Curr Probl Cancer 39 (2015) 297–308
Contents lists available at ScienceDirect
Curr Probl Cancer journal homepage: www.elsevier.com/locate/cpcancer
Neutropenia: A nursing perspective Roberta Kaplow, PhD, APRN-CCNS, AOCNS, CCRNa, Renee Spinks, MSN, APRN, ACNS-BC, AOCNS, NP-Cb a
Oncology Clinical Nurse Specialist, Emory University Hospital, 1364 Clifton Road, E734, Atlanta, GA 30322 b Oncology Clinical Nurse Specialist, Emory University Hospital, 1364 Clifton Road, E834, Atlanta, GA 30322
Neutropenia: A nursing perspective Neutropenia is the most common dose-limiting toxicity of chemotherapy. It is considered an unpreventable side effect of many types of cancer treatment. It may be a side effect of therapy or a planned aspect of a conditioning regimen for bone marrow or hematopoietic stem cell transplantation (HSCT).1 The definition of neutropenia differs among institutions, ranging from an absolute neutrophil count (ANC) of less than 500 cells/mm3 to less than 1500 cells/mm3.2–4 Neutropenia can lead to infection, increased length of stay (LOS), delay, reduction, or discontinuation of cancer treatment, and increased morbidity and mortality.1,5–7 More than 60,000 patients with cancer are hospitalized annually in the United States for chemotherapyinduced neutropenia (CIN).8 Older patients with cancer may be more vulnerable for infection and death than their younger counterparts.5 The typical duration of neutropenia is 7-10 days but will vary based on the patient’s age, chemotherapy agent(s) received, comorbidities, and bone marrow reserve.7 Although patients cannot prevent CIN from occurring, there are a number of actions nurses and patients can take in order to help mitigate developing an infection while neutropenic. Hematopoietic colony-stimulating factors A common pharmacologic approach to infection prevention in patients undergoing cancer treatment is the use of hematopoietic colony-stimulating factors such as growth colonystimulating factors (G-CSF). Use of these agents has been shown to shorten the duration of neutropenia and LOS for febrile neutropenia (FN) and decrease the likelihood of infectionrelated mortality.9 Results of a systematic review suggest that hematopoietic colony-stimulating factors shorten the time a patient is neutropenic but the data about decreased mortality rates from CIN are unclear.10 According to American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines, patients who have at least a 20% chance of http://dx.doi.org/10.1016/j.currproblcancer.2015.07.009 0147-0272/& 2015 Elsevier Inc. All rights reserved.
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developing neutropenic fevers should receive growth factor support. Evidence supports using G-CSF in the autologous HSCT population based on accelerated neutrophil engraftment and reduction in neutropenia duration.11 Filgrastim and tbo-filgrastim Filgrastim is a G-CSF commonly administered after chemotherapy in order to decrease the occurrence of infection. It is administered daily via subcutaneous injection, beginning 24 hours after chemotherapy, and continued for up to two weeks. Filgrastim should be discontinued when the ANC has reached 10,000/mm3.12 Tbo-filgrastim is another G-CSF approved to reduce duration of CIN.13 Common side effects include bone pain, headache, fatigue, muscle aches, nausea and vomiting, and stomach pain. Bone pain was the most common side effect for both agents in clinical trials, with most patients rating their discomfort as mild or moderate and easily controlled with non-narcotic pain medications. Nurses should be aware that rare cases of splenic rupture, myocardial infarction, and acute respiratory distress syndrome (ARDS) have been observed in those receiving filgrastim.12 Patients receiving tbo-filgrastim are also at risk of splenic rupture, ARDS, and capillary leak.13 Pegfilgrastim Pegfilgrastim is a G-CSF similar to filgrastim. The major difference between the two drugs is that pegfilgrastim is designed to prevent rapid removal by the kidneys. As the drug stays in the body longer than filgrastim does, only one subcutaneous pegfilgrastim injection is needed after each cycle of chemotherapy. Side effects and risks are similar to filgrastim.14 Nurses must teach patients how to self-inject if they are being discharged after chemotherapy, when therapy will be discontinued, laboratory tests that require monitoring (e.g., complete blood count with differential), and management of side effects.
Antimicrobial prophylaxis Chemotherapy-induced neutropenia predisposes the patient to infection with a plethora of organisms. The organisms include Gram-positive cocci, Gram-negative bacilli, and fungi;7 these can vary by geographic location. A standard practice in the care of oncology patients is the use of antimicrobial prophylaxis to protect patients during the period of severe CIN. Institutions vary widely in the choice of antibiotics as well as the dosage and route.11 Typically, prophylactic antimicrobials are reserved for times when the risk of developing antimicrobial resistance is outweighed by the benefit of therapy and the risk of infection.15 Fluoroquinolones such as levofloxacin and ciprofloxacin are recommended for antimicrobial prophylaxis in neutropenic patients.16 Individuals expected to have a long duration of neutropenia, including patients undergoing bone marrow transplantation, typically receive antimicrobials to prevent GI Gram-negative organisms, Candida, Pneumocystis jiroveci, and cytomegalovirus (CMV).15 Antifungal prophylaxis is not advised for patients whose CIN is expected to last less than seven days.16
Intravenous immune globulin (IVIG) Intravenous immune globulin has been shown to help prevent some viral infections, most notably CMV, in HSCT recipients.17 While it is relatively safe, nurses should be aware that hypersensitivity reactions may occur. It is essential to start the infusion slowly and titrate up based on the patient’s tolerance.17 Premedications are commonly given. Baseline vital signs must be obtained, with subsequent vital signs measured at 15 to 30-minute intervals throughout the infusion.18
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Infection Prevention Bundles Hospital-associated infections (HAIs) pose a serious threat to inpatients and place a significant financial burden on the health care system.19 Patients with CIN are at increased risk of developing HAIs. The most common HAIs are catheter-associated urinary tract infections (CAUTIs), surgical site infections, central line-associated bloodstream infections (CLABSIs), and pneumonia.20 The Centers for Disease Control and Prevention (CDC) has published guidelines on prevention of HAIs, with several of the guidelines consisting of bundles.21 Bundles are “a small set of straightforward set of evidence-based practices – generally three to five – that when performed collectively and reliably, have been proven to improve patient outcomes.”22 Several other organizations publish clinical practice guidelines for the prevention and management of CIN. Despite their being readily available, a number of barriers to their use have been reported. Although expected to use NCCN guidelines for CIN and febrile neutropenia (FN) patient education and risk assessment, in one study, 56% of nurses reported that no institutional requirements were present for which guidelines be used. In this same study, 46% reported not having time to access the guidelines, 9% reported being too busy to use them, and 10% reported they did not have access to the educational materials to assist in their use.6 CLABSI prevention Many oncology patients require a central venous catheter (CVC) as part of their treatment plan. CLABSIs represent 14% of HAIs and are the second leading cause of death in patients who develop HAIs.19 The CDC guidelines for insertion and maintenance of CVCs are listed in Box 1. Nurses play a major role in prevention of CLABSIs because of their involvement in CVC dressing changes, flushing, and connector changes. In addition, nurses provide education for patients being discharged from the hospital with their CVC in place. It is not uncommon for a patient with CIN to develop a CLABSI. If a CLABSI develops, it may be necessary to remove the CVC.23 Nurses should feel empowered to participate in decision-making about removing CVCs as soon as possible when no longer indicated. Box 1–Insertion and maintenance of central venous catheters.21,24 Insertion
Perform hand hygiene before beginning the procedure Avoid use of the femoral vein Use maximal sterile barrier precautions Perform skin preparation with chlorhexidine (CHG), alcohol, or iodine Apply a sterile dressing application after line placement
Maintenance
Perform hand hygiene before touching the central venous catheter Use a chlorhexidine-based antiseptic to cleanse the skin for 30 seconds during the dressing change and allowing the CHG to dry Use a standardized protocol for cleansing the catheter hubs and injection ports prior to accessing the device Use a no-touch technique as much as possible Minimize the frequency of catheter manipulations
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Box 2–Indications for urinary catheter placement.24
Urinary retention or bladder outlet obstruction Necessity for accurate urinary output measurement in critically ill individuals Specific perioperative use for certain surgical procedures Assistance with healing of open perineal or sacral wounds in those who are incontinent Prolonged immobilization Palliative care in end-of-life situations
CAUTI bundle Indwelling urinary catheters also serve as a portal for infection in immunocompromised patients. CAUTIs comprise approximately 36% of HAIs outside the intensive care units.20 Urinary catheters should only be inserted in specific circumstances. These are listed in Box 2. An indwelling catheter should not be kept in place simply because a patient is incontinent, for obtaining a urine specimen for those who can void voluntarily, or for prolonged periods after a surgical procedure without a justifiable reason. One of the best methods of preventing CAUTI is early identification of indwelling catheters that are no longer necessary and removing them as soon as possible.24 Nursing care is crucial in preventing CAUTI. The CDC has developed guidelines for catheter insertion, which include hand hygiene before placement and adherence to sterile technique in the inpatient setting. Care and maintenance guidelines are outlined in the Guideline for Prevention of Catheter-Associated Urinary Tract Infections. Some of the key maintenance guidelines include ensuring a closed system, keeping the drainage bag below the level of the bladder, verifying the urine is free-flowing, and daily cleansing of the meatal surface while the catheter is in place.
Hand hygiene Hand hygiene is the best method of preventing infection in the inpatient setting.25 All health care workers and visitors must cleanse their hands before entering and after leaving patient rooms.16 Hand hygiene is also a crucial component of many of the infection prevention bundles.21,24
Diet Despite a lack of data supporting the usefulness of cancer patients following a neutropenic (low bacterial, sterile, or low microbial) diet, many providers continue to recommend it. While proponents appreciate food possibly containing harmful organisms and the possibility of bacterial translocation, studies do not reveal differences in mortality between patients who follow a neutropenic diet and those who do not. Opponents site a decrease in quality of life, malnutrition, vitamin deficiency-related immunodeficiency, gastrointestinal side effects, and distaste for food.26 As there are not significant data to support a traditional neutropenic diet, practice should move toward a focus on safe food handling, proper food preparation, and appropriate food choices (such as avoidance of unpasteurized dairy products).27 Common sense guidelines regarding food preparation include washing produce carefully, thoroughly cooking foods before eating, and discarding freshly made foods that have been refrigerated for more than 2-3 days.15 In general, uncooked fruits and vegetables can be consumed as long as they have been cleaned thoroughly. Patients with CIN should avoid prepared luncheon meats.16 Nurses should work with the multidisciplinary team to determine the best approach to dietary guidelines for their specific patients.
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Environmental concerns The CDC recommends keeping patients with CIN separated from individuals with transmissible infections.28 Nurses must ensure that plants and dried or fresh flowers are not brought into the hospital rooms of patients with CIN due to the risk of exposure to molds such as Aspergillus and Fusarium.16 All multipurpose equipment must be cleaned between patient use, with an emphasis on opting for single-use equipment and supplies wherever possible.15 Private rooms are not imperative for patients with CIN who are not undergoing HSCT. Guidelines recommend private rooms for HSCT patients.16,28
Personal protective equipment and isolation practices There are no professional recommendations for routinely wearing gloves, gown, and mask in hospital rooms of patients with CIN. There is a lack of evidence supporting the practice of keeping patients with CIN in protective isolation.11 Visitors with a respiratory virus should be discouraged from visiting patients with CIN. In addition, health care workers with an illness should report their symptoms and ideally be relieved of their assignments if they have symptoms of an infection that can be spread through air, droplet, or direct contact.16 Masks should be worn by staff and visitors in the rooms of patients with CIN if there is a chance of transmitting a respiratory virus.15 Data support use of high-efficiency particulate air (HEPA) filtration and laminar air flow to reduce the spread of Aspergillus and other airborne fungal infections on oncology units.11 All allogeneic HSCT patients should be placed in a room with greater than 12 air exchanges per hour as well as HEPA filtration.16
Antimicrobial treatment of febrile neutropenia Guidelines have been developed by the Infectious Diseases Society of America (IDSA) for the management of FN. The recommendations are based on whether the patient is at high or low risk for complications. Antimicrobial therapy is the mainstay of management of FN and should be based on the most likely suspected infecting organism(s). International guidelines corroborate a suggested initiation time of one hour for antimicrobial therapy from presentation of FN; blood cultures should be obtained before beginning therapy unless this causes more than a one-hour delay.4,23 It is essential for nurses to assure minimal to no delays in initiating antimicrobial therapy. Data support a substantive increase in mortality when comparing antimicrobial therapy started in less than one hour of diagnosis, or over one, four, or twelve hours of diagnosis.29,30 Nurses play a pivotal role in terms of antimicrobial administration and as a collaborator with the multidisciplinary team as stewards of antimicrobial therapy. In addition to monitoring for allergies, effectiveness, and side effects, nurses’ contributions may include validating that the antimicrobials prescribed are in synch with the microbiology reports. They should assure that antimicrobial levels are obtained at the correct time intervals, and interpreted and acted upon promptly. They should also assure that antimicrobial therapies are administered on time and that doses are not missed.31 Barriers to timely administration of antibiotics during times of FN have been reported. Patient-, staff-, and procedure-related variables have been identified. The main patient-related factor is lack of knowledge to promptly report fevers. Nursing staff-related barriers include not appreciating the immediacy required to start antimicrobial therapies and not establishing IV access and obtaining blood cultures promptly. Pharmacists’ failure to schedule the initial dose of antimicrobial therapy immediately and schedule the therapy to correspond with meals or around the clock were also identified. Procedure-related barriers included delays in nursing
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triage, assessment by a provider, transporting patients for diagnostic studies, or transferring the patient to another unit before initiating antimicrobial therapy.30
Fever workup Presence of FN should be deemed a medical emergency.32 Guidelines for prevention and treatment for FN have been developed. These include the 2010 IDSA and the 2013 ASCO guidelines.33 When patients present with FN, obtaining a targeted patient history is essential to help identify potential sources of infection. A physical examination will further help identify potential infection sources. Areas that should be targeted include the mouth, oropharynx, lungs, abdomen, and perianal areas. A digital rectal exam should not be performed on neutropenic patients. Presence of pain may suggest an infection source. Purulent drainage from a site is unlikely in neutropenia. If the patient reports abdominal tenderness, this may indicate enterocolitis. Presence of perianal tenderness may suggest a Gram-negative or anaerobic infection. A complete blood count with differential should be obtained to determine the degree of neutropenia. Renal and liver function tests and a metabolic panel should be obtained to help identify presence of any comorbidities. Blood cultures (both peripheral and from a central venous catheter) should also be procured. Specific imaging studies, such as computed tomography, may be obtained if certain specific sources of infection are suspected.23 If the patient presents with diarrhea, a specimen should be sent for Clostridium difficile toxin assay. A urine culture should be sent if signs of a urinary tract infection are present. Sputum cultures should be sent if the patient has a productive cough.34 Nurses should collaborate with the provider to arrange for appropriate testing to be performed.
Patient and family education Patient- and family-centered education is required throughout the cancer disease trajectory. During this period of vulnerability when CIN is present, education addressing why patients are at risk for neutropenia, degree of risk based on ANC, and self-care preventive strategies are indicated. Content to be included in education is listed in Box 3. Patient education tailored to the health literacy level, learning preferences, and addressing barriers to learning will help adherence with the recommendations. Patients and families should be reminded that the greatest risk of infection may occur after hospital discharge and that the patient is still at risk to develop an infection despite being discharged home.1 Obviating as many barriers to learning is critical. Although not conducted on patients with cancer, a direct relationship was found among education, adherence with instructions, and patient outcomes. That is, patients who received education that they were able to understand demonstrated increased levels of adherence with instructions.35 Furthermore, it has been demonstrated in patients who are receiving oral chemotherapy that adherence and follow-up are augmented when education includes use of a combination of educational materials, behavioral interventions, and reinforcing information.36 Dong and colleagues37 reported that patient-centered communication was essential to optimize outcomes of patients who are receiving radiotherapy. Although patient education materials have been developed by organizations such as the American Cancer Society (ACS), NCCN, and ASCO, they are not all evidence-based.38 The most comprehensive guidelines have been developed by the two former organizations.
Monitoring/When to notify the provider When providing education about temperature monitoring, it is essential to verify if the patient has a thermometer at home. An oral or tympanic thermometer is recommended.33 Temperature
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Box 3–Patient and family education.1,4,6,9,16,25,33,38
When to call the provider
Who to contact based on signs and symptoms present When first signs or symptoms of infection or neutropenic sepsis (e.g., fever, chills, rigors, diaphoresis) develop Report even a low-grade fever Report development of mouth sores, dysphagia, abdominal pain, rectal soreness, tenderness of the sinuses, or diarrhea. Report respiratory symptoms (e.g., shortness of breath, cough, or sore throat.) Report GU symptoms (e.g., burning on urination.) Report redness or swelling of any area of open skin or injury. How to report symptoms of infection
Monitoring
Signs and symptoms for which to observe Temperature monitoring: Check your temperature 1-4 times/day if you are not feeling well or suspect you are ill. Fever may be the only sign of infection in patients with neutropenia. Need for frequent CBC monitoring, especially when receiving a new drug with a high probability to cause neutropenia.
Risks
Treatment-related Degree of risk based on absolute neutrophil count
Medication knowledge
When most vulnerable for infection based on chemotherapeutic agents received Mechanism of action of agent(s) received Effect of chemotherapy on neutrophils Anticipated time of nadir
Knowledge specific to colonystimulating factors
Information about colony-stimulating factors (e.g., mechanism of action, rationale for use) Timing of administration (i.e., do not take earlier than 24 hours after chemotherapy administration.) Side effects management (e.g., bone pain with acetaminophen) Side effects are temporary and usually dissipate following discontinuation of therapy. Self-injection techniques (e.g., sites to use, rotation of sites, do not aspirate for blood prior to injecting) Remove medication from refrigerator 30 minutes prior to administration to help prevent stinging at the injection site When to notify provider (e.g., temperature over 38 1C, shortness of breath, increased heart rate, any new rash)
Activities
Wear gloves when cleaning. Wear protective gloves when participating in outdoor work (e.g., gardening).
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Box 3 - Continued
Avoid contact with compost heaps, manure, hay, and moldy areas. Avoid participating in contact sports or other activities where you can be injured. Diet
Check with your provider regarding any dietary restrictions. (Neutropenic diet is not supported with evidence.)
Hygiene
Hand hygiene: Wash hands often with soap and water or alcohol-based gel, especially before meals and after touching pets. Wash all surfaces of fingers and hands for at least 15 seconds. Dry hands thoroughly to prevent bacterial colonization. Personal hygiene: Bathe or shower daily; showers are preferred. Wipe the perineum from front to back after toileting (females) to avoid contamination. Use sanitary pads versus tampons.
Oral care
Brush teeth 2-3 times a day, including after eating and before going to bed. Use a toothbrush with soft bristles. Use warm salt water to rinse your mouth. Chlorhexidine 2% mouthwash after brushing teeth; keep in mouth for approximately 1 minute. Keep lips and mouth moist. If mucositis is present, cleanse mouth 4-6 times daily with sodium bicarbonate or normal saline. Floss daily if it does not cause trauma or bleeding. Mucositis prevention See dentist before receiving antineoplastic therapy. Remove dentures and other orthodontic appliances during the nadir to prevent trauma and infection.
Environmental hygiene
Do not place fresh flowers or potted plants in the home.
Skin protection
What to do at home?
Avoid getting scratches or other breaks in the skin. Use an electric razor. Keep nails trimmed short and clean. If breaks in the skin occur, wash thoroughly with soap and water or antimicrobial liquid and apply antibiotic ointment (e.g., bacitracin). Avoid tampons. Use water soluble lubricant during sexual intercourse. Maintain a sterile occlusive dressing on the CVC. Perform sterile dressing change to CVC. Flush CVC as prescribed. Actions to take if treatment-related toxicities occur at home.
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Box 3 - Continued
Pets
Environmental exposure
Avoid people who have a cold, flu or other respiratory tract infection. (Data are only available on BMT patients.) Avoid people who recently (within the past 3 weeks) received a live vaccine. Avoid places with crowds (e.g., shopping mall, movie theater, public transportation). Wear face masks in public places if ANC o 1000. Change air filters each month. Do not place fresh flowers or potted plants in the home. Care for plants should be performed by those not providing care to the patient. If this is not possible, the caregiver should wear gloves when handling plants and perform hand hygiene after gloves are removed.
Information to give to providers in triage areas
Recent chemotherapy agents received Dates of chemotherapy administration within the past 6 months
General
Patients are still at risk for infection following discharge home. Maintain schedule for routine dental check ups. Consult your provider before undergoing a dental procedure. If used, clean humidifiers each day and wash with a diluted bleach solution each week. Avoid constipation to maintain integrity of anal mucosa (e.g., by avoiding dehydration, stool softeners); avoid enemas and suppositories as these can break the integrity of the anal mucosa. Get the flu shot each year.
Avoid contact with pet feces, urine, or saliva. Do not handle used cat litter. Do not clean fish tanks. Do not clean pet cages. No direct or indirect contact with reptiles. Wash hands after any contact with animals. Prompt hand hygiene of broken or scratched skin or any loss of skin integrity
monitoring is critical, as a fever may be the first and only indication that the patient has an infection.1 The provider should be notified upon identification of a fever or other suspicion of an infection. Information to give the provider It is important for patients and families to tell providers in triage areas about chemotherapy received in the past 6 weeks. It is equally important to know what agents were administered and when the last dose was received so that the provider can assess whether the patient has reached nadir.23
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Nursing practice implications Identification of patients at risk Neutropenic events typically occur with the first cycle of chemotherapy.7 Risk of mucositis and constipation development should be minimized. When hospitalized, assessment of pressure sites should be performed at least each shift.1 Nurses should conduct a complete oral assessment before treatment to establish a baseline and then twice daily. Nursing assessment A thorough, detailed, and ongoing assessment is essential in order to identify potential sources of infection, assure early recognition of infections, and detect improvement or clinical deterioration and organ dysfunction. Fever is the most common sign of infection and should indicate the need for further investigation. Monitoring of vital signs including SpO2 and intake and output is equally critical. A minimum urine output of 0.5 mL/kg/h should be sustained.23 Signs and symptoms of organ dysfunction by system are listed in Table 1. A general assessment should include evaluation of any area with loss of skin integrity, including catheter insertion sites, an oral assessment, auscultation of breath sounds, assessment of use of accessory muscles and for increased work of breathing. An abdominal assessment should include auscultation of bowel sounds and palpating for abdominal tenderness.32 Nurses should completely assess the skin of all patients with CIN, with particular attention to sites that can easily become infected, such as the perineum and vascular access insertion sites.16 Frequent, methodical oral assessments are necessary to recognize ulcers and infections. Evaluation of the patient’s ability to have sufficient oral intake is vital. Fever can cause fluid and electrolyte depletion. If patients are being managed on an outpatient basis, they should be telephoned at least daily to determine if the fever has resolved.33 Nurses should remain aware that patients with CIN might have a life-threatening infection despite being afebrile or hypothermic. Hospitalized patients should also be checked for the presence of systemic inflammatory response syndrome criteria. Patients with mental status changes, hypotension, tachypnea, tachycardia, shaking chills, or decreased urine output should prompt the nurse to assess the patient for an infectious source. All significant findings and changes should be communicated to the provider in a timely manner. Recognition and treatment of febrile neutropenia As nurses are often the patient’s first contact, they play a pivotal role in identifying the possible presence of FN. When identified, prompt intervention is crucial. Early intervention should include alerting the provider, establishing intravenous access, obtaining peripheral blood cultures and a baseline serum lactate level, and initiating intravenous fluids.8,39 Table 1 Signs and symptoms of organ dysfunction. System
Signs and symptoms
General Neuro/Brain Cardiovascular Pulmonary GI/GU Hematologic
Fever or hypothermia, chills, malaise, fatigue, rigors New onset confusion, anxiety, disorientation, apprehension, agitation, obtunded, comatose Tachycardia, hypotension Tachypnea, decreased pCO2, respiratory alkalosis, shortness of breath Nausea and vomiting, jaundice, decreased albumin, oliguria WBC (increased or decreased), decreased platelets, increased INR, increased aPTT, disseminated intravascular coagulation Increased lactate, increased blood glucose
Metabolic
aPTT, activated partial thromboplastin time; GU, genitourinary; INR, international normalized ratio; WBC, white blood cell.
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Implementation of order sets and a checklist A standardized strategy for assessment of CIN and FN risk should be developed.5 To help mitigate barriers that affect timely antimicrobial administration in patients with FN, order set development has been suggested. Standardization of care with order sets for antimicrobial therapy has improved outcomes for patients with FN. Order sets with suitable antibiotic selections may decrease delays in medication administration.40
Conclusion Chemotherapy-induced neutropenia is a life-threatening condition. Nurses play a pivotal role in identifying patients at risk and potential sources of infection, caring for and educating patients about CIN, symptoms for which to monitor, implementing infection prevention strategies, and promptly taking action if an infection manifests. Evidence-based guidelines must direct efforts to manage CIN. As such, oncology nurses must remain updated on published guidelines. They must also work collaboratively with the rest of the multidisciplinary team to assure that quality care is delivered and that outcomes are optimized for this vulnerable population. References 1. Coughlan M, Healy C. Nursing care, education, and support for patients with neutropenia. Nurs Stand 2008;22(46): 35–41. 2. Berliner N. Approach to the adult with unexplained neutropenia. Uptodate.com. http://www.uptodate.com/ contents/approach-to-the-adult-with-unexplained-neutropenia?source=search_result&search=neutropenia&selected Title=1%7E150; Accessed 09.03.15. 3. Seth R, Bhat S. Management of common oncologic emergencies. Indian J Pediatr 2011;78(6):709–717. 4. Bow E, Wingard JR. Overview of neutropenic fever syndromes. Uptodate.com. http://www.uptodate.com/contents/ overview-of-neutropenic-fever-syndromes?source=search_result&search=neutropenia&selectedTitle=3%7E150. 5. Flores IQ, Ershler W. Managing neutropenia in older patients with cancer receiving chemotherapy in a community setting. Medscape.com. http:/www.medscape.com/viewarticle/729485. Accessed 09.03.15. 6. Nirenberg A, Reame NK, Cato KD, et al. Oncology nurses’ use of National Comprehensive Cancer Network clinical practice guidelines for chemotherapy-induced and febrile neutropenia. Onc Nurs Forum 2010;37(6):765–773. 7. Caggliano V, Weiss RV, Rickert TS, et al. Incidence, cost, and mortality of neutropenia hospitalization associated with chemotherapy. Cancer 2005;103(9):1916–1924. 8. Demshar R, Vanek R, Mazanec P. Oncologic emergencies: New decade, new perspectives. AACN Adv Crit Care 2011; 22(4):337–348. 9. Johnson GB. Hematologic issues. In: Eggert J, editor. Cancer Basics, 2010. Pittsburgh, PA: Oncology Nursing Society; 2010:433–437. 10. Mhaskar R, Clark OAC, Lyman G, et al. Colony-stimulating factors for chemotherapy-induced febrile neutropenia. Cochrane Database Syst Rev 2014:CD003039. http://dx.doi.org/10.1002/14651858.CD03039. 11. Saria M. Preventing and managing infections in neutropenic stem cell transplantation. Clin J Onc Nurs 2011;15(2): 133–139. 12. DailyMed. NEUPOGEN-filgrastim. DailyMed.gov. http://dailymed.nlm.nih.gov. Accessed 09.03.15. 13. Teva Pharmaceutical Industries, Ltd. GRANIX TBO-FILGRASTIM Injection. http://granixrx.com/. Accessed 03.09.15. 14. Amgen. Neulasta full prescribing information. http://pi.amgen.com/united_states/neulasta/neulasta_pi_hcp_english/ pdf; 2014 Accessed 09.03.15. 15. Shelton BK. Myelosuppression. In: Holmes B, Triest-Robertson S, Vogel WH, eds. Pittsburgh, PA: Oncology Nursing Society; 2009:405–442. 16. 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(4):e56–e93. 17. McAdams FW, Burgunder MR. Transplant treatment course and acute complications. In: Ezzone SA, editor. Hematopoietic Stem Cell Transplantation: A Manual for Nursing Practice, 2011. Pittsburgh, PA: Oncology Nursing Society; 2013:47–66. 18. Shelton BK, Griffin JM, Goldman FD. Immune globulin IV therapy: optimizing care of patients in the oncology setting. Onc Nurs Forum 2006;33(5):911–921. 19. Boubekri A. Reducing central line-associated bloodstream infections in the blood and marrow transplantation population: a review of the literature. Clin J Onc Nurs 2013;17(3):297–302. 20. Klevens RM, Edwards JR, Richards CL, et al. Estimating health care-associated infections and deaths in U.S. hospitals, 2002. Public Health Rep 2007;122(2):160–166. 21. O’Grady NP, Alexander M, Burns LA, et al. Healthcare Infection Control Practices Advisory Committee (HICPAC). Guidelines for the prevention of intravascular catheter-related infections, 2011. Cdc.gov. http://www.cdc.gov/hicpac/ pdf/guidelines/bsi-guidelines-2011.pdf. Accessed 09.03.15.
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22. Institute of Healthcare Improvement. Evidence-based care bundles. Ihi.org. http://www.ihi.org/topics/bundles/Pages/ default.aspx. Accessed 09.03.15. 23. Wingard JR. Treatment of neutropenic fever syndromes in adults with hematologic malignancies and hematopoietic cell transplant recipients (high-risk patients). Uptodate.com. http://www.uptodate.com/contents/treatment-of-neu tropenic-fever-syndromes-in-adults-with-hematologic-malignancies-and-hematopoietic-cell-transplant-recipientshigh-risk-patients?source=search_result&search=cancerþ neutropenia&selectedTitle=2%7E150; Accessed 09.03.15. 24. Centers for Disease Control and Prevention. Guideline for prevention of catheter-associated urinary tract infections. 2009 Cdc.gov. http://www.cdc.gov/hicpac/pdf/CAUTI/CAUTIguidelines2009final.pdf. Accessed 09.03.15. 25. Boyce JM, Pillet D. Guideline for hand hygiene in health-care settings: recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Infect Control Hosp Epidemiol 2002;23(suppl 12):S3–S40. 26. Jubelirer SJ. The benefit of the neutropenic diet: fact or fiction? Oncologist 2011;16(5):704–707. 27. Foster M. Reevaluating the neutropenic diet: time to change. Clin J Onc Nurs 2014;18(2):239–241. 28. Centers for Disease Control and Prevention. 2007 Guideline for isolation precautions: preventing transmission of infectious agents in healthcare settings. Cdc.gov. http://www.cdc.gov/hicpac/pdf/isolation/Isolation2007.pdf. Accessed 09.03.15. 29. Frost R, Newsham H, Parmar S, et al. Impact of delayed antimicrobial therapy in septic ITU patients. Crit Care 2010; 14(suppl 2):P20. 30. Puskarich MA, Trzeciak S, Shapiro NI, et al. Association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol. Crit Care Med 2011;39(9):2066–2071. 31. Edwards R, Drumright LN, Kiernan M, et al. Covering more territory to fight resistance: covering nurses’ role in antimicrobial stewardship. J Infect Prev 2011;12(1):6–10. 32. Wingard JR. Diagnostic approach to the adult presenting with neutropenic fever. Uptodate.com. http://www. uptodate.com/contents/diagnostic-approach-to-the-adult-presenting-with-neutropenic-fever?source=search_result &search=neutropenia&selectedTitle=5%7E150. Accessed 09.03.15. 33. Bow E. Treatment and prevention of fever syndromes in adult cancer patients at low risk for complications. Uptodate. com. http://www.uptodate.com/contents/treatment-and-prevention-of-neutropenic-fever-syndromes-in-adult-can cer-patients-at-low-risk-for-complications?source=search_result&search=neutropenia&selectedTitle=9%7E150. Accessed 09.03.15. 34. Hirsch HH, Martino R, Ward KN, et al. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis and treatment of human respiratory syncytial virus, parainfluenza virus, metapneumovirus, rhinovirus, and coronavirus. Clin Infect Dis 2013;56(2):258–266. 35. Engel KG, Buckley BA, Forth VE, et al. Patient understanding of emergency department discharge instructions: where are knowledge deficits greatest? Acad Emerg Med 2012;19(9):1035–1044. 36. Boyle D, Bubalo J. Enhancing patient adherence to improve outcomes with oral chemotherapy. US Pharm 2007;32(10):1–8. 37. Dong S, Butow PN, Costa DSJ, et al. The influence of patient-centered communication during radiotherapy education sessions on post-consultation patient outcomes. Patient Educ Couns 2014;95(3):305–312. 38. Nirenberg A, Bush AP, Davis A, et al. Neutropenia: state of the knowledge Part II. Onc Nurs Forum 2006;33(6): 1202–1208. 39. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Crit Care Med 2013;41:580–637. 40. Vogtländer NP, Van Kasteren ME, Natsch S, et al. Improving the process of antibiotic therapy in daily practice: interventions to optimize timing, dosage adjustment to renal function, and switch therapy. Arch Int Med 2004;164(11): 1206–1212.
Contents lists available at ScienceDirect
Curr Probl Cancer journal homepage: www.elsevier.com/locate/cpcancer
Neutropenia: A nursing perspective Roberta Kaplow, PhD, APRN-CCNS, AOCNS, CCRNa, Renee Spinks, MSN, APRN, ACNS-BC, AOCNS, NP-Cb a
Oncology Clinical Nurse Specialist, Emory University Hospital, 1364 Clifton Road, E734, Atlanta, GA 30322 b Oncology Clinical Nurse Specialist, Emory University Hospital, 1364 Clifton Road, E834, Atlanta, GA 30322
Neutropenia: A nursing perspective Neutropenia is the most common dose-limiting toxicity of chemotherapy. It is considered an unpreventable side effect of many types of cancer treatment. It may be a side effect of therapy or a planned aspect of a conditioning regimen for bone marrow or hematopoietic stem cell transplantation (HSCT).1 The definition of neutropenia differs among institutions, ranging from an absolute neutrophil count (ANC) of less than 500 cells/mm3 to less than 1500 cells/mm3.2–4 Neutropenia can lead to infection, increased length of stay (LOS), delay, reduction, or discontinuation of cancer treatment, and increased morbidity and mortality.1,5–7 More than 60,000 patients with cancer are hospitalized annually in the United States for chemotherapyinduced neutropenia (CIN).8 Older patients with cancer may be more vulnerable for infection and death than their younger counterparts.5 The typical duration of neutropenia is 7-10 days but will vary based on the patient’s age, chemotherapy agent(s) received, comorbidities, and bone marrow reserve.7 Although patients cannot prevent CIN from occurring, there are a number of actions nurses and patients can take in order to help mitigate developing an infection while neutropenic. Hematopoietic colony-stimulating factors A common pharmacologic approach to infection prevention in patients undergoing cancer treatment is the use of hematopoietic colony-stimulating factors such as growth colonystimulating factors (G-CSF). Use of these agents has been shown to shorten the duration of neutropenia and LOS for febrile neutropenia (FN) and decrease the likelihood of infectionrelated mortality.9 Results of a systematic review suggest that hematopoietic colony-stimulating factors shorten the time a patient is neutropenic but the data about decreased mortality rates from CIN are unclear.10 According to American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines, patients who have at least a 20% chance of http://dx.doi.org/10.1016/j.currproblcancer.2015.07.009 0147-0272/& 2015 Elsevier Inc. All rights reserved.
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developing neutropenic fevers should receive growth factor support. Evidence supports using G-CSF in the autologous HSCT population based on accelerated neutrophil engraftment and reduction in neutropenia duration.11 Filgrastim and tbo-filgrastim Filgrastim is a G-CSF commonly administered after chemotherapy in order to decrease the occurrence of infection. It is administered daily via subcutaneous injection, beginning 24 hours after chemotherapy, and continued for up to two weeks. Filgrastim should be discontinued when the ANC has reached 10,000/mm3.12 Tbo-filgrastim is another G-CSF approved to reduce duration of CIN.13 Common side effects include bone pain, headache, fatigue, muscle aches, nausea and vomiting, and stomach pain. Bone pain was the most common side effect for both agents in clinical trials, with most patients rating their discomfort as mild or moderate and easily controlled with non-narcotic pain medications. Nurses should be aware that rare cases of splenic rupture, myocardial infarction, and acute respiratory distress syndrome (ARDS) have been observed in those receiving filgrastim.12 Patients receiving tbo-filgrastim are also at risk of splenic rupture, ARDS, and capillary leak.13 Pegfilgrastim Pegfilgrastim is a G-CSF similar to filgrastim. The major difference between the two drugs is that pegfilgrastim is designed to prevent rapid removal by the kidneys. As the drug stays in the body longer than filgrastim does, only one subcutaneous pegfilgrastim injection is needed after each cycle of chemotherapy. Side effects and risks are similar to filgrastim.14 Nurses must teach patients how to self-inject if they are being discharged after chemotherapy, when therapy will be discontinued, laboratory tests that require monitoring (e.g., complete blood count with differential), and management of side effects.
Antimicrobial prophylaxis Chemotherapy-induced neutropenia predisposes the patient to infection with a plethora of organisms. The organisms include Gram-positive cocci, Gram-negative bacilli, and fungi;7 these can vary by geographic location. A standard practice in the care of oncology patients is the use of antimicrobial prophylaxis to protect patients during the period of severe CIN. Institutions vary widely in the choice of antibiotics as well as the dosage and route.11 Typically, prophylactic antimicrobials are reserved for times when the risk of developing antimicrobial resistance is outweighed by the benefit of therapy and the risk of infection.15 Fluoroquinolones such as levofloxacin and ciprofloxacin are recommended for antimicrobial prophylaxis in neutropenic patients.16 Individuals expected to have a long duration of neutropenia, including patients undergoing bone marrow transplantation, typically receive antimicrobials to prevent GI Gram-negative organisms, Candida, Pneumocystis jiroveci, and cytomegalovirus (CMV).15 Antifungal prophylaxis is not advised for patients whose CIN is expected to last less than seven days.16
Intravenous immune globulin (IVIG) Intravenous immune globulin has been shown to help prevent some viral infections, most notably CMV, in HSCT recipients.17 While it is relatively safe, nurses should be aware that hypersensitivity reactions may occur. It is essential to start the infusion slowly and titrate up based on the patient’s tolerance.17 Premedications are commonly given. Baseline vital signs must be obtained, with subsequent vital signs measured at 15 to 30-minute intervals throughout the infusion.18
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Infection Prevention Bundles Hospital-associated infections (HAIs) pose a serious threat to inpatients and place a significant financial burden on the health care system.19 Patients with CIN are at increased risk of developing HAIs. The most common HAIs are catheter-associated urinary tract infections (CAUTIs), surgical site infections, central line-associated bloodstream infections (CLABSIs), and pneumonia.20 The Centers for Disease Control and Prevention (CDC) has published guidelines on prevention of HAIs, with several of the guidelines consisting of bundles.21 Bundles are “a small set of straightforward set of evidence-based practices – generally three to five – that when performed collectively and reliably, have been proven to improve patient outcomes.”22 Several other organizations publish clinical practice guidelines for the prevention and management of CIN. Despite their being readily available, a number of barriers to their use have been reported. Although expected to use NCCN guidelines for CIN and febrile neutropenia (FN) patient education and risk assessment, in one study, 56% of nurses reported that no institutional requirements were present for which guidelines be used. In this same study, 46% reported not having time to access the guidelines, 9% reported being too busy to use them, and 10% reported they did not have access to the educational materials to assist in their use.6 CLABSI prevention Many oncology patients require a central venous catheter (CVC) as part of their treatment plan. CLABSIs represent 14% of HAIs and are the second leading cause of death in patients who develop HAIs.19 The CDC guidelines for insertion and maintenance of CVCs are listed in Box 1. Nurses play a major role in prevention of CLABSIs because of their involvement in CVC dressing changes, flushing, and connector changes. In addition, nurses provide education for patients being discharged from the hospital with their CVC in place. It is not uncommon for a patient with CIN to develop a CLABSI. If a CLABSI develops, it may be necessary to remove the CVC.23 Nurses should feel empowered to participate in decision-making about removing CVCs as soon as possible when no longer indicated. Box 1–Insertion and maintenance of central venous catheters.21,24 Insertion
Perform hand hygiene before beginning the procedure Avoid use of the femoral vein Use maximal sterile barrier precautions Perform skin preparation with chlorhexidine (CHG), alcohol, or iodine Apply a sterile dressing application after line placement
Maintenance
Perform hand hygiene before touching the central venous catheter Use a chlorhexidine-based antiseptic to cleanse the skin for 30 seconds during the dressing change and allowing the CHG to dry Use a standardized protocol for cleansing the catheter hubs and injection ports prior to accessing the device Use a no-touch technique as much as possible Minimize the frequency of catheter manipulations
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Box 2–Indications for urinary catheter placement.24
Urinary retention or bladder outlet obstruction Necessity for accurate urinary output measurement in critically ill individuals Specific perioperative use for certain surgical procedures Assistance with healing of open perineal or sacral wounds in those who are incontinent Prolonged immobilization Palliative care in end-of-life situations
CAUTI bundle Indwelling urinary catheters also serve as a portal for infection in immunocompromised patients. CAUTIs comprise approximately 36% of HAIs outside the intensive care units.20 Urinary catheters should only be inserted in specific circumstances. These are listed in Box 2. An indwelling catheter should not be kept in place simply because a patient is incontinent, for obtaining a urine specimen for those who can void voluntarily, or for prolonged periods after a surgical procedure without a justifiable reason. One of the best methods of preventing CAUTI is early identification of indwelling catheters that are no longer necessary and removing them as soon as possible.24 Nursing care is crucial in preventing CAUTI. The CDC has developed guidelines for catheter insertion, which include hand hygiene before placement and adherence to sterile technique in the inpatient setting. Care and maintenance guidelines are outlined in the Guideline for Prevention of Catheter-Associated Urinary Tract Infections. Some of the key maintenance guidelines include ensuring a closed system, keeping the drainage bag below the level of the bladder, verifying the urine is free-flowing, and daily cleansing of the meatal surface while the catheter is in place.
Hand hygiene Hand hygiene is the best method of preventing infection in the inpatient setting.25 All health care workers and visitors must cleanse their hands before entering and after leaving patient rooms.16 Hand hygiene is also a crucial component of many of the infection prevention bundles.21,24
Diet Despite a lack of data supporting the usefulness of cancer patients following a neutropenic (low bacterial, sterile, or low microbial) diet, many providers continue to recommend it. While proponents appreciate food possibly containing harmful organisms and the possibility of bacterial translocation, studies do not reveal differences in mortality between patients who follow a neutropenic diet and those who do not. Opponents site a decrease in quality of life, malnutrition, vitamin deficiency-related immunodeficiency, gastrointestinal side effects, and distaste for food.26 As there are not significant data to support a traditional neutropenic diet, practice should move toward a focus on safe food handling, proper food preparation, and appropriate food choices (such as avoidance of unpasteurized dairy products).27 Common sense guidelines regarding food preparation include washing produce carefully, thoroughly cooking foods before eating, and discarding freshly made foods that have been refrigerated for more than 2-3 days.15 In general, uncooked fruits and vegetables can be consumed as long as they have been cleaned thoroughly. Patients with CIN should avoid prepared luncheon meats.16 Nurses should work with the multidisciplinary team to determine the best approach to dietary guidelines for their specific patients.
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Environmental concerns The CDC recommends keeping patients with CIN separated from individuals with transmissible infections.28 Nurses must ensure that plants and dried or fresh flowers are not brought into the hospital rooms of patients with CIN due to the risk of exposure to molds such as Aspergillus and Fusarium.16 All multipurpose equipment must be cleaned between patient use, with an emphasis on opting for single-use equipment and supplies wherever possible.15 Private rooms are not imperative for patients with CIN who are not undergoing HSCT. Guidelines recommend private rooms for HSCT patients.16,28
Personal protective equipment and isolation practices There are no professional recommendations for routinely wearing gloves, gown, and mask in hospital rooms of patients with CIN. There is a lack of evidence supporting the practice of keeping patients with CIN in protective isolation.11 Visitors with a respiratory virus should be discouraged from visiting patients with CIN. In addition, health care workers with an illness should report their symptoms and ideally be relieved of their assignments if they have symptoms of an infection that can be spread through air, droplet, or direct contact.16 Masks should be worn by staff and visitors in the rooms of patients with CIN if there is a chance of transmitting a respiratory virus.15 Data support use of high-efficiency particulate air (HEPA) filtration and laminar air flow to reduce the spread of Aspergillus and other airborne fungal infections on oncology units.11 All allogeneic HSCT patients should be placed in a room with greater than 12 air exchanges per hour as well as HEPA filtration.16
Antimicrobial treatment of febrile neutropenia Guidelines have been developed by the Infectious Diseases Society of America (IDSA) for the management of FN. The recommendations are based on whether the patient is at high or low risk for complications. Antimicrobial therapy is the mainstay of management of FN and should be based on the most likely suspected infecting organism(s). International guidelines corroborate a suggested initiation time of one hour for antimicrobial therapy from presentation of FN; blood cultures should be obtained before beginning therapy unless this causes more than a one-hour delay.4,23 It is essential for nurses to assure minimal to no delays in initiating antimicrobial therapy. Data support a substantive increase in mortality when comparing antimicrobial therapy started in less than one hour of diagnosis, or over one, four, or twelve hours of diagnosis.29,30 Nurses play a pivotal role in terms of antimicrobial administration and as a collaborator with the multidisciplinary team as stewards of antimicrobial therapy. In addition to monitoring for allergies, effectiveness, and side effects, nurses’ contributions may include validating that the antimicrobials prescribed are in synch with the microbiology reports. They should assure that antimicrobial levels are obtained at the correct time intervals, and interpreted and acted upon promptly. They should also assure that antimicrobial therapies are administered on time and that doses are not missed.31 Barriers to timely administration of antibiotics during times of FN have been reported. Patient-, staff-, and procedure-related variables have been identified. The main patient-related factor is lack of knowledge to promptly report fevers. Nursing staff-related barriers include not appreciating the immediacy required to start antimicrobial therapies and not establishing IV access and obtaining blood cultures promptly. Pharmacists’ failure to schedule the initial dose of antimicrobial therapy immediately and schedule the therapy to correspond with meals or around the clock were also identified. Procedure-related barriers included delays in nursing
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triage, assessment by a provider, transporting patients for diagnostic studies, or transferring the patient to another unit before initiating antimicrobial therapy.30
Fever workup Presence of FN should be deemed a medical emergency.32 Guidelines for prevention and treatment for FN have been developed. These include the 2010 IDSA and the 2013 ASCO guidelines.33 When patients present with FN, obtaining a targeted patient history is essential to help identify potential sources of infection. A physical examination will further help identify potential infection sources. Areas that should be targeted include the mouth, oropharynx, lungs, abdomen, and perianal areas. A digital rectal exam should not be performed on neutropenic patients. Presence of pain may suggest an infection source. Purulent drainage from a site is unlikely in neutropenia. If the patient reports abdominal tenderness, this may indicate enterocolitis. Presence of perianal tenderness may suggest a Gram-negative or anaerobic infection. A complete blood count with differential should be obtained to determine the degree of neutropenia. Renal and liver function tests and a metabolic panel should be obtained to help identify presence of any comorbidities. Blood cultures (both peripheral and from a central venous catheter) should also be procured. Specific imaging studies, such as computed tomography, may be obtained if certain specific sources of infection are suspected.23 If the patient presents with diarrhea, a specimen should be sent for Clostridium difficile toxin assay. A urine culture should be sent if signs of a urinary tract infection are present. Sputum cultures should be sent if the patient has a productive cough.34 Nurses should collaborate with the provider to arrange for appropriate testing to be performed.
Patient and family education Patient- and family-centered education is required throughout the cancer disease trajectory. During this period of vulnerability when CIN is present, education addressing why patients are at risk for neutropenia, degree of risk based on ANC, and self-care preventive strategies are indicated. Content to be included in education is listed in Box 3. Patient education tailored to the health literacy level, learning preferences, and addressing barriers to learning will help adherence with the recommendations. Patients and families should be reminded that the greatest risk of infection may occur after hospital discharge and that the patient is still at risk to develop an infection despite being discharged home.1 Obviating as many barriers to learning is critical. Although not conducted on patients with cancer, a direct relationship was found among education, adherence with instructions, and patient outcomes. That is, patients who received education that they were able to understand demonstrated increased levels of adherence with instructions.35 Furthermore, it has been demonstrated in patients who are receiving oral chemotherapy that adherence and follow-up are augmented when education includes use of a combination of educational materials, behavioral interventions, and reinforcing information.36 Dong and colleagues37 reported that patient-centered communication was essential to optimize outcomes of patients who are receiving radiotherapy. Although patient education materials have been developed by organizations such as the American Cancer Society (ACS), NCCN, and ASCO, they are not all evidence-based.38 The most comprehensive guidelines have been developed by the two former organizations.
Monitoring/When to notify the provider When providing education about temperature monitoring, it is essential to verify if the patient has a thermometer at home. An oral or tympanic thermometer is recommended.33 Temperature
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Box 3–Patient and family education.1,4,6,9,16,25,33,38
When to call the provider
Who to contact based on signs and symptoms present When first signs or symptoms of infection or neutropenic sepsis (e.g., fever, chills, rigors, diaphoresis) develop Report even a low-grade fever Report development of mouth sores, dysphagia, abdominal pain, rectal soreness, tenderness of the sinuses, or diarrhea. Report respiratory symptoms (e.g., shortness of breath, cough, or sore throat.) Report GU symptoms (e.g., burning on urination.) Report redness or swelling of any area of open skin or injury. How to report symptoms of infection
Monitoring
Signs and symptoms for which to observe Temperature monitoring: Check your temperature 1-4 times/day if you are not feeling well or suspect you are ill. Fever may be the only sign of infection in patients with neutropenia. Need for frequent CBC monitoring, especially when receiving a new drug with a high probability to cause neutropenia.
Risks
Treatment-related Degree of risk based on absolute neutrophil count
Medication knowledge
When most vulnerable for infection based on chemotherapeutic agents received Mechanism of action of agent(s) received Effect of chemotherapy on neutrophils Anticipated time of nadir
Knowledge specific to colonystimulating factors
Information about colony-stimulating factors (e.g., mechanism of action, rationale for use) Timing of administration (i.e., do not take earlier than 24 hours after chemotherapy administration.) Side effects management (e.g., bone pain with acetaminophen) Side effects are temporary and usually dissipate following discontinuation of therapy. Self-injection techniques (e.g., sites to use, rotation of sites, do not aspirate for blood prior to injecting) Remove medication from refrigerator 30 minutes prior to administration to help prevent stinging at the injection site When to notify provider (e.g., temperature over 38 1C, shortness of breath, increased heart rate, any new rash)
Activities
Wear gloves when cleaning. Wear protective gloves when participating in outdoor work (e.g., gardening).
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Box 3 - Continued
Avoid contact with compost heaps, manure, hay, and moldy areas. Avoid participating in contact sports or other activities where you can be injured. Diet
Check with your provider regarding any dietary restrictions. (Neutropenic diet is not supported with evidence.)
Hygiene
Hand hygiene: Wash hands often with soap and water or alcohol-based gel, especially before meals and after touching pets. Wash all surfaces of fingers and hands for at least 15 seconds. Dry hands thoroughly to prevent bacterial colonization. Personal hygiene: Bathe or shower daily; showers are preferred. Wipe the perineum from front to back after toileting (females) to avoid contamination. Use sanitary pads versus tampons.
Oral care
Brush teeth 2-3 times a day, including after eating and before going to bed. Use a toothbrush with soft bristles. Use warm salt water to rinse your mouth. Chlorhexidine 2% mouthwash after brushing teeth; keep in mouth for approximately 1 minute. Keep lips and mouth moist. If mucositis is present, cleanse mouth 4-6 times daily with sodium bicarbonate or normal saline. Floss daily if it does not cause trauma or bleeding. Mucositis prevention See dentist before receiving antineoplastic therapy. Remove dentures and other orthodontic appliances during the nadir to prevent trauma and infection.
Environmental hygiene
Do not place fresh flowers or potted plants in the home.
Skin protection
What to do at home?
Avoid getting scratches or other breaks in the skin. Use an electric razor. Keep nails trimmed short and clean. If breaks in the skin occur, wash thoroughly with soap and water or antimicrobial liquid and apply antibiotic ointment (e.g., bacitracin). Avoid tampons. Use water soluble lubricant during sexual intercourse. Maintain a sterile occlusive dressing on the CVC. Perform sterile dressing change to CVC. Flush CVC as prescribed. Actions to take if treatment-related toxicities occur at home.
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Box 3 - Continued
Pets
Environmental exposure
Avoid people who have a cold, flu or other respiratory tract infection. (Data are only available on BMT patients.) Avoid people who recently (within the past 3 weeks) received a live vaccine. Avoid places with crowds (e.g., shopping mall, movie theater, public transportation). Wear face masks in public places if ANC o 1000. Change air filters each month. Do not place fresh flowers or potted plants in the home. Care for plants should be performed by those not providing care to the patient. If this is not possible, the caregiver should wear gloves when handling plants and perform hand hygiene after gloves are removed.
Information to give to providers in triage areas
Recent chemotherapy agents received Dates of chemotherapy administration within the past 6 months
General
Patients are still at risk for infection following discharge home. Maintain schedule for routine dental check ups. Consult your provider before undergoing a dental procedure. If used, clean humidifiers each day and wash with a diluted bleach solution each week. Avoid constipation to maintain integrity of anal mucosa (e.g., by avoiding dehydration, stool softeners); avoid enemas and suppositories as these can break the integrity of the anal mucosa. Get the flu shot each year.
Avoid contact with pet feces, urine, or saliva. Do not handle used cat litter. Do not clean fish tanks. Do not clean pet cages. No direct or indirect contact with reptiles. Wash hands after any contact with animals. Prompt hand hygiene of broken or scratched skin or any loss of skin integrity
monitoring is critical, as a fever may be the first and only indication that the patient has an infection.1 The provider should be notified upon identification of a fever or other suspicion of an infection. Information to give the provider It is important for patients and families to tell providers in triage areas about chemotherapy received in the past 6 weeks. It is equally important to know what agents were administered and when the last dose was received so that the provider can assess whether the patient has reached nadir.23
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Nursing practice implications Identification of patients at risk Neutropenic events typically occur with the first cycle of chemotherapy.7 Risk of mucositis and constipation development should be minimized. When hospitalized, assessment of pressure sites should be performed at least each shift.1 Nurses should conduct a complete oral assessment before treatment to establish a baseline and then twice daily. Nursing assessment A thorough, detailed, and ongoing assessment is essential in order to identify potential sources of infection, assure early recognition of infections, and detect improvement or clinical deterioration and organ dysfunction. Fever is the most common sign of infection and should indicate the need for further investigation. Monitoring of vital signs including SpO2 and intake and output is equally critical. A minimum urine output of 0.5 mL/kg/h should be sustained.23 Signs and symptoms of organ dysfunction by system are listed in Table 1. A general assessment should include evaluation of any area with loss of skin integrity, including catheter insertion sites, an oral assessment, auscultation of breath sounds, assessment of use of accessory muscles and for increased work of breathing. An abdominal assessment should include auscultation of bowel sounds and palpating for abdominal tenderness.32 Nurses should completely assess the skin of all patients with CIN, with particular attention to sites that can easily become infected, such as the perineum and vascular access insertion sites.16 Frequent, methodical oral assessments are necessary to recognize ulcers and infections. Evaluation of the patient’s ability to have sufficient oral intake is vital. Fever can cause fluid and electrolyte depletion. If patients are being managed on an outpatient basis, they should be telephoned at least daily to determine if the fever has resolved.33 Nurses should remain aware that patients with CIN might have a life-threatening infection despite being afebrile or hypothermic. Hospitalized patients should also be checked for the presence of systemic inflammatory response syndrome criteria. Patients with mental status changes, hypotension, tachypnea, tachycardia, shaking chills, or decreased urine output should prompt the nurse to assess the patient for an infectious source. All significant findings and changes should be communicated to the provider in a timely manner. Recognition and treatment of febrile neutropenia As nurses are often the patient’s first contact, they play a pivotal role in identifying the possible presence of FN. When identified, prompt intervention is crucial. Early intervention should include alerting the provider, establishing intravenous access, obtaining peripheral blood cultures and a baseline serum lactate level, and initiating intravenous fluids.8,39 Table 1 Signs and symptoms of organ dysfunction. System
Signs and symptoms
General Neuro/Brain Cardiovascular Pulmonary GI/GU Hematologic
Fever or hypothermia, chills, malaise, fatigue, rigors New onset confusion, anxiety, disorientation, apprehension, agitation, obtunded, comatose Tachycardia, hypotension Tachypnea, decreased pCO2, respiratory alkalosis, shortness of breath Nausea and vomiting, jaundice, decreased albumin, oliguria WBC (increased or decreased), decreased platelets, increased INR, increased aPTT, disseminated intravascular coagulation Increased lactate, increased blood glucose
Metabolic
aPTT, activated partial thromboplastin time; GU, genitourinary; INR, international normalized ratio; WBC, white blood cell.
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Implementation of order sets and a checklist A standardized strategy for assessment of CIN and FN risk should be developed.5 To help mitigate barriers that affect timely antimicrobial administration in patients with FN, order set development has been suggested. Standardization of care with order sets for antimicrobial therapy has improved outcomes for patients with FN. Order sets with suitable antibiotic selections may decrease delays in medication administration.40
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