Oncology Emergencies and Critical Care Issues: Spinal Cord Compression, Cerebral Edema, Superior Vena Cava Syndrome, Anaphylaxis, Respiratory Failure, Tumor Lysis Syndrome, Hypercalcemia, and Bone Metastasis
Roland T. Skeel
Spinal cord compression, cerebral edema, superior vena cava syndrome (SVCS), anaphylaxis, respiratory failure, tumor lysis syndrome, hypercalcemia, and bone metastasis can be major causes of morbidity and, in some cases, potential mortality in patients with cancer. Because of the critical nature of these complications of cancer and its treatment, oncologists, oncology nurses, and other oncology health professionals must be prepared to recognize the signs and symptoms of these disorders promptly so that appropriate therapy can be instituted without delay.
I. SPINAL CORD COMPRESSION
A. Tumors
The most common tumors resulting in spinal cord compression are breast cancer, lung cancer, prostate cancer, and renal cancer, although it may also occur with sarcoma, multiple myeloma, and lymphoma. Purely intradural or epidural lesions are uncommon because more than three-fourths of cases arise from metastasis to either a vertebral body or other bony parts of the vertebra or, less commonly, by direct extension from a paravertebral soft-tissue mass. Seventy percent of the bone lesions are osteolytic, 10% are osteoblastic, and 20% are mixed. More than 85% of patients with metastases to the vertebra have lesions that involve more than one vertebral body.
B. Symptoms and signs
The most common early symptoms seen in patients with spinal cord compression are localized vertebral or radicular pain. These are not from the cord compression per se but rather from involvement of the vertebral structures and nerve roots at the level of the compression. Localized tenderness to pressure or percussion over the involved vertebrae is often found on physical examination. Because pain is seen initially in up to 90% of patients, localized back pain, radicular pain, or spinal tenderness in a patient with cancer should evoke clinical suspicion and prompt further evaluation to determine whether the patient has potential or early cord compression. Muscle weakness, evidenced by subjective symptoms or objective physical findings, is present in 75% of patients by the time of diagnosis. The clinician must be aware that progression of this symptom can vary from a gradual increase in weakness over several days to a precipitous loss of function over several hours that may worsen rapidly to the point of paraplegia. If muscle weakness is present, it is incumbent on the physician to act urgently to obtain consultation with the neurosurgeon and the radiation oncologist. It is not appropriate to wait until the next morning! By the time there is muscle weakness, most patients also have sensory deficits below the level of the compression and often have changes in bladder and bowel sphincter function. When compression is diagnosed late or if treatment is not started emergently, only 25% of patients who are unable to walk when treatment is started regain full ambulation.
C. Diagnosis
Magnetic resonance imaging (MRI) is the diagnostic modality of choice, although high-resolution computed tomography (CT) with myelography is an alternative. Plain radiographs and bone scans give evidence of metastases to vertebrae, but in and of themselves are not diagnostic of spinal cord involvement.
When there is evidence of bony involvement of the spine on a plain radiograph, CT scan, or bone scan, the approach is to
obtain an MRI for those patients who have subjective or objective evidence of weakness, radicular pain, paresthesia, or sphincter dysfunction, because these patients are at highest risk of spinal cord compression. Routine MRIs in patients who have completely asymptomatic bony spine metastases (without pain, tenderness, or neurologic findings on a comprehensive clinical examination) are not cost-effective. In patients with only localized pain or tenderness to correspond with the bone scan or radiographic findings, the yield of additional tests is also low. Thus, the clinical determination of whether to obtain additional invasive or costly diagnostic tests is more difficult and requires a careful assessment of all clinical features of the patient. All patients with metastasis to the spine require close follow-up, and they and their families must be urged to report relevant symptoms immediately.
D. Treatment
As noted above, immediate consultation with radiation oncology and neurosurgery is imperative. Because of potentially precipitous deterioration when neurologic deficits have developed, treatment should be started immediately.
1. Corticosteroids. When a radiologic study identifies the level of cord compression or a neurologic deficit is detected on physical examination, dexamethasone should be started immediately to reduce spinal cord edema. A recommended dose is 10 to 20 mg intravenously (IV) as a loading dose and then 4 to 6 mg by mouth or IV four times daily to be continued through the initial weeks of radiation therapy. Higher doses up to 96 mg daily have marginal benefit and toxicity is clearly greater. At the completion of the radiotherapy, the dexamethasone therapy may be tapered.
2. Initial interventional therapy
a. Although the preferences of individual physicians and centers vary, the immediate initiation of radiotherapy once cord compression is diagnosed and corticosteroids have been started, providing the spine is stable and the tumor is likely to be sensitive to radiotherapy, is generally recommended. This is based on several studies that showed no significant improvement in outcome for patients treated with surgery plus radiation versus those treated with radiation alone. However, when there is spine instability, a tumor that is not likely to be sensitive to radiotherapy, or rapid progression of weakness, the surgical option may be preferable. One recent randomized study found that initial surgery was better for preserving the patient’s ability to walk, perhaps owing to improved surgical techniques.
b. Dose and schedule of radiotherapy. Radiation therapy is most frequently given at a total dose of 30 to 45 Gy with daily dose fractions of 200 to 250 cGy. Alternatively, 400 cGy daily may be
given initially for the first 3 days of therapy and then subsequently decreased to standard-dose levels for the completion of the radiation course. Short-course therapies with higher dose fractions have also been used. These appear to have similar functional outcome in patients with a short prognosis, but local control is maintained for a longer time when longcourse (standard) therapy is used. The longer course is thus recommended for patients with better prognosis from their overall disease.
c. The clinical response to radiation is dependent not only on the degree of cord involvement and the duration of symptoms but also on the underlying cell type. In general, patients with severe deficits such as complete paraplegia or a long duration of neurologic deficit are unlikely to have return to normal function. This underscores the need to diagnose and treat these patients rapidly. Lymphoma, myeloma, and other hematologic malignancies, along with breast, prostate, and small cell lung carcinoma, tend to be more responsive than adenocarcinomas of the gastrointestinal tract, non-small-cell lung cancer, renal cancer, and others.
3. Surgery plays a crucial role for some patients. Traditional approaches include decompressive laminectomy for posterior lesions or anterior approaches for other lesions. Newer treatment options include minimally invasive vertebroplasty and kyphoplasty, which may effectively maintain function, reduce pain in appropriately selected patients, and have a shorter recovery time than other procedures. Clear indications for surgery include worsening of neurologic signs or symptoms or the appearance of new neurologic findings during the course of radiation treatment, vertebral collapse at presentation, a question of spinal stability, tumor type expected to be refractory to radiotherapy, and disease recurrence within a prior radiation port. In selected patients, the use of surgery to remove disease in the vertebral bodies followed by stabilization can result in dramatic improvement in pain and function.
II. CEREBRAL EDEMA
A. Clinical evaluation
1. Neurologic signs and symptoms. Intracranial metastases are commonly manifested by a variety of neurologic symptoms and signs, including headache, change in mentation, visual disturbances, cranial nerve deficits, focal motor or sensory abnormalities, difficulty with coordination, and seizures. In the more critical condition of brainstem herniation, there may be gradual to rapid loss of consciousness, neck stiffness, unilateral or bilateral pupillary abnormalities, ipsilateral hemiparesis, or respiratory
dysfunction; the specific findings depend on whether there is uncal, central, or tonsillar herniation. Any new neurologic complaint from a patient with cancer should be viewed with a high index of suspicion that it represents metastasis, especially if metastasis to the brain is commonly associated with the patient’s tumor type.
The history and physical examination provide the first clue to the presence of a metastatic lesion or associated cerebral edema. In general, a history of gradual progression of neurologic symptoms before the development of a significant deficit is more consistent with a metastatic lesion, whereas the absence of symptoms followed by the abrupt onset of a severe deficit is suggestive of a cerebrovascular event.
2. Radiologic studies. MRI is the imaging modality of choice because it has greater sensitivity than CT in detecting the presence of metastatic lesions, evaluating the posterior fossa, and determining the extent of cerebral edema. While CT is sufficient to detect the presence of cerebral edema in a majority of patients, it is necessary to realize that CT fails to diagnose some lesions and may underestimate cerebral edema. If CT of the brain with and without contrast reveals no definite abnormality in the presence of persistent neurologic findings, MRI is the recommended next step. Delay of appropriate imaging studies (either CT or MRI) to examine plain skull radiographs or to obtain radionuclide studies in patients experiencing neurologic difficulties is not warranted.
Warning: In a patient with cancer who has focal neurologic signs or symptoms, headache, or alteration in consciousness, a lumbar puncture to evaluate for possible neoplastic meningeal spread should not be done until a CT scan or MRI shows no evidence of mass, midline shift, or increased intracranial pressure. To do the lumbar puncture without this assurance could precipitate brainstem herniation, which is often rapidly fatal.
B. Treatment
1. Symptomatic therapy. Once the presence of cerebral edema is established, dexamethasone 10 to 20 mg IV to load followed by 4 to 6 mg IV or by mouth four times daily should be started. The rationale for the use of steroids centers around the etiology of cerebral edema. It appears that the invasion of malignant cells releases leukotrienes and other soluble mediators responsible for vasodilation, increased capillary permeability, and subsequent edema. Dexamethasone inhibits the conversion of arachidonic acid to leukotrienes, thereby decreasing vascular permeability. Additionally, steroids appear to have a direct stabilizing effect on brain capillaries. There is some evidence to suggest that patients who do not have lessening of cerebral
edema with the dexamethasone dose just described may respond to higher doses (50 to 100 mg/day). Because of the risk of gastrointestinal bleeding and other side effects of doses higher than 32 mg/day, higher doses are usually not given for more than 48 to 72 hours.
Patients with severe cerebral edema leading to a life-threatening rise in intracranial pressure or brainstem herniation should also receive mannitol 50 to 100 g (in a 20% to 25% solution) infused IV over approximately 30 minutes. This may be repeated every 6 hours if needed, although serum electrolytes and urine output must be monitored closely. Patients with severe cerebral edema should be intubated to allow for mechanical hyperventilation to reduce the carbon dioxide pressure to 25 to 30 mm Hg in order to decrease intracranial pressure.
2. Therapy of the intracerebral tumor. Once the patient has been stabilized, appropriate therapy for the cause underlying the cerebral edema should be implemented. Radiation is the usual modality for most metastases, but surgery may be considered in addition for suitable candidates with easily accessible lesions; combined surgery and radiotherapy may result in a longer disease-free and total survival if there are only one or two metastatic lesions and the systemic disease is controlled. Stereotactic radiosurgery combined with whole brain radiation is an effective and equivalent alternative to surgery plus whole brain radiation, providing the lesions are not too large and limited in number.
3. Nonmalignant causes of cerebral edema, such as subdural hematoma in thrombocytopenic patients and brain abscess, toxoplasmosis, or other infections in immunocompromised patients, must always be considered.
III. SUPERIOR VENA CAVA SYNDROME (SVCS)
The superior vena cava is a thin-walled vessel located to the right of the midline just anterior to the right mainstem bronchus. It is ultimately responsible for the venous drainage of the head, neck, and arms. Its location places it near lymph nodes that are commonly involved by malignant cells from primary lung tumors and from lymphomas. Lymph node distention or the presence of a mediastinal tumor mass may compress the adjacent superior vena cava, leading to SVCS. Similarly, the presence of a thrombus due to a hypercoagulable state secondary to underlying malignancy or a thrombus developing around an indwelling central venous catheter may also lead to the development of this syndrome.
A. Symptoms and signs
Patients who develop SVCS commonly complain of dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and facial, neck, and upper-extremity swelling. Associated symptoms may include cough,
hoarseness, and chest or neck pain. Headache and mental status changes also may be seen. A patient’s symptoms may be gradual and progressive, with only mild facial swelling being present early in the course of this disorder. These early changes may be so subtle that the patient is unaware of them. Alternatively, if a clot develops in the superior vena cava in association with narrowing of the vessel, as often happens when the caval compression is severe, the signs and symptoms may appear suddenly. Physical examination may reveal a spectrum of findings from facial edema to marked respiratory distress. Neck vein distention, facial edema or cyanosis, and tachypnea are commonly seen. Other potential physical findings include the presence of prominent collateral vessels on the thorax, upper-extremity edema, paralysis of the vocal cords, and mental status changes.
B. Radiologic evaluation
Patients may often be diagnosed by physical findings plus the presence of a mediastinal mass on chest radiographs. CT scan with contrast will confirm the diagnosis and delineate the extent of obstruction. It permits a detailed examination of surrounding anatomy, including adjacent lymphadenopathy, may differentiate between extrinsic compression and an intrinsic lesion (primary thrombus), and aids in treatment planning for radiation therapy.
SVCS may also occur in patients with subclavian or internal jugular IV catheters. The injection of contrast material into these catheters is useful to determine the origin and extent of the thrombus. Determination of the cause and the appropriate treatment depends on both the clinical situation and the radiologic findings.
C. Tissue diagnosis
Although some patients present with such severe respiratory compromise as to require emergent treatment, most patients are clinically stable and may undergo biopsy for a tissue diagnosis if they are not previously known to have cancer. Tissue may be acquired through multiple methods including bronchoscopy, CT-guided biopsy, mediastinoscopy, mediastinotomy, and thoracoscopy. Thoracotomy is the most invasive option and is rarely needed. Because of increased venous pressure and dilated veins distal to the obstruction, extreme care must be taken to ensure adequate hemostasis after any biopsy procedure.
D. Treatment
Initially, patients with SVCS may be treated with oxygen for dyspnea, furosemide 20 to 40 mg IV to reduce edema, and dexamethasone 16 mg IV or by mouth daily in divided doses. The benefit of dexamethasone is not clear. In patients with lymphoma, there is probably a lympholytic effect with resultant decrease in tumor mass; in patients with most other tumors, the effect is probably limited to decreasing any local inflammatory reaction from the tumor and from subsequent initial radiotherapy.
1. Neoplasms. Therapy for SVCS ultimately involves radiation therapy for most tumors but possibly chemotherapy as a single modality for particularly sensitive tumor types such as small-cell lung cancer, lymphomas, and germ cell cancers. Radiation therapy may be given in relatively high-dose fractions (e.g., 4 Gy) for several days, followed by a reversion to “standard doses” thereafter. Dexamethasone is continued for about 1 week after the start of radiation treatment.
2. Thrombi.Related posts:
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