What is the management for a patient who develops metabolic acidosis and twitching of the lips and tongue after receiving chemotherapy with carboplatin (carboplatin) and etoposide (etoposide)?

Management of Metabolic Acidosis with Perioral Twitching After Carboplatin and Etoposide Chemotherapy

Immediate treatment should include IV calcium gluconate administration, sodium bicarbonate infusion, and discontinuation of carboplatin and etoposide to address the metabolic acidosis and neuromuscular symptoms.

Diagnosis and Pathophysiology

The patient's presentation with metabolic acidosis and perioral twitching (lips and tongue) after carboplatin and etoposide chemotherapy suggests:

1. Chemotherapy-induced metabolic acidosis: Both carboplatin and etoposide can cause metabolic acidosis through:

   • Mitochondrial toxicity leading to lactic acidosis 1
   • Renal tubular damage affecting acid-base regulation
   • Benzyl alcohol in etoposide formulation potentially contributing to acidosis 2

2. Perioral twitching: The twitching of lips and tongue indicates neuromuscular irritability, likely due to:

   • Hypocalcemia (common with metabolic acidosis)
   • Direct neurotoxic effects of platinum compounds
   • Acid-base disturbance affecting neuromuscular function

Management Algorithm

Immediate Management (First 1-2 Hours)

1. Assess and stabilize:

   • Obtain arterial blood gas, serum electrolytes, calcium, magnesium, and lactate levels
   • Monitor vital signs, cardiac rhythm, and neurological status
   • Secure airway if respiratory compromise is present

2. Treat neuromuscular symptoms:

   • Administer IV calcium gluconate 10% (10 mL over 10 minutes)
   • Check ionized calcium and repeat calcium gluconate if twitching persists

3. Correct metabolic acidosis:

   • Administer sodium bicarbonate IV bolus (1-2 mEq/kg) followed by infusion if pH < 7.2
   • Target pH > 7.25 to reduce neuromuscular irritability

4. Discontinue offending agents:

   • Stop carboplatin and etoposide immediately 3
   • Consult oncology regarding alternative chemotherapy regimens

Secondary Management (2-24 Hours)

1. Electrolyte management:

   • Correct magnesium deficiency (common with platinum agents)
   • Monitor and replace potassium as needed (acidosis correction can lower potassium)
   • Continue calcium supplementation if needed

2. Fluid management:

   • Ensure adequate hydration to enhance renal clearance of platinum compounds
   • Monitor urine output (target >0.5 mL/kg/hr)

3. Renal support:

   • Consider hemodialysis for severe, refractory acidosis or if renal function is significantly impaired 4
   • Monitor creatinine and BUN closely

Monitoring and Follow-up

1. Frequent reassessment:

   • Repeat arterial blood gases every 2-4 hours until stable
   • Monitor electrolytes every 4-6 hours
   • Continuous cardiac monitoring for arrhythmias

2. Watch for complications:

   • Seizures (may require benzodiazepines)
   • Cardiac arrhythmias (acidosis-induced)
   • Progressive renal dysfunction

Special Considerations

1. Carboplatin nephrotoxicity: While less nephrotoxic than cisplatin, carboplatin can still cause significant renal impairment, especially at high doses 4. Nephrotoxicity occurred in 29% of patients receiving high-dose carboplatin with etoposide.

2. Mitochondrial toxicity: Carboplatin can damage mitochondrial DNA leading to respiratory chain dysfunction and lactic acidosis 1. This is a rare but potentially fatal complication.

3. Neurological complications: Both agents can cause neurotoxicity. Monitor for progression to more severe manifestations like seizures or reversible posterior leukoencephalopathy syndrome 5.

Prevention of Recurrence

1. Chemotherapy modification:

   • Consider dose reduction of platinum agents in future cycles
   • Evaluate alternative regimens with lower risk of metabolic complications
   • More intensive hydration protocols for subsequent chemotherapy

2. Enhanced monitoring:

   • More frequent electrolyte and renal function monitoring during future chemotherapy
   • Pre-emptive calcium and magnesium supplementation

Pitfalls to Avoid

1. Delayed recognition: Perioral twitching may be mistaken for anxiety or other non-specific symptoms. Always consider metabolic causes in chemotherapy patients.

2. Inadequate calcium replacement: Hypocalcemia can persist despite bicarbonate correction and requires separate management.

3. Overlooking magnesium deficiency: Low magnesium can perpetuate hypocalcemia and neuromuscular symptoms despite calcium replacement.

4. Focusing only on acidosis: While correcting the acidosis is important, addressing the underlying cause (chemotherapy toxicity) is essential for complete resolution.