NEUTROPENIC

SEPSIS

GATHER THE FACTS …NOT JUST THE

FIGURES

Mary Kelly
ANP Haematology
Midland Regional Hospitals
CASE STUDY: PAUL

BACKGROUND
• 66 yr Male attended with wife Ann Medications
• Referred with lymphadenopathy inguinal
•Methotrexate once weekly
• No B symptoms
•Hydroxychloroquine od

PMH •Omeprazole 40mg

• RA
• Barrett's oesophagus Work-up / diagnosis

CT- mesenteric, para-arotic and inguinal nodes

Biopsy –

Diffuse Large B Cell Lymphoma

TREATMENT

TREATMENT BASELINE BLOODS

• Stop RA medications Hb 15.0

WBC 6.1
• Commence Prophylactic medications
(valaciclovir & co trimoxazole)

• Combination chemotherapy Plts 305

R-CHOP x 6 + Day 8 Rituximab with # 1&2
Neuts 3.2
• GCSF 24 hrs post chemotherapy R-CHOP – Rituximab, cyclophosamide, doxorubicin, vincristine and
prednisolone

GCSF- granulocyte-colony stimulating factor – stimmulates the B< to produce

granulocytes and stem cells and release them into the bloodstream.
DAY 8

NEUTROPENIC CLINICAL SUSPICION

MILD THROMBOCYTOPENIA OF INFECTION
• Attended with wife Anne
for day 8 Rituximab
MANAGEMENT

• Expected response to chemotherapy Discharged with advice on

•Signs and symptoms of infection
• No evidence of infection •Thermometer
•Contact details
• Has received GCSF •Report to A&E / Day unit if symptoms
develop

• Await Expected neutrophil recovery

• Review 2 days in Day unit
DAY 10

DAY UNIT REVIEW

Apyrexial
Hb 14.8
WBC 3.7
No signs / symptoms of infection
Plts 139
Tolerating chemotherapy well Neuts 1.29
NEUTROPHILS - “SOLDIERS OF INNATE
IMMUNE SYSTEM”
• Very abundant -60%
Of the immune cells

• Heavily armed-
antimicrobial effectors damage
& kill in different ways

• First responders –
frontline migrate to site of infection
• Ingest and kill microorganisms
• Mainly against bacterial and fungal infection
NEUTROPENIA

• Neutropenia – An abnormal decrease in the number of neutrophils

in the blood.

• Neutropenia is associated with a profound impairment in the

inflammatory response, leading to a lack or minimisation of the usual
signs and symptoms of infection.
NEUTROPENIA
• An abnormal decrease in the number of neutrophils in the
blood. Neutropenia is associated with a profound impairment
in the inflammatory response, leading to a lack or
minimisation of the usual signs and symptoms of infection.

Neutropenia is a common problem in oncology patients either

following chemotherapy, or less commonly secondary to
radiation treatment or marrow infiltration by malignancy.

Neutropenia is most likely to occur 10-14 days post

chemotherapy but should remain a consideration after this
period.
CAUSES OF NEUTROPENIA
Congenital Acquired
Constitutional Neutropenia Infection-associated

Risk of infection varies depending on Ethnic Post infectious

Benign Familial Active infections- sepsis ,
• Level of neutropenia viruses
Cyclical Drug induced
• Context in which occurs
Autoimmune
Primary
Secondary
Felty syndrome
Chronic – no of neutrophils
Malignancy
decreased
Acute leukaemia
No decrease in functionality LGL, Leukaemia
MDS
VS Myeloma, Lymphoma

Sepsis induced neutropenia caused Myelophthisic processes

by the consumption of neutrophils Dietary

from the overwhelming infection B12 deficiency
Copper deficiency
Global Caloric malnutrition
CANCER PATIENTS- HIGH RISK GROUP

• Febrile neutropenia – common

• Presentation may be non specific

• SIRS may not be present

• Patients receiving anticancer treatment who present unwell & at risk of

neutropenia are treated as sepsis until proven otherwise.
CHEMOTHERAPY PATIENTS

• All infective episodes must be • Fungal infections occur after

treated seriously pt has received broad
spectrum antibiotics or
• 50-60% of febrile neutropenic prolonged neutropenia
pts will prove to have infection

• 16-20% with ANC 0.1 x 109/L

will have bacteriaemia
CHALLENGES FOR HAEMATOLOGY
PATIENTS
• Disease features –
hypogammaglobulinaemia
• Complex treatment regimes
• Age
• Protracted treatment
• Many become chronic
VS
• Outpatient regimes – oral just as
toxic as IV
• Drugs associated with
neutropenia e.g. lenalidomide
• Clinical trials
FEBRILE NEUTROPENIA

• Patient has a fever and a significant reduction in

their neutrophil counts.
• The fever may be caused by an infectious agent,
and when it is, prompt treatment is required.

• Needs assessment- possible source, type of

infection and treatment until the cause is found or
it subsides.
• The risk of infection increases directly in
proportion to the degree of neutropenia and its
duration.
CASE STUDY 2 – MARY
BACKGROUND
• 79 yr – female
• MDS -2013
• Azacitidine x 31 cycles
• Progressed to AML – April
• Pancytopenia
• Symptom support
PMH
Ischaemic cardiomyopathy
Osteoarthritis
High cholesterol
•Medications
•Co-trimoxazole 480mg OD
•Valacliclovir 500mg OD
•Transemic Acid 1g TDS
MANAGEMENT

INFORMATION,
SUPPORT & TRAINING
• Partnership with patient, family and MDT

Hb 8.5
Education and advice on:

•
Disease

Complications
WBC 1.1
•

•
Signs and symptoms to report

QOL
Plts 8
Neut 0.12
• Psychological care

• Palliative care

• Support networks

• Contacts
 SEPT 2ND

SYMPTOMS
Phoned ANP

Feeling unwell

Shivers

Hot, red & swollen left hand

Attended A&E

History & Physical

Septic screen

DIAGNOSIS – CELLULITIS @
PREVIOUS IV CANNULA SITE
 IF  YES THIS IS SEPSIS

TIME ZERO:
TAKE 3 SEPSIS SIX - aim to complete within 1 hour GIVE 3

Blood cultures: Take before giving antimicrobials (if no Oxygen: Titrate O2 to saturation of 94-98% or

significant delay i.e. > 45 minutes) and other cultures 88 – 92% in chronic lung disease
as per examination. IV Fluids: Start IV fluids resuscitation if evidence
Bloods: Check point of care lactate & full blood count.  of hypovolaemia. 500ml bolus of isotonic

Other tests and investigations as per history and crystalloid over 15 mins & give up to 30ml/kg
examination. Consider source control. reassess ing for signs of hypovolaemia,
Urine output measurement: Assess urine output and euvolaemia, or over load
consider urinary catheterisation for accurate Antimicrobials: Give IV antimicrobials

measurement in severe sepsis/septic shock. according to the site of infection and following
 local antimicrobial guidelines.
Type: Dose: Time Given:
Laboratory tests must be requested as EMERGENCY aiming to have results available and reviewed within the hour.
OUTCOME

ADDITIONAL
MEASURES OUTCOME
Cellulitis resolved

Inpatient x 8/7

Oral antibiotic on D/C

Apyrexial Day 2

Discharged with advice on

IVAB x 7 days •Signs and symptoms of infection

•Thermometer

Platelet transfusion •Contact details

•Report to A&E / Day unit if symptoms develop

NEUTROPENIC SEPSIS

Medical emergency

•Diagnosed in patients having anti-cancer treatment

who present unwell with a neutrophil count 0.5 x 109
or lower, or less than 1 x 109 with a downward trend.

•Sepsis is a life-threatening condition that

occurs when the body's response to an
infection damages its own tissues and organs

Patients with Neutropenic sepsis will not necessarily

have a fever
SEVERITY OF NEUTROPENIA

ANC Risk of infection

Normal
1.5 (2.0)– 8 x 109/L

Mild Mild
< 1.5 x 109/L but >1.0 x 109/L

Moderate Moderate
< 1.0 x 109/L but <0.5 x 109/L

Severe Severe
< 0.5 but >0.2 x 10 9/L with
predicted decrease to <0.5 x 10 9/L

and fever >38 degrees

Febrile Severe
< 0.5 but >0.2 x 10 9/L with
predicted decrease to <0.5 x 10 9/L

and fever >38 degrees

CASE STUDY 3- JOHN

BACKGROUND MEDICATIONS
•Valciclovir 500mg od

• 68 yr old male •Dapsone 100mg od

•Metroclopramide 10mg TDS

• Multiple relapses of CLL •Alloporinol 300mg od

•Esomeprazole 40mg od

• •GCSF 48 million units S/C daily

Richters transformation

Chemotherapy protocol

Combination chemotherapy
R-ESHAP
 A&E PRESENTATION

BACKGROUND

•Unwell
•Temp 38. 5
•Rigours

Hb •Facial swelling
9.7
WBC 4.0
Plts 15
Neuts 0.06
 IF  YES THIS IS SEPSIS

TIME ZERO:
TAKE 3 SEPSIS SIX - aim to complete within 1 hour GIVE 3

Blood cultures: Take before giving antimicrobials (if no Oxygen: Titrate O2 to saturation of 94-98% or

significant delay i.e. > 45 minutes) and other cultures 88 – 92% in chronic lung disease
as per examination. IV Fluids: Start IV fluids resuscitation if evidence
Bloods: Check point of care lactate & full blood count.  of hypovolaemia. 500ml bolus of isotonic

Other tests and investigations as per history and crystalloid over 15 mins & give up to 30ml/kg
examination. Consider source control. reassess ing for signs of hypovolaemia,
Urine output measurement: Assess urine output and euvolaemia, or over load
consider urinary catheterisation for accurate Antimicrobials: Give IV antimicrobials

measurement in severe sepsis/septic shock. according to the site of infection and following
 local antimicrobial guidelines.
Type: Dose: Time Given:
Laboratory tests must be requested as EMERGENCY aiming to have results available and reviewed within the hour.
DIAGNOSTIC
INVESTIGATIONS
REVEALED
SINUSITIS
DAY 5 - PNEUMONIA
ON-GOING MANAGEMENT AS
INPATIENT
• IVAB & Antifungal
• Apyrexial after 21 days
• Remains profoundly Neutropenic
• At risk of further infections and septic shock
• Unsuitable for further chemotherapy
• Disease progression
• Supportive care
• Palliative care
• Prognosis poor
COMMON SOURCES OF SEPSIS
Site
Respiratory 38%
Urinary tract 21%
Intra-abdominal 16.5%
Cather Related Blood 2.3%
Stream Infection
Devices 1.3%
CNS 0.8%
Others e.g. cellulitis 11.3%
RISK OF SEPTIC SHOCK WITH
NEUTROPENIA
High Risk Patients Low Risk Patients
•Inpatient at the time of developing •Outpatient at the time of developing
fever fever
•Significant medical co-morbidities or •No associated acute co morbid illness
clinically unstable •Anticipated short duration of
•Anticipated prolonged severe neutropenia
neutropenia •Good performance status
•Hepatic insufficiency •No hepatic or renal insufficiencies
•Renal insufficiency
•Uncontrolled/progressive cancer
•Pneumonia or other complex
infection
•Mucositis grade 3-4
LOOK FOR SIGNS OF ORGAN
DYSFUNCTION
Look for signs of organ dysfunction
 Systolic BP < 90 or Mean Arterial Pressure < 65 or Systolic BP
more than 40 below patient’s normal
 New need for oxygen to achieve saturation > 90%
 Lactate > 2 mmol/L (following administration of fluid bolus)
 Urine output < 0.5ml/kg for 2 hours – despite adequate fluid
resuscitation
 Acutely altered mental status
 Glucose > 7.7 mmol/L (in the absence of diabetes)
 Creatinine > 177 micromol/L
 Bilirubin > 70 micromol/L
 PTR > 1.5 or aPTT > 60s
Platelets < 100 x 109/L
Any new organ dysfunction
Inform Registrar or Consultant immediately. Reassess frequently in 1st hour.
Consider other investigations and management +/- source control if patient
does not respond to initial therapy as evidenced by haemodynamic
stabilisation then improvement.
 SIGNS OF SEPTIC SHOCK
Look for signs of septic shock
(following administration of fluid bolus)
Lactate > 4 mmol/L
Hypotensive (Systolic BP < 90 or MAP < 65)
If either present:
Critical care consult required
 Consultant referral
 Consider transfer to a higher level of care
 Critical care consult requested
A critical care consult may be requested at any point during this
assessment, but is required for patients with Septic Shock. In a
hospital with no critical care unit, a critical care consult should be
made and transfer to a higher level of care, if appropriate,
following the consult.
FACTS…..

HISTORY PHYSICAL
Symptoms point to source of infection • Signs of infection

e.g. cough, skin, dysuria,hickman line, skin, mouth, ENT, GU • Respiratory

symptoms, diarrhoea
• Hickman line site

• Skin
Co morbidities
• Abdominal
Treatment history
• CNS
Cancer diagnosis, stage, prior treatment,date of last treatment
• Oral cavity

Drug history
• Do not perform a PR- may cause additional sepsis in neutropenic
•Antibiotics, no of days since chemo, drugs that cause neutropenia pt
FIGURES ….

INVESTIGATIONS MDT
• Bloods & blood cultures • Medical
• Vitals • Nursing
• Urinalysis • Laboratory
• CXR • Microbiologist
• CT etc • Critical care consultant
• Input / output etc
MANAGEMENT- MAXIMISE
SURVIVAL, MINIMISE BURDEN

• Team based approach

• Critical 1st hour
• ISBAR
• Sepsis identified – complete Sepsis 6
• Severe sepsis/septic shock registrar
or higher
• Time dependent medical emergency
• Critical care consult
 ANTIBIOTICS
• Backbone of Neutropenic sepsis management

• Piperacillin tazobactam- gram neg e.g. E coli,

pneumonias
• Gentamicin

• Add other antibiotics based on other factors

e.g. indwelling catheter, CVAD’s etc

• Refer to Own hospital policy

• Review regularly with microbiology in light

of resistance patterns
PREVENTIVE MEASURES

• Prophylactic antibiotics dictated by chemotherapy protocols Standard – specific for PCP

and Herpes Virus's
• Antifungal prophylaxis for patients with protracted neutropenia e.g. Leukaemia,
transplant

• Vaccinations-Flu, pneumonia, Hib

• IVIG

• GCSF – as part of chemotherapy management selected regimes e.g. lymphoma

protocols or to treat Neutropenic episode
INFORMATION, SUPPORT &
TRAINING • Patient chemotherapy consent

• Chemotherapy counselling with patient & family

• Before & throughout treatment

• Important to consider Social supports as

will influence management

• Advice re Specific -drugs, side effects

Neutropenic diet
• What are rigours?
• How to use thermometer?
• Avoid anti-pyrexia medications
• You may not develop fever.
• Ancillary medications
TRAINING

• Healthcare professionals & staff who come in contact with

patients having anticancer treatment should be provided
with training n neutropenic sepis.

• Training should be tailored according to the type of contact.

NICE clinical guideline 151 (2012)

NEW TOOLS – THINK SEPSIS
 COMMUNICATION – WHERE CAN
I GET HELP?
Good communication
between patient &
& HCP important

Good communication
Between MDT essential

How & when to seek emergency care

CLINICAL GUIDELINES

• Improve health care outcomes

• Reduce variations in practice
• Improve quality of clinical decisions

• www.hse.ie/sepsis
 CONCLUSIONS
• Case studies represent cases of neutropenia
from mild to severe
• Improtant to establish the facts and not just
the figures
• Patients receiving chemotherapy are at risk of Neutropenic
sepsis Neutropenia
fever
• Prompt treatment essential
• Chemotherapy patients must be fast tracked
• Not all patients will have fever
• When in doubt Always assume pt is high risk
of neutropenic sepsis
• Education of pt/family is essential – what/
when to report Neutropenic
• Follow sepsis 6 = reduces risk of death sepsis
• Unwell & Neutropenic must cover with
antibiotic even if no source of infection
found
PERSONAL CONCLUSIONS

• Welcome focus on Neutropenia

• Improve patient experience, minimise burden and maximise
health
• Tools focus on key priorities – education and training
• New to me - Lactate
• On-going History & Physical
• Education and support
Thanks to Dr G. Crotty , Nursing colleagues MRHT &
Michelle Connolly CNM11 Clinical Trials