NATIONAL INSTITUTE FOR HEALTH AND

CARE EXCELLENCE
SCOPE
1 Guideline title
Sepsis: the recognition, diagnosis and management of severe sepsis

1.1 Short title

Sepsis

2 The remit
The Department of Health has asked NICE: ‘to produce a guideline on Sepsis:
the recognition, diagnosis and management of severe sepsis’.

3 Need for the guideline

3.1 Epidemiology
a) Sepsis is a clinical syndrome caused by the body's immune and
coagulation systems being switched on by the presence of an
infection (bacteria, viruses or fungi). Severe sepsis is defined as
organ dysfunction or tissue hypoperfusion (decreased blood flow)
in addition to sepsis, usually requiring a stay in an intensive care
unit (ICU). Septic shock is a life-threatening condition that is
characterised by low blood pressure despite adequate fluid
replacement in addition to organ dysfunction and sepsis. The UK
Sepsis Trust estimates that 37,000 people die from sepsis in the
UK every year.

b) According to the Parliamentary and Health Service Ombudsman

Annual Report (2013), the most common causes of severe sepsis
in adults are pneumonia, bowel perforation, urinary infection and

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 severe skin infection. That report, based on example cases in
children and adults, recommended that guidelines were needed to
support the recognition and management of severe sepsis,
particularly in its early stages, and they should cover areas such as
initial recognition, timely use of antibiotics and fluid resuscitation.

3.2 Current practice

a) It can be difficult to identify cases of sepsis that need urgent
treatment to prevent progression to severe sepsis. The current
definitions of sepsis and severe sepsis were established in critical
care and paediatric critical care to define whether people were
eligible to join clinical trials. These definitions are used in
International Critical Care guidelines and provide a framework for
current intensive care management, but because sepsis is a
variable syndrome affecting 1 or more organ systems, the existing
critical care definitions and guidelines do not translate simply into
diagnostic pathways for initial diagnosis and management.

b) Current standard practice varies according to the clinical

experience of the physician or practitioner making the initial
assessment, and the facilities immediately available. In secondary
care, sepsis can present to any speciality involved in direct clinical
care. Groups that are particularly at risk of missed diagnosis of
sepsis are infants and young children, people who are
immunocompromised for any reason (including those being treated
for cancer), people who have recently had surgery, people with
indwelling medical lines or devices and women following childbirth.
These subgroups all have specific physiological factors that can
lead to a missed or delayed diagnosis of sepsis.

c) Treatment involves immediate recognition, resuscitation, early

treatment with antibiotics and continual monitoring and
reassessment. Although many current guidelines include the
assessment and management of sepsis in specific subgroups
within their remit, most do not provide guidance for all healthcare

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 professionals in any situation to assess whether sepsis is present,
and to guide initial assessment and treatment.

d) This guideline will provide recommendations for recognising sepsis

and instituting treatment to prevent development of severe sepsis
and septic shock in any person in any clinical environment, linking
to other relevant existing NICE guidance. This guideline will not
replicate the existing International Guidelines for Management of
Severe Sepsis and Septic Shock: 2012, which cover the critical
care management of sepsis in children or adults.

4 The guideline
The guideline development process is described in detail on the NICE website
(see section 6, ‘Further information’).

This scope defines what the guideline will (and will not) examine, and what the
guideline developers will consider. The scope is based on the referral from the
Department of Health.

The areas that will be addressed by the guideline are described in the
following sections.

4.1 Population

4.1.1 Groups that will be covered

a)

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 Group Rationale
 All populations will be included. This guideline will include all
populations. There are a
number of different NICE
guidelines that may cover
aspects of recognition and
management of sepsis and
severe sepsis in subgroups of
the population. We will cross-
reference existing guidance
when it makes sepsis-specific
recommendations.

b) The following subgroups have been identified:

Group Rationale
 Pregnant women People may be at higher risk of
 People at higher risk of infection. sepsis when they have other
medical conditions. This
includes immunodeficiency from
various causes, for example,
treatment for cancer, people
with indwelling catheters or
devices and people who have
recently had surgery.

4.1.2 Groups that will not be covered

a) There are currently no groups that are excluded.

4.2 Setting
a) All healthcare settings.

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4.3 Management

4.3.1 Key issues that will be covered

(a) Recognition and early assessment of sepsis and severe sepsis:
clinical signs and symptoms.

Key clinical areas Rationale

 Clinical risk assessment, Recognition of people at risk of
including history and severe sepsis allows
examination. appropriate treatment to be
 ‘Red flags’ for early started quickly and this is likely
identification of sepsis and to improve outcomes. Evidence
severe sepsis. indicates that delayed
 Scoring tools. recognition of sepsis and severe
sepsis is common. Initial
assessment in primary and
community settings and on
hospital wards consists of
evaluating physical signs and
symptoms. Scoring systems
may be used to predict which
people are likely to develop
severe sepsis and/or to help
make a diagnosis in people with
sepsis or severe sepsis.

a) Value of blood markers for predicting and detecting sepsis and

severe sepsis.

Key clinical areas Rationale

 Blood gas (arterial, venous or Early identification of sepsis
capillary). allows appropriate treatment to
 Glucose. be started quickly. However, the

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  Lactate. use of markers of infection can
 Full blood count be misleading in sepsis as
(haemoglobin, platelets, white apparently normal test results
cell count and differential). (such as for white cell count)
 Urea and electrolytes. may be associated with an

 Clotting screen. overwhelmed immune response.

 C-reactive protein (CRP). Blood markers may be useful

alone or in combination with
other tests. Consideration will
need to be given to the timing of
tests and the feasibility of
different tests in different
settings.

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b) Initial treatment for people with sepsis and with severe sepsis.

Key clinical issues Rationale

(i) Intravenous fluids and Sepsis can cause major
electrolytes in early systemic effects; severe sepsis
management of people with with clinical shock is the worst of
sepsis and with severe sepsis. these. The products of the
infecting organism (for example,
endotoxin or exotoxin) cause the
release and activation of
inflammatory mediators which
cause vasodilatation (the
widening of blood vessels) and
leakage from capillaries; this
leads to people becoming
hypovolemic (decreased blood
volume). The initial choice of
replacement fluid (that is,
crystalloid, colloid or albumin),
the timing of fluid treatment and
the amount to be given will need
to be considered.

Note: NICE has developed

guidelines on Intravenous fluid
therapy in adults in hospital
(CG174) and is developing
guidance on Intravenous fluids
therapy in children.

(ii) Empirical antimicrobial It is not always possible to

treatment strategies in early identify the cause of sepsis.
management of people with Early use of antibiotics is part of
sepsis and severe sepsis. the treatment for suspected
meningococcal disease in all

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 healthcare settings, and advice
would be useful about how best
to use antibiotics in suspected
sepsis, due to any cause, in any
setting (for example, pre-
hospital treatment comparing
immediate broad spectrum
antibiotics to later targeted
treatment).

The incidence of different

causes of sepsis in different
populations and settings may be
an important consideration.

(iii) Early treatment with oxygen There is increasing reference in

and correcting the acid–base the literature to optimal early
balance in people with sepsis treatment being within shorter
and with severe sepsis. time frames than the previous
‘golden hour’. Correcting the
acid–base balance and the
delivery of oxygen may be
appropriate once sepsis is
suspected or has been
diagnosed.

c) Escalating care for people with sepsis or with severe sepsis.

Key clinical issue Rationale

 Timing of escalation of care in The care of a person with sepsis
early management of sepsis. is a medical emergency and
 Early treatment with inotropic their care should be directed by
agents in people with sepsis. senior specialists. The threshold

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  Central venous access and at which senior health
arterial lines. professionals and/or critical care
providers should be involved
and central arterial or central
venous access is needed will be
considered.

Inotropic drugs may be indicated

for sepsis, and their use
considered as soon as severe
sepsis is suspected.

d) Identifying the source of infection.

Key clinical issues Rationale

 The use of clinical symptoms Identifying the source of
and signs to identify the source infection will allow treatment to
of infection. be targeted in the management
 Tests, for example: pathway. This may need
- blood culture appropriate healthcare staff
- lumbar puncture (clear (see 4.3.1.(d)) such as
contraindication criteria for obstetricians and surgeons to
lumbar puncture) be involved early on,
- chest X-ray and other depending on the clinical
imaging. presentation. There may also
be a need for prompt surgical
treatment.

Some investigations such as

lumbar puncture may be
contraindicated.

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e) Early monitoring of people with sepsis.

Key clinical issue Rationale

What parameters to continually People with sepsis or suspected
assess, how often and by whom, sepsis can deteriorate quickly,
for example: and appropriate monitoring can
identify this deterioration and
 heart rate
detect response to treatment.
 respiratory rate
 blood pressure
 blood gases
 other blood markers, for
example, lactate.

f) Information and support for patients and carers.

Key clinical area Rationale

Information and support. Information and support is
needed for:

 people with sepsis or severe

sepsis
 people who are diagnosed as
not having sepsis and are
discharged from medical care
 families and carers of people
who have sepsis or severe
sepsis
 people who survive episodes
of severe sepsis.

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g) Training and education.

Key clinical area Rationale

All healthcare providers. Evidence indicates that sepsis is
often not suspected or
recognised. For some
healthcare professionals the
care of a person with severe
sepsis will be an unusual event,
but their suspicion of the
diagnosis may be critical for that
person.

4.3.2 Issues that will not be covered

Key clinical areas Rationale
(i) Procalcitonin. Assessment commissioned from
NICE Diagnostics Assessment
Programme.

(ii) Managing sepsis in This is a specialist area for which

neonates, children and adults in speciality guidelines already
the ICU. exist.

Specialist treatments of
conditions that result from sepsis
and experimental interventions
within the ICU will also be
excluded. These may include:

 blood products
 corticosteroids
 supportive therapies
 treating sepsis caused by
ventilator-associated

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 pneumonia
 neuromuscular blockade
 renal replacement therapy
 venous thromboembolism
prophylaxis
 pressure ulcers
 glucose control
 immunoglobulins.
(iii) Treatment and care of Sepsis can lead to multisystem
secondary effects on other failure; however, managing this
organs. requires specialist ICU care,
which we propose is excluded.

(iv) Preventing sepsis. The guideline will not cover

measures to prevent sepsis.

This includes vaccination

programmes; infection control
and prevention measures;
personal protective equipment;
use of particular types of
catheters/feeding tubes;
preventing sepsis arising from,
for example, mechanical
ventilation or surgery; antibiotic
prophylaxis to prevent infection;
screening for pathogens in at-risk
populations.

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4.4 Main outcomes
a) Mortality.

b) Progression to severe sepsis.

c) Duration of hospital stay.

d) Duration of ICU stay.

e) Number of organs supported.

f) Change in physical signs and symptoms.

g) Adverse events.

h) Health-related quality of life (for example, as assessed by SF-12 or

EQ-5D).

i) Psychological outcomes.

j) Outcomes indicating severity of long-term disability/rehabilitation

needs.

k) Patient-reported outcome measures.

4.5 Economic aspects

Developers will take into account both clinical and cost effectiveness when
making recommendations involving a choice between alternative
interventions. A review of the economic evidence will be conducted and
analyses will be carried out as appropriate. The preferred unit of effectiveness
is the quality-adjusted life year (QALY), and the costs considered will usually
be only from an NHS and personal social services (PSS) perspective. Further
detail on the methods can be found in The guidelines manual.

4.6 Status

4.6.1 Scope
This is the final scope.

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4.6.2 Timing
The development of the guideline will begin in July 2014.

5 Related NICE guidance

5.1 Published guidance

 Acute kidney injury. NICE clinical guideline CG169 (2013).
 Critical illness rehabilitation. NICE clinical guideline CG83 (2013).
 Intravenous fluid therapy in adults in hospital. NICE clinical guideline
CG174 (2013).
 Feverish illness in children. NICE clinical guideline CG160 (2013).
 Patient experience in adult NHS services. NICE clinical guideline CG138
(2012).
 Antibiotics for early-onset neonatal infection. NICE clinical guideline CG149
(2012).
 Infection control. NICE clinical guideline CG139 (2012).
 Neutropenic sepsis. NICE clinical guideline CG151 (2012).
 Diabetic foot problems - inpatient management. NICE clinical guideline
CG119 (2011).
 Bacterial meningitis and meningococcal septicaemia. NICE clinical
guideline CG102 (2010).
 Chronic heart failure: Management of chronic heart failure in adults in
primary and secondary care. NICE clinical guideline CG108 (2010).
 Venous thromboembolism - reducing the risk. NICE clinical guideline CG92
(2010).
 Diarrhoea and vomiting in children under 5. NICE clinical guideline CG84
(2009).
 Induction of labour. NICE clinical guideline CG70 (2008).
 Intrapartum care. NICE clinical guideline CG55 (2008) (update due for
publication October 2014).
 Surgical site infection. NICE clinical guideline CG74 (2008).
 Acutely ill patients in hospital. NICE clinical guideline CG50 (2007).
 Urinary tract infection in children. NICE clinical guideline CG54 (2007).

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 Nutrition support in adults. NICE clinical guideline CG32 (2006).
 Postnatal care. NICE clinical guideline CG37 (2006).

5.2 Guidance under development

NICE is currently developing the following related guidance (details available
from the NICE website):

 Pneumonia. NICE clinical guideline. Publication expected December 2014.

 Intravenous fluids therapy in children. NICE clinical guideline. Publication
expected October 2015.
 Antimicrobial stewardship guideline. NICE medicines practice guideline.
Publication expected March 2015.
 Acute medical emergency guideline. NICE clinical guideline. Publication
date to be confirmed.

6 Further information
Information on the guideline development process is provided in the following
documents, available from the NICE website:

 How NICE clinical guidelines are developed: an overview for stakeholders

the public and the NHS: 5th edition
 The guidelines manual.

Information on the progress of the guideline will also be available from the
NICE website.

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