105. ICU Acquired Weakness

Today we’re talking about a topic that is relevant for all critical care physicians but under-examined: ICU Acquired Weakness. We are joined by two excellent guests to walk through a case and discuss the diagnosis, pathophysiology, prevention, and treatment of … Continue reading →

Episode Transcript

(00:16):
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.

(00:37):
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

(00:59):
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

(01:21):
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.

(01:44):
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.

(02:04):
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

(02:25):
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

(02:46):
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.

(03:07):
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

(03:28):
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,

(03:49):
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,

(04:11):
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

(04:33):
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

(04:55):
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

(05:18):
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

(05:38):
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

(05:59):
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,

(06:20):
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

(06:40):
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,

(07:02):
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

(07:22):
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,

(07:42):
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

(08:03):
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

(08:24):
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

(08:46):
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

(09:09):
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

(09:29):
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

(09:50):
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

(10:11):
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.

(10:34):
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

(10:55):
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

(11:15):
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.

(11:35):
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

(11:56):
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.

(12:17):
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

(12:38):
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.

(12:58):
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

(13:19):
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

(13:40):
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.

(14:01):
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

(14:21):
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

(14:42):
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,

(15:03):
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

(15:25):
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

(15:46):
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.

(16:07):
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

(16:28):
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

(16:49):
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

(17:11):
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

(17:33):
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

(17:55):
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

(18:17):
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

(18:40):
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

(19:01):
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

(19:21):
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.

(19:42):
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

(20:03):
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

(20:24):
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

(20:46):
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

(21:06):
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

(21:28):
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

(21:48):
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

(22:10):
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

(22:30):
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.

(22:52):
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

(23:12):
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,

(23:35):
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

(23:56):
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,

(24:19):
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,

(24:42):
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

(25:03):
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

(25:24):
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

(25:45):
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

(26:06):
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

(26:27):
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

(26:49):
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

(27:10):
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,

(27:31):
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

(27:53):
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

(28:15):
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

(28:37):
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

(28:58):
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

(29:19):
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?

(29:40):
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.

(30:00):
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

(30:23):
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

(30:43):
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.

(31:05):
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.

(31:26):
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

(31:46):
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

(32:08):
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

(32:29):
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

(32:50):
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

(33:11):
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

(33:32):
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

(33:53):
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

(34:14):
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

(34:36):
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

(34:56):
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.

(35:17):
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

(35:39):
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

(35:59):
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.

(36:19):
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?

(36:40):
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

(37:03):
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

(37:26):
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

(37:46):
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

(38:07):
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

(38:27):
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?

(38:49):
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.

(39:09):
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

(39:31):
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.

(39:51):
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

(40:14):
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

(40:34):
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

(40:56):
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

(41:17):
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

(41:38):
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

(42:00):
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

(42:21):
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

(42:42):
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,

(43:05):
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

(43:25):
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

(43:45):
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

(44:05):
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

(44:25):
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

(44:46):
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.

(45:07):
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

(45:27):
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

(45:49):
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

(46:09):
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.

(46:30):
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

(46:51):
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

(47:11):
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.