Ross J. Fleischman
BONE METASTASES AND PATHOLOGIC FRACTURES
EPIDEMIOLOGY
Breast, lung, and prostate cancers are the most common causes of bony metastases, which may cause pain, pathologic fractures, and spinal cord compression.
CLINICAL FEATURES AND DIAGNOSIS
Approximately 90% of patients with malignant spinal cord compression will have back pain.
Patients with spinal cord compression may also exhibit muscular weakness, radicular pain, and bowel or bladder dysfunction (late findings).
Obtain plain radiographs to assess for fractures or bony involvement. Plain radiographs may show a moth-eaten appearance, periosteal reaction, or poorly demarcated areas of increased density (osteoblastic activity).
Follow with CAT scan or magnetic resonance imaging (MRI) scan to further delineate lesions.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Treat pain with opioid analgesics.
Most pathologic fractures require surgical intervention.
Painful bone metastases are treated with radiotherapy.
SPINAL CORD COMPRESSION
EPIDEMIOLOGY
Up to one in five patients with vertebral metastases and 3% to 6% of all cancer patients will develop spinal cord compression.
The thoracic spine is involved in 70% of cases.
PATHOPHYSIOLOGY
Neurologic symptoms occur when the spinal cord or nerve roots are compressed or directly infiltrated by tumor.
CLINICAL FEATURES
Back pain is progressive and usually worse when supine.
Proximal motor weakness usually occurs before sensory changes because of compression of the anterior portion of the cord from the vertebral bodies.
Intrinsic involvement of the spinal cord usually presents with unilateral weakness.
Sensory changes (hyperesthesia or anesthesia) and bladder or bowel retention or incontinence are late findings.
Physical examination may reveal vertebral percussion tenderness, decreased rectal tone, saddle anesthesia, lower extremity hyporeflexia, and absent anal “wink.”
DIAGNOSIS AND DIFFERENTIAL
Plain radiographs or CT scan can identify vertebral involvement, but should be followed by a gadolinium-enhanced MRI scan of the whole spine.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Consider administering dexamethasone 10 milligrams IV followed by 4 milligrams IV or PO every 6 hours if imaging will be delayed.
Emergent radiation therapy is generally the first-line treatment.
Surgery may be necessary for rapidly progressive symptoms, unstable vertebral column, and overall status and prognosis compatible with surgery.
AIRWAY OBSTRUCTION
PATHOPHYSIOLOGY
Patients with respiratory tract tumors may experience acute airway compromise due to edema, bleeding, infection, or loss of protective mechanisms.
CLINICAL FEATURES
Presenting symptoms and signs include dyspnea, tachypnea, wheezing, and stridor (an ominous sign).
DIAGNOSIS AND DIFFERENTIAL
Imaging involves plain radiographs, CT scan, and/or endoscopic visualization.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Temporizing measures include supplemental humidified oxygen, upright patient positioning, and possibly administration of a helium-oxygen mixture.
If intubation is required, an “awake look” with a fiberoptic bronchoscope with a 5-0 or 6-0 endotracheal tube is preferred.
An emergency surgical airway, such as cricothyroi-dotomy, transtracheal jet ventilation, or tracheotomy, may be needed.
Consult with an oncologist or surgeon for definitive management.
MALIGNANT PERICARDIAL EFFUSION AND TAMPONADE
EPIDEMIOLOGY
Pericardial effusions are seen in up to 15% of patients with cancer but are often asymptomatic.
PATHOPHYSIOLOGY
Common causes include carcinomas of the breast and lung, lymphoma, leukemia, and malignant melanoma. They can also be caused by therapeutic irradiation and chemotherapy.
Symptoms depend on the rate of accumulation and distensibility of the pericardial sac.
Sudden or large (>500 mL) effusions may compress the heart, preventing cardiac filling and reducing cardiac output (cardiac tamponade).
CLINICAL FEATURES
Patients may present with chest heaviness, dyspnea, cough, and syncope.
Physical examinations findings include tachycardia, narrowed pulse pressure, hypotension, distended neck vein, muffled heart tones, and pulsus paradoxus.
DIAGNOSIS AND DIFFERENTIAL
Obtain an echocardiogram to evaluate 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.
Cardiomyopathy related to chemotherapy, such as dox-orubin, and radiation therapy may have similar findings.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Oxygen, volume expansion with crystalloid, and dopamine, up to 20 micrograms/kg/min IV, can be temporizing measures for cardiac tamponade.
Emergent ultrasound-guided pericardiocentesis may be required to relieve cardiac tamponade in an unstable patient. For a more stable patient with a symptomatic effusion, consult a cardiologist for intervention, which may include pericardial window or placement of a pericardial catheter.
Consult the patient’S oncologist, as malignant effusion without symptoms or tamponade may not require treatment.
SUPERIOR VENA CAVA SYNDROME
PATHOPHYSIOLOGY
Superior vena cava (SVC) syndrome most commonly occurs due to external compression by a malignant mass such as lymphoma (70%) or lung cancer (20%). Less common causes include thrombosis and benign masses.
CLINICAL FEATURES
The most common symptoms are gradual onset of dyspnea, chest pain, cough, distended neck veins, and face or arm swelling.
DIAGNOSIS AND DIFFERENTIAL
Obtain a CT of the chest with IV contrast.
Chest radiograph may show a mediastinal mass.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Patients with neurologic symptoms require urgent treatment including supplemental oxygen and elevation of the head and upper body.
Dexamethasone 20 milligrams IV or methyl-prednisolone 125 to 250 milligrams IV may benefit 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 OF MALIGNANCY
EPIDEMIOLOGY
Hypercalcemia is seen in 10% to 30% of patients with advanced cancer.
Hypercalcemia is most commonly seen with breast and lung cancer, lymphoma, and multiple myeloma.
PATHOPHYSIOLOGY
Hypercalcemia is most often caused by a parathyroid hormone–related peptide secreted by the cancer cells. This hormone stimulates osteoclastic activity and promotes renal reabsorption of calcium.
CLINICAL FEATURES
The symptoms are nonspecific and include polydip-sia, polyuria, generalized weakness, lethargy, anorexia, nausea, constipation, abdominal pain, volume depletion, and altered mentation.
DIAGNOSIS AND DIFFERENTIAL
Clinical signs and symptoms are related to the rate of rise and occur above 12 milligrams/dL (ionized >5.5 milligrams/dL).
Measure ionized calcium or correct total serum calcium for albumin level: Corrected Ca = {0.8 × (4 − Pt’S Albumin [grams/dL])} + Serum Ca (milligrams/dL).
ECG may show shortened QT interval, ST depression, and atrioventricular blocks.
Medications (diuretics), granulomatous disorders, primary hyperparathyroidism, and other endocrine disorders can also cause hypercalcemia.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Treat initially with an infusion of normal saline.
Further treatment should be discussed with the patient’S oncologist.
Bisphosphonates such as zoledronic acid 4 milligrams IV over 15 minutes or pamidronate 60 to 90 milligrams IV over 4 to 24 hours can prevent bone resorption, but should be given slowly to prevent the formation of calcium–bisphosphonate precipitants.
Calcitonin 4 international units/kg 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.
Furosemide is no longer recommended unless needed to prevent volume overload in patients with impaired cardiac or renal function.
SYNDROME OF INAPPROPRIATE SECRETION OF ANTIDIURETIC HORMONE
EPIDEMIOLOGY
Inappropriate ADH secretion is most commonly associated with bronchogenic lung cancer, but is also caused by chemotherapy and medications.
PATHOPHYSIOLOGY
Antidiuretic hormone (ADH, vasopressin) normally acts on the collecting tubule of the kidneys to increase water absorption during hypovolemia.
In SIADH, excess ADH is secreted by ectopic tumor cells or through abnormal secretory stimulation of or cytotoxicity to the paraventricular and supraoptic neurons.
CLINICAL FEATURES
Symptoms include anorexia, nausea, headache, altered mentation, and seizures.
Mild hyponatremia (>125 mEq/L) is usually asymptomatic.
DIAGNOSIS AND DIFFERENTIAL
SIADH should be suspected in patients with cancer who present with normovolemic hyponatremia.
Lab abnormalities include serum osmolality <280 mOsm/L, urine osmolality >100 mOsm/L, and urine sodium >20mEq/L. The differential diagnosis includes hypothyroidism, renal failure, cirrhosis, adrenal crisis, and hypo/hypervolemia.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
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/kg PO with normal saline infusion to maintain volume.
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. Titrate an infusion of 25 to 100 mL/h to a correction of 0.5 to 1 mEq/h with a maximum of 12-mEq/L change per day.
ADRENAL CRISIS
PATHOPHYSIOLOGY
Adrenal crisis occurs when the adrenal glands decrease hormone production because of long-term exogenous steroid administration and are then unable to produce adequate hormones if those exogenous steroids are discontinued or to meet the additional steroid requirements imposed by physiologic stress.
Destruction of the adrenal glands by malignancy may also impair steroid production.
Mineralocorticoid (aldosterone) deficiency impairs sodium conservation (hyponatremia), potassium secretion (hyperkalemia), and proton secretion (acidosis).
Glucocorticoid (cortisol) deficiency impairs metabolism of carbohydrate, lipid, protein, and water (hypoglycemia and hypotension).
In secondary adrenal insufficiency, the hypothalamic-pituitary axis malfunctions. Production of cortisol is impaired due to a low level of adrenocorticotropic hormone, but aldosterone production is still appropriate.
CLINICAL FEATURES
Symptoms include weakness, nausea, and hypotension unresponsive to fluids.
DIAGNOSIS AND DIFFERENTIAL
Laboratory abnormalities may include hypoglycemia, hyponatremia, hyperkalemia, and low bicarbonate.
Consider septic, cardiogenic, and hypovolemic shock in the differential diagnosis.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Empirically administer stress-dose hydrocortisone 100 to 150 milligrams IV, methylprednisolone 20 to 30 milligrams IV, or dexamethasone 4 milligrams IV, isotonic IV crystalloids, and supportive care.
Check for hypoglycemia with a capillary blood glucose.
Draw a serum cortisol level before treatment if time permits.
TUMOR LYSIS SYNDROME
PATHOPHYSIOLOGY
Tumor lysis syndrome occurs when dying tumor cells release massive quantities of potassium, phosphate, and uric acid.
Calcium binds to phosphate, causing hypocalcemia.
Uric acid and calcium phosphate deposit in the kidneys, causing renal failure.
CLINICAL FEATURES
Tumor lysis syndrome usually occurs 1 to 3 days after chemotherapy for acute leukemia or lymphoma.
Patients may present with fatigue, lethargy, nausea, vomiting, and cloudy urine.
Hypocalcemia may cause neuromuscular irritability, muscular spasms, seizures, and altered mentation.
Acute renal failure exacerbates hyperkalemia, which together with hypocalcemia may cause serious cardiac arrhythmias.
DIAGNOSIS AND DIFFERENTIAL
Obtain a 12-lead ECG, basic electrolyte levels, complete blood count, uric acid, and phosphorus.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Aggressive infusion of isotonic fluids reverses volume depletion and helps to prevent renal deposition of uric acid and calcium phosphate crystals.
Hyperkalemia is the most immediate life threat. Treat hyperkalemia with insulin, glucose, bicarbonate (if acidotic), albuterol, and kayexalate (see Chapter 6 for regimens).
Calcium gluconate 1 gram IV = 10 mL of 10% solution should be given for ventricular arrhythmias or widened QRS complexes. Otherwise, avoid calcium administration, as it may worsen calcium phosphate precipitation in the kidney.
Hyperuricemia may be treated with rasburicase 0.2 milligram/kg 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.
Admit the patient to an intensive care unit.
NEUTROPENIC FEVER
CLINICAL FEATURES
Neutrophil counts typically reach a nadir 5 to 10 days after chemotherapy and rebound 5 days later.
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.
Patient with neutropenic fever can deteriorate rapidly and should be assessed and given empiric antibiotics promptly when indicated.
DIAGNOSIS AND DIFFERENTIAL
Febrile neutropenic patients often lack localizing signs and symptoms because of an attenuated immune response.
Meticulously examine 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.
Obtain complete blood count with differential, blood cultures through all lumens of indwelling catheters as well as a peripheral site, urinalysis, urine culture, chest radiograph, electrolytes, and 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).
A chest radiograph may appear normal in neutro-penic patients with pneumonia since neutrophils are required for an infiltrate to appear.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Give empiric antibiotics (Table 141-1) and admit to the hospital for an ANC below <500/mm3. For neu-trophil counts between 500 and 1000, the decision for antibiotics and admission is based on the patient’S presentation and should be made with the oncologist.
TABLE 141-1 Suggestions for Initial Empiric Antibiotic Therapy in Febrile Neutropenia
Add vancomycin, 1 gram IV, for severe mucositis, catheter site infection, recent use of fluoroquinolone prophylaxis, hypotension, residence in an institution with methicillin-resistant Staphylococcus aureus(MRSA), or known colonization with other resistant gram-positive organisms.
HYPERVISCOSITY SYNDROME
PATHOPHYSIOLOGY
Hyperviscosity syndrome refers to impaired blood flow due to abnormal elevations of paraproteins or blood cells.
It is most common in patients with acute leukemia, polycythemia, and dysproteinemias (Waldenström macroglobulinemia and myeloma).
The hyperviscosity causes sludging, stasis, impaired microcirculation, and tissue hypoperfusion.
CLINICAL FEATURES
Initial symptoms include fatigue, abdominal pain, headache, blurry vision, dyspnea, fever, or altered mental status. Thrombosis or bleeding may occur.
Fundoscopic examination findings may include retinal hemorrhages, exudates, and “sausage-linked” vessels.
Symptoms are worsened by dehydration.
DIAGNOSIS AND DIFFERENTIAL
Hematocrits above 60% and WBC counts above 100,000/mm3 often cause hyperviscosity syndromes.
Elevated serum viscosity (>5 cP), rouleaux formation (red cells stacked like coins), or abnormal protein electrophoresis (IgM >4 grams/dL) support the diagnosis.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Administer intravenous isotonic fluids and consult a hematologist regarding plasmapheresis or leuko-pheresis.
A temporizing measure in patients with coma is 1000 mL phlebotomy with simultaneous infusion of 2 to 3 L isotonic fluids.
Red cell transfusion is not recommended, as it may increase blood viscosity.
THROMBOEMBOLISM
EPIDEMIOLOGY
Thromboembolism is the second leading cause of death in cancer patients.
Symptomatic deep vein thrombosis occurs in approximately 15% of all patients with cancer and up to 50% of those with advanced malignancies.
PATHOPHYSIOLOGY
Malignancy is a hypercoagulable state. Neoplastic cells and chemotherapy can cause intimal injury. Obstructive tumors often cause venous stasis, which is exacerbated by decreased mobility.
Angiogenesis inhibitors such as thalidomide, sunitinib, and bevacizumab are associated with thrombosis.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
See Chapter 27 for 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.
NAUSEA AND VOMITING
PATHOPHYSIOLOGY
Chemotherapy commonly causes nausea and vomiting.
CLINICAL FEATURES
Patients present with a history of recent chemotherapy and may show signs of dehydration.
DIAGNOSIS AND DIFFERENTIAL
Other causes of nausea and vomiting include radiation enteritis, bowel obstruction, infection or tumor infiltration, and increased intracranial pressure.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Rehydrate patients with isotonic crystalloids and treat electrolyte abnormalities as needed.
Administer antiemetics (Table 141-2).
TABLE 141-2 Antiemetic Agents for Chemotherapy-Induced Vomiting
EXTRAVASATION OF CHEMOTHERAPEUTIC AGENTS
CLINICAL FEATURES
Extravasation may cause pain, erythema, and swelling, usually within hours of the infusion.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
If irritation develops during infusion through a peripheral line, stop the infusion and attempt aspiration through the line.
Consult an oncologist to discuss the use of antidotes for extravasation of anthracyclines, vinca alkaloids, mitomycin, cisplatin, mechlorethamine, and paclitaxel.
For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 235, “Emergency Complications of Malignancy,” by Paul Blackburn.