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Abstract
Oncologic emergencies can occur at any time during the course of a malignancy, from the presenting symptom to
end-stage disease. Although some of these conditions are related to cancer therapy, they are by no means confined
to the period of initial diagnosis and active treatment. In the setting of recurrent malignancy, these events can occur
years after the surveillance of a cancer patient has been appropriately transferred from a medical oncologist to a
primary care provider. As such, awareness of a patient’s cancer history and its possible complications forms an im-
portant part of any clinician’s knowledge base. Prompt identification of and intervention in these emergencies can
prolong survival and improve quality of life, even in the setting of terminal illness. This article reviews hypercalcemia,
hyponatremia, hypoglycemia, tumor lysis syndrome, cardiac tamponade, superior vena cava syndrome, neutropenic
fever, spinal cord compression, increased intracranial pressure, seizures, hyperviscosity syndrome, leukostasis, and
airway obstruction in patients with malignancies. Chemotherapeutic emergencies are also addressed. CA Cancer J
Clin 2011;61:287-314. VC 2011 American Cancer Society.
Introduction
In this review, we discuss the pathophysiology, presentation, diagnosis, and treatment of commonly encountered
emergencies in hematology and oncology. We have chosen to categorize emergencies as metabolic, cardiovascu-
lar, infectious, neurologic, hematologic, or respiratory to highlight their lack of disease specificity and to facilitate
their recognition during system-by-system assessment of the patient. These conditions require prompt recogni-
tion and treatment. For providers administering chemotherapy, we also address the problems of extravasation
and anaphylactic reactions.
Metabolic Emergencies
Hypercalcemia
Pathophysiology
Hypercalcemia will be experienced by up to one-third of cancer patients at some point in their disease course.1
Among patients hospitalized for hypercalcemia, malignancy is the most common cause, although primary hyper-
parathyroidism is much more prevalent in the general population.2 Breast, lung, and renal cell carcinomas; multi-
ple myeloma; and adult T-cell leukemia/lymphoma are the prevailing causes of hypercalcemia.1,3 A variety of
mechanisms can explain elevated calcium in cancer patients: systemic release of parathyroid hormone-related
peptide (PTHrP) by the tumor, which does not require the presence of bone metastases; local paracrine stimula-
tion of osteoclasts by metastases to bone, leading to osteolytic effects; and systemic secretion of vitamin D ana-
logues by the tumor, which also does not require the presence of bone metastases.4
1
Senior Hematology and Oncology Fellow, Division of Hematology, Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN; 2Senior
Medical Oncology Fellow, Division of Hematology, Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN; 3Associate Professor, Medical
Oncology, Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN.
Corresponding author: Timothy J. Moynihan, MD, Department of Oncology, Mayo Clinic, 200 First St SW, Rochester, MN 55905; Moynihan.Timothy@mayo.edu
DISCLOSURES: The authors report no conflicts of interest.
C
V
2011 American Cancer Society, Inc. doi:10.3322/caac.20124.
Up to 80% of malignant hypercalcemia is caused Even in the setting of profound hypercalciuria, not
by PTHrP released by the tumor into the systemic all patients will form kidney stones, which may be
circulation.4 Given its homology to parathyroid hor- due to differences in the urine mineral concentration
mone (PTH), PTHrP can mimic the action of PTH needed to precipitate calculi.10 Abdominal pain can
on the bones and kidneys but, unlike PTH, PTHrP arise from dysregulated intestinal motility, pancreati-
does not influence intestinal absorption of calcium.5 tis, or severe constipation. Changes in sensorium can
The effects of PTHrP represent a true paraneoplastic occur along a spectrum from lethargy to coma. In
syndrome (ie, systemic signs and symptoms caused addition, hypercalcemia shortens the QT interval
by a tumor, but not confined to the area in direct and can produce arrhythmias.
proximity to the tumor), with circulating PTHrP
causing bone resorption and renal retention of cal- Diagnosis
cium. Squamous cell carcinomas from the aerodiges- Ionized calcium is the most reliable laboratory test
tive and genitourinary tracts commonly cause this with which to detect hypercalcemia and is consid-
type of ‘‘humoral’’ hypercalcemia but this can also be ered to be elevated when above 1.29 mmol/L.11 If
seen in breast, kidney, cervical, endometrial, and measuring total calcium, it is important to correct
ovarian cancer. for hypoalbuminemia, using the following formula:
Bone metastases may cause a local paracrine effect corrected calcium in mg/dL ¼ measured total cal-
by producing several factors that stimulate osteo- cium in mg/dL þ 0.8(4 measured albumin in g/
clasts, leading to bone resorption with resultant dL).12 There is no absolute level of calcium at which
hypercalcemia and bone destruction.6 This is most patients will become symptomatic, and the rate of
commonly seen in metastatic breast cancer and mul- increase is likely more significant than the magni-
tiple myeloma. Prostate cancer, despite the frequency tude of elevation; relatively high levels may be well
with which it metastasizes to bone, only rarely causes tolerated if the rate of increase has been gradual.13
hypercalcemia, underscoring that it is not just osse- Measuring PTHrP has not been proven to affect
ous involvement but the specific tumor-bone inter- outcome and should not guide initial management.
action that determines calcium liberation from bone. PTHrP-driven hypercalcemia should be suspected
New agents, such as those that alter the receptor on the basis of the underlying tumor type, especially
activator of nuclear factor jB ligand (RANKL) when bony metastases are not evident. However,
(denosumab) or inhibit osteoclastogenesis (osteopro- patients presenting with PTHrP levels above 12
tegerin), can be used to modify the tumor microen- pmol/L may be less responsive to bisphosphonates
vironment to control hypercalcemia and bone and more prone to develop recurrent hypercalce-
resorption. mia.14 Serum chloride is a more readily available
Very rarely, a tumor will manufacture PTH test, and hypochloremia less than 100 mEq/L sup-
itself.7 ports a diagnosis of humoral hypercalcemia.15 PTH
Tumor production of vitamin D analogues is a levels can be checked to investigate the possibility of
less common etiology of malignant hypercalcemia, primary hyperparathyroidism; however, PTH levels
with non-Hodgkin lymphoma and Hodgkin lym- are often low in patients with humoral hypercalce-
phoma each capable of producing elevated calcitriol mia due to suppression of endogenous PTH release
levels.8 by PTHrP-mediated negative feedback.
Presentation Treatment
The symptoms of hypercalcemia are nonspecific, and The 30-day mortality rate of cancer patients hospi-
delayed recognition of this metabolic derangement talized with hypercalcemia has been shown to
can worsen morbidity and mortality.9 The mne- approach 50%.16 Even in patients with advanced
monic ‘‘bones, stones, moans, and groans’’ is used to malignancies in whom efforts to lower calcium do
emphasize skeletal pain, nephrolithiasis, abdominal not demonstrably prolong life, there can be a pallia-
discomfort, and altered mentation as presenting tive benefit to improving the symptoms of hypercal-
symptoms. Bone pain is usually related to discrete cemia.16 Urgent intervention is needed to normalize
metastases rather than diffuse liberation of calcium. symptomatic hypercalcemia (Table 1).
Normal saline Rapid infusion 300-500 cc/h until euvolemic Use caution in patients with heart failure
Furosemide 20-40 mg iv every 12-24 h Only after adequate hydration
Pamidronate 60-90 mg iv Adjust infusion time to creatinine clearance
Zoledronic acid 4 mg iv Consider alternative treatment in patients with renal failure
Calcitonin 4-8 IU/kg sq or iv every 12 h Tachyphylaxis occurs quickly
Steroids Hydrocortisone, 100 mg iv every 6 h Role usually limited to lymphomas; anticipate hyperglycemia
or prednisone, 60 mg orally daily
Mithramycin and gallium Of historical interest only
Denosumab Under investigation Currently approved only for the prevention
of skeletal-related events from bone metastases
and appreciably lower the calcium level within 3 to 5 stored.34 Laboratory measurement of the sodium
days of administration.8 The duration of use should concentration thus reveals the distribution of water
be limited to minimize glucocorticoid toxicities. among the body’s fluid compartments, and hypona-
Gallium and mithramycin are increasingly becom- tremia means that intravascular water is present in
ing of historical interest. Gallium has to be given as excess relative to sodium, either through water
a continuous 5-day infusion25 and does offer a retention and/or sodium loss.
higher response rate than bisphosphonates for hu-
moral hypercalcemia but at the expense of greater Presentation
nephrotoxicity.26 Mithramycin (also known as plica- The amount of sodium in the body, not the plasma
mycin) inhibits osteoclast RNA synthesis and lowers sodium concentration, determines the volume of
calcium during infusion27 while being given as a sin- fluid outside the cells, and this volume can be readily
gle dose over 4 to 6 hours, but carries significantly measured by physical examination. If the total body
more side effects than the bisphosphonates, includ- sodium is high, then the extracellular fluid volume is
ing hematologic and hepatic derangements.28 large and the patient will appear edematous. If the
Receptor activator of nuclear factor jB (RANK), total body sodium is low, then the extracellular space
found on the surface of osteoclast precursors, and its (including the circulatory volume) will contract and
ligand (RANKL), which is secreted by lymphocytes the patient will progressively develop tachycardia
and found on the surface of osteoblasts and bone and hypotension. A low plasma sodium concentra-
marrow stromal cells, stimulate osteoclast precursors tion can thereby be associated with clinical hypervo-
to complete their differentiation and begin bone lemia, hypovolemia, or euvolemia, depending upon
resorption, liberating calcium.3 PTH and 1,25- total sodium content. The physician must correctly
dihydroxyvitamin D3 drive osteoclast formation by evaluate the hyponatremic patient’s volume to
increasing RANKL expression on osteoblasts and understand both their sodium and water balance and
bone marrow stroma.29 Denosumab is a fully then select the appropriate treatment.35
humanized monoclonal antibody with high affinity Euvolemic hyponatremic patients with cancer
and specificity for RANKL that is approved for use have normal extracellular fluid volume, reflecting
in the management of postmenopausal osteoporo- appropriate total sodium content, but excessive water
sis30 as well as in the prevention of skeletal events in the intravascular space, most commonly mediated
from bone metastases,31 and has potential applica- through the syndrome of inappropriate antidiuretic
tion in hypercalcemia of malignancy.32 Osteoprote- hormone (SIADH). Antidiuretic hormone promotes
gerin, a decoy receptor of RANKL and an inhibitor free water uptake in the distal tubules by binding to
of osteoclast maturation, has been demonstrated to the vasopressin 2 (V2) receptor. Compounding the
correct hypercalcemia more quickly and durably than problem is continued free water intake because the
bisphosphonates.33 thirst mechanism is not sufficiently inhibited.36
SIADH should be suspected based upon the loca-
tion of primary and metastatic tumors because
Hyponatremia SIADH is more commonly encountered in diseases
Physiology originating in or involving the lungs, pleura, thymus,
The assessment of hyponatremia in cancer patients, and brain. Between 10% to 45% of patients with
as in all patients, requires a critical determination of small cell lung cancer will show evidence of
volume status. Fluid in the body is divided among SIADH.37 Iatrogenic causes of hyponatremia
compartments: the circulatory volume (plasma), the include cisplatin,38 cyclophosphamide,39 ifosfa-
interstitial space outside the vasculature, and the mide,40 the vinca alkaloids,41,42 and imatinib.43
cells. Osmotic gradients drive fluid between com- Each of these drugs can cause SIADH, but all can
partments, with movement toward higher concen- also produce hyponatremia through a variety of
trations. The sodium concentration is the largest other mechanisms (eg, platinum-induced salt-wast-
contributor to plasma osmolarity and reflects how ing nephropathy), and therefore careful evaluation is
much water is present in the blood relative to the required to determine the underlying etiology of hy-
cells, in which the majority of the body’s water is ponatremia in patients receiving these medications.
Drugs with high emetogenic potential can stimulate pseudobulbar palsy, ‘‘locked-in’’ syndrome, coma,
ADH release through nausea, an appropriate physio- and death.18 The sodium correction per L of infusate
logic response that may be confused with SIADH. can be estimated by the following formula: change in
Diagnosis serum sodium (Na) in mEq/L ¼ [(infusate Na
serum Na)/(total L of body water þ 1)] (reference
Hyponatremia can be classified as mild (131-135
values: infusate Na ¼ 513 mEq in 3% saline, infusate
mmol/L), moderate (126-130 mmol/L), or severe
Na ¼ 154 mEq in 0.9% saline, total L of body water
(<125 mmol/L). Serum glucose should be measured
¼ weight in kg 0.6).48
to ensure that hyperglycemia is not creating a spuri-
Asymptomatic, euvolemic hyponatremic patients
ous finding of hyponatremia. The serum sodium can
with cancer are treated by removing the offending
be adjusted for elevated glucose through the follow-
stimulus for their ADH secretion, such as control-
ing formula: corrected sodium in mmol/L ¼ mea-
ling nausea, lessening pain, and treating the underly-
sured serum sodium in mmol/L þ .016 (measured
ing malignancy. Restriction of free water intake to
glucose in mg/dL, 100).
500 to 1000 mL/day will increase plasma osmolality
SIADH is diagnosed when, after exclusion of ad-
and normalize the sodium level in many patients
renal insufficiency and hypothyroidism,44 the effec-
with SIADH. Demeclocycline, a tetracycline antibi-
tive osmolality (calculated by subtracting [blood urea
otic with the side effect of inducing nephrogenic dia-
nitrogen (BUN)/2.8] from the measured osmolality)
betes insipidus, can be used at a dosage of 600 to
is less than 275 milliosmoles (mOsm)/kg of water,
1200 mg/day,36 but patients need to be monitored
and the urine osmolality exceeds 100 mOsm/kg of
for profound polyuria and can actually develop
water.45 Urine sodium greater than 40 mmol/L in
hypernatremia if their restriction to free water is
the absence of excessive dietary sodium intake, hypo-
continued. The vaptans bind competitively to the V2
uricemia less than 4 mg/dL,46 and BUN less than 10
receptors in the collecting duct where ADH exerts
mg/dL all support the diagnosis of SIADH.47
its effect on the kidney. Intravenous conivaptan49
Treatment of Hyponatremia (20 mg infused over 30 minutes, followed by 20 mg
Treatment of hyponatremia in malignancy is de- infused over 24 hours) and oral tolvaptan50 (starting
pendent upon the underlying cause. Low serum at a dose of 15 mg daily) have been shown in clinical
sodium concentrations, especially those below 125 trials to achieve rapid correction of hyponatremia
mmol/L, can create the life-threatening consequence through almost pure aquaresis. The rate of vaptan-
of cerebral edema. However, it is primarily the rate induced sodium correction needs to be closely moni-
at which the hyponatremia develops that determines tored to ensure it is not excessive.51
the patient’s symptomatology. A patient with
chronic hyponatremia that is ‘‘severe’’ by laboratory
criteria may actually tolerate their electrolyte disturb- Hypoglycemia
ance better than a patient whose ‘‘moderate’’ hypona- Pathophysiology
tremia develops acutely within 48 hours.37 The most Hypoglycemia can arise in the patient with cancer
concerning symptoms of hyponatremia are neuro- through several etiologies. Some tumors are capable
logic, including lethargy, delirium, seizures, and of ectopic production of substances that affect glu-
coma, all of which merit urgent treatment. cose metabolism. Insulin is made in excess by insuli-
Hypovolemic hyponatremic patients have lost nomas and nesidioblastosis.52 Mesenchymal tumors
sodium and management involves infusing sodium- like sarcoma, including gastrointestinal stromal tu-
containing fluids. Severe hyponatremia with neuro- mor53 and solitary fibrous tumor,54 can produce
logic symptomatology can merit very careful use of insulin-like growth factors (IGFs) such as IGF-2,
hypertonic (3%) saline. Otherwise, normal (0.9%) which increases glucose utilization by tissues and
saline is an appropriate infusate. The serum sodium blunts the secretion of growth hormone.55 Levels of
should not be corrected at a rate greater than 0.5 a related protein, IGF-1, have been reported to be
mEq/L/hour to avoid central pontine myelinolysis, a elevated in rare cases of lung cancer.56,57 Rapidly
condition in which rapid, osmotically driven shrink- proliferating neoplasms can consume glucose prodi-
age of brainstem cells can result in quadriparesis, giously. Overexpression of the mitochondrial
enzyme hexokinase II allows some cancer cells to cessation of nonselective beta-blockers that blunt ad-
maintain glycolysis even in the presence of oxygen.58 renergic response to low blood sugar.68 Exogenous
In fact, this disproportionate uptake through the glucocorticoids and regimented frequent carbohy-
Warburg effect is exploited in 18-fluorodeoxyglucose drate intake have also been proposed as
positron emission tomography imaging to visualize interventions.69
tumors against a background of normal tissue. Given
the anabolic and biosynthetic demands of dividing Tumor Lysis Syndrome
cells, tumors with high mitotic rates may consume Pathophysiology
glucose with sufficient briskness as to induce hypo- Tumor lysis occurs when cancer cells release their
glycemia; this is most often seen in aggressive lym- contents into the bloodstream, either spontaneously
phomas (eg, Burkitt lymphoma) but has also been or following antineoplastic therapy,70,71 leading to
described in small cell lung cancer. The swift prolif- an influx of electrolytes and nucleic acids into the
eration may be associated with increased lactic circulation. The sudden development of hyperkale-
acid,59 even in the absence of hypoxemia. Tumors mia, hyperuricemia, and hyperphosphatemia can
can infiltrate organs that play crucial roles in normal have life-threatening end-organ effects on the
glucose metabolism,60 such as hepatocellular carci- myocardium, kidneys, and central nervous system
noma replacing the liver parenchyma or pheochro- (CNS). Recent animal models further suggest a det-
mocytoma overtaking the adrenal gland.61 It is rare rimental effect on the microvasculature by emboli
for metastases to the adrenal gland to precipitate formed from the nuclear and cytoplasmic debris
hypoadrenalism.62 of lysed tumor cells.72 Hypocalcemia, a consequence
Presentation of hyperphosphatemia, is included in the constella-
Signs and symptoms of hypoglycemia arise both tion of metabolic disturbances known as tumor lysis
from neuroglycopenia and adrenergic counterregula- syndrome (TLS).
tion.63 Neurologic manifestations range from confu- Presentation
sion and blurred vision to seizures and coma. The Patients are variably symptomatic from the metabolic
catecholamine response to hypoglycemia can result derangements of TLS. Clinical TLS is diagnosed
in diaphoresis, palpitations, and dilation of the when one or more of 3 conditions arise: acute renal
pupils. failure (defined as a rise in creatinine to 1.5 times or
Diagnosis more the upper limit of normal that is not attributable
The Whipple triad, initially developed to determine to medications), arrhythmias (including sudden car-
eligibility for pancreatic surgery in patients with diac death), and seizures. Acute renal failure can man-
insulinoma, includes measured hypoglycemia, symp- ifest as a decrease in urine output, uremia-related
toms attributable to hypoglycemia, and reversal of altered sensorium, or crystalline obstructive uropathy.
symptoms when normoglycemia is restored. In the Arthralgias can arise from gout flare.
absence of insulin secretagogues, an otherwise TLS is more common in the rapidly proliferative
healthy adult can usually maintain a glucose level hematologic malignancies such as acute lymphoblas-
above 50 mg/dL throughout a 72-hour fast.64,65 tic leukemia (ALL), acute myeloid leukemia
High insulin and C-peptide levels implicate islet cell (AML), and Burkitt lymphoma, but has been
tumors whereas an elevated IGF-2 to IGF-1 ratio documented in solid tumors, notably small cell lung
suggests a mesenchymal tumor.66 cancer,73 germ cell tumors,74 inflammatory breast
cancer,75 and melanoma.76 Liver metastases may
Treatment increase TLS risk.71
The treatment of cancer-related hypoglycemia can Treatment-provoked TLS can occur following
include surgical removal of the underlying tumor, or chemotherapy, treatment with single-agent cortico-
chemotherapy and radiation for unresectable tumors. steroids in patients with sensitive tumors,77,78 radia-
Interim management may include the administration tion,79 surgery, or ablation procedures.71 The onset
of glucagon at a dose of 1 mg iv/im, dextrose of TLS can be delayed by days to weeks in a patient
infusion, diazoxide (3 mg/kg/day initially),67 and with a solid malignancy.71
6-MP indicates 6-mercaptopurine; CHF, congestive heart failure; EKG, electrocardiogram; G6PD, glucose-6-phosphate dehydrogenase; iv, intravenously; TLS,
tumor lysis syndrome.
necessary to treat any refractory, life-threatening noncontiguous breast and lung cancer, as well as in
electrolyte derangements, especially in the context of melanoma.92 Primary neoplasms of the pericardium
volume overload and renal insufficiency. are exceedingly rare, but include mesothelioma.93
Cancer treatment, especially thoracic irradiation, can
cause transudative effusions. Immunosuppression
Cardiovascular Emergencies can also allow suppurative infections to develop in
the pericardial space.
Pericardial Effusion and Cardiac Tamponade
Pathophysiology Presentation
The pericardial sac is distensible up to a volume of 2 Pericardial effusions can be asymptomatic, although
L, if stretching occurs over a slow time period.89 Ris- their presence portends a poor prognosis, especially
ing intrapericardial pressure affects all 4 cardiac if larger than 350 mL.94 Pericarditis symptoms may
chambers, but the right ventricular wall is much precede the emergence of tamponade. Tamponade
thinner and more susceptible to extrinsic compres- classically presents with the Beck triad: hypotension,
sion. Diastolic pressures throughout the chambers elevated jugular venous pressure, and a muffled pre-
begin to equalize and adversely affect cardiac output cordium. However, only a minority of patients
by compromising filling.90 At this point, tamponade actually demonstrate all 3 signs.95 Most patients com-
physiology emerges. plain of dyspnea and chest discomfort, which may
Malignant pericardial effusions develop through begin abruptly. Tamponade physiology can arise from
direct or metastatic involvement of the pericardial volumes of as little as 100 mL if they accumulate rap-
sac. Direct extension is most common in those idly. Even if the effusion forms over a longer period
tumors with sites of origin adjacent to the heart: of time, the ‘‘last drop’’ phenomenon describes the
lung cancer, breast cancer, and mediastinal lym- critical point of physiologic collapse at which intra-
phoma.91 Metastases to the epicardium are seen in pericardial pressure finally overcomes the compensatory
mechanisms of the heart and causes cardiac output Instillation of chemotherapy into the pericardial
to drop precipitously.96 In this manner, a chronic space has been explored as a means of lowering re-
effusion can cause hyperacute symptomatology. currence rates of malignant pericardial effusions.102
However, one study found that systemic control of
Diagnosis
the underlying neoplasm was the only significant
The diagnostic utility of the physical examination
factor influencing survival.103 Before undertaking
should not be discounted but should be coupled with
elective invasive pericardial procedures, their risks
appropriate studies. Tachycardia is nearly universal,
should be carefully weighed alongside expectations
and pulsus paradoxus is an ominous finding,97 with a
for overall treatment efficacy and life expectancy.103
value greater than 10 mm Hg having been arbitrarily
defined as abnormal.
Superior Vena Cava Syndrome
Chest x-rays may show cardiomegaly and the clas-
sic ‘‘water bottle’’ cardiac silhouette. Electrocardiog- Pathophysiology
raphy can show low voltage and electrical alternans The thin-walled superior vena cava (SVC) returns
(Fig. 1) from the shifting axis of the heart as it all blood from the cranial, neck, and upper extremity
moves like a pendulum within the fluid-filled sac. vasculature to the right side of the heart. Primary or
Echocardiography is the definitive test, demonstrat- metastatic tumors can cause compression. Nononco-
ing right ventricular collapse during early diastole. logic etiologies include syphilitic aortic aneurysms
(vanishingly rare since the advent of penicillin),
Treatment
fibrosing mediastinitis (classically associated with
Sonographically guided pericardiocentesis has histoplasmosis), substernal hypertrophy of the thy-
decreased complication rates 4-fold over blind subxi- roid, granulomatous disease (such as tuberculosis
phoid pericardiocentesis, which should be reserved and sarcoidosis), and thrombosis, particularly that
for patients in extremis.98,99 A catheter can be placed due to an underlying hypercoagulable state or endo-
into the sac to drain residual or reaccumulating fluid. thelial damage from an indwelling vascular device.
Adenocarcinoma-provoked pericardial effusions are
more likely to recur and these patients may be more Presentation
appropriate for a pericardial window or pericardiec- The extent of SVC obstruction and acuity of devel-
tomy, whereas virtually all other histologies can be opment dictate the patient’s presentation. Blockage
managed with pericardiocentesis and insertion of a is better tolerated when there has been time for col-
drainage catheter.100 lateral veins to develop in adjacent venous systems
Patients often report immediate symptomatic like the azygos and internal mammary, a process that
improvement from pericardiocentesis but still usually takes weeks. The veins on the patient’s chest
require close monitoring. Decompression can pro- wall may be visibly distended (Fig. 2). Edema in the
duce paradoxical hemodynamic instability requiring arms, facial plethora (not necessarily unilateral), che-
admission to the intensive care unit and pressor sup- mosis, and periorbital edema may also occur. Stridor
port. The risk of such decompensation increases is an alarming sign that edema is narrowing the
with hematologic malignancies and also rises in luminal diameter of the pharynx and larynx. Hoarse-
direct proportion to pericardial fluid volume.101 ness and dysphagia can result from edema around
Diagnosis
Radiographic imaging is crucial to diagnosis and treat- Infectious Emergencies
ment planning, especially if radiation and endovascular
Neutropenic Fever
stents are potential interventions. While the gold
standard for localizing obstruction remains selective Pathophysiology
venography, multidetector computed tomography A patient’s absolute neutrophil count (ANC) can
(CT) or magnetic resonance imaging (MRI) are usu- decline through a cancer’s direct interference with
ally preferable for their noninvasiveness, easier avail- hematopoiesis, as in leukemia or metastatic replace-
ability, and decreased contrast load.104 ment of the bone marrow, but neutropenia is most
commonly seen as an effect of cytotoxic therapy. For
Treatment the majority of outpatient chemotherapy regimens,
SVC syndrome requires prompt recognition and the nadir in ANC occurs 5 to 10 days after the last
treatment, but the clinical course typically permits dose. Inpatient regimens, especially those used to
completion of appropriate diagnostic studies before treat hematologic malignancies, tend to produce a
definitive therapy begins.105 In a review of 1986 neutropenia of greater depth and duration, both of
patients with this presentation, there was only one which amplify risk.109 Other risk factors include the
well-documented case in which death was directly at- rapidity of the ANC decline; exposure to prior
tributable to SVC obstruction.106 Thus, when SVC chemotherapy or current immunosuppression; pre-
syndrome heralds malignancy, the practitioner usually treatment elevations in alkaline phosphatase, biliru-
still has time to perform biopsies or other diagnostic bin, or aspartate aminotransferase levels; reduced
procedures without endangering the patient, although glomerular filtration rate; and cardiovascular comor-
therapy should not be delayed unnecessarily.106 bidities. The classes of chemotherapy with the
highest risk of inducing neutropenia are the include funduscopy, palpation of the maxillary
anthracyclines, taxanes, topoisomerase inhibitors, and frontal sinuses, and inspection of vascular access
platinums, gemcitabine, vinorelbine, and certain sites.
alkylators like cyclophosphamide and ifosfamide.110 At a minimum, 2 sets of blood cultures should be
A minority of cases of febrile neutropenia will drawn in each patient. If an intravascular device is
have an offending infectious agent identified. Of present, at least one set of blood cultures should be
those that do have a documented infectious source, a obtained through that route, and ideally through
variety of organisms can be responsible. Gram-posi- each lumen of a multiple-port catheter. The collec-
tive cocci, which are now responsible for the majority tion times of peripherally and device-drawn cultures
of culture-positive cases of neutropenic fever, include ought to be carefully recorded; when catheter-
Staphylococcus aureus, Staphylococcus epidermidis (espe- obtained blood cultures have a time to positivity that
cially in patients with indwelling devices), Streptococ- is at least 120 minutes earlier than that of peripheral
cus pneumoniae, Streptococcus pyogenes, the Streptococci cultures, it strongly suggests that the catheter is the
viridans, and Enterococcus faecalis and faecium. Cory- source of infection.115 Urinalysis and urine culture
nebacterium is the most likely gram-positive bacillus. should also be obtained, but the lack of neutrophils
Gram-negative bacilli include Escherichia coli, may preclude pyuria. Chest x-rays can be ordered to
Klebsiella species, and Pseudomonas aeruginosa.111 evaluate respiratory symptoms.
Candida is the most common fungal infection,112 Treatment
but Aspergillus and Zygomycetes are more feared for Prior to the era of empiric antibiotics, 50% to 75%
their angioinvasive predilection. of chemotherapy-related mortality was due to infec-
Presentation tions.116 Empiric therapy is justified by the acuity
Infection is responsible for at least half of the cases with which the neutropenic patient can develop fever
of neutropenic fever.113 Fever is a single oral temper- and progress to sepsis. Antimicrobial coverage can
ature of 38.3 C (101 F) or higher, or temperatures then be narrowed as more microbiologic data
of 38.0 C (100.4 F) or higher measured 1 hour become available. While the minority of blood cul-
apart.113 A patient’s reduced ability to mount an tures obtained at presentation will yield identifiable
inflammatory response can limit localizing signs and organisms, it is still vital to adapt management to
symptoms, and therefore fever may be the only positive culture and susceptibility results; failure to
abnormal finding at presentation. Skin and soft tis- change therapy appropriately in response to this in-
sue infections may not be associated with erythema formation doubles the patient’s mortality risk.117
or induration, and abscesses will not accumulate in Empiric antibiotic therapy can be administered in
the absence of pus-generating neutrophils. Pulmo- the inpatient or outpatient setting depending upon
nary infections may not result in audible or radio- the patient’s initial risk assessment (Fig. 3). The
graphically visible infiltrates. Infectious Disease Society of America has recently
updated its febrile neutropenia guidelines to define
Diagnosis high-risk patients as those in whom neutropenia is
When the ANC is less than 500/mm3, or the ANC anticipated to last longer than a week with an ANC
is less than 1000/mm3 with a predicted decline to of 100/mm3 or less, and/or worrisome aspects of pre-
less than 500/mm3 within 48 hours, the patient is sentation, including hypotension, acute abdominal
considered neutropenic. The vulnerability to infec- pain, neurologic changes, or suspicion of pneumonia.
tion substantially rises at an ANC less than 1000/ Such patients require hospitalization for close moni-
mm3,114 but the risk continues to increase as the toring and iv antibiotics. Monotherapy is acceptable
ANC falls. At least one-fifth of all patients with an only with a sufficiently broad-spectrum agent such
ANC less than 100/mm3 are bacteremic.113 as the fourth-generation cephalosporin cefepime, a
A careful, thorough physical examination is crucial. carbapenem, or piperacillin-tazobactam, all of which
Particular attention should be given to any focal areas offer antipseudonomal activity. Vancomycin can be
of pain or disruption of mucosal barriers, especially added for skin and soft tissue infections, pneumonia,
the gums, pharynx, perineum, and anus, avoiding digi- or suspicion of an infected device, but it should not
tal rectal examination. Examination should also be used as monotherapy.118
FIGURE 3. Initial Management of Febrile Neutropenia. IV indicates intravenous. Reprinted with permission from Freifeld AG, Bow EJ, Sepkowitz KA, et al.
Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America.
Clin Infect Dis. 2011;52:427–431, by permission of Oxford University Press on behalf of the Infectious Diseases Society of America. V C 2011.
In low-risk patients without significant comorbid- Pseudomonas aeruginosa, fungi, or mycobacteria, de-
ities whose neutropenia is expected to last less than a vice removal followed by at least 14 days of antimi-
week and who have not been receiving quinolone crobial therapy is recommended.118
prophylaxis, oral empiric therapy with ciprofloxacin The most recent American Society of Clinical
and amoxicillin-clavulanate (both at a dose of 500 Oncology guidelines on the applications of myeloid
mg every 8 hours) is appropriate, but patients still colony-stimulating factors (CSFs) do not routinely
require daily outpatient monitoring to ensure com- recommend their use in the active treatment of
pliance and clinical improvement. If fever persists at patients with febrile neutropenia.120 However, the
48 hours, the patient should be hospitalized.118 prophylactic use of CSFs has benefit in patients with
Antibiotic therapy should be continued at least an anticipated risk of febrile neutropenia that equals
until the ANC improves to above 500/mms. The or exceeds 20%.120 CSFs should then be employed
addition of antifungal coverage should be considered during subsequent cycles of any regimen in which
in high-risk patients who remain febrile after 4 to 7 febrile neutropenia has previously occurred.121
days of broad-spectrum antibiotics with no identified Due to the accompanying risk of respiratory decom-
causative organism.118 Diagnosis of an iv catheter- pensation, especially in patients being treated for pneu-
related infection does not necessarily require removal monia, granulocyte infusions should be considered only
of the catheter if the culprit organism is a coagulase- in cases of prolonged neutropenia when bone marrow
negative Staphylococcus, but retention of the device recovery is expected. They have been more demonstra-
does incur a higher risk of recurrent infection.119 For bly effective in refractory gram-negative and fungal
catheter infections caused by Staphylococcus aureus, infections than in gram-positive infections.122
focal neurologic deficits and papilledema. The triad performed depending on tumor location and is the
of signs referred to as the Cushing response (hyper- most rapid way to alleviate ICP. Chemotherapy can
tension with wide pulse pressure, bradycardia, and be used in highly chemosensitive disease such as germ
an irregular respiratory rate) is a late effect and indi- cell tumors, lymphoma, or small cell carcinomas, or in
cates impending herniation. cases in which radiation therapy is not an option.
Diagnosis
Once an intracranial malignancy is suspected, Seizures
contrast-enhanced MRI is the preferred method of Seizures are the presenting symptom of intracranial
diagnosis. Contrast-enhanced MRI is more sensitive metastases in 10% to 20% of patients with intracra-
than either nonenhanced MRI or CT scanning nial involvement. Seizures may or may not be associ-
in differentiating metastases from other ated with ICP. Status epilepticus requires emergent
CNS lesions. 162,163
Noncontrast CT scan is the treatment, usually with lorazepam, phenytoin, val-
preferred scanning technique, however, in an acute proic acid, or fosphenytoin.13,109,157 Patients with
situation when hemorrhage or hydrocephalus is brain metastases who have not had a seizure do not
suspected.109,157,164 benefit from the prophylactic administration of anti-
seizure medication. A meta-analysis of 5 randomized
Treatment trials using phenobarbital, phenytoin, or valproic
Glucocorticoids are the initial treatment of choice acid as prophylactic anticonvulsants concluded that
and can reduce peritumoral edema and local brain there was no evidence to support their use, regardless
compression within hours by repairing the leaky cap- of tumor type.171 A subsequent systemic Cochrane
illary permeability.165,166 There is no consensus con- review also concluded that there was no significant
cerning dose, but dexamethasone is the standard difference between placebo and treatment with phe-
agent because of its relative lack of mineralocorticoid nobarbital, phenytoin, or valproic acid in preventing
activity and because it is associated with a lower risk a first seizure.172 These drugs also have significant
of infection and cognitive impairment compared side effects such as bone marrow suppression, as well
with other glucocorticoids.167,168 The mechanism of as interactions with chemotherapeutic and targeted
action is not fully understood but has been shown to agents, many of which are metabolized via the same
downregulate VEGF, upregulate angiopoeitin-1, cytochrome P450 system induced by antiepileptic
and increase clearance of peritumoral edema by facil- medications.157
itating the transport of fluid into the ventricular sys-
tem.169 In general, the dose consists of a 10-mg to
24-mg iv bolus followed by 4 mg every 6 hours or Hematologic Emergencies
8 mg twice daily.109,157 In severe cases, mannitol and
hyperventilation are used. Mannitol can be adminis- Hyperviscosity Syndrome
tered as an iv bolus or as a continuous infusion to Hyperviscosity syndrome (HVS) refers to the clinical
decrease cerebral edema. Intubation and controlled sequelae caused by increased blood viscosity. Increased
hyperventilation lead to a rapid decrease in cerebral serum viscosity (SV) is a result of excess proteins, usu-
edema. The effects of both mannitol and hyperventi- ally immunoglobulins (Igs), most commonly arising
lation are transient and not definitive therapy. These from Waldenström macroglobulinemia (WM) (85%)
should be reserved for critical cases in patients with and multiple myeloma (MM). Increased blood viscos-
rapidly declining clinical states.170 ity can result from elevated cellular components seen
More definitive treatment modalities include in hyperproliferative states such as leukemia and mye-
whole-brain radiation therapy (WBRT), surgery, or loproliferative diseases such as polycythemia vera (PV).
stereotactic radiosurgery. WBRT generally improves When hyperviscosity results from elevated white blood
the median survival by 3 to 6 months compared with 1 cells, it is referred to as hyperleukocytosis or, if symp-
to 2 months with supportive care alone and is used tomatic, leukostasis.173,174
most commonly in patients with multiple brain lesions Similarly, polycythemia can cause elevated blood
or tumors that are too large for surgery or stereotactic viscosity due to increased red blood cell mass. PV can
radiosurgery.157,170 Surgical debulking can also be cause vascular symptoms and complications secondary
All these actions, however, are temporizing measures. recognize because packed red blood cell transfusions
Unless the underlying dysproteinemia is addressed, in patients with asymptomatic hyperleukocytosis can
the serum concentration will rise again. Red cell rapidly lead to leukostasis.13,185
transfusions should be avoided unless critically neces-
Presentation
sary, as this can increase SV, thus worsening HVS.13
Leukostasis can involve any organ system, but the initial
symptoms most commonly are related to the respiratory
Leukostasis
system and the CNS.174 Pulmonary symptoms can
Leukostasis is a hematologic emergency that is asso-
range from exertional dyspnea to severe respiratory dis-
ciated with respiratory failure, intracranial hemor-
tress, with diffuse interstitial or alveolar infiltrates often
rhage, and early death.174,181 If it is not recognized
present on chest x-ray, although these are not required
and treated promptly, the mortality rate can be as
for the diagnosis. Arterial blood gases should be inter-
high as 40%.181 Risk for leukostasis increases with a
preted with caution, especially if the sample is not im-
white blood cell count (WBC) greater than 100,000/
mediately placed on ice, because pseudohypoxia with
mm3. The incidence ranges from 5% to 13% in
artifactually low arterial oxygen tension may be seen
patients with AML and 10% to 30% in adult
secondary to the rapid consumption of plasma oxygen
patients with ALL.181 Other risk factors include
from the abundant leukocytes.174,181 Neurologic mani-
younger age (with presentation in infants being most
festations span the spectrum from mild confusion to
common); ALL with 11q23 rearrangement or the
somnolence. Patients commonly report headache, dizzi-
Philadelphia chromosome; and AML subtypes M3,
ness, tinnitus, blurred vision, or visual field defects.
M4, and M5. Hyperleukocytosis portends a poor
Physical examination can reveal papilledema, retinal
prognosis, with a higher risk of early mortality, espe-
vein bulging, and retinal hemorrhage. Intracranial hem-
cially in patients with ALL. The WBC count is the
orrhage can present with focal neurologic deficits.
most important prognostic factor in ALL, and
Other symptoms include myocardial infarction, limb is-
patients who present with a WBC greater than
chemia, renal vein thrombosis, and disseminated intra-
50,000/m3 have a particularly poor prognosis; very
vascular coagulation. Fever is almost always seen and
few children with hyperleukocytosis become long-
can be greater than 39 C. Although infection is found
term survivors.174,181,182
in only a few cases, it does need to be ruled out because
Pathophysiology this syndrome can mimic sepsis. Thrombocytopenia is
The pathophysiology of leukostasis is not completely also usually present and underestimated because WBC
understood. There is believed to be a component of fragments can be counted as platelets in some auto-
‘‘sludging’’ by the leukemic blasts in the microvascula- mated cell counters.109,174,181 Disseminated intravascu-
ture secondary to increased whole blood viscosity. On lar coagulation is often seen in association with this
average, the leukemic myeloblasts have a mean cell syndrome, most commonly in the M3 subtype of
volume that is almost twice that of the leukemic lym- AML, although it can occur in all types of leukemia.181
phoblasts and therefore the manifestations are more Diagnosis
common in patients with AML than those with The diagnosis of leukostasis is made by the combi-
ALL. There is also differential expression of adhesion nation of patient symptoms and the WBC.
molecules on the lymphoblast and myeloblast cells
that has been implicated in the higher incidence of Treatment
leukostasis noted in patients with AML versus Rapid cytoreduction is the initial treatment in these
patients with ALL.174,183 Evidence also suggests that patients. Ideally, this is achieved by induction chem-
there are leukemic blast/endothelial cell interactions otherapy, which can dramatically reduce the WBC
that lead to vascular wall disruption as well as comple- within 24 hours. These patients are at very high risk
ment-induced granulocyte aggregation.174 for TLS and require close monitoring of electrolytes,
In general, whole blood viscosity is not dramati- with prophylaxis by allopurinol or rasburicase
cally increased in leukostasis because the rise in depending on renal function and fluid resuscita-
the WBC is often counterbalanced by a decrease in tion.13,174,181 The use of leukapheresis is a widely
the erythrocyte count.174,184 This is important to accepted initial treatment and was commonly
believed to reduce early mortality; however, it lacks airway obstruction, more commonly in the pediatric
randomized controlled trials and retrospective stud- population.13 Primary bronchogenic carcinomas are
ies have not shown a survival benefit.174,186 Leuka- the most common cause of malignant airway
pheresis is usually initiated when the blast count is obstructions, and up to 30% of patients with primary
greater than 100,000/m3 or regardless of blast count lung tumors will develop airway obstruction. Airway
in the presence of symptoms. In patients with ALL, obstruction does not appear to adversely affect over-
leukapheresis is usually not done unless symptoms all survival, with a median survival of 8.2 months
develop or the WBC is greater than 200,000/m3.187 versus 8.4 months when comparing patients with
Cytoreduction can also be achieved by hydroxyurea, airway obstruction with those without.190 Prompt
but is usually reserved for patients with asymptom- recognition and treatment can lead to a markedly
atic hyperleukocytosis who are unable to receive im- improved quality of life, with up to 95% of patients
mediate induction chemotherapy.188 Hydroxyurea reporting a decrease in dyspnea and a significant
can be given at doses of 1 to 2 g every 6 hours and increase in quality of life after treatment.191
can reduce the WBC by 50% to 80% within 24 to 48
Pathophysiology
hours.174,189 Induction chemotherapy should be ini-
tiated immediately or as soon as possible because Airway obstruction may result from external compres-
leukapheresis and hydroxyurea are only temporizing sion of the trachea or bronchi by the tumor, or by an
measures.174,181 Leukapheresis is generally not used involved lymph node. The obstruction can also occur
in patients with acute promyelocytic leukemia by infiltration of the tumor within the oropharynx,
because it may worsen the intrinsic coagulopathy trachea, and bronchi, causing severe narrowing.192
associated with this subtype of leukemia. These Presentation
patients are also at high risk of thrombosis with the The clinical manifestations of malignant airway
placement of the large-bore central venous catheter obstruction depend on the severity and location of
that needs to be inserted for the procedure.181 Con- the obstruction. The symptoms are nonspecific and
versely, careful monitoring of the platelet count is can be mistaken for more common conditions
required because these patients can present with including chronic obstructive pulmonary disease
thrombocytopenia and disseminated intravascular exacerbations, asthma, or bronchitis. The most com-
coagulation. Subsequent leukapheresis can worsen mon presentation of malignant airway obstruction is
the thrombocytopenia as a small portion of platelets dyspnea. The symptoms usually worsen at night and
are removed during the procedure.174 while lying supine. Patients will often have a produc-
The role of cranial radiation is still debated, but is tive cough and wheezing, and may also present with
currently used less frequently, especially in adults. stridor, especially if the obstruction is located in the
Single-fraction radiation to the cranium for severe trachea or carina. In these cases, the symptoms may
neurologic symptoms due to cerebral leukostasis, or be quite minimal until the airway is critically narrow,
to the lungs for pulmonary leukostasis causing hy- but then appear rapidly and pose a life-threatening
poxia, has been used as a temporizing measure in situation.192 ‘‘Tracheal stenosis syndrome’’ refers to a
select patients, more commonly in the pediatric pop- constellation of symptoms consisting of dyspnea,
ulation, although there are no controlled studies cough, wheezing, and stridor, and is seen in approxi-
confirming benefit.109,181,186 mately 85% of patients with primary tracheal
tumors.192,193 Hemoptysis is reported in up to 45%
of patients with obstructing neoplasms.194
Respiratory Emergencies
Diagnosis
Malignant Airway Obstruction Airway obstruction needs to be considered in the
Airway obstruction can be caused by virtually any differential diagnosis of patients with a history of
malignancy, but the most common culprits include malignancy who are presenting with new respiratory
tumors of the tongue, oropharynx, thyroid, trachea, symptoms. Crackles or fremitus, along with poor
bronchi, and lungs. Mediastinal tumors such as expansion of the lung, may be found on physical ex-
lymphomas and germ cell tumors can also cause amination.194 Chest x-rays should be rapidly
Chemotherapeutic Emergencies
Treatment
The mainstay of treatment is stenting via bronchos-
copy because it aids in diagnosis and treatment.
Rigid bronchoscopy is preferred in patients with
significant airway obstruction as flexible bronchos-
copy can potentiate the airway obstruction, and it
allows for placement of metallic self-expanding
stents that are particularly useful for cases of extrinsic
airway compression or for the control of bleeding.
Stents are the treatment of choice in patients with FIGURE 6. Bilateral Mainstem Bronchial Obstruction Shown on Coronal
acute airway obstruction due to extrinsic tumor Computed Tomography.
FIGURE 7. Anthracycline Extravasation From a Peripheral Intravenous FIGURE 8. Photograph of the Extravasation Site Shown in Figure 7
Administration in the Right Hand Occurred on November 18, 2009. A Taken on February 22, 2010 (photograph courtesy and reprinted with kind
photograph of the extravasation site was taken on December 28, 2009 permission of Herbert and Elaine Peterson).
(photograph courtesy and reprinted with kind permission of Herbert and
Elaine Peterson).
sensation. Obesity and movement during chemo-
platinum compounds, taxanes, and topoisomerase I therapy administration also increase the risk of
inhibitors cause an inflammatory reaction but not extravasation.202,206
tissue necrosis. This classification is not absolute Diagnosis
because the severity of tissue injury is dependent on
Extravasation is usually diagnosed by local symptoms
drug concentration and volume. For example, plati-
of pain, erythema, and swelling, or by leakage of
nums or taxanes can behave like vesicants and induce
fluid around the iv site, but a change in the rate of
ulcerations at high concentrations or at large vol-
infusion or absence of blood return from the vascular
umes.203 Nonaggressive agents are drugs that rarely
access may be the initial sign. Once suspected, even
cause any reaction when extravasation occurs.
if asymptomatic, the infusion needs to be discontin-
ued and treatment initiated immediately.202,205,206
Presentation
Treatment
Extravasations vary in their clinical presentation and
severity. Symptoms may occur immediately after the The best approach to an extravasation injury is pre-
incident or develop in subsequent days or weeks. In vention. Once extravasation is suspected, treatment
most cases, initial symptoms include pain, blistering, should be initiated as quickly as possible. The On-
induration, and discoloration. Ulceration may not cology Nursing Society and the European Oncology
appear for several days and may continue to worsen Nursing Society have published comprehensive
for months, as the drug diffuses into the adjacent tis-
sue. In severe cases, necrosis of the skin and the
underlying tissues may develop, leading to infection,
scars, treatment delay, functional deficits, amputa-
tion, and, rarely, death.202,204-206 In the case of irri-
tant extravasation, symptoms include erythema,
swelling, and tenderness. Phlebitis, hyperpigmenta-
tion, and sclerosis can subsequently develop along
the vein. These symptoms usually resolve within
weeks and long-term sequelae are extremely rare.
Patients with small, deep veins or those with dam-
aged veins secondary to multiple venipunctures are
at higher risk, as are patients with neurologic deficits
because of an inability to follow instructions or sec- FIGURE 9. Photograph of the Extravasation Site Shown in Figure 7
Taken on March 7, 2010 (photograph courtesy and reprinted with kind
ondary to an impaired ability to detect changes in permission of Herbert and Elaine Peterson).
infusion reactions, with some being as severe as ana- associated symptoms (such as syncope); and/or
phylaxis, particularly after repeated cycles. Carbopla- 4) persistent GI symptoms (such as abdominal pain,
tin hypersensitivity is seen in up to 2% of patients diarrhea, or emesis). The third criterion requires
receiving carboplatin, and is as high as 16% in the reduced blood pressure after exposure to a known
gynecologic oncology population, because these allergen of that patient.
patients typically receive repeated exposure to plati-
num agents.214,215 Treatment
Taxanes have been known to cause anaphylaxis Infusion reactions can vary significantly in severity.
as well. Acute reactions to paclitaxel and docetaxel In mild cases, without any features of anaphylaxis,
tend to present shortly after the infusion is initi- the infusion should be temporarily discontinued
ated, and nearly 95% of the cases develop within until proper evaluation of the patient has occurred.
the first 2 cycles of therapy.216,217 However, due to Diphenhydramine at a dose of 50 mg iv can help
the timing of these reactions, the release of hista- relieve mild symptoms. The infusion can be restarted
mine and the associated cytokines does not appear at a slow rate with close monitoring. In cases of ana-
to always be immune-mediated.217 There is also phylaxis, the infusion should be discontinued imme-
evidence that anaphylaxis can occur from the drug diately, with subsequent treatment identical to the
vehicle rather than the agent itself. Paclitaxel is management of other causes of anaphylaxis. Close
formulated with Cremophor (BASF SE, Ludwig- assessment of the airway, breathing, and circulation
shafen, Germany), a polyethoxylated castor oil that should occur. Epinephrine (0.3-0.5 mg im; 1:1000)
is also used to deliver other drugs such as ixabepi- should be given immediately and can be repeated ev-
lone, diazepam, and vitamin K.218 Paclitaxel should ery 3 to 5 minutes as necessary. Patients should also
be avoided in patients who have had a severe reac- be given oxygen and iv fluids as well. Antihistamines
tion to one of these drugs, although Abraxane and glucocorticoids also can be administered. Epi-
(micro albumin-bound paclitaxel particles; Celgene, nephrine infusions, vasopressors, and glucagon may
Summit, NJ) can be considered.219 need to be used if the patient is refractory to the ini-
Agents such as docetaxel and iv etoposide are also tial therapies.
formulated with vehicles that can cause infusion In instances in which there has been an infusion
reactions, some of which are severe. These agents are reaction but not anaphylaxis, premedications can
formulated with polysorbate 80 and can cause symp- been used to allow the patient to continue therapy
toms that include chest discomfort, bronchospasm, with the offending agent; however, such techniques
and angioedema.220 are beyond the scope of this review. Desensitization
has been used in cases in which the antineoplastic
Diagnosis agent is necessarily being used with curative
In 2005 and 2006, diagnostic criteria were published intent, even when patients have had an anaphylactic
by a multidisciplinary group of experts to aid clini- response. If, however, the skin test remains
cians in recognizing the full spectrum of signs and positive after desensitization, a rechallenge is not
symptoms of anaphylaxis.211,212 Anaphylaxis should recommended.216
be highly suspected if any one of the 3 following cri-
teria is present. The first criterion defines an acute
illness that develops over minutes to hours of the
Conclusions
offending exposure and should involve changes in Oncologic emergencies can threaten the well-being of
the skin and/or mucosal tissue, as well as evidence of almost any patient with a malignancy. Because these
respiratory compromise (such as stridor or dyspnea) conditions span the chronologic spectrum of a dis-
or hypotension. The second criterion requires that 2 ease’s natural history, from initial presentation to late
or more of the following signs and/or symptoms de- recurrence to end-stage disease, all clinicians should
velop rapidly after exposure to a likely allergen. be familiar with the manner in which these conditions
These symptoms are: 1) involvement of skin/muco- emerge, as well as understand the methods for their
sal tissue (such as hives or angioedema); 2) respira- prompt assessment and treatment. This review is not
tory compromise; 3) reduced blood pressure or intended to address these techniques in an entirely
comprehensive fashion, but may provide a framework exciting new advancements in radiology and pharma-
for the physician to process these alarming events cology that should continue to improve the care of the
from physiology to intervention, permitting room for cancer patient in their hour of greatest need. n
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