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CHAPTER 93: Oncologic Emergencies 877

The clinical presentation of ICH can vary from focal deficits to severe Dehydration can lead to renal failure and worsening hypercalcemia.
changes in mental status. If ICH is suspected as a cause for neurological Aggressive hydration should be initiated with normal saline at a rate
deficits, a CT scan of the brain should be rapidly performed. Findings on of 200 mL/h with close monitoring of volume status to avoid fluid
CT include intraparenchymal, intraventricular, and subarachnoid hemor- overload. Loop diuretics such as furosemide (40 mg IV every 12-24 h)
rhage (SAH), and subdural and epidural hematomas. Although studies were previously used to promote calciuresis. However, their use is no
have not been able to correlate imaging findings with clinical diagnosis, longer recommended as a recent meta-analysis showed that they did not
several reports have suggested that subdural hematomas are usually consistently decrease calcium levels, and were associated with further
secondary to thrombocytopenia and dural disease, SAH to leptomeningeal volume depletion and electrolyte imbalances. 98
disease and neoplastic aneurysms, and massive intraparenchymal hemor- Bisphosphonates are the most efficient and recommended treatment
rhages to coagulopathies that are usually encountered in patients with for hypercalcemia. 96,99 These agents block bone resorption by osteoclasts.
hematologic malignancies. 81,88,89 Early MRI has proven useful in diagnosing Double-blind RCTs have shown zoledronic acid at a dose of 4 mg IV
and managing ICH. MRI is also helpful to diagnose TRH when associated over 15 minutes to be more efficient than pamidronate (60-90 mg IV)
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with specific findings such as heterogeneity of hematoma signal, decreased regardless of tumor type, calcium levels, number of bone metastasis, and
or absent hemosiderin, and delayed pattern of hematoma evolution. 88 PTHrP levels. Renal failure has been observed in animals treated with
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Treatment of malignancy-related ICH does not differ largely to that bisphosphonates, and while uncommon, it is recommended to monitor
offered to the general population. Immediate reversal of coagulopathy renal function and to avoid the administration of bisphosphonates in
should be performed with platelets, plasma, and prothrombin protein patients with a glomerular filtration rate <30 mg/dL. 92,99
concentrate transfusions, as needed. Factor VII infusion has not Because bisphosphonates are effective only after 48 hours and hydration
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improved outcomes of massive ICH in patients with leukemia and has can only aid with calciuresis to a certain degree, other immediate measures
been associated with a higher incidence of thrombotic events. Control such as calcitonin administration should be taken. Calcitonin (4-8 IU/kg
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of blood pressure to maintain adequate cerebral perfusion has also subcutaneously or iv every 12 h) decreases calcium levels by inhibiting
been beneficial in cancer patients. Evacuation of hematomas and large osteoclasts and inducing calciuresis 2 hours after administration. 92,94,96
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collections, especially when there are early signs of increased intra- Patients can develop resistance (tachyphylaxis) to calcitonin; therefore, its
cranial pressure, has been performed satisfactorily in cancer patients. administration should be limited to two doses. Cases of anaphylaxis have
97
However, it is important to note that complications related to bleeding also been reported requiring that patients be monitored closely. 97
can be higher in the setting of coagulopathy while performing these Glucocorticoids have also been effective in the treatment of lymphoma-
procedures. Corticosteroids have also been used effectively for the treat- related hypercalcemia. Corticosteroids inhibit calcitriol production by
ment of edema related to TRH. Prophylactic brain radiation and leuka- macrophages and therefore decrease gut calcium absorption and osteo-
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pheresis have not been useful in preventing ICH in patients with APML blast activity. Prednisone (60 mg orally daily) or hydrocortisone 100 mg
95
but administration of all-trans-retinoic acid was shown to decrease the iv every 6 h is commonly used.
incidence of ICH in these patients. 91
■ TUMOR LYSIS SYNDROME
METABOLIC EMERGENCIES Tumor lysis syndrome (TLS) is characterized by electrolyte and metabolic
■ HYPERCALCEMIA derangements that occur after rapid breakdown of proliferating malig-
nant cells. TLS can be spontaneous in rapidly growing tumors or present
Hypercalcemia is present in 20% to 30% of patients with malignancy. 92,93 after treatment with chemotherapy, corticosteroids, or radiation. 100,101
Malignancy-associated hypercalcemia (MAH) is common in solid TLS has an incidence of 5% to 10% and is typically associated with
tumors such as metastatic lung and breast cancer, and in hematologic acute leukemias particularly acute lymphoblastic leukemia and highly
malignancies such as Hodgkin and non-Hodgkin lymphomas, and aggressive lymphomas, such as Burkitt lymphoma. 100,101 TLS has also
adult T-cell leukemia/lymphoma. MAH can be divided into humoral, been reported in solid malignancies such as breast cancer, small cell lung
94
osteolytic, and calcitriol-associated hypercalcemia. In humoral hyper- carcinoma, and germ cell tumors. 102
95
calcemia, parathyroid hormone–related protein (PTHrP) and cytokines During cell breakdown the released potassium may lead to hyperka-
(IL-1, IL-6, TNF-α, TGF-β) are released by tumor cells and increase lemia, which if left untreated can lead to arrhythmias and death. Uric
calcium reabsorption by the kidney and inhibit osteoblasts. 92-94,96 acid, a metabolite of free nucleic acids, may crystallize and deposit in
Osteolytic MAH, observed in 20% of cases, is associated with increased the renal tubules, causing acute kidney injury which can further worsen
osteoclastic activity secondary to bone metastasis. Calcitriol-associated hyperkalemia. Rapid cell breakdown also causes hyperphosphatemia
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hypercalcemia compromises less than 1% of MAH and is associated with that, if severe, can cause vomiting, diarrhea, lethargy, and seizures.
hematologic malignancies. 93,95 Although physiopathology of calcitriol- Hypocalcemia occurs due to calcium binding to phosphorus. When
associated hypercalcemia is not completely understood, it is believed severe, hypocalcemia can result in muscular cramping, cardiac arrhyth-
that WBCs in lymphoma and leukemias have increased calcitriol mias, and hypotension.
production. In a majority of cases, the hypercalcemia is secondary to The management of TLS should include identification of patients with
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a combination of all of these presentations. Despite available treatments predisposing risk factors, early recognition, and treatment according to
for hypercalcemia, patients with MAH have a very poor prognosis and severity stratification. Common risk factors for TLS are preexisting
their median survival is less than 35 days; when hypercalcemia is refrac- hyperuricemia, a large tumor burden, rapidly growing malignancies,
tory to treatment, palliation should be considered. 97 fluid depletion, and renal dysfunction. Recently patients have been
103
Symptoms of hypercalcemia include muscular cramping, constipa- characterized into low, intermediate, and high risk for TLS according to
tion, dehydration, polyuria, changes in mental status, and cardiac their malignancy and laboratory findings. This stratification improves
100
dysrhythmias. The severity of symptoms is usually associated with the early recognition and serves as a guide for treatment. In 2004, Cairo
degree of hypercalcemia, with central nervous system symptoms being and Bishop developed laboratory and clinical diagnostic criteria for TLS
present with calcium levels >14 mg/dL. Moreover, elderly patients, (Fig. 93-3). The presence of two or more laboratory abnormalities
65
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and those with acute elevation of calcium levels may be more symptom- 2 days before or 7 days after cytotoxic treatment is indicative of TLS and
atic. Initial workup for hypercalcemia should include measurements of should trigger aggressive management.
ionized calcium, PTH, PTHrP, and 25-hydroxy vitamin D levels. Supportive care of patients at risk for TLS should be initiated with
Almost all patients with hypercalcemia have significant intravascular aggressive hydration to maintain a urine output of 100 mL/h. Close
volume depletion due to polyuria, vomiting, and decreased oral intake. monitoring of electrolytes and lactate dehydrogenase and uric acid

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