Dr Phil Haji-Michael, Director of Acute and Critical Care, The Christie Hospital

1. The Christie NHS Foundation Trust
Sepsis and Neutropenic Sepsis in
cancer patients
Phil Haji-Michael
The Christie
National Acute Oncology 2017 - Manchester

2. The Christie NHS Foundation Trust

3. The Christie NHS Foundation Trust
Mr Onc.
Mr Heam
PUS
FICTION
A film by Piperacillin Tarantino

4. The Christie NHS Foundation Trust

5. The Christie NHS Foundation Trust
Oncology sepsis - guidelines
• NCAT Acute Oncology Peer review
• “Door to Needle” time of 1 hour
• NICE CG151 (Neutropenic sepsis)
• No time, but early antibiotics
• NICE NG51 (Sepsis recognition, definition &
management)
• Little mention of antibiotics, risk stratification and early
clinical (ST3) review

6. The Christie NHS Foundation Trust
New Definitions
Traditional New
Sepsis Infection
Severe Sepsis Sepsis
(Moderate risk)
Septic Shock Sepsis
(High risk)

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Management of neutropenic sepsisin secondary and tertiary careManagement of neutropenic sepsisin secondary and tertiary care NICE Pathways
NICE CG 151 – Neutropenic sepsis
Temp above 38ºC
Neutrophil Count less than 0.5x109/l
Suspicion of a focus
A lot of attention towards low risk patients,
who are poorly described

8. The Christie NHS Foundation Trust
Person with possible infection
• Think ‘could this be sepsis?’ if they present with signs or symptoms that indicate infection, even if they do not have a high
temperature.
• Be aware that people with sepsis may have non-specific, non-localising presentations (for example, feeling very unwell.
• Pay particular attention to concerns expressed by the person and family/carer.
• Take particular care in the assessment of people who might have sepsis who are unable, or their parent/carer is unable, to give a good
history (for example, young children, people with English as a second language, people with communication problems)
ASSESSMENT
Assess people with suspected infection to identify:
• likely source of infection
• risk factors (see righthand box)
• Indicators of clinical of concern such as
abnormalities of behaviour, circulation or
respiration.
Healthcare professionals performing a remote
assessment of a person with suspected infection
should seek to identify factors that increase risk of
sepsis or indicators of clinical concern.
People more vulnerable to sepsis
• the very young (under 1 year) and older people (over 75 years) or very frail people
• recent trauma or surgery or invasive procedure (within the last 6 weeks)
• Impaired immunity due to illness or drugs (for example, people receiving steroids, chemotherapy or
immunosuppressants)
• Indwelling lines / catheters / intravenous drug misusers, any breach of skin integrity (for example, any cuts,
burns, blisters or skin infections).
If at risk of neutropenic sepsis - refer to secondary care
Additional risk factors for women who are pregnant or who have been pregnant, given birth, had a termination
or miscarriage within the past 6 weeks -gestational diabetes, diabetes or other co-morbidities; needed invasive
procedure such as caesarean section, forceps delivery, removal of retained products of conception, prolonged
rupture of membranes, close contract with someone with group A streptococcal infection, have continued vaginal
bleeding or an offensive vaginal discharge).
Stratify risk of severe illness and death from sepsis using algorithm appropriate to age and setting
SUSPECT SEPSIS
If sepsis is suspected, use a structured set of observations to assess people in a face-to-face setting.
Consider using early warning scores in hospital settings.
Parental or carer concern is important and should be acknowledged.
Sepsis not suspected
• no clinical cause for concern
• no risk factors.
Use clinical judgment to treat the
person, using NICE guidance relevant
to their diagnosis when available.
NICE NG51 - Sepsis

9. The Christie NHS Foundation Trust
Person with possible infection
• Think ‘could this be sepsis?’ if they present with signs or symptoms that indicate infection, even if they do not have a high
temperature.
• Be aware that people with sepsis may have non-specific, non-localising presentations (for example, feeling very unwell.
• Pay particular attention to concerns expressed by the person and family/carer.
• Take particular care in the assessment of people who might have sepsis who are unable, or their parent/carer is unable, to give a good
history (for example, young children, people with English as a second language, people with communication problems)
ASSESSMENT
Assess people with suspected infection to identify:
• likely source of infection
• risk factors (see righthand box)
• Indicators of clinical of concern such as
abnormalities of behaviour, circulation or
respiration.
Healthcare professionals performing a remote
assessment of a person with suspected infection
should seek to identify factors that increase risk of
sepsis or indicators of clinical concern.
People more vulnerable to sepsis
• the very young (under 1 year) and older people (over 75 years) or very frail people
• recent trauma or surgery or invasive procedure (within the last 6 weeks)
• Impaired immunity due to illness or drugs (for example, people receiving steroids, chemotherapy or
immunosuppressants)
• Indwelling lines / catheters / intravenous drug misusers, any breach of skin integrity (for example, any cuts,
burns, blisters or skin infections).
If at risk of neutropenic sepsis - refer to secondary care
Additional risk factors for women who are pregnant or who have been pregnant, given birth, had a termination
or miscarriage within the past 6 weeks -gestational diabetes, diabetes or other co-morbidities; needed invasive
procedure such as caesarean section, forceps delivery, removal of retained products of conception, prolonged
rupture of membranes, close contract with someone with group A streptococcal infection, have continued vaginal
bleeding or an offensive vaginal discharge).
Stratify risk of severe illness and death from sepsis using algorithm appropriate to age and setting
SUSPECT SEPSIS
If sepsis is suspected, use a structured set of observations to assess people in a face-to-face setting.
Consider using early warning scores in hospital settings.
Parental or carer concern is important and should be acknowledged.
Sepsis not suspected
• no clinical cause for concern
• no risk factors.
Use clinical judgment to treat the
person, using NICE guidance relevant
to their diagnosis when available.
NICE NG51 - Sepsis

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NICE NG51 - Sepsis

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Oncology sepsis - context
• SACT review of mortality within 30 days of
chemotherapy
• Infection control advice
• Microbiology advice & “stewardship”
• The press and “killer bugs”
• Perception that sepsis treatment is “basic care”
• Initiatives for reduction of healthcare associated infection
• RiCON - critical care network
• HII - High impact intervention
• “World Sepsis Day” 13/9
• Global Sepsis Alliance
• Sepsis Trust

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What works for sepsis?
• Removal of focus if possible
• Correct/appropriate antibiotic choice
• Early administration of antibiotics
• Early recognition of deterioration to enable
escalation of care

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General hospital mortality
from severe sepsis
Proportion (%) of admissions to ICU with severe
sepsis in the first 24 hours
Hospital mortality (%)
0
10
20
30
40
50
60
70
Age group (years)
%

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Sepsis/Infection outcomes in
Oncology
Neutropenic
n (71)
Non Neutropenic
n (210)
Mean length of stay,
days (SE)
6.9 (0.49) 5.0 (0.44)
% admission to
CCU (n)
2.8% (2) 1.9% (4)
30 day Mortality %
(n)
4.2% (3) 5.7% (12)

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Long term outcome from
Oncological Sepsis 2008
Proportionsurviving
Days following admission
Neutropenic sepsis
30 days- 93.7%
1 year- 58.2%
Non-Neutropenic sepsis
30 days- 92.5%
1 year- 47.6%

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Pathogens causing sepsis
• Only 60% of severe sepsis/septic shock cases are
associated with confirmed infection
• Disease progression is similar regardless of
causative organism
Gram negative
Gram positive
Fungal infection
Mixed bacterial
Other mixed
Unconfirmed
20%
19%
10%
45%
3% 3%

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Nosocomial infections
• Nosocomial infection and drug-resistant
pathogens are real and growing concerns
• multi-resistant Staphylococcus aureus
• vancomycin-resistant enterococci
• multi-drug resistant Gram-negative bacteria
• Clostridium Difficile
• At any one time, 9% (mean prevalence) of all
general in-patients have infection, acquired
following admission
• Microbial resistance increases the threat to
patients with nosocomial infection

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Other pathogens in oncology
sepsis
• Candida spp. are the most common fungal
pathogens associated with sepsis
• Candidaemia is associated with a high
mortality of 50%
• Viruses (e.g. RSV, influenza virus) or parasites
(e.g. malaria) may be associated with sepsis
• Specific Lymphoma/BMT risks for PCP, CMV,
Aspergillus
RSV: respiratory syncytial virus

20. The Christie NHS Foundation Trust
When does the clock
start ticking for sepsis?

21. The Christie NHS Foundation Trust
A non-specific clinical response including
>2 of the following:
As well as infection, SIRS can also be caused by
trauma, burns, pancreatitis and other insults
Old model of sepsis:
The disease continuum & SIRS
SepsisSIRSInfection
Severe
sepsis
Death
 Temperature >38oC or <36oC
 Heart rate >90 beats/min
 Respiratory rate >20/min
 White blood cell count >12,000/mm3 or
<4,000/mm3 or >10% immature neutrophils
SIRS: systemic inflammatory response syndrome

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Pathogenesis of Sepsis Organ Failure
Tissue injury
Microvascular
coagulation/
thrombosis
Organ
dysfunction
Death
Mitochondrial
dysfunction
Activation of
coagulation
Inhibition of
fibrinolysis
Endothelial
dysfunction
Tissue factor expression
Microvascular
flow
redistribution
Inflammation
Leucocyte activation
Anti-inflammatory
mediators
e.g. IL-10, IL-1ra receptor
antagonists
Pro-inflammatory
mediators
e.g. Tumour necrosis
factor, IL-1, IL-6, IL-8,
nitric oxide
Pathology Trigger
Host
responses

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Timing of antibiotics
Kumar, CCM 2006; 34

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0
20
40
60
80
100
0 1 2 3 4 5
%mortality
No. of organ failures
Hospital mortality of by number of organ
failures in septic patients admitted to ICU
Overall
Reason for admission
Past medical history

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“New” Sepsis - Diagnosis
• Suspicion – “could this be sepsis”
• Presentation suggestive of a focus
• Chest, skin, wound tenderness etc
• Presence of risk factors & risk stratification

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Sepsis Risk Factors
• Age ( < 1yr & > 75yr)
• Immune suppression
• Recent surgery
• Trauma
• Post partum
• Invasive lines/implants

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Managing risk
High Risk
• Objective change in
cognition
• RR ≥25
• HR ≥130
• Syst BP ≤90
• U/O ≤0.5ml/kg/hr
• Mottled skin/Cyanosis
• Non blanching rash
Medium Risk
• Identifiable focus
• History of behavior
change
• Impaired immunity
• Other Risk factor
• RR 20-24
• HR 90-130
• Syst BP 90-100
• Not P/U for >12hrs
• T <36°C

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Managing risk
High Risk (1 present)
• Immediate clinical review
by CT3/ST3/ANP
• Full set of bloods incl:
ABG, lactate, CRP, Blood
cultures
• i.v. antibiotics without
delay (<1hr from
presentation)
• Discuss with consultant
Medium Risk (2 present)
• Urgent review (<1hr) by
CT3/ST3/ANP
• Clinical review, take
bloods including ABG &
lactate
• Review status hourly if
cause unclear
• Consultant review <3hrs
for consideration of
antibiotics
If Lactate >4 and/or BP <90mmHg give immediate fluid
resuscitation and refer to Critical Care

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Natural history of Sepsis related
Organ Failure
Day of peak dysfunction
• Cardiovascular Day 0
• Respiratory Day 1
• Renal Day 2
• Coagulation Day 3
• Musculoskeletal Day 3-4
• GIT & Liver Day 5-7
• CNS Day 0-last to resolve

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Sepsis prodromal features
• Paroxysmal AF with no clear cause
• Failure to absorb food
• Nausea/vomiting
• Off meals
• Low grade encephalopathy
• GCS >14
• “he’s not himself…”

31. The Christie NHS Foundation Trust
Summary
• Oncology sepsis guidance is changing
• There is little difference between neutropenic
and non-neutropenic sepsis
• Effective treatment remains
• Early recognition
• Prompt appropriate antibiotics
• Early recognition of deterioration and
escalation if appropriate
• The main opportunity for the NHS is the
ambulatory care of low risk patients

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