Bethesda Handbook of Clinical Oncology, 2nd Edition

Supportive Care


Oncologic Emergencies and Paraneoplastic Syndromes

Muhammad K. Siddique*

Richard A. Messmann

*Division of Hematology/Oncology, Department of Medicine, Michigan State University, East Lansing, Michigan

Great Lakes Cancer Institute, Lansing, Michigan


  • Spinal cord compression (SCC) is a true oncologic emergency.
  • Delay in evaluation and treatment can result in permanent bowel and bladder dysfunction or paralysis.
  • Most cord compression cases involve tumor or collapsed bone fragments in the epidural space, a few cases are subdural, and intramedullary metastases are very rare.
  • The thoracic spine is most often involved (60% to 70%), followed by the lumbosacral (20% to 30%) and cervical spine (10%) (1).

Etiology of Spinal Cord Compression

  • Metastatic tumors from primary breast, lung, and prostate cancer; lymphoma; multiple myeloma; renal and gastrointestinal tumors (1).
  • SCC, infrequently, is the first sign of cancer.

Clinical Signs and Symptoms of Spinal Cord Compression

  • Back or radicular pain
  • Muscle weakness
  • Acute or slowly evolving changes in bowel or bladder function
  • Sensory loss or autonomic dysfunction.

Any of these signs and symptoms should bring about the initiation of a prompt clinical evaluation for SCC (2,3).

A thorough physical and neurologic examination should be performed (4), including

  • gentle percussion of the spinal column
  • evaluation for motor or sensory weakness
  • passive neck flexion
  • straight-leg raising
  • rectal examination (to evaluate the sphincter tone)
  • pinprick testing from toe to head to establish whether a “sensory level” is present


A clinical suspicion of SCC should prompt the initiation of steroid therapy (see Treatment, in subsequent text) (5).


The choice of diagnostic imaging should be suggested by the results of the neurologic examination.

  • Magnetic resonance imaging (MRI) with gadolinium contrast is the standard for diagnosis because of its high sensitivity and specificity for detecting SCC (2,4,5). The entire neuraxis is readily imaged such that the superior and inferior extent of the compression can be used to target radiotherapy.

Some limitations include limited availability in some communities, inability of the patient to lie absolutely still and supine for 30 to 60 minutes of imaging, and issues that preclude MRI [e.g., history of metallic vertebral stabilization surgery, earlier pacemaker/automatic implantable cardioverter–defibrillator (AICD) placement, or presence of certain other implanted devices].

  • Computerized tomography (CT) scan of the spinal region combined with myelogram (CT-myelogram) provides an excellent assessment of the epidural space and surrounding soft tissue and is useful in diagnosis and therapy planning.

It is generally more available than MRI and is an acceptable imaging modality when MRI is not possible.

Technical limitations include the need for lumbar puncture to administer radiocontrast, as well as a requirement that the ordering physician identifies the expected spinal region to be imaged. The procedure is impractical for the entire neuraxis and may require supplemental studies to exclude a more superior level of compression.

  • Conventional radiographs are readily obtained and are inexpensive. Radiographs exploit the finding that almost all SCC begins as vertebral bone metastases that lead to subsequent fracture and cord compression by the bone and tumor. The value of conventional radiographs is limited to verifying a diagnostic impression of SCC, assessing surgical options, and evaluating spinal stability. Radiographs do not exclude the diagnosis of SCC even if they are “normal” and are insufficient to plan radiotherapy.

Diagnosis of Spinal Cord Compression

Symptomatic patients with abnormal neurologic examination:

  • Receive steroid therapy at once, as detailed in subsequent text.
  • Conventional radiographs detect abnormalities in most patients with SCC, which aids prompt confirmation of the diagnosis.
  • MRI is then done to define the proximal and distal extent of the compression to facilitate the therapeutic plan.

Symptomatic patients with normal neurologic examination:

  • Conventional radiographs of the spine should be followed by MRI if the conventional radiograph is abnormal (as for the patients with abnormal neurologic examination) or if clinical progression occurs or if the symptoms fail to resolve. It should be noted that a very small percentage of intradural tumor metastasis will be visible only in MRI.
  • In addition, any abnormal findings should prompt initiation of steroid therapy. Myelography (often assisted by simultaneous CT scan) may be useful if an MRI is not available.

Treatment of Spinal Cord Compression

The goals of treatment for SCC include pain control, recovery of normal neurologic function, local tumor control, and avoidance of complications.



  • Once SCC is suspected, administer steroids as follows:

Begin treatment with a “loading” dose of dexamethasone, 10 mg by i.v. infusion.

Six hours after the loading dose, and every 6 hours thereafter, administer dexamethasone, 4 mg by i.v. infusion (5,6).

An alternative treatment strategy includes an initial bolus dose of dexamethasone, 100 mg by i.v. infusion, followed 6 hours later by dexamethasone, 4 mg by i.v. infusion every 6 hours; however, this regimen is associated with additional toxicities related to high-dose steroid administration (7) and no improvement has been seen compared to low-dose therapy with respect to pain, ambulation, and bladder function (8).

  • Surgical and radiation oncology consultation(s) are required immediately after diagnosis, and further therapy is decided on the basis of the clinical signs and symptoms, availability of histologic diagnosis, spinal stability, and previous treatments. All symptomatic patients with SCC should be considered for decompression radical resection of metastatic tumor within 24 hours of onset of symptoms, regardless of spinal stability.

In symptomatic patients with SCC caused by metastatic tumors other than lymphoma, initial debulking surgery followed by radiation results in a four times longer duration of maintained ambulation after treatment, and a three times higher chance of regaining ambulation for nonambulatory patients, than that with radiation alone. In addition, patients who receive combined-modality therapy achieve superior pain control and bladder continence. Patients treated with radiation therapy alone require more steroids and narcotics and are less likely to maintain continence (9).

Patients with spinal instability even in the absence of clinical signs and symptoms should undergo surgery unless otherwise contraindicated.

Additional surgical candidates include patients with relapsed compression at a site of earlier irradiation and patients with progression of deficits during radiation therapy.

  • Radiotherapy is used to treat radiosensitive tumors in asymptomatic individuals and in those individuals who are symptomatic but are poor surgical candidates.

Radiosensitive tumors include breast and prostate tumors, lymphoma, multiple myeloma, and neuroblastoma.

Radiotherapy candidates may also include patients with multiple areas of compression.

Standard radiation doses range from 2,500 to 4,000 cGy delivered in 10 to 20 fractions.

  • Select patients with chemosensitive tumors may benefit from chemotherapy in addition to either radiation or surgical intervention (6,10).
  • Chemotherapy may be an appropriate first-line therapy for patients with chemosensitive tumors (i.e., lymphoma, myeloma, germ cell tumors, and breast and prostate cancer) and in individuals who are not candidates for radiation or surgery. The reader is directed to a number of references for specific details (2,11,12,13,14,15,16,17,18).


  • Superior vena cava syndrome (SVCS) is a common occurrence in cancer patients and may occur as a manifestation of either primary or metastatic tumor, or as a thrombosis associated with central venous access devices.
  • Superior vena caval obstruction can result in life-threatening cerebral edema (increased intracranial pressure) or laryngeal edema (airway compromise).

Etiology of Superior Vena Cava Syndrome

SVCS is most often caused by extrinsic compression of the SVC by a tumor (intrathoracic) in the setting of (1,4)

  • lung cancer, especially right-sided bronchogenic carcinoma
  • non-Hodgkin lymphoma, especially diffuse large cell or lymphoblastic lymphoma in the anterior mediastinum



  • metastatic disease to the mediastinum, from primary
  • breast cancer
  • testicular cancer
  • gastrointestinal (GI) cancers
  • primary tumors:
  • sarcomas (e.g., malignant fibrous histiocytoma)
  • melanomas.

Other causes include:

  • central line thrombus and other iatrogenic causes
  • fibrosing mediastinitis, either idiopathic or secondary to infections like histoplasmosis, tuberculosis, actinomycosis, aspergillosis, blastomycosis, or bancroftian filariasis
  • retrosternal goiter.

Clinical Signs and Symptoms of Superior Vena Cava Syndrome

  • Clinical evolution of SVCS may occur acutely or gradually.
  • Physical examination findings may include neck or chest wall superficial venous distension, facial and periorbital edema, cyanosis, facial plethora, mental status changes, lethargy, or edema of the upper extremities.
  • SVCS symptoms include dyspnea, orthopnea, facial swelling, complaint of head “fullness,” cough, arm swelling, chest pain, dysphagia, hoarseness, and positional worsening of symptoms (5).

Diagnosis of Superior Vena Cava Syndrome

  • A thorough physical examination may be sufficient to establish the diagnosis of SVCS (19).
  • Noninvasive imaging that may facilitate the diagnosis of SVCS includes:
  • contrast-enhanced CT scan or MRI
  • chest radiograph that may show mediastinal widening.

Doppler ultrasonography examination of the jugular or subclavian vein may help differentiate thrombus from extrinsic obstruction.

Radiocontrast or other injections into veins of the affected extremity are not recommended because of the risk of extravasation and the delayed entry of the contrast into central circulation.

Treatment of Superior Vena Cava Syndrome

  • Options for the treatment of SVCS depend on the underlying etiology and on the pace of symptom progression (19,20).
  • Emergent radiation therapy is required when respiratory compromise (e.g., stridor) or central nervous system (CNS) symptoms are present.
  • The endpoints of the nonemergent treatment are symptom relief and treatment of the malignant or infectious or other process causing the SVCS.
  • If SVCS is a presenting symptom (i.e., no history of cancer), and if time allows (i.e., no respiratory distress or changing neurologic status), tissue should be obtained to establish a diagnosis before treatment (21).
  • Diagnostic strategies may be limited by the patient's inability to lie supine (i.e., worsened SVCS symptoms). Most malignancies that cause SVCS can be identified without major thoracic surgical procedures by using thoracentesis, bronchoscopy, lymph node biopsy, and bone marrow biopsy, or by analyzing sputum cytology. Limited thoracotomy and mediastinoscopy may be required in some cases.
  • Conservative treatment includes elevation of the head of the bed, supplemental oxygen, and bed rest.



  • The emergent treatment of malignancy, or treatment once the histologic diagnosis is established, may include the following:
  • Adjunct medical therapy with steroids can be used, but the benefit is not well established (22). For severe respiratory symptoms, hydrocortisone, 100 to 500 mg i.v., may be administered initially, followed by lower doses of hydrocortisone every 6 to 8 hours.
  • Cautious use of loop diuretics may provide transient, symptomatic relief of edema. Overdiuresis may lead to dehydration and cardiovascular compromise.
  • Endovascular stent insertion provides relief of symptoms more rapidly and in higher proportion of patients than that with radiation or chemotherapy (4,5,22,23). The use of a stent is limited when intraluminal thrombosis is present.
  • Radiation therapy [especially for non–small cell lung cancer (NSCLC)].
  • Chemotherapy (for lymphoma or germ cell tumor).
  • Chemotherapy and radiation therapy is used for limited-disease small cell lung cancer.
  • Anticoagulant or thrombolytic therapy (for caval thrombosis and in catheter-associated thrombosis).
  • In cases of SVCS caused by catheter-associated thrombosis, removal of the catheter with a brief period of anticoagulant therapy remains an option. Alternatively, the catheter can be retained (if functional) and the patient can be treated indefinitely with therapeutic-dose warfarin.
  • Surgery (especially in the setting of refractory disease or nonmalignant causes).


Etiology of Hypercalcemia

Hypercalcemia most often occurs in the setting of the following cancers:

  • Non–small cell lung cancer: squamous cell/bulky disease
  • Breast: adenocarcinoma/during hormonal therapy
  • Genitourinary tumors: renal, small cell ovarian cancer
  • Multiple myeloma
  • Head and neck tumors
  • Lymphoma: older patients with Hodgkin lymphoma who have bulky disease, intermediate or high-grade non-Hodgkin lymphoma (NHL)/adult T-cell lymphoma
  • Leukemias and unknown primary neoplasms (1,4)
  • Patients with solid tumor metastasis to the bone comprise a large percentage of patients with cancer who have hypercalcemia (small cell lung and prostate cancers are seldom associated with hypercalcemia).

Clinical Signs and Symptoms of Hypercalcemia

The clinical signs and symptoms of hypercalcemia:

  • May be general: dehydration, weakness, fatigue, and pruritus
  • May involve many organ systems including CNS (i.e., hyporeflexia, mental status changes, seizure, coma, and proximal myopathy) and GI or genitourinary tract (GI: weight loss, nausea/vomiting, constipation, ileus, polyuria, polydipsia, azotemia, dyspepsia, and pancreatitis)
  • May involve cardiac symptoms: bradycardia, short-QT interval, wide T wave, prolonged PR interval, arrhythmias, and arrest.

Diagnosis of Hypercalcemia

  • It may be difficult to distinguish between hypercalcemia as a paraneoplastic syndrome and the hypercalcemia that results from metastatic disease to the bone.



  • Hypercalcemia of malignancy: serum intact parathormone (iPTH) level is low or undetectable; serum parathormone-related peptide (PTH-RP) levels are elevated, whereas both 1,25-dihydroxyergocalciferol and inorganic phosphate levels are low or normal. Serum PTH-RP level has a high prevalence in malignancy-related hypercalcemia, which results from osteoclastic bone resorption and increased renal resorption of calcium.
  • Osteolytic hypercalcemia is seen in the setting of multiple myeloma, NSCLC, and breast cancer.
  • Calcitriol-mediated hypercalcemia is seen in relation to Hodgkin and non-Hodgkin lymphomas.
  • In general terms, the degree of hypercalcemia can be characterized as follows: Mild hypercalcemiais characterized by a serum calcium level >10.5 mg/dL but <12 mg per dL, whereas in moderate hypercalcemia, serum calcium level ranges from 12 to 13.5 mg per dL, andsevere hypercalcemia occurs at levels >13.5 mg per dL, although patients with chronic hypercalcemia may tolerate levels well in excess of 14 mg per dL without any apparent symptoms. The reader is cautioned, therefore, that the clinical manifestations and severity of hypercalcemia do not necessarily correlate with the absolute serum level of calcium but may be more directly related to the speed with which hypercalcemia develops (1).
  • Albumin and certain serum proteins bind serum calcium and may distort “true” serum calcium levels; for example, in cases of myeloma, in which dramatic elevations in serum calcium levels simply reflect elevated concentrations of serum calcium–binding proteins as opposed to severe hypercalcemia. Approximation of the “corrected” serum calcium level can be calculated using one of several formulas that account for serum albumin levels, for example (15):

Formulae for corrected serum calcium concentration:

General Principles of Treatment of Hypercalcemia

  • The most effective treatment of hypercalcemia requires effective therapy directed at the underlying malignancy (i.e., the source of the hypercalcemia). Unfortunately, hypercalcemia most often occurs in advanced states of disease and in patients who have progressed through available standard chemotherapy. In patients with solid tumor primary cancers, survival is often less than 6 months.
  • Any symptomatic patient with hypercalcemia, regardless of absolute serum calcium level, should be treated for correction of the hypercalcemia (24,25,26,27).
  • Symptomatic patients with severely elevated calcium levels often require profound fluid volume replacement, which makes outpatient therapy impractical and unsafe.
  • Mild asymptomatic hypercalcemia with serum calcium concentration in range of 11 to 12 mg per dL should be treated, when there is associated hypercalciuria, because of the risk of nephrolithiasis and nephrocalcinosis.

Practical Management of Hypercalcemia

  • Therapy for mild chronic hypercalcemia usually includes observation and oral rehydration. Corticosteroids can be considered in select patients. Corticosteroid administration inhibits osteoclastic bone resorption and is useful in patients with tumors responsive to this steroid effect. These tumors include lymphoma, leukemia, myeloma (prednisone, 40 to 100 mg per day), and breast cancers (prednisone, 15 to 30 mg per day) during hormonal therapy (4, 28,29,30. The hypocalcemic effect of corticosteroid administration is inconsistent, however, in steroid-resistant tumor types, and caution is advised (4). Oral phosphate (1 to 3 g per day) can also be considered as long as serum phosphate concentrations do not exceed 4 mg per dL.


Oral phosphate usually lowers the serum calcium concentration by 0.5 to 1.0 mg per dL, but its use is frequently complicated by gastrointestinal symptoms.

  • Acute therapy of patients with symptomatic or more severe hypercalcemia, (i.e., serum calcium concentration exceeding 12 mg per dL) requires hospitalization. Therapy should be initiated by increasing urinary calcium excretion through vigorous hydration and by decreasing bone resorption through osteoclast inhibition (see subsequent text).
  • The fluid and hemodynamic status should be assessed by evaluating blood pressure, pulse, orthostatics, urine volume, and appropriate laboratory values of the patient (4,27). Patients with hypercalcemia are often severely dehydrated (i.e., they need many liters of fluid) and require immediate administration of isotonic saline (1 to 2 L over 1 hour followed by 300 to 400 mL per hour, unless the patient has heart failure or renal failure) to increase renal blood flow and calcium excretion. Small doses of furosemide may be used when the patient's volume status has first been restored.
  • During treatment, patients require frequent monitoring of clinical status and metabolic laboratory testing because forced diuresis may be complicated by hypomagnesemia, hypokalemia, fluid overload, or subsequent pulmonary edema.
  • Once rehydration is complete and urinary output is optimized, the need for bisphosphonate administration should be assessed. These pyrophosphate analogs interfere with osteoclast function, thereby inhibiting calcium release.
  • Intravenous zoledronic acid (4 mg i.v., infused over at least 15 minutes) or pamidronate (60 or 90 mg i.v., infused over 2 to 4 hours) is commonly used in malignancy-induced hypercalcemia (31,32). Zoledronic acid has replaced pamidronate as the agent of choice. In a recent phase III trial, zoledronic acid was shown to normalize serum calcium level in 87% to 88% of patients as compared to 70% of patients who received pamidronate. The duration of response (32 to 43 days versus 18 days) was also in favor of zoledronic acid (33). Bisphosphonate administration is well tolerated by patients except for occasional i.v. site irritation and fever during infusion. Its onset of action is within 24 to 48 hours of administration; the maximal effect may not be achieved until 72 hours after treatment.
  • An additional and perhaps more effective intervention for hypercalcemia includes the use of gallium nitrate (not the radioisotope), which also inhibits bone resorption (4).
  • Intravenous administration (100–200 mg/m2/day over 24 hours or up to 5 days) of gallium nitrate in rehydrated nonoliguric (target urine output: 1,500 to 2,000 mL per day) patients is highly effective (70% to 90%) in the treatment of hypercalcemia. Care should be taken to discontinue gallium nitrate once normocalcemia is achieved, but close metabolic monitoring should be maintained because maximal drug effect occurs days after cessation of administration. The concomitant use of nephrotoxic drugs should be avoided when using gallium nitrate.
  • Patients with hypercalcemia who do not respond to pamidronate may benefit from subsequent gallium nitrate administration. Conversely, patients who do not respond to gallium nitrate may benefit from pamidronate (1,4).
  • Calcitonin has a rapid onset of action (within 4 hours) and is often useful in severe and symptomatic hypercalcemia until the more slowly acting agents become effective (e.g., zoledronic acid, pamidronate, and gallium nitrate).
  • Salmon calcitonin is initially given at 4 units per kg (body weight) s.c. or i.m. every 12 hours. If response is not satisfactory after 1 to 2 days, the dosage may be increased to 8 units per kg s.c. or i.m. every 12 hours. If response is still not adequate after a 1- to 2-day trial at the higher dose, the dosing interval should be decreased to 8 units per kg s.c. or i.m. every 6 hours. Although many patients initially will respond to calcitonin, tachyphylaxis often develops rapidly, which renders patients refractory to its hypocalcemic effect (26,27,28,29,30,31,32,34).
  • Plicamycin (mithramycin) also has a rapid onset of hypocalcemic activity (<12 hours), with a duration of response ranging from 3 to 7 days.
  • The hypocalcemic effect of plicamycin is attributed to a direct cytotoxic effect on osteoclasts. Single doses of plicamycin, 0.025 mg per kg (body weight) in 150 to 250 mL of 0.9% sodium chloride injection or 5% dextrose injection by i.v. infusion over 30 to 60 minutes,


are usually well tolerated. The duration of the hypocalcemic response with plicamycin is typically 3 to 7 days; however, it is essential to note that a maximal hypocalcemic effect may not be achieved until 48 hours after treatment. Consequently, repeated doses should not be given more frequently than every 48 hours if hypocalcemia is to be avoided. Higher doses and shorter treatment intervals also increase the risk of plicamycin-induced hepatic and renal toxicities, hemorrhagic diathesis, and thrombocytopenia (4,34). Plicamycin is not commonly used in the United States because of its toxicities.

  • Hemodialysis should be considered, in addition to the other treatments listed for hypercalcemia, in patients who have serum calcium level in the range of 18 to 20 mg per dL and/or in those who have neurologic symptoms but are hemodynamically stable.


Etiology of Tumor Lysis Syndrome

  • The administration of antitumor agents can lead to cell death, with subsequent release of intracellular contents.
  • Tumor lysis syndrome (TLS) occurs when cellular disruption results in life-threatening lactic acidosis, with concomitant hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia (4). The patient rapidly develops renal failure or has renal insufficiency at presentation.

Clinical Setting, Signs, and Symptoms of Tumor Lysis Syndrome

  • TLS usually occurs in bulky disease treated with cytotoxic agents directed at rapidly proliferating tumors (1).
  • TLS occurs most often during the treatment of leukemia or high-grade lymphomas but may also occur during the treatment of other solid tumors (35).
  • Cardiac arrhythmias may result from the severe hyperkalemia or hypocalcemia that accompanies the TLS.
  • Hypocalcemia can result in tetany, whereas hyperphosphatemia and hyperuricemia can result in acute renal failure.

Prevention and Treatment of Tumor Lysis Syndrome

  • Preemptive measures include the pretreatment identification of individuals at risk, along with 24 to 48 hours of prehydration, use of pretherapeutic allopurinol, and vigilant metabolic monitoring (every 3- to 4-hour laboratory tests) after institution of therapy. These actions are the hallmarks of TLS prevention and management (35,36). Elevated levels of lactate dehydrogenase (LDH), uric acid, or creatinine at presentation identify a particularly high-risk patient.
  • Corrective measures should be directed toward any metabolic abnormalities that occur in patients after starting cytotoxic therapy, and particular care should be given to the appropriate monitoring of responses [e.g., continuous or serial electrocardiograms (ECGs)] and to the provision of early interventions while correcting hyperkalemia, while admitting the patient to the intensive care unit (ICU) for severe hemodynamic instability, and during hemodialysis, when the patient is faced with worsening or severely compromised renal function (4).
  • The correction of metabolic abnormalities during TLS is similar to the general management of ICU patient, with specific interventions for the following conditions.


  • In mild hyperphosphatemia, dietary phosphate is restricted to 0.6 to 0.9 g per day, and oral phosphate binder such as calcium carbonate is added.



  • Severe hyperphosphatemia with symptomatic hypocalcemia can be life threatening. The hyperphosphatemia usually resolves within 6 to 12 hours if renal function is intact. Phosphate excretion can be increased by saline infusion, although this can further reduce the serum calcium concentration by dilution. Phosphate excretion can also be increased by administration of acetazolamide (15 mg per kg every 3 to 4 hours). Hemodialysis is often indicated in patients with symptomatic hypocalcemia, particularly if renal function is impaired.


  • The most appropriate treatment of hypocalcemia, in the absence of hypomagnesemia, is intravenous calcium, at a dose of 100 to 200 mg of elemental calcium (1 to 2 g of calcium gluconate) in 10 to 20 minutes. Such infusions do not raise the serum calcium concentration for more than 2 to 3 hours and, therefore, should be followed by a slow infusion of 10% calcium gluconate (90 mg of elemental calcium per 10 mL ampule) at the rate of 0.5 to 1.5 mg per kg i.v. per hour.
  • Calcium chloride, 10% (272 mg of elemental calcium per 10 mL ampule) can also be used, with 5 to 10 mL given initially i.v. slowly over 10 minutes or diluted in 100 mL of 5% dextrose in water and infused over 20 minutes. This dosage should be repeated as often as every 20 minutes if the patient is symptomatic. Serum calcium levels should be monitored every 4 to 6 hours and hypomagnesemia be corrected as needed.
  • Primary management of the hyperphosphatemia is critical to minimize metastatic deposition of insoluble calcium phosphate. Hemodialysis is almost always required by this time.


  • Confirm that the elevation in potassium level is genuine.
  • If the patient is asymptomatic, with a plasma potassium concentration of 6.5 mEq per L and with an ECG that does not manifest signs of hyperkalemia, then withhold potassium and initiate the administration of cation exchange resins. If the patient is symptomatic, with peripheral neuromuscular weakness, electrocardiographic signs of hyperkalemia, or plasma potassium concentration above 7 mEq per L, consider calcium gluconate, 10% solution, 10 mL i.v. given over 2 to 5 minutes (dose can be repeated after 5 minutes if electrocardiographic changes persist), followed by glucose with insulin, sodium bicarbonate, or a nebulized β-agonist. Prepare for hemodialysis (37,38).
  • Measures to reduce serum potassium level:
  1. Regular insulin, 10 U plus 50% glucose, 50 mL i.v. as a bolus (onset 15 to 60 minutes; duration 4 to 6 hours), followed by glucose infusion to prevent hypoglycemia. Insulin along with glucose lowers the potassium level by driving it into the cell.
  2. Adrenergic β2-agonist such as nebulized albuterol, 10 to 20 mg in 4 mL normal saline, inhaled over 10 minutes (onset 15 to 30 minutes; duration 2 to 4 hours) is effective in reducing serum potassium concentration. Adrenergic β2-agonists induce hypokalemia by stimulating the transport of potassium into skeletal muscle.
  3. Sodium bicarbonate, at the dose of is 45 mEq (1 ampule of a 7.5% sodium bicarbonate solution), is infused slowly over 5 minutes (onset 30 to 60 minutes; duration several hours); this dose can be repeated in 30 minutes if necessary. This also temporarily drives the potassium inside the cell.
  4. Kayexalate, orally or rectally, 15 to 50 g in 50 to 100 mL of 20% sorbitol solution, is repeated every 3 to 4 hours, as needed, for up to five times per day (onset, 1 to 3 hours, duration of several hours).
  • Minimize administration of drugs that can cause or potentiate hyperkalemia [e.g., nonsteroidal antiinflammatory drugs (NSAIDs), β-blockers, angiotensin-converting enzyme (ACE) inhibitors, and potassium-sparing diuretics].



Hyperuricemia and Renal Failure

  • Hyperuricemic acute renal failure following chemotherapy may be avoided by (a) prechemotherapeutic identification of patients at risk for developing TLS and (b) administration of allopurinol at doses of 600 to 900 mg every day, starting several days before chemotherapy, with tapering doses to maintain uric acid levels of <7 mg per dL.
  • The therapy for hyperuricemic acute renal failure before chemotherapy consists of administering allopurinol (if it has not already been given) and attempting to wash out the obstructing uric acid crystals by a loop diuretic and by fluids. Sodium bicarbonate should not be given at this time because it is difficult to raise the urine pH in this setting. Hemodialysis to remove the excess circulating uric acid should be used in patients in whom a diuresis cannot be induced.
  • Hyperuricemic acute renal failure following chemotherapy is usually refractory to conservative intervention (hydration, diuretics, etc.), and patients require hemodialysis for supportive therapy and renal recovery.

In an effort to improve the control of hyperuricemia in patients with leukemia or lymphoma, Pui et al. tested the recombinant urate oxidase (rasburicase) by i.v. administration of the uricolytic agent for five to seven consecutive days to children, adolescents, and young adults with newly diagnosed leukemia or lymphoma (39).

The recombinant enzyme produced a rapid and sharp decrease in plasma uric acid concentrations in all patients. Despite cytoreductive chemotherapy, plasma uric acid concentrations remained low throughout the treatment. The toxicity of the agent was negligible, and none of the patients required dialysis. The mean plasma half-lives of the agent were 16.0 ± 6.3 [standard deviation (SD)] hours and 21.1 ± 12.0 hours, respectively, in patients treated at doses of 0.15 and 0.20 mg per kg. Seventeen of the 121 assessable patients developed antibodies to the enzyme.

The authors concluded that rasburicase was safe and effective for the prophylaxis for or treatment of hyperuricemia in patients with leukemia or lymphoma.


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