Myasthenia Gravis in the ICU: How It Presents and How It Crashes

A Comprehensive Review for Practitioners

Dr Neeraj Manikth ,claude.ai

Abstract

Myasthenia gravis (MG) presents unique challenges in the intensive care unit (ICU), with potentially life-threatening complications that require immediate recognition and management. This review examines the pathophysiology, clinical presentation, differential diagnosis, and management of MG in critically ill patients, with particular emphasis on myasthenic crisis, cholinergic crisis, and respiratory failure. We provide evidence-based approaches to monitoring, therapeutic interventions, and prognostic indicators that are essential for optimal patient outcomes.

Keywords: Myasthenia gravis, myasthenic crisis, cholinergic crisis, respiratory failure, intensive care

Introduction

Myasthenia gravis affects approximately 20 per 100,000 individuals globally, with a bimodal age distribution peaking in the second and third decades for women and the sixth and seventh decades for men¹. While many patients with MG maintain stable disease with appropriate treatment, approximately 15-20% will experience at least one myasthenic crisis during their lifetime². The mortality rate for myasthenic crisis has decreased from 40% in the 1960s to less than 5% today, largely due to advances in critical care management³.

Understanding MG in the ICU setting is crucial for several reasons: patients may present with crisis as their initial manifestation, established MG patients may develop crisis due to various triggers, and the condition can be easily overlooked or misdiagnosed in critically ill patients with multiple comorbidities.

Pathophysiology and Clinical Presentation

Neuromuscular Junction Dysfunction

MG is an autoimmune disorder characterized by antibodies directed against components of the neuromuscular junction. The most common target is the acetylcholine receptor (AChR), found in 85-90% of generalized MG cases⁴. Muscle-specific kinase (MuSK) antibodies account for 5-10% of cases, while lipoprotein-related protein 4 (LRP4) antibodies represent a smaller subset⁵.

The hallmark of MG is fatigable weakness that worsens with repetitive use and improves with rest. This weakness follows a predictable pattern:

Ocular symptoms: Ptosis and diplopia (present in 85% of patients)
Bulbar symptoms: Dysarthria, dysphagia, and facial weakness
Limb weakness: Typically proximal > distal, affecting neck extensors early
Respiratory weakness: Diaphragmatic and intercostal muscle involvement

ICU Presentation Patterns

🔸 Clinical Pearl: The "ice pack test" can be performed at the bedside - applying ice to ptotic eyelids for 2-3 minutes often produces temporary improvement in MG patients.

MG patients present to the ICU in several scenarios:

Myasthenic crisis (80% of ICU admissions)
Post-operative complications following thymectomy
Drug-induced exacerbations
Concurrent illness with respiratory compromise
Newly diagnosed MG with severe symptoms

Myasthenic Crisis: Recognition and Management

Definition and Epidemiology

Myasthenic crisis is defined as MG exacerbation requiring mechanical ventilation or intensive respiratory support. It occurs in 15-20% of MG patients, with the highest risk in the first two years after diagnosis⁶.

Triggers: The "INFECTIONS" Mnemonic

🔸 Clinical Pearl: Remember common triggers with "INFECTIONS":

Infections (most common - 30-40% of cases)
New medications (especially antibiotics, antiarrhythmics)
Fatigue and stress
Electrolyte imbalances
Corticosteroid tapering or initiation
Thyroid dysfunction
Immunizations
Operations (especially thymectomy)
Neonatal period (for neonatal MG)
Surgery and anesthesia

High-Risk Medications

🚨 Oyster Alert: Several medications can precipitate crisis and should be avoided:

Antibiotics: Aminoglycosides, fluoroquinolones, macrolides
Cardiovascular: Beta-blockers, calcium channel blockers, procainamide
Neurologic: Phenytoin, lithium, gabapentin
Neuromuscular blockers: Avoid or use with extreme caution
Magnesium: Can worsen weakness at therapeutic doses

Clinical Assessment

The progression to crisis often follows a predictable pattern:

Early signs: Increased ptosis, diplopia, dysarthria
Intermediate: Dysphagia, neck weakness, limb fatigue
Crisis: Respiratory failure, aspiration risk, inability to clear secretions

🔸 Clinical Pearl: The "head drop test" - ask the patient to lift their head off the pillow for 60 seconds. Inability to maintain this position suggests significant weakness.

Myasthenic Crisis vs Cholinergic Crisis

Pathophysiology

Myasthenic Crisis:

Insufficient acetylcholine effect at neuromuscular junction
Results from disease progression or medication non-compliance
Responds to anticholinesterases

Cholinergic Crisis:

Excessive acetylcholine due to anticholinesterase overdose
Leads to depolarization block and paradoxical weakness
Worsens with additional anticholinesterases

Clinical Differentiation

Feature	Myasthenic Crisis	Cholinergic Crisis
Pupils	Normal or dilated	Miotic (constricted)
Secretions	Normal or decreased	Profuse (SLUDGE syndrome)
Fasciculations	Absent	Present
Edrophonium test	Improvement	Worsening
Timing	Gradual onset	Acute, post-medication

🔸 Clinical Pearl: SLUDGE syndrome (Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis) suggests cholinergic excess.

The Edrophonium (Tensilon) Test

🚨 Safety Alert: The edrophonium test should only be performed in a monitored setting with:

Atropine 0.5-1mg readily available
Cardiac monitoring
Resuscitation equipment accessible

Protocol:

Baseline assessment of weakness
Test dose: 1-2mg IV edrophonium
Wait 60 seconds, assess for improvement
If no response and no side effects, give remaining 8mg
Assess at 1, 3, and 5 minutes post-injection

🔸 Clinical Pearl: Video record the test to document objective changes in ptosis or limb strength.

Respiratory Assessment and Monitoring

Arterial Blood Gas Analysis

ABGs provide crucial information but have limitations in MG:

Expected findings in respiratory failure:

Early: Normal pH, mild hypoxemia, CO₂ retention
Progressive: Respiratory acidosis (pH < 7.35, PCO₂ > 45mmHg)
Severe: Mixed acidosis with hypoxemia

🔸 Clinical Pearl: A normal ABG doesn't exclude impending respiratory failure in MG. The patient may compensate until sudden decompensation occurs.

🚨 Oyster Alert: Relying solely on ABGs can lead to delayed intubation. Clinical assessment and functional measures are equally important.

Forced Vital Capacity (FVC) Monitoring

FVC is the gold standard for respiratory monitoring in MG:

Normal values:

Men: 4,000-5,000 mL
Women: 3,000-4,000 mL

Thresholds for action:

FVC < 20 mL/kg: High risk for respiratory failure
FVC < 15 mL/kg: Consider intubation
FVC < 10 mL/kg: Intubation usually required

🔸 Clinical Pearl: Serial FVC measurements are more valuable than single values. A declining trend (>30% reduction from baseline) is concerning even if absolute values appear adequate.

Bedside FVC Measurement

Equipment needed:

Handheld spirometer or smartphone app
Nose clips
Disposable mouthpieces

Technique:

Patient seated upright
Deep inspiration to total lung capacity
Rapid, forceful expiration
Repeat three times, record best value
Monitor every 4-6 hours or more frequently if declining

🔸 Clinical Pearl: If formal spirometry unavailable, use the "counting test" - ask patient to count to 50 in one breath. Inability to reach 25 suggests significant weakness.

Intubation Thresholds and Considerations

Indications for Intubation

Absolute indications:

FVC < 10 mL/kg
Inability to handle secretions
Aspiration or high aspiration risk
Severe hypoxemia (PaO₂ < 70mmHg on supplemental O₂)
Hypercarbia with acidosis (pH < 7.30)

Relative indications:

FVC 10-15 mL/kg with declining trend
Weak cough with retained secretions
Severe bulbar weakness
Anxiety and fatigue from work of breathing

🔸 Clinical Pearl: The "20/30/40 rule" - Consider intubation if FVC < 20 mL/kg, maximum inspiratory pressure > -30 cmH₂O, or maximum expiratory pressure < 40 cmH₂O.

Anesthetic Considerations

🚨 Critical Alert: MG patients are extremely sensitive to neuromuscular blocking agents.

Safe approach:

Avoid depolarizing agents (succinylcholine)
Reduce non-depolarizing agents by 50-75%
Prefer short-acting agents (atracurium, mivacurium)
Use train-of-four monitoring
Consider awake intubation in stable patients

🔸 Clinical Pearl: Propofol and etomidate are preferred induction agents as they have minimal effects on neuromuscular transmission.

Therapeutic Interventions

Anticholinesterase Therapy

Pyridostigmine (Mestinon):

Standard dose: 30-120mg every 4-6 hours
Maximum: 600mg/day
Onset: 30-60 minutes
Duration: 3-6 hours

🔸 Clinical Pearl: Convert IV to PO dosing using 1:30 ratio (1mg IV = 30mg PO pyridostigmine).

Crisis management:

Myasthenic crisis: May increase cautiously if certain of diagnosis
Cholinergic crisis: Discontinue until crisis resolves
Uncertain: Withhold and treat supportively

Plasmapheresis

Indications:

Myasthenic crisis
Pre-operative preparation for thymectomy
Refractory MG

Protocol:

5 exchanges over 7-10 days
Replace 1-1.5 plasma volumes per exchange
Use albumin or fresh frozen plasma as replacement

🔸 Clinical Pearl: Improvement typically begins after 2-3 exchanges, peaks at 1-2 weeks, and lasts 1-2 months.

Intravenous Immunoglobulin (IVIG)

Dosing:

2g/kg divided over 2-5 days
Alternative: 1g/kg/day for 2 days

Advantages over plasmapheresis:

No vascular access requirements
Fewer hemodynamic effects
Can be used with anticoagulation

🔸 Clinical Pearl: IVIG and plasmapheresis show equivalent efficacy in most studies, with IVIG being slightly safer⁷.

Corticosteroids

Acute management:

Avoid in acute crisis (may cause initial worsening)
Start after stabilization with plasmapheresis/IVIG
Begin with prednisone 1-1.5mg/kg/day

🚨 Oyster Alert: Corticosteroids can initially worsen weakness in 30-50% of patients, typically within the first week.

Monitoring and Prognostic Indicators

ICU Monitoring Parameters

Essential monitoring:

Serial FVC measurements
ABG analysis
Neurologic examination
Swallowing assessment
Cardiac monitoring (for arrhythmias)

🔸 Clinical Pearl: Create a "MG scorecard" tracking daily FVC, bulbar function, and limb strength using standardized scales.

Weaning from Mechanical Ventilation

Criteria for weaning trials:

FVC > 15 mL/kg
Adequate cough and secretion clearance
Stable bulbar function
Hemodynamic stability

🔸 Clinical Pearl: MG patients often require longer weaning periods due to respiratory muscle fatigue. Consider gradual pressure support reduction rather than T-piece trials.

Prognostic Factors

Good prognosis:

Young age at onset
Ocular symptoms only
Rapid response to treatment
Absence of thymoma

Poor prognosis:

Age > 50 years at onset
Bulbar onset
Thymoma presence
MuSK antibody positivity

Special Populations and Considerations

Pregnancy and MG

Key points:

Pregnancy can worsen, improve, or not affect MG
Neonatal MG occurs in 10-15% of babies
Plasmapheresis is safe during pregnancy
Certain medications require adjustment

🔸 Clinical Pearl: Magnesium sulfate (used for eclampsia) can precipitate crisis in MG patients - use calcium gluconate as an alternative.

Perioperative Management

Pre-operative:

Optimize therapy with plasmapheresis/IVIG
Reduce anticholinesterases gradually
Pulmonary function testing

Post-operative:

Close respiratory monitoring
Early mobilization
Gradual medication resumption

Concurrent Illness

Infections:

Most common precipitant of crisis
Requires aggressive treatment
Avoid contraindicated antibiotics

🔸 Clinical Pearl: Maintain high suspicion for aspiration pneumonia in MG patients with bulbar weakness.

Clinical Pearls and Practical Hacks

Bedside Assessment Tricks

The "Peek sign": Inability to keep eyes completely closed suggests facial weakness
The "Snarl test": Ask patient to show teeth - asymmetric smile indicates facial weakness
The "Tongue blade test": Patient cannot maintain bite on tongue depressor for 60 seconds
The "Shoulder shrug test": Cannot maintain shoulder elevation against resistance

Medication Hacks

🔸 Clinical Pearl: Create a "MG medication alert" card for the patient listing contraindicated drugs and emergency contacts.

Dosing conversions:

Pyridostigmine: 1mg IV = 30mg PO
Neostigmine: 0.5mg IV = 15mg PO
Edrophonium: 10mg IV (diagnostic dose)

Crisis Prevention

The "WATCH" approach:

Watch for early warning signs
Avoid trigger medications
Treat infections aggressively
Compliance with medications
Hematologic monitoring during immunosuppression

Future Directions and Emerging Therapies

Novel Treatments

Complement inhibitors:

Eculizumab (approved for refractory MG)
Ravulizumab (longer-acting alternative)

Neonatal Fc receptor antagonists:

Efgartigimod (recently approved)
Reduces pathogenic antibodies

B-cell targeting therapy:

Rituximab for refractory cases
Belimumab under investigation

Biomarkers and Monitoring

Emerging markers:

Antibody levels for monitoring
Cytokine profiles
Complement activation markers

Conclusion

Myasthenia gravis in the ICU requires a systematic approach combining clinical acumen, appropriate monitoring, and timely intervention. The key to successful management lies in early recognition of crisis, differentiation from cholinergic crisis, aggressive respiratory monitoring, and prompt initiation of immunomodulatory therapy.

Critical care practitioners must maintain high vigilance for respiratory failure, as MG patients can decompensate rapidly. The integration of clinical assessment, pulmonary function monitoring, and blood gas analysis provides the foundation for optimal patient care.

With proper recognition and management, the prognosis for MG patients in the ICU has improved dramatically, with mortality rates now below 5%. Continued advances in immunomodulatory therapies and critical care techniques promise even better outcomes in the future.

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Conflicts of Interest: None declared
Funding: None

Monday, July 14, 2025