What is the appropriate workup and monitoring plan for a patient with suspected tumor lysis syndrome?

Tumor Lysis Syndrome Workup

For patients with suspected tumor lysis syndrome, immediately obtain a comprehensive metabolic panel including uric acid, potassium, phosphorus, calcium, creatinine, BUN, and LDH, then monitor these parameters every 6 hours for the first 24 hours, transitioning to daily monitoring thereafter, while simultaneously assessing vital signs and urine output every 6 hours during the critical first day. 1

Initial Laboratory Assessment

Obtain baseline measurements of the following parameters before initiating any therapy:

• Metabolic markers: Uric acid, potassium, phosphorus, calcium, sodium 1
• Renal function: Creatinine, BUN, creatinine clearance or estimated GFR 1
• Cellular breakdown markers: LDH, complete blood count 1
• Additional parameters: Albumin, serum osmolality 1
• Imaging: Renal ultrasound in all patients scheduled for chemotherapy to assess for obstruction 1

The European Hematology Association consensus emphasizes that no formal studies have validated optimal monitoring intervals, so these recommendations derive from expert clinical practice principles rather than randomized evidence. 1

Risk-Stratified Monitoring Protocols

High-Risk Patients (Not Yet With TLS)

Monitor every 12 hours for the first 3 days, then every 24 hours:

• LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, calcium 1

High-risk features include pre-existing renal impairment, dehydration, obstructive uropathy, hyperuricemia (>8 mg/dL in children, >10 mg/dL in adults), bulky disease, high-grade lymphomas (Burkitt's, T-cell lymphoblastic NHL), adult ALL, LDH >2× upper normal limit, or intensive polychemotherapy. 1

Patients With Established TLS

Monitor every 6 hours for the first 24 hours, then daily:

• Vital parameters: Heart rate, blood pressure, urine output, respiratory rate 1
• Metabolic parameters: Serum uric acid, potassium, phosphorus, calcium 1
• Renal function: Serum creatinine, BUN, urine pH, urine osmolality, urine specific gravity 1

Monitor every 24 hours:

• Blood cell count, serum LDH, albumin, serum osmolality, blood gases and acid-base status, electrocardiogram, body weight 1

The rationale for intensive 6-hour monitoring in the first 24 hours is that TLS represents an ongoing process of cell breakdown with unpredictable and potentially rapid electrolyte rises that can precipitate life-threatening arrhythmias or seizures. 2

Critical Monitoring Considerations

Urine Output Surveillance

Target urine output of ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg). 1

• Measure urine osmolality and fractional excretion of sodium to assess hydration status 1
• Maintain urine specific gravity at 1.010 3
• Check hemodynamic status before administering loop diuretics 1
• Avoid diuretics in patients with obstructive uropathy or hypovolemia 1

Electrocardiogram Monitoring

Perform continuous ECG monitoring in all hyperkalemic patients. 1

Hyperkalemia poses immediate risk of cardiac arrhythmias and sudden death, making ECG surveillance mandatory rather than optional. 1

Special Laboratory Handling for Rasburicase Patients

Place blood samples immediately on ice to prevent continued ex vivo enzymatic degradation by rasburicase, which falsely lowers measured uric acid levels. 3

This is a critical pitfall—failure to ice samples can lead to artificially low uric acid readings, causing clinicians to underestimate disease severity or prematurely discontinue therapy. 3

Renal Function Assessment

Use creatinine clearance or estimated GFR (via MDRD formula or Cockcroft-Gault equation) as surrogates for renal excretion function. 4

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend eGFR for assessing renal function in TLS patients. 4 Reliable renal function measurement is essential because renal impairment amplifies all metabolic complications of TLS. 4

Diagnostic Criteria Recognition

Laboratory TLS is defined by ≥2 of the following abnormalities:

• Uric acid increase >25% from baseline or ≥476 μmol/L (8 mg/dL) 4
• Potassium >6.0 mmol/L or 25% increase 4
• Phosphorus >1.45 mmol/L (4.5 mg/dL) or 25% increase 4
• Calcium <1.75 mmol/L (7 mg/dL) or 25% decrease 4

Clinical TLS is defined by laboratory TLS plus ≥1 of:

• Renal failure (creatinine ≥1.5× upper limit of normal) 4
• Cardiac arrhythmia or sudden death 4
• Seizure 4

The distinction between laboratory and clinical TLS is crucial because clinical TLS requires immediate aggressive intervention including potential dialysis, whereas laboratory TLS may be managed with intensified medical therapy alone. 4

Common Pitfalls to Avoid

Do not correct mild asymptomatic hypocalcemia with calcium gluconate—this increases tissue and renal precipitation of calcium phosphate. 1 Calcium should only be given for symptomatic hypocalcemia (tetany, seizures) at 50-100 mg/kg as a single cautious dose. 1

Do not alkalinize urine in patients receiving rasburicase—alkalinization increases calcium phosphate precipitation without improving biochemical abnormalities and has been progressively abandoned since rasburicase availability. 1

Do not delay nephrology consultation in high-risk patients—the threshold for initiating renal replacement therapy may be lower in TLS than other clinical situations because cell breakdown is ongoing and electrolyte rises cannot be predicted. 2 Early hemodialysis should be considered for oliguria, severe hyperkalemia (≥6 mmol/L), severe hyperphosphatemia, acidosis, or fluid overload unresponsive to diuretics. 1

Ensure facility has ready access to dialysis—high-risk patients should receive cytotoxic chemotherapy only in facilities with immediate dialysis capability and a pre-established nephrology treatment plan. 2