Tumor lysis syndrome (TLS) is a serious and often life-threatening emergency condition that occurs when tumor cells die and release their contents into the bloodstream. It can occur without provocation, but usually occurs due to chemotherapy or radiation, which leads to the massive destruction of tumor cells. As the cells lyse (break apart), phosphorus, potassium and nucleic acids are released into systemic circulation. This is problematic for multiple reasons:
- Hyperphosphatemia – Recall that phosphorus and calcium have an inverse relationship, so while elevated phosphorus levels aren’t good for your patient, it’s the resulting hypocalcemia that is significantly dangerous.
- Hypocalcemia – Low calcium levels can lead to cardiac dysfunction, seizure, tetany and death.
- Hyperkalemia – High potassium levels can lead to cardiac dysfunction and cardiac arrest.
- Hyperuricemia – Catabolism of the nucleic acids that are released leads to hyperuricemia, which we’ll discuss further when we dive into pathophysiology.
Who is at risk for tumor lysis syndrome?
The patients who are at most risk for TLS are those with leukemia and a very elevated white blood cell count, those with lymphoma that is being aggressively treated with chemotherapy, and those with neuroblastoma or hepatoblastoma. A study that analyzed data from the National Inpatient Sample found that 30% of cases were associated with non-Hodgkin lymphoma, while 20% were associated with solid tumors, and 19% associated with AML. Some cancers that are lower risk for TLS are multiple myeloma, solid cancers, chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL).
Though not common, TLS can be associated with certain medications. These include steroids, monoclonal antibodies and biologic immunomodulators.
The pathophysiology of tumor lysis syndrome
In the most basic terms, the main causes of death in TLS are cardiac arrest and renal failure. The pathophysiology is actually quite complex, so we’ll hone in on the basics.
In a healthy individual, excess uric acid is transformed into a soluble substance the kidneys can easily excrete. With the rapid influx of uric acid produced by tumor lysis syndrome, the uric acid builds up and crystallizes in the renal tubules causing obstruction and acute kidney injury. The uric acid also leads to vasoconstriction in the kidney, which further exacerbates the injury and leads to tissue ischemia. Additionally, the uric acid causes the release of tumor necrosis factor which attracts white blood cells and leads to further renal injury. When the TLS is directly associated with cancer therapy, elevated uric acid levels occur 48-72 hours after the initiation of therapy.
Hyperphosphatemia – As tumor cells break down, they release phosphorus into the bloodstream. In a healthy individual, excess phosphorus is excreted by the kidneys. However, our patient has acute kidney injury from elevated uric acid, so the body is unable to manage this high level of phosphorus. The key reason we are concerned about hyperphosphatemia is because of the inverse relationship between phosphorus and calcium. The signs of hyperphosphatemia are going to be associated with hypocalcemia. You will typically see hyperphosphatemia (and the concurrent hypocalcemia) about 24 to 48 hours after treatment initiation.
Hypocalcemia – Low calcium levels in TLS are almost always due to a concurrent hyperphosphatemia, and is certainly the more dangerous of the two imbalances. As the excess phosphorus enters the bloodstream, calcium ions bind to the phosphorus, which creates calcium-phosphate salts. The resulting hypocalcemia can cause seizure, tetany, severe cardiac dysrhythmias, and even death.
Hyperkalemia – As tumor cells lyse, they release significant amounts of potassium into the bloodstream. Because the kidneys aren’t functioning properly due to obstructive uropathy from high levels of uric acid, this limits the kidneys’ ability to excrete excess potassium. The biggest risk with hyperkalemia is cardiac arrest. You will typically see hyperkalemia occur approximately 6 to 72 hours after chemotherapy initiation.
Now that you have a general overview of tumor lysis syndrome, let’s go through it using the Straight A Nursing LATTE method.
L: How does the patient LOOK?
This element of the LATTE method dives into what you may notice and what the patient will state as their symptoms.
Signs and symptoms of hyperuricemia:
The signs and symptoms of hyperuricemia can be quite varied and include:
- Decreased urine output due to obstructive uropathy and acute kidney injury
- Pain in the joints and flank pain, which may be described as “colicky” pain
- Coarse lung sounds due to fluid volume overload, possible decreased O2 saturation with increased RR and WOB
- Metallic taste in the mouth
- Weakness and lethargy
- Nausea and vomiting
- Muffled heart tones if pericarditis occurs. The buildup of uric acid leads to the release of pro-inflammatory markers that ultimately damage the pericardium.
Signs and symptoms of electrolyte imbalance:
- Hyperphosphatemia: The signs and symptoms of hyperphosphatemia are typically due to the resulting hypocalcemia
- Hypocalcemia: Positive Chvostek’s sign, positive Trousseau’s sign, seizure, tetany, and possibly wheezing (which indicates bronchospasm)
- Hyperkalemia: The classic EKG sign you’ll see most often is tall and peaked T-waves. As the condition continues, the QRS will widen and P wave will have decreased amplitude. Eventually, and without treatment, the P wave flattens out and the QRS widens further. Asytole or ventricular fibrillation follows. Other signs of hyperkalemia are muscle cramping, weakness, diarrhea, nausea, vomiting, hyperactive bowel sounds, confusion, irritability, and numbness of the face/hands/feet.
A: How do you ASSESS the patient?
- Monitor I/O; monitor weight (these patients are at risk for hypervolemia)
- Assess for pain, especially flank pain
- Listen to lungs as the patient may have wheezing secondary to hypocalcemia or coarse lung sounds secondary to fluid overload
- Monitor RR, O2 saturation level and WOB
- Grade edema which may be present due to fluid overload
- Listen to heart, making note of muffled heart tones
- Monitor for EKG changes, which can occur with hypocalcemia and hyperkalemia
- Assess for presence of Chvostek’s and Trousseau’s signs (hypocalcemia)
- Assess patient for nausea, vomiting, diarrhea
- Obtain BP, patient may be hypotensive due to volume losses or cardiac dysfunction
T: What TESTS will be ordered?
- A BMP or CMP will be conducted and reveal abnormal levels of potassium, calcium, phosphorus and uric acid. Additionally, BUN and Cr will be elevated.
- ABG will show metabolic acidosis.
- If not already conducted, the patient will be on continuous ECG monitoring and may also get a 12-lead ECG as well.
T: What TREATMENTS will be provided?
Medical management of TLS will focus on preventing or addressing serious complications, maintaining adequate fluid balance, correcting electrolyte disturbances and managing excess uric acid levels.
- Fluids – 0.9% NaCl will likely be utilized if the patient’s condition shows a need for further hydration. This isotonic crystalloid will help dilute the high levels of potassium, phosphate and uric acid in the bloodstream.
- Diuresis – To promote ideal renal function, non-thiazide diuretics may be utilized.
- Hyperkalemia treatments – To decrease dangerously elevated potassium levels, medications can be given to either shift K back into the cellular space, or remove it from the body via the GI tract. Kayexalate will bind to excess potassium, which is then passed in the stool. Insulin + glucose are utilized together to move potassium into the intracellular space. Insulin will unlock the cell, glucose will enter and take potassium along. Albuterol is another medication that can causes a potassium shift into the cell.
- Calcium gluconate – Though given in cases of hyperkalemia, calcium gluconate does not affect potassium levels. It is administered because it will make the cardiac muscle less excitable, leading to lowered risk for dangerous dysrhythmias associated with hyperkalemia. It will also help correct hypocalcemia, but should be used carefully since the calcium level will improve as the hyperphosphatemia is addressed.
- Sodium bicarbonate – This increases urine pH, making uric acid more soluble and less likely to form harmful crystals.
- Allopurinol – This medication helps inhibit uric acid formation.
- Phosphorus binding antacids – This is used to bind up excess phosphorus with a goal of improving calcium levels. These antacids are constipating, so the patient may need a stool softener as well.
- Nasogastric tube – May be utilized if the patient has severe nausea/vomiting.
- Dietary changes – The patient may need to consume a diet low in potassium and phosphorus. The antacids may cause constipation, so the patient should be directed to consumer high-fiber foods.
- Seizure precautions if hypocalcemia is present.
E: How do you EDUCATE the patient and family?
Education for tumor lysis syndrome ideally occurs prior to the initiation of treatment. It is imperative that patients and families know what signs/symptoms to watch for. Early signs of TLS are fluid retention, weakness/lethargy, muscle cramps, paresthesia, nausea/vomiting and diarrhea. If the individual experiences any of these, they should seek emergency medical care immediately.
If the patient is hospitalized with TLS, explain all aspects of care, the need for continuous ECG monitoring, frequent labs, and dietary modifications.
- Tumor lysis syndrome is a medical emergency that ensues when tumor cells are destroyed by chemotherapy or radiation and spill excess potassium, phosphorus and nucleic acids into the bloodstream.
- This leads to hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia.
- The excess uric acid crystallizes in the kidneys leading to renal failure.
- Electrolyte imbalances (K and Ca) lead to significant cardiac dysfunction, seizures and death.
- Treatment is aimed at maintaining renal flow with hydration and diuretics.
- Hyperuricemia is treated with allopurinol and sodium bicarbonate.
- Electrolyte imbalances are addressed.
- The patient is monitored for complications – namely cardiac dysrhythmias, renal failure and seizure.
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