Febrile neutropenia
BMJ 2010; 341 doi: https://doi.org/10.1136/bmj.c6981 (Published 17 December 2010) Cite this as: BMJ 2010;341:c6981All rapid responses
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We agree with the authors that febrile neutropenia [FN] is a medical
emergency associated with morbidity and mortality if not managed
appropriately with urgency.1 We would like to point out that available
guidelines are specific with definition of fever as either single oral
temperature of 38.3C (101F) or a temperature of 38.0C (100.4F) for 1 hour
while neutropenia is defined as a neutrophil count of 500 cells/c.mm or a
count of 1000 cells/c.mm with a predicted decrease to 500 cells/mm3.2,3,4
The guidelines from Christie hospital stratify risk on basis of counts
<1000; <500 and <100 and suggest this stratification should only
be applied at specialist centres to deal with patients as out or
inpatients.3 The DH report and practice at most specialist units offering
chemotherapy includes treatment plan and patient information (verbal and
written) on likely side effects, 24/7 helpline numbers and facility for
direct admission to the unit.5 The data from NCEPOD suggests a failing in
such high-risk patients being optimally informed.6 Diagnosis of FN
requires rapid access to a full blood count results and DH guidance
mandates administration of intravenous broad spectrum antibiotics within
one hour. Timely and specialist clinical assessment and prompt management
of such high risk and vulnerable population would be sub optimal in
primary care.
The DH report (August 2009)5 includes a formal request to National
Institute for Health and Clinical Excellence to urgently develop national
guideline on the clinical management and prevention of FN. However, such a
guideline is still awaited. A regional re-audit (autumn 2010) on
management of FN across 17-hospitals in Merseyside, Cumbria and Lancashire
reported considerable variation in the management of FN (high risk and
vulnerable population) in absence of a national guidance that would apply
to both district hospitals and specialist centres.
References:
1.Naik J, Sathiyaseelan S, Vascudev N. Easily Missed? Febrile neutropenia.
BMJ 2010;341:c6981.
2.Hughes WT, Armstrong D, Bodey GP, et al. 2002 guidelines for the use of
antimicrobial agents in neutropenic patients with cancer. Clin Infect
Dis. 2002;34(6):730-751.
3.Taylor M, Mutton K, Kaczmarksi E, et al. 2008 Guidelines for the
management of neutropenic sepsis. Christie Hospital.
4.National Comprehensive Cancer Network Clinical Practice Guidelines in
Oncology. Prevention and treatment of cancer-related Infections
(v.2.2009).
http://www.nccn.org/professionals/physician_gls/PDF/infections.pdf.
5.National Chemotherapy Advisory Group. Chemotherapy services in England:
ensuring quality and safety. 2009.
www.dh.gov.uk/en/Publicationsandstatistics/Publications/DH_104500.
6.National Confidentional Enquiry into Patient Outcome and Death. For
better, for worse? 2008. www.ncepod.org.uk
Competing interests: No competing interests
The authors are right that this is important and easily missed, but
we do not agree that all patients in whom this is a possibility (ie
everyone on chemotherapy with a fever or history of fever) hospital
referral is mandatory.From our out of hours centre (situated next to a
hospital) we can obtain a full blood count result within an hour, and if
this is normal and the patient not otherwise seriously ill we can send the
patient home with appropriate treatment.
Competing interests: No competing interests
Comparison of the management of neutropenia in chemotherapy and that in Clozapine treatment
As cited in the article,
(i) the risk of febrile neutropenia is 5-50%
depending on the chemotherapy regimen. This refers to patients receiving
chemotherapy for malignancies.
(ii) even treated appropriately, febrile neutropenia has an overall
mortality rate of about 5%.
It appears that there is no institutional mechanism agreed in the UK
for early diagnosis and treatment of febrile neutropenia in patients
receiving chemotherapy.
Contrast this with the management of neutropenia and agranulocytosis
as a side effect of Clozapine. Clozapine is an antipsychotic medication
used in treatment resistant schizophrenia. Around 2.7% of patients treated
with Clozapine develop neutropenia; approximately 0.8% develop
agranulocytosis. In the UK, the risk of death from agranulocytosis is
probably less than 1 in 10 000 patients exposed . The risk is very well
contained by the pharmaceutical company run clozapine-monitoring systems.
White blood cell count and differential counts are performed before
starting Clozapine as baseline and are repeated weekly for the first 18
weeks. Then it is monitored 2-weekly for the remainder of the first year.
Thereafter the monitoring is done on a monthly basis.This monitoring
system is a time tested one and has kept the mortality due to neutropenia/
agranulocytosis at a minimum, thereby benefitting treatment resistant
patients.
I believe a similar mechanism of serial blood counts should be adopted in
patients receiving chemotherapy for cancer. This will go a long way in
minimising the deaths due to febrile neutropenia.
Reference:
Maudsley prescribing guidelines 10th ed. by Taylor, Paton and Kapur.
Competing interests: No competing interests