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Nursing care,education and support
for patients with neutropenia
Coughlan M, Healy C (2008) Nursing care, education and support for patients with neutropenia.
Nursing Standard. 22, 46, 35-41. Date of acceptance: November 2 2007.
Summary
Neutropenia is reduced white blood cell count. It is a side effect of
cytotoxic chemotherapy for cancer and haematological patients.
This article aims to help nursing students and qualified nurses who
are novices in caring for neutropenic patients to become familiar
with the usual body defences against infection; understand how the
body’s ability to fight infection is affected by neutropenia; recognise
potential sources of infection; and support the patient who is at risk
of infection as a result of neutropenia.
Authors
Michael Coughlan is lecturer, School of Nursing and Midwifery
Studies, Trinity College Dublin and Colette Healy is clinical
facilitator, HOPE Directorate, St James’s Hospital, Dublin, Ireland.
Email: [email protected]
Keywords
Haematology; Immunocompromised patients; Neutropenia;
Oncology nursing
These keywords are based on the subject headings from the British
Nursing Index. This article has been subject to double-blind review.
For author and research article guidelines visit the Nursing Standard
home page at www.nursing-standard.co.uk. For related articles
visit our online archive and search using the keywords.
MYELOSUPPRESSION, and in particular
neutropenia or reduced white blood cell count,
is a major dose-limiting side effect for cancer and
haematological patients who are receiving
cytotoxic chemotherapy (Tervit and Phillips
2006). Patients with neutropenia have a greater
susceptibility to infection than healthy
individuals and a reduced ability to fight it.
Infection is often not easily identifiable as the
reduction or absence of white cells results in a
blunting or absence of an inflammatory response
(Crawford et al 2004). The result can be a severe
NURSING STANDARD
chest infection without purulent sputum, a
urinary tract infection without dysuria, or painful
urination. In many instances, the first and only
sign of infection is a rise in temperature
(Crawford et al 2004). Neutropenia-associated
infections substantially increase morbidity and
mortality, and are a burden on the patient and the
healthcare system (Kuderer et al 2006).
Natural defences against infection
The skin is the largest body organ and acts as a
barrier to infective organisms. Resident bacteria
(commensals) that colonise the surface of the skin
and prevent the build up of pathogenic organisms
assist in this defence. However, if these
commensal bacteria gain access to the body
through a break in the skin, or to a sterile body
cavity such as the bladder, then they can become
opportunistic pathogens (Hinchliff et al 1996).
Where natural portals of entry to the body exist,
other local defence mechanisms restrict microbial
access (Box 1).
If pathogenic organisms gain access to the
tissues, the first line of defence is an
inflammatory response. This involves two groups
of white cells. The first group are granulocytes
(leukocytes), which consist of neutrophils,
basophils and eosinophils. The second group are
monocytes, which mature into macrophages
(histocytes) (Traynor 2006) (Table 1). The
immune system works in tandem with the
inflammatory response. The immune system
consists of two responses: a cellular response,
which involves different groups of T
lymphocytes, and a humoral response involving
antibodies derived from B lymphocytes (Table 1).
All the cells involved in both the inflammatory
and immune responses are produced by the bone
marrow (Traynor 2006).
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Under normal conditions the body’s natural
defences offer reasonable protection from
everyday infective organisms. However, in
patients who are myelosuppressed, some or all
of these natural defences may be compromised,
leaving these individuals highly susceptible to
infection. For patients with neutropenia,
infection is a major cause of morbidity and
can lead to unplanned hospital admissions and
disruptions to treatment schedules and regimens
(Crawford et al 2004, Kuderer et al 2006). It is
also a leading cause of death (Kuderer et al 2006).
In patients with cancers and haematological
malignancies the risk of myelosuppression (and
subsequent neutropenia) is increased because
of damage to the bone marrow which can result
BOX 1
Innate body defences at portals of entry
Gastrointestinal tract:
Mouth – the mouth has a tough mucosal lining and the mucus produced contains immunoglobulin A, which has
antiviral properties. Saliva, which keeps the mouth moist, contains lysozyme which is antibacterial. Commensals
reside in the mouth and help to control the number of pathogenic organisms.
Stomach – the stomach produces hydrochloric acid which kills the majority of organisms that gain access to it.
Intestines – commensals such as Escherichia coli reside in the intestines and help to control the number of
pathogenic organisms.
Respiratory tract:
Ciliated mucosa in the airway restrict the access of microorganisms by trapping them, along with any other
particles, in mucus and wafting them out of the respiratory tract.
Genitourinary tract:
Bladder and urethra – the flow of urine from the bladder helps to clear away organisms ascending through the
urethra. This is more effective in males, where the urethra is longer, than in females.
Vagina – the vagina contains acid-forming bacteria called lactobacillus which create an environment that
militates against pathogenic organisms.
(Hinchliff et al 1996)
TABLE 1
White cells and their functions
White cells
Functions
Neutrophils
Neutrophils constitute 60% of the total white cell count. They are phagocytes and the
granules in their cytoplasm contain lytic enzymes. They are the first white cells to respond
to invading organisms. They also induce the inflammatory response.
Basophils
These granulocytes contain histamine and can induce allergic and anaphylactic reactions
in response to foreign organisms and proteins.
Eosinophils
These granulocytes are less active than neutrophils, but contain similar enzymes in their
cytoplasm. They also assist in protecting against parasites and in controlling the
inflammatory response.
Monocytes
(known as
macrophages or
histocytes when
in tissues)
These agranulocytes (without granules) share a common stem cell to the neutrophil. They
are phagocytic, but respond much more slowly to infections than neutrophils. They are
also natural sources of colony-stimulating factors, which promote growth of neutrophils
and other monocytes.
T lymphocytes
(T cells)
A number of different T cells are involved in an immune response known as cell-mediated
immunity. These include: cytotoxic T cells that destroy foreign material; memory T cells
that can recognise foreign organisms encountered previously and destroy them; helper T
cells which support the immune response; and suppressor T cells that control and switch
off the immune response.
B lymphocytes
(B cells)
B lymphocytes are involved with humoral immunity, which involves the production of
antibodies (immunoglobulins (Ig)). These immunoglobulins are: IgG, IgM, IgA, IgE,
and IgD.
(Traynor 2006)
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from the disease or treatment (Hart 2005).
Depending on the type of malignancy and the
stage of treatment, myelosuppression may be a
side effect of cytotoxic medication, or a
planned part of a myeloablative conditioning
regimen that aims to prepare patients for bone
marrow or stem cell transplant (Tervit and
Phillips 2006). The result, from a white cell
perspective, is a diminishing or absence of the
normal signs and symptoms associated with
the inflammatory response and infection. The
first and only sign of infection may be a sudden
onset of fever (Crawford et al 2004). The
immune response is affected by the decrease in
the number of T and B lymphocytes. This
further increases the risk of infection
(Linc et al 2001), and leaves patients
susceptible to infections to which they had
previously developed resistance.
Management and nursing care
The aim when caring for patients who are
neutropenic is to reduce the risk of exposure
to pathogens by identifying and eliminating
potential sources of infection. In addition it is
vital to observe for and recognise the signs and
symptoms that may indicate the onset of an
infection, and initiate the appropriate treatment.
Careful ongoing assessment is essential if these
aims are to be achieved. Educating patients and
their families about the risks associated with
neutropenia and the possible sources of infection
can also reduce the likelihood of some of these
potential threats becoming actual problems.
White cell counts offer an insight into the level
of neutropenia and the potential risk of infection
patients may incur. It is therefore essential that
nurses caring for neutropenic patients can
interpret these blood tests. White cell counts are
checked daily and an emphasis is placed on the
absolute neutrophil count (Marrs 2006), which
identifies the total number of neutrophils in
circulation and the degree of risk this poses
(Table 2).
Sepsis can develop rapidly in neutropenic
patients. It is therefore essential that clinical
observations, with a special emphasis on
temperature, are recorded at least every four hours
and more frequently as necessary. It is vital that
patients understand the importance of reporting
symptoms such as chills or rigors immediately
(Marrs 2006) so that appropriate interventions
can be taken. A temperature greater than 38.3˚C,
or one of 38˚C for an hour or more, requires
intervention (Marrs 2006). It is important to
consider all fevers as an indication of infection
until tests show otherwise (Linc et al 2001).
A single peripheral blood sample, as well as
samples from all lumen of venous access devices,
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TABLE 2
Infection risks associated with absolute
neutrophil count
Absolute neutrophil count
Increased infection
risk
1.5–2.0 x 109/l
None
1.0–1.5 x 109/l
Slight
0.5–1.0 x 109/l
Less than 0.5 x
Moderate
109/l
Severe
(Adapted from the National Comprehensive Cancer Network
and American Cancer Society 2006)
should be taken and sent for culture and sensitivity
(Marrs 2006). It is recommended that appropriate
prescribed broad-spectrum antibiotics are
administered, rather than waiting for sensitivity
results from blood tests (Hart 2006). When the
sensitivity results are known, specific antibiotics
can then be prescribed and administered.
Single room The benefits of protective isolation
for patients who are neutropenic are still under
debate. Rooms fitted with laminar airflow or
high efficiency particulate air filtration appear to
reduce the risk of airborne fungal infections such
as Aspergillus fumigatus (Dunleavey 2001, Hahn
et al 2002). The latter is an important
consideration for patients who are receiving
myeloablative chemotherapy for example, or
who have prolonged neutropenia. Protective
isolation, however, does not shield patients from
their own body flora, which are the most
common source of infections for
myelosuppressed patients (Hart 2005). Mank
and van der Lelie (2003) found no difference in
outcomes when patients were nursed in
protective isolation or in open single rooms.
However, they state that one advantage of
isolation can be that it increases staff and visitors’
awareness of the patient’s risk of infection.
For patients with short-term neutropenia
there appear to be conflicting views on whether it
is better that those patients with a similar
condition be nursed as a cohort in a small ward,
or in single rooms (Fenelon 1998, Shelton 2003).
Current practice tends to favour a cohort
approach with early discharge and outpatient
follow up. This approach appears to help reduce
the risk of iatrogenic infection and can help to
minimise the psychological distress induced by
protective isolation (Dunleavey 2001). Fenelon
(1998) recommends the use of single rooms for
the source isolation of haematological patients
who have an infection, as they are likely to infect
other immunocompromised patients.
Environmental hygiene A high standard of
cleanliness is essential at all times, irrespective of
whether patients are being cared for in protective
isolation or not (Linc et al 2001). Rooms should
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be free of clutter and unnecessary equipment to
allow for more thorough cleaning. Neutropenic
patients should avoid exposure to flowers and
potted plants which can be sources of water and
soil-based opportunistic fungal and bacterial
organisms (Shelton 2003).
Preventing cross-infection Good hand hygiene
is the single most effective method of reducing
cross-infection. All staff and visitors should wash
their hands, using an antiseptic hand wash,
before and after contact with the neutropenic
patient (Hart 2006). Alcohol hand washes are a
useful alternative when hands are physically
clean and should be available at the patient’s
bedside (National Patient Safety Agency 2004).
The patient must also be aware of the importance
of hand washing after toileting and before eating
(Hart 2005, Marrs 2006). Hands that are poorly
dried can become a breeding ground for bacteria
so patients, staff and visitors need to be advised
on the importance of good hand drying
(Nirenberg et al 2006a).
All staff caring for or in contact with
neutropenic patients must be free from infection.
Patients and their relatives require a clear
understanding of the dangers of neutropenic
sepsis and the potential of cross-infection. It is
recommended that family members or friends
who have colds, influenza or other contagious
conditions do not visit patients with neutropenia
(Hart 2006). Individuals who have had recent
live or attenuated vaccinations are also advised
to avoid contact for at least 48 hours
post-vaccination (Fishman and
Mrozek-Orlowski 1999). Relatives should be
asked to contact a member of the nursing staff if
there is any doubt about their fitness to visit.
Protecting the skin The skin is a natural
barrier against infection. It is therefore
essential to assess pressure sites and the general
condition of the skin at least once during each
standard shift (Linc et al 2001) and at least
twice a day. Education can help patients to
avoid activities that are likely to cause skin
damage. Bladed razors can nick the skin,
therefore the use of an electric razor is
recommended (National Comprehensive
Cancer Network (NCCN) and American
Cancer Society 2006). Keeping nails short and
clean is also important (Hart 2006).
It is recommended that invasive procedures,
such as the insertion of central catheters, be
avoided if possible when the patient is
neutropenic and especially at the neutropenic
nadir, when the white cell count is at its lowest,
which is usually 10-14 days post-treatment
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(Shelton 2003). If an invasive procedure has to be
undertaken then strict aseptic techniques must be
used to prevent pathogens gaining access to the
tissues (Linc et al 2001). It is important that
access sites for intravenous (IV) and central
catheters are checked regularly for signs of
inflammation and infection. Evidence suggests
that IV administration sets and cannulae should
be changed every 72 hours (Centers for Disease
Control and Prevention 2002). Blood needs to
be regularly cultured from central catheters, and
if a central catheter is removed due to infection or
suspected infection, best practice suggests that
the catheter tips should be cultured for bacterial
growth (Held-Warmkessel 1998). When
administering blood or blood products, it is
recommended that giving sets are changed at
least every six hours (National Blood Users
Group 2004).
A large proportion of infections that occur in
patients who are neutropenic are due to resident
bacteria becoming opportunistic and invading
the tissues (Nirenberg et al 2006a). Daily
showers or baths can help to reduce the number
of bacteria on patients’ skin and so help reduce
the risk of infection (Hart 2006).
Oral care The oral cavity is a common site for
infections in patients with neutropenia. Poor
dental health, such as decaying teeth and
inflamed gums, can result in life-threatening
sepsis. Antibiotic therapy can reduce or destroy
the normal oral commensals, exposing the
patient to the risk of infection (Dickinson and
Porter 2006). Cytotoxic drugs can cause
xerostomia (dry mouth), which can interfere
with usual defences against infection due to
reduced or absence of saliva.
Pre-treatment, if time permits, it is advisable
that patients have an oral assessment performed
by a dentist and if necessary remedial care given
before commencement of chemotherapy (Soady
2005). Cawley and Benson (2005) recommend
that nurses undertake an oral assessment before
the patient starts chemotherapy which will then
be used as a baseline. They suggest that
following the initial assessment oral
assessments are then performed at least twice
daily, and patients encouraged, as far as
possible, to be active participants in their own
assessment and care (Cawley and Benson
2005). Numerous oral assessment tools are
available, however no one tool is universally
accepted (Cawley and Benson 2005). Dickinson
and Porter (2006) state that Eilers et al’s (1988)
oral assessment guide has been shown to be
useful in practice and appears to have good
reliability (Andersson et al 1999).
Patients should understand the importance of
brushing their teeth after eating and before going
to bed to remove food debris (Dickinson and
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Porter 2006). A soft toothbrush reduces the risk
of damage to the oral mucosa and is
recommended (Fishman and Mrozek-Orlowski
1999). As long as the platelet count is not low,
gentle flossing may be undertaken to remove
food debris from areas inaccessible to brushing
(Marrs 2006). The routine use of antimicrobial
mouthwashes and antifungals is no longer
recommended (Nirenberg et al 2006a); however,
where patients are at risk of secondary infections
their use is considered appropriate (Dickinson
and Porter 2006). Where recommended, the
evidence suggests that mouthwashes such as
chlorhexidine gluconate 0.2% be used after
brushing and held in the mouth for
approximately one minute before being spat out
(Soady 2004). If an antifungal agent is also to be
used, Soady (2005) recommends that 30 minutes
should be allowed to elapse between the use of
the mouthwash and the antifungal agent as the
mouthwash can neutralise the antifungal effect.
Mucositis is a common and painful side effect
of cytotoxic chemotherapy that can occur
anywhere along the gastrointestinal tract
including the oral cavity. In the mouth it can
make eating difficult and oral care distressing
(Honnor and Law 2002). The resulting damage
to the mucous membrane can allow
microorganisms to gain access to the tissues
(Cawley and Benson 2005). The effects of oral
mucositis can be minimised by keeping the
mouth and lips moist, maintaining a good fluid
intake, and avoiding spicy foods, foods that are
very hot or cold, alcohol and smoking (Cawley
and Benson 2005).
Diet The debate regarding the benefits of a
reduced microbial diet for neutropenic patients
is ongoing. There appears to be a lack of
empirical evidence to support this diet (Rust et
al 2000, Shelton 2003, DeMille et al 2006).
Rust et al (2000) and Shelton (2003)
recommend educating patients and their
families about good food hygiene, including
washing raw vegetables and fruit before eating
and cooking meat and eggs thoroughly. It is
advisable that patients avoid drinking milk or
beer that has not been pasteurised, or eating
yogurts or cheeses made from unpasteurised
milk (Rust et al 2000, Marrs 2006). Pre-cooked
meats, pre-made sandwiches and cold cooked
pies can be sources of infection if poorly stored
or unhygienically handled (Rust et al 2000,
Shelton 2003), and are best avoided. Visitors
bringing in favourite foods to neutropenic
patients in hospital should consult with nursing
staff about safe foods.
Tap water usually has low microbial
levels but can occasionally become
contaminated by microorganisms such as
coliforms or Pseudomonas aeruginosa, among
NURSING STANDARD
others. While Shelton (2003) states that bottled
water offers a safe alternative to tap water,
Hart (2006) argues that controls on the
bacterial content of bottled water are less
stringent than that of tap water and
recommends filtered tap water.
Other gastrointestinal risks The integrity of the
anal mucosa can be impaired because of injury
and tears resulting from constipation (NCCN
and American Cancer Society 2006).
Constipation can result from a number of factors
such as pain medication, anti-emetics, reduced
mobility or cytotoxic drugs such as the vinca
alkaloids. Constipation needs to be anticipated
and prevented using active measures such as
prophylactic stool softeners. Hart (2006)
advocates against invasive remedies, such as
suppositories or enemas, which can damage the
rectal mucosa.
The disease process, cytotoxic medications
and superimposed infection resulting from
alterations in bowel flora due to antibiotics
can all cause diarrhoea (Mehmet 2006).
Patients require advice about observing the
consistency of their bowel motions and
reporting any abnormalities or changes. Stool
cultures will be required to exclude infection
before the administration of anti-diarrhoeal
medication (Held-Warmkessel 1998). Gentle
washing of the perineum after bowel motions,
cleaning from front to back, and the use of
barrier creams can help to reduce the risk of
excoriation and genitourinary infection
(Held-Warmkessel 1998).
Genitourinary risks Protection of the
genitourinary tract from ascending infection
and trauma is important in preventing infection.
Evidence suggests avoiding invasive procedures,
such as urinary catheterisation where possible,
especially during the neutropenic nadir.
Tampons can cause trauma and are also best
avoided (NCCN and American Cancer Society
2006). Sexual intercourse can also cause trauma
to the mucous membranes so water-soluble
lubricants are recommended (NCCN and
American Cancer Society 2006).
Medical prophylaxis
The risk of infection and the duration of the
neutropenic nadir can be reduced by the use of
prophylactic medications (Shelton 2003).
However, the routine use of prophylactic
antibiotics is no longer recommended.
Aspergillus fumigatus and Candida albicans
are the two most common fungal pathogens
and both can present as systemic infections
(Johnson et al 2000). They occur commonly in
patients with severe, or prolonged, neutropenia
(Nirenberg et al 2006a) (Table 3).
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Advice to neutropenic patients on discharge
Depending on treatment regimens, patients
receiving cytotoxic chemotherapy may still
have low white cell counts or may only
become neutropenic after discharge. The
advice that patients and their families
receive should emphasise that patients
with neutropenia are still at risk of infections
at home.
It should also reinforce the information that
patients received in hospital, for example in
relation to hand washing, personal hygiene and
diet, and highlight that these measures are still
pertinent post-discharge. Other advice is
included in Box 2.
TABLE 3
Medical prophylaxis
Colony-stimulating factors
Colony-stimulating factors can be given to stimulate the bone marrow to
produce granulocytes and macrophages.
They can reduce the risk of infection and duration of the neutropenic nadir.
They are recommended where:
There has been a previous occurrence of febrile neutropenia.
The patient is receiving high-dose chemotherapy (Marrs 2006).
There is a risk of febrile neutropenia (Nirenberg et al 2006b).
Antifungal prophylaxis
These drugs are recommended for patients who are at risk of severe, or
Prophylactic antibiotics
Co-trimoxazole is recommended for patients at risk of Pneumocystis carinii
who have prolonged, neutropenia (Nirenberg et al 2006a).
pneumonia (Nirenberg et al 2006a).
Routine use of prophylactic broad-spectrum antibiotics is no longer
recommended because of the risk of bacterial resistance and the lack
of empirical evidence to support a reduction in mortality
(Crawford et al 2004).
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Conclusion
Infections in patients with neutropenia are a
major cause of morbidity (Crawford et al 2004)
and mortality (Kuderer et al 2006). Nurses have
an important role in recognising potential
sources of infection, reducing the risk of
exposure, and educating and supporting
neutropenic patients in relation to these.
Infections can arise from activities that healthy
individuals take for granted and it can often be
difficult for neutropenic patients to accept the
lifestyle changes required. However, good
nursing care, education and support can promote
patients’ understanding and concordance, and
ultimately improve treatment outcomes NS
BOX 2
Patient education and advice in preparation for discharge
Signs and symptoms of infection:
Look for signs of infection and be aware that fever may be the first symptom (Hart 2006).
Check temperature at least once a day or if he or she is feeling unwell (Nirenberg et al 2006a).
Contact the GP or hospital at the first sign of infection rather than waiting to see if the condition gets worse
(Hart 2006).
Cross-infection:
Avoid contact with people who have infections.
Avoid crowded, smoky environments (Hart 2006).
Pets:
Pets are a potential source of infection.
Avoid contact with pet faeces, urine and saliva (Hart 2006).
Do not clean fish tanks as these can expose neutropenic patients to bacterial and fungal infections
(National Comprehensive Cancer Network and American Cancer Society 2006).
Cleaning and gardening:
Wear protective gloves for cleaning or for outdoor work, including gardening, to reduce the risk of injury
(Shelton 2003).
Avoid contact with compost heaps as they are a potential source of fungal spores (Johnson et al 2000).
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