Editorial

Spring 2012 and momentum is building up as delirium features more

often and more prominently in published medical literature. Last

month the British Medical Journal published the largest intensive care

unit (ICU) delirium study to date. In the accompanying editorial I

tried to make the point that the science is clear: failing to detect and

manage delirium adequately is failing the patients. Professor

MacLullich went further in a personal communication “excellence in

delirium care should be the expectation in all ICUs; anything less,

given the resources and expertise in ICU, is frankly unacceptable.”

Delirium in UK critical care patients has been particularly topical in

the lay press with a videocast and an article from Times columnist

David Aaronovitch describing his own experience then the Scottish

newspaper, Sunday Post, publishing an interview with Peter Gibb of

ICUsteps. Consequently the website www.icudelirium.co.uk has had

an increase in patients sharing their own experiences relieved to

know they are not “going mad”. Will this lead to patients and relatives

wanting to know more about delirium and what we, the health care

professionals are going to do about it?

How can we influence this? Let us gather our previously low ranking

cards into a winning hand. I believe we need to keep doing what we

are all doing already, making a difference one patient at a time. In

addition if we each aim to inform two clinicians a month one or two

facts about delirium, and they inform two other clinicians a month, by

the end of 10 months each of us could be responsible for an additional

500 clinicians knowing more about delirium!

This bumper edition includes a collaborative article highlighting the

importance of subsyndromal delirium, Dr Davis tells us all we need to

know (and we do need to know) about epidemiology and Dr Wilson

has provided an inspiring descriptive piece about altering the ward

environment for at risk patients with dementia. The news section will

bring you up to date with events and initiatives including the first

European Delirium Survey and an announcement for the next annual

meeting.

Finally, I am pleased to announce that Dr Andrew Teodorczuk will be

a co-editor of the Annals of Delirium from the next edition.

Contributions all welcome for the summer edition – prose or poetry!

Valerie Page

Capturing psychiatric phenomena: what delirium

researchers can learn from dementia epidemiologists

Daniel Davis and Carol Brayne

Institute of Public Health, University of Cambridge

At delirium conferences, we often hear the call for ‘more research on

the epidemiology of delirium’. There have been very few studies on

delirium prevalence in the general population. Perhaps this is because

such studies are difficult to undertake and is compounded by

problems of how to define psychiatric syndromes in epidemiology.

Research in dementia has faced similar obstacles – what lessons have

been learned?

What do we mean by ‘population’? Epidemiology is concerned with the inter-relationship between

populations, exposures and outcomes. Intrinsic to this is the problem

of definitions and how they are conceived, framed and articulated. In

considering the importance of defining a population, we are asking: Is

the chosen population one that is relevant to the full spectrum of

persons with delirium? How does the approach to sampling enable a

valid capture of the chosen population? These are critical questions as

the provenance of the sample population has the potential to

systematically bias findings both in magnitude and direction.

The majority of studies in delirium have been undertaken in hospital

settings, and these have been comprehensively reviewed.1 These

studies indicate that delirium is a common problem in inpatients with

serious adverse outcomes. However, there are two limitations to the

inferences that can be drawn about delirium as a whole. Firstly, one

cannot assume that all persons with delirium will actually present to

hospital. Secondly, once in hospital, there is only retrospective (and

therefore limited) information of a person’s cognitive and

performance function before the onset of delirium. Ideally, one would

start with a broad, unselected denominator (i.e. a true population-

based study) followed-up with serial cognitive assessments. This

would represent a comprehensive range of symptoms (and severities),

but also identify what happens, to whom, and when. This is essential if

we are to understand the determinants and effects of delirium most

completely. A working definition for population-based study might be:

‘a study where all subgroups of the population are sampled, regardless

of disease or residential status’.2 Of course, ensuring that a study

population is comprehensive in this way requires substantial effort,

but there are gains of equal degree in terms of achieving results with

external generalisability.

Psychiatric epidemiology: a problem of standardisation

In order to reliably track states of health in populations, looking for

emerging patterns and trends, one must be able to define exposures

and outcomes of interest in a standardised way. All diseases can be

nosologically classified, each with their ‘reference-standard’

definitions. However, where these conditions are psychiatric

syndromes, the reference-standard is necessarily a set of clinically

agreed descriptions of psychopathology rather than any objective

quantities.

There are two different approaches for neuropsychiatric definitions,

the International Classification of Diseases (World Health

Organization) and the Diagnostic and Statistical Manual of Mental

Disorders (American Psychiatric Association). There are some

differences between these two systems (see references for a

discussion on how these might affect case-ascertainment in dementia3

and delirium4). However, both are subject to common problems.

Firstly, these definitions are not stable over time (ICD-9 vs 10, DSM-

III-R vs DSM-IV, with further iterations in evolution). Nor are these

definitions easily transferrable across cultural contexts. Yet more

problematic is that these clinical criteria have the potential to vary,

and so can be interpreted differently by different clinicians. An

example is how the definition might be applied to persons of different

ages depending on the expectations of normality for that age group. In

other words, the threshold for abnormal cognitive or functional

impairment may decrease with age, in line with a belief that some

impairment is to a degree expected (and therefore not abnormal) in

older age.5 Finally, in the research setting, a core problem is how to

operationalise these criteria so that case-ascertainment can be

achieved in a consistent manner.

Underlying these difficulties is the problem of how to agree the

boundaries for a spectrum of psychiatric symptoms. While there is

relatively little disagreement about moderate and severe dementia,

studies that include milder cognitive deficits lead to much less

consistent estimates of prevalence (see references for review6). Mild

cognitive impairment (MCI) has been regarded to be of possible

relevance to dementia, but applying the MCI construct to population-

based cohorts has not been straightforward.7, 8 The equivalent entity

in delirium – i.e. subsyndromal delirium – also needs to be considered

in light of these issues.

Dementia epidemiology: some approaches

Dementia is clinically defined by identifying progressive deficits in

two or more cognitive domains sufficient to impair function in

activities of daily living. Three population-based studies can be used

as examples to illustrate the different ways in which this definition has

been operationalised in the context of research (Table 1). Vantaa 85+

defined dementia cases through the agreement of two neurologists at

clinical examination.9 While this is more reliable than assessment by a

single clinician, there remain difficulties with inter-rater reliability

and this can hamper cross-study comparisons. In the City of

Cambridge over-75 Cohort (CC75C),10 as well as other studies in both

Europe11 and North America,12 this has been addressed through the

agreement of dementia diagnoses at multidisciplinary consensus

meetings, held after all study information becomes available. This

method of case-ascertainment is labour-intensive and so limits the

breadth of coverage to some extent.

In parallel to the development of the multidisciplinary conference to

standardise case-ascertainment, use of the Present State Examination

(PSE)13 led to the possibility of creating diagnostic categories through

algorithms. The PSE – and the version validated in older persons, the

Geriatric Mental State (GMS)14 – is a systematic operationalisation of

the psychiatric mental state examination. It uses answers generated

from the interview to group symptom clusters which can then be used

to derive diagnostic groups. Once these categories have been validated

against clinician-applied diagnoses, this algorithm approach can be

automated and applied by non-medical interviewers. The MRC

Cognitive Function and Ageing Study (MRC-CFAS) used such an

approach with the Automated Geriatric Examination for Computer

Assisted Taxonomy (AGECAT).15 This allowed for much greater

numbers of persons to be studied and MRC-CFAS remains one of the

largest population-based studies of dementia incidence ever to be

conducted. The algorithm diagnosis has been considered again more

recently by studies such as the Health and Retirement Study, mainly

driven by attempts to reduce the cost of case-ascertainment.16 In

addition, an algorithm approach has been applied to the consensus

diagnosis itself, with the aim of making the process more time-

efficient.17

Accounting for attrition

Loss to follow-up is common to all longitudinal studies of older

persons. Usually, this is due to death between interviews. This is also

known as censoring – where people contribute to the observed period

of follow-up, but where loss to follow-up means that case-status

cannot be ascertained. This information must still be included in the

analysis because it is still useful to know that persons weren’t cases

until the point they were last observed.

One of the underlying assumptions of this type of cohort analysis

(known as survival or time-to-event analysis) is that censoring is ‘non-

informative’. This means that characteristics of persons retained in

follow-up are similar to those that are lost. Particularly for studies of

ageing, this assumption is overly strong. It is clear that attrition in

ageing studies does not occur at random, and lower cognitive and

functional scores at last interview predict drop out. While this makes

intuitive sense, very few studies explicitly use statistical techniques

such as ‘last observation carried forward’ to account for missing data.

These approaches have been important in the dementia field18-20 but

have yet to be systematically applied to follow-up studies in delirium

and almost certainly under estimate the effect of drop out.

Case-ascertainment in delirium epidemiology

There are a handful of population-based studies in delirium. In each of

these, the diagnosis of delirium was based on the DSM criteria, though

again operationalised in different ways (Table 2). The East Baltimore

Survey and Girona studies used validated interview schedules

(Standardised Psychiatric Examination and Cambridge Mental

Disorders of the Elderly Examination respectively), whereas the

Canadian Study of Health and Ageing (CSHA) applied diagnoses

through consensus meetings. None used an algorithm

operationalisation.

There is a consistent finding that community prevalence of delirium is

relatively low, but it remains a condition with poor prognosis,

comparable to hospital series. Nonetheless, it is important to note that

intercurrent illness and/or delirium might well reduce response rates

in epidemiological surveys. In this regard, while these studies have

also reported characteristics of participants and nonparticipants, none

have related these to acute illness and estimates of delirium

prevalence.

The Vantaa 85+ did ascertain delirium. To apply a retrospective

diagnosis, participants were assessed along with their informant(s)

for a history of any episodes of delirium, specifically assessing:

changes in cognitive functioning, level of alertness and psychotic

symptoms, as an operationalisation of the DSM-III-R criteria.21 The

reported history and number of episodes of delirium were

corroborated with hospital case notes that were available at the time

of assessment. As noted above, there are problems with the reliability

of determining both delirium and dementia. However, it remains an

important study because it is the only population-based cohort to

have specifically attempted to relate history of delirium with dementia

outcomes.

Combining these approaches for delirium epidemiology

It is clear that standardisation is a complex issue in psychiatric

epidemiology. One general consequence of not identifying delirium

accurately is a reduction in the observed effect size between the

intervention and control groups (known as non-differential

misclassification bias). Thus insufficient attention to standardising

case-ascertainment results in loss of power in trials. At the very least,

we can conclude that clinical delirium research would benefit from

case-ascertainment consensus conferences and/or algorithmic

operationalisation. It should not be considered sufficient for case-

ascertainment to be decided by single assessors. Scores for individual

diagnostic items – and their temporal fluctuations – should be

submitted for agreement at the level of a consensus panel. At the same

time, there is potential to develop algorithm diagnoses in delirium.

Already there are semi-automated some neuropsychological tests (e.g.

the Edinburgh Delirium Test Box for attentional deficits22), and it

would be logical to incorporate these. These new approaches will

require careful validation studies. This shift toward better-informed

epidemiological techniques may seem daunting, but must be regarded

as essential for generating valid clinical research in delirium. The

future may bring innovative approaches, as has been proposed for

dementia: improving coverage through proxy / participant telephone

interviews (validated against face-to-face interviews); newer versions

of algorithm-generated computer information; online consensus

conferences.16 Some delirium collaborations are beginning to adopt

these ideas.23

Even these measures will not be enough. The challenges for delirium

epidemiology are greater than those for dementia. There are

particular features of the syndrome that make standardisation even

more complicated. Fluctuating symptoms are a core feature of

delirium, and this will not be reliably captured without specific

attention to how this is to contribute to case-ascertainment. There is

scope for delirium research to benefit from approaches in other fields

within neuroepidemiology, particularly acute conditions such as

stroke or epilepsy. These efforts will be rewarded by generating

methodologically rigorous clinical data applicable to the broad

generality of patients with delirium.

Table 1. Characteristics of studies comprising the EClipSE

database.

Making Marjory Warren Proud

Marjory Warren ward is a 30-bedded inpatient ward at Kings College

Hospital in South East London, named after the founder of modern

geriatric medicine. I am lucky enough to share the consultant duties

with Dr Catherine Bryant and as we both have interests in cognitive

disorders the ward attracts a high number of patients with dementia,

delirium or both. I have tried to write a descriptive piece that tells the

story of the transformation of the ward to make it a more suitable

environment for patients with cognitive problems. I make no

apologies for the relatively few specific mentions of delirium. We

wanted to create neither a delirium ward nor dementia ward, but a

more inclusive place where expertise in managing frailty in the

context of a wide range of cognitive disorders would prevent and

reduce harm from delirium as one of many facets improving patient

care.

Before I go further however, a disclaimer. I am extremely proud to

have been part of the project I am about to describe, but I want to take

no credit for its inception or realisation. The transformation was

due entirely to Emma Ouldred our Dementia Nurse Specialist at Kings

and a team of nurses working with her. The transformation certainly

would not have happened without their tireless optimism,

commitment and unerring belief that the patients we treat deserve to

be cared for in an environment that is not just practical and functional

but welcoming, safe, orientating and stimulating.

Since 2000 the King’s Fund has been supporting a number of projects

in UK hospitals under the umbrella “Enhancing the Healing

Environment”. There are a range of projects and in 2009 some funding

was specifically directed towards projects that improved the

experience of patients with dementia. We applied for a second tranche

of funds made available in 2010. The initial ambition was to

transform the day room on one of our Gerontology wards into a

sensory room that would provide a healing environment for patients

with dementia, recognising that this might help treat and prevent

other cognitive problems including delirium. We would promote

activities such as reminiscence, in a newly designed, uncluttered room

with lighting and furnishing that encouraged patients to use a space

that had become increasingly used by staff to host professional

meetings. Sensory equipment and memory boxes that were also

portable would be available to be taken to the beds of less mobile

patients.

The views from our 7th floor ward are stunning, looking across to the

city of London (St Paul’s, the London Eye) as well as the local area. By

introducing interpretation panels that described the views we hoped

to stimulate conversation and reminiscence. Along with an easily

operated multi-media centre we intended build a library of music and

films that patients could enjoy. The projector could be used to play

other moving images (a roaring log fire was particularly popular over

Christmas when the plans finally became realised) as well as stills

from a staff photography competition that was run during the

redesign project.

During the early stages of this transformation it became clear that to

focus on one room on Marjory Warren ward would not be enough to

truly enhance the environment for our patients. Rather than be

limited by the money (a not insignificant £50,000) from the Kings

fund, supported by a further £15,000 from the hospital, the initial

plans became a springboard for a complete redesign of the ward and

its entrance area. Patients past and present along with their carers, as

well as nursing and therapy leads and our hospital estates and

communications teams all contributed to lively meetings.

Redecorating the whole ward with colourful (and colour coded)

simple designs, and clearly labelling bed numbers in bays and rooms

was proposed. We wished to replace the highly polished, plastic

flooring as patients told us they often thought the floor looked wet,

leading to fear of falling. Other important equipment such as cardiac

arrest trolleys and clinical waste bins needed to be housed discreetly

whilst remaining clinically accessible. Artwork was proposed that was

relevant to our local population (a fantastically ethnically and socially

diverse population) and projects were set up that the patients could

contribute to during their activity groups or therapy sessions. Dulwich

Picture Gallery, (Britain’s first public art gallery founded in 1811)

brought their experience from an “Art For Older People” project and

commissioned an artist to help patients, carers, visitors and staff

create an embroidered panel fittingly titled “The Urban Jungle” that

now sits in the entrance of the ward.

The Kings Fund and hospital were delighted with the ambition

encouraging Emma to apply for more funding without concerns that

their own contribution might in any way become diluted or stifled. We

were extremely lucky that the Friends of King’s Charity had been left a

£200,000 legacy that the trustees felt was ideal to support this project.

Now a much broader transformation could take place. We continued

with the proposals mentioned above (the flooring is now a matt, non-

slip wood effect to provide a more homely feel). Panels of pictures

around the corridors of the ward reflect the London skyline outside,

and new hand rails and regularly spaced seats mean patients can

wander more safely and have recognisable images to look at, enjoy

and discuss. More seating nearer to the two nursing stations and a

very open plan design means patients at high risk of falls or those in

need of company and conversation can be closer to the staff. At one

end of the ward are also some sensory panels that are very simple in

design for those with more advanced cognitive problems to interact

with. The experience, from ward entrance, around the ward and into

the sensory room is now part of a sensory walk for patients, their

carers, and staff which shows the range of the transformation which

can now be experienced as a whole or in smaller chunks.

Of course there is more to this than ambition and a loose sense that

change was just needed and would inevitably be for the good. We tried

to look for guiding principles to inform the design, though

interestingly there is little out there that is “evidence-based”. We

tapped the University of Stirling’s Dementia Services Development

centre, utilised extensive resources provided by the King’s Fund, and

Dr Jim George’s experience from the delirium unit at Carlisle.

Architects who have been involved in designing hospital and care

home environments for those who are frail and with cognitive

problems were consulted, as were the Alzheimer’s Society. We are

aware that much of what we have done “just makes sense” to us as

experts in dementia and delirium care. We hope the lessons we learn

form the transformation will contribute to a future evidence base to

inform others.

We are also aware that changing an environment alone will not be

sufficient to improve patient care. Fortunately there seems to already

be an appreciable change in both the patients and the staff working on

the ward. We have also seen an increase in nursing and therapy staff

expressing a desire to work on Marjory Warren. Formally measuring

and evaluating both patient and staff outcomes are therefore key. We

also need to continue other work we were already doing in the

education and training of staff and carers about frailty and particularly

dementia and delirium.

Some early indicators are promising. Patient satisfaction in all areas,

both clinical and environmental, measured in our “How Are We Doing”

survey has been consistently higher for the last three months since the

project was completed, exceeding our internal benchmarks. Even

before completion, with some building work still going on around the

patients, our length of stay had fallen. Of course the environmental

effect will be difficult to prove emphatically as this is not a randomised

trial. More specific indicators around delirium rates or intensity,

reduction in special one: one nursing or use of more extreme

measures such as sedation will take more time to collect and analyse.

What does the future hold other than evaluation? Our Activities

Coordinators continue to try and expand the range of groups they

hold, to use art, music, reminiscence as well as tea parties or bingo

mornings to engage patients. The current Occupational Therapists are

setting up a lunch club and even the junior doctors have committed to

helping with that! We now have some volunteers too who provide

vital support for the patients on the ward. We are meeting a film

company who do stop-motion animation (the same technique used to

make “The Wrong Trousers”). They would like to make a film,

facilitating the patients on the ward to create a story and direct their

own piece of work.

These are therefore exciting times at Kings and the potential to

influence the care of frail patients more widely (both within the

hospital and outside) will hopefully come from this. We launched the

ward in mid-December 2011 in a week when a high profile report on

dementia care in the NHS was published. Marjory Warren ward was

chosen as an exemplar for both local and national news coverage. We

are very aware that with such publicity comes the need for great

responsibility, to our patients first, but also to those who have backed

us both financially and with moral support. We know we are one of

many transformative projects and we have been exceptionally lucky to

get the money we secured.

We would encourage visitors, feedback and opportunities to

collaborate and share experience.

Sensory Room with log fire projection

Nurses Station Before

Nurses Station After

Ward Before

Ward After

Fathers with delirium

My Dad was diagnosed with lymphoma and was admitted with

a huge blood clot in his arm. The pain was terrible. He was

given morphine which initially resolved the acute pain.

However within hours he was staring at the ceiling counting

the dots. He became quiet and withdrawn and it was hard for

him to break his stare to look at us. I told the nurse that I

believed my Dad was suffering from delirium and she said she

would call the GP. She obviously did not know the symptoms

of delirium.

My Dad, an Anglican priest in the community where he was in

hospital (i.e. well known) had terrible dreams about robbers

attacking him in his hospital bed, and he climbed out of bed in

the night. After that he was physically restrained, had his

glasses taken away, and he was given just 0.5 mg haloperidol

IV twice a day for nausea! The delirium was never addressed

by the GP because when my dad spoke to the GP, he was polite,

and quiet. He wouldn’t share his fears with him. The GP paid

no attention to our complaints.

My Dad stayed in that state for 5 weeks. He was confused,

irritable and ended up in diapers because no one wanted to go

near him. When a pain doctor came to visit my Dad (he

happened to play golf with my Dad and saw he was in

hospital), he immediately recognized the delirium and just

changed the narcotic to a fentanyl patch. My Dad became

reasonable again. Sadly, he died 10 days later of an aspiration

pneumonia following chemotherapy.

My mother grieves for him, and feels such a sense of loss for

those 5 weeks when my Dad was so confused and afraid. I am

an ICU nurse with many years of treating delirium. I was so

frustrated by the lack of knowledge the GP seemed to have

about delirium, even though he was the most responsible

physician, I was powerless to convince him that he was

witnessing delirium related to narcotics. I will always regret

not making a big enough stink to get help for my Dad. Maybe

this testimonial will help some readers understand the impact

of delirium on patients and families. It was so unnecessary that

my Dad had such an end of life experience when the treatment

seemed to be so simple.

Authors name withheld, posted on www.icudelirium.co.uk

My Father’s Delirium A routine hip operation. But he looks quiet now. The earlier rage all whimpered away. A ravaged body, emptied and spent. A living husk that somewhat recalls, A happier memory: a father. A routine hip operation. An apologetic limp into the ward. A nervous smile, polite handshake. An anxious curiosity of who, And what, and when. A perfectly, perfect person, Extends his gift of trust. This is routine stuff for us! “We badge you, stamp, and wrap you. Then cut you, mend and dispatch you.” All proclaimed with a smile, But the eyes are distant, detached. Another day, another hip. The operation was quite routine. But my father somehow troubled, Subtly not there; with us, but not of us. Tea cups lie untested; Stagnant and dismal. And a restless fidget speaks of unease. A routine hip operation. But my father visibly shrivels, Into a secret, deep, inner space. “Dehydration, infection and constipation.”

So we are told. An oddly innocent litany, To inflict so grave an ill. And surely foreseen, and …….. preventable? A routine hip operation. Now an imprisonment within an internal world, Of blazing, crazy hues. Of ghostly faces, horrid forms. Evil voices murmuring evil thoughts, Shimmering moments in bewilderment. A soul adrift, sinking, sinking, Into the unseen, the in-between. But that was yesterday, And those several days before. A perfectly, perfect man, utterly undone. “Dehydration, infection and constipation.” The mantra plays and plays. A well oiled machine, all spoiled, For a wink of humanity. The merest pinch of care! It was…….a routine hip operation. John Young Bradford Royal Infirmary, UK

Subsyndromal delirium: Relevance to dementia

Elizabeta B. Mukaetova-Ladinska, Joaquim Cerejeira, Andrew

Teodorczuk

Institute for Ageing and Health, Campus for Ageing and Vitality,

Newcastle University, Newcastle upon Tyne, NE4 5PL, UK

Introduction

With the newly published National Dementia Strategy (2009)

and the recent RCPsych Dementia Audit (2011), we expect routine

screening for cognitive impairment and dementia in general hospitals

to increase. This will put pressure on both medical and mental health

services looking after the wellbeing of the older adults to have readily

access to adequate services for older adults with dementia.

Only during the last year, our Liaison Old Age Psychiatry team

has noted a high increase in referrals for dementia diagnosis for older

adults from various medical and surgical wards in the Newcastle area,

with many of them referred either shortly after their admission on

medical wards in the absence of delirium symptomatology, or after a

‘resolved’ delirium episode (still with some clinical symptoms of

delirium) and having problems in numerous cognitive domains. Yet,

not all of them will fulfil the DSM-IV criteria either for delirium or

dementia. This raises a number of clinical issues regarding the

management of such patients on medical wards, including both

pharmacological and non-pharmacological treatments, further

investigations of their cognitive decline, discharge plans, as well as

involvement of various support services to facilitate the latter.

Although several parameters have been associated with full recovery

of delirium (e.g. lack of apoE 4 allele, being female and lower levels of

IGF-1), severity of delirium, underlying presence of dementia and/or

advanced age do not appear to be relevant for the full recovery from

delirium (Adamis et al, 2007), thus further arguing for the seriousness

in managing of this clinical syndrome. The purpose of this opinion

piece is to explore the interface between subsyndromal delirium and

dementia and make recommendations for future research.

Clinical symptomatology of sybsyndromal delirium

The most recent study on sybsyndromal delirium (SSD) in

medically ill patients reported presence of 27% in all subjects post

delirium (Maegher et al, 2012). However this figure came from a

heterogeneous sample of subjects with delirium, ranging from 36-90

years of age, of which only 27% had known dementia. Marcantonio et

al (2005) reported higher prevalence rates of SSD in older adults (up

to 51%), and especially those with pre-existing dementia, similar to

the older subjects with delirium. In one of our studies, we have

highlighted the problems in diagnosing delirium in older subjects with

advanced dementia (Yates et al, 2007). We propose that delirium,

including SSD, may go largely under-diagnosed in many older adults

with dementia.

The clinical symptoms of SSD are characterised by less severe,

especially motor activity, disturbances (e.g. less agitation and

hyperactivity), less psychotic symptoms (e.g. delusions and

hallucinatory experiences), higher level of thinking, and higher

cognitive performance (e.g. attention, orientation, better working and

long-term memory) (Meagher et al, 2012) (table 1). Longitudinal

studies have also shown that SSD is not characterised by unstable

circadian (Meagher et al, 2012), and the lack of overt fluctuating level

of consciousness and symptomatology, makes the differentiation

between SSD and dementia even more difficult. This is especially so in

the light of lack of adequate clinical tools and peripheral biomarkers

that may aid the clinical differentiation, and thus help with the clinical

management of subjects with SSD.

How to diagnose subsyndromal delirium: use of clinical

and peripheral blood biomarkers

People with SSD have worse outcomes in terms of hospital

readmissions and mortality, they are less likely to return back to the

community within 30 days of admission have longer hospital stays

and overall more medical complications, including higher risk for falls

(Marcantonio et al, 2005), lower cognitive and functional level at

follow-up (Cole et al, 2003) compared to subjects devoid of delirium.

In the light of the numerous poor outcomes, there is a need not only to

improve the clinical recognition of SSD, but also its proactive

management.

Sadly, many of the subjects with SSD will be either referred to

the Liaison Psychiatry Services for diagnosis of dementia, or will be

misdiagnosed for dementia rather early in the course of their delirium

recovery. Since SSD can coexist with dementia, having good collateral

information about baseline functioning is an imperative. However, in

many of the SSD subjects this information will be unavailable. In the

absence of reliable collateral history, the diagnosis of the syndrome

largely relies on clinicians’ skills. However, since the latter are not

always in place, increase in awareness, education as well as

improvement of currently available diagnostic tools are urgently

needed.

Future challenges and areas for further investigation

In addition to the above, a number of SSD topics still remain

largely unknown:

the predictive value of individual symptoms in respect to poor

prognosis at short and long term;

the natural course of subsyndromal delirium and its temporal

interrelation with syndromal delirium, severe or otherwise;

the impact of non-pharmacological or pharmacological

interventions on individual symptoms of delirium.

An additional problem for SSD management is the current

widespread clinical culture refusing to acknowledge presence of the

syndrome once the causes of delirium are treated and the laboratory

findings are normalised. Thus, although elevated CRP levels are

largely associated with delirium (both prevalent and incident

delirium; McDonald et al, 2007), these findings have not been

replicated in further studies (White et al, 2008, van den Boogaard et

al, 2011), and even opposite findings have been reported for older

adults with co-existing dementia (Yates et al, 2009). Similarly, the

values of serum albumin and blood urea appear not to be useful in

discriminating between subjects with and without SSD (Cole et al,

2003, Yates et al, 2009).

Although various biomarkers have been associated with

delirium (van den Boogaard et al, 2011) their relevance to SSD legs

behind. Elevated levels of homocysteine are not only associated with

dementia, but also with alcohol withdrawal (Bleich et al, 2000),

suggesting that values of homocysteine above the 14µmol/l values

maybe indicative of SSD. Lower levels of esterases preoperatively also

help distinguish people at risk to develop delirium post-operatively

(Cerejeira et al, 2011), and this may also help identify SSD in clinical

setting. However, further work is needed in older adults with co-

existing dementia to validate the above findings.

Conclusion

The importance of correct diagnosis of the SSD in older adults,

especially those with a previous diagnosis of dementia, is highlighted

daily in clinical setting. One crucial question to clinicians is to

determine if subtle changes in mental status (e.g. level of

consciousness, disorientation) not fulfilling all the criteria for delirium

should be a relevant and meaningful target for clinical attention and

intervention. There are two good reasons to believe so. Firstly, in the

absence of a peripheral, non-invasive and easy test to guide clinicians,

SSD is the only available way to recognize early signs of brain

dysfunction which has enormous clinical relevance. For example, in

acute systemic inflammatory conditions, the delay between insult and

neuroinflammatory events associated with full-blown delirium offers

a window of opportunity to implement therapeutic interventions.

Secondly, many non-pharmacological interventions are "good clinical

practice" that should be always implemented and have no associated

risks.

However, in the current climate of diminishing resources,

lowering the threshold for clinical significance of symptoms of

delirium can impose a very high burden of work for the Liaison

Psychiatry services if education on medical wards, as well as nursing

homes and community, is not adequately implemented. Similarly,

further research into the clinical course and outcomes of SSD is

urgently required. We can conceptualise SSD treatment as being

similar to treating early psychosis in mental health units, and, if

resourced adequately, we may even have early intervention in

delirium teams. In the absence of adequate peripheral blood

biomarkers at present, one of the research goals needs to be further

development of novel blood peripheral biomarkers to aid the

diagnosis.

References:

1. Adamis D, Treloar A, martin FC, Gregson N, Hamilton G,

Macdonald AJD: APOE and cytokines as biological markers for

recovery of prevalent delirium in elderly medical inpatients.

Int J Geriatr Psychiatry 2007; 22: 688-94.

2. Bleich S, Degner D, Wiltfang J, Maler JM, Niedmann P, Cohrs S,

Mangholz A, Porzig J, Sprung R, Rüther E, Kornhuber J:

Elevated homocysteine levels in alcohol withdrawl.

Alcol&Alcoholism 2000; 35: 351-4.

3. Cerejeira J, Batista P, Nogueira V, Firmino H, Vaz-Serra A,

Mukaetova-Ladinska EB. Low preoperative plasma

cholinesterase activity as a risk marker of postoperative

delirium in elderly patients. Age Ageing 2011; 40: 621-6.

4. Cole M, McCusker J, Dendukuri N, Han L: The prognostic

significance of subsyndromal delirium in elderly Medical

inpatients. J Am Geriatr Soc 2003; 51: 754-60.

5. Department of Health: Living well with dementia: A National

Dementia Strategy. 2009.

6. Macdonald A, Adamis D, Treloar A, Martin F. C-reactive

protein levels predict the incidence of delirium and recovery

from it. Age Ageing 2007; 36: 222-5.

7. Maegher D, Adamis D, Trzepacs P, Leonard M. Features of

subsyndromal and persistent delirium. Br J Psychiatry 2012;

200: 37-40.

8. Marcantonio ER, Kiely DK, Simon SE, Orav EJ, Jones RN,

Murphy KM, Bergmann MA. Outcomes of older people

admitted to postacute facilities with delirium. JAGS 2005; 53:

963-9.

9. Royal College of Psychiatrists: National Audit of Dementia:

Report of the first round of the National Audit of Dementia.

2011

10. van den Boogaard M, Kox M, Quinn KL, van Achterberg T, van

der Hoeven JG, Schoonhoven L, Pickkers P. Biomarkers

associated with delirium in critically ill patients and their

relation with long-term subjective cognitive dysfunction;

indications for different pathways governing delirium in

inflamed and non-inflamed patients. Crit Care. 2011;15:R297.

[Epub ahead of print]

11. White S, Eeles E, O’Mahony S, Bayer A. Delirium and C-

reactive protein. Age Ageing 2008, 37: 123-4.

12. Yates C, Stanley N, Cerejeira JM, Jay R, Mukaetova-Ladinska

EB. Screening instruments for delirium in older people with

an acute medical illness. Age Ageing 2009; 38: 235-7.

Table 1: Symptoms of subsyndromal delirium. Please note that

subsyndromal delirium does not fulfil the DSM-IV defined criteria for

delirium (DSM-IV recognize subclinical presentations that precede or

follow delirium, as well as presentations that never progress to

delirium), and the clinical symptoms are less severe in relation to the

full-blown delirium. Maegher et al (2012) suggested DRS-R98 cut-off

scores of 16 for diagnosis of the syndrome. Modified according to Cole

et al (2003) and Maegher et al (2012).

Symptoms of subsyndromal delirium

1. Motor activity (restlessness, agitation, irritability, drowsiness,

hypersensitity to stimuli)

2. Higher cognitive functioning (reduced ability to think or

concentrate; impairment in attention, orientation, working

memory and long-term memory)

3. Perceptual and mood disturbances (anxiety, delusions and

hallucinatory experiences, nightmares)

4. Relatively stable circadian rhythm

5. ? Lack of overt fluctuating level of consciousness and

symptomatology

Announcing An Italian Textbook on Delirium

Alessandro Morandi, MD, MPH 1,2,3, E Wesley Ely, MD, MPH, 4,5,6,7,8 Marco

Trabucchi, MD9

1 Department of Rehabilitation and Aged Care Unit, Ancelle della Carità

Hospital, Cremona, Italy; 2Geriatric Research Group, Brescia, Italy; 3Center

for Quality of Aging, Vanderbilt Medical Center, Nashville, TN, USA;

4Center for Health Services Research, Vanderbilt Medical Center,

Nashville, TN, USA;5Division of Allergy/Pulmonary/Critical Care Medicine,

Vanderbilt Medical Center, Nashville, TN,USA; 6VA Tennessee Valley

Geriatric Research, Education and Clinical Center (GRECC), USA; 7

University of Tor Vergata, Rome, Italy

Delirium is a complex and multifaceted syndrome, and though it has a

long history in the annals of medicine, few textbooks are currently

available on this geriatric syndrome. Caraceni and Grassi1 published “The

Acute Confusional States in Palliative Medicine” specifically addressing

the concept of delirium in palliative care patients. Subsequently, Page and

Ely2 targeted a different setting focusing on “Delirium in Critical Care”.

Lindesay3 published a textbook evaluating delirium in the elderly:

“Delirium in the old age.” In the Italian literature there was an important

existing gap on this topic. In fact no textbook has been published to

inform health care providers on this important syndrome, which affects

thousands of patients every year. Therefore, we undertook the efforts to

create an Italian textbook on delirium, named “Il delirium.” 4 The book is

available to buy online

(http://www.vitaepensiero.it/volumi/9788834321591) and it is

structured in five chapters: 1) Epidemiology, classification and risk factors

of delirium in different clinical settings; 2) Pathogenesis of delirium; 3)

Clinical aspects of delirium; 4) Prevention and treatment of delirium; 5)

Future directions.

(1) Caraceni A, Grassi L. Delirium Acute confusional states in palliative

medicine. Second Edition ed. Oxford University Press, 2011.

(2) Page V, Ely EW. Delirium in Critical Care (Core Critical Care).

Cambridge University Press, 2011.

(3) Lindesay J, Rockwood K, MacDonald A. Delirium in Old Age. Oxford

Medical Publications. 2002

(4) Morandi A, Ely E.W., Trabucchi M. Il delirium. Vita e Pensiero, 2012.

Papers to look out for A: Dr Meera Agar Biomarkers associated with delirium in critically ill patients and their relation with long-term subjective cognitive dysfunction; indications for different pathways governing delirium in inflamed and non-inflamed patients. van den Boogaard M, Kox M, Quinn KL et al

Crit Care. 2011 Dec 29;15(6):R297. [Epub ahead of print]

This is an exploratory observational study of 100 ICU patients with or without

delirium and with ("inflamed") and without ("non-inflamed") infection/SIRS.

Delirium was diagnosed using the confusion assessment method-ICU (CAM-

ICU), and biomarker analysis occurred 24 hours following the onset of

delirium. In the non delirious group blood was taken at a similar time point as

the ICU length of stay at time of delirium in the delirium group. In

multivariate regression analysis this study found IL-8 was independently

associated (odds ratio 9.0; 95%CI 1.8-44.0) with delirium in inflamed patients

and IL-10 (OR 2.6; 95%CI 1.1 - 5.9) and A-beta1-42/40 (OR 0.03; 95%CI 0.002 -

0.50) with delirium in non-inflamed patients.

Full abstract available at:

http://www.ncbi.nlm.nih.gov/pubmed/22206727

Randomised control trials for delirium: Current evidence and statistical methods.

Tahir TA, Farewell D, Bisson J.

J Psychosom Res. 2012 Jan;72(1):84-5. Epub 2011 Nov 25.

This is a welcome discussion on the complexities of delirium RCT analyses,

and proposes some statistical methods and approaches which have been

undertaken. Well worth a read for those pondering trial design.

B: Editors Choice

Two papers with haloperidol in mind with results designed to confuse.

Differential risk of death in older residents in nursing homes

prescribed specific antipsychotic drugs: population based cohort

study

Huybrechts et al. British Medical Journal 2012;344:e977 (Published

23 February 2012)

Haloperidol prophylaxis decreases delirium incidence in elderly

patients after noncardiac surgery: A randomized controlled trial*.

Wang et al Critical Care Medicine 2012 Mar;40(3):731-9.

March news

Conferences

The Second Annual Meeting for the American Delirium

Society. Indianapolis, Indiana June 3-5, 2012

The second annual conference of the American Delirium Society in

Indianapolis, Indiana, June 3-5, 2012, promises to be a very exciting

program with the following two main goals:

• To disseminate knowledge on the state-of-the-art in delirium

identification, treatment, and prevention, and

• To discuss new directions for delirium identification, prevention and

treatment strategies.

Dr. Sharon Inouye, MD, MPH and Dr. Anne Kolanowski, PhD, RN as

keynote speakers will be discussing current knowledge and

innovations in delirium treatment and prevention from the

perspectives of both medicine and nursing. Sessions include the

following: 1) Pathophysiology of Delirium will examine work on

biomarkers for delirium diagnosis, prognosis, and therapy response;

2) Measurement of Delirium will focus on “cutting edge” research on

delirium identification tools; 3) Postoperative Delirium will review

issues pertaining to the brain undergoing the stress of surgery and

current research strategies regarding detection and treatment of

delirium following surgery; 4) Long-Term Outcomes of Delirium will

present current knowledge regarding the impact of delirium on

subsequent mood, cognition, morbidity and mortality; 5) Delirium

Care in the 21st Century will center on new prevention, evaluation

and treatment techniques; and 6) Clinical Trial Updates will highlight

new and ongoing treatment trials with regard to delirium and

delirium prevention.

Sorry about late notice but! March 15, 2012 – Abstract

Submission Deadline ~ submit abstracts in a Word document (for

formatting and publication purposes) to

abstracts@americandeliriumsociety.org.

For more information, please contact the ADS at

info@americandeliriumsociety.org.

Videocast – Patient experience

David Aaronovitch on the “abject terror” of ICU psychosis. 2011. BBC

News

www.bbc.co.uk/news/health-15881720.

In this Annals – see how to take part in the first Europe-

wide delirium assessment survey!

Delirium and Dementia

The British Geriatric Society and Royal College of Physicians are

holding a joint conference on 26 June in London. The conference was

organised by Alasdair MacLullich. The keynote talk is by the excellent

Ed Marcantonio (Harvard) on delirium treatment. If you were unable

to get to last years European Delirium Association here is your chance

to hear him speak - along with our own experts including Professor

John Young, Chair of the NICE guideline committee.

http://events.rcplondon.ac.uk/details.aspx?e=2573

European Delirium Congress:

7th EDA Scientific Congress: 18-19 October 2012, Bielefeld, Germany

We are delighted to announce that our 7th annual meeting will be held

in Bielefeld, the principal city of Eastern Westphalia in the north west

of Germany. The programme will cover the full spectrum of the latest

advances in delirium research and clinical practice, from basic science

to clinical implementation. Details will follow shortly.

Bielefeld is easily accessible from all parts of Europe. Please see here

for more details: http://www.bielefeld.de/en/travel/

Announcing the first European Delirium Association

survey

Dear Colleague Although there have been many advances in our knowledge of

delirium there are still substantial uncertainties and a lack of

consensus over best practice. The European Delirium Association

(EDA) has been disseminating knowledge of delirium within the

European Union in the last several years. The EDA has decided to

conduct a survey to help understand the range of opinions among

mailing list members on various aspect of delirium care. We greatly

appreciate your expertise and we believe that this survey will provide

a significant advancement in our understanding of current practice.

The findings will inform future directions in education, training,

governance, and research.

The results will be presented at the next EDA conference. You can find

the survey following this link:

http://kwiksurveys.com?s=LODJNH_6c7dc879. The survey takes

about fifteen minutes to complete. We are extremely grateful for your

time.

Please send any queries to : morandi.alessandromail.com;

dhjd2@medschl.cam.ac.uk

More information about the EDA can be found here:

www.europeandeliriumassociation.com

Kind Regards,

Alessandro Morandi, MD, MPH Board Member, EDA Daniel Davis, MB, MPhil Board Member, EDA Alasdair MacLullich, MRCP (UK), PhD President, EDA On behalf of the EDA