Malignant cardiac involvement is common, occurring in 11% to 12% of patients with cancer. Of these patients, three fourths have epicardial involvement, and one third of these patients have a pericardial effusion.¹ The most common malignant primary tumor that progresses to involve the pericardium is lung cancer. Breast cancer, gastrointestinal cancers, melanoma, sarcoma, lymphoma, and leukemia account for most other cases. These tumors invade the pericardium through direct or metastatic spread. Less commonly, malignant primary pericardial tumors such as mesothelioma and sarcoma or benign tumors such as angioma, fibroma, or teratoma may occur. In a study conducted from 1996 to 2005, malignant disease was the primary cause of medical cardiac tamponade (65%), followed by unknown causes (10%), viral disease (10%), and anticoagulant medication–related intrapericardial bleeding (3%).²

Pathophysiology

The pericardium is a fibroelastic sac surrounding the heart that normally contains a thin layer of fluid. When a larger amount of fluid accumulates and exceeds the elastic limit of the pericardium, the heart begins to compete for the now fixed amount of intrapericardial space. As more fluid accumulates, the cardiac chambers become compressed, and diastolic compliance lessens.

Throughout this process, the decline in intrathoracic pressure associated with inspiration continues to be transmitted through the pericardium to the heart. Thus, venous return to the heart is still increased with inspiration. However, the free wall of the right ventricle cannot expand to accommodate this increased volume, thus leading the intraventricular septum to bow to the left. The result is decreased left ventricular filling during inspiration. When the size of the effusion progresses further, total venous return diminishes, and cardiac output and blood pressure deteriorate.

Cardiac tamponade is generally classified as acute or subacute. In acute cardiac tamponade, the relatively stiff pericardium can become rapidly filled with blood that causes tamponade with only a small effusion. This generally occurs in the setting of trauma, myocardial or aortic rupture, or invasive medical interventions. In subacute cardiac tamponade, a much larger effusion accumulates slowly and allows the pericardium to stretch over time. This type of tamponade occurs most commonly in the setting of malignant disease or renal failure, and it may not occur until the amount of pericardial fluid reaches 2 L or more. In either setting, very little additional fluid may cause cardiac tamponade once the limits of pericardial elasticity have been reached.

Presenting Signs and Symptoms

Classic

Cardiac tamponade is a physiologic continuum, from mild to severe. Classically, patients present with tachypnea and dyspnea on exertion. As the disease progresses, patients may have shortness of breath at rest, peripheral edema, or orthopnea. Patients with severe disease may be obtunded on presentation, thus obscuring the diagnosis of cardiac tamponade. A history of malignant disease or symptoms and signs of malignant disease such as weight loss, fatigue, or anorexia may help to guide the clinician toward a diagnosis of malignant pericardial effusion.

Physical Findings

Patients with pericardial tamponade most commonly present with shortness of breath, hypotension, and often with clear lungs. Unfortunately, physical examination holds little value for diagnosing the presence of a pericardial effusion. However, as a malignant effusion becomes large enough to cause cardiac tamponade, some distinct physical findings may become evident. The Beck triad, first described in 1935, consists of increased jugular venous pressure, hypotension, and muffled heart sounds. However, this triad is most useful in acute cardiac tamponade, and it may be uncommon or difficult to assess in patients with atraumatic cardiac tamponade.³

Sinus tachycardia is seen in most patients with cardiac tamponade. This physiologic response allows for maintenance of cardiac output despite decreased cardiac filling volumes. Patients may present with slightly lower heart rates if they are taking beta-blocking medications or if they suffer from hypothyroidism. Significant tamponade also manifests with absolute or relative hypotension. Patients with early tamponade may present with normotension or even hypertension, especially if they have preexisting hypertension.

Pulsus paradoxus is defined as a drop of more than 10 mm Hg in systolic blood pressure during normal inspiration. Most patients with moderate to severe cardiac tamponade have pulsus paradoxus, which is often palpable in the peripheral arteries. As cardiac output drops, however, pulsus paradoxus may be difficult to measure without invasive monitoring. Pulsus paradoxus results when the effusion limits expansion of the free wall of the right ventricle as venous return increases during inspiration. The right ventricle is then forced to expand by bulging the intraventricular septum into the left ventricle, thus leading to greatly reduced filling and stroke volume during inspiration.

To quantify pulsus paradoxus noninvasively, a sphygmomanometer is used in the standard fashion. The cuff is inflated to more than the systolic blood pressure and then is slowly deflated until the first Korotkoff sounds are audible only during exhalation. This condition is typified by hearing Korotkoff sounds for several beats during exhalation, followed by silence during inspiration, and then followed by Korotkoff sounds for several beats during exhalation. The pressure is noted on the sphygmomanometer at this point, and slow deflation is continued until all beats are audible. The amount of pulsus paradoxus is determined by subtracting the pressure at which all beats are heard from the pressure at which beats were heard only during exhalation.

Multiple conditions may alter the physiology of cardiac tamponade and may cause pulsus paradoxus to be absent. The most common conditions are elevated left ventricular diastolic pressures and increased heart rate. Other conditions include severe hypotension, irregular rhythm, atrial septal defect, regional cardiac tamponade, and severe aortic regurgitation.

Medical Decision Making and Diagnostic Testing

Electrocardiography

The electrocardiogram is abnormal in most, but not all, patients with pericardial effusion. The most common findings are nonspecific ST-segment and T-wave abnormalities and sinus tachycardia. The electrocardiogram may mimic that seen in acute pericarditis.

Low QRS voltage may be a sign of a large pericardial effusion, but it is more likely to be associated with tamponade physiology. In one small study, Bruch et al.⁴ studied 43 patients with a pericardial effusion. Of those patients, 14 of 23 with tamponade demonstrated low-voltage QRS complexes, as opposed to none of the 23 patients with effusion but without tamponade⁴ (Fig. 202.1). Electrical alternans (Fig. 202.2), demonstrated as beat-to-beat alterations in the amplitude of the QRS complex, is relatively specific but not very sensitive for cardiac tamponade. Electrical alternans may also rarely occur in patients with very large effusions without tamponade. Electrical alternans is caused by swinging of the heart in the pericardial effusion, and it generally disappears after removal of even modest amounts of pericardial fluid.

Fig. 202.1 A, Patient’s electrocardiogram on a prior visit to the emergency department (ED). B, Patient’s electrocardiogram on presentation to the ED with cardiac tamponade.

Fig. 202.2 A, Electrocardiogram demonstrating electrical alternans most notable in the lead II rhythm strip. This patient’s electrocardiogram also has atrial flutter with 2 : 1 conduction. B, Electrocardiogram performed on the same patient several days after drainage of his pericardial effusion.

Chest Radiography

The typical finding on chest radiograph is an enlarged cardiac silhouette (the “water bottle”–shaped heart), as seen in Figure 202.3. In most cases, the lung fields are clear unless preexisting lung disease (e.g., malignant disease) is present. Cardiac tamponade may manifest without an enlarged cardiac silhouette if a small, rapidly accumulating effusion is the cause.

Fig. 202.3 A, Patient’s chest radiograph 1 year before presentation with cardiac tamponade. B, Same patient’s chest radiograph on presentation to the emergency department with cardiac tamponade.

Echocardiography and Emergency Medicine Bedside Ultrasound

Echocardiography and emergency medicine bedside ultrasound play crucial roles in the diagnosis of cardiac tamponade. The first steps are to suspect a problem and to perform a screening cardiac ultrasound examination ⁵ (Fig. 202.4).

Fig. 202.4 Bedside ultrasound image showing large pericardial effusion.

The patient subsequently had 2 L drained from this effusion. LV, Left ventricle; RV, right ventricle.

Echocardiographic findings indicative of cardiac tamponade include the presence of pericardial fluid with accompanying diastolic collapse of the right atrium and right ventricle. During atrial relaxation at the end of diastole, pericardial pressure is maximal, whereas right atrial volume is minimal. This situation results in right atrial collapse that, if lasting more than one third of the cardiac cycle, is sensitive and specific for cardiac tamponade. Right ventricular diastolic collapse occurs early in diastole when ventricular volume is minimal. Left atrial collapse is less common, but it is also very specific for cardiac tamponade. Collapse of the left ventricle is uncommon because of its greater muscular thickness.

As discussed earlier, left- and right-sided volumes vary with the respiratory cycle. During inspiration, the atrial and ventricular septa bulge to the left. During expiration, the atrial and ventricular septa bulge rightward.

Treatment

Patients with mild hemodynamic compromise require urgent drainage of pericardial fluid. If the patient is sufficiently stable, cardiology and cardiothoracic surgery consultation may be appropriate to decide whether emergency catheter drainage or surgical creation of a pericardial window is the most appropriate therapy. In such cases, the emergency physician (EP) should be prepared to perform emergency pericardial drainage if the patient’s clinical condition should deteriorate.

Patients with severe hemodynamic compromise require immediate removal of pericardial fluid. Pericardiocentesis should be performed to remove as much of the pericardial effusion as possible. Percutaneous aspiration of even 50 to 100 mL has been demonstrated to reverse cardiac tamponade physiology temporarily.

Pericardiocentesis may be performed under electrocardiographic or echocardiographic guidance. Echocardiographic guidance is preferred when available, because it allows greater precision of procedure direction and needle angle. Placement of an indwelling catheter is advisable, to prevent reaccumulation of fluid. The technique used for pericardiocentesis can be found in the “Tips and Tricks” box. Fluid obtained from pericardiocentesis should be sent for Gram stain, culture, acid-fast stain and culture, cytologic study, carcinoembryonic antigen determination, and polymerase chain reaction evaluation. Complications of pericardiocentesis are listed in Box 202.1.

Tips and Tricks

Technique for Pericardiocentesis Using Ultrasound Guidance

• Using bedside ultrasound, locate the ideal site of skin puncture where the largest fluid collection lies closest to the skin surface. This site is usually located on the left anterior chest wall. The clinician can choose either to mark the skin or to use the ultrasound device with a sterile sheath for dynamic guidance at this point.

• Prepare the skin in sterile fashion, and anesthetize the skin if time permits.

• Attach a 20-mL syringe to an 18-gauge spinal needle.

• Insert the needle at the site and trajectory determined by bedside ultrasonography. Take care to avoid the neurovascular bundle at the lower rib border and the internal mammary artery, which lies 3 to 5 cm lateral to the sternal border.

• Gently aspirate as the needle is advanced until fluid is obtained.

• Aspirate as much fluid as possible using the three-way stopcock.

• Alternately, use an over-the-needle catheter or the Seldinger technique if prolonged drainage is necessary. The Seldinger technique is performed using the same methods as outlined, but the clinician may use a thin-walled 18-gauge needle to pass a guidewire, followed by a catheter (e.g., a pigtail catheter) that may be left in place.

Disposition and Prognosis

Patients with cardiac tamponade are admitted to the hospital, typically in a cardiac care or intensive care unit (see the “Priority Actions” box). Emergency referral to cardiology for a pericardial window procedure is determined if the patient is hemodynamically stable for the procedure. Documenting the hemodynamic instability and emergency intervention is important (see the “Documentation” box). Initial in-hospital mortality is high for patients with malignant effusion and pericardial tamponade; the median survival is 150 days, and the 1-year mortality rate is 76.5%. This mortality results jointly from the underlying cancer and the cardiovascular compromise.²

Priority Actions

• Consider malignant pericardial effusion in patients with a history of cancer who have tachypnea and dyspnea on exertion.

• Determine whether the patient has cardiac tamponade physiology by physical examination (i.e., Beck triad, pulsus paradoxus) or diagnostic evaluation (i.e., emergency bedside ultrasound).

• Perform an emergency pericardiocentesis or refer to cardiology for a pericardial window, based on hemodynamic instability.

• Assess for postprocedure reversal of tamponade physiology and for complications.

• Admit to a cardiac care or intensive care unit so that vital sign monitoring and follow-up diagnostics can be performed.

Documentation

• Vital signs, examination findings, and diagnostics supporting hemodynamic instability and cardiac tamponade physiology

• Informed consent for the emergency pericardiocentesis

• Postintervention assessment of vital signs, examination findings, or diagnostics to support therapeutic reversal of tamponade and improved patient clinical condition

• Code status to support the patient’s wishes given the underlying cancer history and invasiveness of the procedure

Superior Vena Cava Syndrome

Medical Decision Making and Diagnostic Testing

The initial test of choice when SVC syndrome is suspected is chest plain film radiography. Most of these radiographs are abnormal; one series found 84% of films to be abnormal. The most common abnormal findings were mediastinal widening in 64% (Fig. 202.5) and pleural effusion in 26%.⁹ A mass may also be seen in the superior mediastinum, right hilum or perihilum, or right upper lobe. Less commonly, right upper lobe collapse or rib notching may be apparent. However, a normal chest radiograph does not rule out the possibility of SVC syndrome.⁹

Fig. 202.5 Chest radiograph showing widened mediastinum.

The next test is a contrast-enhanced computed tomography (CT) scan (Fig. 202.6). CT defines the level and extent of blockage, provides detail on the amount of collateral flow, and is often able to identify the cause of obstruction. The presence of collateral vessels with compression of the SVC on CT is a reliable indicator of SVC syndrome, with a sensitivity of 96% and a specificity of 92%.^10,¹¹

Fig. 202.6 Computed tomography scan showing blockage of the superior vena cava (arrows).

Treatment

Rarely, SVC syndrome requires emergency care, as in the case of cerebral edema, airway obstruction, or hemodynamic compromise. In these situations, airway and vascular support and a specialist to assist in managing the obstruction are required. More commonly, symptomatic therapy should be instituted, including elevation of the head of the bed, oxygen, and bed rest. Diuretics and steroids have been used without clear evidence of efficacy. Anticoagulation may be of benefit in patients with thrombotic causes, after the origin is determined. Endovascular stenting has been successful in symptomatic improvement, and it has been steadily gaining favor as a treatment modality.

Disposition and Prognosis

All patients diagnosed with the SVC syndrome should be admitted to the hospital (see the “Priority Actions” box). The level of care should be chosen based on the clinical stability of the patient. Oncology specialists should be consulted to help begin the work-up necessary to establish a histologic diagnosis, if one is not already known.

Priority Actions

• Diagnose the SVC syndrome in a patient with lung cancer or lymphoma with head or neck swelling, engorged upper extremity veins, plethora, or dyspnea.

• Determine whether the patient has any emergency obstructive SVC syndrome findings of cerebral edema, airway obstruction, or hemodynamic compromise, and provide supportive measures and specialist consultation on an emergency basis.

SVC, Superior vena cava.

Survival of patients with the SVC syndrome depends on the underlying diagnosis and the treatments chosen. The median survival is 6 months, but it may differ considerably based on the type of malignant disease.

Neurologic Oncologic Emergencies

Perspective

The primary neurologic oncologic emergencies encountered in the ED can be divided into those that affect the central nervous system (CNS), including altered mental status, increased intracranial pressure (ICP), and seizures from brain tumors or metastatic lesions, and those that affect the peripheral nervous system, such as epidural spinal cord compression (ESCC). Generally, these emergencies involve acute to subacute presentations and result from mechanical obstruction of normal neurologic function. Patient morbidity and mortality can be improved by early recognition and management directed at relieving the neurologic obstruction or preventing secondary injury.

Central Nervous System Emergencies

Epidemiology

The most important CNS manifestations include altered mental status, elevated ICP, and seizures. Brain tumors represent a diverse group of neoplasms that can originate primarily from the CNS or metastatically through hematogenous spread from distant organs.

Although brain tumors account for only 2% of all tumors, they have significant sequelae. The 5-year survival rate of patients of all ages and all races who have malignant brain tumors is 33%; for children less than 14 years old, it is 62%; and for adults 65 years or older, it is 4.9%.¹² In children, brain tumors are the most common solid malignant tumors and the second leading cause of cancer death after leukemia. Box 202.2 illustrates the differences in primary tumor types between adults and pediatric patients.

Box 202.2 Approximate Differences in Primary Tumor Types Between Adults and Children

Brain metastases are more common than primary tumors in adults and account for more than half of all intracranial brain tumors. In adults with systemic malignant diseases, brain metastases occur in 10% to 30% of patients. The most common primary tumors responsible for brain metastases in adults are carcinomas, and they include lung cancer, renal cell cancer, melanoma, breast cancer, and colorectal cancer. In children with systemic malignant diseases, brain metastases occur in 6% to 10% of patients. The most common primary tumors responsible for brain metastases in children are sarcomas, neuroblastomas, and germ cell tumors.

In general, a slight male predominance is seen in the incidence of malignant brain tumor. Whites have the highest incidence, with a descending incidence in Latinos and African Americans, and the lowest incidence in Native Americans and Asian Americans.¹² The rising incidence of brain tumors in industrialized countries is thought to be mostly a result of environmental exposures and improved detection using diagnostic imaging.

Although cancers typically are indolent in their evolution, the neurologic manifestations may be acute or chronic, and they may be local or distant from the primary source. Rapid diagnosis and treatment are imperative to prevent irreversible damage, primarily from cerebral hypoxia, inflammation, or swelling, which can have catastrophic consequences. The long-term prognosis of patients with cancer and significant neurologic complications is poor, and recurrence of illness is common despite optimal management.

Pathophysiology

The pathogenesis of tumor-related neurologic dysfunction involves disruption of the blood-brain barrier leading to vasogenic edema. This condition is caused primarily by factors that increase the permeability of the tumor vessels (vascular endothelial growth factor, glutamate, and leukotrienes) and by the absence of tight endothelial cell junctions in tumor blood vessels. This process culminates in leakage of protein-rich fluid into the extracellular space, predominantly in the white matter of the brain. When this peritumoral edema begins to accumulate, the synaptic transmission can be disrupted and thus can lead to altered neuronal excitability and neurologic sequelae (Fig. 202.7). Vasogenic edema is what causes patients to suffer from headaches, nausea or vomiting, seizures, cognitive dysfunction, focal neurologic deficits, encephalopathy, or increased ICP leading to syncope or fatal herniation. Intratumoral hemorrhage, obstructive hydrocephalus, and tumor embolization can also have tumor-related consequences, but these entities are much less common than vasogenic edema.

Fig. 202.7 Pathophysiology of vasogenic edema.

A, Tumor vessel with factors that increase vascular permeability. VEGF, Vascular endothelial growth factor. B, Protein-rich fluid leaking into extracellular spaces. C, Disruption of synaptic transmission. D, Neurologic sequelae.

Brain metastases arrive through hematogenous spread. They are usually located in two places. The first is directly at the junction of the gray and white matter, where smaller vessels begin to trap tumor cells. The second is at terminal “watershed areas” of arterial circulation. Metastases distribute according to weight and blood flow and are seen in the cerebral hemispheres (80%), in the cerebellum (15%), and in the brainstem (5%). Pelvic (prostate and uterine) and gastrointestinal tumors commonly metastasize to the posterior fossa, whereas small cell lung carcinoma distributes equally through all regions of the brain.

Presenting Signs and Symptoms

A classic presentation to the ED for brain metastasis is a patient with known cancer who has a sudden onset of a neurologic deficit or change in mental status, syncope, or seizure. Patients with primary or metastatic disease can present with either generalized or focal signs or symptoms. Generalized symptoms include headaches, nausea or vomiting, generalized seizures, cognitive dysfunction, and loss of consciousness. Focal symptoms include weakness, sensory loss, aphasia, focal seizures, and visual spatial dysfunction.

Headache is the most common symptom of brain tumor, and headaches occur in approximately 40% to 50% of patients with primary or metastatic brain tumors. In one retrospective review, headaches were described variably, but most were described as tension-type headaches. The patients described the headaches as bifrontal and worsening ipsilateral to the lesion.¹³ Tumor-related headaches were differentiated from tension headaches by complaints of nausea and vomiting or especially by worsening of the headache with changes in body positioning that increased ICP (i.e., leaning forward). Worsening of the headache typically occurred following maneuvers that increase intrathoracic pressure, such as coughing, sneezing, or the Valsalva maneuver.

Seizure represents the most common presenting symptom of gliomas and cerebral metastases. In these tumor types, one study showed that seizure was the initial complaint in approximately 20% to 25% of patients.¹⁴ Patients who present with seizure activity usually have smaller primary tumors or fewer metastatic lesions in the brain compared with other presenting symptoms, because the seizure leads to earlier diagnostic imaging and diagnosis. Seizures can be generalized or focal, depending on the location in the brain of the tumor. Frontal lobe tumors may cause tonic-clonic movements in an extremity, and occipital lobe tumors may cause visual disturbances. Temporal lobe seizures may cause abrupt personality changes. Patients with a history of tumor-related seizures commonly present in a similar fashion on each visit, with or without a prodromal phase followed by a postictal period. If the seizures are generalized, the patient will be fatigued and sleepy; if the seizures are focal, however, the patient may have Todd paralysis.

Acute mental status change describes a deficit in cognitive function and is a presenting complaint in approximately 30% to 35% of patients with brain metastases.¹⁵ Cognitive dysfunction includes memory problems and mood or personality changes. Patients commonly present with fatigue, low energy, increased urge to sleep, and apathy toward daily activities.

Medical Decision Making and Diagnostic Testing

Diagnostic neuroimaging is the standard for confirming brain tumors and subsequent neurologic manifestations of oncologic emergencies. For the EP, CT scanning is the initial test of choice because of its speed and availability. Contrast-enhanced magnetic resonance imaging (MRI) is the preferred study for primary and metastatic brain tumors, but it does not need to be performed on an emergency basis (Figs. 202.8 through 202.12).

Fig. 202.8 Noncontrast computed tomography scan of the head showing an intratumoral hemorrhage.

Fig. 202.9 Noncontrast computed tomography scan of the head showing a brain tumor (arrow).

Fig. 202.10 Noncontrast computed tomography scan of the head showing peritumoral edema (arrow).

Fig. 202.11 Contrast computed tomography scan of the head showing a brain tumor (arrow).

Fig. 202.12 A and B, Magnetic resonance images showing brain tumor with hemorrhage and edema.

Treatment

The main goals of treatment for neurologic manifestations of oncologic emergencies are to preserve and maintain cerebral oxygenation and perfusion, to decrease inflammation and swelling, and to identify and correct the underlying condition. In the severely neurologically depressed patient with a declining Glasgow coma scale and an inability to protect the airway, rapid-sequence endotracheal intubation should be performed, with supplemental oxygen administered to prevent cerebral hypoxia. Before intubation, care should be taken to prevent a rise in ICP, and appropriate choices for sedation and paralytic agents should be used.

Pretreatment with 1 to 1.5 mg/kg of lidocaine to blunt the rise in ICP from intubation has limited supporting evidence, but it can be used as an adjunct. Etomidate is the best choice for sedation, at a dose of 0.3 mg/kg, and it induces general anesthesia without raising ICP or dropping blood pressure. Another agent for sedation, propofol, at a dose of 2 mg/kg, induces general anesthesia without raising ICP with the advantage of rapid onset of action and a short half-life. A defasciculating dose of a nondepolarizing agent (e.g., 0.01 mg/kg of vecuronium) may help to blunt the fasciculations caused by succinylcholine (1.5 mg/kg).

Diagnostic neuroimaging must be performed immediately following stabilization to ascertain the underlying cause of neurologic dysfunction. Once the patient is stabilized and the brain is adequately oxygenated, secondary treatments must be performed to protect the brain from further injury such as increasing edema or herniation.

Corticosteroids, specifically dexamethasone, help to reduce the inflammatory response by decreasing the permeability of tumor capillaries and by clearing edema through transport of fluid into the ventricular system. Dexamethasone is the standard agent of choice because of its antiinflammatory effects and its relative lack of mineralocorticoid activity, which may cause fluid retention. The initial dose is typically a 10-mg loading dose. If the drug is given orally, absorption is completed within 30 minutes. Tumor-related weakness is very responsive to dexamethasone treatment.

Reduction of ICP and improvement of neurologic symptoms usually begin within hours. The permeability of the blood-brain barrier has been found to improve within 6 hours, and changes in MRI demonstrating decreased edema have been shown within 2 to 3 days. The long-term side effects of corticosteroid use include gastrointestinal complications, steroid myopathy, and opportunistic infection.

If steroids alone cannot effect adequate reduction of ICP, increasing ICP can evolve into a medical emergency leading to herniation. The neurologic intensive care specialist will consider placement of a ventriculostomy to monitor the ICP and to drain cerebrospinal fluid to reduce ICP. The goal of ICP monitoring and treatment should be to keep ICP to less than 20 mm Hg and cerebral perfusion pressure (CPP) between 60 and 75 mm Hg. In the patient who has required intubation, the head of the bed should be elevated 30 degrees to decrease ICP.

Osmotic agents (e.g., mannitol, at a dose of 1 g/kg) reduce ICP by 50% in 30 minutes, peak after 90 minutes, and last 4 hours. Loop diuretics (e.g., furosemide, 1 mg/kg) also decrease ICP without increasing serum osmolality. The use of mannitol or diuretics can be discussed with the neurologic intensive care specialist. Hyperventilation to reduce ICP is controversial; if it is performed after discussion with the neurologic intensive care specialist, however, all efforts should be made to keep the partial pressure of carbon dioxide between 30 and 35 mm Hg. Sedation should also be continued to reduce metabolic demand.

Blood pressure control should attempt to maintain CPP higher than 60 mm Hg, because systemic hypotension and resultant low CPP actually increase ICP. Pressors can be used safely without further increasing ICP if the blood pressure becomes too low. Hypertension should generally be treated only when CPP is higher than 120 mm Hg and ICP is higher than 20 mm Hg, to prevent further damage. The patient should be kept euvolemic with 0.9% normal saline to ensure that no hypotension from hypovolemia or hydrocephalus from hypervolemia occurs. The patient should also be kept in the normal osmolarity range (295 to 305 mOsm); hyponatremia may be managed with hypertonic saline after discussion with the intensive care specialist because its use is controversial. Euglycemia (80 to 120 mg/dL) should be maintained for metabolic needs.

Antiemetic medications should be used so that vomiting does not increase ICP. Barbiturate therapy can be considered to reduce ICP based on the ability of these drugs to reduce brain metabolism and cerebral blood flow. Pentobarbital is often used, with a loading dose of 5 to 20 mg/kg as a bolus, followed by 1 to 4 mg/kg/hour. Treatment should be assessed based on ICP, CPP, and the presence of unacceptable side effects such as hypotension. Continuous electroencephalographic monitoring is generally used. Therapeutic hypothermia has not been reliably studied in increased ICP secondary to oncologic emergencies and is not currently standard management. Treatment alternatives to assist in the care of acute vasogenic edema are listed in the “Tips and Tricks” box.

Tips and Tricks

Treatment Alternatives for Patients with Acute Vasogenic Edema

• Corticosteroids

• Dexamethasone (10-mg loading dose)

• Osmotic agents or diuretics

• Consider mannitol (1 g/kg).

• Consider furosemide (1 mg/kg).

• Antiemetics (phenothiazine of choice or ondansetron for refractory vomiting)

• Euvolemia (0.9% normal saline solution)

• Euglycemia (80 to 120 mg/dL)

• Normal osmolarity (295 to 305 mOsm)

• Consider hypertonic saline after discussion with specialist.

• Blood pressure control (CPP > 60 mm Hg and CPP < 120 mm Hg when ICP > 20 mm Hg)

• Consider pressors for hypotension.

• Consider calcium channel blockers or beta-blocking agents for hypertension.

• Ensure airway protection with intubation if necessary.

• Consider pretreatment with an agent to blunt increased ICP (e.g., 1.5 mg/kg lidocaine).

• Choose a sedative agent that does not increase ICP (e.g., etomidate 0.3 mg/kg or propofol 2 mg/kg).

• Consider a defasciculating dose of a nondepolarizing agent before a depolarizing agent (e.g., 0.01 mg/kg vecuronium before 1.5 mg/kg succinylcholine).

• Elevate the head of the bed to 30 degrees.

• Consider hyperventilation after discussion with a specialist (ensure PCO₂ 30 to 35 mm Hg).

• Consider antiseizure medication or barbiturate therapy (i.e., lorazepam, 2- to 5-mg bolus, or pentobarbital, 5-to 20-mg/kg bolus, then 1 to 4 mg/kg/hour).

CPP, Cerebral perfusion pressure; ICP, intracranial pressure; PCO₂, partial pressure of carbon dioxide.

The main goals of treatment in tumor-related seizures are to ensure adequate oxygenation and perfusion and to stop prolonged seizures or evolving status epilepticus. In addition to supplemental oxygenation and steps to ensure that the patient is not injured, the initial choice of medication is a benzodiazepine such as lorazepam (2 to 4 mg intravenous loading dose). If the seizure is refractory, and monotherapy with escalating doses of benzodiazepines is not working, consider the addition of phenobarbital (20 mg/kg intravenous loading dose) or phenytoin (18 mg/kg intravenous loading dose).

Prophylactic anticonvulsants are commonly considered in patients with diagnosed brain tumors but who have not had a seizure. Prophylactic anticonvulsants were reviewed by the Quality Standards Subcommittee of the American Academy of Neurology, and the summary recommendation stated that prophylaxis did not affect the frequency of subsequent seizures and should not be used in patients with either primary or metastatic brain tumors. Thus, the subcommittee believed the 5% to 25% subsequent seizure risk in brain tumors was outweighed by the deleterious interactions of anticonvulsants with cytotoxic drugs and corticosteroids. In postoperative seizure, the subcommittee recommended that anticonvulsants should be tapered and discontinued after the first postoperative week in patients who have not had a seizure, particularly in patients who are medically stable and are experiencing anticonvulsant-related side effects.

Disposition and Prognosis

Once stabilized, patients presenting with neurologic complications of cancer require admission to the hospital (priority actions for the management of cerebral oncologic emergencies are listed in the “Priority Actions” box). Patients with significantly depressed neurologic function require intubation, neuroprotective interventions, and intensive monitored care by a neurologic intensive care specialist. Patients who are awake, hemodynamically stable, and protecting their airway require admission to a general unit with neurology and medical oncology evaluation. Careful documentation of change in neurologic status is important (see the “Documentation” box). The prognosis of patients with CNS oncologic emergencies is generally poor.

Priority Actions

• Consider a central nervous system emergency in patients with a history of cancer who have mental status change, headache, cognitive dysfunction, seizure, syncope, or focal findings.

• Address life-threatening emergencies with prompt interventions (i.e., intubation to prevent anoxic brain injury; antiepileptic medications for status epilepticus).

• Prevent secondary brain injury by directing therapies to maintain oxygenation and perfusion of the brain and to reduce inflammation and neurologic sequelae of the tumor.

• Obtain prompt neurologic specialist input with the assistance of medical oncology for brain monitoring and admission management.

Epidural Spinal Cord Compression

Epidemiology

Neoplastic ESCC is a common complication of metastatic cancer that has been documented to occur in 5% of patients with cancer.¹⁶ The most widely accepted definition of ESCC includes any radiographic indentation of the thecal sac. Although the cauda equina is not technically considered part of the spinal cord, the pathophysiology of compression of the cauda equina is the same as that of the spinal cord. Thus, compression of the thecal sac by malignant disease at this level is also referred to as ESCC.

The most common tumors are prostate, breast, and lung cancers (each accounting for 15% to 20% of all cases), which tend to metastasize to the vertebral column. Other important tumors are renal cell carcinoma, multiple myeloma, non-Hodgkin lymphoma, and plasmacytoma, which make up most of the remaining cases. In children, the most common causes are sarcomas, neuroblastomas, Hodgkin lymphoma, Wilms tumor, and germ cell tumors. The most common vertebral levels of involvement for ESCC for all age groups are the thoracic spine (60% to 78%), followed by the lumbar spine (16% to 33%), followed by the cervical spine (4% to 15%); multiple levels are involved in up to 50% of patients.¹⁷ Delays in diagnosis and treatment remain common, and reports from multiple countries describe poor neurologic outcome in half or more of patients diagnosed with ESCC, including motor weakness, bladder dysfunction, and inability to ambulate.¹⁸^–²⁰

Pathophysiology

The most common method for hematogenous spread to the spinal column is by direct arterial embolization of tumor cells. The seeding of these cells creates a destructive and expansive mass in the vertebral body. As the vertebral body weakens, both the tumor and collapsed bony fragments place pressure on the epidural space and subsequently on the thecal sac that results in ESCC.

Presenting Signs and Symptoms

The most common presenting symptom of ESCC is back pain, which occurs in more than 80% of patients.¹⁶ In general, pain precedes the onset of neurologic symptoms by several weeks. The pain is generally slowly progressive, although abrupt worsening of pain may signal a pathologic compression fracture. The pain may worsen with recumbency, movement, or the Valsalva maneuver, or it may develop a radicular quality. The radicular pain may be bilateral, especially in thoracic lesions.

Motor weakness is present in most patients with ESCC at the time of diagnosis. When the cauda equina is compressed, the deep tendon reflexes may also be depressed. Laterally situated tumors may cause isolated motor radiculopathy or radiculopathy superimposed on bilateral lower extremity weakness. Weakness tends to be most pronounced in patients with thoracic lesions.

Sensory findings are present in more than half the patients with ESCC. Patients often report ascending numbness or paresthesias. When a sensory level is present, it is generally several levels below the actual level of spinal cord compression. Cauda equina lesions result in saddle anesthesia, whereas higher lesions often spare these sacral dermatomes. Like motor symptoms, sensory symptoms can occur in a radicular pattern.

Bowel dysfunction and bladder dysfunction are often late findings, but these disorders are frequently present by the time of diagnosis of ESCC. The most common presenting symptom is urinary retention, which may be potentiated by the use of narcotic analgesics for the back pain. Other signs and symptoms of myelopathy that may indicate ESCC include diminished proprioception, ataxia, spasticity, reflex hyperactivity, and autonomic dysfunction. The presenting signs and symptoms of ESCC are difficult to diagnose, and cautions for the physician are listed in the “Red Flags” box.

Red Flags