SIGN157

Risk reduction and

management of delirium

A national clinical guideline

March 2019
Key to evidence statements and recommendations
Levels of evidence
1++ High-quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias

1+ Well-conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias

1– Meta-analyses, systematic reviews, or RCTs with a high risk of bias

2++ High-quality systematic reviews of case-control or cohort studies

High-quality case-control or cohort studies with a very low risk of confounding or bias and a high
probability that the relationship is causal

2+ Well-conducted case-control or cohort studies with a low risk of confounding or bias and a moderate
probability that the relationship is causal

2 – 
Case-control or cohort studies with a high risk of confounding or bias and a significant risk that the
relationship is not causal

3 Non-analytic studies, eg case reports, case series

4 Expert opinion

Recommendations
Some recommendations can be made with more certainty than others. The wording used in the recommendations
in this guideline denotes the certainty with which the recommendation is made (the ‘strength’ of the
recommendation).
The ‘strength’ of a recommendation takes into account the quality (level) of the evidence. Although higher-quality
evidence is more likely to be associated with strong recommendations than lower-quality evidence, a particular
level of quality does not automatically lead to a particular strength of recommendation.
Other factors that are taken into account when forming recommendations include: relevance to the NHS in Scotland;
applicability of published evidence to the target population; consistency of the body of evidence, and the balance
of benefits and harms of the options.

R For ‘strong’ recommendations on interventions that ‘should’ be used, the guideline development group is
confident that, for the vast majority of people, the intervention (or interventions) will do more good than
harm. For ‘strong’ recommendations on interventions that ‘should not’ be used, the guideline development
group is confident that, for the vast majority of people, the intervention (or interventions) will do more
harm than good.

R For ‘conditional’ recommendations on interventions that should be ‘considered’, the guideline development
group is confident that the intervention will do more good than harm for most patients. The choice of
intervention is therefore more likely to vary depending on a person’s values and preferences, and so the
healthcare professional should spend more time discussing the options with the patient.

Good-practice points

 Recommended best practice based on the clinical experience of the guideline development group.

NICE has accredited the process used by Scottish Intercollegiate Guidelines Network
to produce clinical guidelines. The accreditation term is valid until 31 March 2020 and
is applicable to guidance produced using the processes described in SIGN 50: a guideline
developer’s handbook, 2015 edition (www.sign.ac.uk/assets/sign50_2015.pdf).
More information on accreditation can be viewed at www.nice.org.uk/accreditation

Healthcare Improvement Scotland (HIS) is committed to equality and diversity and assesses all its publications for
likely impact on the six equality groups defined by age, disability, gender, race, religion/belief and sexual orientation.
SIGN guidelines are produced using a standard methodology that has been equality impact assessed to ensure that
these equality aims are addressed in every guideline. This methodology is set out in the current version of SIGN 50,
our guideline manual, which can be found at www.sign.ac.uk/sign-50.html. The EQIA assessment of the manual can
be seen at www.sign.ac.uk/assets/sign50eqia.pdf. The full report in paper form and/or alternative format is available
on request from the Healthcare Improvement Scotland Equality and Diversity Officer.
Every care is taken to ensure that this publication is correct in every detail at the time of publication. However,
in the event of errors or omissions corrections will be published in the web version of this document, which is the
definitive version at all times. This version can be found on our web site www.sign.ac.uk
Scottish Intercollegiate Guidelines Network

Risk reduction and

management of delirium

A national clinical guideline

March 2019
Scottish Intercollegiate Guidelines Network
Gyle Square, 1 South Gyle Crescent
Edinburgh EH12 9EB

www.sign.ac.uk

First published March 2019

978-1-909103-68-9

Citation text

Scottish Intercollegiate Guidelines Network (SIGN).

Risk reduction and management of delirium. Edinburgh: SIGN; 2019.
(SIGN publication no. 157). [March 2019]. Available from URL: http://www.sign.ac.uk

SIGN consents to the photocopying of this guideline for the purpose

of implementation in NHSScotland.
Contents

1 Introduction 1
1.1 The need for a guideline 1
1.2 Remit of the guideline 1
1.3 Statement of intent 3
2 Key recommendations 5
2.1 Detecting delirium 5
2.2 Risk reduction 5
2.3 Non-pharmacological treatment 5
3 Detecting delirium 6
3.1 Tools for detection and assessment 6
3.2 Tools for measuring severity of delirium 8
3.3 Tools for detecting incident delirium in hospital 8
3.4 Clinical investigations 8
4 Non-pharmacological risk reduction 11
4.1 Introduction 11
4.2 Inpatient care 11
4.3 Intensive care 12
5 Pharmacological risk reduction 14
5.1 Medicines optimisation 14
5.2 Antipsychotics 15
5.3 Dexmedetomidine 16
5.4 Other pharmacological therapies 17
6 Non-pharmacological treatment 18
7 Pharmacological treatment 19
7.1 Antipsychotics 19
7.2 Dexmedetomidine 19
7.3 Acetylcholinesterase inhibitors 20
7.4 Benzodiazepines 20
7.5 Urgent pharmacological intervention 20
8 Follow up 21
9 Provision of information 22
9.1 Checklist for provision of information 22
9.2 Publications from SIGN 24
9.3 Sources of further information 24
10 Implementing the guideline 26
10.1 Implementation strategy 26
10.2 Resource implications of key recommendations 26
10.3 Auditing current practice 26
10.4 Health technology assessment advice for NHSScotland 26
11 The evidence base 27
11.1 Systematic literature review 27
11.2 Recommendations for research 28
11.3 Review and updating 28
12 Development of the guideline 29
12.1 Introduction 29
12.2 The guideline development group 29
12.3 Acknowledgements 30
12.4 Consultation and peer review 30
Abbreviations 32
Annexes 34
References 42
 1 | Introduction

1 Introduction

1.1 The need for a guideline

Delirium is an acute deterioration in mental functioning arising over hours or days that is
triggered mainly by acute medical illness, surgery, trauma, or drugs.1 It was previously termed
‘acute confusional state’. Delirium is independently linked with poor outcomes including medical
complications, falls, increased length of hospital stay, new institutionalisation, and mortality.1
It can cause significant patient and carer distress.2

The main features of delirium are acute cognitive deficits and altered level of arousal, with up to
half of patients also experiencing hallucinations or delusions.3 Delirium varies in duration, mostly
resolving within days, but in some people it can last weeks or months.4

Delirium is among the most common of medical emergencies. A UK study found a prevalence of
20% in adult acute general medical patients.5 The prevalence is higher in particular clinical groups,
such as patients in intensive care units (ICU). It affects up to 50% who have hip fracture and up to
75% in intensive care.1 Several predisposing factors increase the risk of delirium, including older
age, dementia, frailty, the presence of multiple comorbidities, male sex, sensory impairments,
a history of depression, a history of delirium, and alcohol misuse.1,6

Despite its importance, there are deficiencies in care of people with delirium in Scotland. It is
underdiagnosed,7 and the treatment of patients with established delirium is variable. Preventative
measures can reduce the incidence of delirium,1 yet few clinical units have formal delirium risk-
reduction programmes.

Experience gained from quality improvement programmes in Scotland shows that advances can
be made.8 There is potential to improve clinical practice by reducing variation in the standards
of assessment and management of people with delirium. This new national guideline on delirium
provides a critical focal point for Scotland-wide improvements in delirium care. Because delirium
is so common, all healthcare staff having contact with acutely unwell patients need to assume
responsibility for detecting and treating it, as well as aiming to reduce the risk of delirium occurring.
Those working in the long-term care environment should be able to recognise delirium, reduce
risk, and monitor those in their care to resolve delirium.

1.1.1 Patient and carer perspective

Common concerns raised by patient groups and through research into patient and carer issues
identified good communication with family members or carers as crucial. Family members can
provide background information on patient history, changes in behaviour and early warning signs.
Once diagnosed, carers need information and support to enable them to care for the patient (see
section 9).9-11

1.2 Remit of the guideline

1.2.1 Overall objectives

This guideline provides recommendations based on current evidence for best practice in the
detection, assessment, treatment and follow up of adults with delirium, as well as reducing the risk
of delirium. The guideline applies to all settings: home, long-term care, hospital, and hospice. It is
important to note that, to date, much of the existing evidence and the focus of other guidelines,
is in acute care settings. However, this does not preclude application of the recommendations to
other settings, adapted according to clinician judgement. Person-centred care should be the focus
of the implementation of this guideline.

1
Risk reduction and management of delirium

The guideline excludes delirium secondary solely to alcohol and illicit substances use. It also
excludes delirium in children.

1.2.2 Common comorbidities

Common comorbidities which have been considered when reviewing the evidence for this
guideline are:
• critical illness
• dementia
• depression
• frailty
• head injury
• learning disability
• Parkinson’s disease
• cerebrovascular disease.

1.2.3 Definitions

The International Classification of Diseases, version 10 (ICD-10) defines delirium as, “An aetiologically
nonspecific organic cerebral syndrome characterized by concurrent disturbances of consciousness
and attention, perception, thinking, memory, psychomotor behaviour, emotion, and the sleep-wake
schedule. The duration is variable and the degree of severity ranges from mild to very severe.”12

According to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5),
delirium is a disturbance in attention and awareness with an additional disturbance in cognition,
not explained by another pre-existing, established or evolving neurocognitive disorder or coma.
The disturbance develops over a short period of time and tends to fluctuate in severity during the
course of the day with evidence of direct physiological consequence of another medical condition,
substance intoxication or withdrawal, or exposure to a toxin, or is due to multiple aetiologies.
It’s specified as ‘acute’, lasting a few hours or days and ‘persistent’, lasting weeks or months.13

Delirium presents variably but its main characteristics are rapid onset (hours, days) of acute mental
status deterioration. Patients may present with cognitive impairment, but drowsiness to the point
that the patient is not speaking, severe agitation, or psychotic features such as hallucinations or
delusions may be the most prominent features. Delirium is sometimes described using hyperactive,
hypoactive or mixed labels depending on the level of arousal.13 Most delirium has a duration of a
small number of days, but in around 20% of cases, it can persist for weeks or months.14

Delirium is known by several terms, some still in use in clinical practice. These terms include ‘acute
confusional state’, ‘acute confusion’, ‘acute on chronic confusion’, and ‘acute encephalopathy’. The
SIGN guideline group advocates use of the term delirium rather than alternatives to promote more
consistent communication among professionals, more accurate provision of information to patients
and carers, and more consistent use of detection tools and management strategies.

1.2.4 Target users of the guideline

This guideline will be of interest to primary and secondary healthcare professionals, community
and care home staff involved in the care of patients at risk of, or experiencing, delirium, as well
as patients and carers.

2
 1 | Introduction

1.3 Statement of intent

This guideline is not intended to be construed or to serve as a standard of care. Standards of care
are determined on the basis of all clinical data available for an individual case and are subject to
change as scientific knowledge and technology advance and patterns of care evolve. Adherence
to guideline recommendations will not ensure a successful outcome in every case, nor should they
be construed as including all proper methods of care or excluding other acceptable methods of
care aimed at the same results.

The ultimate judgement must be made by the appropriate healthcare professional(s) responsible
for clinical decisions regarding a particular clinical procedure or treatment plan. This judgement
should only be arrived at through a process of shared decision making with the patient (or family
or carers, where appropriate), covering the diagnostic and treatment choices available. It is advised,
however, that significant departures from the national guideline or any local guidelines derived from
it should be documented in the patient’s medical records at the time the relevant decision is taken.

1.3.1 Influence of financial and other interests

It has been recognised that financial interests in, or close working relationships with, pharmaceutical
companies may have an influence on the interpretation of evidence from clinical studies.

It is not possible to completely eliminate any possible bias from this source, nor even to quantify
the degree of bias with any certainty. SIGN requires that all those involved in the work of guideline
development should declare all financial interests, whether direct or indirect, annually for as long
as they are actively working with the organisation. By being explicit about the influences to which
contributors are subjected, SIGN acknowledges the risk of bias and makes it possible for guideline
users or reviewers to assess for themselves how likely it is that the conclusions and guideline
recommendations are based on a biased interpretation of the evidence.

While developing this guideline, one academic conflict of interest was declared. As the main author
of the 4AT test, Co-Chair Professor Alasdair MacLullich did not participate in the process to form
recommendations to address key question 1: tools for detecting delirium (see Annex 1).

Signed copies of declaration of interests forms are retained by the SIGN Executive and a register
of interests is available in the supporting material section for this guideline at www.sign.ac.uk

1.3.2 Prescribing of licensed medicines outwith their marketing authorisation

Recommendations within this guideline are based on the best clinical evidence. Some
recommendations may be for medicines prescribed outwith the marketing authorisation (MA) also
known as product licence. This is known as ‘off-label’ use.

Medicines may be prescribed ‘off label’ in the following circumstances:

• for an indication not specified within the marketing authorisation
• for administration via a different route
• for administration of a different dose
• for a different patient population.

An unlicensed medicine is a medicine which does not have MA for medicinal use in humans.

Generally ‘off-label’ prescribing of medicines becomes necessary if the clinical need cannot be
met by licensed medicines within the marketing authorisation. Such use should be supported by
appropriate evidence and experience.15

3
Risk reduction and management of delirium

“Prescribing medicines outside the conditions of their marketing authorisation alters (and probably
increases) the prescribers’ professional responsibility and potential liability.”15

The General Medical Council (GMC) recommends that when prescribing a medicine ‘off label’,
doctors should:16
• be satisfied that there is no suitably licensed medicine that will meet the patient’s need.
• b
 e satisfied that there is sufficient evidence or experience of using the medicine to show its
safety and efficacy
• t ake responsibility for prescribing the medicine and for overseeing the patient’s care, monitoring,
and any follow-up treatment, or ensure that arrangements are made for another suitable doctor
to do so.
• m
 ake a clear, accurate and legible record of all medicines prescribed and, when not following
common practice, the reasons for prescribing an unlicensed medicine.

Non-medical prescribers should ensure that they are familiar with the legislative framework and
their own professional prescribing standards.

Prior to any prescribing, the licensing status of a medication should be checked in the summary
of product characteristics (www.medicines.org.uk). The prescriber must be competent, operate
within the professional code of ethics of their statutory bodies and the prescribing practices of
their employers.17

1.3.3 Health technology assessment advice for NHSScotland

Specialist teams within Healthcare Improvement Scotland issue a range of advice that focuses on
the safe and effective use of medicines and technologies in NHSScotland.

The Scottish Medicines Consortium (SMC) provides advice to NHS boards and their Area Drug and
Therapeutics Committees about the status of all newly-licensed medicines, all new formulations of
existing medicines and new indications for established products. NHSScotland should take account
of this advice and ensure that medicines accepted for use are made available to meet clinical need
where appropriate.

SMC advice relevant to this guideline is summarised in section 10.4.

4
 2 | Key recommendations

2 Key recommendations

The following recommendations were highlighted by the guideline development group as the key
clinical recommendations that should be prioritised for implementation.

2.1 Detecting delirium

R The 4AT tool should be used for identifying patients with probable delirium in emergency
department and acute hospital settings.

99  here delirium is detected, the diagnosis of delirium should be clearly documented and
W
coded to aid transfers of care (eg handover notes, referral and discharge letters).

2.2 Risk reduction

R The following components should be considered as part of a package of care for patients
at risk of developing delirium:
• orientation and ensuring patients have their glasses and hearing aids
• promoting sleep hygiene
• early mobilisation
• pain control
• prevention, early identification and treatment of postoperative complications
• maintaining optimal hydration and nutrition
• regulation of bladder and bowel function
• provision of supplementary oxygen, if appropriate.

R All patients at risk of delirium should have a medication review conducted by an experienced
healthcare professional.

2.3 Non-pharmacological treatment

R Healthcare professionals should follow established pathways of good care to manage patients
with delirium.
• F
 irst consider acute, life-threatening causes of delirium, including low oxygen level, low
blood pressure, low glucose level, and drug intoxication or withdrawal.
 ystematically identify and treat potential causes (medications, acute illness, etc), noting
• S
that multiple causes are common.
 ptimise physiology, management of concurrent conditions, environment (reduce noise),
• O
medications, and natural sleep, to promote brain recovery.
• S
 pecifically detect, assess causes of, and treat agitation and/or distress, using non-
pharmacological means only if possible (see section 7 for pharmacological treatment).
• C
 ommunicate the diagnosis to patients and carers, encourage involvement of carers and
provide ongoing engagement and support.
• A
 im to prevent complications of delirium such as immobility, falls, pressure sores,
dehydration, malnourishment, isolation.
• Monitor for recovery and consider specialist referral if not recovering.
• Consider follow up (see section 8).

5
Risk reduction and management of delirium

3 Detecting delirium

3.1 Tools for detection and assessment

Delirium is frequently missed in routine clinical care and lack of detection is associated with poor
outcomes.18,19 Delirium detection should ideally be undertaken at the earliest opportunity. Numerous
assessment tools have been developed to help identify probable delirium in patients in a variety of
settings, which can then prompt a more accurate diagnosis and consideration of underlying causes.
For practical reasons, for implementation and acceptability to patients, assessment tools should
be brief, require little or no training and be appropriate to the clinical setting.20 The sensitivity of
the tool is also important, as it is vital not to miss delirium.

A commonly used tool, the Confusion Assessment Method (CAM) and its variants have been
reported as useful tools for detecting delirium.18,21,22 However, sensitivity and specificity varied
broadly, possibly due to the need for users to have training and knowledge of delirium and its
differential diagnoses. The CAM-ICU has particularly broad use within ICU settings but has the
2+
same limitations.19,23 The 4 As Test (Arousal, Attention, Abbreviated Mental Test 4, Acute change) 2++
(4AT) was developed, validated and widely implemented in Scotland in non-ICU settings. It does 2+
not require specific training, is brief and easy to use and has wide applicability in various clinical
settings.24,25 It performed well for sensitivity and patient completion rate compared to other similar
tools within the same patient group.20,26 The 4AT is also applicable as an assessment tool in older
emergency department attendees.27

Other tools had significant disadvantages over CAM and 4AT, such as longer assessment time, poorer
sensitivity and/or specificity, and/or relative lack of validation in published studies (see Table 1).
2+
The 13-item Delirium Observation Screening Scale (DOS) had good specificity and sensitivity but
2++
requires assessment over three shift periods and its authors have suggested it is geared more
towards detection of hyperactive delirium, whereas hypoactive is more common in practice.28-30

The CAM-ICU and Intensive Care Delirium Screening Checklist (ICDSC) have been developed and
2+
validated in ICU settings, and may be better suited than other tests for use in intensive care.31

In all cases, a positive assessment should be followed by additional assessment and diagnosis
against ICD-10 or DSM-5 criteria by a suitably trained clinician.12,13 It is important to be aware that
delirium may still occur in the absence of a positive test result because the condition fluctuates.
Healthcare staff should not rely on the result of a single assessment during hospital admission.

Assessment of the patient’s capacity to make decisions about fundamental health and personal
care must also be taken into consideration. If the person is deemed to be incapacitated appropriate
documentation (eg in Scotland, Adults with Incapacity Act, Section 47 part 5 certificate with
accompanying treatment plan) must be completed.

Table 1 summarises the commonly used and validated brief delirium assessment tools. There is
a wide range of sensitivities and specificities with the different tools as well as in the time taken
to complete assessment. Some are designed for assessment at first presentation, and others for
monitoring for incident delirium. A tool with high sensitivity that requires no training or very
little time to perform, and with additional advantages (for example, suitable for patients with
dementia), will be important in clinical practice to ensure all cases of delirium are identified. In
the case of uncertainty over whether delirium or dementia or both are present in a patient, it is
best to assume it is delirium unless there is clarification from the patient’s notes or from family
members that the mental state is clearly in keeping with their usual mental state.

6
 Tool Time taken Training Staff Settings Reported Reported Delirium Suitable for Suitable for
(min) Required Sensitivity Specificity severity monitoring detecting
% % rating DSD

4AT20,24,26,27,30,32 <2 No Any Multiple 86–100 65–82 No No Yes

AMT20,26 2 No Any Medical 75–87 61–64 No No No

CAM and 3–10 Yes Any Multiple 46–94 63–100 No† No Yes
variants18,20,22,24,30,33

CAM-ICU19,22,30,31 <5 Yes Any ICU 28–100 53–99 No Yes No

DOS (13-item)*28-30 5 Minimal Any Multiple 89–100 87–97 Yes Yes No

DRS- R-9830,34,35 20 Yes Psychiatry Multiple 57–93 82–98 Yes No Yes

ICDSC19,31 7–10 Minimal Any ICU 73–97 69–97 Yes Yes No

Table 1: Overview of delirium assessment tools

MMSE36 5 Minimal Any Multiple 76–91 51–84 Yes No No

Nu-DESC30 <5 No Any Multiple 32–96 69–92 No No No

RADAR37 <1 No Any Multiple 43–84 64–78 No Yes No

mRASS33,38 1 No Any Multiple 65–75 82–90 Yes Yes Yes

SQiD20 <1 No Any Medical 77–91 56–71 No Yes No

Suitability for monitoring refers to the use of a tool daily or more for screening for incident delirium.
†with the exception of CAM-S

*DOS requires assessment over three shifts so time to detection is three days. It is geared towards assessment of hyperactive delirium.

Abbreviations: AMT – Abbreviated Mental Test; CAM – Confusion Assessment Method; DSD – delirium superimposed on dementia; DRS-98-R – Delirium Rating Scale; DOS - Delirium
Observation Screening Scale; ICDSC – Intensive Care Delirium Screening Checklist; Nu-DESC – Nursing Delirium Screening Scale; MMSE – Mini Mental State Examination; RADAR – Recognising
those in intensive care. This need not preclude their use in other settings, such as primary care.
assessed using an assessment tool, but studies are in older people (aged 65 or over) in hospital and

7
Evidence was not identified to determine exactly which groups of patients should be routinely
3 | Detecting delirium

Acute Delirium As part of your Routine; mRASS – Modified Richmond Agitation-Sedation Scale; SQiD – Single Question to Identify Delirium
Risk reduction and management of delirium

R The 4AT tool should be used for identifying patients with probable delirium in emergency
department and acute hospital settings.

R Use of the 4AT tool could be considered for use in community or other settings for identifying
patients with probable delirium.

R For intensive care unit settings, CAM-ICU or ICDSC should be considered to help identify
patients with probable delirium.

99 A formal assessment and diagnosis must be made by a suitably trained clinician whenever
patients with probable delirium are identified.

99  here delirium is detected, patients and their family/carers should be informed of the
W
diagnosis (see section 9).

99  here delirium is detected, the diagnosis of delirium should be clearly documented to aid
W
transfers of care (eg handover notes, referral and discharge letters).

3.2 Tools for measuring severity of delirium

Monitoring patients diagnosed with delirium for changes in severity or response to treatment
may help predict the full clinical impact.39,40 Insufficient evidence was identified to recommend a 3

particular tool for monitoring purposes.

Table 1 lists tools that assess severity. Selection of a tool should take into consideration time
required and ease of use. The 13-item DOS, mRASS, MMSE, DRS-R-98 and ICDSC can be considered
as tools for the purpose of monitoring severity of delirium in suitable clinical areas (see Table 1).

3.3 Tools for detecting incident delirium in hospital

Insufficient evidence was identified to recommend a particular tool for regular monitoring purposes
for detection of incident delirium after initial assessment in hospital. Selection of a tool should
take into consideration time required and ease of use.

Although theoretically any tool listed in Table 1 in section 3.1 could be used, the RADAR, 13 item
DOS, mRASS, CAM-ICU and SQiD are most suitable for monitoring purposes in suitable clinical areas
(see Table 1).

3.4 Clinical investigations

Many conditions can trigger delirium. There is often more than one contributory factor in an
individual person.41 A major part of treating people with delirium is treating the underlying
precipitants or causes. A structured approach should be taken to identify, where possible, the issues
contributing to delirium for an individual (see Annex 2). These include obtaining a good history
from the person, a collateral or informant history, clinical examination (including a neurological
examination), basic and then targeted investigations.

There is little evidence supporting the use of basic investigations because a fundamental standard
of care is assumed in trials, and trials have not been conducted comparing, for example, carrying
out a full blood count or not, in a person with delirium.

8
 3 | Detecting delirium

This section examines the available evidence for advanced investigations which are more invasive
or expensive or where a condition may be identified which significantly alters the management
of a person (eg identifying stroke, subdural haemorrhage or non-convulsive status epilepticus). If
there is suspicion of significant illness (eg meningitis, encephalitis or sepsis) causing the delirium,
these should be managed appropriately.

Strategies for such an approach and systems of care are outlined in the Royal College of Physicians’
‘Acute Care Toolkit 3: Acute medical care for frail older people’ and in the Healthcare Improvement
Scotland TIME Bundle (see Annex 3).42

3.4.1 Brain imaging

The aim of brain imaging is to identify stroke, haemorrhage, trauma or structural abnormality, such
as a tumour, as causes of delirium. The diagnostic yield of computed tomography (CT) in determining
the cause of delirium is low, but may be indicated in some high-risk patients.43 For patients with 3
pre-existing cognitive impairment who have other identified conditions that can precipitate delirium,
such as dehydration or infection, brain imaging is unlikely to change management.44

Observational, mostly retrospective, studies identified abnormal brain imaging with CT in people
aged over 70 years presenting with acute confusion and:
• new focal neurological signs44-48 (defined as acute onset dysphasia, visual field defect, pyramidal
or cerebellar signs).46 There should be awareness that dysphasia (a focal sign) may be mistaken
for confusion (a global brain dysfunction)49 3
4
• presenting after a fall46,48

• a reduced level of consciousness46,47

• a head injury (in patients of any age)50
• taking anticoagulant therapy.48

Cerebral atrophy is more likely in patients presenting with delirium than without.51 This in itself,
3
however, is not a useful finding in making a diagnosis of delirium or changing medical management.

R CT brain scan should not be used routinely but should be considered in patients presenting
to hospital with delirium in the presence of:
• new focal neurological signs
• a reduced level of consciousness (not adequately explained by another cause)
• a history of recent falls
• a head injury (patients of any age)
• anticoagulation therapy.

99 Consideration should be given to imaging patients with non-resolving delirium where no

clear cause is identified or there are features to suggest primary central nervous system
pathology.

9
Risk reduction and management of delirium

3.4.2 Electroencephalogram

Currently electroencephalogram (EEG) is not performed routinely in patients with delirium,

however, three retrospective studies from an epilepsy research group suggest that the incidence
of epileptic activity and non-convulsive status epilepticus (NCSE) are higher than recognised in 3
patients with delirium. One study found that 80% of patients with NCSE had delirium attributed
initially to another cause.52

In one prospective study EEG was carried out in 44 patients aged 60 years or older with “confusion
of unknown origin” (defined as unexplained confusion following screening investigations, including
CT scan and blood sample screening, carried out in an emergency unit). Patients with a known
3
history of epilepsy or in whom seizure-related confusion was highly suspected were excluded.
Seven (15.9%) patients had EEG changes consistent with NCSE. Clinical indications of NCSE, with
statistical significance, were rapid onset (<24 hours), lack of response towards simple commands
and female gender.53

Continuous EEG monitoring is more sensitive than single EEG assessment at identifying epileptic
activities and NCSE (28% v 6%).52
3
Further evidence is needed to determine the efficacy of routine use of EEG in patients presenting
with confusion.

R Electroencephalogram should be considered when there is a suspicion of epileptic activity

or non-convulsive status epilepticus as a cause of a patient’s delirium.

3.4.3 Lumbar puncture

Only one small study from the 1980s was identified on the use of lumbar puncture in the assessment
of patients with delirium. It concluded that most patients with fever and delirium have a cause
other than infection in the central nervous system (80 of 81 samples were negative for bacterial 3

growth). Given the age of the trial, viral polymerase chain reaction (PCR) testing is unlikely to
have been performed.54

Lumbar puncture is not a straightforward procedure and such an invasive investigation may cause
further distress to someone who may be confused or agitated. There is also a risk of adverse
events, such as infection, causing spinal haematoma, cerebrospinal fluid (CSF) leak or low pressure
CSF headache.55

99 Lumbar puncture should not be performed routinely on patients presenting with delirium.

10
 4 | Non-pharmacological risk reduction

4 Non-pharmacological risk reduction

4.1 Introduction
Delirium is often multifactorial. Prevention may merge with treatment when non-pharmacological
practices are used. Risk reduction should therefore be considered throughout the patient’s care.
Many of the acute factors triggering delirium or lowering the threshold of risk are modifiable.
Targeting these modifiable factors forms the basis of reducing the risk of delirium. Up to 50% of
delirium in hospitalised patients arises after hospital admission.1,56 Categories of risk reduction
include preventing physiological derangements such as dehydration and hypoxia, maintaining
sleep, reducing psychological stress through communication and managing the environment, and
correcting sensory impairments when possible. These non-pharmacological strategies have often
been delivered in multicomponent packages, and trials of such packages form the majority of the
evidence. Because of limited resources, targeting higher-risk patients (eg older people, or those with
cognitive impairments) for specific delirium risk-reduction strategies is commonly advocated.57,58
To date, these strategies are considered distinct from the use of medication to reduce the risk of
delirium (see section 5), and are advocated in pathways and guidelines based on expert opinion.58-60

Non-pharmacological practices should be tried before pharmacological interventions are considered.

4.2 Inpatient care

Studies in a variety of patients and settings (acute and perioperative) have found multicomponent
interventions to be effective in reducing incidence of delirium.61-64 Meta-analysis of seven studies
found that compared to usual care there was a significant reduction in incidence of delirium with
multicomponent interventions, with a relative risk (RR) of 0.73, 95% confidence interval (CI) 0.63
to 0.85.62 Pooled analysis in a Cochrane review also reported a reduction in incidence of delirium,
(RR) 0.69, 95% CI 0.59 to 0.81 compared to usual care.63 Interventions included in multicomponent
care varied, but consisted of some of the following; physiotherapy, reorientation, early mobilisation, 2++
1++
identification and treatment of underlying causes or postoperative complications, pain control, 1+
regulation of bowel and bladder function, hydration and nutrition, and oxygen delivery.61-63
Such interventions are considered to be good fundamental care.63 Comprehensive geriatric care,
defined as a specialist geriatric orthopaedics team providing comprehensive medical assessment,
management and initiation of rehabilitation, was also associated with lower incidence of delirium
during the hospital stay and at one month.65 Most of the studies identified in the systematic reviews
were medium or low quality.

Use of a checklist may help to embed good fundamental care and reduce incidence of delirium
in patients after an operation.62,63,66 Educating relatives or carers to deliver non-pharmacological
multicomponent interventions, such as reorientation, can also reduce the incidence of delirium.9 1+
1++
A systematic review identified one randomised controlled trial (RCT) that reported an 8% reduction
2++
in the incidence of delirium in those patients cared for by relatives who were educated in 4
delivering a reorientating intervention versus care as usual, RR 0.42, 95% CI 0.19 to 0.92.61 Advice
on information to provide to family and carers, and suggestions of ways to help are in section 9.

Expert consensus recommends the use of multicomponent interventions as fundamental good

4
practice.58,67,68 Pathways for good practice for risk reduction and management are in Annexes 3 and 4.

11
Risk reduction and management of delirium

R The following components should be considered as part of a package of care for patients
at risk of developing delirium:
• orientation and ensuring patients have their glasses and hearing aids
• promoting sleep hygiene
• early mobilisation
• pain control
• prevention, early identification and treatment of postoperative complications
• maintaining optimal hydration and nutrition
• regulation of bladder and bowel function
• provision of supplementary oxygen, if appropriate.

99 Ward moves should be avoided wherever possible for patients at risk of delirium.

99  rior to surgery patients and carers should be advised of the risk of developing delirium,
P
to alleviate distress and help with management if it does occur.

99  here possible, assistance should be sought from a patient’s relatives and carers to deliver
W
care to reduce the risk of delirium developing.

4.2.1 Anaesthetic management

Using monitoring to avoid episodes of deep anaesthesia in patients aged over 60 under general
anaesthesia for surgery lasting more than one hour can significantly reduce the risk of developing
postoperative delirium. Two RCTs have shown a reduction in incidence of 16.7% in the monitoring
group versus 21.4% in the control group and 15.6%, intervention, versus 24.1%, control.69,70
1++
A substudy from a large RCT showed a risk reduction that did not reach statistical significance (18.8% 1+
in the intervention group and 28% in the control group), however, meta-analysis of the three trials
and one further study of bispectral index-guided sedation reported an odds ratio (OR) of 0.56, 95%
CI 0.42 to 0.73.71 None of the studies included patients with dementia, emergency anaesthesia or
surgery for hip fracture in older patients.

R Depth of anaesthesia should be monitored in all patients aged over 60 years under general
anaesthesia for surgery expected to last for more than one hour, with the aim of avoiding
excessively deep anaesthesia.

4.3 Intensive care

A number of studies of non-pharmacological interventions in ICU settings were identified.72-77
Interventions included acupuncture, mirror therapies, and range of motion exercises. Most of
the studies were underpowered. The largest trial addressed the use of dynamic light therapy to 1+
1–
reduce the incidence and duration of delirium in patients in ICU.77 It did not find the therapy to be
more effective than placebo. Due to the heterogeneity of interventions and populations no single
intervention for patients in ICU can be recommended.

A systematic review of eight studies of a multicomponent care approach reported benefit in five
of the studies.78 The other three studies showed no difference between the treatment and control
groups. However, the multicomponent care approach is considered as standard good practice (see 1+
section 4.2), and the effect of multimodal therapy may not be as evident as in other patient groups,
given that critically ill patients exhibit ongoing risk factors for much of their critical care admission.

12
 4 | Non-pharmacological risk reduction

The use of earplugs, either alone or along with eye shades and other noise-reducing strategies
to promote sleep in ICUs, was associated with a reduction in the incidence of delirium, RR 0.59,
95% CI 0.44 to 0.78, in a systematic review of five low-quality studies (832 patients).79 Suitability 2++

for earplugs should be considered on an individual basis as there may be a risk of exacerbating
confusion in some patients.

R The use of earplugs should be considered as part of a sleep-promotion strategy in intensive

care.

13
Risk reduction and management of delirium

5 Pharmacological risk reduction

5.1 Medicines optimisation

Delirium has numerous causes that interact in any one person to cause delirium. Several classes of
medication can increase the likelihood of delirium occurring, and the probability that a drug will
precipitate delirium should be considered when prescribing, particularly in those at increased risk
1++
of delirium.61,80,81 Observational evidence suggests that exposure to certain medicines increases 2+
the odds of delirium developing and that medication review can decrease rates of delirium.80-83
The following is an approach to medication review and prescribing in people who are experiencing,
or are at increased risk of, delirium, and covers three broad areas.

• A
 ny changes in medications, including over-the-counter and herbal medications. Commencement
of new medications, changes in dosage of medication or abrupt withdrawal of medication could
result in delirium.84,85
• C
 hanges in how the body handles and is affected by medication. The natural physiology of 3
ageing can result in medication, which has been beneficial without side effects for years, 4
2+
now causing or contributing to delirium. The same can also be said for acute derangements in
physiology seen with illness.84
• D
 elirium risk should be considered when assessing the risks and benefits of commencing a
new medication.81,84

It is impossible to cover all medication that may cause or contribute to delirium but some medication
particularly associated with delirium merits discussion.

Benzodiazepines markedly increase the odds of delirium developing in a variety of settings (OR
3.0 95% CI 1.3 to 6.8) and should not be used unless in specific circumstances such as management 1++

of alcohol withdrawal or acute seizure management.81

Opiates can also cause delirium but they remain a vital class of drug for treating pain. It is
important to remember that pain in itself can precipitate delirium. A systematic review cited an OR
of delirium associated with treatment with opioids of 2.5 (95% CI 1.2 to 5.2).81 However, the main
opioid in the review, which carries the highest risk, is pethidine (OR 2.7, 95% CI 1.3 to 5.5), which
1++
is anticholinergic and is rarely used in the UK. More commonly used opioids such as morphine
(OR of delirium 1.2, 95% CI 0.6 to 2.4) and fentanyl (OR of delirium 1.5, 95% CI 0.6 to 4.2) were
not significantly associated with delirium.81 The opioid with the lowest odds of causing delirium
was oxycodone but this still had a confidence interval that crossed 1 (OR 0.7, 95% CI 0.3 to 1.6).81

Probably the most important factor when using opiate analgesia is titrating to the minimal effective
dose to achieve pain control and minimise side effects. If opiates are used it is also important to
be holistic and prescribe laxatives to prevent constipation which can contribute to delirium.

Optimising the dose of analgesic and sedative drugs in a critical care setting is advocated.86 Daily
sedative interruption or nurse-protocolised sedation to facilitate spontaneous breathing trials and 4
daily mobilisation have been associated with improved outcomes, although not directly delirium.86

Although delirium is not specifically covered in the NHSScotland polypharmacy guideline, the
guideline contains information on medication to avoid or reduce in older people, some of which is
aimed at reducing falls by reducing medications that can cause delirium. Medications recommended
4
to avoid, stop or reduce the dose if possible include tricyclic antidepressants, anticholinergic
medications, benzodiazepines, antihistamines and tramadol. The guideline also contains practical
information on how to safely reduce chronic medication with potential for withdrawal such as
benzodiazepines.87

14
 5 | Pharmacological risk reduction

R All patients at risk of delirium should have a medication review conducted by an experienced
healthcare professional.

99  reas with patients at high risk of delirium, such as trauma orthopaedic wards, should have
A
protocols for commonly required medication (eg analgesia and anti-emesis) that contain
choices for first-line treatments which minimise the risk of causing delirium.

5.2 Antipsychotics
Some, low-quality, studies suggest that prophylactic antipsychotic medication may be beneficial
for the prevention of postoperative delirium in patients undergoing cardiac, general, elective joint
replacement and hip fracture surgery.88-91 One systematic review did not support its use.92 Results
1+
in this review may have been skewed by the inclusion of a controlled trial in which an imbalance 1++
in the age of participants could have been a confounding factor. A Cochrane review concluded that
there was no evidence of benefit for the use of haloperidol, but olanzapine compared to placebo,
reduced the incidence of delirium (RR 0.36, 95% CI 0.24 to 0.52).63

A systematic review of several small studies evaluated the use of haloperidol prophylaxis in ICU
or surgical patients compared to placebo and found that haloperidol prophylaxis did not decrease 1++

the incidence of delirium overall or in subgroup analysis of the patient groups (ICU or surgery).93

A systematic review of six RCTs concluded that there appears to be a greater benefit from
antipsychotic prophylaxis in patients at higher risk of delirium.88 If delirium did occur, prophylaxis
did not reduce the severity or duration, length of hospital stay or mortality.88 Two systematic 1++

reviews cited one RCT which found that although prophylactic haloperidol did not reduce incidence
of delirium it was associated with a reduction in delirium duration and severity.88,94

Two small RCTs concluded that daily doses of ≥5 mg haloperidol may reduce the incidence of
1++
delirium in surgical patients.93

Overall no optimal regime for perioperative antipsychotic use was determined from the studies.

A large RCT, designed primarily to investigate the effect of prophylactic haloperidol on survival
of critically ill patients, also measured delirium incidence as a secondary outcome. No difference
1++
was found between the haloperidol and placebo groups: delirium incidence (mean difference 1.5%,
95% CI -3.6% to 6.7%).95

There is insufficient evidence to determine whether antipsychotic prophylaxis is effective in other

hospital inpatients.92,94,96,97 One Dutch multicentre RCT (n=242) examined the efficacy of prophylactic
1++
oral haloperidol in patients ≥70 years of age at risk of delirium, acutely admitted to hospital for 1+
1–
both medical and surgical emergencies. It concluded that haloperidol prophylaxis did not lower
delirium incidence during the first seven days of admission in this patient group.98

Common side effects of antipsychotics include constipation, movement disorders, QTc prolongation,
reduced seizure threshold, urinary retention and neuroleptic malignant syndrome.15 One of the
secondary outcomes of the Dutch RCT was to examine haloperidol safety. No significant differences
were found between oral haloperidol and placebo for changes to QTc interval.98 Similarly, three 1+
other RCTs, in a systematic review, reported no difference in QTc prolongation or extrapyramidal 1++

side effects with haloperidol prophylaxis compared to placebo.93 Otherwise, adverse effects were
rarely noted, but this could be due to lack of reporting in the studies included in the systematic
reviews.

No antipsychotics are licensed for the prophylaxis of delirium. There is insufficient evidence of
benefit to recommend the use of antipsychotic prophylaxis in patients at risk of developing delirium.

15
Risk reduction and management of delirium

5.3 Dexmedetomidine
Dexmedetomidine has been utilised in a perioperative and critical care setting. A meta-analysis
identified 14 trials of medium to low quality, incorporating 3,029 patients in ICU (general and
postoperative).99 Dexmedetomidine was compared to other therapies (propofol, midazolam or
morphine) or placebo to assess reduction of the incidence of delirium, agitation and confusion.
1+
Overall, analysis was associated with a significant reduction in the incidence of delirium with
dexmedetomidine versus controls, RR 0.68, 95% CI 0.49 to 0.96.99 However, not all studies showed
a statistically significant benefit, and the greatest effect was evident when midazolam was used
as the comparator.

An RCT of 90 patients undergoing non-invasive ventilation in ICU found dexmedetomidine to be

superior to haloperidol or placebo (3/30 patients given dexmedetomidine developed delirium
compared to 10/30 given haloperidol and 13/30 in the placebo group; p=0.014).100 However, 1–

patients in both the haloperidol and particularly the placebo group received significantly larger
amounts of supplementary sedatives and analgesics including midazolam.

A two-centre RCT allocated 100 critically ill patients without a diagnosis of delirium to receive
either a nocturnal dexmedetomidine infusion or placebo. Sedatives were halved during the drug
infusion period and opiates were unchanged. Nocturnal dexmedetomidine was associated with 1++

a greater proportion of patients who remained delirium free during their ICU stay (80% v 54%);
RR 0.44, 95% CI 0.23 to 0.82.101

Results of a trial on the use of dexmedetomidine in patients who are mechanically ventilated in
a general ICU setting (Early Goal Directed Sedation Compared with Standard Care in Mechanically
Ventilated Patients in Intensive Care (SPICE III)) are awaited.

A systematic review and meta-analysis of 18 RCTs with 3,309 patients, assessed the efficacy
of perioperative dexmedetomidine on delirium incidence in both adult cardiac and non-cardiac
surgical patients.102 Findings indicated dexmedetomidine reduced postoperative delirium for the
entire surgical population (OR 0.35; 95% CI 0.24 to 0.51). Subgroup analyses of the nine cardiac
surgery studies and nine other surgical studies showed a benefit in both patient groups (OR 0.41;
95% CI 0.26 to 0.63) and (OR 0.33; CI 0.18 to 0.59) respectively. Studies were heterogeneous in
their size, dose and timing of dexmedetomidine administration and in particular the control drug
given. Propofol, midazolam and different opiates were used as comparators, in addition to placebo. 1++
Trials comparing dexmedetomidine directly with placebo were not analysed separately. The largest
study included in the review was in a Chinese population, involving 700 patients given either
dexmedetomidine or placebo postoperatively on arrival in ICU. Delirium was significantly lower
in the group receiving dexmedotimidine (OR 0.35, 95% CI 0.22 to 0.54). However, patients who
were mechanically ventilated were sedated with propofol or midazolam to achieve a set RASS.
Patients in the placebo group received more supplemental sedatives and analgesics compared to
the dexmedetomidine group, which may have increased their delirium risk.102

Two randomised placebo-controlled trials, one each in patients undergoing cardiac and non-
cardiac surgery, showed no reduction in delirium when comparing dexmedetomidine with normal 1++

saline.103,104

Bradycardia and hypotension are known side effects of dexmedetomidine, secondary to its intrinsic
effects as an alpha2-receptor agonist. Dexmedetomidine has been associated with an increased
incidence of bradycardia in patients undergoing cardiac surgery (OR 1.89; 95% CI 1.11 to 3.2) but
this did not appear to be an issue in other surgical groups.102 Neither was there consistent evidence 1++
linking hypotension to dexmedetomidine. Caution should be taken when considering the use of
dexmedetomidine, particularly in patients with low cardiac output states and consideration given
to either omitting or using a lower loading dose prior to starting a continuous infusion.105

16
 5 | Pharmacological risk reduction

There remains controversy over whether dexmedetomidine can reduce the incidence of delirium
in both critically ill patients and those in the perioperative setting. Many of the trials which
indicate a benefit have used other sedative agents, including benzodiazepines in the control group.
It remains unclear if dexmedetomidine can inherently reduce delirium or merely reduce the need
for delirogenic drugs. Since there are potential physiological concerns relating to the widespread
adoption of dexmedetomidine for prophylaxis, in addition to cost implications, dexmedetomidine
cannot be recommended for the prevention of delirium. Large randomised placebo-controlled trials
and cost-effectiveness studies are warranted.

5.4 Other pharmacological therapies

One systematic review included four RCTs which reported the incidence of postoperative delirium
when comparing ketamine to placebo. Overall, the incidence of postoperative delirium did not
differ between the control and intervention groups. The quality of each RCT was low, so the review 1++
concluded that the effect of ketamine on postoperative delirium is unclear. The largest RCT reported
an increase in postoperative hallucinations and nightmares with ketamine use.106

Systematic reviews identified four RCTs on the use of melatonin to prevent delirium in medical and
1++
surgical settings.63,107,108 Results were inconclusive. One small RCT in 88 patients found a melatonin
1+
receptor agonist reduced the incidence (24.4% v 46.5%) and duration (0.78 v 1.4 days) of delirium 2+
in critically ill patients.109

Results from two large RCT are awaited.

17
Risk reduction and management of delirium

6 Non-pharmacological treatment

Other guidelines, narrative reviews and expert opinion on the treatment of patients with established
delirium focus mainly on treating the presumed causes of the delirium, and other aspects of
care such as treating distress and agitation.1,58,60,110 Few trials have been conducted testing such
approaches. There is insufficient high-quality evidence to determine the efficacy of formal packages 4
of non-pharmacological interventions in reducing the severity or duration of delirium when 2++
1++
it does occur.58,61 Meta-analyses did not find a significant difference in the reduction of duration
of delirium with multicomponent care or comprehensive geriatric care, compared to usual care.62,65
One RCT did not find benefit from the use of cognitive-stimulating interventions in patients with
delirium superimposed on dementia.111

Therefore, guidance on treatment of people with delirium relies on expert consensus, which
advocates multicomponent interventions as fundamental good practice.58,67,68 In Scotland a
comprehensive pathway, incorporating the Triggers, Investigate, Manage, Engage (TIME) bundle,
which covers the first two hours of care, and the Scottish Delirium Association (SDA) delirium 4

management pathway provide protocols for good care (see Annexes 3 and 4). NICE recommends
treating the causes, effectively communicating with the patient, providing a suitable care
environment, and specifically addressing distress.58

R Healthcare professionals should follow established pathways of good care to manage patients
with delirium.
• F
 irst consider acute, life-threatening causes of delirium, including low oxygen level, low
blood pressure, low glucose level, and drug intoxication or withdrawal.
 ystematically identify and treat potential causes (medications, acute illness, etc), noting
• S
that multiple causes are common.
 ptimise physiology, management of concurrent conditions, environment (reduce noise),
• O
medications, and natural sleep, to promote brain recovery.
• S
 pecifically detect, assess causes of, and treat agitation and/or distress, using non-
pharmacological means only if possible (see section 7 for pharmacological treatment).
• C
 ommunicate the diagnosis to patients and carers, encourage involvement of carers,
and provide ongoing engagement and support.
• A
 im to prevent complications of delirium such as immobility, falls, pressure sores,
dehydration, malnourishment, isolation.
• Monitor for recovery and consider specialist referral if not recovering.
• Consider follow up (see section 8).

99 Promote cognitive engagement, mobilisation, and other rehabilitation strategies.

Advice on information to provide to family and carers, and suggestions of ways to help are in
section 9.

18
 7 | Pharmacological treatment

7 Pharmacological treatment

7.1 Antipsychotics
Studies of the efficacy of antipsychotics are heterogenous and inconclusive. Most are small and
rated as low or very low quality.92,96,112,113 One meta-analysis concluded that antipsychotics should
not be used in non-ICU settings for the treatment of patients with delirium, while another concluded
that antipsychotics were superior to placebo or usual care in reducing delirium severity scale 2++
scores.92,112 A Cochrane review concluded that antipsychotics did not reduce delirium severity, 1+

resolve symptoms or alter mortality in the acute care setting.113 The Cochrane review also identified
a large RCT of patients receiving palliative cancer care, which found that patients treated with either
risperidone or haloperidol had worse delirium symptom scores than those receiving placebo.113

Comparisons of haloperidol and other antipsychotics did not find any antipsychotic to be more
1+
effective than another.96,112,114 Two RCTs comparing the efficacy of haloperidol and quetiapine 2++
reported conflicting results.112,115

No serious side effects were reported in the studies of haloperidol and overall adverse effects were
poorly or rarely reported.94,96 Haloperidol was associated with a higher incidence of extrapyramidal
side effects and dystonias than second generation antipsychotics, although this may be due to the
high dose of haloperidol used in the trials.112,114 The Cochrane review concluded that extrapyramidal
2++
symptoms were not more frequent with antipsychotics compared to non-antipsychotics and there 2+
was no difference between typical and atypical antipsychotics.94 Haloperidol is contraindicated in
combination with any drug that is associated with QTc prolongation.116 If it is used with other QT
prolonging drugs, treatment is rendered unlicensed. Advise on prescribing unlicensed medicines
can be found in section 1.3.2.

If commenced, antipsychotics prescribed for delirium should be reviewed on a daily basis and
stopped as soon as the clinical situation allows, typically within 1–2 days. In situations where it is
deemed safer to continue antipsychotic therapy for delirium beyond discharge or transfer from
hospital, a clear plan for early medication review and follow up in the community should be agreed.

Pooled subgroup analysis of two small trials of patients in ICU with delirium found use of
antipsychotics to be marginally superior to placebo in response rate at the studies’ endpoint (risk
ratio 0.25, 95% CI 0.06 to 1.02). Second generation antipsychotics were superior to haloperidol in 1++
reducing delirium severity scores in patients in ICU (standardised mean difference (SMD) -0.52,
95% CI -0.85 to -0.19). There was no difference in discontinuation rates or adverse events.112

A systematic review identified five studies, one of which reported that quetiapine reduced the
duration of delirium (1 day v 4.5 days) compared to placebo in 36 patients.97 None of the studies 1+
reported a reduction in length of stay, or mortality.

Because the studies identified are underpowered, further, larger trials are needed before
recommendations can be made on the use of antipsychotics for the treatment of patients in ICU
with delirium.

7.2 Dexmedetomidine
A small RCT on the use of dexmedetomidine in patients with agitated delirium receiving mechanical
ventilation in ICU reported secondary outcomes of a reduction in delirium (23.3 hours v 40 hours 1+

with placebo) and reduced the length of ICU stay.117

19
Risk reduction and management of delirium

7.3 Acetylcholinesterase inhibitors

One systematic review included six small RCTs, comparing either donezepil or rivastigmine to
placebo in patients older than 60 years. Five of the trials were in surgical settings. Four of the
seven studies found no benefit from acetylcholinesterase inhibitors and overall the studies were not 1+

sufficiently powered to detect a difference between the intervention medication and placebo. Four
of the seven studies found acetylcholinesterase inhibitors to have similar tolerability to placebo.118

A systematic review identified one RCT (104 participants) which reported longer duration of
delirium and longer length of hospital stay in patients with delirium in ICU given a combination
of haloperidol and rivastigmine compared to those given haloperidol and placebo.118 There
1+
were three times as many deaths among patients receiving the haloperidol and rivastigmine
combination.118 There is insufficient evidence to draw conclusions on the efficacy and safety of
the use of acetylcholinesterase inhibitors for the treatment of patients with delirium.

7.4 Benzodiazepines
In a systematic review only one small trial (n=30) was identified on the use of lorazepam in the
treatment of patients with delirium. The trial, in patients with acquired immune deficiency syndrome
2+
(AIDS) in a hospital setting, found no benefit from lorazepam and treatment was stopped early
due to intolerable side effects.114

7.5 Urgent pharmacological intervention

While the evidence for pharmacological treatment is insufficient to support a recommendation,
expert opinion supports a role for medication in specific situations such as in patients in intractable
distress, and where the safety of the patient and others is compromised (see Annex 4).

20
 8 | Follow up

8 Follow up
Older patients who develop delirium may have undiagnosed underlying dementia or mild cognitive
impairment.119,120 Delirium is also associated with an increased rate of cognitive decline after the
3
episode of delirium.119,120 The majority of studies identified found that delirium is a risk factor for 2++
future cognitive decline.121-124 Longer duration of delirium has been linked to worse global cognition
at three and 12 months’ follow up.122

A systematic review of non-comparative prospective studies concluded that people may develop
depression after experiencing delirium.125 The length of time before people experience depression
post-delirium in ICU varied between studies, with some reporting no association between delirium
and depression at three months, but higher rates of depression and worse mental health status at 2+
12 months, and others reporting depression at three, four, six and 12 months.125,126 Other studies did 3

not find a significant association between delirium, post-traumatic stress disorder (PTSD), anxiety
or depression.127-129 In these studies the patient groups were younger (mean ages 42, 61 and 62
compared to mean age >80 years in the majority of studies in the systematic review).125,127-129

The studies addressed a variety of population groups, in acute and ICU settings, and used different
measures for delirium, mental and cognitive impairment and depression.

R Healthcare professionals should be aware that older people may have pre-existing cognitive
impairment which may have been undetected, or exacerbated in the context of delirium.
Appropriate cognitive and functional assessment should be considered. Timing of this
assessment must take into account persistent delirium.

R In patients who have experienced delirium in ICU consideration should be given to follow
up for psychological sequelae including cognitive impairment.

99  atient records should be coded to highlight a previous episode of delirium so that hospital
P
staff are aware of the increased risk on readmission.

99 Ensure that delirium is noted in the discharge letter for the primary care team.

99 All patients who have had delirium should be reviewed by the primary care team.

21
Risk reduction and management of delirium

9 Provision of information

This section reflects the issues likely to be of most concern to patients and their carers. These
points are provided for use by health professionals when discussing delirium with patients and
carers and in guiding the development of locally-produced information materials.

9.1 Checklist for provision of information

This section gives examples of the information patients/carers may find helpful at the key stages
of the patient journey. The checklist was designed by members of the guideline development
group based on their experience and their understanding of the evidence base. The checklist is
neither exhaustive nor exclusive.

If a patient is at risk of delirium

Identify the family and/or main carer of the patient.

• Ensure that the patient’s contact details are on file. If the patient lacks capacity, ascertain
whether a family member or carer has Power of Attorney/Guardianship over welfare.

Explain to the patient and the family/carer about delirium:

• Delirium is common amongst hospitalised patients especially following an operation.

• Acute triggers of delirium include:

- infection, dehydration, severe constipation, urinary retention, and pain
- critical illness
- surgery especially heart and hip operations
- side effects of new medicines or medicines withdrawal.

• Those most at risk are:

- older people
- older people on multiple medicines
- people with dementia, Parkinson's disease, stroke or pre-existing cognitive impairment
- people who are hearing or visually impaired.

Ask family/carers to alert medical staff if they notice any change to their relative's normal
behaviour.

Ask the patient and family/carers to complete a ‘Getting to know me’ form (see section 9.3.2),
or similar, to help healthcare staff to take care of the person’s specific needs.

Ask family/carers to help, if they feel able to do so, to reduce the risk of delirium developing
by doing the following:
• ensure hearing aids, glasses and dentures are available at all times
• talk to and keep the patient informed in short, simple sentences
• check that the patient has understood you and be prepared to repeat if necessary
• keep a calendar and/or clock within view
• bring in some familiar objects from home to the hospital to keep next to the bed side
• if required, encourage the patient to eat and drink.

22
 9 | Provision of information

If a patient develops delirium

Explain to the patient and family/carers that delirium is a change in mental state that often starts
suddenly but usually improves when the physical condition improves and the underlying cause
gets better.
Discuss treatment options and possible side effects with the patient and/or carer.
Provide the family/carer with appropriate information leaflets.

It is important for carers and relatives to participate and work together with the clinical team in
hospital or home to clear delirium and give the affected person the best chance of getting back
to good health.
Explain that the person affected with delirium may show many different types of change.
The patient may:
• be less aware of their surroundings
• be unable to speak clearly or follow conversations
• have dreams which can sometimes be frightening and can carry on when they wake up
• hear voices or noises which may not be present (auditory hallucinations)
• see objects or people that are not present or in different context (visual hallucinations)
• get upset that other people are trying to harm them
• be agitated or restless, unable to sit still, and have an increased risk of having a fall
• be sleepy and slow to move and respond
• be reluctant to eat or drink
• have a temporary change in personality
• have all or some of the above and that could quickly change
• have worse symptoms in the evenings or overnight.
Suggest completing a diary so that if the person with delirium cannot remember what has
happened the carer can fill in the blanks and help make sense of the experience once the person
is starting to feel better.
Let the family/carer know how to help someone with delirium:
They can help by reassuring and reorienting the patient, eg:
• ensure hearing aids, glasses and dentures are available at all times
• have a gentle and friendly approach, smiling and providing reassurance
• talk and keep the patient informed in short, simple sentences
• check that the patient has understood you and be prepared to repeat if necessary
• familiarity helps, so try to make sure that someone the patient knows well is with them
• try not to agree with any incorrect ideas but disagree with tact and change the subject
• keep a calendar and/or clock within view and give reminders of the surroundings.
• bring in some familiar objects from home to the hospital to keep next to the bed side
• remind the patient to eat and drink and assist if required.

The key is to remain calm and help the affected person feel calm and in control.

At discharge following an acute episode of delirium

Liaise with the family/carers regarding discharge arrangements. Discuss with family/carers
whether they need extra support. Some patients may still be recovering, not be entirely
themselves or be less able than usual to carry out their daily activities.
Inform carers of their right to have a new or updated adult carer support plan.
Ensure that support is in place before the patient is discharged to their home.
If there are concerns about cognitive impairment in the following months, advise the patient/carers
to see their general practitioner (GP).

23
Risk reduction and management of delirium

9.2 Publications from SIGN

SIGN patient versions of guidelines are documents that ‘translate’ guideline recommendations and
their rationales, originally developed for healthcare professionals, into a form that is more easily
understood and used by patients and the public. They are intended to:
• h
 elp patients and carers understand what the latest evidence supports around diagnosis,
treatment and self care
• e
 mpower patients to participate fully in decisions around management of their condition in
discussion with healthcare professionals
• highlight for patients where there are areas of uncertainty.

A copy of the patient version of this guideline is available from www.sign.ac.uk/assets/patient-

publications

9.3 Sources of further information

9.3.1 Websites

Scottish Delirium Association

www.scottishdeliriumassociation.com
The Scottish Delirium Association consists of healthcare professionals working to share best practice
in delirium by providing education, promoting research and raising awareness of the condition.

Critical Care Recovery

www.criticalcarerecovery.com
This is a website developed by the NHS to offer information, advice and support on recovery
after intensive care.

Minded for Families

www.mindedforfamilies.org.uk
This is a website with videos and information to raise awareness of what delirium is and help
older people and those around them with how to deal with it.

9.3.2 Information leaflets

THINK Delirium
www.knowledge.scot.nhs.uk/media/CLT/ResourceUploads/4052742/20141007%20Delirium%20
leaflet%20(web).pdf
This is patient information leaflet developed by Healthcare Improvement Scotland in collaboration
with NHS boards.

Alzheimers Scotland
www.alzheimers.org.uk/info/20029/daily_living/370/delirium
This is a patient information leaflet on the effects of delirium, treatment and what happens
afterwards. It also includes patient experiences.

www.alzscot.org/information_and_resources/information_sheet/3472_getting_to_know_me
The ‘Getting to Know Me’ form was designed for patients with dementia. It is completed with
information about the person’s likes and dislikes and needs and is held with the patient notes to
allow staff to provide the best care possible.

24
 9 | Provision of information

Dementia UK
www.dementiauk.org/delirium
This web-based leaflet describes the symptoms of delirium and gives suggestions of what carers
can do to help a person with delirium.

Marie Curie
www.mariecurie.org.uk/professionals/palliative-care-knowledge-zone/symptom-control/delirium
This web-based leaflet focuses on delirium occurring towards the end of life. It describes causes,
and offers advice on what carers can do and when to seek expert help.

NHS website
www.nhs.uk/conditions/confusion
This leaflet provides advice on when to contact a GP or phone an ambulance if someone is showing
signs of delirium.

Royal College of Psychiatrists

www.rcpsych.ac.uk/mental-health/problems-disorders/delirium
This leaflet provides information on signs and symptoms, treatment and what may happen after
a person has had delirium.

9.3.3 Telephone helplines

Alzheimers Scotland
0808 808 3000
helpline@alzscot.org
This helpline provides information and emotional support to people with dementia, their families,
friends and professionals.

Dementia UK
0800 888 6678
This helpline is available to support to carers or anyone with dementia.

25
Risk reduction and management of delirium

10 Implementing the guideline

This section provides advice on the resource implications associated with implementing the key
clinical recommendations, and advice on audit as a tool to aid implementation.

10.1 Implementation strategy

Implementation of national clinical guidelines is the responsibility of each NHS board and care
provider and is an essential part of clinical governance. Mechanisms should be in place to educate
staff and review care provided against the guideline recommendations. The reasons for any
differences should be assessed and addressed where appropriate. Local arrangements should then
be made to implement the national guideline in individual hospitals, units and practices.

Implementation of this guideline will be encouraged and supported by SIGN.

10.2 Resource implications of key recommendations

No recommendations are considered likely to reach the £5 million threshold which warrants
resource impact analysis.

10.3 Auditing current practice

A first step in implementing a clinical practice guideline is to gain an understanding of current clinical
practice. Audit tools designed around guideline recommendations can assist in this process. Audit
tools should be comprehensive but not time consuming to use. Successful implementation and audit
of guideline recommendations requires good communication between staff and multidisciplinary
team working.

To assist with the implementation of this guideline the guideline development group has identified
the following as key points to audit:

The percentage of:

• at-risk patients assessed using the 4AT tool
• p
 atients in a critical care environment assessed using CAM-ICU or ICDSC (taking account of
appropriate sedation level)
• p
 atients with confirmed delirium who are recorded and coded with delirium, and the diagnosis
is included in discharge summaries to the GP
• patients who have medication review and medications stopped as a result
• patients followed up by the primary care team after experiencing delirium
• operations compliant with depth of anaesthesia monitoring.

The quality of care for older patients with delirium can be measured against the Healthcare
Improvement Scotland Care of Older People in Hospital standards.130

10.4 Health technology assessment advice for NHSScotland

In May 2012 the SMC accepted dexmedetomidine hydrochloride for sedation in adult patients
in intensive care unit requiring a sedation level not deeper than arousal in response to verbal
stimulation (corresponding to RASS 0 to -3).

26
 11 | The evidence base

11 The evidence base

11.1 Systematic literature review

The evidence base for this guideline was synthesised in accordance with SIGN methodology.
A systematic review of the literature was carried out using an explicit search strategy devised by
a SIGN Evidence and Information Scientist. Databases searched include Medline, Embase, Cinahl,
PsycINFO and the Cochrane Library. The year range covered was 2012–2017. Internet searches
were carried out on various websites including the US National Guidelines Clearinghouse. The main
searches were supplemented by material identified by individual members of the development
group. Each of the selected papers was evaluated by two Evidence and Information Scientists
using standard SIGN methodological checklists before conclusions were considered as evidence
by the guideline development group.

The search strategies are available on the SIGN website, www.sign.ac.uk

11.1.1 Literature search for patient and carer issues or concerns

At the start of the guideline development process, a SIGN Evidence and Information Scientist
conducted a literature search for qualitative and quantitative studies that addressed patient and
carer issues of relevance to patients with delirium and their carers. Databases searched include
Medline, Embase, Cinahl and PsycINFO, and the results were summarised by the SIGN Patient and
Public Involvement Advisor and presented to the guideline development group.

11.1.2 Literature search for cost-effectiveness evidence

The guideline development group identified key questions with potential cost-effectiveness
implications, based on the following criteria, where it was judged particularly important to gain
an understanding of the additional costs and benefits of different treatment strategies:
• treatments which may have a significant resource impact
• opportunities for significant disinvestment or resource release
• the potential need for significant service redesign
• cost-effectiveness evidence could aid implementation of a recommendation.

A systematic literature search for economic evidence for these questions was carried out by a
SIGN Evidence and Information Scientist covering the years 2012–2017. Databases searched
include Medline, Embase and NHS Economic Evaluation Database (NHS EED). Each of the selected
papers was evaluated by a Health Economist, and considered for clinical relevance by guideline
group members.

Interventions are considered to be cost effective if they fall below the commonly-accepted UK
threshold of £20,000 per Quality-Adjusted Life Year (QALY).

27
Risk reduction and management of delirium

11.2 Recommendations for research

The guideline development group was not able to identify sufficient evidence to answer all of
the key questions asked in this guideline (see Annex 1). The following areas for further research
have been identified.
• R
 esearch into detection and management of people with delirium in primary care, community
and long-term care settings.
• V
 alidation of tools for routine monitoring of patients with delirium with clarification of the
frequency of using these tools and their impact on outcomes and cost effectiveness.
• S
 tudies of the practicalities and diagnostic yield of performing EEG in adults presenting with
delirium.
• R
 CTs on the efficacy of depth of anaesthesia monitoring in reducing postoperative delirium
in patients with dementia undergoing surgery and patients undergoing emergency surgery or
trauma orthopaedic surgery.
• T
 rials of multicomponent interventions for the treatment of patients with delirium in general
hospital settings.
• L
 arge multicentre trials detailing a package of non-pharmacological interventions in the ICU
with evidence of implementation.
• R
 CTs on the efficacy and safety of antipsychotics in reducing the risk of delirium in patients
in ICU or other hospital settings.
• R
 CTs on the efficacy and safety of haloperidol in the reduction of the severity and duration of
delirium in non-ICU settings.
• R
 CTs on the efficacy and safety of antipsychotics, benzodiazepines or dexmedetomidine in the
reduction of the severity and duration of delirium in patients in ICU.
• S
 tudies on the impact of follow-up clinics and community mental health support for people
who have experienced delirium, in improving first-year mortality.

11.3 Review and updating

This guideline was issued in 2019 and will be considered for review in three years. The review
history, and any updates to the guideline in the interim period, will be noted in the review report,
which is available in the supporting material section for this guideline on the SIGN website:
www.sign.ac.uk

Comments on new evidence that would update this guideline are welcome and should be sent to the
SIGN Executive, Gyle Square, 1 South Gyle Crescent, Edinburgh, EH12 9EB (email: sign@sign.ac.uk).

28
 12 | Development of the guideline

12 Development of the guideline

12.1 Introduction
SIGN is a collaborative network of clinicians, other healthcare professionals and patient organisations
and is part of Healthcare Improvement Scotland. SIGN guidelines are developed by multidisciplinary
groups of practising healthcare professionals using a standard methodology based on a systematic
review of the evidence. Further details about SIGN and the guideline development methodology
are contained in ‘SIGN 50: A Guideline Developer’s Handbook’, available at www.sign.ac.uk

This guideline was developed according to the 2015 edition of SIGN 50.

12.2 The Guideline Development Group

Dr Ajay Macharouthu Consultant in Liaison Psychiatry for Elderly, University
(Co-Chair) Hospital Crosshouse, Kilmarnock
Professor Alasdair MacLullich Professor of Geriatric Medicine, University of Edinburgh,
(Co-Chair) Honorary Consultant in Geriatric Medicine, Royal Infirmary
of Edinburgh
Dr Anthony Byrne Consultant Physician, Forth Valley Royal Hospital, Larbert
Dr Sweyn Garrioch Consultant Anaesthetist, Borders General Hospital, Melrose
Dr Michael Götz Consultant Psychiatrist, Forth Valley Royal Hospital, Larbert
Ms Maureen Huggins Carer representative, Dumfries
Dr Julie Mardon Consultant in Emergency Medicine, University Hospital
Crosshouse, Kilmarnock
Dr Sharon Mulhern Consultant Clinical Lead – Neuropsychology, Ayrshire
Central Hospital, Irvine
Mr Brian O’Toole Health Economist, Healthcare Improvement Scotland
Dr Gautamananda Ray Consultant Physician, Royal Alexandra Hospital, Paisley
Ms Daisy VE Sandeman Clinical Nurse Practitioner, Royal Infirmary of Edinburgh
Mrs Lynne Smith Evidence and Information Scientist, Healthcare Improvement
Scotland
Dr Roy Soiza Consultant Physician, Aberdeen Royal Infirmary
Ms Christine Steel AHP Consultant (Dementia), West Glasgow Ambulatory
Care Hospital
Ms Ailsa Stein Programme Manager, SIGN
Ms Alyson Warren Lead Pharmacist, Care of the Elderly, Raigmore Hospital,
Inverness
Dr Elizabeth Wilson Consultant in Critical Care Medicine and Anaesthesia,
Royal Infirmary of Edinburgh
Dr Maria Wybrew General Practitioner, Thurso and Halkirk Medical Practice

The membership of the guideline development group was confirmed following consultation
with the member organisations of SIGN. All members of the guideline development group made
declarations of interest. A register of interests is available in the supporting material section for
this guideline at www.sign.ac.uk

29
Risk reduction and management of delirium

Guideline development and literature review expertise, support and facilitation were provided by
SIGN Executive and Healthcare Improvement Scotland staff. All members of the SIGN Executive
make yearly declarations of interest. A register of interests is available on the contacts page of
the SIGN website www.sign.ac.uk

Euan Bremner Project Officer, SIGN Executive

Karen Graham Patient and Public Involvement Adviser, Healthcare
Improvement Scotland
Administration Officer, SIGN Executive
Domenico Romano Publications Designer, SIGN Executive
Gaynor Rattray Guideline Co-ordinator, SIGN Executive
Dr Carolyn Sleith Evidence and Information Scientist, Healthcare
Improvement Scotland

12.3 Acknowledgements
SIGN is grateful to the following former members of the guideline development group and others
who have contributed to the development of the guideline.

Ms Karen Martin Mental Health Development Co-ordinator, Carers Trust,

Glasgow
Mr James McKillop Patient representative, Glasgow
Ms Rachael Wybrew Medical student, Birmingham

12.4 Consultation and peer review

12.4.1 National open meeting

A national open meeting is the main consultative phase of SIGN guideline development, at which
the guideline development group presents its draft recommendations for the first time. The
national open meeting for this guideline was held on 21 June 2018 and was attended by 123
representatives of all the key specialties relevant to the guideline. The draft guideline was also
available on the SIGN website for a limited period at this stage to allow those unable to attend
the meeting to contribute to the development of the guideline.

12.4.2 Specialist review

This guideline was reviewed in draft form by the following independent expert referees, who
were asked to comment primarily on the comprehensiveness and accuracy of interpretation
of the evidence base supporting the recommendations in the guideline. The guideline group
addresses every comment made by an external reviewer, and must justify any disagreement with
the reviewers’ comments. A report of the peer review comments and responses is available in
the supporting material section for this guideline on the SIGN website. All expert referees made
declarations of interest and further details of these are available on request from the SIGN Executive.

SIGN is very grateful to all of these experts for their contribution to the guideline.

Dr Nikhil Agrawal General Practitioner, Southside Road Surgery, Inverness

Dr Jonathan Antrobus Consultant Anaesthetist, Borders General Hospital, Melrose
Dr Janet Bennison Consultant Geriatrician, Borders General Hospital, Melrose
Dr Claire Copeland Consultant Physician, Forth Valley Royal Hospital, Larbert

30
 12 | Development of the guideline

Dr Duncan Gray Associate Specialist Geriatrician, Raigmore Hospital,

Inverness
Dr Conrad Harvey General Practitioner, Ayrshire Central Hospital, Irvine
Ms Lynne Irvine Alzheimer Scotland Dementia Nurse Consultant,
NHS Grampian
Dr Simon McAree Consultant in Anaesthesia and Intensive Care, Borders
General Hospital, Melrose
Mr Scott Murray Older Adults Liaison Psychiatry Nurse Specialist, Borders
General Hospital, Melrose
Dr Terence Quinn Senior Lecturer and Honorary Consultant Physician,
University of Glasgow
Dr Saif Razvi Consultant Neurologist, Queen Elizabeth University Hospital,
Glasgow
Dr Pushkar Shah Consultant Neurologist, Queen Elizabeth University Hospital,
Glasgow
Ms Sandra Shields Alzheimer Scotland Dementia Nurse Consultant, NHS Greater
Glasgow and Clyde
Ms Helen Skinner Alzheimer Scotland Dementia Nurse Consultant, NHS Fife

12.4.3 SIGN editorial group

As a final quality control check, the guideline is reviewed by an editorial group comprising the
relevant specialty representatives on SIGN Council to ensure that the specialist reviewers’ comments
have been addressed adequately and that any risk of bias in the guideline development process as
a whole has been minimised. The editorial group for this guideline was as follows. All members of
SIGN Council make yearly declarations of interest. A register of interests is available on the SIGN
Council Membership page of the SIGN website www.sign.ac.uk

Dr Jenny Bennison Royal College of General Practitioners

Dr Roberta James SIGN Programme Lead; Co-Editor
Professor John Kinsella Chair of SIGN; Co-Editor
Dr Jane Morris Royal College of Psychiatrists
Ms Jacqueline Thompson Royal College of Nursing

31
Risk reduction and management of delirium

Abbreviations

4AT 4 As Test (Arousal, Attention, Abbreviated Mental Test 4, Acute change Test)

AIDS acquired immune deficiency syndrome

AMT Abbreviated Mental Test

CAM Confusion Assessment Method

CI confidence interval

CRP C-reactive protein

CSF cerebrospinal fluid

CT computed tomography

CXR chest X-ray

DOS Delirium Observation Screening Scale

DRS-98-R Delirium Rating Scale

DSD delirium superimposed on dementia

DSM-5 Diagnostic and Statistical Manual of Mental Disorders, fifth edition

ECG electrocardiogram

EEG electroencephalogram

FBC full blood count

GMC General Medical Council

GP general practitioner

ICD-10 International Classification of Diseases, version 10

ICU intensive care unit

ICDSC Intensive Care Delirium Screening Checklist

LFT liver function test

MA marketing authorisation

MMSE Mini Mental State Examination

mRASS Modified Richmond Agitation-Sedation Scale

NCSE non-convulsive status epilepticus

NICE National Institute for Health and Care Excellence

Nu-DESC Nursing Delirium Screening Scale

OR odds ratio

PCR polymerase chain reaction

PTSD post-traumatic stress disorder

32
 Abbreviations

QALY quality-adjusted life year

RADAR Recognising Acute Delirium As part of your Routine

RASS Richmond Agitation – Sedation Scale

RCT randomised controlled trial

RR relative risk

SDA Scottish Delirium Association

SIGN Scottish Intercollegiate Guidelines Network

SMC Scottish Medicines Consortium

SMD standardised mean difference

SPICE III early goal directed sedation compared with standard care in mechanically ventilated
patients in intensive care

SQiD Single Question to Identify Delirium

TCD transcranial doppler

TIME Triggers, Investigate, Manage, Engage

US Ultrasound

UTI urinary tract infection

33
Risk reduction and management of delirium

Annex 1

Key questions used to develop the guideline

This guideline is based on a series of structured key questions that define the target population,
the intervention, diagnostic test, or exposure under investigation, the comparison(s) used and the outcomes
used to measure efficacy, effectiveness, or risk. These questions form the basis of the systematic literature
search.

Section(s) Key question

3.1 1. What tool(s) should be used to detect delirium and when?

Population: Adults at risk of delirium

Assessment tools:
a. 4 As Test (Arousal, Attention, Abbreviated Mental Test 4, Acute change Test) (4AT)
b. Confusion Assessment Method Instrument (CAM)
c. 3D Confusion Assessment Method Instrument (3D-CAM)
d. Delirium Observation Screening Scale (DOS)
e. Single Question to Identify Delirium (SQID)
f. Memorial Delirium Assessment Scale (MDAS)
g. Recognizing Acute Delirium As part of your Routine (RADAR)
h. Delirium Rating Scale – 98 – Revised (DRS-98-R)
i. Intensive Care Delirium Screening Checklist (ICD-SC)
j. CAM for the intensive care unit (CAM-ICU)
k. Richmond agitation sedation score (RASS); Modified RASS
l. Family Confusion Assessment Method Instrument (FAM-CAM)
m. Brief Confusion Assessment Method Instrument (B-CAM)
n. Nursing Delirium Screening Scale (Nu-DESC)
o. Organic Brain Syndrome scale (OBS)
p. Mini Mental State Examination

Comparison: Diagnostic and Statistical Manual (DSM-5) or International Classification of

Diseases (ICD-10) defined diagnosis; between tools
Outcomes: Sensitivity, specificity, evidence of adherence in clinical practical

3.2, 3.3 2. What tool(s) should be used for monitoring purposes and when should they
be used?

Population: Adults at risk of delirium

Assessment tools:
a. 4 As Test (Arousal, Attention, Abbreviated Mental Test 4, Acute change Test) (4AT)
b. Confusion Assessment Method Instrument (CAM)
c. 3D Confusion Assessment Method Instrument (3D-CAM)
d. Delirium Observation Screening Scale (DOS)
e. Single Question to Identify Delirium (SQiD)
f. Memorial Delirium Assessment Scale (MDAS)
g. Recognizing Acute Delirium As part of your Routine (RADAR)

34
 Annexes

h. Delirium Rating Scale – 98 – Revised (DRS-98-R)

i. Intensive Care Delirium Screening Checklist (ICDSC)
j. Confusion Assessment Method Instrument for the intensive care unit (CAM-ICU)
k. Family Confusion Assessment Method Instrument (FAM-CAM)
l. Confusion Assessment Method Instrument (B-CAM)
m. Nursing Delirium Screening Scale (Nu-DESC)
n. Organic Brain Syndrome (OBS) scale

Comparison: Diagnostic and Statistical Manual (DSM-5) or International Classification of

Diseases (ICD-10) defined diagnosis; between tools
Outcomes: Sensitivity, specificity, evidence of adherence in clinical practical

3.4 3. What (other) investigations are useful when assessing a patient for delirium?

Population: Adults with suspected delirium

Intervention:
a. imaging (CT or MRI scans)
b. lumbar puncture
c. electroencephalogram (EEG)
d. testing for antibodies for autoimmune encephalitis
e. toxicology screening

Comparison: Usual care

Outcomes: Sensitivity, specificity, cost effectiveness

4, 5 4. What risk reduction strategies for patients at risk of delirium are effective?

Population: Patients at risk of developing delirium

Interventions:
Multicomponent interventions – non-pharmacological and pharmacological
Non-pharmacological:
a. proactive screening of delirium and pre-existing cognitive impairment including dementia
b. hydration
c. catheterisation avoidance
d. sensory impairment
e. constipation
f. sleep hygiene and promotion
g. falls prevention and mobility
h. providing means of communication
i. impact of ward moves (incl ‘boarding’)
j. environmental factors

Pharmacological:
a. medication reconciliation
b. pain relief
c. antipsychotics and benzodiazepines (medical and surgical patients)
d. sedation for night-time sleep

Comparison: usual care

Outcomes: Incidence of delirium (hospital acquired), prevalence of delirium (community
acquired), duration of delirium, severity of delirium

35
Risk reduction and management of delirium

6 5. What are the most effective non-pharmacological strategies for managing patients
with delirium?

Population: people with delirium

Interventions:
Multicomponent non-pharmacological interventions

(Staff) behavioural adaptations:

• calm non-confrontational manner
• reassurance
• reorientation
• distraction/de-escalation techniques
• one-to-one nursing
• cognitive stimulation

Environmental adaptations:
• single room
• well-lit area
• clear signs re: day, time, season, place
• familiar objects
• family input
• minimise bed moves
• activities and occupational therapy
• address sensory impairment
• sleep promotion
• facilitate mobility

Address specific causes of stress:

• pain
• hunger
• feeling too hot/too cold
• thirst/dry mouth
• urinary retention
• specific fears
• not understanding what is happening
• hallucinations, delusions, aggression, agitation, and wandering/searching

Comparison: Usual care, pharmacological therapies

Outcomes: Mortality, complete response, duration of delirium, severity of delirium, distress in
delirium, length of hospital stay, loss of independent living/new institutionalisation, reduction
in depression and anxiety, reduced dementia risk, worsening of dementia, reduction in long-
term effects, reduction in falls, cost effectiveness

36
 Annexes

7 6. What are the most effective pharmacological strategies for managing patients
with delirium?

Population: Patients with delirium

Consider hyperactive versus hypoactive delirium.
Consider subpopulations:
1. Parkinson’s disease
2. delirium superimposed on dementia
3. patients already taking long-term medication

Interventions:
a. antipsychotics
b. benzodiazepines
c. acetylcholinesterase inhibitors
d. melatonin
e. antidepressants
f. dexmedetomidine
g. clonidine
h. propanolol
i. withdrawal of medicines which may be causing the delirium

Comparison: Usual care, between therapies

Outcomes: Mortality, complete response, duration of delirium, severity of delirium, length of
hospital stay, loss of independent living/new institutionalisation, increased dementia risk,
worsening of dementia, adverse events, reduction in long-term effects, cost effectiveness

8 7. What follow-up care should patients receive after experiencing delirium?

Population: patients who have had delirium

Interventions:
Screening for:
a. dementia
b. functional psychiatry disorders – post-traumatic stress disorder, depression

Comparison: usual care

Outcomes: incidence of dementia after delirium, incidence of psychiatric disorders

37
Risk reduction and management of delirium

Annex 2

Investigations for underlying causes of delirium

The majority of people with delirium are older adults, often with a vulnerability to delirium due to underlying
neurological disease (eg dementia, cerebrovascular disease, Parkinson’s Disease). In each there is commonly
more than one precipitating factor. Identifying these factors and addressing those that are modifiable
underpin the treatment of a person with delirium.

A good clinical history taking into account premorbid illness, cognition and level of function gives key
information. However, the person at risk of delirium may not be able to provide reliable information
themselves due to confusion or diminished attentiveness. A collateral history from the person’s family or
carers should be obtained to confirm and supplement information provided by the person. This collateral
history should be sought at the earliest opportunity. Relatives will often accompany the unwell person when
initially assessed in hospital or at home. Some additional time obtaining this information at an early stage
can assist rapid identification and treatment of precipitants.

A full clinical examination should be undertaken including neurological examination to identify focal signs
and musculoskeletal examination to look for evidence of injury. Confusion and agitation resulting in poor
co-operation or understanding of instructions may make examination difficult.

Severe illness should be identified and rapidly treated as an urgent priority (see Annex 3). This should include
assessment of basic observations, blood oxygen saturations, and blood glucose with near-patient testing to
exclude hypoglycaemia. Intoxication due to medication should be considered in every case.

The information obtained from history and investigation will guide further investigation. Some investigations
would be considered general and applicable to most patients, while others are targeted to specific clues from
history and examination. Investigations will also depend on the setting, whether the person is in hospital
or at home.

These tests are commonly done but this list is not entirely comprehensive.

Blood tests:
• R
 enal function (urea and electrolytes) – to identify dehydration, acute kidney injury, chronic kidney
disease, hyponatraemia.
• Full blood count (FBC) – to identify anaemia, macrocystosis, elevated white cell count
• C-reactive protein (CRP) – to identify inflammation/infection
• L
 iver function tests (LFT) – can identify liver dysfunction which could identify biliary infection, malignant
disease, encephalopathy
• Calcium – hypercalcaemia can cause confusion, and requires further investigation
• Blood cultures – where there is evidence of infection (eg fever or sepsis)
• Thyroid function – thyroid dysfunction can cause confusion
• Vitamin B12 and folate – consider if there are concerns about nutrition or macrocytosis on full blood count.

Electrocardiogram (ECG)
• this may identify clinically silent myocardial ischaemia or arrhythmia which may be significant (such
as atrial fibrillation).

38
 Annexes

Radiological imaging
• C
 hest X-ray (CXR) – should be done if there are symptoms or signs of chest pathology such as infection.
It should be remembered that clinical examination may not reveal all pathology, such as a tumour, and
should be considered.
• Musculoskeletal X-rays – target where there is evidence of injury or suspicion of fracture.
• Other imaging should be guided by history, examination and initial investigations.

Other tests
• Identify hypoxia using pulse oximetry
• U
 rine dipstick and culture – a negative urine dipstick can be useful, in that urinary tract infection (UTI)
would be less likely, but a positive dipstick does not necessarily mean infection. Asymptomatic bacteruria
can also exist in the elderly and delirium may mean that the person is unable to give a history of symptoms
of UTI. This may cloud the situation and treatment of suspected urinary tract infection should be based
on clinical grounds and probability.
• Bedside ultrasound (US) bladder scan – to identify urinary retention
• Pain assessment tools.

This is not a comprehensive list of tests which could be done and investigation should be targeted
from information obtained initially and built on as the clinical situation evolves. Section 3 recommends
investigations which are evidence based.

Where there is consideration of central nervous system pathology as a cause of confusion or delirium, targeted
investigations may be appropriate including brain imaging, lumbar puncture, EEG, auto-antibody testing (such
as for autoimmune encephalitis – antivoltage-gated potassium channel antibodies, anti-NMDA antibodies).

39
Risk reduction and management of delirium

Annex 3

TIME bundle delirium management protocol68

40
 Annexes

Annex 4

Scottish Delirium Association delirium management pathway68

Developed in collaboration with

DELIRIUM MANAGEMENT COMPREHENSIVE PATHWAY

History of Acute Change – Think Delirium

Risk Factors for Delirium
 Acute illness  Dementia  Age over 70 years  Frailty This pathway does
 Sensory Impairment  Polypharmacy  Recent anaesthetic/surgery  Catheterised
 Recent discharge from acute hospital  Use of opioids, benzodiazepines or anticholinergics
NOT relate to
 Restraint  Depression  History of alcohol misuse  Acute or chronic pain alcohol or
substance
misuse.
Clinical suspicion of delirium or “local tool” positive [e.g. 4AT or CAM] If this is suspected
[Screening tools can be negative in the presence of delirium – use clinical judgement] use appropriate
local pathway.
This pathway is
appropriate for Act on acute, severe causes e.g. sepsis, hypoxia, hypoglycemia, medication intoxication
adult patients
(18 years & over) The clinical team should take an informant history and assess capacity to consent to treatment. Delirium is
If the patient is unable to consent to treatment complete an AWI Section 47 (consent to treatment) frequently
form. Treatment plan to be discussed with the patients informant/power of attorney (attach undetected.
certificate to the treatment plan).
This pathway is Be aware that
not exhaustive  An informant should be contacted to provide information about the history of cognitive
impairment and functional ability, in addition to the history of current illness. patients with
Other causes of delirium  The informant should be asked to clarify and quantify alcohol intake and recent changes to delirium may
exist and additional or
prescribed medication, falls, hydration & nutrition and identify current social support. have paranoid
alternative assessments, ideas/delusions:
investigations,  If there is no informant then contact the patient’s GP/social work/carers/care home.
management strategies  Use the IQCODE or AD8 to assist with informant history  Identify current social support risk assess and
or therapies may be manage
necessary for an appropriately.
individual patient. Assess with local tool & record baseline cognitive function.
Clinical judgement &  AMT4 AMT10 MOCA GPCOG  Assess memory, mood, perception, sleep patterns, thinking
decisions should be
made by the Do a full physical examination including detailed neurological examination, speech assessment, and level of
appropriate responsible arousal. Look for local signs of sepsis (e.g. bladder, lungs, skin), constipation and consider PR exam.
healthcare professional. DOCUMENT DIAGNOSIS OF DELIRIUM & SUSPECTED CAUSES; REVISE AS APPROPRIATE

Medication Review Investigation Optimise Management of

 Review age appropriateness Dictated by the history and examination findings Co-morbidity
 Any drugs recently started/stopped?  U&E / LFT / FBC / Glucose / CRP For example;
 Dose changes to medication?  Calcium / Phosphate
 Respiratory disease
 Compliance/concordance issues with medication?  Thyroid function
 Diabetes mellitus
 Carefully consider ongoing needs for:  Oxygen saturation / arterial blood gases
 Cardiac disease / heart failure
Opioids / benzodiazepines / antipsychotics /  ECG
 Thyroid disease
antispasmodics / antiepileptics / antihistamines /  Chest X-ray
antihypertensives (especially if hypotension) /  Parkinson’s disease
 Urinalysis / urine culture
corticosteroids / tricyclic antidepressants / digoxin /  Cerebrovascular disease
 Blood / sputum / stool culture as appropriate
antiparkinsonian medication  CT brain if anti-coagulated (urgent), head
 Avoid abrupt withdrawal of drugs with dependence injury, focal neurological signs, or persistent
potential or possible discontinuationsyndrome. symptoms.

Environmental & General Measures Treatment of Delirium Symptoms

 Approach patient calmly and gently from the front Relax visiting times - use family to reassure and support care
Hypoactive delirium is common in older patients
 Sleep chart; maintain daytime wakefulness with activities
AVOID Treat psychotic symptoms if distressing
 Allow patients to mobilise as much as possible in an area which
Consider additional staff
Bed moves has been deemed safe given confusion/fallsrisk.
 If patient’s symptoms threaten their safety or the safety of others
Unnecessary  Ensure glasses and hearing aids are working, treat ear wax use low dose of one medication (start low – go slow method) and
interventions  Ensure adequate diet taken, keep daily food & fluid charts review every 24 hours
Hypoxia
 Regularly reassure and re-orientate (use clocks & calendars) Consider capacity to consent to treatment (AWI Section 47)
Dehydration
Constipation  Ensure buzzer close to patient and respond promptly to calls Medications for unmanageable agitation/distress:
Catheterisation  Listen to the patient’s expression of needs o * Haloperidol 0.5-1mg orally (max 2mg/24 hours)
 Reduce noise (e.g. monitors and alarms) and background noise o * Haloperidol 0.5mg IM (max 2mg/24 hours) (* Haloperidol is
 If language or hearing problems, consider an interpreter contra-indicated in combination with QTc prolonging drugs, which makes
 Refer to advocacy as appropriate e.g. if patient detained it unlicensed and local “off label” policy should be followed)
under Mental Health (Care and Treatment) (Scotland) Act o Or atypical antipsychotic at low dose, for example, Risperidone 0.25
mgs daily, maximum 1mg in 24 hours
Do not use if signs of Parkinsonism or Lewy Body Dementia
If antipsychotics are contra-indicated (as above),
There are Medical & Nursing Management Lorazepam 0.5-1mg orally (max 2mg/24 hrs); Midazolam 2.5mg IM
often multiple Treat underlying causes (max 7.5mg/24 hours). Younger patients may need higher drug doses

causes of  Infection/sepsis, urinary retention, constipation, hypotension, pain,
delirium but dehydration, hypoxia, hypoglycaemia, hyponatraemia
in up to  Ensure O2 saturation > 95% (except in COPD - type 2 respiratory failure)
 Explain diagnosis to patient & carer and provide information leaflet Triggers for Referral to Liaison Psychiatry
30% of cases
no cause is  Use Butterfly scheme / “Getting to know me” / “This is me” / “Forget me not”  Severe agitation or distress not responding to
 Assess and monitor pain (e.g. by using the Abbey Pain scale or similar) standard measures above
found
 Consider if swallow safe  Doubt about diagnosis
 If detention under the Mental Health Act is
being considered
Psychiatric services may also hold useful information
Patient Improving Repeat delirium screening when on background cognition and mental health.
 Reduce and discontinue antipsychotic treatment clinically indicated until two
 Repeat cognitive assessment successive daily negatives.
 Consider post-delirium distress (eg. recall of delusional states) Improvement may also be seen with Patient NOT Improving
 Encourage patients to share their experience with healthcare staff improving cognition or sleep pattern. After one week or if severe delirium,
refer to the appropriate local specialist

Ongoing Cognitive Impairment No Ongoing Cognitive Impairment Delirium can persist for weeks or
 Document diagnosis of delirium on discharge letter to GP  Document diagnosis of delirium on discharge letter to GP months after the cause is treated
 High risk of recurrent delirium requiring prompt treatment  High risk of recurrent delirium requiring prompt treatment
 Follow Cognitive Impairment Pathway  Increased risk of dementia in the future in older people
Version 1.03 FINAL – Oct 2018; Review by Oct 2020

41
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