Case Presentation by Dr. Claire Jensen
CC: “I have a fever.”
HPI: This is a 61 year-old Caucasian female with recently diagnosed squamous cell carcinoma of the base of the tongue who presents to the Emergency Department after noting a fever of 101.9° F at home approximately one hour ago. She is currently undergoing induction chemotherapy with docetaxel, cisplatin, and 5-FU. She completed her third cycle of chemotherapy 8 days ago, which was administered in the inpatient setting. Prior to hospital discharge, she received a dose of pegfilgrastim for anticipated neutropenia. Apparently, her tumor has responded well to chemotherapy and she is tentatively scheduled to undergo neck dissection with tumor resection in the next four weeks. Her chemotherapy course has been complicated by problems with nausea and mucositis.
She states that she has been seen in her oncologist’s office both earlier today and yesterday for complaints of generalized weakness and twice received infusion of intravenous fluids for “low blood pressure.” She states that she had just returned home from her doctor’s office late this afternoon when she started to feel very cold. She took her temperature, noted the fever, and returned immediately to the hospital on her doctor’s instruction. She has chronic cough since undergoing tracheostomy, but denies changes in sputum. No chest pain or shortness of breath. She denies dysuria or urinary frequency. She reports nausea and diarrhea associated with this most recent round of chemotherapy, but denies melena or hematochezia.
ROS: Per HPI.
PMH: Asthma, T3N2cM0 squamous cell carcinoma of the base of the tongue.
PSH: Hysterectomy, fine-needle aspiration of neck mass, triple endoscopy and tracheostomy, Medi-Port placement.
Allergies: Codeine and shellfish
Medications: Ondansetron, prochlorperazine, acetaminophen/hydrocodone, diazepam, esomeprazole, fluticasone/salmeterol inhaler, docusate, fexofenadine.
FH: Cancer, hypertension, diabetes, “thyroid problems.”
SH: Remote history of tobacco abuse, quit smoking 21 years ago. Denies alcohol or illicit drug abuse.
General:.This is a well-developed, thin female. She is awake and alert. She answers questions appropriately and speaks in full sentences. She is mildly ill-appearing.
Vitals: BP 132/74, P 128, R 18, T 38.6 C, SpO2 100% on room air
Eyes: There is mild conjunctival pallor, no injections, sclerae anicteric. Pupils and equal and reactive. Extraocular movements are full.
Ear, Nose, Mouth and Throat: Tympanic membranes are normal in appearance bilaterally. There is no nasal drainage, no sinus tenderness. The oropharynx has slightly dry mucous membranes. There is mild mucositis, no candidiasis. Good dentition.
Neck: Supple, no lymphadenopathy, no JVD. Uncuffed tracheostomy tube without purulent secretions, no erythema or drainage at insertion site.
Cardiovascular: Tachycardic, normal S1, S2. No murmurs, rubs, gallops. No lower extremity edema or calf tenderness.
Respiratory: Lungs are clear to auscultation bilaterally with good air entry.
Gastrointestinal: The abdomen is flat, soft, non-tender and non-distended. Bowel sounds are present.
Musculoskeletal: The head is normocephalic and atraumatic. No tenderness over the neck or spine. There is normal muscle bulk and tone. No erythema or swelling of the joints.
Skin: Warm and dry. No rashes, bruising or diaphoresis. The skin over the Medi-port is without induration
Neurologic: Awake and alert. Symmetric facies. Normal speech. Moves all extremities spontaneously. Sensation intact to light touch in all extremities. Normal gait.
Alk Phos: 91
Total Protein: 6.1
Lactic Acid: 2.2
Specific Gravity 1.015
Bacteria None seen
Emphesematous lungs. Normal heart size. No active parenchymal disease. Medi-Port and tracheostomy tubes in stable position.
1. What is the patient’s absolute neutrophil count?
2. Which of the following parenteral antibiotics is considered first-line therapy for the high-risk febrile neutropenia patient?
3. Which factor is associated with “low risk” febrile neutropenia patients, who may be candidates for outpatient antibiotic therapy after careful consideration?
a) Age >60 years
b) Hematologic malignancy
c) Predominance of gastrointestinal symptoms, such as nausea, vomiting, diarrhea, or abdominal pain.
d) Presence of underlying structural lung disease, such as COPD.
e) Solid tumors
1. B, 2. A, 3. E
Febrile neutropenia is a medical emergency that requires a rapid and methodical response from the emergency physician. Prior to the era of empiric antibiotic therapy, infection accounted for almost 75 percent of mortality associated with chemotherapy. The definition of neutropenia varies between institutions, but is typically defined as an absolute neutrophil count of less than 500 cells/microL, or less than 1000 cells/microL with a predicted nadir of less than 500 cells/microL. Profound neutropenia is defined as less than or equal to 100 cells/microL.
The absolute neutrophil count is calculated by multiplying the total white blood cell count by the percentage of neutrophils and bands.
ANC = (WBC count in 1000s) x [(% Neutrophils/100) + (% Bands/100)
So, in our patient:
ANC = (0.8 x 1000) x ((14/100) + (0/100)
= 800 x 0.14
Multiple factors are used to categorize patients as high-risk or low-risk for severe infection and include presenting signs and symptoms, the type of underlying malignancy, the type of therapy for the underlying cancer, and the presence of medical comorbidities. Significant comorbidities include uncontrolled cancer, COPD, poor functional status, and advanced age. Patients undergoing induction chemotherapy for acute myelogenous leukemia or a chemotherapeutic conditioning regimen in preparation for hematopoeitic stem cell transplantation are at particularly high risk. Patients with an ANC <100, hemodynamic instability, GI symptoms such as abdominal pain, nausea, vomiting or diarrhea, new-onset neurological symptoms including altered mental status, underlying chronic lung disease, or evidence of hepatic or renal dysfunction are all considered high risk and should be admitted to the hospital for empiric antibiotic therapy. Additionally, it is important to observe neutropenic precautions when the patient is in the emergency department, with placement in a private room if available, use of masks by staff members, and adherence to rigorous hand hygiene. Patients with solid tumors, anticipated short duration of neutropenia (<7 days), and lack of comorbid conditions can be considered for outpatient antibiotic therapy under close supervision, but only after thorough diagnostic evaluation and discussion with their managing oncologist.
Initial evaluation and management of these patients in the emergency department is not tremendously different from that of the septic patient. Emphasis is on immediate and aggressive correction of hemodynamic instability, identification of potential sources using diagnostic studies, early administration of empiric antibiotics, and source control (venous catheters, ports, urinary catheters, etc.). However, it is important to be mindful that severely neutropenic patients are not capable of mounting an immune response the way septic patients are, so a negative chest x-ray or absence of pyuria on urinalysis does not necessarily exclude infection. Standard diagnostic work-up includes CBC with differential, electrolyte studies including renal function, transaminases to assess for hepatic insufficiency, two sets of blood cultures with one from any indwelling catheter if present, chest radiograph, and urinalysis with urine culture. The need for additional studies such as other imaging, lumbar puncture, or fungal cultures are not standard, but should be considered on a case-by-case basis. Neutropenic patients that are afebrile but present with symptoms concerning for infectious illness such as hypothermia, hypotension, abdominal pain, or mental status changes should be treated as high-risk patients.
Early institution of antibiotic therapy is of utmost importance in the setting of febrile neutropenia. Early studies documented mortality rates as high as 70 percent in cases where the administration of empiric antibiotics was delayed. Therapy should be tailored based upon known or suspected sources of infection, the patient’s history as well as any previous culture data or recent antibiotic use, and awareness of institutional nosocomial infection patterns. The Infectious Disease Society of America issued new guidelines in 2010 for the treatment of neutropenic fever, which includes the initiation of monotherapy with an anti-Pseudomonal beta-lactam agent such as cefepime, meropenem, imipenem, or piperacillin-tazobactam. Other antibiotics such as aminoglycosides, fluoroquinolones and/or vancomycin may be added in patients with complicated infections (eg, hypotension or mental status changes) or if antimicrobial resistance is suspected. Vancomycin and other agents that target gram positive organisms are not recommended as part of the standard initial management unless there is suspicion for catheter-related blood stream infection, skin or soft tissue infection, pneumonia or hemodynamic instability is present.
This patient was started on empiric antibiotic therapy with cefepime and vancomycin and admitted to the hospital. She had no further febrile episodes while in the hospital. Her WBC counts started rebounding the next day, and all of her cultures showed no growth. She was discharged in good condition after three days in the hospital and is currently still on schedule to undergo surgical resection of her tumor.