What is the recommended plasma exchange regime in refractory myasthenia crisis?

Plasma Exchange Regime in Refractory Myasthenia Crisis

For refractory myasthenic crisis, plasma exchange should consist of 3-5 treatment sessions over 7 days, with each session exchanging 1.5 liters of plasma (20-25 ml/kg body weight, representing 0.5-0.6 plasma volumes), performed in addition to standard immunosuppressive therapy. 1

Treatment Protocol

Standard Dosing Parameters

• Volume per session: 1.5 liters of plasma or 20-25 ml/kg body weight 1
• Number of sessions: 3-5 treatments (mean 3.4-3.5 sessions) 1
• Treatment duration: 7 days 1
• Plasma volume exchanged: 0.5-0.6 of patient's total plasma volume per session 1

Clinical Context for Use

Plasma exchange is indicated when myasthenic crisis fails to respond to initial treatment with intravenous immunoglobulin (IVIG), as plasmapheresis has demonstrated superiority in certain refractory patients 2. In direct comparison studies, plasma exchange produces faster clinical response than IVIG, with significantly reduced ICU stay length (p=0.018) and earlier improvement in quantitative myasthenia gravis scores at one week off ventilation 3.

Replacement Fluid Selection

Use albumin rather than fresh frozen plasma for volume replacement when possible to minimize transfusion reactions 4. Blood is reconstituted with exogenous albumin and/or fresh-frozen plasma or crystalloid after plasma separation 5.

Monitoring Requirements

Clinical Assessment

• Disease-specific scores: Monitor Myasthenia Gravis Foundation of America Quantitative Myasthenia Gravis (MGFA-QMG) score, Manual Muscle Testing (MMT), and Activities of Daily Living (ADL) scores 3
• Target improvement: Patients should improve to stable Oosterhuis Classes 1 and 2 1
• Respiratory parameters: Assess negative inspiratory force (NIF) and vital capacity (VC) 6
• Bulbar function: Monitor for dysphagia and respiratory muscle weakness 6

Laboratory Monitoring

• Antibody levels: Substantial reduction of anti-acetylcholine receptor (AChR) antibodies occurs after each session 1
• Hemoglobin: Expect significant post-treatment hemoglobin drop 3
• Citrate-induced hypocalcemia: Monitor calcium levels during procedures 4

Hemodynamic Management During Procedures

Critical Precautions

• Maintain adequate volume status throughout to prevent hypotension 4
• Monitor hemodynamic parameters closely during each session 4
• Avoid vasodilators including dihydropyridine calcium channel blockers, ACE inhibitors, and ARBs 4

Hypotension Management

If acute hypotension occurs during plasma exchange:

• Use phenylephrine (pure vasoconstrictor) as first-line agent 4
• Avoid inotropic agents (dopamine, dobutamine, norepinephrine) which can worsen certain cardiac conditions 4

Expected Clinical Response

Short-term Outcomes

• Immediate response: Clinical improvement begins within the first week, with mean Myasthenia scores decreasing equally by Day 14 post-treatment 1
• ICU stay: Plasma exchange significantly reduces ICU length of stay compared to IVIG 3
• Early functional improvement: Significant changes in MGFA-QMG (p=0.003), MMT (p=0.020), and ADL (p=0.011) at one week off ventilation 3

Long-term Considerations

After one month, clinical efficacy becomes comparable between plasma exchange and IVIG 3. The value of plasma exchange lies primarily in short-term control of severe symptoms during crisis 7. Some patients may require long-term intermittent plasma exchange if they remain exchange-dependent, with inter-exchange intervals potentially lengthening to 9-12 weeks over 2-3 years when combined with azathioprine 8.

Safety Profile

Plasma exchange demonstrates acceptable safety in myasthenic crisis, though adverse events occur. In controlled studies, 16 adverse effects (including 7 serious adverse events) were observed in plasma exchange groups versus 10 adverse effects (1 serious adverse event) in immunoadsorption groups 1. Common complications include hypotension, citrate-induced hypocalcemia, and venous access issues 4.

Combination with Immunosuppression

Plasma exchange must always be used in conjunction with immunosuppressive therapy (typically azathioprine with or without corticosteroids), never as monotherapy 5, 7. When using rituximab or IVIG, timing is critical—avoid plasma exchange immediately after these agents to prevent their removal 5.

Alternative: Immunoadsorption

Immunoadsorption represents an equally effective alternative to plasma exchange, using the same treatment frequency (3-5 sessions) and volume parameters, with potentially fewer adverse events 1. However, plasma exchange remains more widely available and is the standard approach in most centers 5.