Download management of patients with low-risk febrile neutropenia

Art & science | The synthesis of art and science is lived by the nurse in the nursing act JOSEPHINE G PATERSON
MANAGEMENT OF PATIENTS
WITH LOW-RISK FEBRILE
NEUTROPENIA
Matt Fowler looks at how new tools to assess the possibility
of septic complications can guide future care options
Correspondence
[email protected]
Matt Fowler is advanced nurse
practitioner for oncology, South
Warwickshire NHS Foundation
Trust
Date of submission
April 28 2015
Date of acceptance
May 15 2015
Peer review
This article has been subject to
double-blind review and checked
using antiplagiarism software
Author guidelines
journals.rcni.com/r/
cnp-author-guidelines
Abstract
The National Institute for Health and Care Excellence
in the UK advocates that patients with neutropenia
who are at low risk of developing septic complications
should be considered for management in the
community rather than in hospital. The Multinational
Association of Supportive Care in Cancer (MASCC)
risk index is widely used to identify patients who
are deemed to be at low risk of developing septic
complications as a result of febrile neutropenia
(FN), but it has limitations. A newer tool, the
Clinical Index of Stable Febrile Neutropenia (CISNE),
CHEMOTHERAPY IS well documented to cause a
plethora of toxicities, however, febrile neutropenia
(FN) is one of the most serious complications
(Innes et al 2003), with a mortality rate of 5%
(de Naurois et al 2010). FN is defined by de
Naurois et al (2010) as ‘an oral temperature >38.5°C
or two consecutive readings of >38.0°C for two hours
and an absolute neutrophil count <0.5 × 109/L, or
expected to fall below 0.5 × 109/L’.
In the nurse-led chemotherapy unit where I work
as an advanced nurse practitioner (ANP) many of
the decisions traditionally made by oncologists and
haematologists are made by the nurse consultant
and me. All patients who present as emergency
admissions with suspected FN are initially managed
by the senior nursing team during office hours.
As an autonomous ANP, it is crucial that my
decisions about patient management are backed
up by robust evidence to safeguard the patient and
16 June 2015 | Volume 14 | Number 5
further stratifies patients who may be suitable for
management in the community. This article uses a
case study to explore the management of a patient
who presented with suspected FN. It examines the
use of the MASCC risk index and the CISNE to make
recommendations for the future management of
patients with low-risk FN in the community.
Keywords
Chemotherapy, low-risk febrile neutropenia,
management, risk, treatment complications
the practitioner. Greenhalgh et al (2014) advocated
the use of evidence-based clinical guidelines,
however, they stressed that care should still remain
individualised. Glasziou et al (2013) cautioned
against over-reliance on pathways/templates for
managing patients as this can result in ‘overtreatment’ because of fear of litigation. Management
of patients with FN is a classic example of protocol/
pathway-driven care. However, the variations in
practice identified in the National Institute for
Health and Care Excellence (NICE) (2012) guideline
on managing patients with neutropenic sepsis
suggest there is justification for examination of the
initial diagnostic and management plan.
Case study
Julie (pseudonym) was a 38-year-old woman
receiving adjuvant chemotherapy post-mastectomy
for breast cancer who presented to the ambulatory
CANCER NURSING PRACTICE
Getty
Art & science | adverse events
chemotherapy unit ten days post-chemotherapy
with a pyrexia of 38.0°C. Julie was at the nadir point
in her chemotherapy cycle. She was cannulated
on arrival, bloods taken for full blood count, urea
and electrolytes, C-reactive protein (CRP), liver
function tests as well as lactate and blood cultures.
In accordance with local guidelines she received
an immediate dose of intravenous (IV) tazocin
and gentamicin empirically while blood results
were processed. This practice was in accordance
with local policy and the NICE (2012) guideline
(Figure 1), as well as the surviving sepsis campaign
(Dellinger et al 2013).
Table 1 outlines the initial examination findings
and investigations requested.
As can be seen from Table 1, Julie had a
temperature of 38.0°C and a neutrophil count of 0.2,
which confirmed a diagnosis of neutropenic sepsis
Figure 1 NICE pathway for suspected neutropenic sepsis in secondary
and tertiary care
Person with suspected
neutropenic sepsis
Emergency treatment
and assessment
Start antibiotic
therapy
Confirm diagnosis
of neutropenic sepsis
Assess the patient’s risk
of septic complications
Patients at low risk of
septic complications
Patients at high risk of
septic complications
Duration of antibiotic
treatment
Discharge
(National Institute for Health and Care Excellence 2012)
18 June 2015 | Volume 14 | Number 5
Patients whose risk of
septic complications is
reassessed as low
(NICE 2012). The National Cancer Institute (1999)
classified neutropenia as follows:
■ Grade 1 ≥1.5-<2.0.
■ Grade 2 >1.0-<1.5.
■ Grade 3 >0.5-<1.0.
■ Grade 4 <0.5.
Although FN carries a mortality rate of 5% (de
Naurois et al 2010), Julie had grade 4 neutropenia,
which can carry a mortality rate as high as 9%
(Lalami et al 2006).
Alternative options
I have worked in haemato-oncology for more
than 15 years and cared for many neutropenic
patients. Julie’s care appeared to represent the
‘gold standard’: safe care in accordance with best
available evidence. She received antibiotics within
30 minutes of arrival at hospital, had an uneventful
stay with successful neutrophil recovery and a fiveday stay that is in accordance with national averages
(Parish et al 2013).
On deeper reflection, however, I considered
whether her care could have been delivered
differently.
The NICE (2012) guideline advocated that
patients with low-risk FN should be considered for
management in the community, which has potential
benefits for patients and healthcare economies.
Worth et al (2011) identified savings of up to 30%
for patients with low-risk FN managed as outpatients
compared with the traditional method of receiving
antibiotics as inpatients. Nonetheless, 25% of all
deaths within 30 days of receiving chemotherapy
have been attributed to FN (Yoong et al 2012).
A literature search revealed a large amount
of research on the subject of low-risk FN.
Table 2 identifies the databases searched and
the number of hits broken down into adult and
paediatric settings. Search terms used were ‘low
risk’, ‘febrile’ and ‘neutropenia’.
Although there appeared to be a large amount
of research available on the adult population
with low-risk FN, there did not appear to be
any published evidence of centres in the UK
implementing the NICE (2012) recommendations
for managing patients with low-risk FN. This notion
was supported by Slavin and Thursky (2013) who,
in a survey of oncologists in Australia and the UK,
found an overwhelming reluctance by clinicians to
manage patients with low-risk FN in the community.
This was not the case in the paediatric setting
as there was clear evidence of children with lowrisk FN being managed at home (Manji et al 2012,
Orme et al 2014). Of further significance is that
children are often at greater risk of developing
CANCER NURSING PRACTICE
Table 1
Initial examination findings and investigations requested
Patient complaint:
History of patient complaint
Pyrexia
Patient received third cycle of adjuvant FEC (fluorouracil/epirubicin/cyclophosphamide) with
prophylactic GCSF (granulocyte-colony stimulating factor) injections ten days previously.
Patient began experiencing shivers on waking this morning. Checked temperature and it was
38.5°C. Contacted acute oncology helpline and advised to attend unit immediately
Temperature
38
Respiratory rate
15
Heart rate
78
Oxygen saturation
99% on room air
Past medical history
Mastectomy for breast cancer
Caesarean section
Blood pressure
120/76
Urine
No abnormalities
detected
Systemic inflammatory
response syndrome
1
Blood glucose
level
5.2
Glasgow Coma
Scale
15
Modified Early Warning
Score
1
Medications
Omeprazole 20mg daily
No known drug allergies
On examination
A: Airway patent
B: Chest clear, no cough/dyspnoea. Chest examination unremarkable; bilateral air entry on auscultation
C: Capillary refill 2 seconds, haemodynamically stable and patient reports good urine output. Pulse strong and
regular. Nil evidence of dehydration. No conjunctival pallor. Calves soft and non-tender with no oedema. No
central venous access device in situ
D: Blood glucose 5.2, GCS 15
E: Abdomen soft and non-tender, bowel sounds auscultated. Patient had bowels opened soft formed stool this
morning. Nil evidence of petechiae and no lymphadenopathy. Nil epistaxis/reports of any bleeding. Oral cavity: nil
evidence of mucositis
Diagnosis
Probable neutropenic sepsis
Plan
Full blood count (including differential)
Urea and electrolytes
Liver function tests
C-reactive protein (CRP)
Lactate
Blood cultures
Urine dipstick
Cannulate
4.5g intravenous (IV) tazocin immediately and 320mg IV gentamicin
1,000ml 0.9% sodium chloride over eight hours
Blood results
Haemoglobin 118 White cell count 0.8 Neutrophils 0.2 Platelets 148
Sodium 136 Potassium 4.2 Urea 5.6 Creatinine 58
Bilirubin 12 Alkaline phosphatase 48 Alanine transaminase 40
CRP 5
Lactate 0.8
Blood cultures negative after five days
complications as a result of FN than adults because
their immune systems are not as well developed,
they often receive intensive chemotherapy regimens
and often have central venous access devices in situ
(Sung et al 2011).
Vidal et al (2013) conducted a systematic
review comparing oral versus IV antibiotics for
the management of patients with FN and found no
significant difference in mortality or morbidity for
CANCER NURSING PRACTICE
those who were identified as low risk. However, they
recommended that further research was required to
stratify low-risk FN patients.
MASCC risk index
The Multinational Association of Supportive Care in
Cancer (MASCC) risk index is the tool most widely
used to identify low-risk FN patients (Klastersky et al
2000) (Table 3).
June 2015 | Volume 14 | Number 5 19
Art & science | adverse events
Table 2
Result of literature search for low-risk febrile neutropenia
Database
Number of hits
Number for
paediatrics
Number for adults
>18 years
CINAHL
9
6
3
Cochrane
2
1
1
Embase
64
39
25
Medline
32
16
16
PubMed
399
205
194
Total
506
267
239
Table 3
Multinational Association of Supportive
Care in Cancer scoring system for
stratification of risk in febrile neutropenia
Characteristic
Weight
Burden of illness:
No or mild symptoms
Moderate symptoms
5
3
No hypotension
4
No chronic obstructive pulmonary disease
4
Solid tumour or no previous fungal
infection
4
No dehydration
3
Outpatient status
3
Age <60 years
2
Risk score >21 identified low-risk patients
(Klastersky et al 2000)
Table 4
Clinical Index of Stable Febrile Neutropenia tool and comparison
with Julie’s score
Score
Julie
Performance status >2
2
0
Stress-induced hyperglycaemia
2
0
Chronic obstructive pulmonary disease
1
0
Chronic cardiovascular disease
1
0
Mucositis grade >2
1
0
Monocytes <0.2
1
0
Characteristic
(Adapted from Carmona-Bayonas et al 2011)
20 June 2015 | Volume 14 | Number 5
Using the MASCC risk index, Julie would have
scored 25 as follows: burden of illness 5; no
hypotension 4; no chronic obstructive pulmonary
disease 4; solid tumour 4; no dehydration 3;
outpatient status 3; and age <60 2.
Julie’s score classified her as having low-risk
FN. Although Klastersky et al (2000) suggested
that low-risk FN patients can be managed in the
community thus avoiding hospital admission,
Talcott et al (2011) advocated the admission of
low-risk FN patients for a period of 24 hours
observation before discharge into the community.
In view of the current perceived reluctance
of clinicians to manage low-risk FN patients in
the community, this option would appear to be
feasible. Teuffel et al (2010) also identified a cohort
of low-risk FN patients who go on to develop
complications necessitating hospital admission;
this further substantiates the case for initial
admission to hospital for observation.
In response to some of the concerns raised
about the MASCC risk index including that it is not
specific to solid tumours, Carmona-Bayonas et al
(2011) devised the Clinical Index of Stable Febrile
Neutropenia (CISNE) tool to identify patients who are
at low risk of developing complications of FN and
can be discharged home after 24 hours if their CISNE
score is 0.
Table 4 demonstrates the CISNE score as well as
how Julie’s FN would have been classified.
The fact that Julie had a MASCC risk index score
of 25 and a CISNE score of 0 further supports
the notion that she could have been managed in
the community after an initial 24-hour inpatient
admission. Although monocytes are recorded on the
differential full blood count they are not routinely
checked, hence I had to examine the results
retrospectively and discovered that Julie had a
monocyte count of 0.42.
A new way of scoring
There is evidence to support early discharge of
low-risk FN patients as long as they fulfil criteria
in accordance with a locally agreed tool. Although
widely used in practice in the US, the MASCC
risk index has limitations and in light of this the
CISNE tool can be used to further stratify patients
identified as low risk by the MASCC risk index
(Carmona-Bayonas et al 2011).
I propose that a combination of Systemic
Inflammatory Response Syndrome (SIRS) score
and CISNE score should be adopted in routine
practice to identify low-risk FN patients who
could be discharged home on oral antibiotics
after a 24-hour hospital admission. NICE (2012)
CANCER NURSING PRACTICE
advocated that low-risk FN patients could be
managed in the community, which also supports
this recommended change in practice from a clinical
governance perspective.
More robust trials are advocated for
management of low-risk FN patients in the UK
(Phillips et al 2012), although this should not
be seen as a barrier to implementing changes in
practice. I intend to conduct a retrospective audit
of notes of patients who have been admitted
with FN over the past six months, an average of
six patients a month, to identify how many would
have been classified as low risk.
As with any change in practice, the management
of change process is important. Liaising with
interested parties in the acute trust as well as
primary care is fundamental, especially considering
how such a change in practice could have
far-reaching implications for both settings.
Conclusion
Although most chemotherapy can be administered
in outpatient settings, it is time to start evaluating
which further elements of the cancer patient
pathway can be delivered in the ambulatory/home
setting. Use of diagnostic tools including SIRS and
the Modified Early Warning Score as well as the
CISNE tool has the potential to revolutionise the
care of patients with low-risk FN. In the case of Julie
their use would have meant she could have been
discharged home after 24 hours with oral antibiotics
and robust education. This has fundamental and
far-reaching implications for the healthcare economy
and most importantly for patients.
Online archive
For related information, visit
our online archive and search
using the keywords
Conflict of interest
None declared
References
Carmona-Bayonas A, Gómez J,
González-Billalabeitia E et al (2011) Prognostic
evaluation of febrile neutropenia in apparently
stable adult cancer patients. British Journal of
Cancer. 105, 5, 612-617.
de Naurois J, Novitzky-Basso I, Gill M et al
(2010) Management of febrile neutropenia:
ESMO Clinical Practice Guidelines. Annals of
Oncology. 21, Suppl 5, v252-v256.
Dellinger R, Levy M, Rhodes A et al (2013)
Surviving sepsis campaign: international
guidelines for management of severe sepsis
and septic shock: 2012. Critical Care Medicine.
41, 2, 580-637.
Glasziou P, Moynihan R, Richards T et al
(2013) Too much medicine; too little care.
BMJ. 347:f4247.
Greenhalgh T, Howick J, Maskrey N (2014)
Evidence based medicine: a movement in crisis?
BMJ. 348:g3725.
Innes H, Smith D, O’Reilly S et al (2003)
Oral antibiotics with early hospital discharge
compared with in-patient intravenous
antibiotics for low-risk febrile neutropenia in
patients with cancer: a prospective randomised
controlled single centre study. British Journal of
Cancer. 89, 1, 43-49.
CANCER NURSING PRACTICE
Klastersky J, Paesmans M,
Rubenstein E et al (2000) The Multinational
Association for Supportive Care in Cancer
risk index: a multinational scoring system
for identifying low-risk febrile neutropenic
cancer patients. Journal of Clinical Oncology.
18, 16, 3038-3051.
Lalami Y, Paesmans M, Muanza F et al (2006)
Can we predict the duration of chemotherapyinduced neutropenia in febrile neutropenic
patients, focusing on regimen-specific risk
factors? A retrospective analysis. Annals of
Oncology. 17, 3, 507-514.
Manji A, Beyene J, Dupuis L et al (2012)
Outpatient and oral antibiotic management
of low-risk febrile neutropenia are effective
in children – a systematic review of
prospective trials. Supportive Care in Cancer.
20, 6, 1135-1145.
National Cancer Institute (1999) Common
Toxicity Criteria, Version 2.0. The National
Cancer Institute, Bethesda MD.
National Institute for Health and Care
Excellence (2012) Neutropenic Sepsis: Prevention
and Management of Neutropenic Sepsis in Cancer
Patients. Clinical guideline 51. NICE, London.
Orme L, Babl F, Barnes C et al (2014) Outpatient
versus inpatient IV antibiotic management for
pediatric oncology patients with low risk febrile
neutropenia: a randomised trial. Pediatric Blood
and Cancer. 61, 8, 1427-1433.
Teuffel O, Amir E, Sung L et al (2010)
Treatment strategies for low-risk febrile
neutropenia in adult cancer patients: a
cost-utility analysis. Journal of Clinical Oncology.
28, 15 Suppl, abstract 6102.
Parish B, Cooksley T, Haji-Michael P (2013)
Effectiveness of early antibiotic administration
in septic patients with cancer. Acute Medicine.
12, 4, 196-200.
Vidal L, Ben Dor I, Paul M et al (2013) Oral
versus intravenous antibiotic treatment
for febrile neutropenia in cancer patients.
Cochrane Database of Systematic Reviews.
Issue 10.
Phillips R, Hancock B, Graham J et al (2012)
Prevention and management of neutropenic
sepsis in patients with cancer: summary of
NICE guidance. BMJ. 345:e5368.
Slavin M, Thursky K (2013) Outpatient
therapy for fever and neutropenia is safe but
implementation is the key. Journal of Clinical
Oncology. 31, 9, 1128-1129.
Sung L, Phillips R, Lehrnbecher T (2011) Time
for pediatric febrile neutropenia guidelines –
children are not little adults. European Journal
of Cancer. 47, 6, 811-813.
Worth L, Lingaratnam S, Taylor A et al (2011)
Use of risk stratification to guide ambulatory
management of neutropenic fever. Australian
Consensus Guidelines 2011 Steering
Committee. Internal Medicine Journal. 41,
1b, 82-89.
Yoong J, Seah J, Hamilton K et al (2012)
Mortality within 30 days of receiving systemic
anti-cancer therapy at a regional oncology unit:
what have we learned? Asia-Pacific Journal of
Clinical Oncology. 8, 4, 325-329.
Talcott J, Yeap B, Clark J et al (2011) Safety
of early discharge for low-risk patients with
febrile neutropenia: a multicenter randomized
controlled trial. Journal of Clinical Oncology.
29, 30, 3977-3983.
June 2015 | Volume 14 | Number 5 21