 |
Delirium in Old Age
August
2005 Update
Chapter
3: The epidemiology of delirium
NB This chapter update includes
updates on predisposing risk factors for delirium
but precipitating causes are discussed in
the update for Chapter 6: The causes of delirium.
Emerging themes
Relationship between delirium
and dementia
Lundstrom et al followed up those 78 patients
without pre-existing dementia from 100 consecutive
hip fracture patients for 5 years (2003).
38% were already delirious pre-admission
or developed delirium during their hospital
stay. All those with preoperative delirium
developed dementia over the following 5
years. Post-operative delirium was also
strongly associated with developing dementia.
Unfortunately they did not use any more
systematic method for the retrospective
diagnosis of dementia than DSM-IV, and in
their logistic regression poorer scores
on cognitive tests was another independent
factor predicting the development of delirium.
It is possible that at least some cases
of early dementia- itself a risk factor
for delirium, were missed, and that this
may explain some of their results. However,
as they say, the possibility that delirium
itself may be a risk factor for dementia
remains. Duppils and Wikblad (2004) claim
over a 6 months follow-up a difference in
decline in MMSE between 115 delirious and
non-delirious hip surgery (fracture and
replacement) patients who completed follow-up,
but also show an important difference in
the impact of delirium on later quality
of life. Lundstrom, Edlund, Bucht et al
(2003) have followed up 78 non-demented
hip fracture for 5 years and report a strong
association between the development of dementia
and pre-operative and post-operative DSM
IV delirium. In response to the evidence
that delirium episodes are at least harbingers
of dementia Meagher (2001) has suggested
that post-delirium dementia may be mistakenly
diagnosed because of the persistence of
delirious symptoms rather than the onset
of a different condition. However Gruber-Baldini,
Zimmerman, Morrison et al (2003) have abandoned
the distinction between delirium and dementia
in their study of cognitive impairment pre-
and post-hip fracture and surgery in 674
patients and confirm the persistence of
new impairment now found in many studies.
Margiotta A, Bianchetti, Ranierei et al
(2005) have briefly presented data suggesting
that the risk factors for delirium differ
significantly between those who have dementia
in those who do not. Further data are awaited.
Subsyndromal delirium
Marcantonio and colleagues have suggested
that patients with some symptoms of delirium
after hip fracture but who fall short of
current diagnostic criteria may have similarly
poor outcomes to those with definite but
mild delirium (2002) . Recognition of just
some delirious symptoms may be as important
as that of the full syndrome. However, a
note of caution has been sounded by Royall
(2004) in a careful and thought-provoking
editorial. He has questioned the nature
of subsyndromal states, and has produced
evidence for his scepticism in relation
to subsyndromal cognitive impairment as
a concept (but not about subsyndromal depression).
He asks if the presence, in a subsyndromal
state, of an outcome intermediate between
that of normals and the full-blown state
necessarily validates the former. He asks
"is shortness of breath equivalent
to subsyndromal pneumonia if it presents
in the absence of fever?". A provoking
questioned for most clinicians, but most
of us are then lost in the remainder of
his argument, in which he suggests that
if the introduction of nonlinear variables
into a regression analysis alongside the
linear one under question subverts its importance
then the case is not made for a subsyndromal
state.
Outcome: death
In contrast to what has been previously
accepted, a careful and important study
by McCusker et al (2002) has shown that
delirium is associated with post-discharge
mortality in medical patients independently
of co-morbidity, physical function, and
severity of illness. Interestingly the association
seemed stronger for patients without dementia,
which has led them to speculate whether
delirium in dementia is different, although
they also consider methodological possibilities
for this. In a large study of patients admitted
with community-acquired pneumonia, “altered
mental state” was found to be an independent
predictor of mortality by Waterer, Kessler,
& Wunderink (2004) along with age, cerebrovascular
disease, cardiovascular disease and a haematocrit
of <35%. Unfortunately, no more precise
description was given.
Delirium in the ICU also seems to be associated
with significant mortality controlling for
severity of physical illness. (Ely, Shintani,
Truman et al (2004). 275 patients who were
mechanically ventilated in ICU were studied,
and only 18.3% never developed delirium
during their time in the ICU. The duration
of delirium had an interquartile range of
one to three days. Dosage levels of medication
were higher in the delirium group., but
in only one drug (Lorazepam) was this significant.
At six months 34 percent of the patients
in the delirium group were dead versus 15
percent of those in the non delirium group.
In a time-dependent multivariate survival
analysis delirium was associated with a
greater than three times higher risk of
dying independently of the other covariates
studied. The question of whether delirium
is simply an epiphenomenon of non cerebral
processes which are themselves largely responsible
for excess mortality, or whether delirium
represents a central process itself in hastening
death is raised by a lot of the work in
intensive care, and is the subject of a
brief commentary by Ferreira and Trow (2005).
Indeed, evidence is mounting the delirium
is itself a contributor to mortality in
many settings independent of serious physical
illness. Possible mechanisms for this are
emerging (see Chapter 4).
The impact of delirium on survival after
hip fracture (Nightingale, Holmes, Mason
et al (2001) has been confirmed.
Pitkala and colleagues examined the long-term
outcome of delirium in acute wards of two
geriatric hospitals and nursing homes (2005).
All patients were over 70 years old and
they were initially classified as either
delirious or not delirious using DSMIV criteria.
Prior dementia was assessed on the basis
of history and clinical records. Outcomes
under study were mortality, admission to
hospital, and new admission to permanent
residential care. In a logistic regression
analysis prevalent delirium had an independent
impact on mortality at one and two years,
and an independent impact on a composite
outcome of either deceased or in institutions
at two years. They also found, interestingly,
that the one-year mortality was lower in
delirious patients with dementia than in
delirious patients without dementia, although
this was not statistically significant.
They took this to mean that a more severe
illness is required to "disturb a brain"
without previous cognitive impairment but
did not speculate as to how this "disturbance"
would itself translate into mortality. Overall
the outlook for patients with delirium was
poor in this group of very frail old people,
with nearly two-thirds dead within two years
Laurila and colleagues present data on
the outcomes for patients with delirium
diagnosed using the different criteria available
(2004). At baseline there were differences
in the presence of pre-existing dementia,
and whether or not living in permanent institutional
care in a total sample of 425 patients.
However, there were no differences in outcome
between patients identified as delirious
by the different criteria but they concluded
that the DSM-IV has identified new subjects
who would not previously have been identified
as delirious but who shared the same dismal
prognosis.
Outcome: Prolonged Hospital
Stay
McCusker et al have carefully distinguished
the contribution of incident and prevalent
dementia to length of stay in a Montreal
acute care hospital and found the former
and not the latter was significant, and
that dementia was less important (2003).
Saravay et al (2004) have asked whether
the association is related to the consequences
of the illness causing the delirium rather
than the delirium itself, or whether prolonged
length of stay increases the chances of
developing a delirium. Incidence studies
which do not control for duration of exposure
are open to this interpretation. However,
in an attempt to determine how cognitive
impairment (acute or chronic) is related
to length of stay they did not attempt to
distinguish dementia from delirium at admission
but used a number of measures to derive
the single factor of “cognitive impairment”,
and related this to data, subsequently entered
routinely on hospital charts, of two sorts-
“mental manifestations” (e.g.
cognitive impairment is noted) and “behavioural
manifestations” (falls, need for restraints,
pulling IV out, incontinence and impaired
decisional capacity) . They suggest their
findings indicate that the former precede
the latter but it is the latter that are
related to increased length of stay. Interventions
aimed at reducing lengths of stay might
be better targeted at those showing “mental
manifestations” before frank behavioural
problems emerge. However, a means of determining
incident events more robust than chart review
is demanded before this interesting idea
can be accepted.
Outcome: Institutionalisation
In a study of 477 patients mean age 82
admitted from home to hospital with hip
fracture, only 20% returned home from hospital
(Boockvar, Litke, Penrod et al (2004). However
at six months 58 percent of survivors had
reached home, usually via a nursing home
or rehabilitation facility. Moves to and
from hospital and care home were common
(average 3.5) in the six months after hip
fracture, and significantly associated with,
amongst other factors, delirium during the
index admission. Interestingly, the presence
of dementia was inversely associated with
frequent relocation. Surprisingly, relocations
were not significantly associated with worse
outcomes at six months, once a raft of risk
factors for poor outcomes had been controlled
for, including delirium.
Delirium in special circumstances
Emergency room (A&E)
Many patients with delirium are seen in
and not admitted- presumably because of
less severe physical illness which may contribute
to mortality- and so Kakuma and colleagues
(2003) have studied mortality in this group
to explore any independent contribution
of delirium. They found only an 8.4% prevalence
of delirium in 1268 patients, but an excess
mortality at 18 months in delirious patients
compared with non-delirious controls, particularly
in the first 6 months after attendance.
However, 72% of the delirious patients in
this study were admitted. Importantly, they
matched their controls for level of pre-existing
dementia. Recognition of delirium by staff
was inversely correlated with mortality,
but the numbers were too small to assess
the contribution of delirium to mortality
in the delirious group who were not admitted.
In another study in an emergency department
Hustey et al found a similar prevalence
(7%) of delirium in 271 emergency department
attenders (Hustey, Meldon, Smith et al (2003).
Recognition rates by the physicians showed
a sensitivity of 16% and a specificity of
98.4%. Over half the 19 delirious patients,
of whom 3 were recognised, were planned
to be discharged home. When CAM scores were
revealed to physicians, no change in management
plan resulted. The study was of a small
proportion of attenders and was not a probability
sample but the results are worrying.
Delirium in the ICU
Roberts, Rickard, Rajbhandari et al (2005)
used the ICDSC in six intensive care units
over six months, incorporated into routine
observations. Of the 2568 patients admitted,
2383 were excluded, mainly because their
stay in the intensive care unit was less
than 36 hours. The average age of the studied
group was 61 years and two-thirds of them
had a medical diagnosis as reason for admission
to the intensive care unit. Only 45 percent
were rated as delirious using the ICDSC.
They suggest that this low rate compared
with N American studies may be related to
them not using the CAM-ICU. Unlike Skrobic
et al (2005) they found that psychoactive
medication was significantly related to
the presence of ICU delirium. McNicoll and
colleagues have reported a prevalence of
delirium of 31% in 118 intensive care unit
patients aged 65 and over using the CAM
(2003), but they also found a complex relationship
between pre-existing dementia and the emergence
and disappearance of delirium at various
stages of the patients’ trajectory
through states of stupor in the ICU and
later in other wards in the hospital. The
cumulative rate of delirium in those with
dementia (i.e. developing delirium at any
time after admission) was over 80% in those
without pre-existing dementia and 63% in
those without. In the latter group there
was a significant incidence of delirium
in the ICU.
Delirium after hip fracture
Bitsch, Foss, Kristensen et al (2004) have
carried out a semi - systematic review of
the literature on risk factors for delirium
and the consequences of interventions in
patients experiencing hip fractures. Twelve
studies published up until 2003 were included.
Perhaps rashly, they concluded from the
variance between these papers that "there
is no common pathway leading to post-operative
delirium". Less controversially, they
concluded by recommending their own "multimodal"
approach after Kehlet and Wilmore (2002).
Kaganski and colleagues have published a
study of delirium in patients with hip fracture
with a surprisingly low incidence rate of
11.4% of delirium (2004). However, they
excluded patients with dementia, hearing
loss and severe visual impairment and it
has been suggested by O'Hanlon (2005) that
this was responsible for the low prevalence.
Kaganski et al admit this, and go further
to explain that they also excluded patients
with "interval" delirium immediately
postoperatively because "this type
of delirium has less influence on the rehabilitation
process” (Kagansky (2005)- an opinion
which will surprise many. Zakriya, Sieber,
Christmas et al (2004) have studied “Brief
post-operative delirium”- lasting
less than 6 weeks- and seem surprised to
confirm the well-known association between
delirium and institutionalization. It is
clear that the exhortations of Segatore
and Adams (2001) bears repeating: “Delirium
is never a ‘normal’ or an acceptable
response to acute surgical stress. Its presence
may be the only indicator of a lethal co
morbidity such as sepsis or myocardial infarction
and the harbinger of irreversible neurological
deterioration. The presence of delirium
should prompt timely and scrupulous evaluation
followed by thoughtful, targeted intervention.”
The nature of delirium after hip fracture
remains obscure. Apart from the Kagansky
findings the incidence of delirium after
emergency hip surgery in older patients
is one of the highest. There is a suspicion
that this is because many hip fracture patients
are already cognitively impaired before
their fall, or alternatively or additionally
their fall is caused by a cerebral event,
perhaps even including delirium itself.
In a study of hip fracture patients from
Sweden Olofsson and colleagues assessed
61 patients three or five days after surgery
(2005). 38 (62%) were delirious. These patients
suffered more complications during hospitalisation,
were more likely to be depressed, and were
also more dependent in activities of daily
living before the fracture. 43% of the patients
who developed delirium were suffering from
dementia prior to admission. 40% of the
delirious patients followed up at four months
were still delirious, and there were continuing
disabilities in this group. The prognosis
of patients with delirium after hip fracture
is very poor
Delirium in “post acute”,
rehabilitation or intermediate care facilities
Acute hospitals in the developed world
increasingly make use of “post-acute”
or “intermediate care” facilities,
but because much delirium persists, it becomes
a problem in these settings- in prevalence,
incidence, recognition and management. The
first published prevalence study at admission
to these post-acute facilities found a rate
of 16%, whilst more had sub-syndromal symptoms
of delirium (Kiely, Bergmann, Murphy et
al (2003). A model including whether or
not patients had all 8 symptoms of the Delirium
Symptom Index (Albert, Levkoff, Reilly et
al (1992), pre-acute admission cognitive
impairment, severe delirium and older age
discriminated between those whose delirium
persisted and those whose state did not
(Kiely, Bergmann, Jones et al (2004)
In an unusual observational study Marcantonio
and colleagues have tracked delirium symptoms
routinely reported by care staff in 85 “post-acute”
facilities (i.e. taking patients from acute
hospitals for rehabilitation or further
assessment (2003). They used a variant of
the Minimum Data Set system originally developed
for long-term care containing the following
six “delirium symptoms”: “easily
distracted, periods of altered perception,
disorganized speech, periods of restlessness,
periods of lethargy, and mental function
varies over the course of a day”.
23% of the 551 admitted patients who also
had an MDS assessment a week later had at
least one of these symptoms reported- episodes
of disorganised speech being the most common.
The majority had the same symptoms a week
later. The study is flawed by the fact that
many of these symptoms may be caused by
dementia, and the MDS-PAC validation and
inter-rater reliability data comes either
from other raters in other institutions
or does not exist at all. However, a Spanish
study of a delirium in a similar facility
have found a 22% rate of CAM delirium, nearly
all in patients at transfer (Pi-Figueras,
Aguilera, Arellano et al (2004). This is
a cause for concern, since moving delirious
patients from one facility to another seems
unlikely to be beneficial (though see Boockvar,
Litke, Penrod, Halm, Morrison, Silberzweig,
Magaziner, Koval, and Siu (2004)).
Delirium in nursing homes
Cacchione et al (2003) report the prevalence
of “acute confusion” as 39%
in 74 residents of two community-based,
for-profit long term care facilities for
older people. However, it is not clear which
of the methods used contributed to this
diagnosis, and the univariate analysis of
risk factors took no account of necessary
corrections for multiple analyses. As dehydration
is a known predisposing risk factor for
delirium in hospital it was reasonable for
Culp and colleagues to examine intensive
measures of hydration in a large sample
of nursing home residents to see whether
it was predicted in this setting as well
(2004). Using the Neecham scale, they identified
22 percent of the 313 residents as delirious
during a period of study. Although patients
with delirium had a higher blood urea nitrogen/creation
in ratio, bioelectrical impedence analysis
was not helpful in distinguishing delirium
from non delirium.
Delirium after stroke
This is widely recognised clinically, but
has not been studied systematically until
recently. Caiero and colleagues have examined
the impact of anticholinergic medications
on the development of delirium after stroke
in consecutive in-patients, matched by age
and gender with non delirious patients after
stroke (2004). 22 out of 190 consecutive
acute stroke patients presented delirium,
and these were more likely to show neurological
neglect, have a higher Glasgow coma scale
at admission, were less likely to have cerebral
infarcts. Logistic regression revealed that
intracranial haemorrhage and anticholinergics
were amongst the most important independent
predictors of delirium.
Delirium after vascular surgery
Bohner, Hummel, Habel et al (2003) studied
the incidence of delirium in 153 vascular
surgery patients including an unknown number
of older ones. 39% developed postoperative
delirium
In a study of risk factors for delirium
after coronary artery bypass surgery, Santos,
Velasco, & Fraguas, Jr. (2004) found
that age, hypertension, heart failure, renal
function, atrial fibrillation, and pulmonary
infection were, unsurprisingly, related
to the emergence of delirium. However they
were the first to directly associate smoking
with delirium. These factors remained important
after logistic regression analysis.
Rothenhausler, Grieser, Nollert et al (2005)
have reported a one-year follow-up of 34
patients undergoing elective cardiac surgery
with cardiopulmonary bypass. Post-operative
delirium developed in 11 of these patients
but in all cases within three days of surgery.
Delirium lasted up to seven days in this
group: there were no prolonged episodes
Minden and colleagues have studied the
incidence of delirium in 35 older patients
undergoing aortic aneurysm surgery (2005).
They use different methods of ascertainment
of delirium to arrive at an incidence figure
of 22.9%. Risk factors for delirium in this
group were preoperative depressive symptoms,
alcohol use and, inevitably pre-existing
cognitive impairment. As might be expected
delirium was associated with longer length
of stay and poorer physical functioning,
social functioning and energy at follow-up.
Rudolph, Babikian, Birjiniuk et al (2005)
have found a high correlation between atherosclerosis
in the aorta and other arteries and post-operative
delirium in 36 patients aged between 49
and 98 years undergoing coronary artery
bypass surgery. The incidence of delirium
was 41.7%.
Delirium after urological and
thoracic surgery
In an intriguing study Hamann and colleagues
have found a very low incidence of acute
confusional state in 100 patients over 60
undergoing urological surgery (2005) . Using
the CAM and ICD 10 criteria they found an
incidence of only 7% in their sample -77%
male, mean age was 71.9 years. These patients
were referred to a university department
and may not have been typical of all urological
patients. However, their results are in
keeping with other studies of urological
surgery. It is possible that patients with
dementia and other risk factors for delirium
are specifically excluded from urological
surgery, or it may be that urological surgery
is particularly un- associated with systemic
and cerebral vascular risk. Similarly, in
a study of comprehensive geriatric assessment
of 120 older patients undergoing thoracic
surgery only 3 developed post-operative
delirium (Fukuse, Satoda, Hijiya et al (2005).
Premorbid dementia predicted delirium, but
it also predicted physical complications
of surgery
Delirium in patients on long-tem
Lithium
In an unusual population-based study Shulman
and colleagues have reported on the association
of lithium or sodium valproate dispensing
with a new diagnosis of delirium one-year
later (2005). As a reference they also examined
this outcome in relation to prescription
of benztropine. Using time to delirium as
an outcome measure in over 10,000 patients
with no previous history of mood disorder
and a further 4000 with such a history,
they found no relationship between the prescription
of lithium and admission for delirium. .
There was a trend for patients with sodium
valproate prescriptions to be more likely
to be admitted with delirium but this was
not statistically significant. When they
analysed the data for only patients in whom
there was no documented history of dementia
whatsoever they found the same result. This
study relies on the recognition of recording
of delirium in clinical records, a weakness
that they freely admit Although the purpose
of their article was to insist that lithium
remains a preferable first line option over
valproate, it also gives heart to those
involved in the development of lithium is
a treatment for dementia.
Table
1: Incidence studies in surgical patients
published since manuscript submission of
Delirium in Old Age
| Study |
Patients |
No. |
Age(years) |
Delirium
%
(incidence) |
|
Andersson, Gustafson, & Hallberg (2001)
|
Hip
surgery |
505 |
65+ |
11 |
|
Litaker, Locala,
Franco et
al (2001)
|
Major
surgery |
500 |
50+ |
11 |
|
Schneider, Bohner, Habel
et
al (2002)
|
Vascular
surgery |
47 |
53-84 |
36 |
|
Marcantonio, Ta,
Duthie et
al (2002)
|
Hip
fracture |
122 |
65+ |
40 |
|
Morrison, Sean, Magaziner et al (2003)
|
Hip
fracture |
541 |
? |
16 |
|
Milstein, Pollack, Kleinman et al (2002)
|
Cataract |
296 |
22-94 |
4.4 |
|
Bohner, Hummel, Habel,
Miller, Reinbott,
Yang, Gabriel, Friedrichs, Muller, Ohmann, Sandmann, and Schneider (2003)
|
Vacsular surgery |
153 |
? |
39 |
|
Edelstein, Aharonoff, Karp et al (2004)
|
Hip
Fracture |
921 |
65+ |
5.1
(post-op assessment only) |
|
Kagansky, Rimon, Naor et al (2004)
|
Hip
Fracture |
137 |
75+ |
11.4
(excluded ”interval” delrium) |
|
Santos, Velasco, and Fraguas, Jr. (2004)
|
CABG
surgery |
220 |
60+ |
33.6 |
|
Fukuse, Satoda, Hijiya, and Fujinaga
(2005)
|
Thoracic Surgery |
120 |
60+ |
2.5 |
|
Yamagata, Onizawa, Yusa
et
al (2005)
|
Head
& Neck cancer Surgery |
38 |
mean
59.2 |
26 |
|
Olofsson, Lundstrom,
Borssen
et
al (2005)
|
Hip Fracture |
52 |
70+ |
62
|
|
Hamann, Bickel, Schwaibold
et
al (2005)
|
Urological surgery |
100 |
60+ |
7 |
|
Rothenhausler, Grieser,
Nollert,
Reichart,
Schelling, and Kapfhammer (2005)
|
Cardiac
surgery with CP bypass |
34 |
mean
68 |
32 |
|
Rudolph, Babikian, Birjiniuk,
Crittenden, Treanor,
Pochay,
Khuri, and
Marcantonio
(2005)
|
Coronary
artery bypass surgery |
36 |
49-98 |
41.7 |
|
Minden, Carbone, Barsky
et
al (2005)
|
Aortic
aneurysm |
35 |
46-88 |
23 |
Footnotes
McCusker et al (2001) have shown a deliriogenic
effect of environmental factors in in-patient
units.
Given that the majority of people with
dementia, possible the biggest predisposing
risk factor for delirium, live in developing
countries, and that they may be subject
o higher rates of incident physical (particularly
infective) precipitating causes, studies
in these countries are needed. The rate,
associations and outcomes of delirium in
older medical patients in Mexico has been
established to be similar to those in developing
countries (Villalpando-Berumen, Pineda-Colorado,
Palacios et al (2003), although the rate
of immediate mortality was low.
The issue of delirium in learning difficulties/disabilities
as then reviewed by van Waarde and van der
Mast (2004). These states appears to correspond
to the model proposed by Inouye (1999) in
which learning disabilities, or their organic
bases are strong predisposing factors.
Why risk factors for delirium after head
and neck cancer surgery should be any different
from any other major surgery is mysterious,
yet Yamagata and colleagues have set out
to examine this (Yamagata, Onizawa, Yusa,
Wakatsuki, Yanagawa, and Yoshida (2005).
Unfortunately they use medical records to
identify delirium, which makes it difficult
to compare their result with those of others
who have used more objective and reliable
means of case identification.
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