Presentation

Classic presentation

• Cancer cells lyse, releasing their intracellular contents. This leads to the following hematological and electrolyte derangements:
  
  
  
  • Release of intracellular potassium leads to hyperkalemia.
    
  • Release of intracellular phosphorus leads to hyperphosphatemia.
    
  • Elevated phosphorus causes secondary hypocalcemia.
    
  • Release of intracellular uric acid leads to hyperuricemia.
  
  
• Primary hyperkalemia may result in:
  
  
  
  • Cardiac arrhythmias
    
  • Muscle cramps or weakness
    
  • Paresthesias
    
  • Fatigue
    
  • Nausea, vomiting, and diarrhea.
  
  
• Primary hyperphosphatemia may result in:
  
  
  
  • Lethargy
    
  • Nausea, vomiting, and diarrhea
    
  • Seizures.
  
  
• Secondary hypocalcemia can result in:
  
  
  
  • Neuromuscular irritability or tetany
    
  • Prolonged QT interval
    
  • Cardiac dysrhythmias
    
  • Seizures.
  
  
• Primary hyperuricemia may result in:
  
  
  
  • Acute kidney injury, including oliguria and anuria
    
  • Lethargy.

Critical presentation

• Life-threatening cardiac arrhythmias.
  
• Renal failure.
  
• Lethargy requiring intervention for airway protection.
  
• Seizures.
  
• Multi-system organ failure.

Diagnosis and evaluation

• The physical symptoms of TLS are usually related to an underlying electrolyte abnormality.
  
• Laboratory studies
  
  
  
  • The laboratory diagnosis of tumor lysis syndrome is made by two or more of the following derangements between 3 and 7 days after the onset of therapy for a hematological malignancy:
    
    
    
    • Hyperuricemia (uric acid >8.0 mg/dL in adults)
      
    • Hyperkalemia (potassium >6.0 mmol/L)
      
    • Hyperphosphatemia (phosphorus >4.5 mg/dL in adults, >6.5 mg/dL in children)
      
    • Hypocalcemia (corrected serum calcium <7.0 mg/dL, or ionized calcium <1.12 mmol/L)
      
      
      
      • Corrected calcium = Serum calcium + [0.8 × (Normal albumin − Serum albumin)].
  
  
• Clinical diagnosis: Laboratory diagnosis + renal failure, seizure, cardiac arrhythmia, or death.
  
  
  
  • Acute kidney injury is defined as an increase in the serum creatinine (increase by 0.3 mg/dL or more), or oliguria (urine output <0.5 mL/kg/hour).

Critical management

• Prevent acute kidney injury:
  
  
  
  • Acute kidney injury is usually related to hyperuricemia. Therapy is therefore aimed at reducing serum uric acid.
    
    
    
    • Intravenous hydration will improve glomerular filtration and minimize acidosis:
      
      
      
      • Bolus 1–2 liters of crystalloids.
        
      • Follow with a crystalloid infusion at two times the maintenance rate, with a goal urine output of 1.5–2 mL/kg/hour.
        
      • Consider loop diuretics in patients with a low urine output despite aggressive hydration.
      
      
    • Therapies that decrease serum uric acid level:
      
      
      
      • Allopurinol inhibits xanthine oxidase, preventing production of uric acid.
        
        
        
        • Give 600–800 mg/day PO in 2–3 divided doses or 200–400 mg/m²/day intravenously (IV) in 1–4 divided doses.
        
        
      • Rasburicase prevents breakdown of uric acid into allantoin, which facilitates renal excretion. It is more efficacious at reducing the serum uric acid level than allopurinol.
        
        
        
        • Administer 0.2 mg/kg IV once, infused over 30 minutes.
        
        
      • Urinary alkalinization may or may not be beneficial and is currently not recommended as a routine intervention. Its use should be discussed in consultation with a hematologist/oncologist. It should be avoided if allopurinol is used as the alkaline environment may cause the precipitation of xanthine and calcium phosphate in the renal tubules.
        
        
        
        • Add 3 ampules (amps) of 8.4% sodium bicarbonate (150 mEq total) to 1 liter of D5W. Start an infusion at twice the maintenance rate and titrate to a urine pH of 7.1–7.5.
    
    
  • Note: for pediatric dosages for hyperuricemia treatments, we recommend consultation with the on-call pediatric oncologist or pharmacist.
  
  
• Prevent cardiac dysrhythmia and neuromuscular irritability.
  
  
  
  • Patients with no evidence of cardiac arrhythmias on ECG can be managed conservatively by limiting potassium and phosphorus intake.
    
  • Maintain continuous cardiac monitoring for arrhythmias.
  
  
• Treat hyperphosphatemia 4.5 mg/dL or 25% increase from baseline.
  
  
  
  • Furosemide 20–40 mg IV.
    
  • Aluminum hydroxide 50–150 mg/kg/day in 4 divided doses.
    
  • Severe or symptomatic hyperphosphatemia may require renal replacement therapy.

Sudden deterioration

Patients with TLS usually decompensate because of worsening electrolyte abnormalities. Interventions should target both the developing condition (cardiac arrhythmia, seizure, etc.) and the underlying electrolyte disorder.

• Obtain a 12-lead ECG immediately to rule out a life-threatening arrhythmia.
  
• Cardiac arrhythmias:
  
  
  
  • May be due to either hypocalcemia or hyperkalemia.
    
  • Administer IV calcium:
    
    
    
    • Calcium gluconate 1–3 ampules (1 g [4.5 mEq] per 10-mL ampule)
      
      
      
      • 100–200 mg/kg for pediatric patients.
      
      
    • Calcium chloride 1 ampule (1 g [13.5 mEq] per 10-mL amp) through central line.
      
    • Note: The use of calcium supplementation in TLS may cause precipitation of calcium phosphate.
    
    
  • If potassium is elevated:
    
    
    
    • Albuterol 10–20 mg nebulized.
      
    • Insulin 10 units IV bolus with 1–2 ampules of D50W IV.
      
      
      
      • Insulin 0.1 units/kg IV with 2 mL/kg of D25W IV in pediatric patients.
      
      
    • Sodium polystyrene sulfonate (Kayexelate) 30 g PO or PR.
      
    • Note that the use of Kayexalate is controversial.
      
      
      
      • 0.5–1 g/kg per dose in pediatric patients.
  
  
• Acute kidney injury:
  
  
  
  • Renal replacement therapy (dialysis) is indicated in the case of:
    
    
    
    • Volume overload with pulmonary edema that is refractory to medical therapy
      
    • Persistent hyperkalemia despite medical therapy
      
    • Metabolic acidosis despite medical therapy
      
    • BUN >100 mg/dL
      
    • Rapidly rising BUN
      
    • Symptomatic uremia or electrolyte imbalances.
  
  
• Seizures:
  
  
  
  • Can be caused by severe hypocalcemia or hyperphosphatemia:
    
    
    
    • Lorazepam 2–4 mg IV
      
    • Diazepam 5–10 mg IV

Vassoressor of choice: none.

References

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