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Critical Care of Neuromuscular Disorders
6 Plays6 years ago
In this episode of Critical Matters, we discuss acute neuromuscular disorders in the intensive care unit with Dr. M. Kamran Athar. The discussion focuses on the Guillain-Barre Syndrome and Myasthenia Gravis.
Dr. M. Kamran Athar is a practicing neuro intensivist at the Farber Institute for Neuroscience in Philadelphia. Dr. Athar is an assistant professor of Medicine and of Neurology at the Jefferson School of Medicine in Philadelphia.
Additional Resources:
The clinical management of neuromuscular disorders in intensive care: https://bit.ly/2wWlYe1
Early predictors of mechanical ventilation in Guillain-Barré syndrome: https://bit.ly/2Icb1vi
International consensus guidance for management of myasthenia gravis: https://bit.ly/2Ic2g4I
Books Mentioned in this Episode:
How Doctors Think by Jerome Groopman: https://amzn.to/2ZmHSmV
Recommended
Transcript
Introduction & Historical Context
00:00:09
Speaker
Welcome to Critical Matters, a sound critical care podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:17
Speaker
And now, your host, Dr. Sergio Zanotti.
00:00:23
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Historically, the growth of intensive care units has been closely linked to polymyelitis,
00:00:28
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and the need its patients has had for prolonged mechanical ventilation support with the iron lung at the initial of these epidemics.
00:00:36
Speaker
With the development of the Salk vaccine, this problem has disappeared from our clinical practice.
00:00:41
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Today, the Guillain-Barré syndrome and myasthenia gravis account for the majority of patients requiring intensive care admission due to acute neuromuscular weakness.
Guest Introduction & Core Topics
00:00:50
Speaker
In today's episode of Critical Matters, we will discuss critical care aspects of these acute neuromuscular disorders.
00:00:57
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Our guest is Dr. Cameron Athar.
00:00:59
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Dr. Athar is a trained in critical care medicine and neurocritical care.
00:01:03
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He's a practicing neurointensivist at the Farber Institute of Neuroscience in Philadelphia.
00:01:08
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Dr. Athar is an assistant professor of medicine and of neurology at the Jefferson School of Medicine in Philadelphia.
00:01:14
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He has published extensively in the field and is an excellent clinical educator.
00:01:17
Speaker
Cameron, welcome to Critical Matters.
00:01:21
Speaker
Thank you, Sergio, for this kind introduction and thanks for the opportunity to participate in this podcast.
00:01:29
Speaker
So I think that we might start by making a differentiation.
00:01:32
Speaker
Today, most of the patients that have neuromuscular weakness in the ICU have acquired it in the ICU in what we know as critical care-induced myopathy, neuropathy, or neuromyopathy, which is more of a chronic consequence of critical illness.
00:01:48
Speaker
But what we really want to talk about today, Cameron,
00:01:50
Speaker
is those patients who present with acute neuromuscular weakness that require admission to the ICU.
Differential Diagnoses & ICU Relevance
00:01:57
Speaker
So perhaps a great place to start would be for you to give us a little bit of a differential diagnosis of that patient that presents to the ED or to the hospital with acute neuromuscular weakness.
00:02:09
Speaker
Yes, thanks, Sergio.
00:02:10
Speaker
That's a very important question.
00:02:13
Speaker
So the differential diagnosis of acute neuromuscular weakness leading to
00:02:18
Speaker
ICU admission is fairly extensive.
00:02:21
Speaker
The most important conditions to be considered are the acute polyneuropathies of Lyon-Buray syndrome is the most common one for which these patients require admission to the ICU.
00:02:36
Speaker
Other causes of acute polyneuropathies less commonly seen include severe thiamine deficiency, acute arsenic poisoning, Lyme disease, vasculitis,
00:02:47
Speaker
glue sniffing, porphyrias, which typically present with psychiatric manifestations in addition to neuropathy, as well as unexplained GI symptoms.
00:02:58
Speaker
Miller-Fisher syndrome is a subtype or clinical variant of Guillain-Barre syndrome, which is also an acute polyneuropathy that frequently requires ICU admission.
00:03:09
Speaker
In addition, other conditions that should be kept in mind in the differential are neuromuscular disorders, which is myasthenia gravis,
00:03:17
Speaker
Lambert-Eaton syndrome and botulism, penia gravis being the most common of the neuromuscular disorders.
00:03:24
Speaker
In addition, motor neuron disorders such as poliomyelitis, West Nile virus encephalitis, amyotrophic lateral sclerosis, as well as progressive spinal muscle atrophy are also in the differential.
00:03:39
Speaker
In addition, certain brainstem conditions which can mimic Miller-Fisher syndrome
00:03:46
Speaker
should always be on the differential as well.
00:03:49
Speaker
These include brain stem strokes, which typically are acute in onset, as well as brain stem encephalitis.
00:03:58
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Other conditions affecting spinal cord should also be considered in the differential, such as the acute myelopathy, the most common causes of which are cord compression and transverse myelitis.
00:04:12
Speaker
Typically in these patients on exam,
00:04:15
Speaker
there will be a sensory level as well as involvement of bowel and bladder.
Diagnostic Tools for Neuromuscular Issues
00:04:22
Speaker
In addition, yes.
00:04:24
Speaker
Go ahead.
00:04:26
Speaker
In addition, myopathies such as polymyositis and dermatomyositis are also included in the differential diagnosis of acute neuromuscular weakness.
00:04:36
Speaker
So clearly, Cameron, I mean, a very extensive list of potential causes
00:04:43
Speaker
all of which are very rare for the common practicing intensivist.
00:04:46
Speaker
But I do think that in terms of how you would initiate the workup, are there some basic diagnostic tools that might help the clinician, whether it be in the ED or in the ICU, kind of guide the diagnosis in the right direction?
00:05:04
Speaker
So in addition to the clinical presentation, there are a number of diagnostic modalities available.
00:05:13
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to us, which in the appropriate clinical setting are helpful in establishing a diagnosis.
00:05:20
Speaker
These include lumbar puncture with analysis of the cerebrospinal fluid, electrodiagnostic studies such as EMG and nerve studies, as well as in the appropriate clinical setting, single fiber EMG, as well as repetitive nerve stimulation testing,
00:05:41
Speaker
And in addition, MRI of the brain and spinal cord can also help in excluding certain other causes of muscle weakness.
00:05:53
Speaker
Serologic testing is also important in certain cases, especially myasthenia gravis and the Miller-Fisher variant of Guillain-Barre syndrome.
00:06:05
Speaker
So in terms of deciding where these patients need to go to an ICU,
00:06:09
Speaker
or another type of setting, what are some of the reasons why patients with acute neuromuscular weakness might benefit from ICU admission, and what are the things that you would recommend our critical care colleagues to have in mind?
00:06:23
Speaker
Yeah, so the most important indication for ICU admission for these patients is typically respiratory failure requiring endotracheal intubation and ventilatory support.
00:06:38
Speaker
Especially in cases of Guillain-Barre syndrome, up to 20 to 30 percent of the patients will need ventilatory support at some point during their disease course.
Understanding Guillain-Barré Syndrome
00:06:47
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In addition, in some cases, especially in patients with Guillain-Barre syndrome, autonomic dysfunction can occasionally be severe enough that they will require closed ICU monitoring.
00:07:00
Speaker
Additionally, significant bulbar dysfunction
00:07:04
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in some patients with inability to clear their secretions increase the risk of aspiration.
00:07:10
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And these patients are also, these patients also require closed monitoring into ICU because they can progress to aspiration pneumonia and progress to respiratory failure.
00:07:24
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So I think that to recap, the real three big things are potential for respiratory failure, oropharyngeal weakness,
00:07:31
Speaker
and autonomic dysfunction.
00:07:32
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And I think as we speak more specifically about Guillain-Barré myasthenia gravis, we'll dive into these again.
00:07:39
Speaker
So why don't we go to Guillain-Barré syndrome, like you mentioned earlier, it's one of the most common reasons why patients with acute neuromuscular disease will come to the ICU.
00:07:48
Speaker
And maybe start by telling us a little bit about just how you think about Guillain-Barré in general, its incidence, and maybe what we understand today of its pathophysiology.
00:07:58
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Right.
00:07:58
Speaker
So Guillain-Barre syndrome is the most common cause of acute neuromuscular weakness.
00:08:02
Speaker
And under Guillain-Barre syndrome are included a number of immune-mediated acute polyneuropathies.
00:08:09
Speaker
And most often it presents as an acute monophasic condition that is typically preceded by an infectious illness.
00:08:17
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It is recognized now as a heterogeneous condition with several variant forms.
00:08:22
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And I will mention a little bit about those variant forms in a little bit.
00:08:26
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In terms of epidemiology, the overall incidence is about one to two per 100,000 population per year.
00:08:34
Speaker
And it's slightly more common in males compared to females.
00:08:42
Speaker
And it's also more common as people get older, right?
00:08:44
Speaker
I mean, there seems to be a spike, I mean, as people get age as well.
00:08:48
Speaker
Is that correct?
00:08:49
Speaker
That is correct.
00:08:50
Speaker
So it has been estimated that there is beyond the first decade of life
00:08:56
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there is a 10% increase in the incidence for every 10 years beyond the first decade of life.
00:09:05
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So the incidence definitely increases with age.
00:09:09
Speaker
And you mentioned that often it's preceded by an infectious disease.
00:09:14
Speaker
Very commonly, Campylobacter degeny has been implicated with gastrointestinal, but there's also respiratory and any other
00:09:23
Speaker
viruses or bacteria that are commonly being associated with Guillain-Barre?
00:09:28
Speaker
Yes.
00:09:28
Speaker
So as you mentioned, Sergio, Campylobacteria is the most commonly identified precipitant of Guillain-Barre syndrome.
00:09:34
Speaker
However, certain other viruses, especially cytomegalovirus, HIV, Epstein-Barr virus, and Zika virus, have also been implicated as precipitants for Guillain-Barre syndrome.
00:09:47
Speaker
And that's why it's kind of considered as a post-infectious condition.
00:09:50
Speaker
Cases have also been reported following certain immunizations, and that's always important in the history as well.
00:09:57
Speaker
And as I said, I mean, it's considered as a post-infectious condition, and what happens is that these infectious agents induce antibody production, and these antibodies are then directed against certain components of peripheral nerves because of molecular mimicry.
00:10:14
Speaker
Specifically, these include the ganglioside and glycolipid components of the peripheral nerves,
00:10:19
Speaker
which then results in lymphocytic infiltration, macrophage-mediated stripping of the myelin, and that's why it's kind of considered a demyelinating process.
00:10:28
Speaker
In more severe cases, damage to the axons can occur.
00:10:31
Speaker
And the end result of all of this is that there is defective propagation of electrical impulses resulting in flaccid paralysis.
00:10:40
Speaker
So that, in a nutshell, is sort of the path of physiology of Guillain-Barre syndrome.
00:10:45
Speaker
And I've read a lot about, like, the differentiation
00:10:49
Speaker
of subtypes from a pathophysiology standpoint with the acute inflammatory, demelinating, polyradiocle neuropathy, ADIP, versus acute motor axonal neuropathy, AMAN.
00:11:01
Speaker
Is that mostly in terms of understanding pathogenesis, but ultimately from a clinical perspective, does it have an implication of how we treat them?
00:11:11
Speaker
So in terms of it has more of prognostic significance.
00:11:15
Speaker
The treatment options for all these
00:11:19
Speaker
various subtypes or variants of GBS essentially the same.
00:11:24
Speaker
AIDP or acute inflammatory demyeldening coronary neuropathy, as you mentioned, is the most common variant.
00:11:30
Speaker
In the U.S. and Europe, about 85 to 9% of the cases of Guillain-Barre syndrome are due to AIDP, followed by the Miller-Fisher variant, which accounts for about 10% of the cases in U.S. and Europe.
00:11:43
Speaker
And the classic triad is ophthalmoplegia, ataxia, and areflexia.
00:11:49
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Acute motor axonal neuropathy and acute sensory axonal neuropathy are more severe forms of injury to the peripheral nerves because the axons are involved.
00:12:01
Speaker
So they typically tend to have more severe weakness, and the time to recovery also tends to be prolonged.
00:12:09
Speaker
And that's why sometimes it's important to differentiate what subtype are we dealing with, which may be important for prognostication purposes.
00:12:19
Speaker
Excellent.
00:12:20
Speaker
And in terms of clinical presentation, you mentioned how one of the variants, very well-known, Miller-Fisher syndrome would present with the ataxia, ariflexia, and apomalplegia, often with diplopia.
00:12:31
Speaker
Why don't you tell us, Cameron, what's a typical clinical presentation of a patient who comes to the hospital because of acute neuromuscular weakness from Guillain-Barre, and how do we usually make that diagnosis initially?
00:12:45
Speaker
Right.
00:12:45
Speaker
So the cardinal feature of Guillain-Barre syndrome clinically is progressive and fairly symmetric muscle weakness along with absent or significantly depressed deep tendon reflexes.
00:12:57
Speaker
And these patients typically present a few days to a week after onset of symptoms and bowel and bladder function usually preserved in GBS.
00:13:09
Speaker
In about 50% of the patients, there is also weakness of the facial muscles,
00:13:14
Speaker
as well as oropharyngeal weakness causing bulbar dysfunction.
00:13:19
Speaker
In about 10% of the patients, the weakness may begin in the arms or facial muscles because typically or classically it is recognized as an ascending paralysis or ascending weakness where the weakness starts in the lower extremities and sort of goes up to involve the respiratory muscles and the upper extremities.
00:13:44
Speaker
As I mentioned earlier, in up to 30% of the patients, the respiratory muscle weakness can be severe enough that they will require endotracheal intubation and mechanical ventilation.
00:13:55
Speaker
Some other features that should also be... Yeah, go ahead.
00:13:59
Speaker
I was going to say that in terms of just recapping, the ascending symmetric paralysis is really something that should make the clinician who's not used to seeing these cases very tuned in that this is probably Guillain-Barre.
00:14:13
Speaker
Correct, and also reflexes, areflexia or significantly depressed, deep tendon reflexes are also kind of point to the diagnosis of Guillain-Barre syndrome.
00:14:28
Speaker
And if you look at the National Institute of Neurological Disorders and Stroke diagnostic criteria, progressive weakness and areflexia are required features, along with other supportive features
00:14:42
Speaker
When you say progressive, can you give me an idea
ICU Management & Respiratory Monitoring
00:14:44
Speaker
of the timeframe?
00:14:44
Speaker
So if somebody's had weakness for months, probably not going to be right.
00:14:50
Speaker
Right.
00:14:50
Speaker
Yeah.
00:14:51
Speaker
So in the, uh, uh, typically in these patients, after the onset of symptoms, they typically progress over a period of few weeks.
00:15:00
Speaker
And in most patients, about 90% of the patients, the symptoms have reached their nadir by anywhere between two and four weeks.
00:15:08
Speaker
If these patients continue to progress with their weakness or if their symptoms continue to progress beyond that period of time, you should be thinking about other causes of neuromuscular weakness.
00:15:23
Speaker
And, you know, beyond eight weeks, typically we should be thinking more if we have, especially on
00:15:30
Speaker
EMG electrodiagnostic testing, some demyelinating pattern, then we should be probably thinking about a diagnosis of chronic inflammatory demyelinating polyradiculineuropathy.
00:15:41
Speaker
Excellent.
00:15:41
Speaker
And two more questions regarding the diagnosis.
00:15:45
Speaker
One related to the physical exam and obviously grading the amount of weakness is going to be very important in triage and understanding what treatments have to be implemented.
00:15:57
Speaker
What is the commonly accepted scale?
00:16:00
Speaker
I think that I've read that the British Medical Research Council scale is what people recommend for muscle strength.
00:16:05
Speaker
Could you just review that for our listeners very quickly, Cameron?
00:16:09
Speaker
Sure, yeah.
00:16:10
Speaker
So the British Medical Research Council graded system for muscle strength is widely used.
00:16:15
Speaker
And what the examiner does is he assesses the patient's ability to move the muscle against resistance, which is provided by the examiner.
00:16:22
Speaker
And the patient's effort is graded on a scale of zero to five.
00:16:26
Speaker
So grade five is that the muscle contracts normally against full resistance.
00:16:31
Speaker
Grade four is when the muscle strength is reduced.
00:16:33
Speaker
However, muscle contraction can still move the joint against resistance.
00:16:38
Speaker
Grade three is when muscle strength is reduced to the point that the joint can be moved only against gravity with the examiner's resistance completely removed.
00:16:49
Speaker
Grade two is the muscle can only move if the resistance of gravity is removed.
00:16:55
Speaker
And in grade one, only a trace or flicker of movement is seen or felt in the muscle, or you can observe, or you may observe the circulations in the muscle.
00:17:05
Speaker
And grade zero is when there is absolutely no movement in the muscle.
00:17:09
Speaker
So in terms of considering severe weakness, anything below three, three or below would be considered severe weakness acutely?
00:17:17
Speaker
That is correct, yes.
00:17:18
Speaker
And that's how it is when we say mild, moderate, severe forms of Deandre syndrome.
00:17:24
Speaker
That's kind of what the, it's based on the muscle grading, strength grading system.
00:17:29
Speaker
So anything below three is considered as severe.
00:17:34
Speaker
And the second question you had mentioned earlier in the differential diagnosis and diagnostic tools, the use of an LP.
00:17:41
Speaker
So that is something obviously that's available immediately.
00:17:43
Speaker
Imaging, I understand, would be useful to exclude other causes but not to make the diagnosis of Guillain-Barre.
00:17:50
Speaker
But could you comment on the CSF that we find with Guillain-Barre typically?
00:17:54
Speaker
So the classic finding on CSF analysis in patients with Guillain-Barre syndrome is what we call albuminocytological dissociation, where you have an elevated CSF protein with a normal WBC, a white blood cell count, typically left in five cells per millimeter cube.
00:18:13
Speaker
as many as 66 or two-thirds of the patients by week one will have this finding on CSF.
00:18:20
Speaker
And by week three, more than 75 to 80 percent of the patients will have albuminopsychological dissociation on examination of their CSF.
00:18:32
Speaker
There was a series, prospective series, done at Mass General Hospital of 110 patients where they looked at their CSF profile, and what they found was that
00:18:43
Speaker
87% of these patients had a cell count of less than 5, and another 9% of the patients had a cell count between 5 and 10.
00:18:51
Speaker
So this is a finding that is fairly often seen, and it's classic for patients with Guillain-Barre syndrome.
00:19:02
Speaker
So high protein and no cells or very low cells is what we're looking for.
00:19:06
Speaker
And also, I guess it allows us to differentiate or test for other potential differential diagnosis.
00:19:12
Speaker
which I think is always important.
00:19:14
Speaker
That is correct, yes.
00:19:16
Speaker
Now, in terms of once we see the classical presentation, we make some initial diagnosis, let's say that we feel comfortable with a Guillain-Barré syndrome patient, what would prompt you in your practice, Cameron, to say this patient needs to go to the ICU?
00:19:31
Speaker
Yeah, it's a very important question because, you know, these patients, when they come in, initial triage is important.
00:19:39
Speaker
Some studies have actually looked at clinical predictors in these patients of the need for under-tratubation and mechanical ventilation.
00:19:49
Speaker
And so, as I mentioned earlier, you know, in addition to... So some of these parameters are based on bedside assessments of respiratory muscle strength or spirometry.
00:20:04
Speaker
So patients who have a vital capacity
00:20:09
Speaker
of less than 20 mL per kg.
00:20:13
Speaker
These are patients who are likely or will likely need endotracial intubation and cataclysmal ventilation.
00:20:20
Speaker
This is what we call sort of the 20, 30, 40 rule.
00:20:23
Speaker
So on spirometry, you assess your vital capacity, negative inspiratory force or maximal inspiratory force, and maximum inspiratory pressures.
00:20:30
Speaker
So a number of retrospective studies have shown that a vital capacity less than 20, a negative instaurary force less than 30,
Interventions & Recovery Strategies
00:20:39
Speaker
or a maximum instaurary pressure less than 40 is likely going to result in the need for endotracheal intubation and mechanical ventilation.
00:20:49
Speaker
And so these are some of the criteria that we use to initiate intubation and mechanical ventilation in these patients.
00:20:59
Speaker
And I think that this is very important because, like you mentioned, the 20-30-40 rule with bedside spirometry is very important in predicting who will need intubation.
00:21:09
Speaker
But I would imagine that way before you get there, you want to put them in an ICU so that you're monitoring them, right?
00:21:18
Speaker
So these numbers that you mentioned would be more in terms of crossing the threshold for intubation as opposed to crossing the threshold for let's put this patient in the ICU for close monitoring.
00:21:29
Speaker
Correct, yeah, and actually there is one fairly large study that actually has looked at very early predictors of the need for mechanical annihilation.
00:21:41
Speaker
And this was from the French cooperative group on plasma exchange and Guillain-Barre syndrome.
00:21:47
Speaker
And what they looked at were 700 plus patients with Guillain-Barre syndrome who were enrolled in trials for Guillain-Barre.
00:21:55
Speaker
And the main outcome variable that they looked at was need for mechanical ventilation.
00:21:59
Speaker
And in the cohort, 43% of the patients required mechanical ventilation.
00:22:04
Speaker
And when they looked at the multivariate model, they identified six predictors that predicted the need for an intubation.
00:22:15
Speaker
One was time of onset to admission of less than seven days, which kind of goes on to shows you that these patients have a more aggressive course.
00:22:25
Speaker
patients who are unable to cough, unable to stand, unable to lift the elbows above the bed, unable to lift their head.
00:22:33
Speaker
And then for some reason, they found that liver enzyme increase in this multivariate model.
00:22:38
Speaker
All these six variables were predictive of the need for endotracheal intubation and mycanal ventilation.
00:22:44
Speaker
And what they found was that if a patient at the time of presentation had four out of these six predictors, more than 85% of the time, they required
00:22:54
Speaker
mechanical methylation.
00:22:56
Speaker
And they also looked at a subgroup.
00:22:58
Speaker
Yeah, go ahead.
00:23:00
Speaker
But I was just going to say that we really should have a very low threshold when we see a patient who is acutely admitted and has the early phases of their syndrome because we don't know how they're going to respond to treatment or how they may deteriorate over the next couple of days, right?
00:23:17
Speaker
Yes, that's correct.
00:23:18
Speaker
And these six variables that they identified, they're very, very simple
00:23:24
Speaker
bedside exam, bedside maneuvers that you can do to kind of triage patients.
00:23:32
Speaker
You know, very, very simple bedside tests.
00:23:36
Speaker
In addition, also an important feature of Guillain-Barre syndrome that kind of just differentiates it from myasthenia is that some of these patients, a lot of these patients can actually, from a respiratory standpoint, may remain fairly stable.
00:23:48
Speaker
However, sudden respiratory decline is not uncommon.
00:23:52
Speaker
in these patients, which again argues for close monitoring in a more intensive care setting for these patients because then these patients will require or may require emergent intubation.
00:24:05
Speaker
And in terms of once they come to the ICU, obviously the monitoring is with serial spirometry since I presume that ABGs would be too late in terms of determining the need for intubation once they're hypoxemic and hypercapnic.
00:24:19
Speaker
we probably passed the time when we should have intubated that patient.
00:24:22
Speaker
Is that correct?
00:24:24
Speaker
Yeah, that is correct because, you know, if you have hypoxemia and hypercarbia on ABG, then that already sort of indicates established respiratory failure as a result of respiratory muscle weakness.
00:24:38
Speaker
So that's kind of late in the game.
00:24:41
Speaker
And that's why these early predictors are important.
00:24:44
Speaker
Clinical variables as well as bedside spirometry testing
00:24:48
Speaker
And the trends in these numbers, the bed size parameter testing, are more important.
00:24:53
Speaker
And also, they have to be interpreted in the appropriate clinical setting, looking at the whole big picture as well.
00:25:01
Speaker
And also, take into account bulbar dysfunction, ability to handle secretions, and all those things as well.
00:25:08
Speaker
Yeah.
00:25:08
Speaker
So then, it's not only the absolute number, like you mentioned, with the 20, 30, 40 rule, but like
00:25:14
Speaker
rapidly falling vinal capacity might be as good as an indicator that the patient needs to be intubated as a vinal capacity below 20, right?
00:25:24
Speaker
That is correct.
00:25:25
Speaker
Always, you know, these numbers should be interpreted in the appropriate clinical setting, taking into account, as I said, the big picture clinical clues like signs of respiratory muscle involvement or distress, as well as trend in these measures.
00:25:43
Speaker
They have to be.
00:25:44
Speaker
And also, one must also keep in mind that these numbers, although important, there are caveats because some patients who have facial muscle weakness may not be able to make a good seal.
00:25:57
Speaker
And sometimes these numbers can be, in those cases, misleading as well.
00:26:03
Speaker
So they're not perfect tests.
00:26:04
Speaker
And patient effort and also quality of the testing, I guess, also can impact the numbers.
00:26:09
Speaker
So I think those are great points, Cameron, to
00:26:12
Speaker
to make sure that people are aware of.
00:26:13
Speaker
So since we're talking about intubation and mechanical ventilation, let's just go down this rabbit hole a little bit more, and then I want to go backwards and talk about other treatment modalities.
00:26:24
Speaker
So once the patient's intubated, obviously, like you mentioned, the course, especially the very severe cases, can be prolonged.
00:26:33
Speaker
The good news is that the majority of patients will improve at one point, and many will get back, I mean, maybe to normal function.
00:26:41
Speaker
So you might be in for the long run.
00:26:43
Speaker
How do you think about weaning these patients?
00:26:47
Speaker
And when did you start thinking about trichostomy in these patients, Cameron, in your practice?
00:26:52
Speaker
Yeah, so while these patients are intubated, we should be following their, again, their bedside pulmonary function test or spirometry values closely.
00:27:05
Speaker
And again, decision to initiate weaning
00:27:09
Speaker
and precede vental liberation should be individualized for each patient.
00:27:14
Speaker
You could consider these patients as ready for vental liberation if they have objective evidence of improving respiratory muscle strength, because that is the most important clinical feature, which would be shown by an improvement in their vital capacity.
00:27:31
Speaker
as well as an improvement in their negative inspiratory force or maximal inspiratory pressure.
00:27:36
Speaker
So if the vital capacity is improving, it's about 20 cc per kg, and the negative inspiratory force is more negative than negative 30, the patients on a spontaneous breathing trial, they do not appear fatigued, they're breathing comfortably, there are no signs of respiratory distress, their ABGs are relatively normal.
00:27:56
Speaker
These are some of the patients whom you could
00:28:00
Speaker
a critter activation trial.
00:28:03
Speaker
And also, again, a lot of it depends upon clinicians' individual experience with this type of patient population.
00:28:10
Speaker
There is no perfect way to proceed with weaning in these patients, but some of the rules to remember are that weaning should proceed in a manner that prevents respiratory muscle fatigue and it allows for adequate rest between weaning trials.
00:28:26
Speaker
Excellent.
00:28:26
Speaker
And in terms of tracheostomy,
00:28:28
Speaker
A lot of these patients will be on mechanical ventilation for a long period of time, so early tracheostomy makes sense if we can identify those patients.
00:28:36
Speaker
How do you approach this decision?
00:28:41
Speaker
So vent liberation, the assumption is that those patients that are going to respond to therapy and are going to start the recovery process in a
00:28:58
Speaker
sort of reasonable amount of time, their respiratory muscle will improve, strength will improve, that will allow us to liberate these patients from the ventilator.
00:29:08
Speaker
If that is not happening and the PFTs, pulmonary function testing, those numbers are not improving, probably after 10 days or so, 10 to 14 days is sort of a cutoff, these patients should probably be considered for tracheostomy
00:29:26
Speaker
this patient population is likely going to have a much longer recovery time.
00:29:33
Speaker
However, if you see trends that show improvement over a period of time, those 10 to 14 day cutoff is not set in stone.
00:29:44
Speaker
You could, if you see a positive trend, maybe wait a few more days to allow more time for recovery of respiratory muscle strength and then attempt mental liberation
00:29:56
Speaker
and maybe possibly avoid tracheostomy.
Autonomic Dysfunction & Prognosis
00:29:59
Speaker
So that's kind of like our general approach to these patients.
00:30:03
Speaker
And you mentioned treatment.
00:30:05
Speaker
So why don't we talk a little bit about what are the currently accepted treatments for Guillain-Barré?
00:30:11
Speaker
There's been obviously a lot of discussion back and forth regarding plasma exchange versus IVIG and permutations of this.
00:30:18
Speaker
Why don't you just tell us what would be current state-of-the-art treatment and how you think about it?
00:30:23
Speaker
So...
00:30:26
Speaker
The treatment options available for Gabri syndrome are plasmapheresis or plasma exchange.
00:30:32
Speaker
And the other option available is intravenous immunoglobulin.
00:30:36
Speaker
A number of studies have looked at IVIG versus PLEX.
00:30:43
Speaker
And really, what we have found from all these trials is that they're equally efficacious.
00:30:49
Speaker
And the choice essentially between this and the number of factors
00:30:53
Speaker
of local availability, patient preference, if there are contraindications to one treatment modality versus the other, patient risk factors.
00:31:03
Speaker
So all those are factors that have to be taken into account.
00:31:06
Speaker
But in terms of efficacy, both are equally efficacious.
00:31:12
Speaker
And in terms of differentiating, I guess, with plasma exchange, obviously, the question is you have to put a dialysis catheter, so it's an invasive procedure.
00:31:21
Speaker
But it might be available in certain settings where IVIG is not available.
00:31:28
Speaker
IVIG has an increased expense of the drug.
00:31:31
Speaker
There's been some call-out, not call-outs, there's been like a limited availability of IVIG in certain situations.
00:31:40
Speaker
And in some institutions, it might not be something that is readily available.
00:31:44
Speaker
So I guess those are things or factors that might go into the decision-making as well, correct?
00:31:51
Speaker
That is correct.
00:31:51
Speaker
Yes, absolutely.
00:31:52
Speaker
And, you know, although it's not as common, patients with eye deficiency, if they are given IVIG, they could develop an anaphylaxis.
00:32:03
Speaker
So that would be a contraindication.
00:32:04
Speaker
In addition, I mean, IVIG is also, there's a cost factor that you mentioned.
00:32:11
Speaker
Also, it has some side effects or adverse events as well.
00:32:15
Speaker
Acute kidney injury, septic meningitis, and sometimes intractable headaches.
00:32:21
Speaker
And also, it can sort of occasionally induce a prothrobotic state.
00:32:24
Speaker
So all these factors have to be taken into account in terms of choice between plasma exchange and IVIG.
00:32:33
Speaker
And my understanding of the literature, Cameron, I just want to make sure that, correctly if I'm wrong, is that both IVIG and the plasma exchange, when studied against placebo and controlled studies, have shown to improve outcomes.
00:32:48
Speaker
That is correct.
00:32:48
Speaker
Go ahead.
00:32:52
Speaker
Yes, what the studies have shown is that they both shorten disease duration and they hasten recovery.
00:33:06
Speaker
So the time to recovery from the condition is shortened.
00:33:10
Speaker
So in some ways, they sort of shorten the disease course.
00:33:15
Speaker
And again, addition of IVIG after plasma exchange
00:33:21
Speaker
or vice versa, at least in studies, has not been shown to confer any significant extra benefit.
00:33:30
Speaker
And what about, and the studies that you said earlier, when they compare one against the other have shown no difference in favor of one in particular, but what about combining them for very severe cases?
00:33:41
Speaker
Is there any thoughts or studies on that?
00:33:48
Speaker
Some studies have looked at a combination approach as well, and found is that, and the studies that were done, IVIG was used after plasma exchange treatments had been done.
00:34:04
Speaker
And the addition of IVIG did not actually confer any extra benefit in terms of recovery time and disease progression.
00:34:13
Speaker
So really no benefit, as far as we know, in combining them.
00:34:18
Speaker
And I guess what I have understood from some of my neuro critical care and neurology colleagues is that in very severe cases, what they might do is they might extend the treatment period with the modality they were using a little bit longer.
00:34:30
Speaker
But that is not based on any particular randomized trial, just kind of an expert opinion.
00:34:35
Speaker
That is correct.
00:34:36
Speaker
And, you know, again, it's sort of based on expert opinion, as you said, and also, you know, experience of the clinician, you know, after patients, clinicians who take care of a lot of these patients,
00:34:48
Speaker
and have more experience.
00:34:50
Speaker
And, you know, so some of these decisions are based on their clinical experience.
00:34:55
Speaker
So is there any role for corticosteroids in Yambara?
00:35:01
Speaker
So that's a good question.
00:35:02
Speaker
And a number of systematic reviews and a meta-analysis that have looked at trials that used corticosteroids for patients with Yambara syndrome have shown that
00:35:17
Speaker
steroids do not hasten recovery from DeAndre syndrome or affect the long-term outcome.
00:35:23
Speaker
And actually, there are a number of smaller trials which have shown that actually oral corticosteroids given to these patients may, in some cases, delay recovery.
00:35:32
Speaker
So as of now, the way things stand, corticosteroids have no role in the management of patients with DeAndre syndrome.
Defining Myasthenia Gravis & Its Challenges
00:35:42
Speaker
And what about, we talked about, obviously, the most important
00:35:45
Speaker
Likely reason they will require critical care is mechanical ventilation support.
00:35:49
Speaker
But autonomic dysfunction can also cause severe problems and even mortality in these patients.
00:35:54
Speaker
Could you give us some comments on autonomic dysfunction and how you go about it in the ICU?
00:36:00
Speaker
Yes.
00:36:01
Speaker
Autonomic dysfunction or dysautonomia is a fairly well-recognized feature of Guillain-Barre syndrome.
00:36:06
Speaker
And it can be a cause of significant morbidity and mortality.
00:36:10
Speaker
And it can be seen in up to 70% of the patients with Guillain-Barre.
00:36:14
Speaker
The typical medications are tachycardia, the most common sinus tachycardia.
00:36:21
Speaker
In addition, these patients can have urinary retention, widely fluctuating blood pressures, alternating from hypertension to hypotension.
00:36:31
Speaker
They can also have orthostasis, bradycardia, other cardiac arrhythmias, conduction abnormalities.
00:36:40
Speaker
In addition,
00:36:41
Speaker
Ilias and loss of sweating has also been seen in these patients due to the dysautonomia.
00:36:49
Speaker
In about 20% of the patients, the autonomic disturbances can be severe.
00:36:54
Speaker
And this is typically in patients who have more profound muscle weakness and or respiratory failure.
00:37:01
Speaker
And in these patients, they actually can be threatening the autonomic disturbances.
00:37:08
Speaker
And that's why these patients need to be very closely monitored in the intensive care setting.
00:37:13
Speaker
Their fluid status, their hemodynamics, their vital signs, and of course, their cardiac rhythms.
00:37:19
Speaker
These should be monitored very closely.
00:37:23
Speaker
What's the prognosis of these patients, Cameron, overall?
00:37:28
Speaker
Yeah, so, you know, the outcomes for these patients, in spite of the fact that, you know, they may look very sick when they come in,
00:37:37
Speaker
patient with severe GPS, especially at the nature of their disease, are actually reasonably good.
00:37:42
Speaker
80% of the patients will be able to walk independently in six months.
00:37:49
Speaker
And the number goes up to about 85% by one year.
00:37:55
Speaker
As much as 60% of the patients by one year, there will be full recovery of motor strength.
00:38:02
Speaker
However, a small subset, about 15% of the patients, severe motor problems can persist.
00:38:09
Speaker
In terms of ventilator dependency, about 5% to 10% of the patients will become ventilator dependent.
00:38:19
Speaker
And these are the patients who obviously have more severe form of disease and have more severe weakness.
00:38:27
Speaker
The mortality is about 5% at one year.
00:38:32
Speaker
However, patients who become ventilator-dependent, the mortality, as expected, would be higher, and that is about 20%.
00:38:38
Speaker
And in addition, relapse can happen in about 10% of the patients.
00:38:46
Speaker
This occurs, and these are typically treated with an course of IVIG or plasmapheresis.
00:38:54
Speaker
And I think it's an important point because we usually have a very narrow view of patients in the ICU.
00:39:01
Speaker
And in this particular case, even though the road would be long with rehab and support, but the outcomes are quite good overall in terms of improvement and for many even getting back to a normal life.
00:39:13
Speaker
So I think it's important for intensivists when they talk about goals of care and when they talk with patients and counsel them on what to expect.
00:39:22
Speaker
That is correct.
00:39:22
Speaker
And that's a very important point.
00:39:24
Speaker
You know, you have to sort of...
00:39:27
Speaker
make it clear to the family as well as the patient that they may look really, really bad from a clinical standpoint in terms of their weakness at the height of their disease or condition when they're at the ICU.
00:39:42
Speaker
However, the road to recovery may be long and requiring a lot of physical therapy rehab, but most patients will recover fairly well, reasonably well, over the course of the next six months to a year.
00:39:58
Speaker
Excellent.
00:39:59
Speaker
So why don't we switch topics and talk a little bit about myasthenia gravis, which as you mentioned, is a neuromuscular plate disease that is also commonly seen in acute patients with neuromuscular disorders in the ICU.
00:40:12
Speaker
And just tell us a little bit about what's the incidence, what is myasthenia gravis, and we can start there.
00:40:19
Speaker
Yeah.
00:40:20
Speaker
So myasthenia gravis, you know, it's an acquired autoimmune disorder.
00:40:23
Speaker
It's the most common disorder of neuromuscular transmission.
00:40:27
Speaker
Classic clinical features are weakness of the scalpel muscles and fatigability on exertion.
00:40:34
Speaker
And in terms of incidence, the annual incidence is 7 to 20 new cases per million population.
00:40:42
Speaker
The prevalence anywhere from 70 to 320 cases per population.
00:40:46
Speaker
And the prevalence actually has been increasing over the last 60 to 70 years, and that is primarily because of the increased recognition of this condition.
00:40:57
Speaker
aging population and also patients with myasthenia gravis are living longer so the prevalence obviously has increased in the last 60 to 70 years or so in terms of what age group can it affect it can affect patients in any age however there's a biomodal distribution to the age of onset there's an early peak which is seen in the second and third decade of life and
00:41:23
Speaker
And typically, these patients tend to be females.
00:41:27
Speaker
So there's a female predominance in this subgroup patient.
00:41:32
Speaker
Then there's another late peak that is seen in the sixth to eighth decade of life with a more male predominance.
00:41:38
Speaker
And in terms of pathophysiology, you mentioned autoimmune disease.
00:41:44
Speaker
Can you just give us a little more details in terms of what are the antibodies that occur and what happens
00:41:52
Speaker
Yes, so as I said earlier, it's an acquired autoimmune disorder, and it's characterized by production of autoantibodies to the acetylcholine receptors, as well as the acetylcholine receptor-associated protein on the post-synaptic muscle membrane.
00:42:09
Speaker
This leads to blockage or prevents binding of acetylcholine to the receptors.
00:42:16
Speaker
In addition, these autoantibodies also induce
00:42:19
Speaker
sort of what we call complement-mediated degradation of the acetylcholine receptors.
00:42:24
Speaker
The result of all of this is that these muscle weakness develops.
00:42:29
Speaker
And in addition, over time, the synaptic cleft widens in these patients, and also the number of postsynaptic muscle membrane folds decreases, which is what we expect in a patient where the number of acetylcholine receptors available to the neurotransmitter is decreased.
00:42:49
Speaker
And in terms of diagnosis, how do you diagnose myasthenia gravis?
00:42:54
Speaker
So the diagnosis is suspected on clinical grounds.
00:43:01
Speaker
And other diagnostic modalities available are serological testing to check for or look for acetyl-coating receptor antibodies or muscle-specific receptor, tri-parison kinase receptor antibodies.
00:43:16
Speaker
And in very occasional cases, lipoprotein receptor-related protein 4 can also be seen.
00:43:27
Speaker
And in addition to serological testing, electrodiagnostic testing can also be helpful.
00:43:34
Speaker
These include single fiber EMG and repetitive nerve stimulation.
00:43:39
Speaker
The repetitive nerve stimulation, typically you would see a decremental action potential with repeated nerve stimulation, whereas single fiber EMG is probably the most sensitive test for diagnosis.
00:43:54
Speaker
However, it's technically quite, it's technically a little difficult, but it's also in the, you know, if you have the expertise available, it does help establishing the diagnosis.
00:44:07
Speaker
And I think that my impression, correct me if I'm wrong, Cameron, is that most patients that we see as intensivists with myasthenia gravis will have a diagnosis of myasthenia gravis made.
00:44:19
Speaker
And we usually see them in the context of a myasthenia gravis crisis or in the context of they are undergoing surgery or other critical illness and they come to the ICU.
00:44:30
Speaker
So it's not very common that we do a de novo diagnosis in the ICU.
00:44:35
Speaker
Is that true?
00:44:37
Speaker
That is correct, yeah.
00:44:39
Speaker
Most that will present to the ICU will come with what we call a myasthenic crisis, which essentially is defined as neuromuscular weakness to the point that these patients need some sort of ventilatory support, which could be either intubation and mechanical ventilation or noninvasive ventilation, or muscle weakness that delays recovery after surgery.
00:45:06
Speaker
or prolongs recovery or delays extubation after surgery.
00:45:10
Speaker
So these patients, I agree, most of the time already have established diagnosis of myasthenia gravis.
00:45:17
Speaker
And one of the features in terms of diagnosis that is very common, I guess, is ptosis or weakness in the eyelid.
Crisis Management & Immunomodulation
00:45:25
Speaker
And I remember, I mean, as a resident, we would talk about the ice pack test.
00:45:30
Speaker
Could you tell us a little bit about that?
00:45:32
Speaker
The test is essentially based on the principle that neuromuscular transmission improves at lower muscle temperatures.
00:45:39
Speaker
And if you, in patients with myasthenia, ptosis can be overcome by application of direct cooling to the eyelid muscle.
00:45:48
Speaker
That's what the ice pack test is.
00:45:50
Speaker
It's very simple.
00:45:51
Speaker
What you do is you take a surgical glove, fill it with ice, and place it on the closed eyelid for two minutes.
00:45:56
Speaker
And then when the ice is removed, the extent of ptosis is immediately assessed and in ptosis is considered a positive test result.
00:46:04
Speaker
It's a very simple bedside test.
00:46:07
Speaker
And I think that those are probably much more safe than doing neostigmine or endonoculum injections at the bedside, correct?
00:46:17
Speaker
That is correct.
00:46:18
Speaker
And actually, as of, I think, 2016 or 2017, hydrofonium is actually no longer available in the U.S.
00:46:26
Speaker
So it essentially has pretty much gone out of favor, that Adrophonian test.
00:46:31
Speaker
And just to go back to the ice pack test, the sensitivity is approximately 80% for the test.
00:46:40
Speaker
And I think that one of the things that you were mentioning was obviously the characteristic of articability or the fact that with repetitive contractions, the weakness comes up.
00:46:50
Speaker
How does that impact your evaluation of respiratory weakness?
00:46:55
Speaker
perhaps you do vital capacity and it's normal, right?
00:46:57
Speaker
So it doesn't really give you a clear indication of how to follow these patients.
00:47:02
Speaker
Yes.
00:47:03
Speaker
So, again, in these patients, you know, in patients with generalized myasthenia, that's where you will have variable sort of combination of bulbar, limb, and respiratory muscle weakness.
00:47:23
Speaker
And in some cases, the muscle weakness, respiratory muscle weakness, can be severe enough to necessitate some sort of ventilatory support.
00:47:33
Speaker
And again, the initial assessment of these patients would require some basic clinical bedside testing so you can ask them to
00:47:49
Speaker
start counting, so single breath, how many numbers they can count.
00:47:55
Speaker
You can look at any evidence of respiratory muscles fatigue.
00:48:00
Speaker
And again, if you want to get more objective, you can do bedside spirometry testing, including assessment of vital capacity, negative respiratory force, and or maximum expiratory pressures in these patients.
00:48:13
Speaker
And one of the differences that I think is important to highlight for the audience
00:48:19
Speaker
and you mentioned it briefly, but I want you to dive in a little bit more, Cameron, is that in general, for Guillain-Barré syndrome, noninvasive positive pressure ventilation is not recommended.
00:48:29
Speaker
So usually when they have issues, we go directly to endopracheal intubation.
00:48:33
Speaker
But you did mention the Guillain-Barré, sorry, in the myasthenia gravis population that noninvasive ventilation might be helpful.
00:48:40
Speaker
It might be a way of supporting them early on.
00:48:42
Speaker
Could you mention that a little bit more, please?
00:48:45
Speaker
Yes.
00:48:47
Speaker
Again, as, Sergio, you mentioned, in patients with Guillain-Barre syndrome, noninvasive ventilation, as things stand out now today, really has no role because there are very small case series that have shown that patients who were tried on noninvasive ventilation in Guillain-Barre syndrome required emergent intubation because after staying stable for a while, these patients developed sudden respiratory deterioration.
00:49:17
Speaker
However, in patients with myasthenia gravis, again, there are small case series where noninvasive ventilation has been used as a bridge to prevent or avoid intubating these patients, sort of as a bridge to recovery.
00:49:34
Speaker
And also, patients who are intubated and you want these patients to be liberated from the ventilator, it has also been used as a bridge to ventral liberation.
00:49:46
Speaker
So there is some limited literature on that, which again kind of points to the fact that myasthenia and Guillain-Barre syndrome are two somewhat different conditions that can present both with respiratory failure, but the pathophysiology is different.
00:50:04
Speaker
So in small case series in patient myasthenia, where non-invasive isolation was tried as an initial ventilatory strategy,
00:50:14
Speaker
Well, the factors that predicted BIPAP failure or non-invasive ventilation failure were baseline hypercapnia, which means that by the time these patients start to get hypercapnia, that probably you would not be able to bridge them to recovery just using non-invasive ventilation.
00:50:33
Speaker
So the key point is that if you do want to try non-invasive ventilation, try it early.
00:50:40
Speaker
While at the same time, other treatment modalities are being administered,
00:50:44
Speaker
to hasten recovery in these patients.
Medication Cautions & Weaning Strategies
00:50:49
Speaker
So why don't we talk about the treatment modalities that are commonly utilized for myasthenia gravis.
00:50:55
Speaker
And I think that there's a distinction between maintenance therapy for myasthenia gravis, this is a chronic disease, as opposed to acute Guillain-Barré, versus how we treat the myasthenia gravis crisis.
00:51:10
Speaker
So why don't you tell us a bit more about that, Cameron?
00:51:14
Speaker
Yeah, so my stenic crisis, in addition to assessment of the need for ventilatory support, other medical therapies available to us include immunomodulating treatments, and these can be subdivided into rapid modulating treatments, which include the plasma exchange or plasmapheresis and the venous immunoglobulin or IVIG.
00:51:39
Speaker
In addition, chronic immunomodulating treatments include
00:51:42
Speaker
glucocorticoids, or other immunosuppressive drugs, which in most cases should be initiated at the same time because the effect of the rapid immunomodulating treatment typically lasts for about three to six weeks.
00:51:59
Speaker
In addition, anticholinesterase agents are typically used for symptomatic treatment, and patients who are in a myasthenic crisis
00:52:12
Speaker
it is still somewhat controversial whether these patients in the midst of a myasthenic crisis should be on anticholinerous rate agents or not.
00:52:22
Speaker
Some people argue that because they do provide some symptomatic improvement, that they may be helpful as long as patients are able to handle their secretions, and secretions is not a major or significant factor in these patients.
00:52:39
Speaker
So in terms of rapid immunomodulating treatments, again,
00:52:42
Speaker
IVIG and Plex are the two therapeutic modalities.
00:52:47
Speaker
Typically, the onset of their action can take anywhere from a few days to up to a week, and the maximal effect takes up to three weeks or can take up to three weeks.
00:53:00
Speaker
And the effect of these therapies lasts anywhere from three to six weeks.
00:53:06
Speaker
The dose for IVIG is 0.4 grams per kg per day.
00:53:11
Speaker
for five days for a total dose of two grams per kg.
00:53:14
Speaker
And for plasma exchange, typically four to six sessions are given over a period of eight to ten days.
00:53:28
Speaker
And in terms of patients that you mentioned, so here another distinction is that corticosteroids do have a very prominent role in the treatment of Mycenae Gravis both
00:53:39
Speaker
chronically, but also in crisis, we initiate them because their effects will occur later, correct?
00:53:45
Speaker
That is correct.
00:53:46
Speaker
And generally, the gluocorticoids are started initially at relatively high doses, anywhere from 60 to 80 milligrams daily preptone.
00:53:56
Speaker
And their onset of action is relatively later, about two to three weeks from the initiation of the medication, and peaks at about five to six months.
00:54:10
Speaker
And although, as you mentioned, Sergio, transient weakness or worsening of symptoms can be seen in these patients, which can be actually significant in as many as 50% of the patients, what you do want is the glucocorticoids to be initiated because after the effects of the plasmapheresis and IVIG, which typically, as I said, lasts for three to six months,
00:54:39
Speaker
wears off, these patients can have a rebound of their symptoms.
00:54:45
Speaker
And what you want is to be on an immunosuppressive agent to suppress the production of autoantibodies.
00:54:55
Speaker
And also, in terms of the worsening of symptoms, typically the period where you can have worsening secondary to
00:55:07
Speaker
initiation of corticosteroid is five to 10 days after the initiation.
00:55:11
Speaker
And that worsening can last anywhere from five to seven days.
00:55:15
Speaker
So be very cognizant of that time period when glucocorticoids are initiated and should be in terms of worsening of symptoms that could be related to the use of glucocorticoids.
00:55:28
Speaker
Excellent.
00:55:29
Speaker
And the next question I have for you, Cameron, relates to when these patients are in mechanical ventilation,
00:55:35
Speaker
They are receiving, obviously, acute treatment for their crisis.
00:55:39
Speaker
The regular life or the regular time frame of these diseases is different than Guillain-Barre, right?
00:55:49
Speaker
So, in theory, these patients should have a lower proportion of prolonged mechanical ventilation and tracheostomy.
00:55:56
Speaker
Could you talk about the weaning of these patients?
00:55:59
Speaker
So, again, weaning for patients with myasthenia gravis
00:56:03
Speaker
The general principles are similar, however, in terms of which is that if you have serial measurements of bedside spirometry showing trends in the right direction, improving respiratory muscle strength,
00:56:25
Speaker
In addition, if these patients, while on the ventilator, on spontaneous breathing trial, they do not have any signs of significant respiratory distress or fatigue, these patients should be concerned for mental liberation.
00:56:42
Speaker
And there's one clinical rule of thumb, especially in myasthenic patients, that ready to wean when they can actually hold their head above the bed.
00:56:50
Speaker
That's a very significant sign that the muscle strength is improving.
00:56:55
Speaker
And again, you know, there is also the option in these patients, just because the way the disease course is in patients with myasthenia gravis, that of putting these patients on non-invasive mammylation following extubation as a bridge to recovery.
00:57:13
Speaker
So the percentage of patients who require tracheostomy in this patient population is definitely less than the patients with Guillain-Barre syndrome.
00:57:23
Speaker
And again, a lot of this kind of like
00:57:25
Speaker
goes back to clinicians' experience with these patients, how comfortable they are with trying non-invasive ventilation as a bridge to recovery or as a bridge to ventricular duration.
Reflections & Personal Insights
00:57:38
Speaker
And I think that the other thing that is commonly associated with myasthenia gravis is worsening of symptoms due to drug interactions.
00:57:47
Speaker
And obviously, in today's ICU, we really appreciate the input of our pharmacy colleagues
00:57:54
Speaker
in all these critical ill patients, but are there any specific drugs in the ICU that we should avoid in myasthenia gravis patients?
00:58:02
Speaker
Yeah, so the list of medications that can actually worsen myasthenic symptoms is fairly long.
00:58:07
Speaker
And, you know, and I was actually looking at some of these medications, and some very commonly used medications can actually exacerbate myasthenic symptoms.
00:58:18
Speaker
Antibiotics, including aminoglycosides, are well known to do that.
00:58:23
Speaker
some of the fluoroquinolones, and some of the beta-lact antibiotics, anthocelin, and then macrolides such as azithromycin, clarithromycin, and erythromycin, they can all exacerbate myasthenic symptoms.
00:58:41
Speaker
Some of the commonly used cardiovascular drugs, such as beta blockers and calcium channel blockers, they can also make symptoms worse.
00:58:50
Speaker
In addition, prednisone we already talked about.
00:58:53
Speaker
Patients can get worse before they get better, so that is well recognized.
00:58:58
Speaker
Some of the antipsychotic agents, such as lithium and chlorpromazine, some anticonvulsants like dilantin and gabapentin.
00:59:07
Speaker
So these are some of the medications that can make symptoms of myasthenia worse.
00:59:12
Speaker
So I think just, I mean, a word of caution for our listeners when you're dealing with a myasthenic patient is to be very cognizant
00:59:19
Speaker
that several drugs that we commonly utilize can exacerbate symptoms and understand where we stand with that and really, I mean, look into this as we treat these patients.
00:59:32
Speaker
I think, Cameron, that this has been a phenomenal conversation.
00:59:35
Speaker
I really appreciate, I mean, a lot of the insight that you have on these patients.
00:59:39
Speaker
Like you said earlier, Guillain-Barre is the most common cause of neuromuscular weakness in the ICU acutely.
00:59:46
Speaker
I think that every clinician has seen these.
00:59:49
Speaker
maybe not in great numbers, but I think that most of our intensivist colleagues have treated these patients or have heard of people who had a Guillain-Barré, so clearly something that happened.
01:00:00
Speaker
And as you said, the incidence of Myasthenia Gravis continues to increase, so it's more likely that we will see them post-surgically or with crises as they come to the ICU.
01:00:11
Speaker
We'd like to finish the podcast by asking our guests a couple of questions not related to the clinical topic we discussed.
01:00:18
Speaker
Would that be okay, Cameron?
01:00:20
Speaker
Yes, sure, absolutely.
01:00:23
Speaker
So my first question is, what book or books have influenced you the most or what books have you gifted most often to others?
01:00:31
Speaker
Yeah, that's an interesting question.
01:00:35
Speaker
Not recently, but maybe three years ago, I read this book.
01:00:40
Speaker
I've read others since then, but I think that book kind of made an impact on me.
01:00:45
Speaker
And it's fairly well known.
01:00:47
Speaker
but it's called How Doctors Think by Jerome Groopman, who is an oncologist and chair of Medicine at Harvard Medical School.
01:00:55
Speaker
And it's actually based on his experiences as an oncologist and also based on his interviews with other prominent physicians.
01:01:03
Speaker
And it's kind of like, I found it very interesting because it's not a very technical book.
01:01:08
Speaker
It's very easy reading.
01:01:10
Speaker
And it just kind of gives you a window into the mind of physicians.
01:01:16
Speaker
and kind of like, you know, explores, you know, some of the top processes, some of the forces behind the decisions that we as physicians make on a daily basis.
01:01:27
Speaker
And I think it's kind of why I found it kind of helped me in sort of analyzing myself in terms of my decision-making process every day as I see patients and, you know,
01:01:39
Speaker
and the way the risks benefit, pros and cons of each decision, clinical decision that we make on a daily basis.
01:01:48
Speaker
Excellent.
01:01:48
Speaker
I would recommend that book actually.
01:01:51
Speaker
I have not read it, but I'll definitely pick it up, and I definitely will include it in the show notes so our audience, our listeners can take a look at it.
01:01:59
Speaker
The second question relates to what do you believe to be true in medicine or life that most other people don't believe?
01:02:10
Speaker
Yeah, I think that over time as you sort of age, mature, gain more experience, I'm kind of like becoming more and more convinced that in medicine, a lot of times, not in all cases, but a lot of times, and it's a well-known dictum, that less is more, and that more is not always better.
01:02:30
Speaker
We're kind of like sold this idea that all these technological advances, they're all good, they all help, they all make a difference.
01:02:40
Speaker
Whereas the truth in a lot of the cases is different.
01:02:46
Speaker
So I think that we should be advocates for application of the right amount of medicine.
01:02:53
Speaker
And sometimes the age-old age that may actually be the right approach.
01:03:03
Speaker
I'm kind of realizing more and more as time goes on.
01:03:06
Speaker
And I think that even though some people have heard that dictum,
01:03:10
Speaker
It's not something that people frequently practice on a regular basis, right?
01:03:13
Speaker
And I think that the recognition at all levels that sometimes less not only is more, but it's better is, I think, very valuable from design to how we offer treatment to patients.
01:03:25
Speaker
I think very powerful.
01:03:27
Speaker
And clearly, I think that most people do not behave in a way that would support this.
01:03:32
Speaker
So I think it's very, very, very great insight, Cameron.
01:03:36
Speaker
And my final question is,
01:03:38
Speaker
What would you like or want every intensivist and advanced practice provider who's listening to this podcast to know?
01:03:45
Speaker
Would it be a quote or a fact?
01:03:50
Speaker
I think that in the ICU, we deal with a lot of life issues, end-of-life decisions.
01:03:59
Speaker
And I think that what I'm sort of realizing more and more, it's very, very important to
01:04:07
Speaker
understand and respect what the priorities, what the goals, what the needs of our patients who may be dying in the ICU are, and to sort of minimize suffering as much as possible.
01:04:25
Speaker
Because I think that in our quest to do more and our quest to help patients, sometimes we'll forget that
01:04:34
Speaker
Dying with dignity is also a basic human right.
01:04:38
Speaker
So that's kind of what I would say about sort of what I've learned and the message that I would pass on to my color intensers.
01:04:51
Speaker
I think it's a great place to stop, Cameron.
01:04:52
Speaker
I think that it's something that we've all very acutely aware of as we experience this wonderful profession.
01:04:59
Speaker
But definitely, I mean, listening to the voice of our patients
01:05:03
Speaker
to their preferences, and respecting that, I think, is of utmost importance, especially in patients who are dying.
01:05:10
Speaker
So, again, thank you so much for a wonderful conversation.
01:05:15
Speaker
I learned a lot, and I'm sure this will be very valuable for our
Closing Remarks & Call to Action
01:05:18
Speaker
audience.
01:05:18
Speaker
And we hope to have you back to talk about other neurocritical care topics.
01:05:23
Speaker
Thank you so much, Sergio, again, for having me and for the opportunity to participate in this podcast.
01:05:29
Speaker
Thank you.
01:05:32
Speaker
Thanks again for listening to Critical Matters.
01:05:34
Speaker
Make sure to subscribe to this podcast on iTunes or Google Play.
01:05:39
Speaker
You can also listen at www.soundphysicians.com backslash podcast.