Neutropenic Sepsis – Acute General Management and Support Ernie Marshall Macmillan Consultant in Medical Oncology Clatterbridge Centre for Oncology
Neutropenic Sepsis – Acute General Management and Support
Ernie MarshallMacmillan Consultant in Medical
OncologyClatterbridge Centre for Oncology
Who Am I ?
• I am– A Medical Oncologist (MCCN)– Site specialist and general remit– Awareness of FN issues across Centre/Unit– Awareness of FN issues at National level (as failed CI
for ORANGE Trial!)– Keen interest in reducing unnecessary hospital stays– Enthusiast for AO
• I am NOT:– Sepsis Expert – or reader of ITU weekly chronicle
Aims
• Overview & Background
• General Principles of management
• Risk Stratification
• Low risk strategies
• FN management in the real world
Why is FN important ?
• Remains a life threatening complication (5% in high risk but 1% in low risk)
• Compromise survival with dose delays, reductions
• FN is not going away– Significant increase in chemo use
– Remains an issue with new therapies
• Well recognised but poorly managed (NCEPOD)
• Increasing burden on DGHs
• Poor patient experience
• Limited high quality research
How Big a Problem?
• We don’t know• Limited data on incidence, mortality, LOS...• No recognised code: current hospital coding uses:
– A41.9 (sepsis)– D70.X (neutropenia)– Y43.3 (‘chemo-related)
• Predominantly Breast/Lung Cancer• Cancer Centre
– CCO audits : 100 over 6mths (4/week)– SWLCN 71 episodes over 3months (6/week)
• DGH data– SH&K FN and AOT Audit: 1-2 per week
Prevention strategies
• Prophylactic Antibiotics
• CSFs: FN risk > 20% in curative cancer where no other regimen available
• Decision to Treat– PT SELECTION
– CHEMO Protocol
NCEPOD:
86% palliative intent
‘20% of cases, decision to treat was assessed as inappropriate’
Background
• Fever ≥ 380C on 2 occasions AND neutrophilcount ≤ 0.5 x 109/l
• Duration in solid tumour 3-5days ( Acute Leukaemia:23-27days)
• 50% of febrile pts have clinically documented infection
Presentation
• Awareness
• Fever, non-specific symptoms
• Usually 7-14days post chemotherapy
• Mucosal damage, catheter-related
• May present with no fever, confusion, (steroids, overwhelming infection)
Investigations
• Immediate FBC and differential
• Urea, creatinine, electrolytes
• Blood cultures– <10% positive*
• Routine cultures unhelpful
• CXR (chest symptoms/signs)
• C –Reactive Protein not routine
• IL-6/IL-8 investigational
Risk Assessment
• Underlying Disease
• Patient Fitness
• Age
• Outpatient episode
• Peak temperature
• Hypotension
• Neutrophil count
• Focus of infection
• Comorbidity
• Duration of neutropenia
• Controlled malignancy
• Fungus
• Gram negative
• Talcot Risk Index*
Multinational Association of Supportive Care in Cancer Risk Index (MASCC)
Characteristics Score
Burden of Illness
no/mild symptoms 5
moderate symptoms 3
No hypotension 5
No COPD 4
Solid tumour/lymphoma 4
No dehydration 3
Outpatient 3
Age over 60yrs 2
Maximum theoretical score is 26:
A score ≥21 denotes low risk
Optimal FN ManagementTemp >38.5 and ANC < 0.5
Prompt assessment & Resuscitation
Calculate MASCC Risk Index
High Risk Low Risk
Antibiotic Protocols
Investigations
High Risk Patients & Sepsis Bundles (www.severesepsis.org)
Job 1: Blood Cultures; FBC U&E
Job 2: Antibiotics
Job 3: Fluid ResuscitationSystolic BP < 90 and/or HR > systolic BP
Job 4: ECGJob 6: Monitor blood glucose
Job 5: Check serum lactate
CVP monitoring and Ventilation
Drug Therapy• Which Antibiotic?
– Beta lactam and aminoglycoside– Monotherapy– Vancomycin only in high risk gram positive
• Time to modification– 72hours or clinical deterioration– Duration of Abs not defined
• Anti-fungals– Rarely required, consider if persistent fever 4-6days
• Growth Factors– Therapy: routine cases not required
Aims and Endpoints?
• Primary Success (response and mortality)– Time to treatment
– Optimal antibiotic (s)
• Secondary Success (benefit)– length of stay
– Toxicity
– Cost
– Quality of life & patient experience
– Hospital acquired infection
Low Risk Strategies
Inpatient Care• Low dose Monotherapy• ‘Step down’ policies
– POCs
• Inpatient oral combination• Inpatient oral monotherapy
– EORTC 46001 moxifloxacin vs co-amoxyclav/Cipro
• Early discharge policiesOutpatient Care• Outpatient parenteral antibiotics• Outpatient oral antibiotics
Inpatient Oral Antibiotics
• 2 International randomised trials*
• Systematic review & metaanalysis (15)
• Low risk inpatients
• Oral co-amoxyclav & ciprofloxacin vs iv standard
• RR, duration of antibiotics and smc rate: equivalence
Freifeld et al NEJM, 1999
Kern et al NEJM, 1999
Vidal et al, J of Antimicro. Chem, 2004
UK Audit of managementInnes et al BJC 2005
• 128 Clinicians from 50 Cancer Departments
• 22% use oral antibiotics from outset
• 38% stratify but variable risk indices
• 51 % of stratifiers use oral antibiotics vs 4% not (p< 0.0001)
• Phillips et al 2007: UK Childrens Cancer Study Group survey: Wide variation in all aspects of care
CCO Experience
• Single Centre oral versus iv trial & sequential audits (1997-)
• Findings (Innes et al 2003, 2008)– Routine clerking proforma incorporating MASCC index
– Majority are low risk patients
– Oral antibiotics safe and effective
– Median duration of stay: Reduced to 2days
– 50% cost savings and reduced nursing time (GRASP)
Do all patients need Antibiotics!Nijhuis et al JCO: 2005
• 36/196 Low risk episodes (clinical and IL-8)
• Standard FN definition
• Median ANC 0.08
• Blood culture negative
• No antibiotics
• Hospitalised until afebrile > 12hrs
• Daily telephone contact
• No episodes of deterioration or readmissions
The Real World
The ORANGE Trial
A Randomised phase III trial evaluating early hospital discharge in low risk patients receiving oral antibiotics
Trial Closed Early April 2007:27 patients registeredNo SMCs, No readmissions, LOS 2 days.
34 sites declined entry due to:Complex admission pathwaysMajority of patients not managed within treating centreInability to carry out MASCCTrial management & out of hours careConflicting local antibiotic policyConflict with C Difficile policies
Patient PathwaysAll familiar with Standards
– Patient information– 24 hour specialist triage– Speedy access to specialist care and antibiotics– FN guidelines
– Compliant with standards BUT does it work in practice?
– NCEPOD• 94% have policies in place BUT• ? Suboptimal patient information• Dislocation of care with many admitted to units under
general physicians
St Helens & Knowsley NHS TrustAudit (2007)
• Snap shot analysis revealed:
– Lack of awareness of care pathways in A&E
– Conflicting triage pathways (FN & Manchester)
– Negative impact of 4hr targets
– No iv antibiotics in A&E
– Delays in first antibiotics up to 12hours
– Delayed antibiotics on Day unit and inpatient Facility due to lack of medical staff and beds.
New pathway • Talk to A&E! (joint working Group)
• Patient alert card introduced• Electronic alert system• Integrated Triage with A&E
pathway• Antibiotics before pt transferred• AO review 24hrs• Re audit 2008:
– 22 patients (9 months) – All received abs < 4hrs– Improved awareness and
communication– High risk LOS 6 days, low risk LOS
4 days
STH&K A&E FN Management Chart
CCO Triage for Suspected FNAudit findings ( Ford, 2009)
• 3 month Triage calls (164 calls)
• 73 attended CCO: majority low risk
• 66 ‘other’: hospital, GP, community nurse
• 50% of cases not neutropenic
• Average Time from triage call to arrival 4 hours (range - 13hours)
• Low risk LOS = 2.7days, High risk LOS = 7days
• Examples of dislocated care at DGH
DGH: Case I
• Cancer Centre Triage call 16.30• Advised to attend local A&E 18.30• ‘Low risk’ : • CCO informed and advice sought• Patient commenced oral antibiotics at 22.00• On call pharmacy input with switch to Imipenem and
G-CSF• Patient continued capecitabine further 24hrs• Hospital LOS : 9days
DGH: Case II
• Cancer Centre Triage call: 9.15
• Advised to attend local A&E 10.20
• ‘Low risk’ :
• CCO informed and advice sought 14.20
• CCO transfer
• Arrived CCO 16.30 – MASCC Score low risk
• IV antibiotics commenced at 18.30
• Hospital LOS 4 days
‘Winning principles’www.improvement.nhs.uk/winning_principles
Transforming Inpatient Cancer Care
• I: Assess before admission: – Improve triage, A&E risk stratification, alerts
• II: Patients should be on a defined inpatient pathway– A&E, AOT review
• III : Daily review– AOT
• IV : Pt information and self management
Summary
• FN is a potentially lethal complication BUT in a minority• We need to improve pathways for all FN patients• Progress requires integrated approach with triage,
Centres, A&E and AOT• Need to improve Pt selection and introduce risk
stratification• AO offers significant opportunities to reduce mortality,
improve pt experience and reduce hospitalisation• AO offers new opportunities to develop real world R&D
and link with NCRN• Forthcoming NICE guidance