ACUTE SPINAL CORD COMPRESSION Multiple myeloma
Non-Hodgkin and Hodgkin lymphomas
Carcinoma of lung
Carcinoma of prostate
Carcinoma of breast

The emergency physician's role includes not only suspicion and recognition of cord compression but also institution of measures to prepare the patient for potential emergency surgery. This includes assessment of fluid status, hematologic parameters and cardiorespiratory functions. CT scanning of the thoracolumbar spine may demonstrate the level of compression. Myelography is definitive. Decadron, 10 mg IV, or Solumedrol, 30 mg/kg IV, as recommended for acute traumatic spinal cord injury, should be given. Emergency surgical decompression or emergency radiotherapy is necessary to prevent irreversible neural damage.

UPPER AIRWAY OBSTRUCTION

UPPER AIRWAY OBSTRUCTION Carcinoma of larynx
Thyroid carcinoma
Lymphoma
Metastatic lung carcinoma

Fiberoptic laryngoscopy is usually necessary to evaluate airway lumen size, because local anatomy is generally greatly distorted. Lateral soft-tissue x-rays are of value in assessing laryngotracheal patency. Establishment of an effective airway is primary and surgical tracheostomy may be required prior to the intitiation of radiotherapy.

CARDIAC EMERGENCIES

Malignant Pericardial Effusion with Tamponade

Malignant Pericardial Effusion with Tamponade Malignant melanoma
Hodgkin lymphoma
Acute leukemia
Carcinoma of lung
Carcinoma of breast
Carcinoma of ovary
Radiation pericarditis

The hemodynamic consequences of malignant pericardial effusions are a function of the volume and speed of accumulation. Even collections greater than 500 mL may be well tolerated if development is slow. Sudden intrapericardial bleeding is associated with dyspnea, chest pain, and hypotension. If the myocardium is also involved with metastatic disease, cardiac dysfunction will result in a decrease in cardiac output as well.

The classical clinical features of cardiac tamponade are (1) hypotension and a narrowed pulse pressure; (2) jugular venous distension; (3) diminished heart sounds; (4) pulsus paradoxus greater than 10 mmHg; (5) low QRS voltage; and (6) cardiomegaly without evidence of congestive heart failure on chest x-ray. Diagnosis is confirmed by echocardiography. Emergency percutaneous pericardiocentesis may be life-saving. It can be done blindly, if extreme haste is needed, or under fluoroscopic guidance. Definitive treatment consists of pericardiectomy, establishment of a pericardial window, radiation, or intrapericardial chemotherapy.

Coronary Artery Disease

Coronary Artery Disease Many cancer patients also have coronary artery disease. Anemia from bone marrow suppression or malignant infiltration can result in decreased myocardial oxygen supply. Interferon and interleukin 2 (IL-2) can increase cardiac output, resulting in an increased myocardial oxygen demand. Several chemotherapeutic agents have been associated with cardiac ischemia, including 5-fluorouracil, vinblastine, and IL-2. Sternal pain mimicking angina has been associated with GM-CSF.

Many agents have been associated with tachyarrhythmias, bradyarrhythmias, and blocks. These include the anthracyclines, 5-fluorouracil, interferon, IL-2, GM-CSF, and taxol. Myocarditis has been reported in association with anthracyclines and cyclophosphamide. Anthracyclines are directly toxic to myocardial cells, while cyclophosphamide toxicity appears to be vascular. Anthracycline-induced cardiomyopathy may occur months to years after cessation of treatment and is thought to be related to both the total cumulative dose and mode of administration.

Superior Vena Cava Syndrome

Superior Vena Cava Syndrome Small-cell (oat-cell) carcinoma of lung
Squamous cell carcinoma of lung
Lymphoma

On physical examination, neck vein and upper chest vein distension may be apparent. Facial plethora and telangiectasia often are prominent, but edema of the face and arms is generally subtle. Papilledema on fundoscopic examination indicates critical intracranial pressure and justifies early diuretic therapy. A palpable supraclavicular mass due to direct tumor extension can occasionally be noted with tumors of the superior mediastinum. Chest x-ray will demonstrate an enlarged mediastinum and possibly an isolated primary lesion in the lung parenchyma.

Prompt administration of diuretics and glucocorticoids may help reduce venous pressure prior to initiation of mediastinal irradiation. Furosemide, 40 mg intravenously, and methylprednisolone, 120 mg intravenously, are frequently used to reduce intracerebral edema. In advanced disease, radiotherapy to improve cardiodynamics is frequently necessary before tissue diagnosis can be obtained.

HYPERCALCEMIA OF MALIGNANCY

HYPERCALCEMIA OF MALIGNANCY Renal cell carcinoma
Multiple myeloma
Bone metastases from carcinoma of breast, prostate, or lung
Humoral-induced non-Hodgkin lymphoma and adult T-cell lymphoma-leukemia

Approximately 40 percent of patients with multiple myeloma will have hypercalcemia. An often encountered clinical triad includes back pain, constipation, and depression in the level of consciousness. Hypercalcemia from any cause may induce hypertension, constipation, and an altered sensorium. Elevated ionized calcium is responsible for neuromuscular dysfunction and therefore serum calcium levels should be interpreted with phosphorus, serum albumin, and blood pH determinations. The QT interval of the electrocardiogram may shorten as the serum calcium rises.

The majority of patients with malignancy-induced hypercalcemia will improve with saline infusion and intravenous furosemide (1 to 2 L saline load and 80 mg of IV furosemide). This will promote renal calcium excretion but depends upon adequate renal function and glomerular filtration. Because renal insufficiency is a common accompaniment in myeloma, assessment of blood urea nitrogen and creatinine levels is important to ensure both adequacy of response and avoidance of iatrogenic fluid overload. Hemoconcentration and dehydration may additionally aggravate elevating calcium. For severe hypercalcemia, hemodialysis or peritoneal dialysis against a low- or no-calcium dialysate may be necessary. The IV administration of inorganic phosphate is a rapid and effective method for decreasing blood calcium, but its use is controversial because of the associated adverse effects. Phosphate administration can initiate and accelerate metastatic soft tissue calcification and can cause hypocalcemia, hypotension, renal failure, and death. The dose of intravenous phosphate is 1 g infused over 8 h. Serum calcium may fall within minutes, and decline in calcium levels may continue for several days. Oral phosphate, given as 1 g of sodium acid phosphate daily, produces maximum effect after several days. Glucocorticoids can be given empirically in comatose or obtunded patients with serum calcium levels greater than 13 mg/dL. The dose is 100 mg of prednisone or equivalent, but the hypocalcemic effect takes several days to develop. The effect of glucocorticoids is greatest in the hematologic malignancies and breast cancer and is unpredictable in solid tumors. Mithramycin acts by inhibiting bone resorption. The dose is 25 mg/kg delivered as an IV infusion. Its effect is usually evident in 24 to 48 h.

SYNDROME OF INAPPROPRIATE ADH

SYNDROME OF INAPPROPRIATE ADH Malignancy of the brain, lung, pancreas, duodenum, thymus, prostate
Lymphosarcoma

HYPERVISCOSITY SYNDROME

HYPERVISCOSITY SYNDROME Multiple myeloma
Waldenström macroglobulinemia
Chronic myelocytic leukemia

Fatigue, headache, anorexia, and somnolence are early nonspecific symptoms. As blood flow slows, microthromboses may occur, with the advent of local symptoms such as deafness, visual disturbances, and jacksonian or generalized seizures. The diagnosis of hyperviscosity must be considered in the emergency department when patients with unexplained stupor or coma are found to have anemia, with rouleau formation on the peripheral blood smear. The most readily appreciated physical findings are in the ocular fundi and include sausage-linked retinal vessels, hemorrhages, and exudates. Laboratory evaluation should include coagulation, renal, and electrolyte profiles. Hypercalcemia can coincide, and when M-component protein concentrations are high, factitious hyponatremia may also be present. A clue to the presence of hyperviscosity may be the laboratory's inability to perform chemical tests because of the serum stasis in the analyzers, undoubtedly due to too thick blood. Serum viscosity and protein electrophoresis determinations are diagnostic.

The emergency physician's role is predominantly suspicion and recognition of the syndrome in patients with unexplained stupor and coma. Hyperviscosity is generally a presenting manifestation of certain plasma cell dyscrasias, and a history of previously documented disease is often lacking. Initial therapy is rehydration followed by emergency plasmapheresis. When coma is present and the diagnosis rapidly established, a temporizing measure may be a two-unit phlebotomy with saline infusion and replacement of the patient's red cells.

ADRENAL INSUFFICIENCY AND SHOCK

ADRENAL INSUFFICIENCY AND SHOCK Carcinoma of the lung
Carcinoma of the breast
Malignant melanoma
Retroperitoneal malignancies
Withdrawal of chronic steroid therapy

Laboratory clues to the possible concomitant presence of adrenal insufficiency may be mild hypoglycemia, hyponatremia, hyperkalemia, and eosinophilia. Azotemia is, however, nonspecific and is often present in dehydration from any cause. In suspected cases, a serum cortisol should be drawn prior to steroid treatment.

Normal adrenal glands maximally produce approximately 300 mg per day of hydrocortisone when stressed. This has served as a guideline for replacement therapy. Adrenalectomized individuals are maintained on average doses of 35 to 40 mg of hydrocortisone per day and this is increased during potential stress. Appropriate emergency doses of hydrocortisone would be 250 to 500 mg intravenously. Somewhat larger doses have been employed in septic shock.

GRANULOCYTOPENIA, IMMUNOSUPPRESSION, AND INFECTION

GRANULOCYTOPENIA, IMMUNOSUPPRESSION, AND INFECTION Overwhelming infection is a common cause of death in the immunocompromised host. A variety of factors may contribute to increased susceptibility to infection in cancer patients. Important factors include

1.       Malnutrition and cachexia

2.       Granulocytopenia

3.       Impaired humoral immunity and antibody production, as in chronic lymphocytic leukemia or multiple myeloma

4.       Altered cellular immunity, as in Hodgkin and other lymphomas

5.       Postsplenectomy susceptibility to serious pneumococcal infections

6.       Reactivation tuberculosis with concurrent glucocorticoid therapy

7.       Polymicrobial enteric sepsis from bowel organism entry; carcinoma of colon or mucosal damage from chemotherapy

8.       Nosocomial infections transmitted through blood transfusion and blood products

9.       Immunosuppression and myelosuppression of chemotherapy

Both the frequency of infection and the mortality rate increase significantly when the circulating granulocyte pool is below 1000 to 1500 per cubic millimeter. Cancer patients are at risk for a variety of bacterial, viral, and fungal infections. Frequently encountered infections include pneumococcal sepsis and pneumonia; Staphylococcus aureus infection; enteric gram-negative pneumonia or sepsis, including Pseudomonas infections; and localized or disseminated varicella zoster viral and cytomegaloviral infections. Immunosuppression predisposes to invasion by organisms that are normally held at bay by host defenses and biocompetition from normal body flora. Such opportunistic infections include Pneumocystis carinii pneumonia (protozoal), disseminated candidiasis, aspergillosis, cryptococcal meningitis, pulmonary nocardiosis, and histoplasmosis.

For fever in the presence of malignancy or a history of chills and rigor, the emergency physician should assume an infectious etiology and initiate appropriate laboratory studies and cultures. Life-threatening gram-negative sepsis with hypotension should be aggressively treated after appropriate cultures. Fluids, broad-spectrum antibiotics, and intravenous glucocorticoids are advised. Few bacterial organisms would be missed with regimens containing a second- or third-generation cephalosporin (cefazolin, cefoxitin, cefoperazone, cefotaxime) and an aminoglycoside (gentamicin, tobramycin, amikacin). Anaerobic coverage may be added (clindamycin) if peritonitis or abdominal symptomatology exists. Other choices include piperacillin/lazobactam, 3.375 g IV q6h, or ampicillin/sulbactam, 3.0 g IV q6h, or ticarcillin clavulanate, 3.1 g IV q6h.

HEMATOLOGIC SYNDROMES

HEMATOLOGIC SYNDROMES Thromboembolism is not uncommon in cancer patients and is due to a number of factors such as a hypercoagulable state; decreased proteins C, S, and antithrombin III; and the effect of metastases on activation of the coagulation pathway. Cancer patients are at increased risk for both deep venous thrombosis and pulmonary embolism. However, anticoagulation may result in bleeding at sites of metastatic disease, so that treatment options are more complex and may include placement of a filter in the inferior vena cava.

Polycythemia is enhanced production of red cells due to increases in sensitivity of erythropoietin. Any organ system can be affected by resultant thrombosis, bleeding, or hyperviscosity, but CNS affects are the most devastating. Celiac or mesenteric vessel ischemia, or Budd-Chiari syndrome, is seen when GI vessels are involved. If the hematocrit is >60 percent and symptoms are present, emergency phlebotomy is necessary.

Either acute or chronic leukemias can result in white blood cell counts >100,000 per mL. A leukocrit of > 10 percent is often associated with clinically significant hyperviscosity, and CNS dysfunction and respiratory distress can occur from capillary leukostasis. Diuretics worsen symptoms because they will increase the leukocrit. Treatment is directed at the underlying malignancy, and allopurinol should also be administered in anticipation of massive tumor lysis, to prevent acute gouty arthropathy and renal failure.

GASTROINTESTINAL SYNDROMES

GASTROINTESTINAL SYNDROMES Acute gastrointestinal complications may or may not be related to the underlying malignancy. In patients with cancer, even gastric cancer, the major causes of GI bleeding are still hemorrhagic gastritis and peptic ulcer disease. Intraarterial hepatic chemotherapy infusions have been associated with GI bleeding, especially from the duodenum. Chemotherapy or radiotherapy can cause vomiting, resulting in Mallory-Weiss tears or reflux esophagitis.

Cancer patients with acute abdominal processes present with typical signs and symptoms unless they are receiving exogenous steroids. Acute appendicitis has been reported to occur in up to 4 percent of patients with leukemia.

ACUTE RENAL FAILURE

ACUTE RENAL FAILURE Prerenal azotemia can be a result of dehydration from vomiting and disease, from chemotherapy, anorexia, or diuretics. Hepatic and peritoneal disease may cause sequestration of fluid in the peritoneal cavity, leading to intravascular volume depletion. Interleukin 2 and cyclosporine can also cause prerenal azotemia.

Multiple myeloma and lymphoma can cause amyloid deposition in the glomeruli, resulting in rapidly progressive renal failure. Interstitial nephritis can also result from renal infiltration by lymphoma. Intratubular obstruction can result from tumor lysis syndrome, hypercalcemia, and gammopathies and has also been reported with high-dose methotrexate and acyclovir.

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