What is the explanation for a patient with myasthenia gravis (MG) and respiratory failure, who developed hemodynamic instability and refractory metabolic acidosis after Therapeutic Plasma Exchange (TPE), despite normal lactate levels and bicarbonate therapy?

Refractory Metabolic Acidosis Post-TPE: Citrate Toxicity

The most likely explanation is citrate toxicity from the therapeutic plasma exchange procedure, which causes metabolic acidosis with normal lactate levels and hemodynamic instability despite bicarbonate therapy.

Mechanism of Citrate-Induced Metabolic Acidosis

• Citrate anticoagulation during TPE is metabolized to bicarbonate in the liver, but this process can be impaired in critically ill patients, leading to citrate accumulation 1
• The citrate itself causes metabolic acidosis through direct acid load, while simultaneously chelating ionized calcium, which explains the hemodynamic instability 1
• This creates a unique clinical picture: refractory metabolic acidosis with normal lactate levels, distinguishing it from tissue hypoperfusion or septic shock 1

Why This Patient Is Particularly Vulnerable

• Missed sepsis diagnosis means the patient likely has impaired hepatic metabolism, reducing citrate clearance during the TPE procedure 1
• Respiratory failure from myasthenia gravis may have caused pre-existing respiratory acidosis, which when combined with citrate-induced metabolic acidosis, creates a severe mixed acidosis 1
• The combination of critical illness, potential hepatic dysfunction from sepsis, and large volume plasma exchange (typical TPE exchanges 1-1.5 plasma volumes) maximizes citrate exposure 1

Clinical Presentation Matches Citrate Toxicity

• Hemodynamic instability occurring 6 hours post-TPE is consistent with citrate accumulation, as citrate levels peak during and immediately after the procedure 1
• Refractory response to 100 mEq bicarbonate therapy is pathognomonic for citrate toxicity, because the acidosis is caused by citrate accumulation, not bicarbonate depletion 1
• Normal lactate levels effectively rule out tissue hypoperfusion as the primary cause, pointing away from septic shock or cardiogenic shock 1

Alternative Considerations (Less Likely)

• Unmasked sepsis could contribute but would typically show elevated lactate 1
• The timing (6 hours post-TPE) and normal lactate make primary septic deterioration less likely as the sole explanation 1
• Respiratory acidosis from myasthenia gravis would show elevated CO2, not isolated metabolic acidosis 1

Immediate Management Algorithm

• Check ionized calcium immediately - hypocalcemia from citrate chelation directly causes myocardial depression and vasodilation 1
• Administer calcium gluconate or calcium chloride for ionized calcium <1.0 mmol/L, which treats both the acidosis and hemodynamic instability 1
• Obtain arterial blood gas with full electrolyte panel to calculate anion gap and assess for mixed acid-base disorders 1
• Support hemodynamics with vasopressors (norepinephrine preferred) while addressing the underlying citrate toxicity 1

Critical Pitfall to Avoid

• Do not continue aggressive bicarbonate therapy without addressing citrate toxicity - this will not correct the acidosis and may worsen ionized hypocalcemia through alkalosis-induced calcium binding 1
• The bicarbonate given (100 mEq) should have improved metabolic acidosis if it were from lactate or other organic acids; failure to respond indicates citrate as the culprit 1

Monitoring and Prevention

• Future TPE sessions in this patient require reduced citrate exposure: use lower citrate concentrations, slower flow rates, or consider heparin anticoagulation if not contraindicated 1
• Serial ionized calcium and pH monitoring during TPE procedures is essential in critically ill patients with sepsis or hepatic dysfunction 1