Assessment, Diagnosis and
Management of Neutropenic Sepsis
Best Practice Statement
Publication date: September 2011
Contact:BetterCancerCare@scotland.gsi.gov.uk
1
KEY RECOMMENDATIONS:
A. Alert cards should be provided to all patients on commencement of
chemotherapy, advising them of the symptoms they should be aware of
that may indicate the development of neutropenic sepsis.
B. 24 hour contact numbers should be provided to patients (detailed on alert
card), providing both ‘in hours’ and ‘out of hours’ triage facilities.
C. Local pathways for the admission of patients with suspected neutropenic
sepsis should be available in all general practices/out of hours
facilities/Acute Medical Receiving Units/Emergency Departments.
D. Local policies for the management of neutropenic sepsis should be
available in all admission areas.
E. Experienced clinical staff should carry out an assessment of patients to
determine severity of suspected neutropenic sepsis within 15 minutes of
presentation to secondary care.
F. Clinical staff should initiate resuscitation following local sepsis guidelines
and request clinical investigations in line with local policy within 1 hour of
presentation to secondary care.
G. Intravenous antimicrobial therapy, according to local policy, should be
administered to all patients with suspected neutropenic sepsis within 1
hour of presentation to secondary care.
H. Admitting teams should inform the appropriate Oncology or Haematology
speciality team in their hospital at the earliest opportunity and contact
should be clearly documented in the medical notes.
I. Locally identified teams should undertake regular audit of clinical practice
using the identified quality performance indicators and national webbased database.
1
A:
ALERT CARDS SHOULD BE PROVIDED TO ALL PATIENTS
ON COMMENCEMENT OF CHEMOTHERAPY, ADVISING
THEM OF THE SYMPTOMS THEY SHOULD BE AWARE OF
THAT MAY INDICATE THE DEVELOPMENT OF
NEUTROPENIC SEPSIS.
Patients receiving chemotherapy do not always mention their treatment to
healthcare professionals and doctors working in out of hours facilities.
These staff may not have access to the patient’s records1. All patients
undergoing chemotherapy should receive both verbal and written
information on their treatment, possible side effects and details of who to
contact if problems arise2. The urgency of prompt contact for advice and
the importance of telling the healthcare professional that they are
receiving/have recently received chemotherapy should be emphasised.
There is currently variation between Health Boards, hospitals and
specialities as to what and how information is given to patients and
family/carer.
RECOMMENDATIONS:
 Each patient is given an ‘alert’ card containing the following
information:



Symptoms
- Have a temperature of 37.5°C or above
- Feel shivery or flu like
- Feel generally unwell
Local contact details of who to contact if unwell
An alert stating that they are on chemotherapy and at risk of
neutropenic sepsis
 It should be documented in the patient’s notes that they have received
both verbal and written information including an alert card before they
commence chemotherapy
 The sample template (see appendix 1) is recommended unless a card
is already in use which contains all the relevant information as listed.
This card has been copied and the contact details section amended
from the UK Oncology Nursing Society Oncology/Haematology 24-hour
triage rapid assessment and access toolkit 4
2
B:
24 HOUR CONTACT NUMBERS SHOULD BE PROVIDED TO
PATIENTS (DETAILED ON ALERT CARD), PROVIDING BOTH
‘IN HOURS’ AND ‘OUT OF HOURS’ TRIAGE FACILITIES
Neutropenic sepsis is a medical emergency and prompt treatment with
antibiotics improves the prognosis2. Patients receiving chemotherapy
should have a 24 hour telephone number to provide advice and facilitate
prompt admission if required3.
There is currently variation between Health Boards, hospitals and
specialities in advice given as to who to contact if a patient is unwell.
RECOMMENDATIONS:
 It should be documented in the patient’s notes that they have received
an alert card containing information on who to contact if they become
unwell.
 Patients should be advised to show/tell the healthcare provider about
the alert card when seeking emergency care/advice.
 During normal working hours, units administering chemotherapy should
be responsible for providing telephone triage/advice and further
assessment at the unit, when necessary, for their own patients.
3
C:
LOCAL PATHWAYS FOR THE ADMISSION OF PATIENTS
WITH SUSPECTED NEUTROPENIC SEPSIS SHOULD BE
AVAILABLE IN ALL GENERAL PRACTICES/OUT OF HOURS
FACILITIES/ACUTE MEDICAL ASSESSMENT
UNITS/EMERGENCY DEPARTMENTS
As already stated, neutropenic sepsis is a medical emergency and prompt
treatment with antibiotics improves the prognosis2. It is important that
triaging systems are optimised and once the decision has been made that
a patient needs assessment/admission, it is equally important that local
pathways exist in order for the person triaging to know where to direct the
patient. These should be available in all general practices/out of hours
facilities/Acute Medical Receiving Units/Emergency Departments.
RECOMMENDATION:
 Local pathways for the assessment and urgent admission of patients
receiving/recently received chemotherapy who are unwell (and where
neutropenic sepsis is a possible diagnosis) should be agreed and be
immediately available to all clinical staff working in front-line facilities.
4
D:
LOCAL POLICIES FOR THE MANAGEMENT OF
NEUTROPENIC SEPSIS SHOULD BE AVAILABLE IN ALL
ADMISSION AREAS
Neutropenic sepsis is a medical emergency and ongoing review by NICE
reports a dramatic reduction in mortality in such patients when a policy of
aggressive use of in-patient antimicrobial therapy is adopted5. It is vital that
medical and nursing staff responsible for triaging and assessing patients
have immediate access to local pathways for urgent admission.
Immuno-compromised patients present to secondary healthcare through
many channels including:
-
Acute Medical Assessment Units
Emergency Departments
Clinical Decision Making Units/Assessment Units
Specialist/tertiary cancer units
Policies therefore need to be consistent and provide clinical staff with
guidance on:





Appropriate antimicrobial therapy, including alternatives for penicillinallergic patients
Baseline investigations
A time frame for stages of management and therapy which translates
easily for purposes of audit
Guidance on resuscitation in severe sepsis and septic shock (or
reference to guidance resuscitation)
Information and contact details for speciality oncology/haematology
advice
RECOMMENDATIONS:
 Develop and implement local policies for management of neutropenic
sepsis that include the information above (see appendix 2).
 Ensure immediate availability of local policies to all clinical staff working
in areas potentially involved in the care of these patients.
 Undertake an annual review of policies and education of staff.
5
E:
EXPERIENCED CLINICAL STAFF SHOULD CARRY OUT AN
ASSESSMENT OF PATIENTS TO DETERMINE SEVERITY OF
SUSPECTED NEUTROPENIC SEPSIS WITHIN 15 MINUTES
OF PRESENTATION TO SECONDARY CARE
Timely physiological resuscitation and antimicrobial therapy in the
management of severe sepsis and septic shock are proven to reduce
mortality. The systemic inflammatory response syndrome criteria (SIRS)6
form an internationally recognised and validated assessment tool for
patients with suspected infection. Although the white cell count (WCC)
forms part of the syndrome, categorisation of a patient’s degree of sepsis
can be performed in the absence of this result using either the MASCC risk
index for febrile neutropenia (see appendix 3) or Scottish Early Warning
Score (SEWS) performed at the patient’s bedside. This assessment
requires clinical experience to interpret correctly and the ability to prescribe
- or have immediate access to someone who can prescribe - appropriate
treatment. It should be performed by a member of clinical staff competent
to recognise and manage severe sepsis and septic shock.
RECOMMENDATIONS:
 All areas where patients with suspected neutropenic sepsis are
expected to present should have experienced clinical staff available to
assess and manage patients within 15 minutes of presentation to
secondary care.
 The assessment performed should include:
 clear documentation of the time of assessment
 the SEWS score (or local equivalent)
 grading of severity of suspected sepsis
 Assessing staff should be able to (or have immediate access to
medical staff able to) prescribe appropriate antimicrobial therapy and
fluid resuscitation.
6
F:
CLINICAL STAFF SHOULD INITIATE RESUSCITATION
FOLLOWING LOCAL SEPSIS GUIDELINES AND REQUEST
CLINICAL INVESTIGATIONS IN LINE WITH LOCAL POLICY
WITHIN 1 HOUR OF PRESENTATION TO SECONDARY CARE
Investigation by the Surviving Sepsis Group2 has shown a reduction in the
morbidity of severe sepsis and septic shock with timely, appropriate
intravenous resuscitation and antimicrobial administration. The application
of early, goal-directed therapy for fluid resuscitation as recommended by
this group and the UK-based sepsis group is suitable for patients with
confirmed or suspected neutropenic sepsis in the initial hours of
management in a secondary care setting. Each hospital should ensure that
clinical staff involved in the assessment and management of patients with
suspected neutropenic sepsis have training and readily available guidance
on this.
The following investigations should be performed in the initial stages of
assessment:
- Full Blood Count (with differential WCC)
- U&Es, LFTs, Bicarbonate and Lactate
- Peripheral blood cultures (x2)
- Blood cultures from any indwelling venous catheters (e.g. Hickmann
lines)
- Coagulation screen
The following investigations should be performed where possible once
resuscitation is underway
-
CXR
Urine sample for culture and sensitivity
Throat and nasal swabs (for influenza)
Swab of any visible skin lesions or indwelling line sites (as potential
source of infection)
(plus stool cultures and toxin for C.difficile, Virology and arterial blood
gases depending on likely source of sepsis and clinical presentation)
RECOMMENDATION:
 For patients with suspected neutropenic sepsis, in addition to
antimicrobial management, local guidance should include the
resuscitation and investigation of patients. This guidance should refer
to the Surviving Sepsis Campaign guidelines.
7
G:
INTRAVENOUS ANTIMICROBIAL THERAPY, ACCORDING TO
LOCAL POLICY, SHOULD BE ADMINISTERED TO ALL
PATIENTS WITH SUSPECTED NEUTROPENIC SEPSIS
WITHIN 1 HOUR OF PRESENTATION TO SECONDARY CARE
International guidance on time to antimicrobial therapy in severe sepsis
and septic shock recommends administration within 1 hour of suspected
diagnosis2. There is growing opinion amongst haematological and
oncological speciality teams internationally that this is an appropriate and
achievable goal in the management of suspected neutropenic sepsis.
Work at improving recognition of neutropenic sepsis in the community
should aid this.
RECOMMENDATIONS:
 There should be clear documentation of time of admission and of
administration of antimicrobial therapy in the medical case notes/drug
chart.
 Antimicrobial therapy, as per local policy, should be made readily
available in all areas where patients with suspected neutropenic sepsis
enter the secondary care system.
 Antimicrobial therapy should be administered within one hour of
presentation with neutropenic sepsis (within one hour of diagnosis if
initial suspicion is raised in the secondary care setting).
8
H:
ADMITTING TEAMS SHOULD INFORM THE APPROPRIATE
ONCOLOGY OR HAEMATOLOGY SPECIALITY TEAM IN
THEIR HOSPITAL AT THE EARLIEST OPPORTUNITY AND
CONTACT SHOULD BE CLEARLY DOCUMENTED IN THE
MEDICAL NOTES
Early involvement of the specialist cancer teams is required for the
ongoing care of these patients as well as determining appropriate ceiling of
treatment and Do Not Attempt-CPR decisions. Many hospitals within NHS
Scotland do not have direct access to speciality teams dealing with
patients receiving anti-cancer therapy and at risk of neutropenic sepsis.
Local guidance should be readily available for the assessing clinical team
to ensure that contact with cancer services is made promptly for care of
the patient beyond the initial stages of assessment, resuscitation and
treatment.
RECOMMENDATIONS:
 Clear guidance on how to contact local haematology or oncology
specialist services with relevant contact numbers should be included in
local neutropenic sepsis policies.
 The responsible oncology/haematology team should be informed of
admission as soon as possible, and certainly within 72 hours, and
contact should be clearly documented in the medical notes
9
I:
LOCALLY IDENTIFIED TEAMS TO PERFORM REGULAR
AUDIT OF CLINICAL PRACTICE USING THE IDENTIFIED
QUALITY PERFORMANCE INDICATORS AND NATIONAL
WEB-BASED DATABASE
Regular audit of clinical practice should be performed using the following
quality indicators identified for management of neutropenic sepsis. Where
standards are not being met, case note review to identify areas for
improvement should be undertaken.
RECOMMENDATIONS:
 Data relevant to following key Quality Indicators should be collected:

% of patients admitted with neutropenic sepsis, either following or
during chemotherapy, who have followed instructions provided on
alert card.

% of patients with documented diagnosis of suspected neutropenic
sepsis and documented clinical severity of sepsis as per local
guidance

% of patients who received IV antibiotic therapy compliant with local
policy within one hour of first assessment by secondary care
 Audit data should be collected using the national data collection and
aggregation form (Appendix 4).Data to be analysed using the webbased Scottish Antimicrobial Prescribing Group (SAPG) Extranet
system http://www.ihi.org/extranetng. This password protected
database allows teams to enter audit data, produce reports and share
results with other teams in Scotland. Audit results should be shared
regularly with local teams to support improvement of clinical practice.
 Other areas of care local teams could consider auditing:

% of patients assessed by ≥ST1 doctor within 15 minutes of
presentation

% of patients with initial resuscitation in accordance with local early
goal-directed therapy guidance

% of patients where the haematology/oncology teams were
informed within 72 hours of admission.
10
Appendix 1 - Alert Card
This card has been copied and the contact details section amended from the
UK Oncology Nursing Society Oncology/Haematology 24-hour triage rapid
assessment and access toolkit.
11
Appendix 2 – Example of a Suspected Neutropenic Sepsis Protocol
(Included with the permission of NHS Tayside)
First Line Investigations
 Peripheral blood cultures x 2
 Central blood cultures where
present
 U&E, LFT, Phospate,
Bicarbonate
 Lactate
 FBC & coagulation screen
 Throat and nasal swabs
 MSU
 CXR
 Swab skin lesions & line exit
site
 Stool culture and CDiff if
diarrhoea
Known or Suspected
neutropenia
(≤ 0.5x109/L) in patients
displaying signs or symptoms of
infection
Remember:
All patients recently undergoing anticancer treatment are at risk of new or
imminent neutropenia.
Patients with neutropenia may not be able
to mount a temperature response so may
apyrexial at presentation.
Penicillin or Beta-lactam
Allergy
Includes ceftazidime, Tazocin
merpenem
Allergy = rash or
anaphylaxis
Recommend ciprofloxacin
400mg IV bd
See separate penicillin
hypersensitivity guideline for
more detail
Consider viral investigations –
seek specialist advice
First Hour Management
- Assess & grade severity of sepsis according to local sepsis management policy
• Initiate IV fluid resuscitation & early goal-directed therapy as per sepsis policy
• Initiate immediate investigations as per the advice box
• Administer 4.5g of IV Tazocln stat (see box for advice on penicillin-allergy)
• Consider Gentamicin stat if signs of septic shock
• Consider Teicoplanin if previous significant infection with MRSA or obvious central catheter-related infection
• Add Clarithrormycin 500mg IV if suspected source is respiratory
(See local antimicrobial policy for guidance on dosing of antibiotics)
First 6 Hour Management
• Continue
IV resuscitation as per local sepsis management policy
• Prescribe regular antimicrobial therapy according to suspected source & antibiotic guidance
• Contact the patient's cancer speciality team on call
- Haematology Page 1234 (or ext. 33344 Mon-Fri 0900-1700)
- Oncology Page 5678 (or ext. 55566 Mon-Fri 0900-1700)
• Transfer to appropriate care setting according to severity of sepsis
• Initiate barrier nursing
Afebrile within first 2-3
days of treatment
Ateiology identified
No ateiology identified
If general condition
improving &
symptoms
resolving convert
to oral antibiotics
as guided by
sensitivities
If general condition
improving &
symptoms resolving
convert to oral
ciprofloxacin 500mg
BD unless otherwise
advised
Reassess after 38-72
hours
Seek specialist
advice from ID or
microbiology if
required
Persistent fever during first
3 days of treatment
Repeat cultures
Consider change to
meropenam 1g TDS
If persisting fever after 96hrs and
no focus contact microbiology/ID
for specialist advice
12
Appendix 3 – MASSCS Score
Scoring system for risk of complications among febrile neutropenic patients, based on the
Multinational Association for Supportive Care in Cancer (MASCC) predictive model.
Characteristic
Point score
Burden of illness
*No or mild symptoms
*Moderate symptoms
No hypotension
5
3
5
No chronic obstructive pulmonary disease
4
Solid tumour or no previous fungal infection in hematologic tumour
4
Outpatient status
3
No dehydration
3
Aged <60 years
2
The maximum value in this system is 26, and a score of >21 predicts a <5% risk for severe
complications and a very low mortality (<1%) in febrile neutropenic patients. 7, 8
13
Appendix 4 - Scottish Antimicrobial Prescribing Group
Neutropenic sepsis – audit of clinical practice
National Data Collection & Aggregation Form
Ward:
Month: Jan
___________________________
Feb
Mar
Apr
May
Data Collector: _________________
Jun
Jul
Aug
Measures
Sep
Oct
Nov
Patients
5
6
1
2
3
4
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Dec
Year: 20___
7
8
9
10
Total
Y/N
Y/N
Y/N
Y/N
Y/N
/
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
/
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
/
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
/
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
/
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
/
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
Y/N
/
Alert card
Alert card issued by oncology/
haematology staff
Alert card used to seek
advice/admission
Diagnosis
Suspected neutropenic sepsis
documented in notes
Clinical severity of sepsis as per
local guidance documented
Antibiotic therapy
IV antibiotics prescribed as per
local policy
Comments on deviation from policy
Antibiotics administered within 1
hour of presentation
Comments if time > 1 hour
e.g. actual time, reasons for delay
Follow-up
Documented in notes that
responsible oncology/
haematology team informed of
admission within 72 hours
Data in the ‘Total’ column should be added to the SAPG Extranet.
Scottish Antimicrobial Prescribing Group May 2011
14
Appendix 5 – References
1
2
3
4
5
6
7
8
Naik JD, Sathiyaseelan SRK, Vasudev NS. Febrile neutropenia. BMJ
2010;341:c6981 doi: 10.1136/bmj.c6981
Dellinger R.P. et al. Surviving Sepsis Campaign: International guidelines for
management of severe sepsis and septic shock: 2008. Intensive Care Med. 2008
January; 34(1): 17–60.
www.ncbi.nlm.nih.gov/pmc/articles/PMC2249616
.National Chemotherapy Advisory Group. Chemotherapy services in England:
ensuring quality and safety. 2009.
www.dh.gov.uk/en/Publicationsandstatistics/Publications/DH_104500
UKONS. Oncology/Haematology 24-hour Triage – Rapid Assessment and Access
Toolkit – Evaluation. 2010.
http://www.greatermidlandscancernetwork.nhs.uk/Oncology-Haematology-24-HourTriage-Rapid-Assessment-and-Access-Toolkit/226
NICE. Neutropenic sepsis draft scope for consultation. c2010. Available from:
http://guidance.nice.org.uk/CG/Wave23/11/Scope/ScopeConsultation
The systemic inflammatory response syndrome criteria (SIRS): American College
of Chest Physicians/Society of Critical Care Medicine Consensus Conference:
definitions for sepsis and organ failure and guidelines for the use of innovative
therapies in sepsis. Crit. Care Med. 20 (6): 864–74. 1992
Klastersky J. Management of fever in neutropenic patients with different risks of
complications. Clin Infect Dis. 2004 Jul 15;39 Suppl 1:S32-7
Antoniadou A, Giamarellou H. Fever of unknown origin in febrile leukopenia. Infect
Dis Clin North Am. 2007 Dec; 21(4):1055-90.
15
Appendix 6 – Group Membership
Member
Jennifer Armstrong, Senior Medical
Officer (Chair)
Rachael Dunk , Head of Cancer
Strategies and Long Term Conditions
Jacqui Sneddon, Project Lead for
Scottish Antimicrobial Prescribing Group
Dilip Nathwani, Consultant in Infectious
Diseases, NHS Tayside
Gail Caldwell, Director of Pharmacy,
NHS Forth Valley
John Murphy, Consultant Haematologist,
NHS Lanarkshire
Marianne Nicolson, Consultant Medical
Oncologist, NHS Grampian
Mark Parsons, Lead Cancer Pharmacist,
NOSCAN
Fiona Campbell, Macmillan CNS
Oncology / Chemotherapy, NHS
Highland
Liz Preston, Head of Service, Edinburgh
Cancer Centre, NHS Lothian
Ursula Mackintosh, Emergency Medicine
consultant, NHS Forth Valley
Keith Farrer, Lead Nurse, NHS Orkney
Nicola Irvine, Consultant in
Acute Medicine, NHS Tayside
Sarah Couper, SpR in Public Health
Medicine, NHS Forth Valley
Representing
Scottish Government Health and Social Care
Directorates
Scottish Government Health and Social Care
Directorates
Scottish Antimicrobial Prescribing Group
Laura Steele (Secretariat), Cancer Policy
Officer
Scottish Government Health and Social Care
Directorates
Scottish Antimicrobial Prescribing Group
Scottish Antimicrobial Prescribing Group
Chemotherapy Advisory Group
Chemotherapy Advisory Group
Chemotherapy Advisory Group
Chemotherapy Advisory Group
Chemotherapy Advisory Group
Accident and Emergency
Remote/Rural
General Medicine
Scottish Government (now Health Protection
Scotland)
16