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CHAPTER 93: Oncologic Emergencies 879

and mortality is as high as 40% to 60%. 102,103,115 Certain chromosomal SVCS are due to lung cancer and lymphoma; 50% are due to nonsmall cell
mutations in AML and ALL are thought to be associated to higher white lung carcinoma (NSCLC), 25% due to small cell lung carcinoma (SCLC),
blood cell (WBC) counts and higher risk for leukostasis. 102,114 and 10% due to non-Hodgkin lymphoma. 122,123 Once SVCS is present in the
Hyperviscosity, secondary to elevated WBC counts, was thought to be the setting of malignancy, life expectancy is only 2 to 9 months. 123
main factor in the physiopathology of leukostasis. However, in vitro stud- Most common findings on physical examination in patients with
ies have shown that when hyperleukocytosis is present, there is decreased SVCS include facial flushing and edema, facial plethora, and distention
platelet and erythrocyte production to avoid increased viscosity. of neck and superficial veins (Fig. 93-5). Patients will present with com-
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Thus, a more important role has been contributed to the interaction plaints of arm edema, dyspnea, orthopnea, dizziness, and presyncope.
of leukemic blasts with the endothelium. First, there is evidence that When SVC compression occurs, collateral flow is created through the
there is increased expression of adhesion markers such as ICAM-1 and azygos and intercostal veins within 2 weeks. 122,123 If obstruction is acute,
VCAM-1 in blasts during leukostasis. 85,102,115 Second, increased produc- no collateral flow is formed and symptoms are severe. Patients can
tion of inflammatory markers such as TNF-α and IL-1β also plays an sometimes present with hypotension and orthostasis due to decreased
important role in blast aggregation during leukostasis. 85,114 venous return; however, hemodynamic compromise is usually present
A definitive diagnosis of leukostasis is made during pathological when there is associated cardiac compression by the mass. In the past,
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examination at autopsy; however, clinical suspicion should be enough to SVCS was considered an emergency; however, current data suggest that
lead to prompt treatment. The most commonly involved organs are the high rates of immediate death are only observed when there is airway
respiratory and central nervous system (CNS). 102,114 Symptoms such as compromise or cerebral edema. 122,124 Airway compromise is usually
dyspnea, hemoptysis, respiratory distress, and hypoxemia should suggest secondary to laryngeal or vocal cord edema and patients commonly
pulmonary compromise. Dizziness, headache, confusion, tinnitus, gate present with hoarseness and stridor. Typical symptoms suggestive of
instability, and blurry vision are common CNS symptoms, and in many cerebral edema include headache, confusion, and obtundation. It is
cases are caused by intracranial hemorrhage. 102,114,117 Other clinical syn- important to perform in all patients a complete neurologic examination
dromes are limb and gut ischemia, renal vein thrombosis, heart failure that includes fundoscopy since initial findings of cerebral edema can be
or ischemia, and priapism. 114,115 In patients with a WBC >50,000/mm subtle and therefore missed. Presentation of airway compromise and
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a risk staging model has been created to grade the probability of cerebral edema are considered an emergency, and aggressive and imme-
leukostasis. 117,118 This grading system, while not always used, should diate treatment should be pursued. 122,125
guide treatment in patients with elevated WBC counts. Initial diagnosis of SVCS should be clinical, and both history-taking
For the past two decades, there has been very little progress in the and imaging studies should help identify the cause of obstruction and its
treatment of leukostasis, and mortality continues to be extremely high. extent. Chest x-ray is abnormal in about 84% of patients with SVCS.
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Current available treatment of leukostasis consists of cytoreduction with CT scan with contrast should be performed to further elucidate the
leukapheresis, hydroxyurea, and chemotherapy. Leukapheresis is usually size of the mass, extent of obstruction, and whether there is associated
initiated in cases of AML if WBC >50,000/mm , and in ALL if WBC is thrombosis. Magnetic resonance imaging can be performed if there are
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>250,000/mm . 3 113,115 A reduction of WBC >40% can be observed after contraindications for intravenous contrast. 120,123
just one treatment. However, some studies suggest that lower WBC Initial symptomatic treatment for SVCS includes oxygen supplemen-
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counts are not associated with lower mortality. While leukapheresis tation, head elevation, and avoiding the supine position. Some authors
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is still used in many institutions, its timing, number of treatments, and suggest a short diuretic trial while other treatments are implemented;
target WBC count have not been defined. Moreover, retrospective however, the literature has failed to show significant improvement with
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studies have failed to show that leukapheresis improves mortality, and diuretics. 122,124 Management of airway compromise requires rapid stabili-
no prospective RCTs have been performed. 85,119 Currently, the use of zation of the airway. Use of corticosteroids has been described; however,
leukapheresis continues to be based on incidental reports of patients there are no RCTs suggesting that their use is beneficial. Moreover, use
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who have had clinical response after its use. 113,115 of corticosteroids prior to biopsy can alter the yield of pathologic diag-
Hydroxyurea, also used to treat hyperleukocytosis, has comparable nosis, especially if lymphoma is suspected. 120,123 Therefore, the use of
efficiency and outcomes to leukapheresis. While malignancies associ- corticosteroids should be limited only when as part of protocols for
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ated with leukostasis carry a poor long-term prognosis, early treatment chemotherapy or radiotherapy. Some have suggested anticoagulants
with chemotherapy has shown to improve mortality in the short term. be used routinely in SVCS due to the high incidence of pulmonary
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Cranial irradiation has been utilized in some centers to treat CNS
symptoms and reduce intracranial hemorrhage. However, studies have
failed to show any benefits from cranial irradiation and thus this is no
longer recommended. Patients with hyperleukocytosis are at high risk
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for tumor lysis syndrome and should be monitored closely for this syn-
drome. Future treatments for leukostasis should aim to inhibit adhesion
molecules and inflammatory markers. Dexamethasone, which decreases
cytokine production and suppresses adhesion markers, has been shown to
be effective in acute promyelocytic leukemia; nevertheless, further studies
to look at its role in AML and ALL are necessary. A better understand-
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ing of the physiopathology of leukostasis may lead to further development
of new treatments and probably improvement of its prognosis.
SUPERIOR VENA CAVA SYNDROME
Superior vena cava syndrome (SVCS) is a group of signs and symptoms
that present after obstruction of the superior vena cava. In the past, vascu-
litis, thrombophilia, and infections causing fibrosing mediastinitis (histo-
plasmosis) or aortic aneurysms (syphilis) were the most common causes FIGURE 93-5. Superior vena cava syndrome. (Reproduced with permission from Lewis
of SVCS. 102,120 Currently >85% of cases are associated with malignancy, MA, et al. Determination of cetirizine in human plasma using high performance liquid chroma-
and an increasing number are due to thrombosis after placement of central tography coupled with tandem mass spectrometric detection: application to a bioequivalence
venous catheters and pacemakers. Ninety percent of malignant causes of study, CA. Can J Clin. September-October 2011;61(5):287-289.)
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