Definition:

  • Tumor Lysis Syndrome (TLS) is an oncologic emergency due to massive tumor cell lysis, characterized by metabolic abnormalities that can lead to renal failure, seizures, and dysrhythmia.

Etiology:

  • Occurs after the initiation of chemotherapy in patients whose cancers have a high proliferative rate (leukemias, lymphomas)
  • Cell lysis leads to hyperkalemia, hyperphosphatemia, hyperuricemia
    • Rapid cell turnover in malignant cells leads to upregulation of DNA synthesis
      • Uric acid is a breakdown product of the purines in DNA
  • Secondary hypocalcemia develops from the precipitation of calcium with phosphate

image from EM Clinics

Epidemiology:

  • TLS as been documented in virtually all cancer subtypes
  • Hematologic malignancies carry the greatest risk, as these are defined by large, rapidly-growing, chemosensitive cells 
  • There has been an increase in case reports documenting TLS in solid tumor malignancy, thought to be due to increased efficacy of treatment (Howard CS et al.)

Complications:

  • Clinical manifestations largely secondary to metabolic abnormalities leading to nausea, vomiting, diarrhea, muscle cramps, tetany, or syncope
  • Uric acid and calcium phosphate deposits in the renal tubules, leading to acute uric acid nephropathy and subsequent acute kidney injury
  • Seizures and dysrhythmias can occur secondary to metabolic derangements

Differential Diagnosis:

  • Nonspecific symptoms of fatigue, myalgia, nausea, vomiting in an immunocompromised patient warrant workup for an infectious source 
  • Malignancy-associated hypercalcemia can lead to myalgias, abdominal pain, altered mental status, and ECG changes 
  • Initial presentation with dysrhythmia warrants consideration for acute coronary syndrome, pulmonary embolism, and other causes of metabolic derangements
  • Seizures may be due to CNS infection, metastasis, other cancer related metabolic abnormalities, and cerebrovascular disease

History:

  • Key component of history is recent induction of cytotoxic therapy (although spontaneous TLS can be seen outside of therapeutic schedule as well)
  • Assess for signs of seizure, dysrhythmia, or urinary obstruction

Physical Exam:

  • Patients will generally appear unwell
  • Cytotoxic chemokines released from malignant cells can produce a similar picture to sepsis: hypotension, tachycardia, altered mental status 
  • Patients undergoing chemo may have a port-site that can be a helpful clue in an undifferentiated, altered patient

Diagnostic Testing:

  • Measurement of serum potassium, phosphate, calcium, BUN, creatinine, uric acid, and lactate dehydrogenase 
  • Evaluation for infectious source: CBC, UA, urine and blood cultures, chest x-ray
  • ECG may demonstrate signs of hyperkalemia such as T-wave peaks, P-wave flattening, QRS interval prolongation
    • Hypocalcemia can present as QT interval prolongation on ECG
  • Renal ultrasound can be used to assess for obstructive nephropathy

ED Management:

  • If possible, consult patient’s hematology-oncologist and/ or your institution’s hematology-oncology service
  • IV fluid resuscitation is the mainstay of treatment for TLS
    • Most sources agree on a target fluid intake of 3L per day (Howard SC et al)
    • In patients with hyponatremia or dehydration, normal saline is suggested
    • In all other patients, D5 ¼ NS is acceptable (to limit sodium retention)
  • Allopurinol inhibits the conversion of xanthine to uric acid (see image below from Cairo-Bishop)
    • Decreases generation of uric acid but will not improve existing hyperuricemia
    • Xanthine precursor is also a poorly soluble crystal and can deposit in renal tubules
    • Allopurinol dosing:
      • PO 100 mg/m2 q8 hours (maximum of 800 mg per day) 
      • IV 200-400 mg/m2 q8-24 hours (maximum 600 mg per day)
      • The dose must be adjusted in the setting of renal insufficiency or when the patient is also receiving thiopurine medications
  • Rasburicase catalyzes the conversion of uric acid to a more soluble molecule allantoin (see image below from Cairo-Bishop)
    • Some studies have found rasburicase to be superior to allopurinol in achieving lower uric acid levels, but rates of kidney failure did not differ between groups (Coretes et al)
    • Rasburicase is prohibitively expensive and can lead to devastating hemolytic anemia in G6PD deficiency patients
    • Rasburicase is dosed at 0.05-0.2 mg/kg IV daily for 5-7 days
  • It is generally not recommended to supply calcium to these patients, as this can increase the calcium x phosphate product and lead to further renal deposition and damage (Wilson FP et al)

Cairo-Bishop Classification of TLS

Disposition:

  • For laboratory tumor lysis syndrome, most sources agree that patients can be admitted to a ward bed with telemetry 
  • For clinical tumor lysis syndrome (nephropathy, dysrhythmia, seizures), sources agree on ICU placement
  • Note: MDAnderson has a comprehensive “cheat sheet” to TLS that can be found here

References

  • Ron M. Walls et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice. Philadelphia, PA: Elsevier/Saunders. 
  • Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol 2004; 127:3. PMID 15384972
  • DeConti RC, Calabresi P. Use of allopurinol for prevention and control of hyperuricemia in patients with neoplastic disease. N Engl J Med 1966; 274:481. PMID 5904287
  • Dubbs, Sarah. Rapid Fire: Tumor Lysis Syndrome. Emerg Med Clin N Am 36 (2018) 517-525.  https://doi.org/10.1016/j.emc.2018.04.003
  • Coiffier B, Altman A, Pui CH, et al. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol 2008; 26:2767. PMID 18509186
  • Howard SC, Jones DP, Pui CH. The tumor lysis syndrome. N Engl J Med 2011; 364:1844. PMID 21561350Wilson FP, Berns JS. Tumor Lysis Syndrome: New Challenges and Recent Advances. Adv Chronic Kidny Dis 2014 Jan;21(1): 18-26. PMID: 24359983
  • Neerumlla R, Tumor Lysis Syndrome.  Retrieved 11/14/19.  https://www.medindia.net/patientinfo/tumor-lysis-syndrome.htm