Transcript Sepsis

Neutropenic
Sepsis
Gather the facts …not just the figures
Mary Kelly
ANP Haematology
Midland Regional Hospitals
Machiavelli (1513)
• “ as the physician says it
happens in hectic fever, that
in the beginning malady it is
easy to cure but difficult to
detect, but in the course of
time, not having been either
detected or treated in the
beginning, it becomes easy
to detect but difficult to
cure”
Case study: Paul
Background
• 66 yr Male attended with
wife Ann
• Referred with
lymphadenopathy inguinal
• No B symptoms
PMH
• RA
• Barrett's oesophagus
Medications
• Methotrexate once weekly
• Hydroxychloroquine od
• Omeprazole 40mg
Work-up / diagnosis
CT- mesenteric, para-arotic and
inguinal nodes
Biopsy –
Diffuse Large B Cell Lymphoma
Treatment
Treatment
• Stop RA medications
• Commence Prophylactic
medications (valaciclovir & co
trimoxazole)
• Combination chemotherapy
R-CHOP x 6 + Day 8 Rituximab
with # 1&2
• GCSF 24 hrs post
chemotherapy
Baseline bloods
Hb
WBC
Plts
Neuts
15.0
6.1
305
3.2
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
Mild thrombocytopenia
• Attended with wife Anne for
day 8 Rituximab
Clinical suspicion of Infection
Management
• Expected response to
chemotherapy
• No evidence of infection
• Has received GCSF
• Await Expected neutrophil
recovery
• Review 2 days in Day unit
Discharged with advice on
• Signs and symptoms of
infection
• Thermometer
• Contact details
• Report to A&E / Day unit if
symptoms develop
Day 10
Day unit review
Apyrexial
No signs / symptoms of
infection
Tolerating chemotherapy well
Hb
WBC
Plts
Neuts
14.8
3.7
139
1.29
Neutrophils - “Soldiers of innate
immune system”
• Very abundant -60%
Of the immune cells
• Heavily armedantimicrobial 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
Risk of infection varies depending
on
• Level of neutropenia
• Context in which occurs
Chronic – no of neutrophils
decreased
No decrease in functionality
VS
Sepsis induced neutropenia
caused by the consumption of
neutrophils from the
overwhelming infection
Congenital
Acquired
Constitutional Neutropenia
Infection-associated
Ethnic
Post infectious
Benign Familial
Active infections- sepsis , viruses
Cyclical
Drug induced
Autoimmune
Primary
Secondary
Felty syndrome
Malignancy
Acute leukaemia
LGL, Leukaemia
MDS
Myeloma, Lymphoma
Myelophthisic processes
Dietary
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 treated seriously
• 50-60% of febrile
neutropenic pts will prove
to have infection
• 16-20% with ANC 0.1 x
109/L will have
bacteriaemia
• Fungal infections occur after
pt has received broad
spectrum antibiotics or
prolonged neutropenia
Challenges for haematology patients
• Disease features –
hypogammaglobulinaemia
• Complex treatment regimes
• Age
• Protracted treatment
• Many become chronic
• Outpatient regimes – oral
just as toxic as IV
• Drugs associated with
neutropenia e.g.
lenalidomide
• Clinical trials
VS
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
Education and advice on:
• Disease
• Complications
• Signs and symptoms to report
• QOL
• Psychological care
• Palliative care
• Support networks
• Contacts
Hb
WBC
Plts
Neut
8.5
1.1
8
0.12
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
Blood cultures: Take before giving antimicrobials (if no

significant delay i.e. > 45 minutes) and other cultures

IV Fluids: Start IV fluids resuscitation if evidence

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

Oxygen: Titrate O2 to saturation of 94-98% or 88
– 92% in chronic lung disease
as per examination.
Bloods: Check point of care lactate & full blood count.
GIVE 3
euvolaemia, or over load
consider urinary catheterisation for accurate
Antimicrobials: Give IV antimicrobials according
measurement in severe sepsis/septic shock.
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
Apyrexial Day 2
IVAB x 7 days
Platelet transfusion
Oral antibiotic on D/C
Discharged with advice on
• Signs and symptoms of infection
• Thermometer
• 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
< 1.5 x 109/L but >1.0 x 109/L
Mild
Moderate
< 1.0 x 109/L but <0.5 x 109/L
Moderate
Severe
< 0.5 but >0.2 x 109/L with
Severe
predicted decrease to <0.5 x 109/L
and fever >38 degrees
Febrile
< 0.5 but >0.2 x 109/L with
predicted decrease to <0.5 x 109/L
and fever >38 degrees
Severe
Case study 3- John
Background
• 68 yr old male
• Multiple relapses of CLL
• Richters transformation
Medications
•
•
•
•
•
•
Valciclovir 500mg od
Dapsone 100mg od
Metroclopramide 10mg TDS
Alloporinol 300mg od
Esomeprazole 40mg od
GCSF 48 million units S/C daily
Chemotherapy protocol
Combination chemotherapy
R-ESHAP
A&E presentation
Background
•
•
•
•
Unwell
Temp 38. 5
Rigours
Facial swelling
Hb
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
Blood cultures: Take before giving antimicrobials (if no

significant delay i.e. > 45 minutes) and other cultures

IV Fluids: Start IV fluids resuscitation if evidence

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

Oxygen: Titrate O2 to saturation of 94-98% or 88
– 92% in chronic lung disease
as per examination.
Bloods: Check point of care lactate & full blood count.
GIVE 3
euvolaemia, or over load
consider urinary catheterisation for accurate
Antimicrobials: Give IV antimicrobials according
measurement in severe sepsis/septic shock.
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
Stream Infection
2.3%
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
fever
•Significant medical co-morbidities or
clinically unstable
•Anticipated prolonged severe
neutropenia
•Hepatic insufficiency
•Renal insufficiency
•Uncontrolled/progressive cancer
•Pneumonia or other complex
infection
•Mucositis grade 3-4
•Outpatient at the time of developing
fever
•No associated acute co morbid
illness
•Anticipated short duration of
neutropenia
•Good performance status
•No hepatic or renal insufficiencies
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
 e.g. cough, skin, dysuria,hickman
line, skin, mouth, ENT, GU
symptoms, diarrhoea
•
•
•
•
•
•
•
 Co morbidities
 Treatment history
 Cancer diagnosis, stage, prior
treatment,date of last treatment
Drug history
• Antibiotics, no of days since chemo,
drugs that cause neutropenia
Signs of infection
Respiratory
Hickman line site
Skin
Abdominal
CNS
Oral cavity
• Do not perform a PR- may
cause additional sepsis in
neutropenic pt
Figures ….
Investigations
• Bloods & blood cultures
• Vitals
• Urinalysis
• CXR
• CT etc
• Input / output etc
MDT
• Medical
• Nursing
• Laboratory
• Microbiologist
• Critical care consultant
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
Contact details- 24hr 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 sepsis
• 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
• Follow sepsis 6 = reduces risk of death
• Unwell & Neutropenic must cover with
antibiotic even if no source of infection
found
Neutropenic
fever
Neutropenia
Neutropenic
sepsis
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