Introduction to Oncologic Emergencies

Published on 10/02/2015 by admin

Filed under Emergency Medicine

Last modified 22/04/2025

Print this page

This article have been viewed 1219 times

201 Introduction to Oncologic Emergencies

Jeremy D. Sperling

Key Points

• Fever in a neutropenic patient with cancer is assumed to be a life-threatening infection; antibiotic therapy must be started immediately.

• Hypercalcemia is common in malignant disease and is often missed. Presenting symptoms may include weakness, vomiting, and mental status changes.

• Tumor lysis syndrome causes acute renal failure, hyperkalemia, hyperphosphatemia, and hypocalcemia; it is a rare but life-threatening complication of chemotherapy.

• Adrenal insufficiency and pericardial tamponade are causes of hypotension.

• Pleural effusions commonly cause dyspnea in the oncology patient. However, always exclude life-threatening causes of dyspnea (e.g., pulmonary embolism, pneumonia, pericardial tamponade) in this patient population.

Epidemiology

As the population ages, cancer prevalence is expected to increase.¹ In 2010, the United States population had more than 1.5 million new cancer diagnoses and more than 569,000 cancer deaths.² The American Cancer Society estimated that the number of new cancer cases will double from 2000 to 2050.¹ At the same time, aggressive treatment strategies, whether involving surgery, chemotherapy, or radiation, are helping oncology patients to live longer and at times overcome their cancer. In fact, U.S. cancer death rates decreased by 1% per year from 2001 through 2006.² Since the 1970s, the 5-year survival rate for all cancers has increased from 50% to 68% in the United States.² Declines in cancer deaths are the result of many factors, including better screening, early detection strategies, public health risk reduction programs, and improved medical and surgical treatment. Emergency physicians (EPs) are routinely called on to recognize and treat emergency complications of cancer and cancer therapies. Interventions that the EP makes to keep a patient alive acutely may allow the patient’s chemotherapy or radiation therapy to work for an overall cure. Today, oncology patients treated in the emergency department (ED) are increasingly more likely to survive to hospital discharge, even if they are admitted to an intensive care unit.³

Triage

Some oncologic emergencies require timely action. One example is the patient with fever and potential neutropenia; this patient requires rapid assessment and early antibiotic administration. Other oncologic emergencies requiring immediate intervention include airway or respiratory complications, spinal cord compression, and possible cerebral herniation.

Isolation and Infectious Control Issues

Each year, approximately 1.9 million nosocomial infections occur in U.S. hospitals, and approximately 88,000 patients die.⁴ Immunocompromised patients with cancer, especially neutropenic patients and bone marrow transplant recipients, are at increased risk for these infections. At-risk patients should be identified on ED arrival and should not be allowed to spend a significant amount of time in waiting rooms or busy ED hallways, where they can be exposed to infections from other patients. Ideally, bone marrow transplant recipients and potentially neutropenic patients should be placed in single rooms with positive air pressure at 12 or more air exchanges per hour. Positive air pressure decreases the number of infectious particles that enter a patient’s room. If such a room is unavailable, the next best option is to place the patient in an individual room with the door closed. Patients with a potential airborne illness (e.g., tuberculosis) are the exception; they should be placed in a negative pressure room to protect other patients and the ED staff.

As with all patients, careful hand washing is essential when dealing with the neutropenic patient. However, when providing noninvasive care, the use of sterile gowns, masks, and gloves does not provide any extra protection. To avoid bacterial contamination, neutropenic patients should generally be offered only cooked (or pasteurized) food and bottled water. However, data supporting this type of “neutropenic diet” is quite limited and may unnecessarily restrict the patient’s nutritional options.

Oncologic History

Although obtaining a complete past medical history from a patient with cancer is not always possible or necessary for the EP, certain questions may prove crucial and are unique to the oncology patient. Pertinent information includes the type of cancer, the stage of the cancer (the extent of its spread), previous cancer-related complications, and previous cancer treatments including surgery, chemotherapy, and radiation therapy. The timing of recent treatments and the names of specific chemotherapeutic agents that have been used are important because these treatments may be the direct cause of the patient’s current illness. Oncology patients may have complicated past medical histories. Reliable sources such as hospital records (if the patient has recently been admitted) or the patient’s oncologist should be used to obtain pertinent data quickly.

Early in the ED encounter with an oncology patient, the patient should be asked whether he or she has any specific wishes or advanced directives. Specifically, patients should be asked whether they have a “do not resuscitate” or “do not intubate” order or a health care proxy. Many patients with cancer, especially those with late-stage disease, may have very defined treatment objectives in mind (e.g., intravenous hydration but no invasive procedures or tests). These objectives and wishes should be documented in the chart and respected. Early inquiry about the patient’s wishes and expectations will help to guide treatment appropriately.

Fever

Fever is a very common chief complaint for oncology patients who present to the ED, especially for those undergoing chemotherapy. Fever can be the first sign of a life-threatening infectious process. In particular, neutropenic patients are highly susceptible to almost any type of bacterial or fungal infection. Fever in the setting of neutropenia must be assumed to be a life-threatening bacterial infection, and antibiotic therapy should be started immediately (see the “Facts and Formulas” box for the definition of neutropenic fever). Besides the immediate infectious risks, a neutropenic fever episode may delay or end future chemotherapy treatment and therefore may compromise the overall chances for a cancer cure.

Facts and Formulas

Neutropenic Fever Defined

Fever: Temperature ≥ 38.3° C once or ≥38.0° C for >1 hour

Neutropenia: Absolute neutrophil count < 500/mm³ or <1000/mm³ with a predicted decline to <500/mm³

Epidemiology

Neutropenic fever is the most common emergency indication for hospital admission among oncology patients. The in-hospital mortality rate in patients with neutropenic fever is approximately 9.5%, and it increases if the patient has any associated comorbidities.⁵ Patients with neutropenic fever have a mean (median) length of stay of 11.5 (6) days, at a mean cost of more than $19,000 per case.⁵

Pathophysiology

Chemotherapy can severely damage a patient’s normal defense mechanisms, including both humoral and cellular immunity, thus leaving the patient defenseless to combat infection. Chemotherapy can weaken or destroy neutrophils, T lymphocytes, macrophages, monocytes, and immunoglobulin production. Radiation and chemotherapy also affect the patient’s mechanical barriers against infection. In particular, they damage the integrity of the mucous membranes and skin. All this injury to the patient’s immune system takes place in an individual who already has cancer and therefore may already have either a weakened immune system or compromised physiologic factors.

Differential Diagnosis and Medical Decision Making

Although the prudent approach is to assume that fever in an oncology patient is from an infectious source, infection is not the only reason that oncology patients may have a fever. Fever can sometimes be a manifestation of the underlying malignant process itself or a side effect of a chemotherapeutic agent. Chemotherapeutic agents such as bleomycin and cytosine arabinoside have been noted to cause fevers. Lymphomas, leukemias, and renal cell carcinoma have been recognized as sources of fever without any concurrent infection, and at times, fever can be their initial presenting symptom. Thrombophlebitis, medications, and transfusion reactions can also be rare causes of fever.

Diagnostic Testing

The EP should search for an infectious source of the fever. A minimum evaluation should include at least two blood cultures, a urinalysis and urine culture, a chest radiograph, a complete blood count with differential (to confirm neutropenia), and baseline chemistry studies including kidney and liver function. Blood cultures should be obtained from all indwelling vascular catheters that are present. At least one blood culture should be drawn from a peripheral vein. Further diagnostic testing should be driven by the patient’s symptoms or physical examination findings. For example, an abdominal and pelvic computed tomography (CT) scan should be ordered if an intraabdominal source of the fever is possible. Other sources to consider culturing in the appropriate clinical setting are the oropharynx, cerebrospinal fluid, peritoneal fluid, pleural fluid, stool, and any purulent skin lesions.

Treatment

Empiric, broad-spectrum antibiotics should be started as early as possible for patients in the ED who have neutropenic fever. Antibiotics should not be delayed while awaiting confirmation of the neutropenia but rather should be started on all febrile patients at high risk (e.g., recent chemotherapy).⁶ Additionally, antibiotics should not be delayed while the EP looks for an infectious source. An obvious source is very often not identifiable in the ED. Rapid antibiotic administration is the likely reason for substantial mortality reductions among bacteremic patients with cancer. With the incorporation of this early antibiotic strategy, a large European research group found an overall mortality decrease from 21% to 7% over a 16-year period.⁷

Patients should be started empirically on antibiotics that reflect the resistance patterns and bacterial profiles of the treating institution. Most institutions have antibiotic protocols based on these bacterial patterns. Gram-positive organisms such as Staphylococcus aureus, Staphylococcus epidermidis, and viridans streptococci are currently more predominant than gram-negative organisms as the source of neutropenic fever. However, gram-negative organisms can be more virulent (e.g., Pseudomonas), and therefore the patient must always be empirically treated for these pathogens.

Single-agent intravenous antibiotics regimens are currently recommended for hemodynamically stable patients whose medical condition is uncomplicated.^6,⁸ Potential monotherapy regimens include cefepime, piperacillin-tazobactam, or a carbapenem (e.g., imipenem-cilastatin, meropenem).^6,⁸ Double coverage with an aminoglycoside (e.g., gentamicin, tobramycin) or a fluoroquinolone (e.g., levofloxacin) should be considered if antibiotic resistance is strongly suspected, if the patient is in shock, or if this approach is needed to manage other complications. Vancomycin should not be started empirically for neutropenic fever.^6,⁸ No significant difference in morbidity or mortality was found in a meta-analysis of 13 randomized control trials when a standard neutropenic antibiotic regimen was compared with the same regimen plus a glycopeptide (e.g., vancomycin).⁹ However, one should consider starting vancomycin if the infection is suspected to originate from an indwelling central venous catheter, a soft tissue infection, or hospital-associated pneumonia or if the patient is in septic shock.^6,⁸ A lower threshold for adding vancomycin should be used if the institution has a high rate of methicillin-resistant S. aureus (MRSA) or resistant viridans streptococcal strains.

Long indwelling catheters should generally be left in place and not removed in the ED. Many catheters in this patient population are buried subcutaneously and are not easily removed. Removal of the catheter in the ED should be considered if the tunnel is grossly infected or if the infected catheter has produced septic emboli or endocarditis.

Granulocyte colony-stimulating factors (G-CSFs) are used by oncologists with certain chemotherapy regimens to decrease the incidence of neutropenic episodes. Current guidelines recommend the prophylactic administration of a G-CSF with chemotherapy to patients who, based on age, past medical history, chemotherapy toxicity, and tumor characteristics, have a greater than 20% chance of developing febrile neutropenia.^8,¹⁰ This G-CSF prophylaxis regimen with chemotherapy has been shown to be effective; for example, in patients with small cell lung cancer, it decreases the incidence, duration, and severity of neutropenic fever.¹¹ Commonly used G-CSFs for prophylaxis are daily injections of filgrastim or lenograstim or a once per chemotherapy cycle injection of pegfilgrastim. Adverse side effects of G-CSF use include bone, joint and musculoskeletal pain and flulike symptoms.¹²

The use of a G-CSF in the acute setting of neutropenic fever is controversial. A meta-analysis of 13 studies with 1518 patients found that patients with neutropenic fever who were treated with G-CSFs had shorter hospitalizations and neutrophil recovery times but only a marginally significant benefit in infection-related mortality and no significant benefit in overall mortality.¹² Because the effects of G-CSFs on mortality are not clear and because these agents are very expensive, a G-CSF should not be given routinely in the ED for neutropenic fever. Rather, until more convincing evidence exists, G-CSFs should be given only after discussion with the patient’s oncologist and considered only for patients who are at high risk for infectious complications or who have prognostic factors predictive of a poor outcome.^10,¹³

Follow-Up and Next Steps

Nearly all patients with neutropenic fever require admission. Outpatient management could be considered for carefully selected low-risk patients within a well-designed institutional protocol and in concert with the patient’s oncologist. Certain decision rules have attempted to determine which neutropenic patients are at low risk for complications and therefore could be eligible for outpatient treatment with oral antibiotics. The most commonly cited decision rule for assessing low-risk patients is the Multinational Association for Supportive Care in Cancer (MASCC) index score ^6,⁸ (Table 201.1). In its initial validation study, the MASCC index score was found to have a positive predictive value of 91%, a specificity of 68%, and a sensitivity of 71%.¹⁴ The MASCC decision rule is likely best applied to select patients who can quickly undergo conversion to oral antibiotics as inpatients and, in the absence of early complications, be targeted for early hospital discharge. If the patient is discharged, an oral antibiotic regimen is prescribed; ideally, the patient is observed taking the first dose in the ED. The two most common regimens used are a quinolone alone (e.g., ciprofloxacin) or a quinolone plus amoxicillin-clavulanate.¹⁵

Table 201.1 Multinational Association for Supportive Care in Cancer Index Score for Identifying Low-Risk Patients at Neutropenic Fever

BURDEN OF ILLNESS*	SCORE
No or mild symptoms/moderate symptoms*	5/3
No hypotension	5
No chronic obstructive pulmonary disease	4
Solid tumor or no previous fungal infection	4
No dehydration	3
Outpatient status^†	3
Age < 60 yr	2
Add together points to obtain score (maximum score, 26)
Risk of complication: high risk < 21; low risk ≥ 21

^* Burden of illness: 5 for no or mild, 3 for moderate, 0 for severe.

^† Outpatient status means onset of fever as an outpatient.

From Klastersky J, Paesmans M, Rubenstein EB, Boyer M. The Multinational Association for Supportive Care in Cancer Risk Index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol 2000;18:3038-51.

Infectious Causes of Fever Unique to the Patient with Cancer

Electrolyte Disturbances in the Oncology Patient

Tumor Lysis Syndrome

Perspective

Tumor lysis syndrome (TLS) is the constellation of metabolic abnormalities that occur in response to the rapid destruction of malignant cells, generally from the initiation of chemotherapy (Table 201.2). The sudden death of many malignant cells results in the release into the bloodstream of their intracellular contents, and this causes sudden increases in potassium, phosphorus, and uric acid levels. TLS is generally predictable. It usually occurs with the initiation of chemotherapy in a patient with newly diagnosed cancer. Acute lymphoblastic leukemia, acute myeloid leukemia, and non-Hodgkin lymphoma (especially Burkitt lymphoma) are the most common cancers associated with TLS.¹⁷ Less commonly, TLS occurs in other leukemias, in multiple myeloma, or after the treatment of some solid tumors such as breast and lung cancer. When initiating chemotherapy, oncologists generally take measures to prevent TLS in at-risk patients by pretreatment with aggressive hydration, diuresis, and allopurinol (in an attempt to decrease uric acid formation). Rarely, TLS develops spontaneously. When it does, it is usually in the setting of relapsing or newly diagnosed (but untreated) cancer.

Table 201.2 Tumor Lysis Syndrome: Electrolyte Disturbances and Treatment

DISTURBANCE	TREATMENT
Hyperkalemia	Sodium polystyrene sulfonate, regular insulin and glucose, calcium gluconate; if severe: dialysis
Hyperphosphatemia	Aluminum hydroxide; if severe: dialysis
Hypocalcemia	Calcium gluconate (only if symptomatic)
Uremia	IV hydration; IV rasburicase (recombinant urate oxidase)
Renal failure	Dialysis

IV, Intravenous.

Pathophysiology

TLS most frequently occurs when the patient has a high tumor burden that is very sensitive to chemotherapy. Chemotherapy rapidly destroys malignant cells; intracellular nucleic acids are released and are broken down into uric acid. Uric acid, which is renally excreted, precipitates in the renal tubules. The precipitation may obstruct flow and can result in renal failure. Clearly, patients with baseline renal dysfunction are at even greater risk. Potassium, found in high concentrations intracellularly, is released with the destruction of the malignant cells. Because of worsening renal function secondary to uric acid precipitation, the kidneys are unable to clear this excess potassium, and the result can be dangerously high potassium levels. Phosphorus is similar to potassium; it is concentrated intracellularly and is generally excreted by the kidney. Therefore, phosphorus levels also rise. The excess phosphorus congregates with available calcium to form calcium phosphate crystals that cause the calcium level to drop. These crystals may precipitate in the renal tubules and worsen renal function.

Presenting Signs and Symptoms

TLS manifests with symptoms reflective of the metabolic abnormalities that are present (e.g., hyperkalemia, renal failure). Therefore, symptoms may be nonspecific. Symptoms of hyperkalemia tend to be vague and may include palpitations, paresthesias, fatigue, muscle cramps, nausea, and weakness; examination findings may include nonfocal reduced muscle strength or decreases in deep tendon reflexes. Mild hypocalcemia causes muscle cramps, paresthesias, and minor mental status changes. With severe hypocalcemia, the patient may have significant mental status changes, tetanic contractions, seizures, hypotension, or dysrhythmias. Classic physical examination findings include the Chvostek sign (facial twitching or spasms with tapping over the facial nerve anterior to the ear) and the Trousseau sign (carpal spasm with inflation of a blood pressure cuff above the systolic blood pressure). Very high levels of phosphorus can cause vomiting, diarrhea, lethargy, and even seizures.

Diagnostic Testing

Laboratory evaluation should include, at minimum, blood urea nitrogen, creatinine, potassium, calcium, magnesium, phosphorus, uric acid, albumin, and urinalysis. The measurement of ionized calcium may be helpful. An electrocardiogram (ECG) should be obtained because it can quickly help diagnose significant hyperkalemia or hypocalcemia. A chest radiograph may be useful if the EP is concerned about fluid overload secondary to renal failure.

Treatment

Despite the widespread oncologic practice of prophylactic measures to prevent TLS, the EP occasionally must manage this potentially life-threatening syndrome. A high index of suspicion must be kept for this clinical entity, especially in high-risk patients who recently started chemotherapy or who may have baseline renal insufficiency. Patients with suspected TLS should be placed on continuous cardiac monitoring because they are at risk for cardiac dysrhythmias. Treatment should be focused on closely monitoring electrolytes and renal function, correcting electrolyte abnormalities, and ensuring appropriate hydration. Patients who do not have acute renal dysfunction should be aggressively hydrated with normal saline solution. Aggressive hydration helps renal blood flow and the excretion of potassium, uric acid, and phosphorus. After adequate hydration, furosemide or mannitol may be added to increase urine output.

Hyperkalemia and hyperphosphatemia should be promptly treated. Only symptomatic hypocalcemia should be treated because infusing calcium into a hyperphosphatemic patient increases the risk of calcium phosphate formation and deposition throughout the body, including in the renal tubules. In clinically significant TLS (e.g., renal dysfunction, hyperuricemia), rasburicase, a recombinant form of urate oxidase, can be used. Urate oxidase is an enzyme (not found in humans) that converts uric acid to allantoin, which is 5 to 10 times more water soluble than uric acid. The recommended rasburicase dose is 0.1 to 0.2 mg/kg/day intravenously in 50 mL of normal saline solution over 30 minutes.¹⁷ Rasburicase is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency. Allopurinol, which has been traditionally used in the prevention and treatment of TLS, works by decreasing uric acid production through competitive inhibition of the enzyme xanthine oxidase, which turns xanthine into uric acid. Once uric acid is present, allopurinol’s effect is limited; therefore, allopurinol is not very useful in the acute treatment of TLS.¹⁷ Finally, when renal failure develops and becomes severe (e.g., uncontrolled hyperkalemia, uncontrolled hypertension, fluid overload), emergency hemodialysis is indicated.

Controversy exists regarding the practice of urine alkalinization, which consists of adding sodium bicarbonate to intravenous fluids in an effort to help excrete uric acid. The theory is that alkalinization (with a goal of achieving a urine pH of 7 to 7.5) decreases uric acid precipitation in the renal tubules and increases uric acid excretion in the form of urate. Although a sodium bicarbonate infusion may help to eliminate uric acid, it may also worsen hypocalcemia and increase phosphate and calcium precipitation, potentially in the heart and kidneys, and therefore worsen renal function. Because hydration alone may achieve adequate uric acid excretion, routine urine alkalinization is not currently recommended.¹⁷

Hypercalcemia

Epidemiology

Hypercalcemia is the most common metabolic abnormality found in patients with cancer. At some point in their illness, at least 10% to 30% of patients with cancer develop hypercalcemia.¹⁸ Unfortunately, the diagnosis is frequently missed and left untreated because the symptoms are nonspecific and are often attributed to other causes (e.g., chemotherapy, infection). Hypercalcemia is most commonly found in breast and lung cancer, but it also occurs in multiple myeloma, leukemias, lymphomas, and cancers of the head, neck, kidney, and gastrointestinal tract.¹⁸

Pathophysiology

Primary hyperparathyroidism is the most common cause of an elevated calcium level in patients who do not have cancer. In malignant disease, hypercalcemia is related not to parathyroid hormone activity, but rather to increased osteoclastic activity in bone. A few mechanisms are responsible for this increased osteoclastic activity. First, metastasis of solid tumors can cause extensive direct bone destruction. Some cancer cells release osteoclast-activating factors. Some cancers produce a parathyroid-like hormone that acts on bone by increasing calcium uptake and also acts on the kidneys by decreasing calcium excretion.

Presenting Signs and Symptoms

Symptoms of hypercalcemia are generally nonspecific. Symptom severity depends more on how rapidly the calcium level has escalated, rather than on the actual calcium level. Symptoms include general weakness, constipation, nausea and vomiting, dehydration, polyuria and polydipsia, personality changes, and bone and muscle pains. Severe symptoms include confusion, drowsiness, and even coma. No physical examination findings are specific only to hypercalcemia. However, the diagnosis must be considered when evaluating an oncology patient with any degree of mental status alteration (from mild confusion to obtundation), hyporeflexia, or dehydration.

Diagnostic Testing

If hypercalcemia is suspected, an ECG should be performed and laboratory tests sent for, at minimum, creatinine, potassium, calcium, phosphate, alkaline phosphatase, and albumin. QT shortening on the ECG may provide the quickest method of diagnosing hypercalcemia. In patients with higher calcium levels, the ECG may have a variety of finding, including T-wave changes, bradycardia, or heart block. The calcium level reported in a basic metabolic profile reports the calcium concentration in serum, the normal value of which is 9 to 11 mg/dL. Calcium levels greater than 12 mg/dL should generate concern, and levels higher than 14 mg/dL require immediate intervention. However, calcium levels correlate poorly with actual symptoms. Because calcium is present both in an ionized form and a protein-bound form, the concentration of calcium depends on plasma protein concentrations. A corrected calcium level should be calculated to assess whether hypercalcemia is truly present (see the “Facts and Formulas” box). The corrected calcium concentration is based on the albumin level. After this calculation, if any uncertainty remains, an ionized calcium level should be obtained.

Facts and Formulas

Corrected Calcium Formula

Notes:

Corrected calcium (normal range) = 9 to 10.6 mg/d

4.0 g/dL = Average albumin level

Treatment

Correcting hypercalcemia not only improves symptoms, but it also may decrease the risk of death during hospitalization.¹⁹ For initial treatment of significant hypercalcemia, aggressive intravenous hydration with normal saline solution should be started. Hypercalcemic patients may be significantly volume depleted and require intravenous fluids. Saline hydration dilutes the calcium concentration, promotes urinary excretion of calcium, and treats dehydration. Patients with severe hypercalcemia should be placed on continuous cardiac monitoring, and their urine output should be closely monitored (with a Foley catheter if necessary).

Electrolyte studies should be obtained every few hours to monitor the calcium level and to ensure that the saline hydration does not cause significant hypokalemia or hypomagnesemia. If the patient is in renal failure and will not tolerate aggressive saline hydration, dialysis may be needed to correct the calcium level.

In addition to saline hydration, a bisphosphonate should be considered (e.g., pamidronate, zoledronic). Bisphosphonates work by inhibiting osteoclastic activity through prevention of osteoclast attachment to bone and interference with osteoclast recruitment; this process decreases bone reabsorption. Pamidronate, the most commonly used bisphosphonate, can be administered at 60 mg intravenously over 2 to 24 hours for moderate hypercalcemia and at 90 mg over 2 to 24 hours for severe hypercalcemia. Another bisphosphonate, zoledronic acid, 4 mg intravenously, may be more effective.²⁰

Calcitonin should be considered next. Calcitonin inhibits bone reabsorption and increases renal excretion of calcium. The effects of calcitonin are short-lived, but they can be seen within 4 hours. Calcitonin is administered at 4 to 8 units/kg either intramuscularly or subcutaneously.

Even though loop diuretics (e.g., furosemide) are unlikely to lower the calcium level significantly, they may be useful if the patient becomes volume overloaded and needs diuresis. Before a diuretic is administered, the patient should have demonstrated adequate urine output; this will ensure that the diuretic will not worsen a volume-depleted state.

Other possible treatments for hypercalcemia include gallium nitrate, mithramycin, and corticosteroids (e.g., hydrocortisone). These agents can be administered in consultation with the patient’s oncologist. Finally, patients with mild calcium elevations or minimal symptoms can be treated with oral hydration.

Follow-up, Next Steps, and Admission and Discharge

Patients with mild calcium elevations can be discharged after hydration in the ED. Discharge can be considered if patients have no other active issues and if close follow-up can be arranged with their oncologist. Patients with significant symptoms (e.g., dehydration, altered mental status) should be admitted, as should patients with baseline renal insufficiency, because they are more difficult to treat.

Hypotension

Differential Diagnosis and Medical Decision Making

The causes of hypotension or shock in an oncology patient in the ED vary to some degree from those seen in the general ED population (Box 201.1). Common causes of hypotension and shock, such as sepsis and hypovolemia (e.g., secondary to gastrointestinal losses or bleeding), are also common in the oncology patient. Severe dehydration is a particular problem because many cancers or cancer treatments make oral intake very difficult and may cause vomiting or diarrhea. Certain clinical entities such as pericardial tamponade and adrenal insufficiency appear with increased frequency in this patient population. Cardiac tamponade is discussed in Chapter 202, but the EP must always consider this disorder in any patient with cancer who presents with hypotension, shock, or dyspnea. Some causes of hypotension are unique to the patient with cancer, such as myocardial dysfunction from a chemotherapeutic agent (e.g., doxorubicin). Because oncology patients are immunocompromised at baseline, they may require more intensive management and may suffer a worse outcome if hypotension is not addressed promptly.

Adrenal Insufficiency

Pathophysiology

In the oncology patient, adrenal insufficiency is most commonly a result of previous treatment with high-dose steroids used in chemotherapy protocols. Many patients with cancer may have subclinical or mild adrenal insufficiency that is not asymptomatic until a significant stress (e.g., infection, dehydration) develops. Adrenal insufficiency can be primary if the adrenal glands are destroyed in some way (e.g., hemorrhage, infarction) or secondary if dysfunction of the hypothalamic-pituitary-adrenal axis causes a deficiency of adrenocorticotropic hormone. Previous exogenous steroid use is a secondary cause. Metastatic infiltration of the adrenal glands is not uncommon because of the adrenal’s rich blood supply; however, metastatic infiltration rarely causes adrenal insufficiency. In one study, only 4.3% (20 of 464) of patients with metastasis to the adrenal glands on CT scan had or developed symptomatic adrenal insufficiency before they died.²¹ Metastasis to the adrenal glands is most common in lung cancer, gastrointestinal malignant disease (stomach, esophagus, liver, pancreas, and bile duct), lymphoma, kidney cancer, and breast cancer.²¹

Presenting Signs and Symptoms

Adrenal insufficiency manifests with vague symptoms such as fatigue, weakness, nausea, vomiting, nonspecific abdominal pain, dehydration, and altered mental status. Laboratory analysis may show any combination of hyponatremia, hyperkalemia, or hypoglycemia. When severe, acute adrenal insufficiency (“adrenal crisis”) produces significant hypotension secondary to distributive shock that may not respond to aggressive fluid resuscitation. The EP must have a high index of suspicion for this entity because the symptoms are often vague and can be incorrectly attributed to other causes.

Diagnostic Testing

According to consensus guidelines, adrenal insufficiency (in the setting of critical illness) can be diagnosed with either a random total cortisol level of less than 10 mcg/dL or by cortisol level nonresponse (less than 9 mcg/dL) to the 250-mcg short corticotropin-stimulation test.²² The short corticotropin-stimulation test can be performed by administering 250 mcg of cosyntropin intravenously after a baseline cortisol level is obtained. The cortisol level is repeated 30 and 60 minutes later. If the patient has adrenal insufficiency, the cortisol level response will be less than 9 mcg/dL (the difference between the baseline level and the highest response).²³ In an effort to increase the sensitivity of detecting adrenal insufficiency, the corticotropin-stimulation test with 1 mcg was studied, but further outcome data are needed.²⁴ If etomidate, which selectively inhibits 11-β-hydroxylase, is used in the ED course (specifically in the previous 4 hours), it may interfere with the cortisol response to corticotrophin. This may give a false-positive result to the corticotropin-stimulation test and the clinician may falsely conclude that the patient is adrenally suppressed.²⁵

Treatment

The treatment of adrenal insufficiency consists of glucocorticoid replacement. The most commonly recommended glucocorticoid is hydrocortisone (initial dose, 100 mg intravenously). Dexamethasone may be preferred over hydrocortisone because dexamethasone is less likely to interfere with the corticotropin-stimulation test, which can be performed later by the inpatient team or in the ED to confirm the diagnosis. A serum cortisol level can be obtained before steroid therapy is initiated. Hypotension, or dehydration is likely to be present and should be treated with fluid resuscitation (either with normal saline solution or 5% dextrose in normal saline). Any electrolyte abnormalities, especially hypoglycemia, should be promptly corrected.

Myocardial Dysfunction Secondary to Chemotherapy

As in the general population, the most common cause of cardiac dysfunction or cardiogenic shock in the oncology population is coronary artery disease. Oncology patients, like any other patient who presents in congestive heart failure or cardiogenic shock, must be evaluated for myocardial infarction. However, a few chemotherapeutic agents, most notably the anthracyclines, can cause cardiomyopathies and congestive heart failure (Table 201.3). A newer drug, trastuzumab (Herceptin), which is a recombinant monoclonal antibody used in the treatment of breast cancer, has been associated with reductions in left ventricular ejection fraction and episodes of congestive heart failure.²⁶

Table 201.3 Chemotherapy Agents That Cause Cardiac Toxicity

AGENT OR DRUG CLASS	TOXICITY
Anthracyclines (e.g., doxorubicin, daunorubicin, epirubicin, idarubicin)	Myocardial cell death, fibrosis, left ventricular dysfunction, CHF
Mitoxantrone (drug class: anthracenedione)	Cardiomyopathy similar to that caused by anthracyclines
5-Fluorouracil	Coronary vasospasm or ischemia
Cyclophosphamide	Acute hemorrhagic myopericarditis
Trastuzumab (Herceptin)	Decrease in left ventricular ejection fraction, CHF
Taxanes (paclitaxel, docetaxel)*	Dysrhythmias (atrial or ventricular), bradycardia
Radiation therapy (to lung, breast, or mediastinum)	Coronary artery disease, chronic pericarditis, valvular disease, dysrhythmias

CHF, Congestive heart failure.

^* These effects may be acute.

Dyspnea and Airway Issues in the Oncology Patient

Airway Management

Pathophysiology

When managing the airway of the oncology patient, the EP must keep some unique issues in mind. Challenging airway situations may develop in patients with certain head, neck, and laryngeal cancers or with cancers of the esophagus, thyroid, or lung whose tumor has impinged on or distorted the airway. Metastatic lesions to the bronchial tree, mediastinal structures, or lymph nodes of the neck may also cause difficulties. The major concern in these patients is that typical rapid-sequence intubation with a paralytic agent may turn a nonobstructing airway lesion into a lesion that, in a patient without any muscular tone, completely obstructs the airway and makes endotracheal intubation and bag-valve mask ventilation difficult or impossible.

Treatment

Clues to a potentially hazardous airway may include complaints of dyspnea (especially if it is worse in the supine position), stridor, hemoptysis, difficulty with handling secretions, hoarseness, or a recent change in voice. If the EP is concerned about paralyzing the patient, a few options exist. One option is to give the patient topical and nebulized lidocaine and a small dose of a sedative (e.g., midazolam, etomidate) and then perform direct laryngoscopy. If the vocal cords can be visualized with this approach and no obvious concerns for airway obstruction are noted, the patient should be either directly endotracheally intubated or intubated with typical rapid-sequence intubation using a paralytic agent. If airway control is not an emergency, awake fiberoptic intubation may be a prudent approach. Whatever method is taken, a cricothyroidotomy kit should be at the bedside, in the event that endotracheal intubation proves impossible. Even cricothyroidotomy may be difficult if the patient has significant alterations in neck anatomy secondary to neck cancer or previous neck radiation.

Specialist consultation (e.g., pulmonology, oncology, thoracic surgery) may be helpful if concern exists that a malignant tumor may be impinging on the airway, but the airway does not need to be secured on an emergency basis. In this nonemergency setting, a specialist may use one of several treatment options, including self-expanding stents (placed by rigid bronchoscopy), airway dilatation (by flexible bronchoscopy), laser therapy, radiation, or chemotherapy.

Difficult airways may arise in oncology patients who have severe mucositis or bleeding disorders. Mucositis, especially, may make the tissues of the airway and oropharynx extremely friable, and the tissues may bleed easily with any manipulation; this problem makes standard endotracheal intubation more challenging. Many patients with cancer have significant thrombocytopenia. Special care must be taken with these patients because multiple or traumatic airway attempts may cause significant bleeding into the airway that may be difficult to control. Rarely performed, nasotracheal intubation, which may cause trauma to the nasal passages, should be avoided in patients with mucositis or bleeding disorders.

Malignant Pleural Effusions

Presenting Signs and Symptoms

Pleural effusion is a common cause of dyspnea in the patient with cancer who presents to the ED. Malignant pleural effusions are most commonly seen in patients with lung and breast cancers but are also seen with lymphoma and ovarian and gastric cancers. The diagnosis of a malignant pleural effusion is associated with increased 6-month mortality. The dyspnea of pleural effusions is generally progressive and may occasionally be associated with cough or chest pain. A chest radiograph usually enables the EP to make this diagnosis. Ultrasound can be useful to diagnose pleural effusion quickly and can simultaneously exclude pericardial effusion or cardiac tamponade. A chest CT scan can confirm the diagnosis and may be especially helpful because it can simultaneously rule out other life-threatening causes of dyspnea (e.g., pulmonary embolism, pneumonia).

Treatment

Thoracentesis should be performed for highly symptomatic patients. Removing pleural fluid may provide instant relief; however, some patients may not respond. Unfortunately, the reaccumulation rate after thoracentesis alone is nearly 100% at 1 month.²⁷ Traditionally, a blind approach was incorporated. Bedside ultrasound scanning makes this procedure much simpler and safer. If thoracentesis is performed for the first presentation of pleural effusion, the fluid should be sent for cytologic study because it may prove useful diagnostically. In general, unless a pleural effusion must be tapped for diagnostic purposes or to provide symptomatic relief, no need exists to tap the effusion in the ED. A chest radiograph should be performed at the completion of the procedure, to ensure that pneumothorax has not developed. More definitive treatment of the pleural effusion should be coordinated by the patient’s oncologist and will be tailored based on the patient’s prognosis, severity of symptoms, and type of malignant disease. Multiple treatment options exist, including supplemental oxygen, radiation therapy, chemotherapy, chemical pleurodesis, and long-term indwelling pleural catheter placement.

Emergency Side Effects of Oncology Treatment

Although some chemotherapeutic agents have unique side effects (Table 201.4), a few side effects are more universal. Bone marrow depression is a very common side effect of most agents. Nausea, vomiting, diarrhea, and mucositis are also quite common. The severity of these symptoms varies, depending on the particular chemotherapy agent.

Table 201.4 Chemotherapeutic Agents and Their Toxicities*

Global Issues

Pain

Pain in the oncology patient may represent an acute process, the progression of disease, or inadequate outpatient treatment. In a survey of physicians directly involved in cancer care (oncologists, hematologists, surgeons, and radiation therapists), 86% believed that most of their patients with cancer-related pain were being undermedicated, and 76% reported performing poor pain assessments for their patients.²⁸ After potentially dangerous or reversible causes of pain have been ruled out and the patient’s pain is under control, usually in response to high doses of intravenous narcotics, a plan for outpatient pain control should be created with the patient and in consultation with the patient’s oncologist. Oncologists tend to use an escalating approach to outpatient pain management, starting with nonsteroidal antiinflammatory drugs, then weaker opioids (e.g., codeine), and finally stronger opioids (e.g., morphine, fentanyl). Some physicians question this escalating approach, especially in advanced cancer, and instead start with small doses of stronger opioids and titrate upward as needed. Because the pain in patients with cancer is ongoing, pain medication with longer half-lives or continuous action, such as very-long-acting oral opioids or a transdermal opiate patch, is preferred. Additional short-acting medications should be provided for breakthrough pain; breakthrough dosing often needs to be 10% to 20% of the patient’s 24-hour total opiate dose. A new or escalating-dose opioid prescription should be accompanied by a prescription for a laxative because constipation is the most common side effect of opioid therapy.

Nausea and Vomiting

Nausea and vomiting, of all the side effects of chemotherapy, are often considered the worst adverse effects. Occasionally, nausea and vomiting can be severe enough to cause patients to discontinue their treatment. Poor antiemetic control with previous chemotherapy, female sex, low alcohol intake, and younger age are all associated with a higher risk of emesis after chemotherapy.²⁹ In an effort to reduce the risk of emesis and to increase the tolerability of the treatment, chemotherapy regimens usually include an antiemetic drug. Chemotherapeutic agents with the highest emetogenic potential are listed in Box 201.2.³⁰

Box 201.2

Chemotherapeutic Agents with the Highest Emetogenic Potential *

From Schwartzberg L, Szabo S, Gilmore J, et al. Likelihood of a subsequent chemotherapy-induced nausea and vomiting (CINV) event in patients receiving low, moderately or highly emetogenic chemotherapy (LEC/MEC/HEC). Curr Med Res Opin 2011;27:837-45.

^* These agents have greater than 90% incidence of emesis without coadministration of an antiemetic. Emetogenic potential is generally dose dependent.

Conversely, nausea and vomiting can be the initial symptoms of a potentially life-threatening issue. Nausea or vomiting can be the first sign of a neurologic condition (e.g., increase in central nervous system pressure, brain metastasis, intracranial bleeding), a gastroenterologic disorder (e.g., bowel obstruction), or even a metabolic problem (e.g., hypercalcemia).

Patients who complain of nausea or vomiting in the ED should be treated promptly with a strong antiemetic and appropriate hydration. Serotonin receptor antagonists (e.g., ondansetron, granisetron) are among the most commonly used antiemetics for patients with cancer. Other commonly used antiemetics in this patient population include phenothiazines (e.g., prochlorperazine), benzamides (e.g., metoclopramide), corticosteroids (e.g., dexamethasone), and benzodiazepines (e.g., lorazepam).

Mucositis

Pathophysiology

Mucositis is inflammation and ulceration of the mucous membranes, and it occurs in up to 58% of patients with cancer, depending on their diagnosis.³¹ Mucositis most commonly manifests in the mouth, but it can occur anywhere in the gastrointestinal, genitourinary, or respiratory tracts. Because mucositis is a breakdown of the normal integrity of mucous membranes, it is associated with an increased risk of infection. Oral mucositis is a side effect of chemotherapy or radiation, or it can result from certain cancers, such as oral cancers and leukemia. Patients obtaining either radiation for head and neck cancers or chemotherapy with 5-fluorouracil, anthracyclines, or irinotecan and patients who are bone marrow transplant recipients have high rates of mucositis (Fig. 201.1).

Fig. 201.1 Oral mucositis caused by radiation therapy.

(From Keefe ZDM, Logan RM. Oral complications of cancer and its treatment. In: Walsh TD, Caraceni AT, Fainsinger R, et al, editors. Palliative medicine. Philadelphia: Saunders; 2008.)

Presenting Signs and Symptoms

Oral mucositis is quite painful and causes significant difficulties with swallowing. Oral mucositis can cause altered taste, halitosis, and dry mouth. Painful swallowing and altered taste may adversely affect the patient’s oral intake and may result in dehydration. Oral mucositis can result in difficulty with speaking. In severe cases, mucositis can be secondarily infected with bacteria or fungi and can bleed.

Treatment

Patients who present to the ED with oral mucositis should be given proper pain control, which may include the use of opiates. Any secondary infections, such as oral candidiasis or herpes simplex, should be treated. A bland, soft diet is recommended, as well as ice chips or other cold products to keep the oral mucosa moist. Special attention to oral hygiene is essential for at-risk patients with cancer, including the use of a soft toothbrush, frequent saline or baking soda rinses, prophylactic anticandidal rinses (e.g., nystatin), and adequate general nutrition. Optimal mucositis treatment is still in question and requires further research. Protocols vary at different institutions. A 2010 Cochrane systematic review did not find any high-level evidence-based treatment options.³² Although not an ED option, low-level laser therapy was the only potentially useful intervention found in two or more clinical trials.³²

Recent Posts

Meta

Categories

Search Engine

Introduction to Oncologic Emergencies

Share this:

Related

Related posts: