Chapter 139. Emergency Complications of Malignancy

Oncologic emergencies arise from the underlying malignancy or as complications of radiation and chemotherapy.

Patients with tumors of the upper and lower respiratory tract may experience acutely worsening airway compromise due to edema, bleeding, infection, or loss of protective mechanisms. Presenting symptoms and signs include dyspnea, tachypnea, wheezing and stridor. Imaging involves plain radiographs, CT scan, and/or endoscopic visualization. Emergency measures include supplemental humidified oxygen, maintenance of airway through optimal patient positioning, and, possibly, administration of a helium-oxygen mixture. If intubation is required, an "awake look" with a fiber optic bronchoscope with a 5-0 or 6-0 endotracheal tube is preferred. An emergency surgical airway, such as cricothyroidotomy, transtracheal jet ventilation, or tracheotomy may be needed. Consult with an oncologist or surgeon for definitive management.

Patient with solid tumors, most commonly breast, lung, and prostate, may present with pain, pathologic fracture, or spinal cord compression caused by bony metastases. Patients with spinal cord compression may also exhibit muscular weakness, radicular pain, and bowel or bladder dysfunction. Plain radiographs are obtained initially to assess for fracture or bony involvement, followed by CAT scan or MRI to further delineate lesions. Treatment priorities include pain control with opioid analgesia and restoration or salvage of function. Most pathologic fractures require surgical intervention. Painful bone metastases are treated with radiotherapy. The presentation, evaluation, and management of malignant spinal cord compromise are described in Table 139-1.

Malignant pericardial effusions are usually asymptomatic but can progress to life-threatening cardiac tamponade. Symptoms depend on the rate of accumulation and distensibility of the pericardial sac (see Chapter 24 "The Cardiomyopathies, Myocarditis, and Pericardial Disease"). Patients with symptomatic effusion may present with chest heaviness, dyspnea, cough, and syncope. Physical examination findings include tachycardia, narrowed pulse pressure, hypotension, distended neck veins, muffled heart tones, and pulsus paradoxus.

Echocardiography is the test of choice as it demonstrates the size of the effusion and the presence of tamponade. Chest radiograph may demonstrate an enlarged cardiac silhouette or pleural effusion. ECG may show sinus tachycardia, low QRS amplitude, and electrical alternans. The differential diagnosis includes cardiomyopathy related to chemotherapy, such as doxorubin and radiation therapy. Emergent ultrasound-guided pericardiocentesis may be required to relieve cardiac tamponade.

Superior vena cava syndrome most commonly occurs due to external compression by an external malignant mass such as lung cancer or lymphoma. Less common causes include thrombosis and benign masses. The most common symptoms are gradual onset of dyspnea, chest pain, cough, distended neck veins, face or arm swelling. CT of the chest with IV contrast is the diagnostic procedure of choice. CXR will usually show a mediastinal mass.

Patients with neurologic symptoms require urgent treatment including supplemental oxygen and elevation of the head and upper body. Dexamethasone 20 milligrams IV or methylprednisolone 125 to 250 milligrams IV may be beneficial in patients with increased intracranial pressure or lymphoma. In patients without neurologic symptoms, SVC syndrome usually does not cause rapid deterioration and can await consultation regarding chemotherapy, radiation, or intravascular stenting. Patients with intravascular thrombosis may require anticoagulation, fibrinolysis, or catheter removal.

Hypercalcemia is most commonly seen with breast and lung cancer, lymphoma, and multiple myeloma. The symptoms are nonspecific and include polydipsia, polyuria, generalized weakness, lethargy, anorexia, nausea, constipation, abdominal pain, volume depletion, and altered mentation.

Clinical signs and symptoms are related to the rate of rise and occur above 12 milligrams/dL (ionized >5.5 milligrams/dL). ECG may show shortened QT interval, ST depression, and atrioventricular blocks.

Normal saline infusion is the mainstay of treatment. Furosemide is no longer recommended. Further treatment should be discussed with the patient's oncologist. Bisphosphonates such as zoledronic acid 4 milligrams IV over 15 min or pamidronate 60 to 90 milligrams IV over 4 to 24 hours can prevent bone resorption. Calcitonin 4 international units/killogram SC or IM causes a more rapid decrease in calcium levels. Glucocorticoids may be helpful in lymphoma and multiple myeloma. Consider hemodialysis for patients with profound mental status changes, renal failure, or those who cannot tolerate a normal saline infusion (see Chapter 4 "Fluids, Electrolytes and Acid Base Disorders").

Inappropriate ADH secretion is most commonly associated with bronchogenic lung cancer, but can also occur from chemotherapy or medications. Symptoms include anorexia, nausea, headache, altered mentation, and seizures. Mild hyponatremia (>125 mEq/L) is usually asymptomatic.

SIADH should be suspected in patients with cancer who present with normovolemic hyponatremia. Laboratory abnormalities include serum osmolality <280 mOsm/L, urine osmolality >100 mOsm/L, and urine sodium >20 mEq/L. The differential diagnosis includes hypothyroidism, renal failure, cirrhosis, adrenal crisis and hypo/hypervolemia.

Mild hyponatremia >125 mEq/L is treated with a water restriction of 500 mL/d and close follow-up. More severe hyponatremia is treated with furosemide, 0.5 to 1 milligram/killogram PO with normal saline infusion to maintain normovolemia. Demeclocycine 300 to 600 milligrams PO twice daily may increase water excretion. Three percent hypertonic saline is reserved for severe hyponatremia <120 mEq/L with seizures or coma. An infusion of 25 to 100 mL/h should be titrated to a correction of 0.5 to 1 mEq/h with a maximum of 12 mEq/L/d (see Chapter 4 "Fluids, Electrolytes and Acid Base Disorders").

Adrenal crisis is most commonly caused by acute physiologic stress in the face of exogenous steroid-induced adrenal suppression or malignant infiltration of adrenal tissue. Symptoms include weakness or nausea, and hypotension unresponsive to fluids. Laboratory abnormalities may include hypoglycemia, hyponatremia, and hyperkalemia. A serum cortisol level is ideally drawn before giving steroids. Treat acute adrenal insufficiency empirically with stress-dose hydrocortisone 100 to 150 milligrams IV, methylprednisolone 20 to 30 milligrams IV, or dexamethasone 4 milligrams IV, IV crystalloids and supportive care (see Chapter 132 "Adrenal Insufficiency and Adrenal Crisis").

Tumor lysis syndrome occurs when massive quantities of potassium, phosphate, and uric acid are released into the systemic circulation. It usually occurs 1 to 3 days after chemotherapy for acute leukemia or lymphoma. The resulting hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia may cause uric acid precipitates and calcium phosphate deposits in the kidney with renal failure, life-threatening arrhythmias, tetany, and seizures. Laboratory evaluation should include 12-lead ECG, basic electrolyte levels, complete blood count, uric acid, and phosphorus.

Preventative measures reduce the incidence of tumor lysis syndrome. Hyperkalemia is the most immediate life threat. Treatment of hyperkalemia is with insulin, glucose, bicarbonate (if acidotic), kayexalate, and albuterol (see Chapter 4 "Fluids, Electrolytes and Acid Base Disorders"). Calcium administration is avoided unless ventricular arrhythmias or widened QRS complexes are seen, as it may worsen calcium phosphate precipitation in the kidney. Aggressive infusion of isotonic fluids reverses volume depletion and helps to prevent renal deposition of uric acid and calcium phosphate crystals. Hyperuricemia may be treated with rasburicase 0.2 milligram/killogram IV. Hyperphosphatemia is managed with IV insulin and glucose. Phosphate binders have a limited effect. Consider hemodialysis for potassium levels above 6.0 mEq/L, uric acid levels above 10.0 milligrams/dL, phosphate levels above 10 milligrams/dL, creatinine levels above 10 milligrams/dL, symptomatic hypocalcemia, or volume overload. Patients with tumor lysis syndrome should be admitted to an intensive care unit.

Febrile neutropenia is defined by temperatures above 38°C for an hour or a single temperature above 38.3°C with an absolute neutrophil count (ANC) below 1000 cells/mm3. Neutrophil counts typically reach a nadir 10 to 15 days after chemotherapy and rebound 5 days later.

Febrile neutropenic patients often lack localizing signs and symptoms because of an attenuated immune response. Meticulous attention must be paid to all skin surfaces, mucosal areas, and vascular access sites in which the patient may have an occult infection. Digital rectal examination is often withheld until after initial antibiotic administration because of the fear of inducing bacteremia.

Laboratory evaluation includes complete blood count with differential, blood cultures obtained through all lumens of indwelling catheters as well as a peripheral site, urinalysis, urine culture, and CXR, electrolytes, renal, and liver function tests. Additional studies based on symptoms may include stool culture (diarrhea), sputum culture (cough), lumbar puncture (headache, stiff neck, altered mental status), wound culture (drainage), and CT or ultrasound (abdominal pain).

The decision for empiric antibiotics and admission should be made with the patient's oncologist. Empiric antibiotics (Table 139-2) are generally indicated for an ANC <500/mm3. For neutrophils counts between 500 and 1000, the decision is based on the patient's presentation. Add vancomycin for severe mucositis, catheter site infection, recent use of fluoroquinolone prophylaxis, hypotension, residence in an institution with hospital-associated methicillin-resistant Staphylococcus aureus, or known colonization with resistant gram-positive organisms.

Hyperviscosity syndrome refers to impaired blood flow due to abnormal elevations of paraproteins or cellular blood components. It is most occurs in patients with dysproteinemia, acute leukemia, or polycythemia. Hematocrits above 60% and WBC counts above >100,000/mm3 often cause hyperviscosity syndromes.

Initial symptoms include fatigue, abdominal pain, headache, blurry vision, dyspnea, fever, or altered mental status. Thrombosis or bleeding may occur. Physical exam findings may include retinal hemorrhages, exudates, and "sausage-linked" vessels. Elevated serum viscosity (>5), rouleaux formation (red cells stacked like coins), or abnormal protein electrophoresis (IgM >4 grams/dL) support the diagnosis.

Initial therapy consists of intravenous isotonic fluids and plasmapheresis or leukopheresis in consultation with a hematologist. A temporizing measure in patients with coma is 1000 mL phlebotomy with simultaneous infusion of 2 to 3 L normal. Red cell transfusion is not recommended, as it may increase blood viscosity.

Thromboembolism is the second leading cause of death in cancer patients. See Chapter 25 for discussion of the diagnosis and management of deep vein thrombosis and pulmonary embolism. Cancer patients, even those with brain metastases, do not appear at increased risk for anticoagulant-related bleeding complications.

Chemotherapy commonly causes nausea and vomiting. Other causes of nausea and vomiting include radiation enteritis, bowel obstruction, infection or tumor infiltration, and increased intracranial pressure. Treatment consists of rehydration, administration of antiemetics, and correction of electrolyte derangements (Table 139-3).

If irritation develops during infusion through a peripheral line, stop the infusion and attempt aspiration through the line. Clinical manifestations of extravasation include pain, erythema and swelling, usually within hours of the infusion. Consult with the patient's oncologist to discuss the use of antidotes for extravasation of anthracyclines, vinca alkaloids, mitomycin, cisplatin, mechlorethamine, and paclitaxel.