Why is sodium bicarbonate not recommended in the treatment of Tumor Lysis Syndrome (TLS)?

Why Sodium Bicarbonate is Not Recommended in Tumor Lysis Syndrome

Sodium bicarbonate is not recommended in the treatment of Tumor Lysis Syndrome (TLS) due to potential complications including calcium phosphate precipitation, metabolic alkalosis, and lack of clear evidence demonstrating benefit. 1, 2

Rationale Against Sodium Bicarbonate Use in TLS

• While historically recommended for TLS prevention and management (especially when using allopurinol), current guidelines no longer support routine use of sodium bicarbonate for urinary alkalinization 1

• Although alkaline urine increases uric acid solubility (from 15 mg/dL at pH 5.0 to approximately 200 mg/dL at pH 7.0), it does not substantially increase the solubility of xanthine and hypoxanthine 1

• Xanthine has particularly low solubility (5 mg/dL at pH 5.0 and only 13 mg/dL at pH 7.0), which can lead to xanthine crystal precipitation in renal tubules when levels increase during allopurinol treatment 1

• Research in animal models demonstrated that increasing urine flow rate was more effective than urinary alkalinization for preventing urate-induced obstructive uropathy 1

• In the absence of increased urine output, increasing urinary pH above 7.0 was ineffective in preventing uric acid crystallization 1

Potential Complications of Sodium Bicarbonate Use

• Calcium phosphate precipitation: Alkalinization decreases calcium phosphate solubility, potentially worsening calcium phosphate deposition in renal tubules 2

• Metabolic alkalosis: Overly aggressive therapy with sodium bicarbonate can result in metabolic alkalosis, associated with muscular twitchings, irritability, and tetany 3

• Hypernatremia: Another potential complication of sodium bicarbonate administration 3

• Tissue damage: Inadvertent extravasation of intravenously administered hypertonic solutions of sodium bicarbonate can cause chemical cellulitis, tissue necrosis, ulceration, or sloughing at the infiltration site 3

Current Recommended Approach for TLS Management

• Aggressive hydration is the cornerstone of TLS prevention and management, starting 48 hours before tumor-specific therapy when possible 1, 2

• Maintain urine output at ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg) 1, 2

• Rasburicase (0.20 mg/kg/day) is recommended for patients with clinical TLS, laboratory TLS, or high-risk patients 1, 2

• For hyperuricemia management:

  • Rasburicase is preferred for rapid reduction of uric acid levels 1, 2
  • Allopurinol can be used for prevention in lower-risk patients 1
  • Note: Sodium bicarbonate is specifically not recommended when using rasburicase 2

• For hyperkalemia management:

  • Hydration, loop diuretics, and sodium polystyrene are first-line treatments 1
  • For severe hyperkalemia: insulin plus glucose, calcium carbonate, and sodium bicarbonate (only for stabilizing myocardial cell membrane and correcting acidosis, not for urinary alkalinization) 1

Special Considerations

• When sodium bicarbonate is used in severe hyperkalemia, it's specifically for stabilizing the myocardial cell membrane and correcting acidosis, not for urinary alkalinization 1

• Increasing urine flow through aggressive hydration is more effective than alkalinization for preventing uric acid nephropathy 1, 4

• Early renal replacement therapy should be considered in cases of severe oliguria, persistent hyperkalemia, hyperphosphatemia with symptomatic hypocalcemia, or hyperuricemia not responding to rasburicase 2, 5

• The threshold for renal replacement therapy initiation may be lower in TLS than in other clinical situations since the process of cell breakdown is ongoing, and rapid increases in serum electrolytes cannot be predicted 5