Neutropenic Sepsis Acute General Management and Support. Ernie Marshall Macmillan Consultant in Medical Oncology Clatterbridge Centre for Oncology

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1 Neutropenic Sepsis Acute General Management and Support Ernie Marshall Macmillan Consultant in Medical Oncology Clatterbridge Centre for Oncology

2 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

3 Aims Overview & Background General Principles of management Risk Stratification Low risk strategies FN management in the real world

4 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

5 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

6 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

7 Background Fever 38 0 C on 2 occasions AND neutrophil count 0.5 x 10 9 /l Duration in solid tumour 3-5days ( Acute Leukaemia:23-27days) 50% of febrile pts have clinically documented infection

8 Presentation Awareness Fever, non-specific symptoms Usually 7-14days post chemotherapy Mucosal damage, catheter-related May present with no fever, confusion, (steroids, overwhelming infection)

9 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

10 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*

11 Multinational Association of Supportive Care in Cancer Risk Index (MASCC) Characteristics Burden of Illness Score 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

12 Optimal FN Management Temp >38.5 and ANC < 0.5 Prompt assessment & Resuscitation Investigations Calculate MASCC Risk Index High Risk Low Risk Antibiotic Protocols

13 High Risk Patients & Sepsis Bundles ( Job 1: Blood Cultures; FBC U&E Job 2: Antibiotics Job 3: Fluid Resuscitation Systolic BP < 90 and/or HR > systolic BP Job 4: ECG Job 5: Check serum lactate Job 6: Monitor blood glucose CVP monitoring and Ventilation

14 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

15 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

16 Low Risk Strategies Inpatient Care Low dose Monotherapy Step down policies POCs Inpatient oral combination Inpatient oral monotherapy EORTC moxifloxacin vs co-amoxyclav/cipro Early discharge policies Outpatient Care Outpatient parenteral antibiotics Outpatient oral antibiotics

17 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

18 UK Audit of management Innes et al BJC 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< ) Phillips et al 2007: UK Childrens Cancer Study Group survey: Wide variation in all aspects of care

19 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)

20 Do all patients need Antibiotics! Nijhuis et al JCO: /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

21 The Real World

22 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 registered No SMCs, No readmissions, LOS 2 days. 34 sites declined entry due to: Complex admission pathways Majority of patients not managed within treating centre Inability to carry out MASCC Trial management & out of hours care Conflicting local antibiotic policy Conflict with C Difficile policies

23 All familiar with Standards Patient Pathways 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

24 St Helens & Knowsley NHS Trust Audit (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.

25 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

26 STH&K A&E FN Management Chart

27 CCO Triage for Suspected FN Audit 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

28 DGH: Case I Cancer Centre Triage call Advised to attend local A&E Low risk : CCO informed and advice sought Patient commenced oral antibiotics at On call pharmacy input with switch to Imipenem and G-CSF Patient continued capecitabine further 24hrs Hospital LOS : 9days

29 DGH: Case II Cancer Centre Triage call: 9.15 Advised to attend local A&E Low risk : CCO informed and advice sought CCO transfer Arrived CCO MASCC Score low risk IV antibiotics commenced at Hospital LOS 4 days

30 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

31 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