Tumor lysis syndrome (TLS) is a life-threatening oncological emergency that occurs when large numbers of tumor cells lyse (break down), releasing their intracellular contents (potassium, phosphate, nucleic acids) into the bloodstream. This metabolic overload can lead to severe electrolyte imbalances and acute kidney injury (AKI).

1. Rapid Clinical Assessment

ABCD Approach:

Airway:

Ensure airway patency, especially in cases of altered mental status or significant metabolic derangements leading to respiratory distress.

Breathing:

Monitor for signs of respiratory compromise due to metabolic acidosis or hyperkalemia, which can lead to respiratory muscle weakness.

Circulation:

Assess for signs of arrhythmia, hypotension, or tachycardia, as severe electrolyte imbalances (e.g., hyperkalemia, hypocalcemia) can lead to life-threatening cardiac arrhythmias.

Disability:

Monitor neurological status, as seizures, confusion, and weakness can result from severe metabolic disturbances (e.g., hyperphosphatemia, hypocalcemia).

Identify Key Presentations:

A. Symptoms of Electrolyte Imbalance:

Hyperkalemia:

Muscle weakness, paresthesia, palpitations, and life-threatening arrhythmias.

Hyperphosphatemia:

May lead to hypocalcemia due to calcium-phosphate precipitation, causing tetany, seizures, and muscle cramps.

Hypocalcemia:

Muscle cramps, Chvostek's or Trousseau's sign, seizures, and prolonged QT interval on ECG.

Hyperuricemia:

Can lead to acute kidney injury due to uric acid crystal precipitation in the renal tubules, causing oliguria, hematuria, or flank pain.

B. Acute Kidney Injury (AKI):

Decreased urine output, rising creatinine, and symptoms of uremia (e.g., nausea, vomiting, confusion).

C. Cardiac Symptoms:

Palpitations, arrhythmias (e.g., peaked T waves or wide QRS complexes in hyperkalemia), and cardiac arrest.

D. General Symptoms:

Fatigue, weakness, muscle cramps, and mental status changes due to metabolic imbalances.

High-Risk Populations:

i. Patients with Hematologic Malignancies:

Particularly those with rapidly proliferating tumors (e.g., acute leukemias, Burkitt lymphoma).

ii. Patients Receiving Chemotherapy:

TLS commonly occurs after the initiation of chemotherapy but can also occur spontaneously.

iii. Patients with High Tumor Burden:

Large tumors, elevated baseline white blood cell (WBC) counts, or preexisting renal dysfunction increase the risk of TLS.

iv. Dehydrated Patients:

Poor fluid intake or preexisting dehydration increases the risk of acute kidney injury in TLS.

2. Key Investigations

Laboratory Tests:

Complete Metabolic Panel (CMP):

Hyperkalemia: Potassium >5.5 mmol/L.
Hyperphosphatemia: Phosphate >1.6 mmol/L.
Hypocalcemia: Calcium <2.1 mmol/L.
Elevated Uric Acid: Uric acid >8 mg/dL (hyperuricemia).
Elevated Creatinine: Reflecting acute kidney injury (AKI).
Blood Gas Analysis:
- Metabolic Acidosis: Low serum bicarbonate and decreased pH may be seen in severe TLS
Urinalysis:
- Hematuria and Uric Acid Crystals: Suggests uric acid nephropathy or acute kidney injury.

Electrocardiogram (ECG):

Hyperkalemia Findings:
- Peaked T waves,
- Widened QRS complex,
- Arrhythmias (e.g., ventricular fibrillation).
Hypocalcemia Findings:
- Prolonged QT interval
- Torsades de pointes in severe cases.

Imaging:

Renal Ultrasound:

May be used to assess for obstructive nephropathy or signs of uric acid crystal deposition in the kidneys, although imaging is often not required unless there is concern for structural renal damage.

3. Management

A. Stabilize the Patient

Airway and Breathing:

Monitor oxygenation and ventilation, especially if the patient has altered mental status or is experiencing respiratory muscle weakness from electrolyte disturbances (e.g., hyperkalemia, hypocalcemia).

Circulation:

IV Access: Ensure two large-bore intravenous lines or central venous access for rapid fluid administration and medication delivery.

Cardiac Monitoring: Continuous ECG monitoring for early detection of life-threatening arrhythmias.

IV Fluids:

Aggressive Hydration: Start with normal saline at 2-3 L/m²/day to promote diuresis and prevent uric acid or calcium phosphate crystal formation in the kidneys.
Goal Urine Output: Target a urine output of 80-100 mL/hour.

B. Specific Treatment of Metabolic Abnormalities

Hyperkalemia:

i. Calcium Gluconate (IV):

To stabilize the cardiac membrane and prevent arrhythmias.

ii. Insulin and Glucose:

Insulin (10 units IV) and dextrose (25 g) to drive potassium back into cells.

iii. Sodium Bicarbonate (IV):

To correct acidosis and shift potassium intracellularly.

iv. Loop Diuretics:

Furosemide to enhance renal potassium excretion, if the patient is not hypovolemic.

v. Potassium Binding Resins:

Such as sodium polystyrene sulfonate (Kayexalate), although these work slowly.

Hyperphosphatemia and Hypocalcemia:

i. Phosphate Binders:

Sevelamer or calcium acetate to reduce phosphate absorption in the gut.

ii. Calcium Gluconate (IV):

Administer for symptomatic hypocalcemia (e.g., tetany, seizures), though caution is advised because increasing calcium levels can worsen calcium phosphate precipitation in tissues.

iii. Dialysis:

For severe hyperphosphatemia and refractory hypocalcemia if medical management fails.

Hyperuricemia:

i. Allopurinol:

To reduce the production of uric acid. Typically started 1-2 days before chemotherapy in high-risk patients.

ii. Rasburicase:

- A recombinant urate oxidase enzyme that converts uric acid to allantoin, which is more easily excreted.

- It is used for patients with high baseline uric acid levels or those who develop hyperuricemia despite allopurinol.

Acute Kidney Injury:

i. Diuretics (e.g., Furosemide):

To maintain high urine output and help clear electrolytes if the patient is well-hydrated and not hypotensive.

ii. Dialysis:

For patients with refractory hyperkalemia, severe hyperphosphatemia, or worsening kidney function despite aggressive medical management.

C. Supportive Care

i. Pain and Nausea Management:

Provide analgesics for pain and antiemetics for nausea, which are common in patients undergoing chemotherapy and experiencing TLS.

ii. Monitor Fluid Status and Electrolytes:

Continuous monitoring of serum electrolytes, creatinine, and urine output is critical for guiding treatment decisions.

5. Disposition

Admission Criteria:

i. TLS Diagnosis:

Requires immediate hospitalization for aggressive fluid resuscitation, electrolyte correction, and monitoring.

ii. Severe Hyperkalemia, Hypocalcemia, or Acute Kidney Injury:

Patients with significant electrolyte abnormalities or renal failure need close monitoring in an intensive care unit (ICU).

iii. Refractory Electrolyte Imbalances or Need for Dialysis:

Patients who fail medical management require ICU admission and potential renal replacement therapy (e.g., hemodialysis).

5. Special Considerations

Children:

i. Higher Risk with Certain Tumors:

- Children with aggressive cancers such as Burkitt lymphoma, ALL, and high-grade lymphomas are at high risk for TLS.

- Treatment protocols should include prophylactic hydration and allopurinol before starting chemotherapy.

ii. Dosing Adjustments:

Pediatric patients require careful weight-based dosing for fluids, medications, and electrolyte replacement.

Elderly:

i. Preexisting Renal Dysfunction:

- Elderly patients often have baseline kidney impairment, increasing their risk of TLS and acute kidney injury.

- Close monitoring and dose adjustments for medications, such as rasburicase and allopurinol, are necessary.

ii. Concurrent Comorbidities:

- Cardiovascular conditions, diabetes, and other age-related comorbidities can complicate management.

- Aggressive fluid resuscitation must be carefully balanced with the risk of fluid overload.

References:

1. Howard, S. C., Jones, D. P., & Pui, C. H. (2011). The tumor lysis syndrome. New England Journal of Medicine, 364(19), 1844–1854.

2. Cairo, M. S., & Bishop, M. (2004). Tumor lysis syndrome: New therapeutic strategies and classification. British Journal of Haematology, 127(1), 3–11.

3. Coiffier, B., Altman, A., Pui, C. H., Younes, A., & Cairo, M. S. (2008). Guidelines for the management of pediatric and adult tumor lysis syndrome: An evidence-based review. Journal of Clinical Oncology, 26(16), 2767–2778.