Carson, Ryan 67

REVIEW Pract Neurol 2010; 10: 67–81

Managing acute behavioural

disturbance in a neurology
ward
Alan Carson,1 Tracy Ryan2

Episodes of behavioural disturbance are commonplace on neurology wards. The

key to their safe management is prior planning, including securing the safety of
the ward environment, and a formal risk assessment. Protocols which define staff
roles and the unit strategy for the management of behavioural disturbance should
be formally agreed and appropriate training provided. The commonest cause of
disturbed behaviour in neurology—and neurosurgical wards—is delirium. This presents
with fluctuating orientation, grossly impaired attention and disruption of the
sleep–wake cycle. The cause is generally multifactorial with a combination of pre-
existing vulnerabilities and acute precipitants. Management reflects this and depends
on a multifaceted approach to medical care, including basic supportive measures,
minimising polypharmacy and promoting orientation, early mobilisation and
nutritional status, as well as treating the underlying medical conditions. Antipsychotic
medication has a specific treatment effect but never as the only approach to the
management of the delirious patient.

ore years ago than I care

M to remember, when work-

ing as a surgical house-
man, I was ambling across
the lawn between the doctor’s residence
and the wards when the morning took
an unusual twist from the normal rou-
tine: an older patient with Parkinson’s
disease appeared on the hospital roof,
and proceeded, at surprising speed, to
the edge. Even more startlingly, my col-
league and lifelong friend, Bill, appeared
in hot pursuit. A decent tackle betrayed
Bill’s prowess as a rugby flanker but the
patient, oblivious to his Parkinson’s, put
up reasonable resistance. Yells for chlor-
promazine were made from the roof
1
Consultant Neuropsychiatrist
and Part-time Senior Lecturer,
Department of Clinical
Neurosciences, Western General
Hospital, Edinburgh, UK
2
Specialist Registrar in Old
Age Psychiatry, Department of
Psychological Medicine, Royal
Infirmary of Edinburgh, UK
Correspondence to
Dr A Carson, Department of
The management of delirium often takes place in an
Clinical Neurosciences, Western
atmosphere of alarm and uncertainty. Careful planning,
leading to a number of practical steps for management, General Hospital, Edinburgh EH4
will help keep staff calm (Wellcome Library, London). 2XU, UK; a.carson@ed.ac.uk

www.practical-neurology.com
68 Practical Neurology
top but none was available in the drug
trolley; and the suggested 10 mg was
probably inadequate. Bill, who like the
editor of Practical Neurology, knew more
about seamanship than psychopharmacol-
ogy, next called for a rope. His bowlines held
firm and the patient was secured to a chimney
stack in an unorthodox but effective inter-
vention until much needed help arrived. We
all returned to the ward round for Bill to be
duly chastised for lateness and dishevelment.
This was the first of a number of incidents in
which I learnt where things can go wrong in
the management of acute behavioural distur-
bance. … Alan Carson.
In this article, we hope to pass on some tips
that may help to ensure such incidents are
better dealt with.
THE FIVE PS: PROPER
PREPARATION PREVENTS POOR
PERFORMANCE
Neurology wards regularly face episodes of
behavioural disturbance. Most units have at
least one substantive incident every 6–12
months, and minor problems are common-
place. The key stage in their management is
advanced preparation. All too often the first
thoughts given to management are in the
midst of an emergency incident and by then
it may be too late to correct the problems. The
incident above did not demand intensive med-
ical training or resources but rather a cheap
lock to prevent the delirious patient getting
Figure 1
An expert risk assessment of the
clinical environment should be
conducted. A window opening more
than 100 mm represents a major
hazard for falls. AC only discovered this
in a tragic incident when one of his
patients, with an acquired brain injury,
squeezed through a third floor window,
opening 130mm; he still struggles to
believe it was possible. Thankfully the
patient survived and made a complete
recovery from her spinal injuries.
10.1136/jnnp.2009.201848
on to the roof. Preparation for the manage-
ment of behavioural disturbance starts with
an examination of the security procedures in
the ward.
• Environmental precautions are impor-
tant yet often not initiated. A professional
risk assessment of the ward environment
should be conducted as it is unlikely that
many of the easily remedied hazards will
be identified by the average clinician. For
instance, it may come as a surprise that
windows opening more than 100 mm are
a major hazard (figure 1). Consideration
should be given to other environmental
measures, including clear strategies to
aid orientation such as adequate light-
ing, signs and clocks, the design of door
latches, nursing observation points and
quiet areas with space where more dis-
turbed patients can be safely nursed.
• The major procedural security consider-
ation is whether or not to have an alarm
system for patients leaving the ward
(figure 2). Such electronic tagging can
be a very effective nursing aid because
it allows for a less restrictive approach
to confused patients which can in turn
lead to fewer ‘flashpoints’ where aggres-
sive behaviour may develop in response
to frequent restrictions imposed on the
patient’s movement.
• However, it is relational security that
is key to the management of disturbed
patients. Staff must appreciate their role
in the management of disturbed patients.
It is never helpful having staff members

(a)
Figure 2
Mechanical restraints, such as straight jackets, are rightly confined to the pages of history (a). There are, however, helpful procedural security measures such as electronic
tagging that can greatly assist patient care (b). (Patient in a strait-waistcoat, by Ambroise Tardieu, 1838. Used with permission from the Wellcome Library, London.)
acting as ‘barrack room lawyers’ and
holding discussions about whether or not
it is their job to restrain patients while a
colleague is holding desperately on to a
confused patient exiting the hospital, or
worse trying to climb out of a window.
There is a duty on the part of the hospital
to provide a safe environment for the care
of patients and, in the case of a neurosci-
ence centre, it is reasonable to expect that
as a ‘system’ it can cope with the manage-
ment of common, and therefore predict-
able, episodes of disturbed behaviour. For
instance, consideration might be given to
potential roles for psychiatrically trained
nurses or security guards. What matters
is that all staff know what their role is
and are aware of their responsibilities—
policy should not be made ‘on the hoof’
mid-incident. Emotions often run high at
such times and therefore a written policy,
defining staff roles and the unit strategy,
for management of behavioural distur-
bance is recommended. In turn, staff must
be provided with the appropriate training
if they lack skills in managing disturbed
patients.
Other considerations
It is helpful to have a protocol or guidance out-
lining the legal principles underpinning care
Carson, Ryan 69
(b)
Table 1 Within the UK, management of acute behavioural
disturbance takes place under Common Law Principles. The recent
incapacity legislation in England and Wales, and separately in
Scotland, does not alter this in an emergency situation. Key
judgments are listed
Re c(mental patients: refusal of treatment) [1994] 1wlr 290.
Adult has the capacity to consent if he or she can
(1) Understand and retain the information relevant to the decision in
question
(2) Believe that information
(3) Weigh the information in the balance to arrive at an informed choice.
Re f (mental health sterilisation) v. West Berkshire Health Authority (1989)
2wlr, 1025: (1989) all er 673.
“not only (1) must there be a necessity to act when it is not practicable
to communicate with the assisted person but also (2) the action taken
must be such as a reasonable person would in all circumstances take,
acting in the best interests of the assisted person.”
“action properly taken to preserve life, health or wellbeing of the assisted
person (which) may well transcend such measures as surgical operations
or substantial treatment and may extend to include such humdrum
matters as routine medical or dental treatment, even such simple care as
dressing and undressing and putting to bed.”
and what staff may or may not do (table 1).
Regulations vary from country to country and
familiarisation with local rules may be help-
ful as part of an induction course for newly
appointed staff.
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70 Practical Neurology

Emergency sedation is a common response

Table 2 An example of an acute sedation protocol for adults over 65
years of age
to significant incidents and should be prepared
for. It carries significant risk; in particular
because physical aggression can alter the ordi-
nary pharmacokinetics of intramuscular drug
administration.1 Wards are advised to have
a protocol for emergency sedation (table 2)
and staff must be aware that drug doses vary
between patients—for example, a typical adult
may require haloperidol 5–10 mg intramuscu-
larly to achieve an adequate effect but a frail
older patient may be over sedated with 0.5 mg
haloperidol. Importantly, wards should ensure
that the drug trolley always has an available
supply of the drugs on their protocol, and be
aware of the need for observation of vital and
other signs after any emergency sedation.

MANAGING AN INCIDENT
It is far better to try to avoid episodes of
behavioural disturbance (see below) but even
with the best of care it is inevitable that some
incidents will still occur. Unlike the manage-
ment of most medical conditions—‘diagnosis
before treatment’—these often require some
treatment to actually allow assessment to
begin. The pattern is often of acute onset of
disturbed behaviour, emergency manage-
ment (sedation), assessment and then further
management.

Adequate staff numbers to calm

and if necessary to restrain
The first step is to ensure adequate staff num-
bers are available at the scene. Help should be
summoned sooner rather than later and one
should aim to have extra staff physically pre-
sent before they are required by necessity. They
should not become immediately involved, or
confront the patient, but be quietly and unob-
trusively available for emergency assistance if
needed. Three or four members of staff should
go to the patient. One staff member, prefer-
ably familiar to the patient, should take the
lead, stand out in front and try to engage the
patient, speaking calmly but clearly, using open
body language and reinforcing what is said
with non-verbal gestures. He or she should
Reprinted with permission from Nimmo G, ed. Acute medical emergencies
handbook. NHS Lothian use frequent repetition to aid orientation.
Confrontation or chastisement is seldom help-
ful, and tactics such as distraction, “why not
come and get a cup of tea”, are usually more
effective. The patient should be contained
within one area but staff should not intrude on
10.1136/jnnp.2009.201848
 Carson, Ryan 71

Table 3 The IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly)

The assessment: Now we want you to remember what your friend or relative was like 10 years ago and to compare it with
what he/she is like now. 10 years ago was 19__. On the next page are situations where this person has to use his/her memory
or intelligence and we want you to indicate whether this has improved, stayed the same or got worse than in that situation
over the past 10 years. Note the importance of comparing his/her present performance with 10 years ago. So if 10 years ago
this person always forgot where he/she had left things and he/she still does this, then this would be considered ‘Not much
change’. Please indicate the changes you have observed by circling the appropriate answer
1 2 3 4 5
1 Remembering things about Much improved A bit improved Not much change A bit worse Much worse
family and friends (eg
occupations, birthdays,
addresses)
2 Remembering things that have Much improved A bit improved Not much change A bit worse Much worse
happened recently
3 Recalling conversations a few Much improved A bit improved Not much change A bit worse Much worse
days later
4 Remembering her/his address Much improved A bit improved Not much change A bit worse Much worse
and telephone number
5 Remembering what day and Much improved A bit improved Not much change A bit worse Much worse
month it is
6 Remembering where things are Much improved A bit improved Not much change A bit worse Much worse
usually kept
7 Remembering where to find Much improved A bit improved Not much change A bit worse Much worse
things which have been put in
a different place from usual
8 Knowing how to work familiar Much improved A bit improved Not much change A bit worse Much worse
machines around the house
9 Learning to use a new gadget Much improved A bit improved Not much change A bit worse Much worse
or machine around the house
10 Learning new things in general Much improved A bit improved Not much change A bit worse Much worse
11 Following a story in a book or Much improved A bit improved Not much change A bit worse Much worse
on TV
12 Making decisions on everyday Much improved A bit improved Not much change A bit worse Much worse
matters
13 Handling money for shopping Much improved A bit improved Not much change A bit worse Much worse
14 Handling financial matters (eg, Much improved A bit improved Not much change A bit worse Much worse
the pension, dealing with the
bank)
15 Handling other everyday Much improved A bit improved Not much change A bit worse Much worse
arithmetic problems (eg,
knowing how much food
to buy, knowing how long
between visits from family or
friends)
16 Using his/her intelligence to Much improved A bit improved Not much change A bit worse Much worse
understand what’s going on
and to reason things through

Scoring the test

1 = Much improved
2 = A bit improved
3 = Not much change
4 = A bit worse
5 = Much worse

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72 Practical Neurology

Score for this question

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16

Total score

To score the test, add up the result for each question (ie, if ‘Much improved’ the result is 1 for that question), then divide this
number by the total number of questions.
Record the final score of the test in the box below and also add this score to the patient’s cognitive assessment record form.

Sum of the results of all of the questions

= =
The total number of questions 16

Interpretation. A score of >3 indicates the likely presence of dementia. A variety of formal ‘cut-off’ scores have been suggested,
varying from 3.3–3.6 in outpatient settings and 3.6–4.0 in inpatient settings.

In major the patient’s personal space but rather stay at
the perimeter of the area allowing some degree
psychotic illness, of movement within the limits of safety. There
hallucinations is no need to rush this stage and, if the sit-
uation is contained, plenty of time should be
tend to be allowed for everything to calm down. Oral sed-
auditory whereas atives, for example liquid haloperidol, should be
offered. If the situation escalates and restraint
in delirium visual is needed, this should be done by a minimum of
hallucinations are three staff, each knowing their role, and med-
ication, according to protocol, administered.
more common Observation and review are mandatory in the
aftermath. A formal debriefing should be held
as soon as is convenient and points of good
and bad practice noted.
Assessment
Inevitably, clinical assessment usually takes
place after emergency sedation rather than
before. The patient is then often drowsy and it
may only be possible to ascertain limited diag-
nostic information, at least to begin with. The
common differential diagnoses are delirium,
10.1136/jnnp.2009.201848
dementia, acute psychotic illness and, more
rarely, personality disturbance. Diagnostic
information is usually a composite of infor-
mation acquired from the case notes, amal-
gamated with witness descriptions during the
incident and any information which can be
gleaned from the patient.
There are two immediate clinical questions.
• What was the patient’s cognitive state
before the incident? Sometimes this
is obvious—for example, if the admis-
sion was after traumatic brain injury. On
other occasions this will be less clear.
Questioning of relatives at the first avail-
able opportunity can be very useful.
A tool such as the IQCODE (Informant
Questionnaire on Cognitive Decline in the
Older) allows a reliable measure of pre-
existing dementia (table 3).2
• Was the patient orientated at the time of
the incident? This can be difficult to ascer-
tain, particularly if the patient is currently
heavily sedated, but can sometimes be
determined by either direct questioning or
 Carson, Ryan 73

by inference from their speech and behav- Hallucinations, where present, can offer diag-
iour during the event. Disorientation is a nostic clues. In major psychotic illness, hal-
cardinal feature of delirium, and may be lucinations tend to be auditory (although
present in dementia, whereas orientation visual and somatic hallucinations do occur)
is usually maintained in acute psycho- whereas in delirium visual hallucinations are
sis even though the patient may appear more common. One should remember that
perplexed. visual hallucinations are also a core symptom
of Lewy body dementia and occur in a num-
Some estimate of the speed of onset should ber of more benign conditions such as Charles
be made. Bonnet syndrome. Critically, hallucinations in
• Delirium usually presents with an acute major psychoses tend to be linked to com-
onset and a fluctuating course. plex and sustained delusional schema which
are firmly held, involve pathologically false
• Dementia by contrast has an insidious
judgement and they have overwhelming per-
onset and is slowly progressive. However,
sonal significance to the patient. In manic ill-
it must be remembered that patients with
ness they are grandiose, frequently involving
dementia are at high risk of developing
special powers and abilities. In schizophrenia
superimposed delirium.
they are classically persecutory. In depression,
• Manic illness can present relatively delusions are mood congruent and generally
acutely over a few days and be mistaken nihilistic. By contrast, in delirium, delusions,
for encephalopathy. although common and often persecutory,
• Schizophrenia tends to be more insidi- tend to be simple, fleeting and more under-
ous, with deterioration over 3–6 months, standable in terms of the immediate circum-
although the development of actual psy- stances of the patient. Delusions are less
chotic symptoms can be over 2–3 weeks. common in dementia and where present tend
• Psychotic depression usually has an insid- to be simple.
ious onset with a period of low mood giv- Mood assessment is helpful too. In delirium
ing way to an empty apathy. and schizophrenia it is usually fearful. By
contrast, in mania there is a shallow veneer
A mental state examination should be con-
of euphoria often giving way to irritability. In
ducted. A key feature is the degree to which
the patient’s behaviour was goal directed
(suggesting psychotic illness) as opposed to
random interactions with the environment
(more suggestive of delirium or dementia). In
delirium there is also marked disturbance of
the sleep–wake cycle and both hyperactiv-
ity and hypoactivity are recognised. Mania is
accompanied by motor overactivity whereas
in schizophrenia motor activity is often less
marked and in depressive psychosis the patient
is usually apathetic.
Speech and language can be significant. As
well as the usual neurological disruptions, one
should look for the pressured speech with
disjointed linkage of thought structure, often
accompanied by rhyming or punning, suggest-
ing an acute manic illness. In schizophrenia ill-
nesses, the patient can show disjointed linkage
of thoughts and ideas, with so-called ‘knight’s
move’ thinking, accompanied by neologisms
and ‘stock’ words imbued with personal signif-
icance. Although formal thought disorder can Figure 3
sound like dysphasia, the construction of indi- Visuo-perceptual skills, such as
vidual sentences is usually more complete, but incomplete letter recognition and dot
counting, may be particularly poor in
with poor linkage between concepts, whereas delirium compared with early dementia
in dysphasia individual sentences may be (source: Addenbrokes Cognitive
incomprehensible. Examination).

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74 Practical Neurology

depressive psychoses apathy and indifference

Table 4 Standard investigations in delirium. In many situations in a are more common than actual sadness.
neuroscience unit the likely cause will be known and investigations Orientation. Delirium has a fluctuating course,
will not be required. The list below is suggested as a ‘standard’ with orientation often preserved by day but
screening battery only deteriorating at night. Serial formal measure-
ment of orientation every 4 h can be helpful in
Exclude hypoglycaemia and hypoxia at the bedside. confirming the diagnosis. This is simple to do
Urine and electrolytes, Ca but often omitted or, perhaps through embar-
Liver function tests rassment, not done properly. The patient must
Full blood count be formally asked the time, date, where they
Erythrocyte sedimentation rate and C reactive protein are and who they are and the results recorded.
Troponin It is not adequate just to have a chat and if the
Glucose patient seems ‘normal enough’ record them as
Blood cultures if any evidence of infection orientated.
Urinalysis ± MSU
Cognitive function. The neuropsychological
Chest x-ray
hallmark of delirium is impaired attention,
ECG
accompanied by disturbance all domains
Consider CT ± lumber puncture if delirium persist without known
of memory and in executive functions.
precipitant
Commonly used bedside tests of attention
Further investigations will be indicated depending on underlying
are tasks such as reciting the months of the
neurological state
year in reverse order or serial 7s (subtract-
ing down from 100 by 7 each time). Bedside
cognitive batteries such as the Mini-Mental
State Examination3 and the more extensive,
and more helpful, Addenbroke’s Cognitive
Examination (ACE-R)4 are of assistance. For
a neuroscience unit we would recommend
Table 5 ‘Standard’ investigations in dementia ACE-R, possibly supplemented by the Frontal
Assessment Battery5 and some bedside tests
of praxis, such as mimicking unusual hand
Neuroimaging:Brain CT or MRI
positions and miming everyday activities.
Blood screen: Full blood count, erythrocyte sedimentation rate
Attention is usually somewhat disrupted in
Urea, electrolytes, calcium, liver function
patients who have active major psychoses but
Glucose, cholesterol
not nearly to the extent of that in delirium.
B12 and folate
In psychoses, memory function and executive
Thyroid function
function are, comparatively, preserved. It has
Syphilis serology
been suggested that visuoperceptual defi-
Additional investigations which may be helpful
cits are particularly pronounced in delirium
Formal neuropsychometric assessment
and that bedside tests such as dot counting,
Neuroimaging: Brain MRI, single photon emission computed tomography
incomplete shape and incomplete letter rec-
Other imaging: eg, chest x-ray
ognition can help distinguish delirium from
Other blood tests Genetic testing, eg Huntington’s, CADASIL, mitochondrial
mild to moderate dementia,6 although their
disorders, familial Alzheimer’s disease, familial prion dementia
administration can be impractical in disturbed
White cell enzyme studies in leucodystrophy
patients (figure 3).
HIV test
Connective tissue serology in suspected CNS inflammation, eg antinuclear Personality disorder. Patients usually lack any
factor, anticardiolipin antibodies, antineutrophil cytoplasmic antibodies, features of substantive psychopathology.
antibodies to extractable nuclear antigens, rheumatoid factor, complement Rather they tend to be sensitive to perceived
fractions slights, and have a ‘paranoid’ but not delusional
Antithyroid antibodies in suspected Hashimoto’s encephalopathy world view. Patient reports of ‘hearing voices’
Caeruloplasmin in suspected Wilson’s disease often take the form of pseudohallucinations;
EEG voices speaking within their head as opposed
CSF examination to a true false perception of voices speaking
Brain biopsy in external space. Mood tends to fluctuate
from upset to irritability. Boredom and low
CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts self-esteem tend to prevail over symptoms of
and leukoencephalopathy. genuine anhedonia (global inability to perceive
pleasure). Incidents tend to develop over a
10.1136/jnnp.2009.201848
 Carson, Ryan 75

period of time and are usually understandable, there is considerable clinical uncertainty, an
if unjustifiable, in terms of causation. EEG can be helpful and will show generalised
diffuse slowing in the vast majority of cases of
Personality disorder can be a difficult area for
delirium and dementia7 but it is generally nor-
clinicians. When the diagnosis has been clearly
mal in the major psychotic illnesses.8
made, related disturbed behaviour is a crim-
The main role for investigations is in iden-
inal not medical matter and should be dealt
tifying the underlying causes of delirium
with via ward staff for minor incidents (ie,
(table 4) and in cases of suspected dementia
an explanation that the person’s behaviour is
(table 5). In some situations investigations
unacceptable), or by hospital security and, if
will be needed urgently if there is reason to
indicated, the police for more significant acts.
suspect that the underlying cause may be a
We do not recommend that staff simply ‘put
up’ with or medicalise violent or aggressive
behaviour.
However, such a ‘zero tolerance’ approach
needs to be considered alongside the degree of Table 6 The Confusion Assessment Method (CAM) Diagnostic
Algorithm
diagnostic certainty. Unfortunately, there can
be little certainty in this field, and regrettably
each year there are malpractice suits against Consider the diagnosis of delirium if 1 and 2, AND either 3a or 3b are
clinicians who have discharged patients from positive:
1. Acute onset and fluctuating course
hospital whose difficult behaviour was the
Is there evidence of an acute change in mental status from the patient’s
direct result of their neurological disease and
baseline? Did the (abnormal) behaviour fluctuate during the day (tend to
not ‘badness’. come and go, or increase and decrease in severity)?
It making such a judgement, as well as the 2. Inattention
features of mental state described above, it Did the patient have difficulty focusing attention (eg, being easily
can be helpful to look at the following. distractible) or have difficulty keeping track of what was being said?
3a. Disorganized thinking
• The consistency of their behaviour—is
Was the patient’s thinking disorganised or incoherent: such as
there evidence to suggest that the dis-
rambling or irrelevant conversation, unclear or illogical flow of ideas, or
played behaviour was in keeping with the
unpredictable switching from subject to subject?
patient’s normal behaviour or was it out of
3b. Altered level of consciousness
character? Personality disorders, by defini-
Overall, how would you rate this patient’s level of consciousness? (alert
tion, refer to enduring patterns of behav-
(normal), vigilant (hyperalert), lethargic (drowsy, easily aroused), stupor
iour that are inflexible and pervasive.
(difficult to arouse) or coma (unrousable)). Positive for any answer other
• The context of the admission: are acute
than ‘alert’
conditions such as head trauma likely?
• The context of the behaviour: aggression
in personality disorder is usually displayed
in the context of being thwarted—that
is, a staff member saying no over some Top-down modulation from
prefrontal, parietal, limbic cortices
matter; something going wrong or caus-
ing displeasure; or receiving information
that the patient does not want to hear. It
is much less common for it to occur ‘out
of the blue’—that is, sudden onset while
lying in bed in the middle of the night. Modality- and domain-specific
• The presence of alcohol and substance attentional modulations
(for sounds, tactile stimuli, colours,
misuse: although be careful, the patient motion, words, spatial targets,
may be going into delirium tremens. faces, objects, memories etc.)

INVESTIGATIONS Figure 4
The diagnosis of delirium and major psychotic The three compartments of an
attentional matrix based on the work
disorders is based almost exclusively on clinical of Mesulam (from Hodges JR. Cognitive
assessment. The role of investigations is con- assessment for clinicians, 2nd edn.
Bottom-up modulation from Oxford: Oxford University Press, 2007,
fined to the exclusion of potential differential ARAS
with permission). ARAS, ascending
diagnoses. In a small number of cases, where reticular activating system.

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76 Practical Neurology
Cortical
areas
Thalamus
Brainstem
nuclei
Figure 5
The ascending reticular activating
system: major stuctures and pathways
involved in normal attentional
processes (from Hodges JR. Cognitive
assessment for clinicians, 2nd Edn.
Oxford : Oxford University Press, 2007,
with permission).
10.1136/jnnp.2009.201848
Prefrontal, posterior parietal and
ventral temporal
Intralaminar and reticular nuclei
Dopaminergic, cholinergic and
serotinergic pathways
Reticular formation, midline raphe,
locus coeruleus and tegmental nuclei
medical emergency (such as hypoglycaemia)
but usually the investigation of the cause of
delirium can wait until the next working day.
PLACEMENT
Major psychotic illness, accompanied by
behavioural disturbance, should be man-
aged in psychiatric inpatient settings. Urgent
transfer should be arranged as soon as it is
safe to do so. The common exceptions are
post-ictal psychoses, steroid induced psy-
choses and dopaminomimetic psychoses,
which all may be better managed in neurology
wards. In such circumstances many units will
favour having arrangements with psychiatric
departments for accessing nursing skills—for
instance, a registered mental nurse to assist
with special observations. The policy for such
arrangements should be agreed as part of the
‘advanced preparation’ and not involve staff
arguing over it in the middle of the night while
feelings are running high.
The management of dementia tends to
depend on local services, but in most areas of
the UK more disturbed patients will be trans-
ferred to old age psychiatry. By contrast, delir-
ium, in all but exceptional cases, will usually
be managed in the neurology ward. We will
therefore concentrate on the management of
delirium for practical neurologists.
DELIRIUM
Clinical features
Although delirium is described as a disorder of
acute onset, there is often a prodromal phase
with mild transient symptoms of fatigue, rest-
lessness, irritability and mood disturbance,
accompanied by disturbance of attention or
perception and sometimes hypersensitivity to
light or noise. Sleep–wake disturbance is central
to the condition; fragmented, disturbed sleep
is often accompanied by daytime somnolence.
Patients describe realistic dream activity at
night and ‘dream-like’ states by day. Perceptual
disturbance ranges from derealisation-like
micropsia and macropsia through illusions
(such as the cord of a dressing gown appearing
like a snake), to frank visual hallucinations vary-
ing from simple shapes to complex forms.
There are three variants of delirium: hyper-
active, hypoactive and mixed. It is the hyper-
active form with autonomic arousal that is
more distinctive but the hypoactive form with
inactivity, and on occasions falls and inconti-
nence, is more common.
Cognitively, the hallmark is decreased ability
to focus, shift or sustain attention. These rapid
shifts in attention have consequences for
memory registration leading to disorientation
and memory deficits. There are however global
cognitive deficits and executive dysfunction,
and disorganised thought can be prominent.
Disturbance of retrograde memory is com-
mon and confabulation occurs. The Confusion
Assessment Method (table 6) is a reliable, sen-
sitive (94%) and specific (89%) tool for the
diagnosis of delirium.9
Aetiology
Delirium has many causes, usually involving
the interaction between pre-existing vulner-
ability factors and exposure to one or more
acute precipitants. The greater the vulnerabil-
ity, the more innocuous the precipitant may
be. Conversely, in less vulnerable patients the
insult will be more noxious and often multi-
ple. Common vulnerabilities include: old age,
male sex, cognitive impairment, depression,
immobility, history of falls, hearing and eye-
sight problems, dehydration, malnutrition,
polypharmacy and chronic medical illness.
The common precipitants include: infections,

(a)
Figure 6
In the management of delirium, clinicians often rush to medication but the key to success lies in high quality general medical care and managing the more ‘mundane’
aspects of the presentation, such as early mobilisation and constipation (Used with permission from the Wellcome Library, London).
acute illness, drugs and surgery but, in vulner-
able patients, can also include factors such as
admission to a strange setting (ie, a hospital
ward), pain, sleep disturbance, minor physical
procedures and emotional distress.
The pathophysiology is poorly understood.
Currently, most attention is directed towards
the role of neurotransmitters, particularly
acetylcholine and dopamine, inflammation
and the stress response. There is extensive
evidence to implicate cholinergic deficiency.10
Central to this theory is the role of cholinergic
transmission in modifying attention which can
be conceptualised as having four components:
arousal, sustained attention, divided attention
and selective attention. Orientation depends
on global attentional processes and so marked
disruption of attention inevitably leads to
disorientation. The maintenance of attention
depends on two major neural systems11: the
ascending reticular activating system which
exerts ‘bottom-up’ modulation of cortical
regions and a cortical ‘top-down’ regulation,
particularly involving prefrontal, limbic and
parietal regions. Additionally, there is domain
specific attentional modulation for such stim-
uli as sounds, faces objects and memories
Carson, Ryan 77
(b)
(figures 4 and 5). Disruption of the top-down
system tends to produce inattention and dis-
tractibility as, for example, after traumatic
brain injury or stoke, whereas disruption of the
‘bottom-up’ system produces delirium.
Acetylcholine is the major neurotransmitter
in the reticulothalamic pathway, and the excit-
atory amino acids, such as glutamate, are rele-
vant to thalamocortical transmission. There are
also dopaminergic projections from the raphe
nucleus and noradrenergic projections from
the locus coeruleus. There is strong evidence
from both human and animal models corre-
lating the extent of cholinergic deficiency with
the severity of delirium.10 A number of mecha-
nisms have been postulated to cause choliner-
gic deficiency involving both direct and indirect
central nervous system insults.10 Direct insults
include stroke or brain injury, which cause
ischaemia and related global impairment of
cerebral metabolism.12 13 There is a glutamate
and cholinergic surge in response12 13 which is
followed by decreased cholinergic synthesis14
and ultimately a cholinergic deficit15 causing
delirium. By contrast, indirect mechanisms
involve a range of environmental and med-
ical stressors which lead to astrocytic and
www.practical-neurology.com
78 Practical Neurology
microglial activation,10 16 and proinflammatory
cytokine release.10 It has been suggested that
these alter blood–brain barrier permeability,17
increasing monoaminergic activity7 and reduc-
ing the number of cholinergic neurons,18 in
turn also causing a cholinergic deficit.15
Management
The mainstay of management is good gen-
eral medical care and supportive symptomatic
relief. Clinical assessment should be aimed at
identifying as many of the pre-existing vul-
nerabilities and immediate precipitants as
possible. When identified, the causative factor
should be treated appropriately.
• Supportive symptomatic relief is critical
to safe patient management yet often
ignored in favour of easily prescribed but
less effective drug treatments.
• Supportive relief includes steps to deal
with any hypoxia, pain, dehydration, mal-
nutrition and constipation (figure 6). Early
mobilisation is very helpful and the time
spent lying in bed should be minimised.19
• Steps should be taken to assist with ori-
entation of the patient, including ensuring
that he or she is using the correct spec-
tacles and hearing aids, have large faced
clocks clearly visible and consider using an
orientation board at the bedside.
• When staff interact with the patient they
should remember that inattention leads
to poor registration of memory; repeating
short simple phrases will aid registration
and is more likely to be reassuring than
long, albeit kindly, discussions.
• Discontinuation or minimisation of drugs
with sedative or anticholinergic adverse
effects is essential. The use of analgesia
is a balance between efficacy in control-
ling pain against the effects of opiates on
cognition; for instance, it has been sug-
gested that substitution of gabapentin for
opioid based analgesia in postoperative
patients helps to reduce the occurrence of
delirium.20
This style of multi-faceted approach reduces
morbidity and saves money. It has been trans-
lated into care pathways such as Hospital Elder
Life Programme (HELP) which translate theory
into practice.21
Antipsychotic drugs
Drug treatment should be reserved for more
severe cases and antipsychotics are the agent
10.1136/jnnp.2009.201848
of choice—they reduce the degree and duration
of delirium.22 There is no evidence to support
any particular antipsychotic over another. Low
dose (<3 mg/day) haloperidol in older people
has equivalent adverse effects to risperidone
and olanzapine; in higher doses (>4.5 mg/day)
it has more extrapyramidal adverse effects. In
physically active younger patients, a daily dose
of approximately 5–10 mg is usually safe. In
terminally ill patients there is evidence to rec-
ommend haloperidol over chlorpromazine.23
However, concern over the use of antipsy-
chotic medication in older patients was raised
by Janssen (the manufacturer of risperidone),
highlighting a possible association between
risperidone and stroke. In 2004, the Committee
of Safety of Medicines in the UK recommended
avoiding the atypical antipsychotic drugs
risperidone and olanzapine in patients with
dementia. Several studies have subsequently
investigated this24–26 and did indeed demon-
strate an increased risk of stroke in patients
receiving antipsychotic drugs. However, there
was no particular association with risperidone,
and if anything the risk was higher with first
generation drugs, in particular the phenothi-
azines (such as chlorpromazine). Although
such data emphasise the need for caution and
restraint in prescribing, such small increases
in risk should be compared with the signifi-
cant risks delirium poses in terms of morbidity,
mortality and patient safety; these risks should
not be regarded as a reason for not treating
delirious patients, at least in the short term.
The reality is that there is often no choice but
to treat delirious patients with some form of
sedative, and the evidence strongly favours
antipsychotic medication.
By contrast to worrying about the long term
risk of stroke in treating delirium, the empha-
sis should be on daily monitoring of the much
more likely adverse effects of antipsychotic
medication, particularly sedation, postural
hypotension, extrapyramidal problems and
worsening of cognitive function, all of which
can lead to an increased risk of falls and in
some cases even worsen the delirium.
We use haloperidol as a firstline agent with
an initial dose of 0.5 mg twice daily in the frail
or older and 5 mg twice daily in younger fit-
ter patients. Whatever dose is used, the drug
should be titrated to the patient’s response
and any antipsychotic medication should be
reduced or discontinued as soon as possible.
 Carson, Ryan 79

The need for regular review of drug dose can-
not be over emphasised. The use of ‘as required’
medication should be avoided, if possible, as
it often results in unnecessary dose escala-
tion. Where extrapyramidal problems develop,
these are generally better managed by reduc-
ing drug dose than prescribing anticholinergic
medications, such as procyclidine, which tend
to worsen delirium.
Benzodiazepines
The 2009 Cochrane Review27 of benzodiaz-
epines in the treatment of delirium found lit-
tle evidence but what evidence there was did
not support their use. Furthermore, the 2004
review of delirium in terminal care23 noted
that lorazepam caused excessive sedation.
The exception is the management of delirium
tremens where there is a specific role for
benzodiazepines28 (a common regimen is chlor-
diazepoxide 20 mg four times a day reducing
over 5 days) and antiepileptic drugs.29
Anticholinesterases
The putative role of impaired cholinergic
activity has led to the attractive hypoth-
esis that acetylcholinesterase inhibitors may
offer not only symptomatic relief but actual
treatment. Despite a number of enthusiastic
early case reports,30–32 the 2008 Cochrane
Review33 found only one trial of donepezil,
in a mere 15 patients, to be methodologi-
cally adequate. Perhaps unsurprisingly there
was no difference between active treatment
and placebo and so there is no current evi-
dence to support its use. But despite the lack
of evidence, acetylcholinesterase inhibitors
are routine in some countries,34 and more
appropriately powered studies are currently
being conducted (Dautzenberg PL, personal
correspondence 2009). In the UK these drugs
are currently unlicensed for the treatment of
delirium.
However, there may be a particular role for
acetylcholinesterase inhibitors in patients who
have delirium in the context of Parkinson’s
disease dementia where complex visual hal-
lucinations are commonplace.35 Therefore, as
well as reducing dopamine agonists, catechol-
O-methyl transferase inhibitors and L-dopa,
an acetylcholinesterase inhibitor, may be
warranted, particularly given the relative con-
traindication of antipsychotics and benzodiaz-
epines. Clozapine is the drug of choice36 but
the limitations on prescribing, in particular
the need to be registered with the monitoring
company, mean that many favour quetiapine37
because it is easier to use.
The main adverse effects of acetylcholin-
esterase inhibitors are cholinergic: dizziness,
insomnia, nausea, vomiting and diarrhoea.
These are dose and time limited and usually
resolve with reduction in dose and when treat-
ment is continued for more than 3–4 weeks.
Other relatively common adverse effects are

PRACTICE POINTS

• Episodes of behavioural disturbance are commonplace events in a neurosciences unit;

there should be adequate planning to deal with such normally encountered incidents.
• The clinical environment should be safe for patients and staff; a formal risk assessment of
clinical areas should be conducted.
• Protocols for dealing with disturbed behaviour are helpful. They should include clinical
strategies, drug administration and define staff roles and responsibilities.
• Delirium is the most commonly encountered cause of behavioural disturbance. It presents
as an acute fluctuating deterioration in cognitive function with altered motor activity and
disrupted sleep–wake cycle.
• The aetiology of delirium is multifactorial—a combination of pre-existing vulnerability and
acute insults. Management reflects this and requires a multifaceted approach, targeting
both underlying vulnerabilities as well as acute precipitants.
• Antipsychotics, such as haloperidol 2–4 mg twice daily, have a beneficial effect but should
never be regarded as a sole strategy for treating delirium.

www.practical-neurology.com
80 Practical Neurology
cardiac arrhythmias, particularly bradycardia,
gastric and duodenal ulcers.
Prevention
There are very few randomised trials on the
prevention of delirium. The Cochrane review in
200738 identified six studies mainly conducted
in the setting of elective surgery in the older.
One found that a proactive geriatrician con-
sultation before elective hip surgery led to a
reduced incidence in the treatment group (odds
ratio 0.48, 95% CI 0.23 to 0.98); 10 areas were
addressed—oxygen delivery, fluid and electro-
lyte balance, pain control, polypharmacy, bowel
and bladder function, environmental stimuli,
nutrition, mobilisation, early detection of post-
operative complications and treatment of agi-
tated delirium where present. One trial of low
dose haloperidol in at risk patients pre-elective
hip surgery showed no benefit but did result in
shorter less severe episodes of delirium.
In terms of identification of ‘at risk’ patients,
evaluation of executive function and intercur-
rent depressive illness39 40 appear more pre-
dictive than memory tests, particularly when
cognitive impairment is less overt.
CONCLUSIONS
The management of behavioural disturbance
and, in particular, delirium can be summarised
in the Boy Scout motto ‘be prepared’. The clin-
ical assessment and subsequent management
encapsulates most of the skills of good general
medical practice in combination with some
interesting cognitive neurology. Unfortunately,
assessment and management often occur in
an emotionally charged atmosphere in which
everyone feels the patient should be someone
else’s problem. Rarely, however, does ‘some-
one else’ appear to take it over and this can
be a source of impotent frustration. We sug-
gest that with proper preparation, both of the
individual patient and the clinical care system,
not only will poor performance be prevented
but patient care will be rewarding and hope-
fully fun too!
ACKNOWLEDGEMENTS
This article was reviewed by Tony Pelosi,
Lanarkshire, UK.
Competing interest: None
Provenance: Commissioned, externally peer
reviewed.
10.1136/jnnp.2009.201848
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