Anaesthesia for Myasthenia Gravis

Quick Answer

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder causing fatigable muscle weakness due to anti-acetylcholine receptor (AChR) antibodies (80-85%) or anti-MuSK antibodies (5-8%). Anaesthetic challenges: Extreme sensitivity to non-depolarizing neuromuscular blockers (use 1/5th-1/10th normal dose or avoid), risk of postoperative respiratory failure (thymectomy or other surgery), aspiration risk (bulbar dysfunction), cholinergic vs myasthenic crisis differentiation. Preoperative optimization: Pyridostigmine continued (morning of surgery), steroids may be continued or stress-dosed, plasmapheresis/IVIG for severe disease. Muscle relaxants: Avoid if possible; if needed use low-dose rocuronium with sugammadex reversal (preferred) or atracurium with neostigmine (less predictable). Monitoring: Train-of-four essential; extubate only when fully recovered. Postoperative: High dependency/ICU, respiratory monitoring, swallow assessment before feeding. [1-15]

Pathophysiology

Myasthenia Gravis Pathophysiology

Autoimmune Mechanism:

• Antibodies:
  • Anti-AChR: 80-85% of patients (generalized MG)
  • Anti-MuSK: 5-8% (more severe, bulbar predominant, female predominance)
  • Anti-LRP4: 1-3% (milder)
  • Seronegative: 10-15% (likely undetected antibodies)
• Target: Postsynaptic acetylcholine receptors at neuromuscular junction
• Mechanism: Antibody binding causes:
  • Complement-mediated destruction of junctional folds
  • Accelerated receptor degradation
  • Blockade of receptor function
• Result: Reduced functional AChR (typically 70-80% reduction needed for symptoms)

Clinical Features:

• Fatigable weakness: Worsens with repetitive use, improves with rest
• Distribution:
  • Ocular (ptosis, diplopia): 85% initial presentation
  • Bulbar (dysphagia, dysarthria, chewing weakness)
  • Proximal limb weakness
  • Respiratory (diaphragm, intercostals - "myasthenic crisis")
• Fluctuating course: Variable day-to-day and within day
• Triggers: Infection, surgery, stress, medication (aminoglycosides, fluoroquinolones, magnesium, beta-blockers)

Classification (Myasthenia Gravis Foundation of America):

• Class I: Ocular only
• Class II: Mild generalized
• Class III: Moderate generalized
• Class IV: Severe generalized
• Class V: Intubation required (myasthenic crisis)

Thymus Gland and MG

Thymic Abnormalities:

• Hyperplasia: 70% of patients (lymphoid follicular hyperplasia)
• Thymoma: 10-15% of patients (age >40 more common)
• Role: Thymus is source of autoimmunity (contains myoid cells with AChR)

Thymectomy:

• Indications:
  • Generalized MG (all ages, seropositive)
  • Thymoma (oncological resection)
  • Some ocular MG if refractory
• Timing: Optimized medical condition (not in crisis)
• Surgical approaches:
  • Transsternal (traditional, complete resection)
  • Transcervical (less invasive, controversial completeness)
  • Video-assisted thoracoscopic (VATS) / Robotic
• Benefit: Improves symptoms, reduces immunosuppression needs (not immediate - takes months-years)

Anaesthetic Implications:

• Transsternal: Similar to cardiac surgery (sternotomy, possible CPB)
• VATS: Thoracic approach, one-lung ventilation, CO₂ insufflation
• Phrenic nerve injury: Risk during dissection (worsens respiratory function)

Myasthenic Crisis

Definition:

• Respiratory failure requiring intubation and mechanical ventilation
• Severe bulbar weakness causing aspiration risk

Triggers:

• Infection (most common - pneumonia, UTI)
• Surgery (thymectomy, any procedure)
• Medication changes (reduced cholinesterase inhibitors, new contraindicated drugs)
• Pregnancy/postpartum
• Stress, emotional upset

Clinical Features:

• Rapidly progressive weakness
• Respiratory distress (tachypnea, shallow breathing, use of accessory muscles)
• Inability to cough or clear secretions
• Bulbar dysfunction (cannot swallow, protect airway)
• Weakness out of proportion to baseline

Management:

• Intubation: Early if FVC <15-20 mL/kg, rising PaCO₂, fatigue
• ICU admission: Mechanical ventilation
• Cholinesterase inhibitors: Stop temporarily (confounding factor for diagnosis)
• Plasmapheresis: 5-7 exchanges (removes antibodies, rapid improvement)
• IVIG: 2 g/kg over 5 days (alternative to plasmapheresis)
• Steroids: High-dose prednisone (may transiently worsen before improving)
• Treat trigger: Antibiotics for infection, etc.
• Differentiate from cholinergic crisis: See below

Prognosis:

• Mortality <5% with modern ICU care
• Recovery typically days to weeks
• May require tracheostomy if prolonged ventilation

Cholinergic Crisis

Pathophysiology:

• Excess cholinesterase inhibition: Pyridostigmine overdose
• Accumulation of acetylcholine: At muscarinic and nicotinic receptors
• Cannot distinguish clinically: From myasthenic crisis (both cause weakness)

Muscarinic Symptoms (SLUDGE):

• S: Salivation
• L: Lacrimation
• U: Urination
• D: Defecation (diarrhea)
• G: GI upset (nausea, vomiting, cramps)
• E: Emesis
• Plus: Miosis (pupillary constriction), bradycardia, sweating, bronchospasm, bronchorrhea

Nicotinic Symptoms:

• Muscle weakness (fasciculations → weakness → paralysis)
• Respiratory muscle weakness
• Cannot distinguish from myasthenic weakness

Differentiation (Edrophonium Test - rarely used now):

• Principle: Short-acting cholinesterase inhibitor (Tensilon)
• Dose: 2 mg IV (test dose), then 8 mg if tolerated
• Interpretation:
  • Myasthenic crisis: Improvement in strength (give more pyridostigmine)
  • Cholinergic crisis: No improvement or worsening (stop pyridostigmine)
• Caution: Can precipitate severe bradycardia/asystole (atropine must be available)
• Modern alternative: Clinical diagnosis + history of medication compliance

Management:

• Stop pyridostigmine: All cholinesterase inhibitors discontinued
• Supportive: Airway protection, ventilation if needed
• Atropine: Treats muscarinic symptoms (bradycardia, secretions)
• Time: Crisis resolves as excess drug eliminated (hours)

Drug-Induced Worsening of MG

Medications to Avoid or Use with Caution:

Definite Worsening:

• Aminoglycosides: Gentamicin, tobramycin, amikacin
• Fluoroquinolones: Ciprofloxacin, levofloxacin
• Macrolides: Erythromycin, azithromycin (less severe)
• Beta-blockers: Propranolol, metoprolol (even topical eye drops)
• Calcium channel blockers: Verapamil (less with others)
• Magnesium: IV magnesium sulfate (antagonizes calcium entry)
• Neuromuscular blockers: All non-depolarizing agents (sensitivity increased)
• Botulinum toxin: Neuromuscular blockade

Possible Worsening:

• Statins: May worsen myopathy
• Iodinated contrast: Rare reports
• Penicillamine: Can induce MG (de novo)
• Chloroquine: Rare
• Phenytoin: Rare
• Lithium: Rare

Safe Alternatives:

• Antibiotics: Penicillins, cephalosporins, vancomycin, metronidazole
• Beta-blockers: If essential, use cardioselective (bisoprolol) at lowest dose
• Analgesia: Paracetamol, NSAIDs, opioids (caution with respiratory depression)

Clinical Presentation

Preoperative Assessment

History:

• Disease severity: Classification (MGFA class), pattern of weakness (bulbar, ocular, generalized)
• Duration: Time since diagnosis, progression
• Current treatment: Pyridostigmine dose, steroids, immunosuppressants, plasmapheresis/IVIG history
• Crisis history: Previous myasthenic crises, precipitants
• Respiratory: Baseline function, sleep apnea symptoms, recent infections
• Swallowing: Dysphagia severity, aspiration history
• Medications: Current drugs, recent changes, potential exacerbating medications
• Thymoma: History, previous thymectomy

Physical Examination:

• Neurological: Detailed weakness assessment
  • Ocular: Ptosis (fatigable - worsens with sustained upgaze), diplopia
  • Bulbar: Nasal speech, poor cough, weak jaw closure
  • Limbs: Proximal weakness (shoulder abduction, hip flexion)
  • Respiratory: Accessory muscle use, paradoxical breathing
• Fatigability testing: Sustained upgaze (ptosis worsens), counting (dysarthria develops)
• Airway: Assessment (difficult intubation risk)
• Respiratory: Auscultation for aspiration, baseline respiratory rate/pattern

Investigations:

MG-Specific:

• AChR antibodies: Present in 80-85%
• MuSK antibodies: If AChR negative
• Anti-striational antibodies: Thymoma marker
• Edrophonium test: Rarely used now (clinical diagnosis preferred)
• Electrophysiology:
  • Repetitive nerve stimulation: Decremental response (>10% decrement diagnostic)
  • Single fiber EMG: Most sensitive (jitter)

Preoperative Baseline:

• Pulmonary function tests: FVC, MIP, MEP
  • FVC <2 L (or <15-20 mL/kg) predicts postoperative respiratory failure
  • MIP <30 cm H₂O (weak cough)
• ABG: Baseline CO₂ retention risk
• CXR: Aspiration, thymoma, cardiac (if transsternal approach)
• CT chest: Thymoma assessment, approach planning
• Swallowing assessment: Speech pathology evaluation if bulbar symptoms

Cardiovascular (if transsternal thymectomy):

• ECG: Baseline
• Echocardiography: If cardiac history, or thymoma compressing heart

Laboratory:

• FBC: Anemia, infection
• Electrolytes: Potassium, magnesium (both affect neuromuscular function)
• Renal function: Drug dosing
• Glucose: Steroid-induced diabetes

Risk Stratification:

• High risk for postoperative ventilation:
  • MGFA Class IV-V
  • FVC <2 L or <15-20 mL/kg
  • Bulbar dysfunction (aspiration risk)
  • Disease >6 years
  • Coexisting COPD/cardiac disease
• Low risk: Ocular MG, well-controlled generalized MG, FVC >2.5 L

Perioperative Medication Management

Pyridostigmine (Mestinon):

• Preoperative: Continue up to and including morning of surgery
  • Dose timing: Ensure adequate duration (3-4 hours) pre-induction
  • Risk of omission: Worsening weakness (myasthenic crisis)
• Intravenous: If NPO, can give IV neostigmine (1 mg IV neostigmine = 60 mg oral pyridostigmine)
• Postoperative: Resume as soon as oral intake possible
  • Start lower dose (may need less after thymectomy)
  • Titrate to response

Corticosteroids:

• Continue: Chronic steroid therapy must not stop abruptly (adrenal suppression)
• Stress dose:
  • Minor surgery: Usual daily dose
  • Moderate surgery: Usual dose + 50 mg hydrocortisone pre-op
  • Major surgery (transsternal thymectomy): Usual dose + 100 mg hydrocortisone pre-op and post-op taper

Immunosuppressants:

• Azathioprine, mycophenolate, cyclosporine, tacrolimus: Continue
• Rituximab: Timing of surgery relative to infusion (immune suppression concerns)
• Eculizumab: Complement inhibitor, continue

Avoid/Discontinue:

• Anticholinesterases overdose: If suspected cholinergic features, hold dose
• Contraindicated medications: Review all new medications for MG safety

Management

Anaesthetic Technique

General Principles:

• Avoidance preferred: Avoid neuromuscular blockers whenever possible
• Regional anaesthesia: Preferred where appropriate (no muscle relaxation needed)
  • Spinal, epidural, peripheral nerve blocks
  • Caution: High blocks affect intercostals (respiratory compromise)
• Short procedures: May use deep inhalational anaesthesia alone
• Monitoring: Train-of-four (TOF) mandatory whenever NMBAs used

Induction (Without Muscle Relaxants):

• Pre-oxygenation: 100% O₂, 3-5 minutes
• Propofol: 2-3 mg/kg (can provide intubating conditions in many patients without relaxant)
• Remifentanil: 3-5 μg/kg (opioid-induced rigidity may provide some relaxation)
• Lidocaine: 1-1.5 mg/kg IV (reduces airway reflexes)
• Airway: Ventilate with high concentration volatile or propofol infusion
• Intubation: Attempt without relaxant; if impossible, use lowest possible dose of rocuronium

If Muscle Relaxants Necessary:

Choice of Agent:

• Rocuronium: Preferred (reversible with sugammadex)
  • Dose: 0.1-0.2 mg/kg (1/5th-1/10th of normal dose - typically 5-10 mg for 70 kg patient)
  • Duration: Unpredictable, may last 2-4× normal duration
• Atracurium/Cisatracurium: Alternative
  • Dose: 0.05-0.1 mg/kg (reduced)
  • Hofmann elimination (organ-independent)
• Avoid: Long-acting agents (pancuronium, vecuronium), high-dose intermediate

Monitoring:

• TOF: Essential throughout
• Baseline: Check TOF before any relaxant given (may show fade even before drugs)
• Intubating dose: Use TOF count 1 (not TOF count 0 as in normal patients)
• Maintenance: Single twitch or TOF count 1-2 (avoid profound block)
• Reversal: Ensure TOF ratio >0.9 before extubation

Reversal Strategies:

1. Sugammadex (Preferred):

• Mechanism: Direct encapsulation of rocuronium/vecuronium
• Dose: 2-4 mg/kg (standard dose effective even with myasthenia)
• Advantages:
  • Rapid (3-5 minutes to recovery)
  • Predictable (independent of MG status)
  • No reliance on acetylcholinesterase function
• Considerations:
  • Only works for rocuronium/vecuronium
  • Ensure adequate dose (4 mg/kg if profound block)

2. Neostigmine (Less Predictable):

• Mechanism: Acetylcholinesterase inhibition (increases ACh at NMJ)
• Dose: 0.02-0.04 mg/kg (reduced dose compared to normal patients)
• Limitations:
  • Less effective (baseline cholinesterase inhibition from pyridostigmine)
  • Requires atropine/glycopyrrolate to treat bradycardia
  • Unpredictable duration of effect
• Use: If sugammadex unavailable or other NMBAs used

3. Spontaneous Recovery:

• Preferred if possible: Short-acting agents (rocuronium low-dose) may wear off spontaneously
• Avoid neostigmine: If patient has received pyridostigmine recently
• Monitoring: Wait for TOF ratio >0.9

Maintenance of Anaesthesia:

• Volatile agents: Sevoflurane, desflurane (minimal neuromuscular effects)
• TIVA: Propofol + remifentanil (avoid muscle relaxants entirely)
• Nitrous oxide: Acceptable (minimal NMJ effects)
• Analgesia: Multimodal (paracetamol, NSAIDs, opioids)
  • Opioids: Use cautiously (respiratory depression additive to MG)
  • Morphine/fentanyl acceptable with monitoring
  • Remifentanil infusion (rapidly titratable)

Ventilation:

• Controlled ventilation: Preferred (patients may have weak respiratory muscles)
• Pressure support: If spontaneous ventilation used, ensure adequate support
• Extubation criteria:
  • Fully awake, following commands
  • TOF ratio >0.9 (if relaxants used)
  • FVC >15-20 mL/kg (if measurable)
  • Adequate cough, head lift >5 seconds
  • ABG acceptable (no hypercapnia)

Thymectomy-Specific Considerations

Transsternal Approach:

• Similar to cardiac surgery: Sternotomy, mediastinal dissection
• Monitoring: Arterial line, central line (for vasopressors if needed)
• Airway: Standard ETT
• One-lung ventilation: Usually not required (unless VATS approach)
• Phrenic nerve: Identify and protect (critical for postoperative respiratory function)
• Hemostasis: Mediastinal bleeding risk

VATS/Robotic Approach:

• Positioning: Lateral decubitus
• One-lung ventilation: Required (double-lumen tube or bronchial blocker)
• CO₂ insufflation: May cause hemodynamic compromise, hypercapnia
• Conversion: To sternotomy if bleeding or incomplete resection

Postoperative Care:

• Extubation: In OR if patient meets criteria
• ICU admission: Most patients (respiratory monitoring)
• Pyridostigmine: Resume when oral intake possible (may need lower dose)
• Respiratory monitoring: FVC monitoring if available
• Swallowing: Assessment before feeding (bulbar dysfunction common)

Non-Thymectomy Surgery

Principles:

• Regional preferred: Whenever possible (spinal, epidural, peripheral blocks)
• Avoid NMBAs: Use propofol/opioid/deep volatile technique
• Monitoring: TOF if any relaxation used
• Extubation criteria: Strict adherence (TOF >0.9, strong cough)

Emergency Surgery:

• Risk assessment: Balance urgency with MG stability
• Myasthenic crisis: May need preoperative plasmapheresis/IVIG if possible
• Airway: Be prepared for difficult extubation
• Postoperative: Plan for possible ventilation

Postoperative Management

Respiratory Monitoring:

• High dependency/ICU: Even for minor surgery in severe MG
• FVC monitoring: Serial measurements if patient cooperative
  • Alert if FVC <15-20 mL/kg or declining >30% from baseline
• ABG: If respiratory distress, hypercapnia
• Clinical signs: Accessory muscle use, paradoxical breathing, weak cough

Reintubation Criteria:

• Rising PaCO₂ >50 mmHg
• FVC <15-20 mL/kg
• Severe dyspnea, fatigue
• Inability to clear secretions
• Aspiration risk (severe bulbar weakness)

Pain Management:

• Multimodal: Paracetamol, NSAIDs (if not contraindicated), regional techniques
• Opioids: Use cautiously (respiratory depression)
  • Morphine PCA (low dose, long lockout)
  • Remifentanil infusion (short-acting) transitioning to oral
  • Avoid in severe MG/bulbar dysfunction
• Avoid: Muscle relaxants for analgesia

Medication Resumption:

• Pyridostigmine: Resume when oral intake possible
  • Start at lower dose post-thymectomy
  • Titrate to strength improvement
• Steroids: Continue/taper stress dose
• Antibiotics: Choose MG-safe agents (penicillins, cephalosporins, vancomycin)
• Prophylaxis: DVT prophylaxis (heparin safe)

Swallowing:

• Assessment: Speech pathology before feeding
• Aspiration risk: High in bulbar MG
• NG feeding: If unsafe swallow
• Silent aspiration: Common (cough reflex weak)

Physical Therapy:

• Respiratory: Incentive spirometry, chest physiotherapy
• Mobilization: Early to prevent deconditioning
• Monitoring: Fatigue with activity

Indigenous Health Considerations

Aboriginal and Torres Strait Islander Patients

Access and Equity:

• Geographic barriers: Remote communities require transfer to major centres for thymectomy or complex MG management
• Delayed diagnosis: MG may be diagnosed late, presenting with crisis
• Specialist access: Neuromuscular specialists concentrated in major cities

Health Disparities:

• Higher comorbidity: Diabetes, renal disease (may affect medication choices)
• Medication adherence: Complex immunosuppressive regimens challenging
• Plasmapheresis/IVIG access: Limited in rural/remote areas

Cultural Considerations:

• Communication: Complex disease requires clear explanation; interpreter services if needed
• Family involvement: Extended family in decision-making
• Aboriginal Liaison Officers: Support for hospitalization
• Medication management: Support for complex regimens (pyridostigmine timing, steroid adherence)

Postoperative Challenges:

• Remote follow-up: Difficult to monitor for deterioration, adjust medications
• Telemedicine: Useful for neurology follow-up
• Rehabilitation: Access to physiotherapy, speech pathology limited remotely

Māori Health Considerations

Health Inequities:

• Autoimmune disease patterns: Similar prevalence but may present later
• Access: Rural Māori face transfer challenges
• Comorbidities: Higher rates of diabetes, cardiovascular disease

Cultural Safety:

• Whānau involvement: Essential for complex disease management
• Communication: Clear explanation of MG, thymectomy rationale
• Māori Health Workers: Liaison support

Practical Considerations:

• Thymectomy access: Major centres only (Auckland, Wellington, Christchurch)
• Follow-up care: Coordination with primary care for ongoing management
• Plasmapheresis: Availability varies by centre
• Medication adherence: Support for long-term immunosuppression

ANZCA Final Exam Focus

SAQ Patterns

Common Questions:

• "Describe the anaesthetic management of a patient with myasthenia gravis undergoing thymectomy."
• "How do you manage neuromuscular blockade in myasthenia gravis?"
• "Differentiate myasthenic crisis from cholinergic crisis."
• "What medications should be avoided in myasthenia gravis?"
• "What are the predictors of postoperative respiratory failure in MG?"

Marking Scheme Priorities:

• Pathophysiology (autoimmune, AChR antibodies)
• Neuromuscular blocker sensitivity (reduced dose, avoidance preferred)
• Reversal strategies (sugammadex preferred over neostigmine)
• Myasthenic vs cholinergic crisis (differentiation, management)
• Medications to avoid (aminoglycosides, beta-blockers, magnesium)
• Postoperative respiratory monitoring and extubation criteria

Viva Scenarios

Scenario 1: Muscle Relaxant Dosing

• Patient requires laparoscopic cholecystectomy, surgeon requests muscle relaxation
• Discuss: Rocuronium 0.1-0.2 mg/kg (reduced dose), TOF monitoring essential, sugammadex reversal preferred

Scenario 2: Postoperative Respiratory Failure

• Patient not meeting extubation criteria after thymectomy
• Discuss: Continue ventilation, FVC assessment, check TOF >0.9, ICU admission, resume pyridostigmine when possible

Scenario 3: Myasthenic Crisis vs Cholinergic Crisis

• Postoperative weakness, unclear if undertreated or overtreated
• Discuss: History (medication compliance), SLUDGE symptoms, edrophonium test (if used), empiric management (withdraw pyridostigmine, supportive care)

Scenario 4: Emergency Surgery in MG

• Appendixtis in MG patient (Class III)
• Discuss: Risk stratification, avoid NMBAs if possible, regional vs GA, postoperative ICU bed, antibiotic choice (avoid aminoglycosides)

Key Points for Examination Success

1. Pathophysiology: Autoimmune anti-AChR antibodies cause postsynaptic failure; fatigable weakness
2. Thymectomy: 10-15% have thymoma; surgery improves symptoms over months-years
3. NMBAs: Extreme sensitivity (1/5th-1/10th dose); avoid if possible; rocuronium with sugammadex if needed
4. Sugammadex: Preferred reversal (direct encapsulation, predictable, no reliance on acetylcholinesterase)
5. Avoid neostigmine: Unpredictable, less effective due to baseline cholinesterase inhibition
6. Myasthenic crisis: Respiratory failure requiring intubation; plasmapheresis/IVIG treatment
7. Cholinergic crisis: Pyridostigmine overdose, SLUDGE symptoms, stop cholinesterase inhibitors
8. Drugs to avoid: Aminoglycosides, fluoroquinolones, beta-blockers, magnesium, botulinum toxin
9. Extubation criteria: TOF >0.9, FVC >15-20 mL/kg, strong cough, awake and following commands
10. Postoperative: High risk for respiratory failure; ICU admission; swallow assessment before feeding

Assessment Content

SAQ 1: Myasthenia Gravis and Anaesthesia (20 marks)

Question: A 35-year-old woman with generalized myasthenia gravis (MGFA Class III) is scheduled for laparoscopic cholecystectomy. She takes pyridostigmine 60 mg QID and prednisone 20 mg daily. Her FVC is 2.8 L (55 mL/kg).

a) Describe the pathophysiology of myasthenia gravis and how it affects anaesthetic management. (6 marks) b) Outline your approach to neuromuscular blockade for this patient, including drug selection, dosing, monitoring, and reversal. (8 marks) c) What specific precautions would you take postoperatively to minimize the risk of respiratory complications? (6 marks)

Model Answer:

a) Pathophysiology and anaesthetic implications (6 marks):

• Autoimmune disorder: Anti-AChR antibodies (80-85%) or anti-MuSK (5-8%) attack postsynaptic receptors at neuromuscular junction (1 mark)
• Reduced functional receptors: Typically 70-80% reduction needed for symptoms; fatigable weakness (1 mark)
• Sensitivity to NMBAs: Markedly increased sensitivity to non-depolarizing blockers (1/5th-1/10th normal dose required) (1.5 marks)
• Reversal challenges: Neostigmine less effective due to baseline cholinesterase inhibition from pyridostigmine (1 mark)
• Respiratory risk: Bulbar and respiratory muscle weakness; aspiration risk; postoperative ventilatory failure (1 mark)
• Drug interactions: Many drugs worsen MG (aminoglycosides, beta-blockers, magnesium) (0.5 marks)

b) Neuromuscular blockade management (8 marks):

Drug selection and dosing:

• Avoid if possible: Use propofol/remifentanil/deep volatile technique for intubation without relaxant (1.5 marks)
• If required: Rocuronium 0.1-0.2 mg/kg (5-10 mg for 70 kg patient - 1/5th to 1/10th normal dose) (1.5 marks)
• Alternative: Atracurium 0.05-0.1 mg/kg (Hofmann elimination, organ-independent) (0.5 marks)

Monitoring:

• TOF mandatory: Baseline, after intubation dose, throughout procedure (1 mark)
• Target: TOF count 1-2 for maintenance (avoid profound block) (0.5 marks)

Reversal:

• Sugammadex preferred: 2-4 mg/kg IV (rapid, predictable, encapsulates rocuronium directly) (2 marks)
• Rationale: Independent of acetylcholinesterase function (affected by pyridostigmine) (0.5 marks)
• Avoid neostigmine: Unpredictable effect, requires atropine, less reliable (0.5 marks)

c) Postoperative precautions (6 marks):

• Extubation criteria strict: TOF ratio >0.9, fully awake, FVC >15-20 mL/kg, head lift >5 seconds, strong cough (1.5 marks)
• ICU/HDU admission: Even for "minor" surgery in Class III MG; respiratory monitoring (1 mark)
• FVC monitoring: Serial measurements; alert if declining >30% or <2 L (1 mark)
• Swallowing assessment: Speech pathology before feeding; high aspiration risk in MG (1 mark)
• Resume pyridostigmine: When oral intake possible; may need lower dose initially (0.5 marks)
• Steroid stress dose: Continue/hydrocortisone 50-100 mg if major surgery (0.5 marks)
• MG-safe antibiotics: Avoid aminoglycosides, fluoroquinolones; use penicillins/cephalosporins (0.5 marks)

SAQ 2: Myasthenic vs Cholinergic Crisis (20 marks)

Question: A 28-year-old man with myasthenia gravis presents to ICU with worsening respiratory distress 24 hours after thymectomy. He is dyspneic, tachypneic, and cannot cough effectively. He has been receiving pyridostigmine 90 mg QID postoperatively (increased from his usual 60 mg QID).

a) How would you differentiate myasthenic crisis from cholinergic crisis in this patient? (6 marks) b) Describe the immediate management priorities. (8 marks) c) How would you determine whether to increase or decrease cholinesterase inhibitor therapy? (6 marks)

Model Answer:

a) Differentiation (6 marks):

Clinical features supporting cholinergic crisis:

• SLUDGE symptoms: Salivation, lacrimation, urination, defecation/diarrhea, GI upset, emesis (2 marks)
• Muscarinic signs: Miosis (small pupils), bradycardia, sweating, bronchospasm (1 mark)
• History: Increased pyridostigmine dose (90 mg vs usual 60 mg) (0.5 marks)
• Timing: 24 hours post-op (rapid onset suggests overdose vs. undertreatment) (0.5 marks)

Clinical features supporting myasthenic crisis:

• Respiratory failure, weak cough, bulbar dysfunction can occur in both (0.5 marks)
• History of severe MG (Class III-IV), recent surgery (stress trigger) (0.5 marks)
• No SLUDGE symptoms suggests myasthenic rather than cholinergic (0.5 marks)

Edrophonium test (rarely used):

• 2 mg IV test dose then 8 mg; improvement = myasthenic, worsening/no change = cholinergic (0.5 marks)

b) Immediate management (8 marks):

Airway and ventilation:

• Intubation: If FVC <15-20 mL/kg, rising PaCO₂, or severe fatigue (2 marks)
• Mechanical ventilation: ICU admission (1 mark)
• Airway protection: Inability to swallow/clear secretions (0.5 marks)

Empiric management (while differentiating):

• Stop pyridostigmine: Withdraw all cholinesterase inhibitors (1.5 marks)
• Atropine: For muscarinic symptoms if cholinergic (0.5 marks)
• Plasmapheresis or IVIG: 5-7 exchanges or 2 g/kg over 5 days (2 marks)
• Steroids: High-dose prednisone 1 mg/kg (may transiently worsen before improving) (0.5 marks)

c) Determining therapy adjustment (6 marks):

History and examination:

• Medication compliance: Missed doses = undertreatment; increased dose = overtreatment (1 mark)
• SLUDGE symptoms: Present = cholinergic; absent = myasthenic (1 mark)
• Pupil size: Miotic = cholinergic; normal = myasthenic (0.5 marks)
• Muscle fasciculations: Suggests cholinergic (excess ACh at nicotinic receptors) (0.5 marks)

Empiric approach:

• Hold pyridostigmine: Safe approach initially (supports either diagnosis) (1 mark)
• If cholinergic: Symptoms resolve as drug eliminated (hours); reintroduce at lower dose when recovered (0.5 marks)
• If myasthenic: Worsens without pyridostigmine; reintroduce when crisis resolving (1 mark)
• Edrophonium test: If uncertain (atropine available for bradycardia) (0.5 marks)

Viva Scenario: Neuromuscular Blockade in MG

Examiner: "You are anaesthetising a myasthenia gravis patient for elective surgery. The surgeon requests muscle relaxation for the procedure. How do you approach this?"

Candidate: "My first approach would be to determine if muscle relaxants are truly necessary. Many procedures can be performed without neuromuscular blockers in MG patients by using deep inhalational anaesthesia, propofol TIVA, or high-dose opioids. If the surgeon absolutely requires relaxation, I would use a significantly reduced dose of a short-acting non-depolarizing agent - rocuronium 0.1-0.2 mg/kg instead of the usual 0.6 mg/kg, which is about one-fifth to one-tenth of the normal dose. I would monitor with train-of-four throughout and ensure sugammadex is available for reversal."

Examiner: "Why is sugammadex preferred over neostigmine?"

Candidate: "Sugammadex is preferred because it directly encapsulates rocuronium molecules, physically removing them from circulation. This mechanism is independent of acetylcholinesterase function. Neostigmine works by inhibiting acetylcholinesterase to increase acetylcholine at the neuromuscular junction, but this is exactly what pyridostigmine does - the patient is already on a cholinesterase inhibitor, so adding neostigmine produces unpredictable and often inadequate reversal. Sugammadex gives reliable, rapid reversal in 3-5 minutes regardless of the patient's MG status."

Examiner: "The patient received rocuronium 10 mg and now has a TOF count of 1 at 60 minutes. How do you manage this?"

Candidate: "This demonstrates the markedly prolonged effect of neuromuscular blockers in myasthenia gravis. Even with a reduced dose, the block is much longer than expected. I would administer sugammadex 4 mg/kg - the higher dose for profound block reversal. This should produce recovery within 3-5 minutes. I would monitor TOF ratio and ensure it reaches greater than 0.9 before considering extubation. If sugammadex were not available, I would continue ventilating the patient and wait for spontaneous recovery, avoiding neostigmine as it would be ineffective and potentially cause cholinergic side effects."

Examiner: "What are your extubation criteria?"

Candidate: "Extubation criteria must be strict in MG patients. I need TOF ratio greater than 0.9 confirmed by quantitative monitoring, not just visual assessment. The patient must be fully awake following commands, able to generate a strong cough to clear secretions, and able to sustain head lift for more than 5 seconds. If available, FVC should exceed 15-20 milliliters per kilogram. Clinical assessment looking for adequate respiratory effort without accessory muscle use or paradoxical breathing. If any doubt exists, it's safer to continue ventilation in ICU rather than risk post-extubation respiratory failure."

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