How is fluid managed in Tumor Lysis Syndrome (TLS)?

Fluid Management in Tumor Lysis Syndrome (TLS)

Aggressive hydration through a central venous access with a target urine output of at least 100 mL/hour in adults (3 mL/kg/hour in children <10 kg) is the cornerstone of fluid management in TLS, ideally starting 48 hours before cytotoxic therapy. 1

Initial Fluid Management Approach

• Hydration should begin at least 48 hours before tumor-specific therapy when possible, though rasburicase administration allows for earlier chemotherapy initiation if needed 1
• Maintain urine output at minimum 100 mL/hour in adults (3 mL/kg/hour in children <10 kg body weight) 1
• Loop diuretics may be required to maintain adequate urine output, except in patients with concomitant obstructive uropathy or hypovolemia 1
• Careful assessment of hydration status is essential before using loop diuretics - measurement of urine osmolality and fractional excretion of sodium may help define hydration status 1

Electrolyte Management in TLS

Hyperkalemia Management

• Mild asymptomatic hyperkalemia (<6 mmol/L): Correct with hydration, loop diuretics, and sodium polystyrene 1 g/kg orally or by enema 1
• Severe hyperkalemia: Administer rapid insulin (0.1 units/kg) plus glucose (25% dextrose 2 mL/kg), calcium carbonate (100-200 mg/kg/dose), and sodium bicarbonate 1
• Continuous ECG monitoring is essential in hyperkalemic patients 1

Hyperphosphatemia Management

• Mild hyperphosphatemia (<1.62 mmol/L): Can be treated with aluminum hydroxide at 50-100 mg/kg/day divided in 4 doses, administered orally or via nasogastric tube 1
• Severe hyperphosphatemia (>6 mg/dL): May require dialysis 1

Hypocalcemia Management

• Asymptomatic hypocalcemia: Does not require treatment 1
• Symptomatic hypocalcemia (tetany, seizures): Administer calcium gluconate 50-100 mg/kg as a single dose, cautiously repeating if necessary 1

Renal Replacement Therapy Indications

Dialysis should be initiated for any of the following conditions:

• Persistent hyperkalemia unresponsive to medical management 1
• Severe metabolic acidosis 1
• Volume overload unresponsive to diuretic therapy 1
• Overt uremic symptoms (pericarditis, severe encephalopathy) 1
• Severe, progressive hyperphosphatemia (>6 mg/dL) 1
• Severe symptomatic hypocalcemia 1

Types of Renal Replacement Therapy

• Intermittent Hemodialysis (IHD): Effectively removes uric acid (clearance 70-100 mL/min) with plasma uric acid levels falling by about 50% with each 6-hour treatment 1
• Continuous Renal Replacement Therapies (CRRT): Preferred for hemodynamically unstable patients and provides better control of fluid overload and azotemia 1
• Peritoneal Dialysis (PD): Seldom used due to lower efficiency in removing solutes and fluid compared to IHD and CRRT 1

Frequency of Dialysis

• Frequent (daily) dialysis is recommended due to the continuous release of purine products, potassium, and other metabolites from lysed tumor cells 1
• The timing and intensity of dialysis should be linked to the purine generation rate 1

Monitoring Approach

• High-risk patients: Monitor LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, and calcium every 12 hours for the first three days, then every 24 hours 1
• Patients with established TLS: Monitor vital parameters, serum uric acid, electrolytes, and renal function every 6 hours for the first 24 hours, then daily 1

Common Pitfalls and Caveats

• Avoid urine alkalinization in patients receiving rasburicase therapy as it provides no additional benefit 1
• Calcium supplementation in asymptomatic hypocalcemia may lead to increased tissue and renal precipitation of calcium phosphate 1
• Delayed recognition and treatment of TLS can lead to acute kidney injury, cardiac arrhythmias, seizures, and death 2
• Patients with pre-existing renal dysfunction, advanced age, and comorbidities (diabetes, cardiovascular disease) are at higher risk for acute renal failure and should be monitored more closely 1