A 19-year-old man with acute lymphoblastic leukemia is found to be lethargic and complains of nausea and muscle cramps after receiving cytotoxic therapy. A basic metabolic panel is notable for:
An ECG is notable for peaked T waves and frequent premature ventricular complexes.
Which one of the following treatment options is MOST appropriate at this time?
Correct Answer: C
The patient has symptomatic hyperkalemia, evidence by peaked T waves and a plasma potassium level of 6.9 mEq/L, which is an indication for emergent dialysis.
Tumor lysis syndrome (TLS) is an oncologic emergency caused by release of large amounts of potassium, phosphate, and uric acid into the plasma in response to tumor cell lysis resulting from cytotoxic therapy, radiation therapy, immunotherapy, or glucocorticoid therapy. Patients with highgrade lymphomas (Burkitt lymphoma) or acute lymphoblastic leukemia, those with large tumor burdens, or highly proliferative tumors are at higher risk for TLS. TLS can also occur spontaneously in highly proliferative tumors due to high cell turnover.
Hyperuricemia leads to precipitation of uric acid crystals in the renal tubules and can cause acute kidney injury (AKI). Hyperphosphatemia and deposition of calcium phosphate crystals in the renal tubules can also lead to AKI. Hyperkalemia can lead to arrhythmias, including ventricular fibrillation and cardiac arrest.
The signs and symptoms of TLS occur from metabolic abnormalities (hyperkalemia, hyperphosphatemia, hyperuricemia) and associated development of AKI and include lethargy, nausea, vomiting, diarrhea, anorexia, muscle cramps, tetany, hematuria, arrhythmias, and cardiac arrest.
Aggressive intravenous fluid therapy to increase renal perfusion and prevent precipitation of uric acid and calcium phosphate crystals in the renal tubules is the mainstay of TLS prophylaxis. Recommended urine output is 2 mL/kg/h. Rasburicase is the first-line hypouricemic agent for patients at high risk for TLS, especially those with renal or cardiac dysfunction, while allopurinol, a xanthine oxidase inhibitor which blocks the metabolism of hypoxanthine and xanthine to uric acid, is the first-line prophylactic agent in patients at intermediate risk for TLS.
A 65-year-old man with a diagnosis of small-cell lung cancer presents to the emergency with complaints of hoarseness, shortness of breath, and swelling of his face and right arm. His vital signs are:
On examination, he is stridorous and unable to speak in full sentences. ECG is notable for sinus tachycardia and a chest x-ray reveals widened mediastinum.
What is the most appropriate next step in management?
Correct Answer: A
The patient has superior vena cava syndrome (SVCS) from malignancy with life-threatening symptoms (eg, stridor, respiratory distress) and require immediate stabilization (endotracheal intubation to secure the airway, circulatory support), followed by definitive intervention (endovenous recanalization, mechanical thrombectomy, SVC filter placement).
Radiation therapy is no longer recommended as the first-line treatment. SVCS occurs in response to mechanical obstruction of the SVC due to external compression, tumor invasion into the vessel, or internal obstruction. Malignancy is the most common cause of SVCS, with lung cancer and non-Hodgkin lymphoma as the most common types of associated malignancy. Dyspnea is the most common presenting symptom. Other symptoms may include facial, neck, and arm swelling, hoarseness, stridor, chest pain, and dysphagia. Physical examination findings in patients with SVCS include facial, neck, and arm edema, engorged neck veins, stridor, and in severe cases, obtundation due to increased intracranial pressure and brain swelling.
Chest radiography and ECG provide nonspecific information in patients with SVCS. Chest radiograph may show widened mediastinum and ECG commonly shows sinus tachycardia. CT venography provides information about the location and extent of the obstruction, and catheter-mediated thrombolysis can be performed concurrently with the imaging.
A 54-year-old woman with breast cancer is brought to the emergency room with progressive confusion, anorexia, constipation, weight loss, and weakness. Vital signs are:
BP 94/57 mm Hg
HR 87 beats/min
SaO2 96% on RA
On examination, she is drowsy but easily arousable and oriented to person. Her neurologic examination is otherwise unremarkable. Lab studies are notable for:
What is the most appropriate initial treatment?
Correct Answer: B
Hypercalcemia accounts for 0.6% of hospital admissions. It can present with a variety of nonspecific symptoms that affect multiple organ systems. Symptoms include neurological disturbances (ranging from anxiety and confusion, to lethargy and coma), gastrointestinal disturbances (anorexia, nausea, constipation, and pancreatitis), renal dysfunction (polyuria, dehydration, AKI), and musculoskeletal abnormalities (weakness, cramping). ECG may show a shortened QT interval, and in severe cases of hypercalcemia, arrhythmias and ventricular tachycardia may be present. Severity of symptoms correlates with the severity of hypercalcemia.
Up to 90% of the cases of hypercalcemia are due to hyperparathyroidism and malignancy (lung cancer, multiple myeloma, and renal cell). Other causes, however, include medications (thiazide diuretics, antacids such as calcium carbonate, vitamin A and D supplements, and lithium), immobilization, granulomatous diseases (sarcoidosis), and thyrotoxicosis. When an elevated plasma calcium level is identified, it should be confirmed to ensure true hypercalcemia (serum calcium level is affected by albumin concentration, and hypoalbuminemia falsely elevates the serum calcium level). In addition ionized calcium levels should be interpreted in the context of the patient’s pH. Parathyroid hormone level and serum phosphorus level should also be measured.
Treatment of hypercalcemia depends on the severity of the patient’s symptoms. While asymptomatic patients can be treated on an outpatient basis, symptomatic patients and those with significantly elevated calcium levels should be hospitalized for IV fluid therapy. If a malignancy is detected as the underlying cause of hypercalcemia, the patient should undergo definitive treatment for malignancy, if possible.
IV fluid therapy with 0.9% NS is the cornerstone of treatment of patients with hypercalcemia. Dehydration is secondary to decreased intake (anorexia, nausea) and increased urine output (polyuria). Calcitonin is quick acting and can be given for initial stabilization in addition to IV fluids. Bisphosphonates take 48 hours to work and are utilized for longterm management of hypercalcemia. Furosemide is no longer recommended due to the risk of dehydration and lack of evidence of benefit.
A 57-year-old woman with a history of breast cancer treated with mastectomy and radiation therapy is admitted with a 4-week history of progressive low back pain. She reports decreased sensation over her buttocks, perineal region, and posterior superior thighs and occasional difficulty with voiding. Her physical examination is noticeable for decreased anal sphincter tone.
Malignant spinal cord compression (MSCC) is a devastating complication of cancer. Cancers of prostate, breast, and lung account for most cases of vertebral metastases; however cancer of any origin can metastasize to the spine.
Back pain occurs in 95% of patients for up to 2 months before signs related to MSCC appear. Pain can be localized or radicular in nature and the severity of pain often increases over time. A higher index of suspicion is required in patients with a known history of cancer and those presenting with unremitting pain or pain localized to middle or upper spine. Motor deficits (eg, weakness, unsteady gait, difficulty walking or standing, etc.) that has progressed over days or few weeks is the second most common symptom in patients with MSCC. Sensory symptoms (eg, parasthesias, numbness, decreased sensation) are less common than motor deficits. Autonomic dysfunction (bowel or bladder incontinence) is a late complication of MSCC. Cauda equina syndrome, characterized by low back pain, unilateral or bilateral radicular pain, saddle anesthesia, erectile dysfunction, loss of bladder or bowel continence, and lower extremity weakness, may be the first presentation of MSCC in patients with metastasis to lumbar spine.
An MRI of full spine within 24 hours of presentation is the imaging study of choice in patients presenting with pain and autonomic dysfunction (bowel/bladder incontinence). CT scan is used for surgery or radiation therapy planning. Definitive therapy for MSCC includes decompressive surgery and radiation therapy. In absence of contraindications, all patients with MSCC should receive corticosteroids as adjunctive therapy.
A 63-year-old man is admitted to the ICU with epistaxis, blurred vision, and altered mental status. His medical history includes hypertension, diabetes mellitus, and Waldenstrom macroglobulinemia. Vital signs are:
His physical examination is notable for bloody nostrils, and he is somnolent but responsive to verbal stimuli. Laboratory studies are notable for:
Which one of the following interventions is not indicated at this time?
Hyperviscosity syndrome (HVS) is an oncological emergency characterized by the triad of neurological symptoms, visual disturbances, and mucosal bleeding and is an oncological emergency. HVS is caused by a pathological increase in serum proteins, RBCs, white blood cells (WBCs), and/or platelets, or by deformed RBCs. Waldenstrom macroglobulinemia is the most common cause of HVS. Other causes include multiple myeloma, rheumatoid disease, polycythemia, sickle cell disease, leukemia, and spherocytosis.
Diagnosis is established by clinical evidence of elevated serum viscosity. Additional laboratory tests to confirm the diagnosis include complete blood count (CBC), peripheral blood smear, and coagulation profile. Measurement of serum immunoglobulins is not necessary for establishing diagnosis of HVS.
Timely treatment can prevent catastrophic ischemic sequalae such as myocardial infarction, stroke, thromboembolic events, and multiorgan system dysfunction. Supportive care in addition to plasma exchange or plasmapheresis is the mainstay of managing HVS. In cases where emergent plasmapheresis cannot be arranged, phlebotomy can be performed (removing 1-2 units of the patient’s blood) as a temporizing measure. Dehydration increases plasma viscosity and should be treated with IV fluids. Chemotherapy for the underlying malignancy is the definitive therapy. RBC transfusion can increase blood viscosity and worsen the thrombotic/ischemic effects.
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