in the lower extremities.

So we could think about some, more like ascending patterns.

We have preserved cranial nerve functions, no sensory deficits, or we're thinking a little bit less of the central nervous system.

We're really thinking a little bit more distal in the nerve sheaths, neuromuscular junction, the myocytes that, might play a role here.

So we're gonna have to get a little bit more detail and a little bit more, studies for sure.

So, Kalaiah, can you tell us what else was obtained, and what were some of the next steps in the work after this?

Yeah.

So the patient's labs were mostly unremarkable.

He did have an elevated glucose in the three hundreds, a mildly elevated c k to four sixty five, but a normal CRP and a flat lactate.

We got imaging of his brain, so brain MRI, CT head.

Those didn't show any acute pathology.

And then he did finally get an LP, which was also unremarkable.

So normal protein, normal glucose, normal opening pressure.

And then on exam, we still didn't note any deficits to his cranial nerves, and there was no fluctuation in his weakness.

So it didn't get worse, like, with a bit of motion, like, better with repetitive movement.

Thanks, Kyla.

Yeah.

I think this is really helpful and brings us to this next step for the workup for these patients.

So we we talk about these broad differentials.

And now as you're giving more info, we're seeing how this presentation is probably gonna fall into this broader spectrum of ICU acquired weakness.

And we'll talk about the components of that in just a second, thinking about biopathy or neuropathy.

But he has all the classic signs.

Oh, he had severe sepsis.

The timing kinda came on after that.

He has generalized symmetric, proximal greater than just a week.

This is what we see.

He has reflexes, that are, you know, and that makes us think less of one where we're absent.

Over time, you could get decrease in these reflexes.

We don't see any cranial nerve lesions.

That's really important.

We don't think there's gonna be, like, a focal deficit, and we've had a really good workup of the central nervous system now.

We're less concerned about infections.

We've been at an LP.

We'd be really thorough about this.

The CK is mildly elevated.

If it was in the 20 thousands, we might be thinking more about a rhabdo or more about, like, a severe inflammatory myositis picture, but it's certainly very common to see low level elevations like this.

And then importantly, in ruling out some of the things that we don't wanna miss, electrolytes are pretty much normal, is what we've heard, the leftmost are normal.

Glucose, a little bit elevated, and we'll talk about that.

But that's just something we're gonna have to control.

And then I think everybody in the ICU also wants to maintain awareness of these types of conditions that are really treatable and reversible.

And so, like, Guillain Barre syndrome is one of these.

After an infection, you can get this progressive weakness, but then ends up leading into areflexia and can respiratory failure.

The LP being re normal with normal protein really makes us feel more reassured about that.

The The timeline seems more like an ICU acquired weakness, but so it just moves much lower down our differential.

And so we're probably not gonna worry about it.

And then some of the other conditions that we always wanna be wary of and think about, like, in med school, like, myasthenia gravis, Lambert Eaton.

You said cranial nerves are intact.

There was no fluctuation of the weakness.

There was no weakness preceding this presentation.

So I feel a lot better about ruling these out.

I don't even usually have to send the testing for these unless I see some, like, red flag symptoms.

So I think this really helps us thinking about the ICU acquired weakness.

And then, yeah, Jim, if you could move into summarizing some of these findings, how you think about it, that'd be great.

Yeah, absolutely.

So importantly, we took that very broad system based approach going proximal to distal and and really worked on that list.

So as you're talking about now, the the CT MRI, everything being clean, it doesn't fully rule out anything central.

Of course, there hasn't been a a EEG done.

However, that's not something that generally just presents as only weakness or anything like that.

And so, that helps me move away from just a a focal seizure, focal status, or something in that nature.

The big thing with with this patient that we discussed and and how he presented is he presented with a a significant illness, no weakness.

And so the important thing is ICU acquired weakness as an entity needs to have started after the onset of of critical illness.

It can't have to be something that preceded it.

Of course, somebody can be weak and then develop ICU acquired weakness, but they're two separate processes.

And so the timeline for for this patient really helps help us focus on on this diagnosis.

And as we've discussed as well, generalized weakness is is is is showing something more systemic.

It's not showing that there is a vocal compression in the spinal cord.

It's not making you think that there's something in one certain location to to go after.

Overall, the picture that we've we've shown and demonstrated has this person that is at high risk of acquiring ICU acquired weakness for reasons that we'll talk about later and presenting as if he has it.

Importantly, and we'll talk about this later as well, ICU acquired weakness, it sounds like a unifying diagnosis.

However, it's an umbrella term.

It disc it describes different entities, specifically critical illness, myopathy, critical illness, neuropathy, and then the combination where both are present at the same time, critical illness, neuromyopathy, which all have different pathophysiologies within and all present in a similar fashion.

Yeah.

Absolutely.

I think this is one of the issues and with ICU bioweaponics, as you said, is it really is this umbrella term.

And importantly, why are we talking about this?

And it's because we know that ICU acquired weakness, a patient just like this compared to a patient who had the same illness but doesn't demonstrate these findings, really has large impact on their outcomes.

And these are with short term and long term.

I get very clear, that patients who have ICU acquired weakness compared to those who don't have longer stays in the hospital, longer time on the ventilators, increased likelihood of being reintubated, increased ICU and hospital mortality as probably a consequence of these, will other short term consequences.

We also know that if you leave the hospital and have with still some level of ICU acquired weakness, like, depending on, what functional level you achieve, you're more likely to go to rehab, than home.

You have long stays at rehab, and that's associated with its own side effects, and you actually have an increased, chance of coming back to the hospital.

And then decreased functioning in a year in this world where we're really focused on post ICU syndrome.

You guys can listen to our episode that we did with Dale Needham and Wes Ely about this.

This is a huge component of that.

Patients year out who just can't do what they used to after an acute illness.

So we care about finding this quite a bit.

Jim, you sort of mentioned that the pathophysiology is not unifying, right, because there's multiple different etiologies that can be lumped into ICU acquired weakness.

Could you tell us a little bit more about some of the factors that do go into developing this?

Yeah.

Absolutely.

And I think just before moving onto that, I think it's such an important connection to make with ICU acquired weakness and post intensive care syndrome and just there's not something that says exactly ICU acquired weakness becomes post intensive care syndrome, but you can definitely infer somebody who's weak and continues to be weak for a year following, intensive care stay.

That significantly impacts their life and and can, of course, impact all the other demands of PICS.

So jumping into critical illness myopathy, as you can tell from the name myop myopathy myopathy has a issue within the muscle itself.

And so the the pathology is is primarily, in this case, related to muscle.

So with this, there's there's a selective loss of myosin at the thick filaments.

It's unclear exactly why the thick filaments are preferentially acted.

However, it might have something to do with the bioenergetic failure as the myosin is what, connects with the ATP to to help the contraction happen.

Within that, the the type two muscle fibers are most frequently associate or are most frequently affected.

So these are the fast twitch powerful fibers.

So you can you can imagine the significant weakness associated with that as opposed to a slower filament that that would be less visible on on exam.

Additionally, with some of the damage to the muscle, there's there's impairment of electrical impulses with inactivation of sodium channels, which can happen with, with acid based changes as well as other other changes within the muscle itself resulting in a decrease excitability.

All of this is also coupled with bioenergetic collapse as I talked about with binding to ADP on myosin.

Mitochondria is is less functional in the state of of critical illness, especially within sepsis and other things that we'll talk about in just a minute.

And, of course, the this all results in an impaired functional outcome.

Now moving to critical illness, neuropathy.

Now this is an a nerve issue, typically.

And so there there's injury to the nerve itself, usually the axons.

One proposed reason is by microvascular dysfunction, and so there's decreased perfusion to the nerve axon itself.

So that can result in ischemia, ultra permeability, changing of the the lining or or the the myelin sheaths that help to propagate the trichlet impulses quicker.

And then with that, you can have degeneration of the axons.

And so this is really helpful in differentiating the the physical exam findings that you see with these patients, and how there can be some some variability in presentation.

However, importantly, this is a continuum that they can happen together as critical illness myopathy, critical illness neuropathy.

They can become something called critical illness neuromyopathy or polyradiculoneuropathy.

And so these are things that, are important to to to differentiate, to try to look for in the patients that you see.

Importantly, as you're having somebody with a more neuropathic picture, if the the nerves themselves are damaged, you can have more of a distal pattern.

As you can imagine, damage to the nerve than along that that track as with a radiculopathy or some of that something of that nature.

The more distal things are more frequently affected and longer to recover.

Things to discuss, as we've alluded to earlier, for pathophysiology reasons why this happens, there are both modifiable and non modifiable risk factors starting with hyper or hypoglycemia, which we've seen in our patient.

High high sugars are are injurious.

They can result in reactive oxygen, species formation and then and then damage for so many different reasons.

So it's important to have a good control of sugar.

However, as we've seen or as multiple studies have shown, overaggressive control of both sugar can also be incredibly damaging as well.

And so having that that general one forty to one eighty goal of of blood sugar is important.

Parenteral nutrition can be a risk factor.

You wanna start with early nutrition, enterally, as possible.

And one of the biggest things for our patients, especially somebody like ours, is immobility.

And so whether it's prolonged ventilation, if you if somebody comes in with sepsis, ARDS, and they also have drugs on board such as neuromuscular blockers, Immobility can result in something called mechanical silencing, which basically leads to disuse atrophy.

Other drugs such as vasoactive drugs necessary, especially for somebody who's in in septic shock or some some other process, can also result in, of course, microvascular, issues with perfusion to to things such as muscle and nerve.

As we've briefly touched on, additives, can also result in delirium and also more, immobility as we go forward.

The things that are non not non modifiable but worth paying attention to are the severity of disease, patients with sepsis and SIRS, and specifically multiple organ failure as reasons for why people are higher risk for ICU acquired weakness.

And then additionally, finally, female sex, older age, and importantly, premorbid functional state are all important things to consider.

If somebody comes in with lower reserve, they're much more risk of having continued injury and continued disability.

They have less, to pull from should something like this happen.

Yeah.

The thanks for walking through that.

It's a interesting spectrum to think about of the myopathy versus the neuropathy.

I know we'll dive into it a little bit more.

But just a word on the risk factors, it's always tough with the non modifiable versus modifiable.

Can one of the non modifiable is where the severity of disease, sepsis, how sick are you?

And then one of the modifiable is a laser active drugs, steroids, neuromuscular blockade, additives.

And these sometimes can feel in practice, sort of non modifiable, You're like, this vision is really sick.

I need to use three pressers to keep their map up.

And so how modifiable is that?

But I do think that just raises the strong attention for us to have very intentional and best practices use when we're using things, like adding a presser, using neuromuscular blockade, adding steroids, sedatives for sure.

Right?

It's like, does this person really need to be on neuromuscular?

Do they really need to be RAS negative five?

Or is it something that makes it easier for us, but is not necessary by their condition?

So I do think and we'll get into prevention and treatment.

A lot of this is just being really mindful and really thoughtful about how we use these things, which is not easy because we're we're also trying to treat this critically ill patient.

And so it takes a lot of awareness as we're going through it.

So anyway.

Totally, Bert.

Thanks so much for for bringing that up.

And and, Jim, some great, great walk through of some pathophysiology and I think for that was such a great point on the on the risk factors.

Right?

Coming coming back and bringing it back to our patients' cases, Kyla mentioned, right, we had a 65 year old gentleman admitted for two weeks in the ICU with with severe sepsis, received corticosteroids.

So exactly is, like, what's what's modifiable and what was it during his two week stay?

Jim, so I would love for you to extend on on two broad topics, which I think learners would probably really wanna hear more about, and myself as well.

So you mentioned that ICU associated weakness encompasses both critical illness myopathy as well as critical illness polyneuropathy.

You talked about the pathophysiology and the difference between them.

But clinically, how can we distinguish between them, and how does that affect your overall management of the patient?

Absolutely.

And also just a quick point on on you talking about what is modifiable and what isn't modifiable as far as the KIDCON dose steroids too.

There's been some discussion of is steroids actually a a real risk factor in these cases for ICU acquired weakness.

Are these people just sicker?

Do they need steroids?

And is this just a a demonstration of of where they are?

And so going into that additionally, so talking about how we differentiate these people, I think the important thing is then getting into the why.

Right?

And so critical illness myopathy versus myopathy.

The the the issue, as we were talking about before, being in the muscle or in the nerve or in the the joint critical illness, neuropathy or radicular neuropathy and myopathy, some combination there.

And and so as we talk about something, an an injury within the muscle, you talk about pure weakness, no sensory loss.

And that's going to be one of the biggest differentiating factors between the two.

But this one also happens more rapidly, and you can have some muscle loss within the first forty eight hours of ICU stay.

You can have up to 2% of lean muscle mass loss per day, for the first two weeks in ISU stay.

So you really see a profound loss of muscle and you that's visible.

Something that you can physically see, which can help point you in those directions as well.

With our patient, there's a slight elevation in CK.

Of course, not to a RAB level, but it also suggests that there's some ruble of muscle damage being happening as well.

For the for the neuropathy, of course, you're gonna see, damage to the entire nerve, not just a a motor nerve, and so you're gonna have sensory impact.

As I started to allude to in the last part, you can also differentiate where the the injury is based on the location of presentation.

So if there's more distal predominant weakness, which is not common at all in in critical illness myopathy, but would potentially be more common in something of the critical illness neuropathy picture because of the length of the axon itself, the the more time in which or more space in which this nerve has to to be injured.

And so those are some of the the big important differentiating factors in general.

And then for the critical illness polyneuropathy and myopathy, the the combination ended up being very murky as as Dave was talking about earlier in in this where where you can have a typical presentation and then somebody who comes in with a presentation that looks like it's it's very different than than what you're taught in the book.

And so that's how I think of the neuromyopathy picture.

It's great.

Thanks, Jim.

We're trying to really put on specific labels to something that is often a hybrid, often difficult to distinguish.

I think this is important both for treatment, but also for, like, ongoing research to understand what the condition is and to name it appropriately, even though out of practicality and convenience, we often will use an all encapturing term.

So for this, as we've mentioned, we've ruled out major things we sometimes think about in the ICU, new ischemic strokes, new hemorrhages.

As you mentioned, we didn't have an EEG yet, but let's assume we got one or we didn't have seizures, and weakness would be very atypical for that.

Ruled out encephalitis and meningitis.

Also, for the sake of argument here, let's assume this is not an a myasthenia gravis, Lambert, and organophosphate poisoning case where someone is missed or and in some cases, you'll have the testing for that, but didn't seem typical.

If we want a sort of diagnostic purist as opposed to diagnostic nihilist for this one, Kaila, what would we do?

How what tools could we use, clinch the diagnosis, and feel pretty comfortable calling this, this umbrella term of ICU required weakness?

Yeah.

So there are a couple of tools that are commonly used.

The most commonly used one to make a diagnosis of ICU acquired weakness is this score called the medical research council score or the MRCSS.

And basically, what that is is that we as physicians will, like, grade 12 different muscle groups and then tally up that total score.

If the total score is less than 48, then we think about someone having ICU acquired weakness.

And if it's less than 36, we think of it as, like, a severe disease.

There are a couple of other scores like the critical care physical assessment tool or the functional status score for the ICU.

These are also just ways to, like, assess someone's, like, functional mobility and, like, cadence and ambulation, but they're less used than the MRCSS.

And then we have something called a handheld dynamometer, which is supposed to be like a screening tool.

And, basically, what that is is that we will, like, assess the maximum exertional strength that someone like, someone's grip strength.

And then if it's, like, less than 11 kilograms in men or less than seven kilograms in female, that's, like, a very good screening tool for someone having ICU acquired weakness.

I think the caveat with all of these is that the patient should be awake and able to cooperate with an exam.

And we know that oftentimes our patients in the ICU are sedated or delirious, and we've talked about that a lot.

So we have a couple of different things we can do outside of these scores.

So we talked about imaging, like maybe a muscle ultrasound.

These are good because we can do it at the bedside repeatedly.

The problem with it is that it sometimes underestimates muscle loss in a patient, and especially if they're really edematous.

I think it's a little bit harder to get good windows.

We can do other imaging like CTs or MRIs, but these are expensive.

And oftentimes, it's like a logistical challenge to get them all the way down to the CT scanner.

The two gold standards for defining ICU acquired weakness are the electrophysiologic evaluations and the muscle biopsies.

So the electrophysiologic evaluations consist of nerve studies, nerve conduction studies, and EMGs.

And these are great because per the patient doesn't have to cooperate with them.

But the problem is that they're time consuming.

There is, like, a little bit of pain that may be involved, a little bit of invasiveness.

And, usually, like, the technicians have to be trained and we need, like, trained physicians to be able to interpret these studies.

And then the last one, like the other part of the gold standard is a muscle biopsy.

And this is really great because we can actually tell the difference between medical illness myopathy and polyneuropathy and whether it's a combination of both.

But, of course, it's invasive, and, we have all of the risks of a procedure like infection, bleeding, etcetera.

Yeah.

This part diagnostic person is so interesting.

As you said, there's some really great tools if your patient is awake and cooperative.

And so that that happens.

If that patient has gotten better, they can participate, they can do some ventilator mechanics, they can use the dynamometer, I probably mispronounced that, but anemometer, right, to give us some hand drum strength.

But a lot of our patients are not in that case going all the way to muscle biopsy then sometimes feels like a lot right I have personally had EMG come in the ICU and I've actually found it pretty helpful The patients I've had it the most is, like, when the history is a little murky of, like, how they've been doing at home.

Obviously, we have a large frailty population in the ICU.

And so sometimes there's just, like, well, they haven't been doing so well.

Maybe they have been weaker at home.

And then you're wondering, like, was there this precondition?

As Jim said, ICU acquired weakness can layer on top, but it really shouldn't have proceeded if there were the weakness shouldn't have proceeded the critical illness.

And so I have had that EMG done just help say, like, look, there's not some isolated muscle problem.

There's not isolated neuromuscular problem.

Like, this looks like we have now this combined polyneuropathy, myopathy.

This is just gonna take time.

And that's influence vision again.

Right?

Giving me a better sense of how I can what course I can anticipate.

Does this patient want a prolonged rehab course?

Do they want a trach?

Things like that, where we have a little bit more diagnostic clarity.

And and then it could say, look, this pure muscle, then maybe I would do a muscle biopsy.

The only caveat I'll also add, I I am much more in the diagnostic purest camp.

Like, I love to really know what's going on, but I've gone through the whole pathway, got an ENG, gotten muscle biopsy, and still people are like, well, I don't know.

Maybe it's all diabetes.

Maybe it's a little critical illness, or it's not always like you get a crystal clear answer.

So you have to decide with your patient and their family how much that's worth it to you.

Jim, anything to add about that diagnostic process?

Yeah.

I think and thank you.

This is this is such a, I think, important part of the conversation.

I think as we've talked about before, as far as prognostication, the the diagnostic purist in me really, really wants something like this.

I think EMG is something that is incredibly helpful in these cases.

The issue, however, is EMG, they all whenever you ask for it, they also push back because there's electrical interference with all the ventilators and everything else.

And so it makes the test that much more murky.

And so as far as, you know, in a perfect world, we have a lack of electrical interference.

We can get this handheld thing because the EMG, machines are are massive, tough to bring into to already crowded rooms.

But as far as talking about what the patient can expect and having those really important family conversations, patient conversations, what do you want, what what can we tell you this is gonna look like?

We've talked about the different differences of myopathy versus neuropathy.

One important difference that that I forgot to include is is the myopathy tends to have a better prognosis.

You you have a much better ability to rebuild muscle than that of nerve, especially because nerve, it it takes time, much more time.

There's willary and degeneration.

There's time, equivalent to the distance that it needs to travel to to recover, and then is it actually going to recover.

And so being able to differentiate via something like an ENG more so than a muscle biopsy because that tells you there's myopathy, but it doesn't tell you the lack of neuropathy.

And so, importantly, the EMG, you can actually differentiate.

Is this a myopathic pattern or is this a neuropathic pattern or is this both?

So if you're able to do that, you can have really informed conversations patient or the family going forward about what to expect as well.

Thanks so much, Jim.

And I as you're saying this, and I'd love I have another question for you as well that I love your expertise on it because I think even just between institutions, there's gonna be variation in what type of tests are available.

I know it's it's quite difficult to get EMG, in many of our ICU.

It's not impossible, but it it does take some, mystical planning.

But I'm wondering for those institutions or or places where EMG is not gonna be ready readily available and the patient's not alert and can't cooperate with, like, the screening tools that Khalilah mentioned and some of the other things.

Where are you left at with that if that's not an option for for some patients?

As far as trying to differentiate between ICU, the critical illness, biopothy, neuropathy Yes.

Then you really get into a murky space.

I think it's still in its infancy, but as far as looking at muscle ultrasound, there there are different grading scales that can be helpful.

But as we've already talked about, there's there's a lot of differences as far as new interator reliability and somebody who's a dentist because they've been able to be actually getting fluids and any other number of reasons that can be an issue.

You can clearly see, and if you track over, do an ultrasound once a week on a patient, you can see that there's a change in the architecture.

That's something that's pretty clear there.

But as far as ruling out a nerve injury, that's really, really hard.

And so so it gets it gets difficult on that.

Ideally, that's potentially something that then can get further elucidated down the road when you're out of the ICU or or you've gotten a trach in a bag and you're more on the rehab side.

So the conversations can continue.

It doesn't ideally, of course, in as intensive as we want to have everything light laid out.

This is where we go from here.

This is what's gonna happen.

But this this, as we've all alluded to quite a few times, becomes quite murky.

Yeah.

Thanks so much for that.

And, Khalilah, I'm hoping we can come back to the cooperate with our exam.

He scored a 32 on the MRCSS, so that is severe IC required weakness.

And then he did the handheld dynamometer dime I'm gonna say it wrong too.

Dynamometer.

And he also had a poor grip strength.

So, overall, we think severe ICU acquired weakness.

Yes.

I think it was confirmed that we we fall squarely into the umbrella term.

Big question is now what can we do about it?

Patient already has it.

And so what are the types of interventions or things that we can do to help them cover?

And then obviously, obviously, we also wanna keep in the back of our mind things we can learn from this patient to the next one to maybe see if we can try to prevent this.

So, Jim, any thing treatments or best practices we can do for patients like this?

Yeah.

Absolutely.

And so as you've alluded to, this person already has this process.

And so as with anything, the the best treatment is prevention.

And so an ounce of prevention is is greater than a pound of cure.

However, as I think the important thing is realizing that this is this is a process that can continue to happen.

And so by doing something now, you're also stepping in and and preventing worsening of it.

And so, in general, I like to think about two different kind of acronyms for thinking about it.

One, the the factors that are associated with this increased weakness and try and simplify it for myself because we talked about things in-depth and there's quite a lot.

So if you're thinking somebody has or is at risk of issue acquired weakness, things that you wanna think about are sepsis and inflammation as risk factors, immol immobilization and inactivity and resource imbalance, whether that be hyperglycemia, hyperglycemia, mitochondrial dysfunction, ATP depletion, any other electrolyte abnormality, hypermagnesemia being a cause of weakness and things like that.

And then exogenous things for the e.

What are we doing to this person that we can potentially try and pull them?

You know, limit neuromuscular blockers, limit corticosteroids.

And then thinking about maybe the vulnerability that you've already talked about.

How what was this person doing before, and how can we best tee them up?

And then thinking about our patient and what we do, you wanna treat the infection.

We we gave coupon dose steroids.

We gave antibiotics.

We gave everything that needed to be done to treat the underlying process.

Another thing, I'm glad that we we talked about kind of Wesley Lee, and and colleagues as far as the AF bundle.

This is something that has been really impactful for a number of a number of different processes, critical illness, and and looking at different outcomes, not just weakness.

But this is something that for those who are are not familiar, the ADF bundle is is a collection of six different interventions that can be and should be done for every patient every day.

Broad strokes talking about choice of sedation, daily SAT, SBT, assessing and managing pain, delirium treatment, and then importantly, early mobility.

And so I think on my own little soapbox, I think early mobility is also a little of a a shortcoming going forward too.

You get early mobility that just talks about walking.

We can also start talking about what we can do with the patient in the bed, yells, and things of that nature.

So trying to get people involved and engaged to have helped their function either improve or or stall the the the downtrend in function.

And then, of course, talking to families, which is something that's very important.

And we already talked about as far as controlling glucose, pretty, pretty important.

And then team based care.

We wanna make sure that everybody who needs to be involved is involved, whether it be therapists or or different consulting services and and things of that nature.

So just really being very vigilant and and trying to to prevent any worsening and and to recognize the the warning signs.

One thing?

Yeah.

One last thing that's that's, based on different meta meta analysis and reviews, can potentially be helpful, but is not yet And it's actually in the the recommendations for anybody in the ICU that can feasibly do it is neuro NMES or dermochecular electric stimulation.

This is helpful for, as we talked about, all the patients who we have who are intubated, sedated, unable to participate in things.

NMES places electrodes on the muscles and causes contraction.

So there's there's improvement as far as lack of mechanical silencing, engagement of these muscles that can potentially prevent this this myopathy or at least atrophy and weakness part.

However, other things associated with critical illness end up being things that really limit the efficacy of this because if you're septic, acidotic, the the stimulation needed for contraction is also higher.

And so, in general, it's it's something that potentially could be helpful if if your hospital is is proficient and able to do it.

Great.

Thank you so much, Jim.

And I know, as you mentioned, so important prevention is key.

But if if you have this, right, there are many steps that you can do to try to prevent or minimize the outcomes from it.

So I know I get I have the opportunity to work with, with del Netam, and early mobility is definitely, something that we try to we try to do.

And I know sometimes when we're rounding in the ICU, like, we're we're coming to the end and everyone's like, well, what would Dell do?

What would Dell say for this patient?

Because if Dell says that we gotta do it.

But definitely so many great things and so many colleagues to get to work with to help patients with ICU acquired weakness.

And, Kalei, I think we're coming to an end on our case.

I would love if you could give us an update in how the the patient was managed and overall outcome.

Yeah.

Of course.

So he underwent aggressive physical therapy.

That's to prevent any muscle any further muscle atrophy, improve his strength.

We did a better job with controlling his sugars with his insulin sliding scale, and we were able to start him on enteral nutrition very quickly.

Fortunately, he had already completed his dose of steroids, so that kind of out of the way.

And, ultimately, he was transferred to an LTAC.

And then after being there for several weeks, he was actually able to improve enough that he was being off of the vent successfully.

Well, that's so great to hear.

And I know definitely I think all of us that take care of patients in the ICU, a lot of the courses can be quite long and extend outside the ICU to the floors as as well as to rehab facilities.

So definitely a long process and a lot of people that help along the way.

But I'm glad that he had a a successful outcome.

Well, I know that Dave and I really want to thank you both for joining today.

This has been a great case and a great topic to introduce.

So thank you so much, Jim and Kyla, for being with us here today.

Jim, just wanted to see if you had any parting words for today or anything that you wanted to add.

Yeah.

So I think first off, I wanna thank you all for for allowing me to be here.

It's really been a pleasure and a really just just a lot of fun to talk about something that that is is really important to me.

This is something that I plan on spending a lot of my career looking further into.

And so the having the the ability to to be here and talk with you guys has been a lot of fun.

I think as as far as a takeaway goes, I'd I'd say be vigilant.

Know that this is something that not just can happen, but does happen frequently.

And to to know the the warning signs and and how to to intervene.

Kala thanks, Jim.

It's great.

Kala, did you have any takeaway points or anything that you wanted to to add for this case?

Yeah.

I'd I'd say a takeaway point for me is what you were mentioning about how sometimes not at like, even the things that we're doing don't feel like modifiable risk factors.

So really just keeping a very close eye on what we're giving the patients and what we can pull back when we need to.

Yeah.

100%.

I think that is attention to detail of these things, and I have also had the pleasure of rounding with Dale, Christina.

And I think he is a prime example of things are modifiable even though we are getting entrenched and think they're not and and beyond just him, but everywhere.

I think the best case scenario for this story is the use of midazolam with benzos, which we know are associated with worse and delirium and outcomes.

And really, this was super common practice basically everywhere.

And now very, very rarely are you gonna see people on sustained drips at high doses unless there's, like, absolutely no other option.

So it does it just takes time.

I think my takeaway is gonna be something Jim was talking about with the spectrum, critical is myopathy to poly to neuropathy and then the mix.

In my own entrenched frameworks, I, like, usually think of ICU acquired weaknesses muscle alone because I'm really thinking about that early myopathy.

But I it's important for me to always remember that you can get these sensory deficits that come on later on, and then you can get this more sort of mixed picture.

And I know that, and I've seen visions of that, but it takes time to build into my illness script for ICU acquired weakness.

So that's one I'll add to it.

Christina?

Awesome.

Yeah.

I think I'm going back to one of Jim's first things that he discussed when thinking about IC acquired weakness, really more of this umbrella term.

And then I think a a nice point that you that was mentioned was this must not precede critical illness, and how we think about that.

So that's one of the one of the many takeaways from today.

That's great.

Well, thank you guys again for coming on the show.

Thank you all for tuning in and listening.

Stay out there.

Be vigilant, about these factors and and and screening for ICU require weakness.

And tune in in two weeks for our next episode.

This episode was written, produced, edited by myself, Christina Montemayo.

Kalaio Paez came up with the idea, and Jim is our expert consultant here.

And the music is original music by Art Rogers.

And we'll see you next time.