Tumor lysis syndrome: Difference between revisions

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==Background==
==Background==
*Associated w/ treatment of ALL, Burkitt lymphoma, NHL
*Typically occurs within 1 to 5 days of initiation of chemotherapy
**Rarely observed in solid tumros or without prior therapy
*Associated with treatment of acute [[leukemia]], Burkitt [[lymphoma]], NHL
*Rapid turnover of tumor cells (spontaneously or after Rx) leading to release of:
**Rarely observed in solid tumors or without prior therapy
*Rapid turnover of tumor cells (spontaneously or after treatment) leading to release of:
**Potassium
**Potassium
**Phosphate
**Phosphate
***Binds Ca > hypocalcemia
***Binds Ca causing [[hypocalcemia]]
**Uric acid (converted from nucleic acids)
**Uric acid (converted from nucleic acids)


==Risk Factors==
===Risk Factors===
#High cell proliferation rate
*High cell proliferation rate
#Large tumor burden (LDH) > 1500 IU/L, WBC ≥ 50 x 103 cells/L
*Large tumor burden (LDH) > 1500 IU/L, WBC ≥ 50 x 103 cells/L
#Extensive BM involvement
*Extensive BM involvement
#Tumor infiltration of the kidney
*Tumor infiltration of the kidney


==Cairo-Bishop Definition==
===Cairo-Bishop Definition<ref>Cairo MS and Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br. J. Haematol. 2004; 127(1):3–11.</ref>===
*Laboratory Tumor Lysis Syndrome
'''Laboratory Tumor Lysis Syndrome'''
**Abnormality in 2 or more of the following, occurring w/in 3d before or 7d after chemo:
*Abnormality in 2 or more of the following, occurring within 3d before or 7d after chemo:
#Uric acid ≥ 8 mg/dL or 25% increase from baseline
**Uric acid ≥ 8mg/dL or 25% increase from baseline
#Potassium ≥ 6mEq/L or 25% increase from baseline
**Potassium ≥ 6mEq/L or 25% increase from baseline
#Phosphate ≥ 4.5 mg/dL or 25% increase from baseline (≥ 6.5 for children)
**Phosphate ≥ 4.5mg/dL or 25% increase from baseline (≥ 6.5 for children)
#Calcium ≤ 7 mg/dL or 25% decrease from baseline
**Calcium ≤ 7mg/dL or 25% decrease from baseline
*Clinical Tumor Lysis Syndrome
'''Clinical Tumor Lysis Syndrome'''
**Laboratory tumor lysis syndrome plus 1 or more of the following:
*Laboratory tumor lysis syndrome plus 1 or more of the following:
#Cr > 1.5 times upper limit of age-adjusted reference range
**Creatinine > 1.5 times upper limit of age-adjusted reference range
#Cardiac dysrhythmia or sudden death
**Cardiac dysrhythmia or sudden death
#Seizure
**Seizure


==Clinical Features==
==Clinical Features==
#Hyperuricemia
*Hyperuricemia
##N/V, lethargy, renal failure
**[[Nausea/vomiting]], [[lethargy]], [[renal failure]]
#Hyperkalemia
*[[Hyperkalemia]]
##Most immediate life-threatening element (due to dysrrhythmias)
**Most immediate life-threatening element (due to [[dysrhythmias]])
#Hyperphosphatemia
*[[Hyperphosphatemia]]
##May combine w/ Ca to precipiate in renal tubules
**May combine with Ca to precipiate in renal tubules
#Hypocalcemia
*[[Hypocalcemia]]
##Anorexia, cramping, tetany, confusion, seizures, V-tach/torsades
**Anorexia, cramping, tetany, [[confusion]], [[seizures]], [[V-tach]]/[[torsades]]
#Acute renal failure
*[[Acute Renal Failure]]
##Most common cause of morbidity
**Most common cause of morbidity
##Usually results from uric acid precipitation within renal tubules
**Usually results from uric acid precipitation within renal tubules


==Work Up==
==Differential Diagnosis==
#CBC
{{Oncologic emergencies DDX}}
#Chemistry
#Calcium, phosphate
#Uric Acid
#LDH
#UA
#ECG
##HyperK, hypoCa
==Imaging==
*Avoid IV contrast


==Treatment==
==Evaluation==
#Agressive hydration
===Work Up===
##Goal urine output is 3L in 24hr
*CBC
*Chemistry
**Elevated Cr
*Calcium, phosphate
*Uric Acid
*LDH - >2-3 fold increase stratifies into higher TLS risk<ref>Held-Warmkessel J. Preventing & Managing Tumor Lysis Syndrome. Oncology Times: 25 April 2010 - Volume 32 - Issue 8 - pp 1-7</ref>
*[[Urinalysis]]
*[[ECG]]
**[[Hyperkalemia]], [[hypocalcemia]]
;Avoid IV contrast


===Hypocalcemia===
==Management==
*≤7 or 25% dec in baseline
Aggressive hydration - Goal urine output is 3L in 24hr
**Treat only if symptomatic (increased Ca leads to increased Ca/phos deposition)
**Calcium gluconate 50-200mg IV


===Hyperphosphatemia===
===[[Hypocalcemia]] Treatment===
*≥4.5 or 25% increase; ≥ 6.5mg/dL in children
*≤7 or 25% decrease in baseline
**Aluminum hydroxide (50-150mg/kg PO q4-6h)
**Treat only if symptomatic (increased Ca leads to increased Ca/phos deposition), such as widened QRS or ventricular arrhythmias
**Dialysis if refractory
**[[Calcium gluconate]] 50-200mg IV


===Hyperuricemia===
{{Hyperphosphatemia treatment}}
*Consider sevelamer 800-1600mg PO tid to avoid side effects of aluminum toxicity and hypercalcemia from aluminum hydroxide treatment
 
===Hyperuricemia Treatment===
*≥8 or 25% increase
*≥8 or 25% increase
**Allopurinol
**[[Allopurinol]]
***Acts slowly; only helpful for preventing future production of uric acid
***Acts slowly; only helpful for preventing future production of uric acid
***10mg/kg/d PO q8 OR 200-400 mg/m2 IV q12; renally dosed
***10mg/kg/d PO q8 '''OR''' 200-400mg/m2 IV q12; renally dosed
***Inhibition of xanthine oxidase can last 18-30h
***Inhibition of xanthine oxidase can last 18-30h
**Urate Oxidase Rx
**Urate Oxidase
***Rasburicase 0.05-0.2mg/kg IV)
***[[Rasburicase]] 0.05-0.2mg/kg IV
***Can be used for BOTH prevention and treatment
***Can be used for BOTH prevention and treatment
***Uric acid final product of purine metabolism
***Uric acid final product of purine metabolism
****Urate oxidase converts uric acid to allantoin (5-10x more soluble)
****Urate oxidase converts uric acid to allantoin (5-10x more soluble)


===Hyperkalemia===
===[[Hyperkalemia]] Treatment===
*Only give Ca for cardiovascular instability (e.g.ventricular arrhythmias, widened QRS)
*Only give Ca for cardiovascular instability (e.g.ventricular arrhythmias, widened QRS)
**Giving Ca leads to increased Ca/phos deposition which leads to renal failure
**Giving Ca leads to increased Ca/phos deposition which leads to renal failure
*See [[Hyperkalemia]] for treatment options
*See [[Hyperkalemia]] for treatment options


===Dialysis (Criteria)===
===[[Dialysis]] Criteria===
#K >6
*Potassium >6
#Significant renal insufficiency
*Significant renal insufficiency (Creatinine >10)
#Uric Acid >10
*Uric Acid >10
#Symptomatic hypocalcemia
*Symptomatic [[hypocalcemia]]
#Serum phosphorus >10
*Serum phosphorus >10
*Volume overload


==Disposition==
==Disposition==
*Admit (often to ICU)
*Admit (often to ICU)


==Source==
==References==
*Tintinalli
<references/>
*EM Practice March '10


[[Category:Heme/Onc]]
[[Category:Heme/Onc]]

Latest revision as of 02:18, 19 March 2020

Background

  • Typically occurs within 1 to 5 days of initiation of chemotherapy
  • Associated with treatment of acute leukemia, Burkitt lymphoma, NHL
    • Rarely observed in solid tumors or without prior therapy
  • Rapid turnover of tumor cells (spontaneously or after treatment) leading to release of:
    • Potassium
    • Phosphate
    • Uric acid (converted from nucleic acids)

Risk Factors

  • High cell proliferation rate
  • Large tumor burden (LDH) > 1500 IU/L, WBC ≥ 50 x 103 cells/L
  • Extensive BM involvement
  • Tumor infiltration of the kidney

Cairo-Bishop Definition[1]

Laboratory Tumor Lysis Syndrome

  • Abnormality in 2 or more of the following, occurring within 3d before or 7d after chemo:
    • Uric acid ≥ 8mg/dL or 25% increase from baseline
    • Potassium ≥ 6mEq/L or 25% increase from baseline
    • Phosphate ≥ 4.5mg/dL or 25% increase from baseline (≥ 6.5 for children)
    • Calcium ≤ 7mg/dL or 25% decrease from baseline

Clinical Tumor Lysis Syndrome

  • Laboratory tumor lysis syndrome plus 1 or more of the following:
    • Creatinine > 1.5 times upper limit of age-adjusted reference range
    • Cardiac dysrhythmia or sudden death
    • Seizure

Clinical Features

Differential Diagnosis

Oncologic Emergencies

Related to Local Tumor Effects

Related to Biochemical Derangement

Related to Hematologic Derangement

Related to Therapy

Evaluation

Work Up

Avoid IV contrast

Management

Aggressive hydration - Goal urine output is 3L in 24hr

Hypocalcemia Treatment

  • ≤7 or 25% decrease in baseline
    • Treat only if symptomatic (increased Ca leads to increased Ca/phos deposition), such as widened QRS or ventricular arrhythmias
    • Calcium gluconate 50-200mg IV

Hyperphosphatemia treatment

  • Treat the underlying cause
  • Restrict calcium phosphate intake
  • IV Normal Saline (if normal renal fx)
  • Acetazolamide (500mg IV q6hr) - if normal renal function
  • Phosphate Binder - Aluminum hydroxide (50-150mg/kg PO q4-6h) - limited effect
  • Dialysis if refractory
  • Consider sevelamer 800-1600mg PO tid to avoid side effects of aluminum toxicity and hypercalcemia from aluminum hydroxide treatment

Hyperuricemia Treatment

  • ≥8 or 25% increase
    • Allopurinol
      • Acts slowly; only helpful for preventing future production of uric acid
      • 10mg/kg/d PO q8 OR 200-400mg/m2 IV q12; renally dosed
      • Inhibition of xanthine oxidase can last 18-30h
    • Urate Oxidase
      • Rasburicase 0.05-0.2mg/kg IV
      • Can be used for BOTH prevention and treatment
      • Uric acid final product of purine metabolism
        • Urate oxidase converts uric acid to allantoin (5-10x more soluble)

Hyperkalemia Treatment

  • Only give Ca for cardiovascular instability (e.g.ventricular arrhythmias, widened QRS)
    • Giving Ca leads to increased Ca/phos deposition which leads to renal failure
  • See Hyperkalemia for treatment options

Dialysis Criteria

  • Potassium >6
  • Significant renal insufficiency (Creatinine >10)
  • Uric Acid >10
  • Symptomatic hypocalcemia
  • Serum phosphorus >10
  • Volume overload

Disposition

  • Admit (often to ICU)

References

  1. Cairo MS and Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br. J. Haematol. 2004; 127(1):3–11.
  2. Held-Warmkessel J. Preventing & Managing Tumor Lysis Syndrome. Oncology Times: 25 April 2010 - Volume 32 - Issue 8 - pp 1-7