Febrile Neutropenia

Febrile Neutropenia 

An ‘A–Z’ of the causes, 

incidence, symptoms, treatment and 

impact in patients with cancer 

Carmel O’Kane 

Oncology Nurse Practitioner Candidate, 

WHCG;SRH;EGHS

Neutropenia 

Facts 

Neutropenia (reduced neutrophil count) is the most common 

dose-limiting toxicity of chemotherapy 

Falling neutrophil count is asymptomatic 

Symptoms are associated with neutropenic complication (e.g. 

infection, which leads to fever) 

Febrile neutropenia (FN) is life-threatening and requires urgent 

attention

Grading neutropenia 

 

 

 

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Highest risk of infection is during 

the nadir period 

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Clinical presentation of infection 

in patients with neutropenia 

Neutropenia 

No signs 

Subtle changes 

• fatigue 

• respiratory 

• mucous 

membranes 

• urinary tract 

• nervous system 

Chills, sweats and 

fever 

Febrile neutropenic episode

Impact of neutropenia/infection 

Clinical outcomes 

dose delays and 

reductions- which is 

shown to reduce life 

expectancy 

IV antibiotics- can 

lead to resistance and super 

bugs etc 

infection 

treatment-related 

death-curative patients 

dying from toxicityunacceptable 

QOL 

hospitalisation-(often 

poor venous access- can 

define choice regarding 

further treatment) 

hospital 

acquired infection 

social isolation 

feeling unwell 

fatigue 

stress 

Economic 

hospitalisation 

costs 

costs of additional 

care 

ability to work 

# &69

Impact on chemotherapy 

delivery: 

Dose delays and reductions 

Dose reductions of ≥ 15% in 

40% 

of patients 

Dose delay of 

≥ 7 days in 24% 

of patients 

53% of patients received < 85% of the minimum 6-cycle 

treatment * 

Neutropenia: the leading cause of dose delays 

and reductions 

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Delivering planned chemotherapy dose on 

time improves outcomes in early-stage breast 

cancer 

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Summary 

 

 

 

 

Neutropenia is a common and serious complication of 

anti-cancer therapy: 

– infections may first be reported when they are already life- 

threatening, due to lack of symptoms 

– highest risk of infection is during the nadir period 

– Newer chemotherapeutic drugs are less predictable than older 

agents 

– duration and severity of neutropenia increase risk of FN 

Neutropenia is the most common reason for reduced 

and delayed chemotherapy 

FN is life-threatening 

Neutropenia and infection: 

– Reduce patient QoL 

– Increase cost of treatment and cost to society

Assessing risk and preventing 

neutropenic complications 

Identify high 

risk patients 

Employ 

preventive 

strategies 

Prevent FN 

Achieve full 

dose on time 

• G-CSF prophylaxis 

• Ongoing assessment 

• Education 

The 

obstacles 

- Guidelines identify 

high risk patients but 

are not always 

incorporated into 

clinical practice. 

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Risk factors for FN 

Treatmentrelated 

risk 

Patient-related 

and other risks 

FN risk 

• High > 20% 

• Medium 10 20% 

• Low < 10% 

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Chemotherapy regimens with moderate 

to high risk of febrile neutropenia (FN) 

Regimen 

Risk of FN 

Breast cancer 

Paclitaxel AC > 20% 

Doxorubicin/Paclitaxel > 20% 

Docetaxel 10 – 20% 

Non-Hodgkin Lymphoma 

CHOP-21 > 20% 

CHOP-21 + R 10 – 20% 

Non-small cell lung cancer 

Docetaxel/Carboplatin > 20% 

Paclitaxel/Cisplatin 10 – 20% 

Ovarian cancer 

Docetaxel > 20% 

Topotecan 10 – 20% 

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Patient-related and other 

risk factors for FN 

Age > 65 

– Twice as likely to experience febrile neutropenia 1 

– Prophylactic G-CSF G 

should be used in all elderly 

patients receiving myelotoxic chemotherapy 2 

 

Other factors 

– Advanced disease stage 

– Previous episode of FN 

– Lack of G-CSF G 

use 

 

4( & 8$ & Aapro et al, 2006

Role of nurses in evaluating 

patient risk 

Assess the FN risk of planned 

chemotherapy regimen 

Evaluate presence of individual 

patient risk factors 

Evaluate overall risk 

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Granulocyte colony-stimulating factor 

(G-CSF) and neutrophil production 

Endogenous G-CSF 

324" 234" 34" 

Stem cells 

Neutrophil 

progenitors 

Precursor 

cells 

Post-mitotic 

cells 

Response is greater and 

more rapid than seen with 

endogenous 

G-CSF alone 

Therapeutic G-CSF 

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G-CSF reduces FN incidence 

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Side effects of G-CSFsG 

 

 

Mild/moderate medullary bone pain 

– most common side effect attributed to G-CSFsG 

– refer to individual product label for prevalence 

– successfully treated with mild analgesics 

Other side effects have been reported at varying levels 

and tend to be: 

– nausea, fatigue, alopecia, vomiting, headache 

– equally reported in placebo and treatment groups 

hence are probably associated with the chemotherapy 

itself 

A preventable death part 1

Febrile neutropenia 

Managing febrile neutropenic 

episodes in patients with cancer

Definition of Febrile neutropenia 

or Neutropenic fever 

 

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The impact of infection in 

patients with cancer 

Severe sepsis 

 

 

 

 

 

9.8% higher risk for sepsis than 

non-cancer patients 

Incidence higher in haematological 

malignancies 

Hospital mortality is higher 

Accounts for up to 10% of cancer 

deaths ( local data) 

Accounts for 4.9% of cancer 

hospitalisations but 14% of costs 

Implications for 

management of FN 

Implications for 

prevention of FN 

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SIRS 

Sepsis 

Systemic Inflammatory Response Syndrome 

(SIRS), the body’s response to a variety of 

severe clinical insults which may not be 

infection 

Systemic inflammatory response to infection 

 

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Sepsis with acute organ dysfunction or 

hypoperfusion, or hypotension 1 

A subset of severe sepsis with hypotension 

despite adequate fluid resuscitation along 

with the presence of perfusion 

abnormalities that may include lactic 

acidosis, oliguria, or alteration of mental 

status 1 

 

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Vital signs of SIRS 

 

Two or more of the following symptoms 

– Temperature > 38 o C or < 36 o C 

– Heart rate > 90 beats/min 

– Respiratory rate > 20 breaths/min or 

PaCO 2 < 32 mm Hg 

– WBC > 12 x 10 9 /L, < 4 x 10 9 /L or 

> 10% immature forms 

– Lowered blood pressure 

This will not delineate between SIRS and sepsis 

: ++2

Careful patient assessment is 

important 

 

Signs of infection are not always obvious 

– Temperature 38.3 °C C and ANC < 500 cells/mm 3 clearly 

indicate febrile neutropenia 

 

Some signs can indicate that patients should be checked and 

hospitalised: 

– Chills/shaking in bed 

– Feeling unwell/different (without clear explanation) 

– Changes in behaviour 

– Feeling faint/changes in skin tone 

Patients should be hospitalised as soon as possible 

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Clinical pathway to manage 

neutropenic complications 

Determine and document patient’s history 

Take Full Blood film, Culture sputum, urine, all lumens of CVC, 

peripheral blood and other suspected sources of infection 

•Obtain a chest X-ray 

Administer empiric antibiotics, gram -ve and 

+ve, until source organism is identified 

Monitor blood culture reports daily 

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Patient group 

Patients without features of systemic compromise 

(Beta-lactam monotherapy is recommended unless allergy to the 

recommended agent/s) 

Recommendation (grading and level of evidence) 

No penicillin allergy: 

Piperacillin-tazobactam 4.5 g IV 6–8 hourly (grade A) OR 

Cefepime 2 g IV 8 hourly 

Other reasonable choice for monotherapy is ceftazidime 2 g IV 8 hourly (grade 

A) 

Non-life threatening penicillin allergy (rash): 

Cefepime 2 g IV 8 hourly (grade C) 

Other reasonable choices for monotherapy are ceftazidime 2 g IV 8 hourly or 

meropenem 1 g IV 8 hourly (grade C) 

Life-threatening (immediate) penicillin allergy or beta-lactam allergy: 

Aztreonam 1-2 g IV 8 hourly OR ciprofloxacin 400 mg IV 12 hourly (expert 

opinion) 

+ vancomycin 1.5 g IV 12 hourly (if CrCl >90 mL/min) OR 1 g IV 12 hourly (if 

CrCl 60-90 mL/min)†* 

Patients with systemic compromise (The combination of a 

beta-lactam antibiotic with an aminoglycoside is the regimen of 

choice) 

Patients with cellulitis, obviously infected vascular devices, or 

MRSA carriers with extensive skin breaks/desquamation 

As for patients without features of systemic compromise (expert opinion) 

(see above): 

+ gentamicin 5 to 7 mg/kg ideal body weight IV once daily, adjusted to level 

+/– vancomycin 1.5 g IV 12 hourly (if CrCl >90 mL/min) OR 1 g IV 12 hourly (if 


As for patients without features of systemic compromise (see above): 

+ vancomycin 1.5 g IV 12 hourly (if CrCl >90 mL/min) OR 1 g IV 12 hourly (if 


Patients with features of abdominal or perineal infection 

As for patients without features of systemic compromise (see above): 

+ metronidazole 500 mg IV/PO 12 hourly if receiving cefepime, ceftazidime or 

ciprofloxacin first-line (grade D) 

Alternatively, piperacillin-tazobactam or meropenem will provide adequate 

anaerobic cover, if required (grade B) other than for suspected or proven 

Clostridium difficile-associated diarrhoea or colitis

The goal is to minimise risk of 

infections and complications 

 

 

 

 

 

Increase vigilance 

Intervene to eliminate risk factors 

Correct preparation of invasive procedures 

Minimise exposure to infection and bacteria 

– Hand hygiene 

– Protective isolation is not considered necessary 

however protection from the general population in an 

ED setting is preferred. 

Educate patients and their families about how to minimise 

their risk 

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Minimising exposure to 

infection and bacteria 

 

 

Hand washing 1 

– Use alcohol wash 

– Use correct hand washing protocol 

– Educate patients about hand washing 

Protective isolation 

Protective isolation is costly, is psychologically distressing for 

patients, and remains controversial 3 

– Consider Low bacterial diet 

– HEPA-filtered rooms or LAF rooms filter bacteria from the 

air 2- 

– Restrict visitors 

 

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Patient and family education: 

Focus on prevention/reduction 

 

Nurses play a key role in educating patients and their families 

about neutropenia and FN 

 

Patients need to know 

– How to avoid infection 

– How to monitor for and report infection 

– When to seek medical care 

– How to balance family life with reducing risk 

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A preventable death 

Part 2

Summary 

 

 

 

 

Febrile Neutropenia is a medical emergency 

Febrile neutropenia has a significant impact on morbidity and mortality 

Treating febrile neutropenia is associated with high healthcare costs 

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Management of febrile neutropenia requires 

– Continuous monitoring 

– The prompt removal of the source of infection 

Local antimicrobial strategies will apply 

Effective hand washing is the most important intervention

Febrile Neutropenia

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