MYASTHENIA GRAVIS 

1. Definition

Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction (NMJ) characterized by:

• Fluctuating skeletal muscle weakness
• Fatigability (worsens with use, improves with rest)
• Normal sensation and reflexes

It is caused by antibodies against postsynaptic acetylcholine receptors or related proteins.

2. Antibody Types

Mechanisms of Damage

• Complement activation
• Postsynaptic membrane simplification
• Decreased ACh receptors
• Increased receptor internalization

Result → ↓ End plate potential → Failure of muscle contraction

3. Thymus & MG

• Thymic hyperplasia → 60–70%
• Thymoma → 10–15%
• Normal thymus → remaining

The thymus plays a role in:

• T-cell education
• Autoantibody production

4. Epidemiology

• Bimodal distribution:
• Young females (20–30 yrs)
• Older males (>50 yrs)
• Associated autoimmune diseases:
• Thyroid disorders
• SLE
• RA

5. Clinical Features 

Fluctuating Weakness – Key Concept

Worsens:

• Evening
• Repeated activity
• Stress
• Infection

Improves:

• Rest
• Morning

Muscle Groups Involved

1. Ocular (Most common initial)

• Ptosis
• Diplopia
• Fatigable weakness
• Ice pack test positive

2. Bulbar

• Dysphagia
• Dysarthria
• Nasal speech
• Difficulty chewing

3. Limb Weakness

• Proximal > distal
• Neck flexor weakness

4. Respiratory Muscles

• Dyspnea
• Reduced FVC
• Myasthenic crisis

6. Myasthenic vs Cholinergic Crisis 

 Edrophonium test now rarely used in ICU.

7. Diagnosis

1. Antibody Testing

• AChR Ab (binding, blocking, modulating)
• MuSK Ab

2. Electrophysiology

Repetitive nerve stimulation:

• Decremental response (>10%)

Single-fiber EMG:

• Increased jitter (most sensitive)

3. Ice Pack Test

Improves ptosis in 2–5 minutes.

4. Imaging

CT chest:Thymoma screening

 8.Drugs That Worsen MG 

• Aminoglycosides
• Fluoroquinolones
• Macrolides
• Magnesium
• Beta-blockers
• Calcium channel blockers
• Neuromuscular blockers

9. Complications

• Aspiration pneumonia
• Respiratory failure
• Sepsis
• Steroid complications
• Thymoma malignancy

ICU Management of Myasthenia Gravis

Myasthenia gravis (MG) becomes a critical care disease when patients develop:

• Myasthenic crisis
• Severe bulbar dysfunction
• Rapid respiratory decline
• Postoperative respiratory weakness
• Refractory exacerbation

1. MYASTHENIC CRISIS – Definition

Myasthenic crisis = Acute respiratory failure due to neuromuscular weakness requiring ventilatory support.

• Occurs in ~15–20% of MG patients
• Mortality <5% in modern ICUs
• Most common trigger: Infection

Common Triggers:

• Infection (most common)
• Surgery
• Pregnancy
• Certain drugs
• Steroid initiation

2. Pathophysiology of Respiratory Failure in MG

Mechanisms:

1. Diaphragm weakness
2. Intercostal muscle failure
3. Bulbar dysfunction → aspiration
4. Ineffective cough → secretion retention

Result:

• Hypoventilation
• Atelectasis
• Pneumonia
• Hypercapnia (late)

ABG changes are late findings – never wait for hypercapnia.

3. ICU ADMISSION CRITERIA

Admit if:

• FVC <20 mL/kg
• Rapidly worsening weakness
• Bulbar symptoms
• Recurrent aspiration
• NIF worse than –30 cmH₂O
• Severe dysphagia
• Postoperative MG patient with risk

4. Respiratory Monitoring Protocol

Serial Bedside Monitoring (Every 2–4 hours)

📌 Single best predictor = FVC trend

Why These Matter in Myasthenia Gravis

MG causes:

• Inspiratory weakness → ↓ NIF
• Expiratory weakness → ↓ MEP

Consequences:

5. NIF vs FVC – Which Is More Important?

Trend matters more than single value

6. AIRWAY MANAGEMENT

When to Intubate?

• FVC <15 mL/kg
• Rapid deterioration
• Inability to handle secretions
• Severe bulbar dysfunction
• Hypercapnia
• Exhaustion

Do NOT delay intubation

Early controlled intubation is safer than crash intubation.

Intubation Strategy in MG

Premedication

Avoid:

• Magnesium
• High-dose opioids

Neuromuscular Blockade

Preferred approach:

• Intubate without paralytic if possible
• If needed → 10–20% normal dose rocuronium
• Mandatory neuromuscular monitoring

7. Mechanical Ventilation Strategy

MG is a pure neuromuscular respiratory failure, lungs are initially normal.

Ventilator Mode

• Volume-controlled or Pressure-controlled
• Tidal volume: 6–8 mL/kg
• PEEP: 5 cmH₂O (unless pneumonia)
• Avoid excessive sedation

Sedation Strategy

• Dexmedetomidine preferred
• Propofol acceptable
• Avoid long-acting benzodiazepines

8. NON-INVASIVE VENTILATION (NIV)

May be attempted if:

• Mild crisis
• No bulbar weakness
• No aspiration
• Cooperative patient

Contraindicated if:

• Severe dysphagia
• Secretions
• Altered sensorium

Failure rate high if bulbar involvement present.

9. Rapid Immunomodulatory Therapy (Cornerstone of ICU Care)

A. Plasma Exchange (PLEX)

Preferred in severe crisis.

• 4–6 exchanges over 7–10 days
• Rapid onset (2–3 days)

Advantages:

• Faster response
• Better in severe weakness

Complications:

• Hypotension
• Line infection
• Hypocalcemia

B. Intravenous Immunoglobulin (IVIG)

Onset:

• 4–7 days

Choose IVIG if:

• Hemodynamically unstable
• No PLEX access
• Sepsis risk high

10. Role of Anticholinesterases in ICU

Intubated Patients

Often temporarily stopped due to:

• Excess secretions
• Bronchorrhea
• Risk of cholinergic crisis

Restart:

• When extubation planned

11. Steroids in ICU

• Continue chronic steroids
• If not on steroids → start cautiously

⚠️ High-dose steroids can initially worsen weakness.

Recommended:

• Start low dose → escalate gradually

12. Treat the Trigger

Most common: Infection

Antibiotics to Avoid

• Aminoglycosides
• Fluoroquinolones
• Macrolides

Safer options:

• Beta-lactams
• Carbapenems

13. Nutritional Management

Bulbar weakness → aspiration risk

If intubated:

• Early enteral nutrition

If non-intubated:

• Swallow assessment
• NG tube if needed

14. Secretion Management

• Aggressive suctioning
• Chest physiotherapy
• Incentive spirometry (if extubated)
• Avoid atropine unless needed

15. Weaning Protocol

Weaning when:

• FVC >15–20 mL/kg
• NIF better than –25 cmH₂O
• Minimal secretions
• Bulbar strength improved

Spontaneous Breathing Trial (SBT)

Perform cautiously.

Common cause of failure:

• Bulbar weakness

16. Tracheostomy

Consider if:

• 2 weeks ventilation
• Failed extubation
• Severe bulbar dysfunction

17. DVT & ICU Prophylaxis

• LMWH prophylaxis
• Stress ulcer prophylaxis
• Glycemic control
• Early mobilization

18. Autonomic & Cardiac Issues

Rare but possible:

• Arrhythmias
• QT prolongation (especially with drugs)

Monitor ECG continuously.

19. Special ICU Situations

A. Postoperative MG Crisis

High risk after:

• Thymectomy
• Major abdominal surgery

Risk factors:

• Disease duration >6 yrs
• High pyridostigmine dose
• Pre-op bulbar symptoms

B. Pregnancy + MG Crisis

• PLEX safe
• Avoid magnesium (contraindicated!)

20. Cholinergic Crisis in ICU

Rare today.

Features:

• Miosis
• Bradycardia
• Diarrhea
• Fasciculations
• Excess secretions

Management:

• Stop anticholinesterase
• Atropine if severe

21. Prognosis in ICU

• 70–80% extubated within 2 weeks
• Recurrence risk ~30%
• Mortality low in tertiary centers

Poor prognostic factors:

• Advanced age
• Sepsis
• Delayed intubation

22. Key Differences: MG Crisis vs Guillain-Barré