Tumor Lysis Syndrome

Definition

Potentially fatal metabolic complication

that occurs in some patients with
cancer
Can result in potentially life
threatening metabolic and electrolyte
abnormalities

Pathophysiology

Involves a complex series of events

related to the liberation of intracellular
contents from tumor cells and inability
of the kidneys to excrete and maintain
normal serum composition

Manifestations

Usually occurs within 24-48 hours

after initiation of chemotherapy and
may persist for 5-7 days post therapy
May occur as early as 6 hours post
chemotherapy administration

Tumor Types

Non-Hodgkins lymphoma
Burkitts
High grade T-cell

Acute Leukemias
Acute Promyelocytic leukemia
Acute lymphoblastic leukemia

Chronic Lymphoblastic leukemia

Solid tumors
Small cell lung cancer
Breast cancer

Symptoms

Cardiac:
Presence of S3
Bradycardia
Heart Block
Cardiac Arrest

Symptoms

Neuromuscular:
Weakness
Lethargy
Cramping
Tetany
Chvosteks sign
Trousseaus sign
Convulsions

Symptoms

Renal:
Oliguria
Renal Insufficiency
Flank pain
Weight gain
Edema
Renal failure

Symptoms

Gastrointestinal:
Nausea
Vomiting
Diarrhea
Constipation

Hyperuricemia

Results from tumor cell destruction

Most common signs and symptoms:
Nausea and vomiting
Azotemia
Oliguria
Anuria
Decreased urine pH
Uric acid crystals found in urinalysis

Hyperkalemia

Results from rapid destruction of cells

Most common signs and symptoms
EKG changes
Peaked t waves
Flat p waves
Wide QRS complexes
Bradycardia
Ventricular tachycardia
Ventricular fibrillation
Asystole
Pulseless electrical activity

Hyperkalemia

Results from rapid destruction of cells

Most common signs and symptoms
Weakness
Twitching
Increased bowel sounds
Nausea
Diarrhea

Hyperphosphatemia

Most common signs and symptoms

Hypocalcemia
Renal failure
Azotemia
Ologuria
Anuria

Hypertension
Edema

Hypocalcemia

Results from hyperphosphatemia and

the inverse relationship between
calcium and phosphorous
Most common signs and symptoms
EKG changes
Prolonged QT
Inverted T waves
Ventricular dysrhythmias
Heart block
Cardiac arrest

Hypocalcemia

Neuromuscular signs and symptoms

Tetany
Twitching
Paresthesias
Seizures

GI Symptoms
Diarrhea

Diagnostic Tests

Chvostek
Tapping the cheek below the temple
where the facial nerve emerges

Diagnostic Tests

Trousseau Sign
Occluding the arterial blood flow in the
arm with the blood pressure cuff for one
to five minutes, if the thumb adducts and
the phalangeal joints extend the test is
positive

Prevention

Identify patients at risk

Monitor for all electrolyte abnormalities
Administer allopurinol,
Decrease uric acid levels by interfering with purine
metabolism through the inhibition of the enzyme xanthine
oxidase that is essential for the conversion of nucleic acids to
uric acid

Alkalinization of the urine

Prevent as much as possible renal damage

Sodium bicarbonate solution

Decreases the risk of renal obstruction, however urinary
alkalinization should be used cautiously because of risk of
precipitation in the kidneys of calcium-phosphorous binding
and the risk of hypocalcemic induced neuromuscular
irritability

Prevention

Rasburicase- recombinant urate oxidase Reduces the uric acid pool

Reduces existing uric acid
Prevents the accumulation of xanthines and
hypoxanthine
Does not require alkalinization
Facilitates phosphorous excretion
Dosing:
IV over 30 minutes
0.2 mg/kg IV QD or BID

Management

Hydration
3 Liters daily
Aggressive hydration starting 1-2 days
prior to chemotherapy and continuing for
a few days post chemotherapy

Management

Diuretics:
Furosemide

Renal dose Dopamine- 2-4 mcg/kg

Prevents:
Fluid overload
Electrolyte imbalance
Complications of uric acid buildup

Management

Hyperkalemia
Kayexalate with sorbitol
PO
Rectal

Calcium Gluconate
Sodium bicarbonate
Hypertonic dextrose and regular insulin
Albuterol (Ventolin) or another beta stimulant

Management

Dialysis: Hemodialysis/CVVH/CRRT( Requires

ICU Care)
Used for patients unresponsive to preventive
measures and electrolyte corrections
Used to remove uric acid
Used in patients with:

Serum potassium >6 mEq/L

Uric acid >10 mg/dl
Phosphorous > 10 mg/dl
Symptomatic hypocalcemia
Presence of volume overload

Medication Management

Avoid nephrotoxic medications

Avoid agents which block tubular
reabsorption of uric acid
Aspirin
Probencid
Thiazide diuretics
Radiographic contrast containing iodine

References

Jeha,S., Pui, C. Recombinant Urate

Oxidase (Rasburicase) in the
Prophylaxis and Treatment of Tumor
Lysis Syndrome, Ronco,R.
Rodeghiero, F. (eds) Hyperuricemic
Syndrome: Pathophysiology and
Therapy, Contrib Nephrol,
Basel,Karger,2005,Vol 147,pp69-79