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Critical care of neuromuscular disorders
3 Plays2 years ago
In this episode, we will discuss critical care management of acute neuromuscular disorders. We will focus on the Guillain-Barre Syndrome and Myasthenia Gravis. My guest is Dr. Kamran Athar, who is trained in critical care medicine and neurocritical care. He is a practicing neurointensivist at the Farber Institute for Neuroscience in Philadelphia. Dr. Athar is an assistant professor of Medicine and Neurology at the Jefferson School of Medicine in Philadelphia.
Additional Resources:
Neuromuscular Disorders in the Intensive Care Unit. T B Birch. American Academy of Neurology 2021: https://pubmed.ncbi.nlm.nih.gov/34618763/
The clinical management of neuromuscular disorders in intensive care. M S Damian and EFM Wijdicks. Neuromuscular Disorders 2019: https://www.sciencedirect.com/science/article/abs/pii/S0960896618304231
Books Mentioned in this Epsiode:
When Breath Becomes Air. By Paul Kalanithi: https://www.amazon.com/When-Breath-Becomes-Kalanithi-Paul/dp/1784701998/ref=tmm_pap_swatch_0?_encoding=UTF8&qid=1706814212&sr=8-1
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Transcript
Introduction to Intensive Care Topics
00:00:06
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Welcome to Critical Matters, a sound podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:14
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Sound provides comprehensive critical care programs to hospitals across the country.
00:00:19
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To learn more about our programs and career opportunities, visit www.soundphysicians.com.
00:00:26
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And now your host, Dr. Sergio Zanotti.
High-Risk Neuromuscular Disorders
00:00:33
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Patients with neuromuscular disorders are at high risk for respiratory failure and other complications, including autonomic dysfunction and infection.
00:00:41
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These patients often require aggressive monitoring and treatment in an ICU setting.
00:00:46
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In today's podcast episode, we will discuss the management of acute neuromuscular disorders in the ICU.
00:00:51
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We will focus on the Guillain-Barrez syndrome and myasthenia gravis.
00:00:55
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Acquired neuromuscular weakness due to critical illness will be a topic of a future podcast episode, and we will not discuss this topic today.
Guest Introduction: Dr. Cameron Athar
00:01:03
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Our guest is Dr. Cameron Athar.
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Dr. Athar is trained in critical care medicine and neurocritical care.
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He's a practicing neurointensivist at the Farber Institute of Neuroscience in Philadelphia.
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Dr. Athar is an associate professor of medicine and neurological surgery at the Jefferson School of Medicine in Philadelphia.
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He has published extensively in the field and is an excellent clinician and clinical educator and a dear friend.
00:01:26
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Cameron, welcome back to Critical Matters.
00:01:30
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Thank you, Sergio.
00:01:31
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Thanks for your kind introduction, and thanks for having me.
00:01:34
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Delighted to be here.
00:01:35
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So we talked about this topic several years ago, and we felt it was always good to do a refresh.
00:01:41
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And we'll see what's new, what's not.
00:01:43
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But like I mentioned in the introduction, acquired neuromuscular weakness due to critical illness is something that obviously is very prevalent in the ICU.
00:01:52
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That will be a topic of a future podcast.
00:01:55
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But acute neuromuscular weakness leading to admission to the ICU is something also that we should all be familiar with as intensivists and working in the ICU.
Differential Diagnosis of Neuromuscular Weakness
00:02:04
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Could you just tell us as a starting point, maybe when you see somebody present to the ICU or to the hospital with acute neuromuscular weakness, what's your broad differential diagnosis and what are you thinking of?
00:02:16
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Yes, yes.
00:02:17
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So patients are presenting with acute neuromuscular weakness.
00:02:19
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The differential diagnosis is fairly broad and extensive.
00:02:22
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And, you know, it can be from conditions that can involve the spinal cord, some myelopathy, also conditions that can affect the anterior horn cells of the spinal cord, spinal nerve roots, peripheral nerves, neuromuscular junction, and muscles.
00:02:40
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So, you know, so just to kind of like go through the differential in terms of myelopathy,
00:02:44
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We're talking about inflammatory or infectious conditions of the spinal cord.
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So acute transverse myelitis is always in the differential.
00:02:53
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Compression of the spinal cord from extrinsic lesions that cause a compressive myelopathy.
00:02:59
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Cord infarctions should be in the differential.
00:03:02
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In terms of conditions that affect
00:03:05
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affect the anterior horn cells, they typically cause an acute flaccid myelitis and some of the infections that can do that include West Nile virus, poliomyelitis, well known historically, you know, an important epidemiological disease, some enterovirus infections, and also motor neuron disease including amyotrophic lateral sclerosis can sometimes, the acute
00:03:32
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presentation can be acute when patients have a decompensation secondary to ALS.
00:03:39
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In addition, nerve root pathologies, typically these are infections that cause nerve root inflammation and also structural abnormalities that can compress nerve roots can also present with weakness, neuromuscular weakness.
Peripheral Neuropathies Discussion
00:03:55
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We should always of course keep in mind peripheral neuropathies, especially acute polyneuropathies,
00:04:01
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the most common of which is Guillain-Barre syndrome, which we're going to talk about in more detail later in the podcast.
00:04:07
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Other conditions that can cause acute polymorphopathies should always be in the differential.
00:04:11
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These include toxins such as certain drugs, alcohol, vitamin B6 deficiency, arsenic, lead poisoning, of course, organophosphate poisoning,
00:04:24
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and certain metabolic and electrolyte abnormalities, including hypothyroidism and porphyrias.
00:04:33
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In addition, of course, critical illness, polyneuropathy, Sergio, you mentioned earlier, would be the differential too, but that's a talk for another podcast.
00:04:44
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Then neuromuscular junction problems, the prototype for which is Myasthenia gravis.
00:04:51
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Other neuromuscular disorders, junction disorders, include Lambert-Eaton-Myasthenic Syndrome, certain neurotoxins that can affect neuromuscular junction transmission, including botulinum toxin, tetanus, tick paralysis, and certain types of snake bites.
00:05:08
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And of course, organophosphate intoxication, certain types can affect neuromuscular junction transmission as well.
00:05:14
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And then of course, we should always keep in mind myopathies, which can be from a variety of causes, metabolic, electrolyte abnormalities, especially hypokalemic, periodic paralysis, which has a number of various subtypes.
Brainstem Pathologies and Diagnosis
00:05:31
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Of course, drug-induced toxic myopathies and critical illness myopathy should always be considered.
00:05:36
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And to sort of round off our differential,
00:05:42
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conversion or functional disorders are always in the picture.
00:05:45
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In addition,
00:05:47
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To all these conditions that I mentioned, always keep in mind brainstem pathologies that can also present with neuromuscular weakness, and these can range from brainstem infarctions to inflammatory or infectious conditions of the brainstem.
00:06:03
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And neuroimaging, as well as spinal fluid examination, can be very helpful in differentiating these brainstem pathologies from other causes of neuromuscular weakness.
00:06:14
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So certainly a very broad differential, like you said, and as intensivists, obviously, we want to narrow down the diagnosis, understand who needs to come to the ICU, and then we can make a specific diagnosis, obviously talk about specific treatments.
Diagnostic Techniques for Neuromuscular Disorders
00:06:31
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So what would be your initial workup or diagnostic tools that would be helpful?
00:06:35
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You mentioned some of them, just as you're approaching these patients from a broad perspective and trying to get into a more narrow categorization of the disease.
00:06:44
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Definitely, yeah.
00:06:45
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You know, so a workup for these patients would start with a detailed clinical history, the type of motor symptoms, sensory symptoms that they have, any cranial nerve abnormalities.
00:06:58
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Essentially, the goal is to localize the lesion.
00:07:01
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So a detailed clinical history along with
00:07:04
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focused but still more detailed, focused but concise neurological examination is a starting point, a very good starting point and that can be supplemented by diagnostic investigations that typically include performing a lumbar puncture and electrophysiologic testing such as EMG nerve conduction studies and in the appropriate
00:07:28
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clinical setting when there is a clinical indication, repetitive nerve stimulation or single fiber EMG can be helpful in certain cases when you suspect, especially when you suspect myasthenia gravis or the Miller-Fisher variant of Guillain-Barre syndrome, serologic testing can be very helpful.
00:07:46
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And of course, you know, if you, you know, are concerned about structural abnormalities in the CNS or the spinal cord, imaging of the neural axis, including an MRI of the brain or spinal cord, can help us in delineating or differentiating these different types of neuromuscular disorders.
00:08:10
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Perfect.
ICU Admission Criteria and Monitoring
00:08:11
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Now, in terms of making decisions of triage, in general terms, and we're going to jump into Guillain-Barre in a second, Cameron, but what are some of the reasons that patients with acute neuromuscular disease might be admitted to the ICU?
00:08:26
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And what are some of the main areas requiring attention from part of the intensivist?
00:08:32
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Yeah, so that's a very good question.
00:08:34
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That's, you know, something that typically in the ICU, we would be called upon to assess patients or evaluate patients for, and then we would be required to obviously take care of these patients.
00:08:44
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So patients who are at risk for
00:08:48
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respiratory failure or impending respiratory failure.
00:08:51
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So these are patients who have rapidly progressive weakness in the extremities, which may progress to involve their respiratory muscles.
00:08:59
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These are the patients that we would be concerned about, patients who have significant bulbar dysfunction because these patients would be at very high risk for aspiration,
00:09:08
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they would have impaired cough reflex, inability to clear the secretions, and again, because of the high risk for aspiration, they are at very high risk for developing respiratory failure.
00:09:19
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And of course, certain conditions, especially Guillain-Barre syndrome, a lot of these patients, significant subset of these patients with Guillain-Barre can have dysfunction of the autonomic nervous system that can result in hemodynamic instability, as well as hemorrhagia.
00:09:35
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cardiac dysrhythmias and that would require monitoring, very close monitoring in the ICU.
00:09:42
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Excellent.
Understanding Guillain-Barre Syndrome
00:09:43
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So let's talk now about Guillain-Barrรฉ syndrome and maybe we can start by if you could share a little bit of the epidemiology incidents and the pathophysiology as a beginning.
00:09:57
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Sure, yeah.
00:09:58
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So, Guillain-Barre syndrome is really the most common cause of acute flaccid paralysis.
00:10:03
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And if you look at the global annual incidence, it's about one to two or 100,000 person years.
00:10:10
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It is slightly more common in males than females, and the incidence increases with age, although all age groups have been affected.
00:10:20
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You know, it has been described in all age groups.
00:10:23
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In terms of the pathophysiology, it's thought that it is caused by an aberrant immune response to an infectious agent.
00:10:32
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And a lot of these patients will report some sort of a preceding infectious illness in the weeks prior to the onset of symptoms of GBS.
00:10:42
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And what happens is that that disinfection induces antibodies, which are then directed against specific gangliosides or glycolipid components of the peripheral nerves.
00:10:54
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And this is due to molecular mimicry.
00:10:56
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between these components and this leads to complement activation, infiltration of lymphocytes, macrophage infiltration activation, and ultimately, and this is happening in the peripheral nerves and nerve roots, and ultimately there's stripping of the myelin sheath and if more severe, axonal injury can happen.
00:11:18
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This leads to, obviously, inability of the nerves to conduct nerve impulses, and there's conduction block, and due to that, ultimately, the muscles become flaccid.
00:11:29
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So you have this acute flaccid paralysis.
00:11:32
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In terms of...
00:11:34
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Infections that have been implicated, Campylobacter jejuni infection is the most commonly identified precipitant or trigger for Guillain-Barre syndrome.
00:11:45
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However, other infections that have been implicated, such as cytomegalovirus, Epstein-Barr virus, HIV,
00:11:55
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as Zika virus and more recently cases of GBS have been reported in association with the COVID-19 infection or SARS-CoV-2 virus.
00:12:06
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And there is epidemiological data suggesting that the incidence of Guillain-Barre syndrome actually increases during certain infectious outbreaks.
00:12:16
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Again, sort of, you know, supporting the post-infectious antibody-mediated damage to the peripheral nerves and nerve roots.
Triggers and Variants of Guillain-Barre
00:12:26
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During the recent Zika virus epidemic, actually, there were some...
00:12:33
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reports of increased incidence of GBS in association with the Zika virus.
00:12:39
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And also there's some emerging data that is associated with the SARS-CoV-2 pandemic with an increased incidence or a number of cases of patients diagnosed with Guillain-Barre syndrome.
00:12:52
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So these are the most common sort of like triggers.
00:12:56
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Vaccines have been implicated.
00:12:59
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The first reports are back in the 70s when there was some association described with the swine influenza vaccine.
00:13:07
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However, only two studies have actually shown some association of Guillain-Barre with the flu vaccine.
00:13:16
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No other vaccines have ever been implicated in terms of associated with
00:13:22
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being associated with GPS.
00:13:25
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And more recently, immunobiological agents have been also associated, also being, you know,
00:13:37
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has been association described with immunobiological agents use, NGBS, including especially the immune checkpoint inhibitors and the TNF, tumor necrosis factor antagonists.
00:13:47
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So those are some of the, you know, common triggers or precipitants or clinical associations for Guillain-Barre syndrome.
00:13:58
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And I think from a practical perspective as clinicians, recognizing these triggers in the history might be useful for diagnostic purposes.
00:14:07
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But like you said, I mean, there's really little you can do to prevent it and anticipate them.
00:14:14
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But it's a good diagnostic clue to maybe what's going on in terms of, in addition with other things that we'll talk about.
00:14:22
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Cameron, I wanted to ask you about the different types of Guillain-Barre.
00:14:26
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I mean, historically, I mean, I know that there's been at least two very predominant and maybe a third type, the acute inflammatory demelinating polyradiculoneuropathy, ADIP, and the acute motor axonal neuropathy.
00:14:39
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Anything that you want to comment on that?
00:14:43
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Yeah, so Guillain-Barre syndrome is a very heterogeneous condition, and a number of variants have been described.
00:14:50
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The clinical variants are obviously based on their clinical history presentation, and then variants have been described based on electrophysiologic testing.
00:15:02
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The most common variants
00:15:02
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common of which is the acute inflammatory, demyelinating poly, radicular neuropathy.
00:15:08
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That's the most common variant, and in the US and Europe, it accounts for about 85 to 90% of the cases of Guillain-Barre syndrome.
00:15:16
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The other variants that I'm describing include the axonal neuropathy and there are two subtypes of the axonal neuropathy, the acute motor axonal neuropathy and the acute motor sensory axonal neuropathy.
00:15:29
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And they account for about 5 to 10 percent of the cases in the U.S. and Europe.
00:15:35
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They are seen somewhat more commonly in China, Japan and Latin America.
00:15:42
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case of acute motor axonal neuropathy obviously as the name implies it involves purely the motor nerves and and there is an association with campylobacter infection especially and in these case in this case especially the deep tendon reflexes may be preserved so that's one sort of difference compared to other more classic type
00:16:07
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of GPS which is the AITP.
00:16:10
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And of course acute motor sensory axoniopathy as the name implies involves both motor and sensory components of the nervous system.
00:16:20
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Miller-Fisher syndrome is a variant of GPS that the classic triade is that they have ophthalmoplegia, ataxia and areflexia and about
00:16:34
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10% of the cases in US and Europe are of GBS are of the Miller-Fisher variant, more common in Asia, and there's a very strong association with GQ1B antibody, presence of that antibody in the serum, and it's seen in about 85% to 9% of the patients.
00:16:51
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And about 15% of these patients with the Miller-Fisher who have Miller-Fisher syndrome, they have like an overlapping syndrome where they have also features of the classic sensory motor neuropathy that we typically see ascending motor and sensory impairment.
00:17:11
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So about 15% of these patients will overlap with that particular clinical variant as well.
00:17:17
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Perfect.
Symptoms and Diagnosis of Guillain-Barre
00:17:18
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In terms of clinical presentation, before we talk about how these patients usually present and the diagnosis, could you go over the British Medical Research Council scale for muscle strength?
00:17:30
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I think it's always important, right, that we talk the same language when we're evaluating these neurological patients.
00:17:36
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Yeah, so the Medical Research Council, you know, scale essentially is used to grade the power of your skeletal muscles and you're assigned a score based on your exam and the score can range from zero to five, zero being no contraction and five being normal strength or normal power.
00:17:59
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So a score of one or grade of one is where you have flicker contraction or very trace contraction.
00:18:05
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Score of two or grade two is where you have some movement along the plane of the bed.
00:18:12
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So active movement, but gravity eliminated.
00:18:15
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Grade three is where you have active movement against gravity.
00:18:20
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Grade four is you have active movement against gravity as well as against resistance.
00:18:25
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And then grade five is you have normal strength.
00:18:27
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So it's a useful tool.
00:18:29
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And again, you know, like you said, it's important to describe motor strength using a scale and especially this scale, which has been validated so that, you know, all clinicians are kind of like talking the same language and, you know, and we're able to communicate more effectively with each other.
00:18:46
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What would be the clinical presentation of a typical GBS patient?
00:18:51
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Yes, so the classic clinical variant or type is the sensory motor form, where patients will typically present with progressive weakness of the muscles, so motor weakness that starts in the legs and then progresses to involve the arms and the cranial muscles and can also, of course, involve the respiratory muscles as well.
00:19:16
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This can often be accompanied by paresthesias or sensory impairment, again, progressing in an ascending fashion.
00:19:25
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And deep tendon reflexes are typically absent or significantly depressed in these patients.
00:19:32
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And usually these patients will present within a few days to a week after the onset of symptoms.
00:19:39
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Patients can also have dysfunction of the autonomic nervous system resulting in hemodynamic instability as well as cardiac arrhythmias.
00:19:47
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And this can be seen in as many as high as up to 70% of the cases.
00:19:53
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And it's actually a major contributor to mortality in these patients, this autonomia.
00:20:01
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In addition to, in addition, about 20% of the patients, you know, can have pretty significant or profound respiratory muscle weakness that results in, you know, and then, like we talked about earlier, needing admission to the ICU and they will require some form of mechanical ventilation.
00:20:19
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So this is like the classic sensory motor form.
00:20:23
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The disease progression can be
00:20:27
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fairly rapid, which is what we call the progressive phase, and most patients will reach maximum disability within like two weeks and almost all by four weeks.
00:20:41
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And after this initial progressive phase, these patients will then enter more like a plateau phase, which can last from anywhere from days to weeks to months, followed by recovery.
00:20:57
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So that's kind of like the typical, you know, sort of progression of symptoms.
00:21:03
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And another symptom that's frequently seen in this patient is pain, which can be muscular, it can be neuropathic, it can be nerve root or radicular pain.
00:21:15
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So, and it can be fairly debilitating for patients.
00:21:19
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So this is the classic sensory motor type of
00:21:21
Speaker
Other variants that have been described include the pure motor, where the symptoms obviously are just weakness, pure sensory, which is quite rare, and of course the Miller-Fisher variant that we talked about earlier, which overlaps with the classic sensory motor variant in about 15% of the cases.
00:21:42
Speaker
And I think that the monophastic course that you describe of how it peaks at two weeks and mostly four weeks is also important because something that peaks in less than 24 hours or becomes very severe is less likely to be Guillain-Barre.
00:21:55
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And on the other hand, something that continues to worsen for more than four weeks is also going to be less likely to be Guillain-Barre.
00:22:02
Speaker
And this should be some of the clues that maybe we have the wrong diagnosis.
00:22:06
Speaker
Correct, that's an excellent point, and that's something we always pay attention to when we are taking a history and, you know, evaluating these patients for how rapidly their symptoms have progressed.
00:22:19
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Yeah, absolutely.
00:22:20
Speaker
And in terms of a diagnosis, my understanding is that the diagnosis is truly clinical.
00:22:25
Speaker
And what you mentioned, obviously, in terms of the presentation.
00:22:31
Speaker
And in addition to that, there are maybe some diagnostic tests that we could use to enhance our diagnosis.
00:22:39
Speaker
Can you comment on those?
00:22:41
Speaker
Yeah, exactly.
00:22:42
Speaker
The diagnosis of Guillain-Barre syndrome is clinical.
00:22:47
Speaker
And it can be supported by ancillary investigations, such as examination of CSF, so a lumbar puncture, as well as EMG nerve conduction studies.
00:22:58
Speaker
So, but yeah, I agree that the diagnosis primarily is a clinical diagnosis.
00:23:06
Speaker
And there are National Institute of Neurological Disorders and Stroke criteria for diagnosis, and there are certain features that are required for diagnosis.
00:23:16
Speaker
I'm not going to go into details, but that's an important point.
00:23:22
Speaker
In terms of spinal fluid examination, a classic finding in these patients is the combination of an elevated CSF protein level and a normal CSF cell count, what we call albuminocytological dissociation.
00:23:39
Speaker
However, we should keep in mind that in about...
00:23:43
Speaker
50 up to up to 50 percent of the patients uh the protein levels may be normal in the first week or so and and then even after that in the second week up to anywhere from 10 to 30 percent of the patients may have normal protein levels so a normal protein level does not necessarily exclude the diagnosis of Guillain-Barre syndrome in terms of cell counts
00:24:11
Speaker
most cases the cell counts are less than five okay there is a mass general hospital case series of more than 100 patients where they looked at who had diagnosed gbs where they looked at protein levels and cell counts and what they found was that as many as 90 percent of the patients in their case series had a cell count of less than five however if you do find
00:24:35
Speaker
significant pleocytosis, especially if the cell count is more than 50, then you have to think of other potential etiologies, especially you have to rule out some sort of an underlying infectious or inflammatory process.
00:24:47
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Even mild pleocytosis, if the cell count is between 10 to 50, you should still keep your differential somewhat broad and you should look for inflammatory or infectious causes
00:25:04
Speaker
that you don't want to miss.
Serology and Clinical Treatment Decisions
00:25:08
Speaker
In terms of other diagnostic tests, is there any value in serology and antibodies?
00:25:12
Speaker
You did mention that in the Fisher variant, there are some associated antibodies, but is there any value in other forms?
00:25:22
Speaker
No, really, Miller-Fisher syndrome or variant of GBS is the only one where, you know, there's a strong association with, you know, GQ1B antibodies.
00:25:30
Speaker
There are other antibodies that have been described, and some of them are, you know, but we typically don't order them routinely, and because...
00:25:43
Speaker
you know, if you look at the guidelines and recommendations, we don't wait for serologic testing to come back.
00:25:49
Speaker
If we suspect it clinically, we start treatment.
00:25:51
Speaker
So it may, you know, even GQ1B antibody may help us later on, you know, sort of in conforming our diagnosis somewhat, but would not really make a difference in terms of, you know, initiating treatment.
00:26:10
Speaker
Going back to just, you know, EMG nerve conduction studies can also be performed and, you know, and they can be useful in confirming a diagnosis and also help in prognosis because they can
00:26:24
Speaker
help us delineate what variant of GPS we're dealing with.
00:26:28
Speaker
Is it a demyelinating neuropathy or is it an axonal neuropathy?
00:26:31
Speaker
Because that would be helpful in prognostication.
00:26:35
Speaker
But, and the typical finding is that there is prolonged or absent F waves.
00:26:40
Speaker
These are pathognomonic and, you know, they obviously reflect damage or demyelination at the level of the spinal nerve roots.
00:26:48
Speaker
However, you know, we must keep in mind that early on in the course, these EMG nerve conduction studies may actually be
00:26:53
Speaker
normal.
00:26:54
Speaker
So typically our approach is that we don't get those EMG nerve conduction studies during their ICU admission, the earliest we would get them would be two weeks after onset of their symptoms.
00:27:11
Speaker
Perfect.
00:27:12
Speaker
So we talked about the clinical diagnosis, some of the ancillary tests that we might use.
00:27:17
Speaker
But like you said, based on clinical criteria, the history and the exam, we are more often going to make clinical therapeutic decisions.
00:27:25
Speaker
And let's talk about treatment, Cameron.
00:27:27
Speaker
So you did mention a little bit in the introduction, but specifically for Guillain-Barre, what prompts you to say this patient needs to go to the ICU?
00:27:36
Speaker
Yeah, so patients, like we talked about a little earlier, patients who are at risk for respiratory compromise and may need vandalatory support, and that's about 20% of the patients, they are the ones who should be going to the ICU.
00:27:56
Speaker
So when you're assessing these patients, we should be looking at, you know, a number of features.
00:28:01
Speaker
Respiratory rate, are they using accessory muscles?
00:28:05
Speaker
Single breath count, how's their cough, how's their ability to clear their
00:28:11
Speaker
any evidence of paradoxical breathing.
00:28:14
Speaker
And of course, we can do certain bedside assessments of respiratory muscle strength that can also help in determining if these patients are more likely to develop respiratory failure requiring mechanical ventilation.
00:28:32
Speaker
These include forced vital capacities, negative inspiratory force, or maximum expiratory pressure.
00:28:37
Speaker
In addition, patients who have significant bulbar dysfunction, like I said earlier, you know, impaired cough, inability to handle their secretions or clear their secretions, high risk for aspiration, these are the patients who should be monitored very carefully in the ICU.
00:28:52
Speaker
And then a patient with significant autonomic dysfunction, because that is a major contributor to mortality.
00:29:00
Speaker
These patients should be in the ICU.
00:29:03
Speaker
Perfect.
00:29:03
Speaker
So once we make a decision to come into the ICU, there's a couple of aspects that we're going to cover.
00:29:09
Speaker
One is specific treatment for the disease, and we'll go into that in a second.
00:29:13
Speaker
Second one is support with mechanical ventilation for the respiratory failure.
00:29:17
Speaker
And third is the autonomic dysfunction support.
00:29:20
Speaker
So let's start with treatment of Guillain-Barrรฉ per se.
Treatment and Recovery in Guillain-Barre
00:29:24
Speaker
What are the current recommended treatments for Guillain-Barrรฉ?
00:29:29
Speaker
Yeah, so in terms of, you know,
00:29:34
Speaker
therapies, the mainstay of therapy is the immunomodulating treatments, and these include either plasma exchange or plasmapheresis or use of intravenous immunoglobulins.
00:29:50
Speaker
So these are two mainstays of treatment, and it really, you know, there's no data from randomized before trial that has shown that one is more effective than the other.
00:30:04
Speaker
And, you know, what these treatments do is that they reduce the duration of illness and also the severity of the maximum disability that they may have, okay?
00:30:21
Speaker
And so those are the two mainstays of treatment.
00:30:25
Speaker
And IVIG, because it's easier to administer and also more widely available, has kind of become the treatment of choice for Guillain-Barre syndrome.
00:30:37
Speaker
The dose is 2 grams per kilogram, typically given over 5 days.
00:30:41
Speaker
For Plex, typically you do anywhere from 3 to 5 sessions every other day.
00:30:48
Speaker
And that's kind of standard for Gambray syndrome acute management.
00:30:56
Speaker
So in terms of the available evidence, they're comparable.
00:30:59
Speaker
And like you said, based on availability and maybe specific patient circumstances, you might choose one or the other.
00:31:08
Speaker
In your practice, Cameron, are you more likely to use IVIG?
00:31:13
Speaker
Yes.
00:31:14
Speaker
So our first choice, typically in most cases, almost all cases, I would say is IVIG.
00:31:20
Speaker
Yes.
00:31:21
Speaker
And obviously a shortage of IVIG, reported allergies, or worsening renal failure could be problems for IVIG.
00:31:28
Speaker
But other than that,
00:31:29
Speaker
Like you said, it's easier to administer, does not require an invasive central line, and it seems to be comparable in terms of results.
00:31:37
Speaker
My second question regarding IVIG is, is there any value of a second course of five in very severe cases?
00:31:45
Speaker
Yeah, so a good question.
00:31:48
Speaker
And, you know, the data is limited, you know, because there are patients, as many as 40% of the patients, who will really not improve in the first few weeks after initiating either Plex or IVIG.
00:32:07
Speaker
So what do we do for these patients?
00:32:10
Speaker
And sometimes we will give them a second dose of the same therapy.
00:32:14
Speaker
So if they got IVIG, we'll wait a little bit and give them another dose.
00:32:16
Speaker
Or if they got Plex, we'll give them another plasmiferycele.
00:32:19
Speaker
Sometimes we will switch to the other immunomodulating therapies.
00:32:24
Speaker
So IVIG followed by Plex or vice versa.
00:32:27
Speaker
But there's really no data to show that
00:32:30
Speaker
any one of these approaches actually is going to improve outcomes.
00:32:36
Speaker
There is a clinical trial in progress that actually is looking at, it's a randomized study, which is looking at the effect of administering a second dose of IVIG, and that trial is currently ongoing.
00:32:48
Speaker
So, you know, GBS trials are typically very hard recruitment, difficult to recruit patients and stuff.
00:32:54
Speaker
So,
00:32:55
Speaker
But this trial, we'll see what the results are.
00:33:00
Speaker
But that's really the options available to us.
00:33:05
Speaker
Perfect.
00:33:05
Speaker
Go ahead.
00:33:05
Speaker
And keep in mind that the reason some of these patients may not have responded or we think may have responded is that maybe their weakness would have been even worse, you know, if we hadn't given them those therapies in the first few weeks after the onset of symptoms.
00:33:24
Speaker
So it's not like the therapy is not effective.
00:33:27
Speaker
It's just that their nature would have been even worse.
00:33:31
Speaker
I think that our scale sometimes for evaluating in terms of time is too short in the ICU.
00:33:36
Speaker
And really what the studies have shown is that long term, right, 12 months later, six months later, the patients who were treated with either IVIG or plasmapheresis have a quicker recovery, quicker weaning from ventilator and better outcomes long term.
00:33:51
Speaker
But in our time frame, maybe they're still super weak, they're still on the ventilator and we feel like we failed.
00:33:56
Speaker
And I think it's important for clinicians to understand what the natural progression is.
00:34:00
Speaker
these patients are not going to get immediately better after you use these treatments.
00:34:05
Speaker
Exactly.
00:34:06
Speaker
Absolutely.
00:34:06
Speaker
I mean, you know, because, you know, remember the plateau phase can last anywhere from days to weeks to months and usually weeks to months.
00:34:14
Speaker
So, so the timeframe that we have these patients for in the ICU is just not long enough for us to be able to see a significant clinical benefit.
00:34:24
Speaker
Excellent.
00:34:24
Speaker
We talked a little bit about corticosteroids before we started recording, and my understanding is that there's no data to support the use of corticosteroids in all comers of Guillain-Barrรฉ, and it's not recommended currently.
00:34:38
Speaker
However, you had mentioned that there might be a very specific group of patients in whom there might be some plausible mechanisms that need to be studied, and in some centers, it might be considered.
00:34:48
Speaker
Could you expand on that, Cameron?
00:34:50
Speaker
Yes, yeah.
00:34:51
Speaker
So you're absolutely right about, you know, that really multiple randomized trials have shown no clinical benefit for corticosteroids in GBS.
00:34:58
Speaker
In fact, there is some suggestion that they may actually have an adverse effect on outcome.
00:35:05
Speaker
However, more recently, there has been an association of GBS described with
00:35:10
Speaker
some of the immunobiological agents, especially the immune checkpoint inhibitors, where there is a biological plausibility that immunosuppression using steroids may actually improve or may be clinically beneficial for these patients with concurrent IBIG or Plex therapy.
00:35:31
Speaker
So what some of these centers are recommending is that in addition to IVIG or Plex, we should concurrently use prednisone, and that may actually be, so it's a very specific, very small subgroup of patients where the corticosteroids may actually be beneficial.
00:35:50
Speaker
And of course, you have to discontinue or stop the immunobiological agent as well, which was the purported trigger for Guillain-Barrรฉ.
00:36:01
Speaker
Perfect.
00:36:02
Speaker
So we talked about initial treatment for Guillain-Barre.
00:36:05
Speaker
The second aspect that obviously is most relevant to us as intensivists is support for respiratory failure.
Ventilation and Intubation Decisions
00:36:13
Speaker
So could you talk a little bit about the decision to intubate and how do you make that as a neuro-intensivist and a critical care physician?
00:36:22
Speaker
And also in that maybe mentioned the 20-30-40 rule that is often mentioned.
00:36:30
Speaker
Yeah, so, you know, like a lot of things in medicine, in the ICU, you know,
00:36:39
Speaker
clinical judgment is very important, you know, and of course in addition to your clinical judgment, you also have to have some objective data to support your clinical decision making.
00:36:49
Speaker
So in these patients, you know, if these patients are at risk for respiratory failure, so if you, you know, if in your clinical assessment they are tachypneic, because these patients may actually have pretty significant
00:37:06
Speaker
or may have impending respiratory failure without significant dyspnea.
00:37:09
Speaker
So that should be kept in mind.
00:37:11
Speaker
So if they have use of accessory muscles, if they have nasal flaring, if they are having paradoxical breathing, if they are t-kypneic, but not dyspneic, okay?
00:37:21
Speaker
If they are...
00:37:23
Speaker
not really able to handle their secretions well, then these are patients that, you know, in combination with certain other objective parameters, and you mentioned the 20-30-40 rule, where essentially, you know, it's being, it's assessment,
00:37:39
Speaker
of the respiratory muscle strength, where if your vital capacity or force vital capacity is less than 20 cc per kg of vital body weight, if your negative inspiratory force is less than negative 30, and your maximum expiratory pressure is less than 40, these patients are more likely to require intubation and mechanical ventilation.
00:38:02
Speaker
So the, you know, so the, um,
00:38:06
Speaker
the decision to initiate mechanical ventilatory support is based on a combination of all of these factors and a number of studies have looked at, you know, some early predictors if there are any that we can identify and, you know, that would predict the, you know, need for mechanical so we can intervene early and intubate these patients and they have sort of like come up with similar
00:38:33
Speaker
clinical criteria for initiating mechanical ventilation.
00:38:39
Speaker
So if these patients are showing signs of respiratory distress, you know, and that's, you know, all of those things that I mentioned earlier.
00:38:46
Speaker
And of course, remember that with the objective parameters like 20, 30, 40, some trends in these numbers that are important, you know,
00:38:55
Speaker
So if their vital capacity is declining, if their NIFs and maximum respiratory pressure numbers are getting worse, in combination with, you know, the patient themselves not looking like they're tiring or they're fatiguing, these patients are, you know, are on the verge of respiratory, are basically having impending respiratory failure and should be supported in mechanical ventilation.
00:39:20
Speaker
And as you mentioned, obviously, the guidelines of the 2030-40, which is 20 centimeters of water per kg of forced vital capacity or less than 30 centimeters of water of inspiratory pressure or 40 centimeters of water of expiratory pressure.
00:39:39
Speaker
pressure.
00:39:40
Speaker
Those are guidelines.
00:39:41
Speaker
But if somebody has a very high and they dropped significantly in the six hours that you're checking them, that should be obviously a signal that you probably should intervene earlier rather than later.
00:39:52
Speaker
And one of the things that is often mentioned, but I think it's worth reviewing for our audience is that ABGs are notoriously unuseful because changes in high
00:40:03
Speaker
hypoxemia or CO2 are usually very, very late, and we would like to intervene much before those occur.
00:40:09
Speaker
Yeah, exactly.
00:40:12
Speaker
If your patient on the ABG is already getting hypoxemic and has early hypercapnia, then they already have respiratory failure.
00:40:22
Speaker
because patients can have pretty significant respiratory muscle weakness, but the ABGs may look normal because they're compensating or trying to compensate.
00:40:31
Speaker
So, ABGs are notoriously not sensitive.
00:40:34
Speaker
That's absolutely a very good point.
00:40:37
Speaker
Also, in terms of assessment of force vital capacity, NIFs, and maximum expiratory pressure, there are certain caveats that should be kept in mind, which is that
00:40:48
Speaker
Patients who have significant facial muscle weakness, they may not be able to make a good seal when you do these tests.
00:40:58
Speaker
And so you can have falsely low four-spiral capacities.
00:41:03
Speaker
So like everything else, you know, these numbers should be interpreted in terms of appropriate clinical context.
00:41:16
Speaker
Yeah, absolutely.
00:41:17
Speaker
So once the patient's intubated, so before we go there, actually, could you mention the role or no role for non-invasive ventilation in Guillain-Barre syndrome?
00:41:27
Speaker
Yeah, so very good question.
00:41:31
Speaker
Non-invasive ventilation in Guillain-Barre has very limited literature on that.
00:41:37
Speaker
Most of it is very small case series.
00:41:40
Speaker
And in almost all of those cases where it was tried,
00:41:44
Speaker
the patients just ended up getting emergently intubated.
00:41:48
Speaker
And what they found also was that there was a quantifiable significant decline in their respiratory mechanics over a short period of time.
00:41:59
Speaker
Because Guillain-Barre syndrome is, you know, as we'll talk about, is very different from the isthenia.
00:42:04
Speaker
These patients can be
00:42:06
Speaker
relatively stable over a period of time, but then can actually decompensate fairly quickly.
00:42:12
Speaker
And so, you know, that's why non-invasive ventilation may not be the best choice for these patients, especially also if they have significant bulbar weakness where it can increase the risk of aspiration because of
00:42:29
Speaker
and their inability to handle their secretions.
00:42:32
Speaker
So the literature is limited and it's currently, it's not recommended to use non-invasive ventilation in most cases of Guillain-Barre syndrome.
00:42:44
Speaker
Perfect.
00:42:45
Speaker
Once they're intubated, Cameron, can you mention a little bit on weaning and tracheostomy, which I think is an important part of care for these patients?
00:42:55
Speaker
Yeah, so, you know, obviously once they're, you know, once they're on the ventilator, you are, you have initiated your immunomodulating therapy, including Plex and IBIG.
00:43:06
Speaker
And then, of course, you're assessing these patients for any signs of clinical improvement, including improvement in their respiratory muscle strength.
00:43:14
Speaker
And weaning, you know,
00:43:17
Speaker
There's some data, obviously you're following their force vital capacity, the NIFs while on the ventilator.
00:43:23
Speaker
There's some data that once their force vital capacity improves by 4 mL per kilogram of vital body weight from their pre-intubation numbers, or if they have a NIF better than negative 50, more negative than negative 50,
00:43:40
Speaker
then they are more likely to be successfully extubated.
00:43:45
Speaker
But remember that in most cases of Guillain-Barre syndrome, the mechanical ventilation is likely going to be fairly, fairly prolonged.
Managing Prolonged Ventilation and Autonomic Instability
00:43:57
Speaker
And, you know, there are some risk factors that have been identified for prolonged mechanical ventilation.
00:44:05
Speaker
There's one study which showed that patients who are
00:44:08
Speaker
unable to lift their arm off the bed one week after being intubated and patients who have the exonotype of the polyneuropathy based on electrodiagnostic or electrophysiologic studies are likely going to need prolonged mechanical ventilation because the recovery time is going to be very, very long.
00:44:31
Speaker
And for these patients, early tracheostomy should be considered or done.
00:44:37
Speaker
Excellent.
00:44:38
Speaker
So the last thing I wanted to talk about in terms of support for Guillain-Barre was autonomic dysfunction, which can also, I think, be very severe and usually might prolong the stay in the ICU once they're intubated or trached and maybe ready to go somewhere else.
00:44:56
Speaker
Could you talk about how we handle that?
00:44:59
Speaker
Yeah, so these patients can, you know, have some of these, up to 70% of these patients can have significant dysautonomia or dysfunctional autonomic nervous system.
00:45:09
Speaker
And so these patients should be very careful, you know, monitored very closely in the ICU.
00:45:15
Speaker
Their blood pressures can fluctuate a lot, and it can be very difficult to sort of manage, even in a critical care setting at times.
00:45:24
Speaker
These patients can differentiate
00:45:25
Speaker
develop heart blocks.
00:45:27
Speaker
These patients can develop all types of atrial specialty and also ventricular arrhythmias.
00:45:32
Speaker
So, you know,
00:45:38
Speaker
Management would be, sometimes, you know, these patients may require temporary or even permanent pacing.
00:45:46
Speaker
So, you know, these are patients even with best possible critical care, you know, can still have an adverse outcome because of their dysautonomia.
00:46:01
Speaker
And for the most part, the treatment really is symptomatic.
00:46:06
Speaker
And, you know, you have to make sure that you don't miss anything structurally.
00:46:12
Speaker
So get an echocardiogram and you should be doing EKGs regularly on these patients.
00:46:19
Speaker
And, you know, just good, solid, supportive critical care.
00:46:25
Speaker
But in spite of all of that, remember that, you know, some of these patients, a small subset may still have a bad outcome, adverse outcome because of the significant dysautonomia.
00:46:36
Speaker
I think it's important also for intensivists to be aware in this acute phase that we probably should be avoiding long-acting cardiovascular therapy because we could get into trouble with these swings and the autonomic dysfunction.
00:46:53
Speaker
Correct, yeah.
00:46:55
Speaker
So short-acting titratable agents would be the preferred choice for these patients because they can fluctuate from one extreme to the other fairly in a very short span of time.
00:47:11
Speaker
Finally, obviously, the course of these patients may be prolonged, but I think it's important in Guillain-Barre especially, but also in many other neuroacute pathologies to talk about prognosis.
00:47:24
Speaker
And as severe these patients may be and as prolonged as some of their courses might be, overall, the prognosis is quite good.
00:47:33
Speaker
Could you comment on that, Cameron?
00:47:35
Speaker
Yeah, yeah, you know, that's exactly true because, you know, sometimes when we see these patients in the ICU and they're very, very sick, they have profound, you know, neurological disability, and, you know, we kind of like think that how are these patients going to, you know,
00:47:53
Speaker
get better, you know, but if you look at outcomes over six months to a year after their acute phase, you know, 60 to 80 percent of the patients are able to walk independently at six months and about anywhere between 85 to 90 percent of the patients by a year.
00:48:09
Speaker
Full recovery of motor strength occurs in about, you know, 60 percent of the patients at about one year.
00:48:17
Speaker
So it takes time, you know.
00:48:20
Speaker
you know, but of course there is a subset that's going to have about 10% of the patients, up to 10% of patients can have a prolonged course where they are vanillary dependent for months and the recovery is delayed and incomplete in those cases.
00:48:37
Speaker
The mortality is anywhere from
00:48:41
Speaker
3 to 5 percent within the first year, despite obviously very good critical care.
00:48:46
Speaker
A lot of it is attributed to the significant dysautonomia that accompanies this condition.
00:48:54
Speaker
And of course, these are the patients who are more likely to die, the patients who become chronically ventilator-dependent from a variety of causes, of course, factors of pneumonia, DBTs, mucus plugging, and so on and so forth, and of course, autonomic dysfunction.
00:49:11
Speaker
Patients who improve can have worsening of their symptoms.
00:49:17
Speaker
So relapses can happen.
00:49:19
Speaker
What has been called as treatment-related fluctuations.
00:49:23
Speaker
And in these cases, you know, about 5% of the cases, overall cases of GBS can have these relapses as well, which obviously, you know, if that does happen, it's treated the same way with either Plex or IVIG.
00:49:39
Speaker
Excellent.
00:49:40
Speaker
So let's move on to myasthenia gravis.
00:49:42
Speaker
And myasthenia obviously falls in the category of acute neuromuscular diseases that we might see in the ICU.
00:49:48
Speaker
It has some important differences with Guillain-Barre.
00:49:52
Speaker
But why don't we start just by telling us a little bit about the incidence and a little bit about the pathophysiology and perhaps the classification.
Introduction to Myasthenia Gravis
00:50:00
Speaker
Yeah, so myasthenia gravis is really the most common acquired disorder of neuromuscular transmission.
00:50:07
Speaker
And essentially, the passive physiology is that there's production of antibodies or autoantibodies that bind to the components of the neuromuscular junction, the most common of which is the acetylcholine receptor.
00:50:22
Speaker
And what happens is that this results in
00:50:29
Speaker
blocking of the acetylcholine that is in the synaptic cleft, binding off that acetylcholine to the acetylcholine receptor.
00:50:39
Speaker
In addition, these autoantibodies also
00:50:45
Speaker
immediate degradation of the acetylcholine receptors.
00:50:48
Speaker
There's decrease in the number of membrane folds on the postsynaptic membrane, and also the synaptic cleft widens.
00:50:58
Speaker
So you have decreased number of acetylcholine receptors as well, and also widening of the cleft, and that interferes with neuromuscular transmission, and of course leads to progressive muscle weakness.
00:51:11
Speaker
In terms of the incidence of myasthenia gravis, it's fairly low, anywhere from 0.3 to 2.8 per 100,000 population.
00:51:24
Speaker
And the prevalence worldwide, global prevalence of myasthenia gravis is 700,000 approximately.
00:51:31
Speaker
And of course, you know, significant advances have been made in improving outcomes in these patients.
00:51:39
Speaker
The mortality has declined significantly, and that's really because of intensive care.
00:51:46
Speaker
So good critical care when these patients have a myasthenic crisis and very effective immunosuppressive therapies that are now available.
00:51:57
Speaker
Perfect.
00:51:58
Speaker
Tell me a little bit more about the diagnosis.
00:52:00
Speaker
And my understanding, Cameron, is that most patients that come to the ICU with myasthenia have a previous diagnosis of myasthenia.
00:52:09
Speaker
They have a myasthenic crisis, and we can talk about that.
00:52:11
Speaker
But once in a while, you might have a new presentation, and we have to make the diagnosis de novo.
00:52:17
Speaker
Yeah, so again, diagnosis of myasthenia would be based on your clinical history, your examination, and when you suspected, serological testing.
00:52:30
Speaker
So in terms of serological testing, you know,
00:52:34
Speaker
acetylcone receptor antibodies, classically very strong association, very highly sensitive for diagnosis of myasthenia gravis.
00:52:44
Speaker
But other antibodies have also been described in these patients, and more and more antibodies are being described now, discovered.
00:52:56
Speaker
So what we used to call zero negative myasthenia gravis, essentially it's becoming a smaller proportion of patients who have myasthenia gravis.
00:53:04
Speaker
So musk antibodies, lipoprotein-related protein, 4-antibodies, and agrin antibodies.
00:53:11
Speaker
These are some of the more recently described antibodies that have been described now in patients with myasthenia gravis.
00:53:21
Speaker
What would be, go ahead, in terms of clinical diagnosis, what would be some of the other clues that you would offer to our listeners to be attentive to?
Diagnosis and Subtypes of Myasthenia Gravis
00:53:32
Speaker
Yeah, so in terms of, there are two basic clinical subtypes.
00:53:37
Speaker
One is the generalized myasthenia, where you have muscle weakness that involves your muscles of your limbs, respiratory muscle, as well as ocular muscles.
00:53:48
Speaker
Fatigability is a very important description in these patients.
00:53:57
Speaker
or where the symptoms as the day progresses, they tend to get worse.
00:54:01
Speaker
So that's the generalized myasthenia gravis.
00:54:04
Speaker
Patients who have the other subtype, less common, ocular myasthenia, they typically have involvement of the extraocular muscles and the muscle of the eyelid.
00:54:13
Speaker
So these patients will present with ptosis and an ophthalmoplegia or diplopia.
00:54:18
Speaker
So those are the two clinical subtypes
00:54:21
Speaker
that have been described.
00:54:22
Speaker
And again, fatigability and exertion is something that we always are asking these patients for.
00:54:29
Speaker
And these patients would classically say that as the day progresses, their symptoms tend to get worse.
00:54:34
Speaker
They feel much better in the morning.
00:54:37
Speaker
Deep tendon reflexes are preserved in most cases.
00:54:41
Speaker
And of course, you know, to confirm the diagnosis, serological testing followed by repetitive neurostimulation that can be helpful, single fiber EMG with repetitive neurostimulation, which typically would show you a decremental action potential as the muscle, neuromuscular junction, muscles get fatigued because of impaired neuromuscular junction transmission.
00:55:05
Speaker
Excellent.
00:55:05
Speaker
And I think that I'll share a story, Cameron, because this is one of my best patient stories of picking up a diagnosis by being attentive.
00:55:16
Speaker
But I think it applies to this patient admitted to the ICU with pneumonia, treated with levoquin, it got intubated.
00:55:25
Speaker
And the only history he had is that he had been intubated before for previous infections, a gentleman in his 50s.
00:55:33
Speaker
And then somebody noticed that he had ptosis on the ventilator.
00:55:37
Speaker
And an astute clinician not to be named said, why don't we do an ice bag test?
00:55:43
Speaker
And an ice bag was placed on the patient's eyelids.
00:55:48
Speaker
And lo and behold, the ptosis got better.
00:55:51
Speaker
And the idea being that the anticholinerous terase activity, right, is impacted by temperature.
00:55:59
Speaker
And that led to a suspicion of myasthenia and led to an eventual diagnosis of myasthenia.
00:56:05
Speaker
So sometimes these patients do come without a diagnosis.
00:56:09
Speaker
And by being observant of the physical exam, we might be able to figure it out.
00:56:14
Speaker
Definitely.
00:56:15
Speaker
You know, that's a great story.
00:56:16
Speaker
And, you know, again, a lot of the astute clinicians on the bedside asking the right questions and, you know, doing a focused but at the same time, you know, concise focused examination can come up with a diagnosis that can be confirmed by further testing.
00:56:37
Speaker
Absolutely.
00:56:38
Speaker
So we talked about the diagnosis and we also mentioned, and I don't know if you want to maybe emphasize or redefine that, that a lot of patients that we see in the ICU come with myasthenic crisis,
Managing Myasthenic Crisis
00:56:52
Speaker
right?
00:56:52
Speaker
What is a myasthenic crisis?
00:56:54
Speaker
So myasthenia crisis is a life-smacking condition, and patients with myasthenia gravis, up to a quarter of these patients at some point during their disease course will have a myasthenia crisis.
00:57:11
Speaker
And it's defined as respiratory muscle weakness due to myasthenia that is severe enough.
00:57:17
Speaker
to necessitate some form of ventilation, either intubation, mechanical ventilation or non-invasive ventilation, or that delays extubation following some sort of surgical procedure.
00:57:34
Speaker
So that is a myasthenia crisis.
00:57:38
Speaker
Also, these patients may have significant bulbar weakness that can often accompany the respiratory muscle weakness.
00:57:48
Speaker
And in some patients, that can be the more predominant feature.
00:57:52
Speaker
And of course, when you have bulbar dysfunction, that can cause upper area obstruction because the upper area is collapsed, or it can cause severe dysphagia, increased risk of aspiration, and again, leading to respiratory failure, hypoxemia, respiratory failure, meaning intubation mechanical ventilation.
00:58:10
Speaker
A number of triggers have been identified that can precipitate a myasthenic crisis, the most common being some sort of concurrent infection.
00:58:21
Speaker
Other triggers include
00:58:24
Speaker
Any type of stress such as surgical procedure, pregnancy and childbirth have also been described as a potential trigger.
00:58:34
Speaker
Tapering of immunosuppressive medications.
00:58:37
Speaker
During that process, these patients can relapse and develop myasthenic crisis.
00:58:42
Speaker
And it can just happen as part of the natural history of myasthenia gravis itself.
00:58:47
Speaker
And of course, we also, we talk, and I think we'll talk about that too later in the podcast, certain other triggers that always should be kept in mind are medications that can increase weakness in myasthenia.
00:59:02
Speaker
And there is a whole list of medications that should be either avoided or used cautiously in these patients.
00:59:08
Speaker
Perfect.
00:59:09
Speaker
So in terms of treatment, obviously, there's long-term treatment for myasthenia, which I think is out of the scope of intensive care.
00:59:18
Speaker
But what would be some of the guidelines for people who are in the ICU in terms of a crisis or for other reasons?
00:59:26
Speaker
Yeah, so, you know, treatment can be...
00:59:32
Speaker
Broad categories are symptomatic treatment, which would be your acetylcholinesterase, anticholinesterase agents, such as spirudostigmine.
00:59:42
Speaker
And then for myasthenic crisis, what you need is basically rapid immunomodulating treatments that includes either PLEX or IVIG.
00:59:52
Speaker
along with chronic immunomodulating treatments, which include your glucocorticoids, as well as other immunosuppressive agents, the most common being azathioprine, cyclosporine, methotrexate, and then more recently, rituximab.
01:00:08
Speaker
And then the other biological agents that have been, there's more data emerging on some of these biological agents that may be helpful.
01:00:16
Speaker
But that again is more long-term chronic treatment.
01:00:19
Speaker
And I know, I guess we'll talk about a little bit about timectomy, or old timectomy as well.
01:00:23
Speaker
But for the myasthenic crisis patient, really, it's initiating the rapid
01:00:27
Speaker
immunomodulating treatments, either Plex or IVIG, concurrently with glucocorticoids, high-dose prednisone.
01:00:36
Speaker
That's your initial first-line therapy.
01:00:40
Speaker
And I think that's an important distinction, obviously, with Guillain-Barre, that glucocorticoids do have a very important role in the myasthenia crisis.
01:00:48
Speaker
In addition, I think it's important to emphasize that usually we hold their chronic medications during a myasthenic crisis, and we will start them once we're thinking of weaning them off the ventilator, and obviously we'll do that in conjunction with neurology.
01:01:02
Speaker
Cameron, could you comment on, is there any difference between IDIG and plasma exchange for myasthenia?
01:01:09
Speaker
So again, you know, like, there's really no difference in terms of efficacy or clinical benefit when you compare plasma exchange or IVIG.
01:01:23
Speaker
They both start to work within a few days, and their benefit typically would last for up to a few weeks.
01:01:34
Speaker
And again, for IBIG, the dose is fairly similar, 2 grams per kilogram over 5 days, and for PLEX, similarly, 3 to 5 sessions every other day.
01:01:45
Speaker
And choice, obviously, would depend upon availability, ease of use, cost.
01:01:52
Speaker
potential for adverse effects, which can be seen with both.
01:01:58
Speaker
And so that's really, but I know the choice is either, you can go with either IVIG or Plex.
01:02:08
Speaker
Perfect.
01:02:08
Speaker
And in that ways, I mean, I guess it's similar to Guillain-Barre.
01:02:11
Speaker
So in terms of mechanical ventilation support, you know,
01:02:16
Speaker
Can you talk a little bit about the same idea?
01:02:18
Speaker
We're monitoring these patients, looking for trends, looking at some data.
01:02:23
Speaker
Obviously, we would want to intervene earlier rather than late.
01:02:26
Speaker
But there is one difference, I guess, that I want you to comment on, which is the role of non-invasive positive pressure ventilation in myasthenia.
Effective Treatments for Myasthenic Crisis
01:02:34
Speaker
Yes, compared to Guillain-Barre syndrome, you know, BiPAP has shown significant benefit in these patients because, you know, the natural history of myasthenia is very different from Guillain-Barre syndrome, and that's really one of the main reasons why non-invasive ventilation can be beneficial because typically the need for mechanical or ventilatory support in myasthenia is, in most cases, is expected to be short-term because the immunomodulating therapies, the rapid immunomodulating
01:03:05
Speaker
therapies, IV, as you reflect, they start to have a beneficial effect within a few days.
01:03:09
Speaker
And so you can kind of use non-invasive ventilation to bridge them to recovery.
01:03:16
Speaker
Okay.
01:03:17
Speaker
However, and there's some data on that.
01:03:22
Speaker
especially from Mayo Clinic, there are like more and multiple decent-sized case series where, you know, BiPAP was actually used as a bridge to recovery in patients who were having a myasthenic crisis.
01:03:38
Speaker
Obviously, patients who have significant ball bar dysfunction,
01:03:42
Speaker
where they are at high risk for aspiration, BiPAP is not an option.
01:03:47
Speaker
So that's one population where you may wanna avoid using BiPAP.
01:03:53
Speaker
In addition, there are other limitations of BiPAP use as well.
01:03:56
Speaker
It's a very close fitting mask, so patient comfort can be an issue.
01:04:00
Speaker
patients are not able to really sleep that well, there may be leaks, you know, that can be associated with use of BiPAP and that can affect their ventilation, especially, of course, gastric distension, you know, it can be an issue as well.
01:04:15
Speaker
However, you know, in most cases, the patients are able to tolerate it well.
01:04:22
Speaker
One important point is that at the time of initiation of BiPAP,
01:04:26
Speaker
If they already have become somewhat hypercapnic, then that is associated with BiPAP failure, which obviously means that their respiratory failure has advanced to the point where they're starting to retain CO2.
01:04:40
Speaker
So that is one of the predictors for BiPAP failure.
01:04:43
Speaker
So again, if you want to use it, use it early.
01:04:48
Speaker
Excellent.
01:04:49
Speaker
And in terms of any other comments on mechanical ventilation in terms of weaning or even the role of tracheostomy in mystinia gravis patients?
01:05:00
Speaker
Yeah, so, you know, weaning in these patients, again, we're
01:05:06
Speaker
should proceed in the same manner as other patients.
01:05:09
Speaker
What you're doing is you are looking at, you know, signs of improvement in muscle strength.
01:05:17
Speaker
You're also looking at signs of improvement in their, including their respiratory muscle strength.
01:05:21
Speaker
So you're assessing their respiratory parameter, looking at their respiratory parameters, they're assessing the strength of respiratory muscles using bedside spireometry, so force vital capacity, if the trends are improving, NIF and maximal expiratory pressures, and
01:05:37
Speaker
there's a clinical rule of thumb is that if the patient with myasthenia, they can hold their head up off the bed, then they are more likely to be successfully extubated.
01:05:51
Speaker
And
01:05:52
Speaker
And again, you know, pressure support trials every day to see how they're doing, how their rapid shallow breathing index looks, you know, that's important.
01:06:05
Speaker
Some people suggest that maybe you should
01:06:08
Speaker
give them very long pressure support trials, maybe as long as up to 24 hours to see if they're able to tolerate coming off the ventilator.
01:06:16
Speaker
There's other people that have a different approach.
01:06:19
Speaker
They want to give patients sufficient time to recover or rest, I should say, between these pressure support trials to prevent respiratory muscle fatigue.
01:06:30
Speaker
None of these approaches have been shown to be better or superior over the other.
01:06:35
Speaker
So I think it all depends on clinician's experience and individual patient characteristics, how experienced a particular clinician is, and especially in managing patients with neuromuscular respiratory failure, especially myasthenic patients.
01:06:53
Speaker
And, you know, there's also literature on non-invasive ventilation being used as a bridge to vent liberation as well.
01:07:01
Speaker
And there is some limited literature on that as well.
01:07:03
Speaker
So, you know, you can bridge them to vent liberation with non-invasive ventilation as well.
01:07:09
Speaker
Because in most cases, the need for ventilatory support in these patients is likely going to be somewhat short-term.
01:07:19
Speaker
And that's a definite difference with what we usually see in Guillain-Barre, and it's important to point out.
Medication Management and Thymectomy Benefits
01:07:26
Speaker
You did mention, Cameron, obviously, that there's a lot of triggers for myasthenic crisis, and they can exacerbate the neuromuscular weakness.
01:07:34
Speaker
One of them that's a big one is drugs.
01:07:37
Speaker
And we'll include a link in the show notes to a more extensive list of drugs that we should be careful in patients with myasthenia.
01:07:46
Speaker
But could you comment on some of the drugs we should be avoiding in the ICU?
01:07:50
Speaker
Yeah, I mean, there's a long list of medications, but some of the common ones would be, you know, this stuff, actually, give me a little list just, you know, because I wanted to, you can't really mention all of them, but some of the common ones, beta blockers, use cautiously.
01:08:12
Speaker
They may worsen, and that's a very commonly used medication.
01:08:16
Speaker
Fluoroquinolone antibiotics, they actually have a black box warning for patients who have Mycena Gravis and try to avoid them in these patients.
01:08:29
Speaker
Macrolide antibiotics, again, we use very cautiously, if at all.
01:08:34
Speaker
Procanamide is another medication that you should use with caution.
01:08:39
Speaker
Statins can also worsen myasthenic symptoms and again use with caution.
01:08:45
Speaker
Aminoglycoside antibiotics again use with caution.
01:08:50
Speaker
Botox of course and so these are probably the more common medication that are used I mean less commonly of course immune checkpoint inhibitors we kind of talked about that a little bit and also remember that corticosteroids when they're initiated in the acute setting for myasthenic
01:09:07
Speaker
myasthenic crisis, they may actually in the short term make your symptoms worse before the patient gets better.
01:09:12
Speaker
And that's why concurrent use of IVIG or PLEX can actually sort of attenuate or ameliorate some of those worsening of some of that worsening of symptoms during the acute phase.
01:09:25
Speaker
Excellent.
01:09:26
Speaker
Go ahead.
01:09:26
Speaker
There's a long list, but a more extensive list that you already mentioned as you'll put in the show notes.
01:09:34
Speaker
Absolutely.
01:09:34
Speaker
And I think this is obviously where true multidisciplinary critical care shines and having our pharmacy colleagues helping us with these patients in this respect is going to be extremely important.
01:09:48
Speaker
The last topic I wanted to ask you about before we close and on myasthenia is obviously there's an association with thymomas that's very important.
01:09:58
Speaker
And in a lot of these patients, a thymectomy is recommended.
01:10:03
Speaker
Anything that you think the intensivist should know on this front?
01:10:07
Speaker
Yeah, so the association with thymomas is very strong.
01:10:14
Speaker
And in patients with myasthenia gravis who have thymomas, the thymectomy should be performed.
01:10:21
Speaker
And it's not just removing the thymoma itself.
01:10:24
Speaker
You actually have to remove the whole thymus gland.
01:10:28
Speaker
In patients who have generalized myasthenia, but non-thymomatous, okay, even in those patients, thymectomy has been shown to be clinically beneficial.
01:10:44
Speaker
So patients with generalized myasthenia who are acetylcholine receptor antibody positive.
01:10:51
Speaker
Even non-thymo-metis patients, thymectomy is beneficial.
01:10:56
Speaker
In terms of other variants or other subtypes of myasthenia like musk antibody or lipoprotein, RELID protein 4 antibody positive or adrin antibody positive myasthenia gravis,
01:11:09
Speaker
there's really no document benefit of a timectomy or it's uncertain in those cases.
01:11:17
Speaker
So it's not really recommended, at least as per the most recent guidelines.
01:11:22
Speaker
Perfect.
01:11:23
Speaker
So I think, Cameron, we had a wonderful discussion of two, I think, fascinating disease processes that require ICU care on a regular basis, maybe not in great numbers, but I think we've all seen these patients and we'll see them again.
01:11:37
Speaker
So I really appreciate you sharing your expertise.
01:11:40
Speaker
You know the drill on critical matters.
01:11:43
Speaker
We like to close with a couple of questions that are unrelated to the clinical topic.
01:11:47
Speaker
So would that be okay?
01:11:49
Speaker
Yes, definitely.
01:11:51
Speaker
Yeah.
01:11:51
Speaker
Yeah.
01:11:53
Speaker
So the first question is about books.
01:11:54
Speaker
Are there any books that have influenced you significantly or books that you have gifted often to other people?
01:12:01
Speaker
Yeah, you know, lately, I used to be an avid reader, but lately with kids and stuff, you know, sort of haven't been able to keep up with that as much.
01:12:13
Speaker
However, I did recently or, you know, over the last year or so, read this book, which, you know, is well known.
01:12:18
Speaker
But it's by Paul Kalaninty.
01:12:22
Speaker
It's called When Breath Becomes Air.
01:12:25
Speaker
It's very profound, you know, very easy reading, not very dense.
01:12:29
Speaker
It's a beautiful memoir, you know, this neurosurgeon, neuroscientist in training, who towards the end of his training period developed stage four lung cancer.
01:12:40
Speaker
And so, you know, it's, it's, it's,
01:12:43
Speaker
somewhat heartbreaking, but also at the same time, you know, kind of life-affirming and beautiful in its own way of how this very, very highly skilled and very highly driven individual is, you know, coping with, you know, sort of the end of his life, you know, in a way.
01:13:06
Speaker
And just tells you that, you know,
01:13:09
Speaker
people who are dying have a lot to teach us in life, you know, and there's a lot to be learned from how they are looking at their life.
01:13:20
Speaker
So, you know, I would highly recommend that book.
01:13:24
Speaker
You know, it also kind of like examines
01:13:26
Speaker
relationship between doctors and their patients and this, you know, in particular, you know, this particular author, you know, being a physician himself and then becoming a patient and how that dynamic, you know, and interaction, you know, how that played out.
01:13:44
Speaker
It's fascinating.
01:13:45
Speaker
You know, it can be a little depressing, but, you know, because of obviously the nature of what, you know, the memoir itself, but I thought that,
01:13:55
Speaker
it was in a way in its own way, very uplifting as well.
01:13:58
Speaker
Awesome.
01:13:59
Speaker
And we'll definitely put a link in the, in the show notes.
01:14:02
Speaker
And I do concur.
01:14:04
Speaker
I mean, this is a wonderful read, I think very powerful, like you said, and very, very sobering because we never know what's around the corner.
01:14:13
Speaker
And I think that makes the present even more valuable.
01:14:16
Speaker
So thanks for sharing that Cameron.
01:14:19
Speaker
The second question is, what do you believe to be true in medicine or in life that most other people don't believe or don't act as they believe?
01:14:27
Speaker
Yeah, I think that maybe I don't want to get too political, but maybe the power of forgiveness and reconciliation is
01:14:46
Speaker
I think that people underestimate it, you know, and that, you know, some, you know, maybe qualities that if there were more,
01:14:58
Speaker
uh prevalent uh uh and maybe actually make a better world well and i think it's not political i think it it might be political but it's also in families it's also in friendships and i think you're you're right and how often we we we tell stories to ourselves that um blind us from seeing the power of like you said the forgiveness of true forgiveness and reconciliation which ultimately i think
01:15:27
Speaker
is much more valuable for everybody.
01:15:29
Speaker
So I definitely can see how that is something that a lot of people don't behave like they believe in.
01:15:35
Speaker
And I think it's a great, great, great answer.
01:15:38
Speaker
So to close, Cameron, if there's anything that you want every listener to know, it could be a quote, a fact, or just a departing thought.
01:15:47
Speaker
I mean, like, I'm always like, as a physician, as you, you know, take care of patients on a daily basis and, you know, deal with very complex medical problems and also care.
01:16:04
Speaker
complex, a lot of times very complex social situations as well, tied to these patients, you just, you know, sort of, I'm kind of learning more and more that medicine can be, or life in general, can be very humbling.
01:16:18
Speaker
And you may think that you know a lot, but especially the world that I live in, acutely brain-injured patients are ability to be able to, you know,
01:16:32
Speaker
tell our patients and in most cases family members with any degree, even close to it, certainty, what the eventual outcome is going to be, very, very tough, very, very difficult and very humbling, you know.
01:16:51
Speaker
So it's like the more I practice, the more I kind of
01:16:57
Speaker
finding out that I just don't know enough you know and yeah so but you know that's that's something that you know is I guess allows me to sort of maybe learn more introspect more and and also stay grounded
01:17:19
Speaker
Perfect.
01:17:19
Speaker
I think this is the right place to stop, Cameron.
01:17:22
Speaker
I appreciate you sharing your expertise and your time with our audience and look forward to having you back on the podcast.
01:17:29
Speaker
Thank you so much, Sergio.
01:17:30
Speaker
And thanks for having me here.
01:17:33
Speaker
Thank you.
01:17:35
Speaker
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01:17:38
Speaker
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01:17:44
Speaker
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01:17:49
Speaker
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