The Journal of Emergency Medicine, Vol. 58, No. 3, pp.

444–448, 2020
Ó 2019 Elsevier Inc. All rights reserved.
0736-4679/$ - see front matter

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Selected Topics:
Oncological Emergencies

EMERGENCY AMBULATORY MANAGEMENT OF LOW-RISK FEBRILE

NEUTROPENIA: MULTINATIONAL ASSOCIATION FOR SUPPORTIVE CARE IN
CANCER FITS-–REAL-WORLD EXPERIENCE FROM A UK CANCER CENTER

William Marshall, MBCHB, Gerry Campbell, RGN, MSC, Thomas Knight, MBCHB, MRCP(UK),
Tamer Al-Sayed, MBCHB, FRCP, and Tim Cooksley, MBCHB, FRCPE
Department of Acute Medicine and Critical Care, The Christie, Manchester, United Kingdom
Corresponding Address: Tim Cooksley, MBCHB, FRCPE, Department of Acute Medicine and Critical Care, The Christie, Wilmslow Road,
Manchester M204BX, United Kingdom

, Abstract—Background: Emergency patient presenta- Eighty-one patients were female and the median age was
tions with febrile neutropenia are a heterogeneous group. 51 y (range 17–79 y). No patients developed serious compli-
A small minority of these patients proceed to develop signif- cations. Eight (8% [95% confidence interval 4.1–15.0%])
icant medical complications. Risk stratification using scores, patients had a 7-day readmission. Conclusion: Outpatient
such as the Multinational Association for Supportive Care in ambulatory care for emergency patients with low-risk
Cancer score, have been advocated to identify patients who febrile neutropenia can be delivered in a safe and effective
are at low risk of adverse outcome suitable for treatment on fashion. Collaboration between acute care physicians and
an ambulatory care pathway. Objectives: We sought to oncologists is required to develop local models based on na-
report the experience of 100 patients presenting acutely tional guidelines to facilitate individualised care for emer-
with neutropenic fever managed in an emergency ambula- gency oncology patients. Ó 2019 Elsevier Inc. All rights
tory fashion. Methods: Patients presenting as an emergency reserved.
with low-risk febrile neutropenia managed in an ambula-
tory setting between January 2017 and February 2019 at a , Keywords—ambulatory emergency care; early
tertiary cancer hospital in England were prospectively stud- discharge; febrile neutropenia; MASCC
ied. Patients with a fever >38.0 C and an absolute neutrophil
count <1.0  109/L were included. All patients with a Multi- INTRODUCTION
national Association for Supportive Care in Cancer score
$21 and a National Early Warning Score #3 were poten-
Suspected neutropenic sepsis is an acute medical emer-
tially eligible for the pathway. Complications were classified
as serious if the patient developed persistent hypotension, gency, and empirical antibiotic therapy should be admin-
respiratory failure, intensive care unit admission, altered istered immediately (1–3). However, neutropenic sepsis
mental status, disseminated intravascular coagulation, renal forms only a small subpopulation within the
failure requiring renal replacement therapy, electrocardio- heterogenous emergency patient presentations of febrile
gram changes requiring antidysrhythmic treatment, and neutropenia (4–6).
30-day mortality. Results: One hundred patients with low- Rigorously developed risk assessment tools, such as
risk febrile neutropenia consecutively managed in an emer- the Multinational Association for Supportive Care in
gency ambulatory fashion were prospectively analyzed. Cancer (MASCC) and the Clinical Index of Stable
Febrile Neutropenia (CISNE) exist for febrile neutrope-
Reprints are not available from the authors. nia (7,8). Outpatient management guided by these scores

RECEIVED: 20 March 2019; FINAL SUBMISSION RECEIVED: 21 September 2019;

ACCEPTED: 21 September 2019

444

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Emergency Ambulatory Management of Low-Risk Febrile Neutropenia 445

is a safe and effective strategy. The benefits of emergency and had repeat bloods performed. All patients managed
ambulatory care include admission avoidance, reducing on the pathway had access to a 24-h specialist oncology
pressure on often overcrowded and overstretched emer- telephone hotline. They were given clear instructions as
gency departments (EDs), cost savings, a reduced risk to the signs and symptoms that should trigger them to
of nosocomial infections, and improved patient experi- seek medical assessment and when they should represent
ence and satisfaction (3,9,10). to the hospital.
However, there is a dearth of prospective data exam- Basic demographic data, site of primary cancer, treat-
ining the ambulatory management of patients with low- ment intent, the MASCC, the CISNE score, and NEWS,
risk neutropenic fever presenting to emergency settings. the neutrophil count on discharge, and subsequent posi-
We report the experience of 100 patients with neutropenic tive microbiologic results were recorded. The CISNE
fever that were managed in an ambulatory fashion after score was not used in the assessment of patients for emer-
they had presented as an emergency to a hospital that is gency ambulatory management and a score >1 was clas-
a cancer center in the United Kingdom. sified as not low risk on this score. Serious complications
were classified as persistent hypotension, respiratory fail-
MATERIALS AND METHODS ure, intensive care unit admission, altered mental status,
disseminated intravascular coagulation, renal failure
Emergency ambulatory care of patients presenting with requiring renal replacement therapy, electrocardiogram
low-risk febrile neutropenia between January 2017 and changes requiring antidysrhythmic treatment, and 30-
February 2019 at a tertiary cancer hospital in the north- day mortality. Seven-day readmissions, readmissions
west of England were prospectively studied. The hospital before the next cycle of chemotherapy, and 30-day read-
has an oncology admissions unit that receives patients via missions were also collected.
several access points, including directly from the hospital
patient telephone hotline and primary care and paramedic RESULTS
referrals.
Patients with a fever >38 C and an absolute neutrophil One hundred patients with low-risk febrile neutropenia
count <1.0  109/L were considered. All patients with a consecutively managed in an emergency ambulatory
MASCC score $21 and a National Early Warning Score fashion were prospectively analyzed. Eight-one (81%)
(NEWS) #3, a marker of physiological stability, were patients were female and the median age was 51 y (range
potentially eligible for the pathway (11). This is consis- 17–79 y). Fifty-three (53%) patients had breast cancer
tent with the UK National Institute for Health and Care and 70 (70%) patients were being treated with curative
Excellence guideline for the management of neutropenic intent. Table 1 shows the demographic data of the pa-
sepsis (12). tients. No patients developed serious complications.
The MASCC score is calculated using 7 criteria asso- Sixteen (16%) had a CISNE score >1, although only 1 pa-
ciated with poor outcome in patients with febrile neutro- tient had a CISNE score of 3.
penia (5,7). Points are accrued for each predictor. The Eight (8% [95% confidence interval {CI} 4.1–15.0%])
maximum score is 26. High-risk patients have a score patients had a 7-day readmission. One patient was read-
<21 and require inpatient care. Patients with a score mitted with Staphylococcus aureus bacteremia and 1
$21 have a low risk of significant complications (7). required inpatient intravenous antibiotics for a confirmed
The NEWS is a simple aggregate scoring system based line infection. Three (3% [95% CI 1.0–8.5%]) patients
on routine physiological variables that is predictive of a represented with further symptomatic fevers. The causes
number of adverse clinical outcomes (13). of the other 7-day readmissions were 1 with severe
Suitable patients were managed with oral amoxicillin/ abdominal pain, 1 feeling fatigued and unwell, and 1
clavulanic acid (500/125 mg thrice daily) and ciprofloxa- with severe pain thought to be related to granulocyte-
cin (500 mg twice daily) or moxifloxacin 400 mg 1 time colony stimulating factor injections.
daily if they were penicillin allergic. All patients had 1 None of the readmitted patients required critical care
dose of intravenous meropenem on arrival to the admission. Twenty-three (23% [95% CI 15.8–32.2%])
oncology admissions unit as part of a nurse-led protocol, patients were readmitted within 30 days, but other than
which gives nurses the responsibility of assessing patients the 8 patients with 7-day readmissions, all of these had
with fever postchemotherapy and prescribing and admin- received further chemotherapy. No patients had readmis-
istering the first dose of intravenous antibiotics with the sions to other local EDs within 7 days.
aim of improving the speed of this intervention (14). Twenty-eight (28% [95% CI 20.1–37.5%]) patients
The initial duration of hospitalization was determined had a positive microbiologic result. Of these, 5 patients
by the treating physicians but was $4 h. All discharged had a bacteremia—4 line-related and 1 Streptococcus
patients were reviewed within 48 h in an emergency clinic parasanguinis caused by oral mucositis. Thirteen patients

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446 W. Marshall et al.

Table 1. Characteristics of Patients with Low-Risk Febrile overstretched EDs, cost savings, a reduced risk of noso-
Neutropenia Managed in an Emergency
Ambulatory Fashion
comial infections, and improved patient experience and
satisfaction (6,9). In addition, late presentation of patients
Characteristic Median (Range) or n (%) with febrile neutropenia remains a significant risk, some-
times driven by concerns of prolonged hospital admis-
Median age, y (range) 51 (17–79)
Gender, n (%) sion—this can be mitigated by a greater awareness of,
Male 19 (19) and access to, ambulatory pathways.
Female 81 (81) The question of how to identify patients with low-risk
Cancer type
Breast 53 (53) febrile neutropenia and which risk score has the best per-
Ovarian 7 (7) formance has dominated recent publications in this field
Sarcoma 7 (7) (17–19). There has also been recent discussion
Lymphoma 6 (6)
Colorectal 6 (6) regarding the role of clinical judgement in this process
Upper gastrointestinal 5 (5) (16). Arguably, this has caused some stasis in the progress
Testicular 4 (4) of emergency ambulatory care and slowed the develop-
Lung 2 (2)
Cholangiocarcinoma 2 (2) ment of safe pathways for their care in the myriad of set-
Prostate 2 (2) tings that deliver emergency oncology.
Pancreas 2 (2) The most challenging aspect for the safe and effective
Thymus 1 (1)
Endometrial 1 (1) delivery of ambulatory care to patients with low-risk
Nasopharynx 1 (1) febrile neutropenia remains the creation of a system
Bladder 1 (1) with good continuity of care between the ED and the
reatment intent
Curative 70 (70) oncology clinic (20–22). All specialists must be aware
Palliative 30 (30) of the systems in place and of the fact that some
Positive microbiologic result 28 (28 [95% CI 20.1–37.5%]) patients with febrile neutropenia can be reasonably
Median neutrophil count at 0.4 (0.0–1.0)
discharge (range) expected to be treated and released from the ED (23).
Median MASCC score on 24 (21–26) These events should be able to occur without the oncolo-
discharge (range) gists casting this practice as unreasonable or unsafe in
Median CISNE score on 1 (0–3)
discharge (range) their discussion with their patients.
Median NEWS on 1 (0–2) The development of emergency ambulatory pathways
discharge (range) for the management of low-risk febrile neutropenia is no
Serious complications 0 (0)
Seven-day readmissions 8 (8 [95% CI 4.1–15.0%]) longer purely the domain of oncologists and requires
collaboration with emergency care practitioners. The
CI = confidence interval; CISNE = Clinical Index of Stable Febrile risk stratification of emergency patients with febrile neu-
Neutropenia; MASCC = Multinational Association for Supportive
Care in Cancer; NEWS = National Early Warning Score. tropenia needs to be a key tenet of the evolving sepsis
strategy with access to locally formulated services based
had a confirmed urinary tract infection of which 1 was an on national and international guidelines. Without this
AmpC-producing organism. Four patients had line exit collaboration, individualized care—the hallmark of
site or wound positive cultures, 1 patient had norovirus, high-quality patient care for patients with low-risk febrile
1 had a Kluyvera species in the sputum, and 4 patients neutropenia—will be not be achieved.
had viral pathogens on nose and throat swabs.
Limitations
DISCUSSION
Our study is limited by its single-center nature and its
Ambulatory outpatient management of emergency pa- generalizability because it was performed in a specialist
tients presenting with febrile neutropenia is safe and tertiary cancer hospital with easy access to acute care
effective in those identified as low risk by validated risk and oncology expertise. This is potentially different
scores, such as the MASCC score (15,16). Our prospec- from a general ED where clinicians may have less experi-
tive data collected from emergency admissions in a hos- ence managing the nuances and potential pitfalls of pa-
pital with a specialization in cancer care adds further tients presenting with febrile neutropenia. Our cohort,
evidence to this strategy. There were no serious complica- comprised largely of patients with breast cancer, is consis-
tions and relatively low 7-day readmission rates in an tent with major studies in low-risk febrile neutropenia and
oncology population. is reflective of the cancer population that may be managed
The benefits of emergency ambulatory care for pa- in an ambulatory setting (24–26). However, it highlights
tients with low-risk febrile neutropenia are plentiful, the need to develop models of care that facilitate
including reducing pressure on often overcrowded and individualized care for emergency oncology patients.

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Emergency Ambulatory Management of Low-Risk Febrile Neutropenia 447

CONCLUSION 12. The National Institute for Health and Care Excellence (NICE). Neu-
tropenic sepsis: prevention and management of neutropenic sepsis
in cancer patients. Available at: https://www.nice.org.uk/guidance/
Outpatient ambulatory care for emergency patients with cg151/evidence/full-guideline-188303581. Accessed October 18,
low-risk febrile neutropenia is safe and deliverable. 2019.
13. Subbe CP. Death after discharge – every heartbeat counts (prob-
Collaboration between acute care physicians and oncolo- ably)!. Acute Med 2019;18:62–3.
gists is required to develop local models based on na- 14. Mattison G, Bilney M, Haji-Michael P, Cooksley T. A nurse-led
tional guidelines to facilitate individualized care for protocol improves the time to first dose intravenous antibiotics in
septic patients post chemotherapy. Support Care Cancer 2016;24:
emergency oncology patients. 5001–5.
15. Taplitz RA, Kennedy EB, Bow EJ, et al. Outpatient management of
fever and neutropenia in adults treated for malignancy: American
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448 W. Marshall et al.

ARTICLE SUMMARY
1. Why is this study important?
Emergency patients presenting with febrile neutropenia
are a heterogeneous group, with only a minority of treated
patients developing significant medical complications.
There is a lack of data examining the outcomes of emer-
gency patients with low-risk febrile neutropenia who are
managed on an ambulatory basis. Individualized care
for patients presenting with febrile neutropenia should
be a key tenet of care in emergency oncology.
2. What does this study attempt to show?
Risk stratification tools such as the Multinational Asso-
ciation for Supportive Care in Cancer can be used to deter-
mine which emergency patients presenting with
neutropenic fever can be safely managed in an emergency
ambulatory fashion. Our study presents a case series that
provides data supporting the safety and efficacy of this
approach.
3. What are the key findings?
One hundred emergency patients presenting with low-
risk febrile neutropenia managed in an emergency ambu-
latory fashion did not develop any serious complications.
There was a relatively low 7-day readmission rate. Ambu-
latory care for emergency patients with low-risk febrile
neutropenia is safe and deliverable.
4. How is patient care impacted?
Individualized care of the emergency oncology patient
should be a key tenet in this growing field. Risk stratifica-
tion and ambulatory emergency management of low-risk
febrile neutropenia can improve patient safety and satis-
faction. Ambulatory emergency oncology care may also
help ease pressures on overcrowded emergency depart-
ments and save costs.

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