Cochrane SCA Sindrome Confusional Agudo

Interventions for preventing delirium in hospitalised patients
(Review)
Siddiqi N, Holt R, Britton AM, Holmes J
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2009, Issue 1
http://www.thecochranelibrary.com
Interventions for preventing delirium in hospitalised patients (Review)

Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ACKNOWLEDGEMENTS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Post surgery administration of DFP v Usual care, Outcome 1 Incidence of delirium in first 7
days after surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.2. Comparison 1 Post surgery administration of DFP v Usual care, Outcome 2 Behavioural disturbance in 1st 7
days after surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.3. Comparison 1 Post surgery administration of DFP v Usual care, Outcome 3 Length of admission. . .
Analysis 2.1. Comparison 2 Epidural anaesthesia v Halothane anaesthesia, Outcome 1 Incident delirium on day 1 or day 7
post surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.2. Comparison 2 Epidural anaesthesia v Halothane anaesthesia, Outcome 2 Physical morbidity. . . . .
Analysis 3.1. Comparison 3 Prophylactic citocoline v Placebo, Outcome 1 Incident delirium. . . . . . . . .
Analysis 4.1. Comparison 4 Prophylactic haloperidol v Placebo, Outcome 1 Incident delirium post surgery.
. . .
Analysis 4.2. Comparison 4 Prophylactic haloperidol v Placebo, Outcome 2 Delirium duration. . . . . . . . .
Analysis 4.4. Comparison 4 Prophylactic haloperidol v Placebo, Outcome 4 Length of admission. . . . . . . .
Analysis 4.5. Comparison 4 Prophylactic haloperidol v Placebo, Outcome 5 Withdrawal from protocol. . . . . .
Analysis 4.6. Comparison 4 Prophylactic haloperidol v Placebo, Outcome 6 Adverse effects. . . . . . . . . .
Analysis 5.1. Comparison 5 Prophylactic donepezil v Placebo, Outcome 1 Delirium incidence after surgery. . . .
Analysis 5.4. Comparison 5 Prophylactic donepezil v Placebo, Outcome 4 Withdrawal from protocol. . . . . .
Analysis 6.1. Comparison 6 Proactive geriatric consultation v Usual care, Outcome 1 Cumulative delirium incidence.
Analysis 6.2. Comparison 6 Proactive geriatric consultation v Usual care, Outcome 2 Delirium duration. . . . .
Analysis 6.3. Comparison 6 Proactive geriatric consultation v Usual care, Outcome 3 Severity- cumulative incidence of
severe delirium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 6.4. Comparison 6 Proactive geriatric consultation v Usual care, Outcome 4 Institutionalisation at discharge.
Analysis 6.5. Comparison 6 Proactive geriatric consultation v Usual care, Outcome 5 Cognitive statusdelirium prevalence
at discharge. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
INDEX TERMS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1
1
2
2
3
3
6
9
11
11
11
15
27
29
29
30
30
31
32
33
33
34
34
35
35
36
36
37
37
38
38
38
40
40
40
40
41
41
[Intervention Review]

Najma Siddiqi1 , Rachel Holt2 , Annette M Britton3 , John Holmes4
1
Academic Unit for Psychiatry and Behavioural Sciences, University of Leeds, Leeds, UK. 2 Leeds, UK. 3 Geriatric Unit, Royal Prince
Alfred Hospital, Sydney, Australia. 4 Academic Unit of Psychiatry, University of Leeds, Leeds, UK
Contact address: Najma Siddiqi, Academic Unit for Psychiatry and Behavioural Sciences, University of Leeds, 15 Hyde Terrace, Leeds,
LS2 9LT, UK. n.siddiqi@leeds.ac.uk.
Editorial group: Cochrane Dementia and Cognitive Improvement Group.
Publication status and date: Edited (no change to conclusions), published in Issue 1, 2009.
Review content assessed as up-to-date: 11 January 2007.
Citation: Siddiqi N, Holt R, Britton AM, Holmes J. Interventions for preventing delirium in hospitalised patients. Cochrane Database
of Systematic Reviews 2007, Issue 2. Art. No.: CD005563. DOI: 10.1002/14651858.CD005563.pub2.
ABSTRACT
Background
Delirium is a common mental disorder with serious adverse outcomes in hospitalised patients. It is associated with increases in mortality,
physical morbidity, length of hospital stay, institutionalisation and costs to healthcare providers. A range of risk factors has been
implicated in its aetiology, including aspects of the routine care and environment in hospitals. Prevention of delirium is clearly desirable
from patients and carers perspectives, and to reduce hospital costs. Yet it is currently unclear whether interventions for prevention of
delirium are effective, whether they can be successfully delivered in all environments, and whether different interventions are necessary
for different groups of patients.
Objectives
Our primary objective was to determine the effectiveness of interventions designed to prevent delirium in hospitalised patients. We
also aimed to highlight the quality and quantity of research evidence to prevent delirium in these settings.
Search methods
We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 30 September 2006. As the
searches in MEDLINE, EMBASE, CINAHL and PsycINFO for the Specialized Register would not necessarily have picked up all
delirium prevention trials, these databases were searched again on 28th October, 2005. We also examined reference lists of retrieved
articles, reviews and books. Experts in this field were contacted and the Internet searched for further references and to locate unpublished
trials.
Selection criteria
Randomised controlled trials evaluating any interventions to prevent delirium in hospitalised patients.
Data collection and analysis
Data collection and quality assessment were performed by three reviewers independently and agreement reached by consensus.
Main results
Six studies with a total of 833 participants were identified for inclusion. All were conducted in surgical settings, five in orthopaedic
surgery and one in patients undergoing resection for gastric or colon cancer.
Only one study of 126 hip fracture patients comparing proactive geriatric consultation with usual care was sufficiently powered to
detect a difference in the primary outcome, incident delirium. Total cumulative delirium incidence during admission was reduced in
the intervention group (OR 0.48 [95% CI 0.23, 0.98]; RR 0.64 [95% CI 0.37, 0.98]), suggesting a number needed to treat of 5.6
patients to prevent one case. The intervention was particularly effective in preventing severe delirium. In logistic regression analyses
adjusting for pre fracture dementia and Activities of Daily Living impairment, there was no reduction in effect size, OR 0.6, but this
no longer remained significant [95% CI 0.3,1.3]. There was no effect on the duration of delirium episodes, length of hospital stay, and
cognitive status or institutionalisation at discharge. There was also no significant difference in cumulative delirium incidence between
treatment and control groups in a sub-group of 50 patients with dementia (RR 0.9 [95% CI 0.59, 1.36]).
In another trial of low dose haloperidol prophylaxis, there was no difference in delirium incidence but the severity and duration of a
delirium episode, and length of hospital stay were all reduced.
We identified no completed studies in hospitalised medical, care of the elderly, general surgery, cancer or intensive care patients. In
outcomes, no studies examined for death, use of psychotropic medication, activities of daily living, psychological morbidity, quality of
life, carers or staff psychological morbidity, cost of intervention and cost to health care services. Outcomes were only reported up to
discharge, with no studies reporting medium or longer-term effects.
Authors conclusions
Research evidence on effectiveness of interventions to prevent delirium is sparse. Based on a single study, a programme of proactive
geriatric consultation may reduce delirium incidence and severity in patients undergoing surgery for hip fracture. Prophylactic low dose
haloperidol may reduce severity and duration of delirium episodes and shorten length of hospital admission in hip surgery. Further
studies of delirium prevention are needed.
PLAIN LANGUAGE SUMMARY

There is a lack of robust information on delirium prevention in hospitalised patients
We were only able to identify one trial with adequate power to demonstrate effectiveness of any preventive strategies. Based on this
single study, proactive consultation by a consultant geriatrician before, or within 24 hours of operation may reduce the incidence and
severity of delirium in patients undergoing surgery for hip fracture. Low dose haloperidol prophylaxis may be effective in reducing the
severity and duration of a delirium episode and may shorten length of hospital admission. Given what is already known about how
common delirium is, and how poor its outcomes are, further trials of delirium prevention are urgently needed.
BACKGROUND
Delirium, a disturbance of consciousness and cognition, with rapid
onset, fluctuating course and underlying causation, has been variously termed acute organic brain syndrome, acute organic mental
disorder and toxic confusional state. Until the 19th century delirium was used to describe a disorder of thinking and later descriptions included disturbances of perception, often with overactive
behaviour, or impaired consciousness. The publication of DSMIII (APA 1987) in 1987 brought together these ideas, combining
disturbance of consciousness with impairment of cognition; the
core features of delirium have been clarified in the DSM-IV (APA

1994) and ICD-10 (WHO 1992). This recent consensus has allowed some standardisation of research, and greater comparability
between studies.
Delirium is common in hospitalized patients. Ten to 30% of admissions to a general hospital develop delirium (Levkoff 1991;
Trzepacz 1996) and in general medical in-patients, occurrence
rates ranging from 11 to 42% have been reported (Siddiqi 2006).
Delirium has a prevalence of up to 60% in frail elderly patients

(Francis 1990), and 7 to 9.6% in elderly patients presenting

to emergency departments (Elie 2000; Hustey 2003). Following
coronary artery bypass grafting in the elderly, incidence has been
reported as 33.6% (Santos 2004), and after bilateral knee replacements 41% (Williams-Russo 1992). Following hip fracture the
overall prevalence is 43 to 61% (Holmes 2000).
Patients in intensive care units (ICU) are at high risk of developing
delirium, with incidence rates of 40% reported (Roberts 2004).
Cancer also increases the risk of developing delirium. 18% of those
admitted to an oncology ward, and 26 to 44% of those admitted to
hospital or a hospice with a diagnosis of advanced cancer developed
delirium (Centeno 2004; Ljubisavljevic 2003). In AIDS patients
who are unwell enough to be admitted, incidence of delirium is
also high, being reported as 46% (Uldall 1997).
Delirium is serious, with significant short and long term outcomes. Death rates are increased (McCusker 2002), functional
abilities reduced (Moller 1998), admission to long-term care increased (Inouye 1998a), and length of stay increased (McCusker
2003a; Stevens 1998). Impairment of cognitive function can persist for at least one year (McCusker 2001), as can the symptoms
of delirium, especially inattention, disorientation and impaired
memory (McCusker 2003b). Increasingly recognised is the distress
an episode of delirium produces in carers (Breitbart 2002).
Research in the elderly has identified a multitude of risk factors.
The condition clearly has a multi-factorial aetiology, and these
risk factors interact (Inouye 1998b); the more risk factors that
are present, the greater the likelihood that the patient will develop delirium. Risk factors that have so far been identified include: increased age, sensory deprivation (visual or hearing impairment), sleep deprivation, social isolation, physical restraint,
use of bladder catheter, iatrogenic adverse events, poly-pharmacy
(more than three new medications added), use of psychoactive
drugs, co-morbidities, severe illness (especially infection, fracture
or stroke), prior cognitive impairment, temperature abnormality
(fever or hypothermia), dehydration, malnutrition and low serum
albumin (Inouye 1998b; Inouye 1999c).
Studies in oncology patients have identified a range of different
risk factors for the development of delirium, for example bone
metastases, the presence of haematological malignancy, advanced
age, cognitive impairment, and low albumin level (Ljubisavljevic
2003).
The identification of such a varied list of aetiological factors suggests several things. Firstly, we may be able to identify patients at
high risk of developing delirium, and by modifying these risk factors could attempt to prevent it; differing groups of patients may
require a different set of preventative measures. Secondly, many of
these risk factors can be seen as hospital quality of care measures,
e.g. malnutrition, dehydration, use of physical restraints, iatrogenic events. Occurrence of delirium can, therefore, be seen as a
proxy measure of the quality of in-patient care (Inouye 1999b).
Prevention of delirium is obviously desirable for both patients and

carers, and to reduce health service costs. A recent study found that
the health care costs in patients who developed delirium in ICUs
were 31% higher ($41,836 versus $27,106) (Milbrandt 2004).
A non-randomised study of a multi-component intervention for
delirium demonstrated overall improved cost-effectiveness (Rizzo
2001).
Possible interventions for preventing delirium in hospitalized patients have been developed. Most of the current studies have taken
a multi-factorial approach, attempting to prevent several risk factors by protocols, education or systems redesign, rather than focusing on one risk factor in isolation (Cole 2002; Inouye 2000a;
Milisen 2001). Interventions include programmes of education
for ward nursing staff (Rockwood 1999), non-pharmacological
intervention protocols targeting specific risk factors and implemented by a trained interdisciplinary team (Inouye 1999a), and
a specialist nursing intervention to educate nursing staff, assess
and change medication, encourage mobilization and improve the
environment of the patient (Wanich 1992).
It is currently unclear whether interventions for prevention of
delirium are effective, whether they can be successfully delivered
in all environments, and whether different interventions are necessary for different groups of patients. Previous reviews (Cole 1999;
Milisen 2005) have suggested possible protocols for delirium prevention, but have not been systematic or have employed less rigorous selection criteria.
OBJECTIVES
Primary objective: To determine the effectiveness of interventions
designed to prevent delirium in hospitalised patients.
Secondary objective: To highlight the quality and quantity of
research evidence to prevent delirium in hospitalised patients
METHODS
Criteria for considering studies for this review
Types of studies
We included only original reports of randomised controlled trials in the review. Because of the difficulties inherent in blinding
of participants and researchers to certain types of interventions,
blinding was not a prerequisite for inclusion. The length of trial
did not influence selection of studies.

Types of participants
We included patients aged 16 years or over, admitted to acute
general hospitals, and at risk of developing delirium. We excluded
studies conducted in community settings e.g. in nursing homes.
We excluded studies in mixed settings unless data could be extracted separately for hospitalised in-patients.
Types of interventions
We included studies of any intervention(s) designed to prevent
delirium with controls receiving standard care. We also included
trials comparing two types of intervention. Trials of co-ordinated
multi-strategy initiatives were included. Examples of interventions
we included are: regular screening of cognitive function or mental
state, protocol driven medical review and investigation, medication review, medication, nursing interventions, education of staff
or family.
We defined standard care as the usual care available on that unit.
Types of outcome measures
The primary outcomes of interest were:
incident delirium (new onset) during admission
death
We only accepted studies in which delirium was identified using
a validated method for diagnosis, such as operationalised clinical
criteria from ICD-10, DSM-III, DSM-IIIR, DSM-IV, (WHO
1992; APA 1987; APA 1994; APA 1999) or using diagnostic tools
based on these e.g. the Confusion Assessment Method (CAM)
(Inouye 2000b), Delirium Rating Scale (DRS) (Trzepacz 1988).
All types of delirium (hypoactive, hyperactive and mixed) were
considered together. We included drug-induced delirium but not
delirium tremens.
Secondary outcomes were:
duration of delirium
severity of delirium, measured by validated instruments
including the Memorial Delirium Assessment Scale (MDAS)
(Breitbart 1997) and DRS
use of psychotropic medication
behavioural disturbance
length of admission
activities of daily living
institutional care at discharge
cognitive status
physical morbidity
psychological morbidity
quality of life
carers psychological morbidity
staff psychological morbidity
withdrawal from protocols by patients
cost of intervention
cost to health care services
We also included adverse events, although this was not specified

in the original published protocol.
Search methods for identification of studies

CDCIG Specialised Register:
The Specialized Register of the Cochrane Dementia and Cognitive
Improvement Group was searched on 30 September 2006 using
the terms: delirium or acute confusion or acute brain failure
or acute organic psychosyndrome or acute brain syndrome or
metabolic encephalopathy or acute psycho-organic syndrome
or clouded state or clouding of consciousness or exogenous
psychosis or toxic psychosis or toxic confusion.
The Specialized Register at that time contained records from the
following databases:
CENTRAL: July 2005 (issue 3);
MEDLINE: 1966 to 2005/08, week 2;
EMBASE: 1980 to 2005/08, week 2;
PsycINFO: 1887 to 2005/07;
CINAHL: 1982 to 2004/07;
SIGLE (Grey Literature in Europe): 1980 to 2004/06;
ISTP (Index to Scientific and Technical Proceedings): to
May 2000;
INSIDE (BL database of Conference Proceedings and
Journals): to June 2000;
Aslib Index to Theses (UK and Ireland theses): 1970 to
March 2003;
Dissertation Abstract (USA): 1861 to March 2003;
http://clinicalstudies.info.nih.gov/;
National Research Register (issue 3/2005)
ClinicalTrials.gov: last searched 1 September 2005;
LILACS: Latin American and Caribbean Health Science
Literature: last searched April 2003
http://www.forestclinicaltrials.com/: last searched 1
September 2005
ClinicalStudyResults.org: last searched 1 September 2005
http://www.lillytrials.com/index.shtml: last searched 28
August 2005
ISRCTN Register: last searched 1 September 2005
IFPMA Clinical Trials Register: http://www.ifpma.org/
clinicaltrials.html: last searched September 2005
The search strategies used to identify relevant records in MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS can be
found in the groups module.
As the searches in MEDLINE, EMBASE, CINAHL and
PsycINFO for the Specialized Register would not necessarily have
picked up all delirium prevention trials (it is primarily a register of
trials with people with dementia or cognitive impairment), these
databases were searched again on 28th October 2005 with the following search strategies:
MEDLINE (1966-2005)

1.Delirium/ all subheadings

2.deliri*
3.acute confusion
4.acute organic psychosyndrome
5.acute brain syndrome
6.metabolic encephalopathy
7.acute psycho-organic syndrome
8.clouded state
9.clouding of consciousness
10.exogenous psychosis
11.toxic psychosis
12.toxic confusion
13.#1 or #2
14.#3 or #4 or #5 or #6
15.#7 or #8 or #9 or #10
16.#11 or #12
17.#13 or #14 or #15 or #16
18.explode Primary-Prevention/ all subheadings
19.prevent*
20.avoid*
21.#18 or #19 or #20
22.#17 and #21
23.random* or placebo* or control*
24.standard treatment or normal treatment or standard care
or normal care
25.#23 or #24
26.#22 and #25
27.Alcohol-Withdrawal-Delirium/ all subheadings
28.delirium tremens in TI
29.#27 or #28
30.#26 not #29
31.((TG=animals) not (TG=humans)) and (TG =animals)
32.#30 not #31
EMBASE (1980-2005)
1 explode delirium tree: 1/ all subheadings
2 deliri*
3 acute psycho-organic syndrome or clouded state or clouding of consciousness or exogenous psychosis or toxic psychosis
or toxic confusion
4 acute brain confusion or acute brain failure or acute organic psychosyndrome or acute brain syndrome or metabolic
encephalopathy
5 #1 or #2 or #3 or #4
6 explode prevention/ all subheadings
7 prevent* or avoid*
8 #6 or #7
9 #5 and #8
10 randomized-controlled-trial/ all subheadings
11 random* or placebo* or control* or normal care or standard
care or standard treatment or normal treatment
12 #10 or #11
13 #9 and #12
14 delirium-tremens/ all subheadings

15 #13 not #14
16 nonhuman* in DER
17 (nonhuman* in DER) and (human* in DER)
18 #16 or #17
19 #15 not #17
PsycINFO (1887-2005)
1 deliri*
2 acute psycho-organic syndrome or clouded state or clouding of consciousness or exogenous psychosis or toxic psychosis
or toxic confusion
3 acute brain confusion or acute brain failure or acute organic
psychosyndrome or acute brain syndrome or metabolic encephalopathy
4 Delirium- in MJ,MN
5 #1 or #2 or #3 or #4
6 explode Prevention
8 #6 or #7
9 #5 and #8
10 random* or placebo* or control* or normal treatment or
normal care or standard care or standard treatment
11 #9 and #10
CINAHL (1982-2004)
1 deliri*
2 acute psycho-organic syndrome or clouded state or clouding of consciousness or exogenous psychosis or toxic psychosis or toxic confusion
3 acute brain confusion or acute brain failure or acute organic psychosyndrome or acute brain syndrome or metabolic
encephalopathy
4 Delirium/ without-subheadings
5 #1 or #2 or #3 or #4
6 Preventive-Trials/ without-subheadings
8 #6 or #7
9 #5 and #8
10 random* or placebo* or control* or normal care or standard
care or normal treatment or standard treatment
11 #9 and #10
12 Alcohol-Withdrawal-Delirium/ without-subheadings
13 delirium tremens in TI
14 #12 or #13
15 #11 not #14
16 (animal in DE) not ((human in DE) and (animal in DE))
17 #15 not #16
CENTRAL (issue 3/2005)
1.(acute next confusion)
2.(acute next brain next syndrome)
3.(acute next organic next psychosyndrome)
4.(clouding next consciousness)
5.(acute next psychosis)

6.(toxic next psychosis)

7.(toxic next confusion)
8.(acute next psychosyndrome)
9.(acute next psycho-syndrome)
10.(#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9)
11.(#10 and (prevent* or avoid*)
12.(#11 and (not delirium tremens))
We reviewed bibliographies of books and review articles on delirium, and also references from retrieved articles. Experts in this field
were contacted for further references and to locate unpublished
trials. The Internet was searched using the search engines Google
and Copernic to try to find further evidence of unpublished trials
using the same terms as stated above.
We did not apply any time restrictions or language constraints.
Data collection and analysis

Selection of Studies
The titles, abstracts and descriptors of citations identified by the
search were examined by two reviewers, NS and RS independently;
those deemed to be clearly irrelevant were discarded. The aim was
to be over-inclusive at this stage to avoid losing potentially relevant
studies. Full text copies of the remaining citations were retrieved
and assessed independently by NS and RS for inclusion using the
criteria described above. Disagreements at any stage of study selection were resolved by referral to JH (this was only necessary with
regard to one study). Reports were checked for multiple publication of the same data.
Quality Assessment
The internal validity of trials relates to how successfully selection,
performance, attrition and detection biases are eliminated (Clarke
1999). The quality of included trials was assessed independently
by NS, RS and AB using predetermined criteria adapted from
the U.S. Preventive Services Task Force (Harris 2001; Table 1). A
consensus process was used to reach agreement. Reviewers were not
blinded to author and source institution. A was used to indicate
a trial in which all the quality criteria were met, B to indicate that
one or more criteria were partially met and the rest fully met, and
C if one or more criteria were not met or if it was not possible to
determine whether one or more criteria were met.
Data Extraction
A data extraction form was designed and piloted. Data were then
independently extracted by three reviewers NS, RS and AB with
disagreements resolved by a consensus process.
To allow an intention-to-treat analysis, data were sought for every
patient randomised to treatment or control group irrespective of
compliance or subsequent exclusion. Where data were only available for participants completing treatment, these were extracted
and reported separately. When individual patient data were not
available, data were extracted from summary statistics for each
study.
Data Analysis
Missing data and drop-out rates were assessed for each of the included studies. We reported the number of participants included
in the final analysis as a proportion of all participants in the study.
For binary outcomes, a standard estimation of the risk ratio with
a 95% confidence interval was calculated.
Where means and standard deviations were available, we analysed
continuous data with a normal distribution (or approximating to
a normal distribution) using Revman Statistical analysis software.
Appropriate non-parametric tests were used to analyse data not
normally distributed.
We pre-determined that if there were sufficient data and it was
appropriate to do so, one or more meta-analyses would be performed. However, no such analyses were possible due to lack of
comparability of interventions and comparators used in individual
studies.
We planned to perform a subgroup analysis of outcomes in patients
with and without dementia, but this was only possible for one
outcome in one study.
RESULTS
Description of studies
See: Characteristics of included studies; Characteristics of excluded
studies; Characteristics of ongoing studies.
Six, very diverse studies met our selection criteria, all conducted
in surgical settings (Aizawa 2002; Berggren 1987; Diaz 2001;
Kalisvaart 2005; Liptzin 2005; Marcantonio 2001). One study
was limited to patients operated on for gastric or colorectal cancer (Aizawa 2002). Five included orthopaedic patients, three conducted in patients requiring surgery for hip fracture, one in acute
or elective hip surgery patients (Kalisvaart 2005) and one in elective hip or knee arthroplasty patients (Liptzin 2005). Most studies
were conducted in older people.
All six studies tested markedly different interventions; one compared two anaesthetic approaches (Berggren 1987), one evaluated
proactive geriatric consultation (Marcantonio 2001), and the others investigated administration of various pharmacological agents.
There were no studies of multi component interventions, and none
conducted in non-surgical settings.
Outcomes examined included incident delirium, duration and
severity of delirium, behavioural disturbance, length of admission,
physical morbidity, cognitive status and institutionalisation at discharge. Although all studies determined the incidence of delirium, there was heterogeneity in both the statistical measures of
frequency, and diagnostic methods used.
Aizawa et al (Aizawa 2002) hypothesised that sleep disorders are
one of the critical factors in the aetiology of postoperative delirium in patients treated in the ICU after surgery and attempted to

control disturbance of the sleep-wake cycle. They devised a Delirium Free Protocol (DFP) employing routine administration of
diazepam, flunitrazepam and pethidine. They compared the effect of this unusual intervention with care as usual on the primary
outcome, delirium incidence in the first 7 days after surgery. A
single psychiatrist performed a screening interview twice daily and
diagnosed delirium according to DSM IV criteria (APA 1994).
In secondary outcomes, behavioural disturbance in the same time
period and length of admission were examined.
A Swedish study (Berggren 1987) compared the incidence of postoperative mental confusion in patients operated on for hip fracture under epidural and under halothane anaesthesia. Again their
primary outcome was incident delirium, but this was defined as
delirium present on day one and/or day seven after surgery. They
also determined length of admission and physical morbidity including stroke, urinary tract infection and decubitus ulcer. Delirium was diagnosed by DSM III criteria (APA 1987) using a modified Organic Brain Syndrome Scale (OBS) (Jensen 1993) by two
trained researchers.
CDP-choline (cytidine 5-diphosphocholine) is a precursor essential for the synthesis of cell membrane components, and animal
studies suggest that it may protect cell membranes, and may also
attenuate the progression of ischaemic cell damage (Fioravanti
2006). A recent Cochrane review (Fioravanti 2006) concluded that
there was some evidence that CDP-choline has a positive effect on
memory and behaviour in at least the short/medium term in older
people, with cognitive deficits associated with chronic cerebral disorders of the brain. A study from Chile (Diaz 2001) compared
the effectiveness of citicoline (CDP-choline) with placebo in preventing delirium in patients undergoing hip fracture surgery. In
addition to administration of the study drug, anticholinergics or
benzodiazepine use was stopped, and anaemia and haemodynamic
disturbances corrected in both groups. The primary outcome of
interest was incident delirium; this was determined immediately
after surgery and on days 1, 2 and 3 postoperatively, using the
Abbreviated Mental Test Score (AMT) (Hodkinson 1972) and
CAM. Cognitive status after surgery was assessed using the MiniMental State Examination (MMSE) (Folstein 1975).
Kalisvaart et al (Kalisvaart 2005) administered daily prophylactic
oral haloperidol (1.5 mg) to elective and non-elective hip surgery
patients at intermediate to high risk of delirium. Controls were
given placebo tablets identical in appearance to the study drug.
All patients were also offered proactive geriatric consultation. If
delirium occurred, the dose of study drug was doubled. In addition
to the primary outcome, postoperative incident delirium, they also
documented delirium duration, severity, length of admission and
adverse effects. Delirium was diagnosed according to DSM IV and
CAM criteria using the Delirium Rating Scale-Revised-98 (DRSR-98) (Trzepacz 2001), MMSE and Digit span administered by
trained assessors.
Several case reports have suggested that donepezil, an acetylcholinesterase inhibitor widely approved for treatment in
Alzheimers disease, might also be helpful in delirium (Gleason

2003; Wengel 1998). A study in patients undergoing elective knee
and hip arthroplasty (Liptzin 2005), investigated the effectiveness
of donepezil 5 mg given for 14 days before and after surgery. Controls were given placebo tablets. Outcomes measured were incident delirium after surgery, duration of delirium and length of
admission. DSM IV delirium was diagnosed on days 7 and 14
after surgery using daily administration of the Delirium Symptom
Interview (DSI) (Albert 1992), CAM and medical records review.
In the only study of non-pharmacological interventions, Marcantonio and colleagues (Marcantonio 2001) tested proactive geriatric
consultation against care as usual. Patients were visited daily by
a consultant geriatrician preoperatively or within 24 hours after
surgery. Targeted recommendations were made based on a structured protocol. They included measures to address 10 areas: i)
maintenance of adequate CNS oxygen delivery, ii) correction of
fluid and electrolyte balance, iii) treatment of severe pain, iv) elimination of unnecessary medications, v) regulation of bowel/bladder function, vi) adequate nutritional intake, vii) early mobilisation and rehabilitation, viii) prevention, early detection and treatment of major postoperative complications, ix) appropriate environmental stimuli and x) treatment of agitated delirium. Recommendations were prioritised, and no more than five were made at
the initial consultation, and three at subsequent visits. The usual
care group received management by the orthopaedics team including internal medicine or geriatric consultation, if required,
on a reactive basis. The primary outcome was total cumulative
CAM-defined delirium incidence during admission. The MMSE,
DSI, MDAS and CAM instruments were administered daily from
admission to discharge by a trained assessor. Delirium duration,
severity, length of admission and institutionalisation at discharge
were also determined. Severity was defined as an MDAS score of
18/30 or more.
Risk of bias in included studies

Studies varied in their methodological quality. Table 2 gives the
overall quality assessments determined using the preset criteria
described above.
Only one study (Marcantonio 2001) clearly achieved adequate
power to test effectiveness of the intervention in prevention of
delirium. Aizawa 2002, Berggren 1987 and Kalisvaart 2005 did
not include a power calculation; the latter comment that the study
was underpowered, given the relatively low delirium incidence
in their trial. Diaz 2001 and Liptzin 2005 did perform a power
calculation, but used much higher estimates of delirium rates than
actually found in these studies.
Randomisation was used in all studies, but adequate allocation
concealment was only described in two studies (Kalisvaart 2005;
Marcantonio 2001). Blinding of participants was used, except in
the three studies in which the nature of the intervention protocols

precluded this (Aizawa 2002; Berggren 1987; Marcantonio 2001).

All studies included blinded assessment of outcomes.
In three studies (Aizawa 2002; Diaz 2001; Liptzin 2005), only
limited information about baseline comparability between intervention and control or comparative groups was given; in these,
there were no statistically significant differences in age, sex, cognitive status or post surgery APACHE score (Knaus 1985). Berggren
1987 also recorded co-morbidity and psychotropic drug use.
The number of patients taking anticholinergic drugs was significantly greater in the intervention group. In Kalisvaart 2005 and
Marcantonio 2001 there were no baseline differences described in
a range of important characteristics.
In investigating the effectiveness of interventions to prevent delirium, clearly assessment for delirium at enrollment will be important. This was done in only three of the studies (Diaz 2001;
Kalisvaart 2005; Marcantonio 2001); however, in Aizawa 2002
and Berggren 1987, the exclusion criteria would in effect have
excluded delirium. In Marcantonio 2001, patients with delirium
were not excluded from enrollment, and despite being examined
for, delirium prevalence at intake assessment was not reported.
Comorbidity with physical illness was not assessed in Aizawa 2002,
Kalisvaart 2005 or Liptzin 2005, and presence of dementia was
only reported in one study (Marcantonio 2001).
An intention to treat analysis was carried out in three studies
(Berggren 1987; Kalisvaart 2005; Marcantonio 2001). In the other
three studies, data were only available for patients completing treatment.
Validated delirium diagnostic criteria consistent with the selection criteria for this review were used in all studies, but in some
there was variability in training of assessors, or training was not
described (Aizawa 2002; Diaz 2001). Moreover, in Aizawa 2002,
the intervention caused sedation in 8/20 patients and may have
interfered with delirium assessment.
In outcomes, although all studies assessed incident delirium as
the primary outcome, other important outcomes including death,
costs and psychological morbidity were not examined.
The study population in Aizawa 2002 included a very specialised
setting, restricting its generalisability. The other five studies have
relevance for management of patients with hip fracture, a common presentation amongst older people requiring hospitalisation
(although the study population in Liptzin 2005 was confined to
elective hip or knee arthroplasty patients).
Effects of interventions
Studies could not be combined for meta-analysis due to heterogeneity in interventions tested, settings, participants and methods.
Results for individual studies are, therefore, presented by outcome.
1. Post surgery administration of Del i rium-Free Protocol v
Usual care (Aizawa 2002)
Primary outcome:
a) Incident delirium in the 7 days after surgery was significantly

lower in the intervention group with an Odds Ratio (OR) 0.10
[95% CI 0.01, 0.89] and Relative Risk (RR) of 0.14 [95% CI
0.02, 1.06].
Secondary outcomes:
b) Behavioural disturbance in the first 7 days after surgery was also
lower for the intervention group, but the difference failed to reach
statistical significance (RR 0.20 [95% CI 0.03, 1.56])
c) In length of admission also, there was no significant difference
between groups.
Analyses were carried out in 40 study participants but do not
include two patients who dropped out of the study.
2. Epidural anaesthesia v Halothane anaesthesia (Berggren
1987)
Primary outcome:
a) Incidence of delirium on day 1 or day 7 after surgery did not
differ significantly between treatment groups (RR 1.32 [95% CI
0.73, 2.39]).
Secondary outcomes:
b) Length of admission was reported to show no significant difference, but no data for this were given.
c) Physical morbidity; there were no differences in the incidence
of stroke, urinary tract infection or decubitus ulcers (RR 1.20
[95%CI 0.51, 2.81])
Intention to treat analyses were performed for all outcomes in 57
study participants. One year mortality was reported as 7% (4/57),
but was not given by treatment group.
3. Prophylactic citicoline v Placebo (Diaz 2001)
Primary outcomes:
a) Incident delirium immediately after surgery
b) Incident delirium on day 1 after surgery
c) Incident delirium on day 2 after surgery
d) Incident delirium on day 3 after surgery
There was no significant difference between groups in incidence
of delirium assessed at any of the above time points.
Secondary outcome:
e) Cognitive status; there was no significant difference between
intervention and control groups in the MMSE score after surgery
.
Results were reported for 81 participants. Seven patients who were
enrolled, but did not proceed with the study protocol, were not
included in the final analyses.
4. Prophylactic haloperidol v Placebo (Kalisvaart 2005)
Primary outcome :
a) Incidence of delirium after surgery was 15.8% in the study
population with a non-significant difference between treatment

and control groups (RR 0.91 [95% CI 0.59, 1.42]).

Secondary outcomes:
b) Delirium duration
c) Delirium severity
Both the duration and severity were reduced in the intervention
group compared with controls, and the differences reached statistical significance (delirium duration RR -6.44 [95% CI -7.64, 5.24] and mean difference in maximum DRS-R-98 score of 4.0
[95% CI 2.0, 5.8], p<0.001).
d) Length of admission was also significantly shorter in the intervention group, with a mean difference in hospital days of 5.5
[95% CI1.4, 2.3], p<0.001.
e) Withdrawal from the protocol did not differ between the two
groups and occurred in 11% of enrolled patients.
f ) Adverse effects were reported in three patients in each group
who withdrew from the protocol. However no drug related side
effects were seen.
This large study included 430 participants, stratified to be at intermediate or high risk of delirium. Intention to treat analyses were
performed for all outcomes.
5. Prophylactic donepezil v Placebo (Liptzin 2005)
Primary outcome:
a) Incident delirium after surgery occurred in 18.8% patients and
did not differ significantly between treatment and placebo groups
(RR 1.2 [95% CI 0.48, 3.00])
Secondary outcomes:
b) Delirium duration
c) Length of admission
Duration of delirium and length of admission were not significantly different in the two groups.
d) Withdrawal from protocol occurred in 11/ 39 intervention and
11/41 control patients.
90 patients were enrolled and randomised. 10 were not operated on
or took no study medication and were excluded from any analyses.
6. Proactive geriatric consultation v Usual care (Marcantonio
2001)
Primary outcome:
a) Total cumulative delirium incidence during admission was reduced in the proactive geriatrics consultation group compared
with usual care. The difference was statistically significant (OR
0.48 [95% CI 0.23, 0.98]; RR 0.64 [95% CI 0.37, 0.98]), suggesting a number needed to treat of 6 patients to prevent one case
of delirium. However, baseline delirium prevalence at enrollment
was not reported, limiting interpretation of findings.
In logistic regression analyses adjusting for pre fracture dementia
and Activities of Daily Living impairment, the authors report no
reduction in effect size, OR 0.6, but this no longer remained significant [95% CI 0.3,1.3].
Secondary outcomes:
b) Delirium duration. There was little difference between the two

groups in number of hospital days with delirium per episode,
suggesting the impact of the intervention on already established
delirium may be limited.
c) Delirium severity; the intervention was particularly effective in
preventing severe delirium, demonstrated by a greater reduction in
cumulative incidence of this in the intervention group compared
to controls (RR 0.4 [95% CI 0.19, 0.89]).
d) Length of admission was similar for both groups.
e) Rates of institutionalisation at discharge did not differ between
groups.
f ) Cognitive status at discharge was assessed by prevalence of delirium, which was present in 15.9% patients (8/62 in the intervention group and 12/64 controls, RR 0.69 [95% CI 0.30, 1.57]).
Outcomes in dementia sub-group analysis:
This was carried out in 50 patients with dementia diagnosed using
the Blessed Dementia Rating Scale (Blessed 1968).
There was no significant difference between treatment and control
groups in cumulative delirium incidence during admission in this
sub-group (RR 0.9 [95% CI 0.59, 1.36]).
The total study population (with and without dementia) numbered 126. Intention to treat analyses were performed for all outcomes.
We identified no completed studies in hospitalised medical, care of
the elderly, general surgery or intensive care settings. In outcomes,
no studies examined for death, use of psychotropic medication,
activities of daily living, psychological morbidity, quality of life,
carers psychological morbidity, staff psychological morbidity, cost
of intervention and cost to health care services. Outcomes were
only reported up to discharge, with no studies reporting medium
or longer-term effects. We did not perform a funnel plot to examine for publication bias due to the limited number of studies.
DISCUSSION
1. We found only a handful of RCTs of interventions to prevent
delirium in hospitalised patients. Of the six which met our selection criteria, no two studies tested the same, or even a similar
intervention. Additionally, there was heterogeneity in methods,
participants and outcomes examined. Methodological limitations
of these studies have been described above; importantly only one
study was sufficiently powered to determine effectiveness of the
intervention, and then only for bivariate analyses.
2. Research evidence for effectiveness of interventions to prevent
delirium in this population is limited. Although Aizawa 2002 report that their intervention reduced postoperative delirium, the
protocol caused sedation and may have interfered with delirium
assessment. The highly specific study population and small study
size, as well as the nature of the intervention, limit generalisability
of findings from this study. Berggren 1987 found no difference in

delirium incidence following surgery under epidural or halothane

anaesthesia. Prophylactic administration of citicoline (Diaz 2001)
and donepezil (Liptzin 2005) did not prevent delirium compared
with placebo.
3. Prophylactic haloperidol was not effective in preventing delirium but did reduce its severity and duration, and also decreased
length of hospital stay (Kalisvaart 2005). Interestingly, proactive
geriatric consultation was also offered to all patients, both in the
intervention and control group; the authors speculate that this
might have been responsible for the overall lower incidence of post
operative delirium compared to other studies in similar populations. Further studies are needed to clarify the role of neuroleptics
in delirium prevention.
3. The most encouraging evidence for successful delirium prevention comes from one large study of proactive geriatric consultation (Marcantonio 2001). Given the multifactorial aetiology of
delirium (Lindesay 2002), their approach targeting a range of risk
factors may be more appropriate than strategies relying on administration of a single pharmacological agent (Inouye 1999a; Milisen
2005) . The recommendations made comprised measures that are
essentially basic aspects of good care, yet they were able reduce
delirium incidence by more than one third.
4. Dementia is the most important risk factor for delirium
(Lindesay 2002); targeting this population makes empirical sense
and may deliver important benefits, not least as many of the measures to prevent delirium should also be helpful in dementia. However, Marcantonio 2001 could not demonstrate effectiveness of
the intervention in preventing delirium in a subgroup analysis of
50 patients with dementia.
5. A high 77% adherence to recommendations was achieved in
this study, but the authors argue that this could be further improved if geriatric consultation were systematically integrated into
care. Problems with adherence to recommendations and protocols
have been described, and implicated in limiting effectiveness by
others (Cole 2002; Inouye 2003; Young 2003) leading to calls to
include strategies to improve implementation and adherence (such
as measures to increase ownership and interactive education and
training (EHC 1999; Grimshaw 2004)) as an integral part of any
delirium intervention package.
6. The study by Kalisvaart and colleagues (Kalisvaart 2005) showed
accurate stratification of delirium risk was feasible based on the
presence of four predictive delirium risk factors. This corroborates
findings in Inouyes study of predictive risk factors (Inouye 1993b)
and provides important validation of this risk identification system
which may be useful in both clinical practice and for delirium
research.
7. Only immediate benefits (up to discharge) were examined in
all six included studies. However, in Marcantonio 2001, the authors indicate that they will be publishing results of longer term
outcomes in future.
8. The most striking finding is the paucity of high quality published research on delirium prevention, particularly given how
common the condition is in hospitalised patients and its seriously
poor outcomes. Reasons for this may include historical difficulties
with case definition and detection, and the challenges of conducting research in often frail and debilitated patients. Further studies
on delirium prevention are urgently needed to guide clinical practice. Future investigations should focus on multi-faceted packages of delirium care in a whole range of hospital settings, and
should include short and longer term outcomes such as mortality,
physical and psychological morbidity, impact on carers and costs
to health care services.
9. Our review has some limitations. Although a fairly extensive
search was performed, resource limitations did not allow searching
of non-English language databases. We can be confident, however,
that we identified most important relevant studies, as our search
retrieved all studies included in recent reviews of this topic and also
identified additional studies. Resource limitations also precluded
blinding to authors and source institutions of studies, which could
potentially bias selection and quality assessment. Given the nature
of the interventions, blinding of study subjects or researchers was
not a prerequisite for inclusion.
10. A strength of our review is that all stages of screening citations,
identification of studies for inclusion, data extraction and quality
appraisal were carried out by at least two of the authors independently, and agreement reached by consensus.
11. Our findings are consistent with those of existing reviews
of delirium prevention (Britton 2004; Cole 1999; Milisen 2005;
Weber 2004). Previous reviews have included studies using unvalidated methods to operationalise delirium or using terms such
as confusional state (without a clear definition of what this term
encompassed). We agree with Milisen (Milisen 2005) that reliance
on terms such as acute confusion contributes to the semantic ambiguity rife in delirium research and is not helpful in furthering
our understanding of the condition; in clinical settings also, it is
unhelpful to efforts to increase recognition of delirium by health
care professionals as a condition warranting an urgent response.
12. This review aimed to consider all interventions designed to prevent delirium rather than testing a specific hypothesis. It provides
a robust update, highlighting the current scarcity of research evidence to guide clinical practice in delirium prevention. Although
based on the findings of only one study, there is some evidence
to recommend implementation of proactive geriatric consultation in patients undergoing surgery for hip fracture. Further trials
are needed of this intervention, and of other delirium prevention
strategies in hospitalised patients in a range of medical and surgical
settings.

10
AUTHORS CONCLUSIONS
Implications for practice
There is little evidence from delirium prevention studies to guide
clinical practice. Based on a single RCT, a programme for proactive
geriatric consultation may reduce delirium incidence and severity
in patients undergoing surgery for hip fracture (Marcantonio
2001). Prophylactic low dose haloperidol may reduce the severity
and duration of a delirium episode, and reduce length of hospital
stay in hip surgery patients (Kalisvaart 2005). There is no trial
evidence available on the effectiveness of any other strategies to
prevent delirium in hospitalised patients.
Implications for research

There is a striking lack of research on delirium prevention. Further
studies are urgently needed to guide clinical practice. Given its
diverse predisposing and precipitating factors, and how common
it is in a range of settings, future investigations should focus on
evaluating multi-faceted packages of delirium prevention in various hospital settings. Drug prevention studies e.g. of haloperidol
are also needed. Studies should use validated delirium screening
and diagnostic methods such as the CAM and DRS and should
include assessment of short and longer term outcomes such as
mortality, physical and psychological morbidity, impact on carers
and costs to health care services.
ACKNOWLEDGEMENTS
We gratefully acknowledge the contribution of Dr Duncan
Forsyth, Consultant Elderly Care Medicine, Addenbrookes Hospital, Cambridge, who provided feedback as the consumer editor
for this review.
We also wish to thank Katherine Hicks, Dymphna Hermans and
Leon Flicker from the Dementia and Cognitive improvement
Group for their support with preparing the review.
REFERENCES
References to studies included in this review

Aizawa 2002 {published data only}
Aizawa K, Kanai T, Saikawa Y, Takabayashi T, Kawano
Y, Miyazawa N, Yamamoto T. A novel approach to the
prevention of postoperative delirium in the elderly after
gastrointestinal surgery.. Surgery today 2002;32(4):3104.
Berggren 1987 {published data only}
Berggren D, Gustafson Y, Eriksson B, et al.Postoperative
confusion after anesthesia in elderly patients with femoral
neck fractures. Anesthesia & Analgesia 1987;66(6):497504.
Diaz 2001 {published data only}
Diaz V, Rodriguez J, Barrientos P, Serra M, Salinas H,
Toledo C, Kunze S, Varas V, Santelices E, Cabrera C,
Farias J, Gallardo J, Beddings MI, Leiva A, Cumsille MA.
[Use of procholinergics in the prevention of postoperative
delirium in hip fracture surgery in the elderly A randomized
controlled trial]. Revista de Neurologia 2001;33(8):7169.
Kalisvaart 2005 {published data only}
Kalisvaart KJ, de Jonghe JF, Bogaards MJ, et al.Haloperidol
prophylaxis for elderly hip-surgery patients at risk for
delirium: a randomized placebo-controlled study. J Am
Geriatr Soc 2005;53(10):165866.
Liptzin 2005 {published data only}
Liptzin B, Laki A, Garb J, Fingeroth R, Krushell R.
Donepezil in the Prevention and Treatment of Post-Surgical
Delirium. American Journal of Geriatric Psychiatry 2005;13:
11001106.
Marcantonio 2001 {published data only}
Marcantonio ER, Flacker JM, Wright RJ, Resnick NM.
Reducing delirium after hip fracture: a randomized trial.
Journal-of-the-American-Geriatrics-Society 2001;49(5):
51622.
References to studies excluded from this review

Baldwin 2004 {published data only}
Baldwin R, Pratt H, Goring H, Marriott A, Roberts C.
Does a nurse-led mental health liaison service for older
people reduce psychiatric morbidity in acute general medical
wards? A randomised controlled trial. Age and ageing 2004;
33(5):4728.
Budd 1974 {published data only}
Budd, S, Brown, W. Effect of a reorientation technique on
postcardiotomy delirium. Nursing Research 1974;23(4):
3418.
Cerchietti 2000 {published data only}
Cerchietti L, Navigante A, Sauri A, Palazzo F.
Hypodermoclysis for control of dehydration in terminalstage cancer.. International journal of palliative nursing
2000;6(8):3704.
Cole 2002 {published data only}
Cole MG, McCusker J, Bellavance F, Primeau FJ, Bailey
RF, Bonnycastle MJ, Laplante J. Systematic detection
and multidisciplinary care of delirium in older medical
inpatients: a randomized trial. Canadian Medical Association
Journal 2002;167(7):7539.
Culp 2003 {published data only}
Culp K, Mentes J, Wakefield B. Hydration and acute
confusion in long-term care residents. Western journal of
nursing research 2003;25(3):251-66; discussion 267-73.

11
Inouye 1993a {published data only}

Inouye SK. A controlled trial of a nursing-centered
intervention in hospitalized elderly medical patients: the
Yale Geriatric Care Program. Journal of the American
Geriatrics Society. 1993;41(12):1353.
Inouye 1999 {published data only}
Bogardus Jr ST, Desai MM, Williams CS, Leo Summers
L, Acampora D, Inouye SK. The effects of a targeted
multicomponent delirium. American Journal of Medicine
2003;114(5):38390.
Inouye SK, Bogardus Jr ST, Williams CS, Leo-Summers
L, Agostini JV. The role of adherence on the effectiveness
of nonpharmacologic interventions: Evidence from the
delirium prevention trial. Archives of Internal Medicine
2003;163(8):958964.
Inouye SK, Bogardus STJr, Charpentier PA, LeoSummers L, Acampora D, Holford TR, Cooney LMJr.
A multicomponent intervention to prevent delirium in
hospitalized older patients see comments. New England
Journal of Medicine 1999;340(9):669.
Leslie DL, Zhang Y, Bogardus ST, Holford TR, LeoSummers LS, Inouye SK. Consequences of preventing
delirium in hospitalized older adults on nursing home costs.
JAGS 2005;53(3):4059.
Rizzo JA, Bogardus ST, Leo-Summers L, Williams CS,
Acampora D, Inouye SK. Multicomponent targeted
intervention to prevent delirium in hospitalized older
patients: what is the economic value?. Medical care 2001;
39(7):74052.
Kaneko 1999 {published data only}
Kaneko T, Cai J, Ishikura T, Kobayashi M, Naka T, Kaibara
N. Prophylactic consecutive administration of haloperidol
can reduce the occurrence of postoperative delirium in
gastrointestinal surgery. Yonago Acta Medica 1999;42(3):
17984.
Landefeld 1995 {published data only}
Landefeld CS, Palmer RM, Kresevic DM, Fortinsky RH,
Kowal J. A randomized trial of care in a hospital medical
unit especially designed to improve the functional outcomes
of acutely ill older patients. New England Journal of
Medicine 1995;332(20):133844.
Lundstrom 2005 {published data only}
Lundstrom M, Edlund A, Karlsson S, Brannstrom B, Bucht
G, Gustafson Y. A multifactorial intervention program
reduces the duration of delirium, length of hospitalization,
and mortality in delirious patients. Journal of the American
Geriatrics Society 2005;53(4):6228.
Mentes 2003 {published data only}
Mentes JC, Culp K. Reducing hydration-linked events in
nursing home residents. Clinical Nursing Research 2003;12
(3):210-25; discussion 226-8.
Milisen 2001 {published data only}
Milisen K, Foreman MD, Abraham IL, De Geest
S, Godderis J, Vandermeulen E, et al.A nurse-led
interdisciplinary intervention program for delirium in
elderly hip-fracture patients. Journal of the American

Naughton 2005 {published data only}
Naughton BJ, Saltzman S, Ramadan F, Chadha N, Priore
R, Mylotte JM. A multifactorial intervention to reduce
prevalence of delirium and shorten hospital length of stay.
Journal of the American Geriatrics Society 2005;53(1):1823.
Tabet 2005 {published data only}
Tabet N, Hudson S, Sweeney V, Sauer J, Bryant C,
Macdonald A, Howard R. An educational intervention can
prevent delirium on acute medical wards. Age and Ageing
2005;34(2):1526.
Tokita 2001 {published data only}
Tokita K, Tanaka H, Kawamoto M, Yuge O. [Patientcontrolled epidural analgesia with bupivacaine and fentanyl
suppresses postoperative delirium following hepatectomy].
Masui; Japanese journal of anesthesiology, The 2001;50(7):
7426.
Wanich 1992 {published data only}
Wanich CK, Sullivan-Marx EM, Gottlieb GL, Johnson
JC. Functional status outcomes of a nursing intervention
in hospitalized elderly. Image - the Journal of Nursing
Scholarship 1992;24(3):2017.
Wong 2005 {published data only}
Wong Tin Niam DM, Bruce JJ, Bruce DG. Quality project
to prevent delirium after hip fracture. Australasian Journal
on Ageing 2005;24(3):174177.
References to ongoing studies

Boustani 2005a {published data only}
Boustani M. Donepezil in the Prevention of Post-Operative
Cognitive Decline. ClinicalTrials.gov 2005.
Boustani 2005b {published data only}
Boustani M. Enhancing Care for Hospitalized Older Adults
with Cognitive Impairment. ClinicalTrials.gov 2005.
Boustani 2005c {published data only}
Boustani M. Preventing Delirium in Hospitalized Elderly.
ClinicalTrials.gov 2005.
Diehl 2005 {published data only}
Diehl J. Prevention of Postoperative Delirium with
Donepezil. ClinicalTrials.gov 2005.
Ely 2004a {published data only}
Ely EW. A Randomized, Double-blind Trial in Ventilated
ICU Patients Comparing Treatment with an Alpha2 Agonist
versus a Gamma Aminobutyric Acid (GABA)-Agonist to
Determine Delirium Rates, Efficacy of Sedation, Analgesia
and Discharge Cognitive Status. ClinicalTrials.Gov 2004a.
Ely 2004b {published data only}
Ely EW. Delirium in the ICU: a Prospective, Randomized,
Trial of Placebo vs Haloperidol vs Ziprasidone.
ClinicalTrials.gov 2004b.
Harari 2005 {published data only}
Harari D. Proactive intervention to improve post-operative
outcomes in at risk older people undergoing surgery: a

12
randomised controlled trial.. National Research Register

2005, issue issue 3.
Steiner 2005 {published data only}
Steiner L. Rivastigmine for the Prevention of Postoperative
Delirium in Patients Undergoing Cardiac Surgery.
ClinicalTrials.gov 2005.
van der Burg 2005 {published data only}
van der Burg BL. Post-Operative Haloperidol Versus
Placebo for Prevention of Post-Operative Delirium After
Acute Hip Surgery. ClinicalTrials.gov 2005.
Additional references
Albert 1992
Albert MS, Levkoff SE, Reilly C, Liptzin B, Pilgrim D,
Cleary PD, Evans D, Rowe JW. The delirium symptom
interview: an interview for the detection of delirium
symptoms in hospitalized patients. Journal of Geriatric
Psychiatry & Neurology 1992;5(1):1421.
APA 1987
American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders. Third Edition. Washington
DC: American Psychiatric Association, 1987.
APA 1994
American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders. Fourth. Washington DC:
American Psychiatric Association, 1994.
APA 1999
American Psychiatric Association. Practice guideline for the
treatment of patients with delirium. American Psychiatric
Association. American Journal of Psychiatry 1999;156:120.
Blessed 1968
Blessed G, Tomlinson BE, Roth M. The association between
quantitative measures of dementia and of senile change in
the cerebral grey matter of elderly subjects. British Journal
Psychiatry 1968;114(512):797811.
Breitbart 1997
Breitbart W, Rosenfeld B, Roth A, Smith MJ, Cohen K,
Passik S. The Memorial Delirium Assessment Scale. Journal
of Pain & Symptom Management 1997;13(3):12837.
Breitbart 2002
Breitbart W, Gibson C, Tremblay A. The delirium
experience: delirium recall and delirium-related distress in
hospitalized patients with cancer, their spouses/caregivers,
and their nurses. Psychosomatics 2002;43(3):18394.
Britton 2004
Britton A, Russell R. Multidisciplinary team interventions
for delirium in patients with chronic cognitive
impairment. Cochrane Database of Systematic Reviews
2004, Issue 2.[Art. No.: CD000395. DOI: 10.1002/
14651858.CD000395.pub3]
Centeno 2004
Centeno C, Sanz A, Bruera E. Delirium in advanced cancer
patients. Palliative Medicine 2004;18(3):184194.
Clarke 1999
Clarke M, Oxman AD, editors. Cochrane Reviewers
Handbook 4.0 [updated July 1999]. In: Review Manager
(RevMan) [Computer program] Version 4.0. The Cochrane
Collaboration, 1999.
Cole 1999
Cole MG. Delirium: effectiveness of systematic
interventions. Dementia & Geriatric Cognitive Disorders
1999 SepOct;10(5):406-11 1999.
EHC 1999
EHC. Getting evidence into practice. Effective Health Care
1999;5:1.
Elie 2000
Elie M, Rousseau F, Cole M, Primeau F, McCusker J,
Bellavance F. Prevalence and detection of delirium in elderly
emergency department patients. CMAJ Canadian Medical
Association Journal 2000;163(8):97781.
Fioravanti 2006
Fioravanti M, Yanagi M The Cochrane Database of
Systematic Reviews 2006 Issue 2 Copyright 2006 The
Cochrane Collaboration. Published by John Wiley &
Sons, Ltd. Cytidinediphosphocholine (CDP-choline) for
cognitive and behavioural disturbances associated with
chronic cerebral disorders in the elderly Fioravanti M,
Yanagi M. Cytidinediphosphocholine (CDP-choline) for
cognitive and behavioural disturbances associated with
chronic cerebral disorders in the elderly Fioravanti M,
Yanagi M. Cochrane Database of Systematic Reviews 2006,
Issue 2.
Folstein 1975
Folstein MF, Folstein SE, McHugh PR. Mini-mental
state. A practical method for grading the cognitive state
of patients for the clinician. J Psychiatr Res 1975;12(3):
18998.
Francis 1990
Francis J, Kapoor WN. Delirium in hospitalized elderly.
Journal of General Internal Medicine 1990;5(1):6579.
Gleason 2003
Gleason OC. Donepezil for postoperative delirium.
Psychosomatics 2003;44(5):4378.
Grimshaw 2004
Grimshaw JM, Thomas RE, MacLennan G, Fraser C,
Ramsay CR, Vale L, Whitty P, Eccles MP, Matowe L, Shirran
L, Wensing M, Diikstra R, Donaldson C. Effectiveness and
efficiency of guideline dissemination and implementation
strategies. Health. Health Technology Assessment 2004;8(6):
172.
Harris 2001
Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD,
Teutsch SM, et al.Current methods of the US Preventive
Services Task Force: a review of the process. Am J Prev Med
2001;20(3 Suppl):2135.
Hodkinson 1972
Hodkinson HM. Evaluation of a mental test score for
assessment of mental impairment in the elderly. Age Ageing
1972;1(4):2338.

13
Holmes 2000
Holmes JD, House AO. Psychiatric illness in hip fracture.
Age & Ageing 2000;29(6):53746.
Hustey 2003
Hustey FM, Meldon SW, Smith MD, Lex CK. The effect
of mental status screening on the care of elderly emergency
department patients. Annals of Emergency Medicine 2003;
41(5):678684.
Inouye 1990
Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP,
Horwitz RI. Clarifying confusion: the confusion assessment
method. A new method for detection of delirium. Annals of
Internal Medicine 1990;113(12):9418.
Inouye 1993b
Inouye SK, Viscoli CM, Horwitz RI, Hurst LD, Tinetti
ME. A predictive model for delirium in hospitalized elderly
medical patients based on admission characteristics. Annals
of Internal Medicine 1993;119(6):47481.
Inouye 1998a
Inouye SK, Rushing JT, Foreman MD, Palmer RM, Pompei
P. Does delirium contribute to poor hospital outcomes? A
three-site epidemiologic study. Journal of General Internal
Medicine 1998;13:23442.
Inouye 1998b
Inouye SK. Delirium in hospitalized older patients:
recognition and risk factors. Journal of Geriatric Psychiatry
& Neurology 1998;11(3):118-25; discussion 157-8.
of nonpharmacologic interventions: Evidence from the

delirium prevention trial. Archives of Internal Medicine
2003;163(8):95864.
Jensen 1993
Jensen E, Dehlin O, Gustafson L. A comparison between
three psychogeriatric rating scales. International Journal of
Geriatric Psychiatry 1993;8(3):215229.
Knaus 1985
Knaus WA, Draper EA, Wagner DP, Zimmerman JE.
APACHE II: a severity of disease classification system.
Critical Care Medicine 1985;13(10):81829.
Levkoff 1991
Levkoff S, Cleary P, Liptzin B, Evans DA. Epidemiology
of delirium: an overview of research issues and findings.
International Psychogeriatrics 1991;3(2):14967.
Lindesay 2002
Lindesay J, Rockwood K, Rolfson D. The epidemiology of
delirium. In: Lindesay J, Rockwood K, Macdonald A editor
(s). Delirium in Old Age. New York: Oxford University
Press, 2002:2750.
Ljubisavljevic 2003
Ljubisavljevic V, Kelly B. Risk factors for development of
delirium among oncology patients. Gen Hosp Psychiatry
2003;25(5):34552.
McCusker 2001
McCusker J, Cole M, Dendukuri N, Belzile E, Primeau
F. Delirium in older medical inpatients and subsequent
cognitive and functional status: a prospective study. CMAJ
Canadian Medical Association Journal 2001;165(5):57583.
Inouye 1999a
Inouye SK, Bogardus ST, Jr, Charpentier PA, Leo-Summers
L, Acampora D, Holford TR, et al.A multicomponent
patients. New England Journal of Medicine 1999;340(9):
66976.
Inouye 1999b
Inouye SK, Schlesinger MJ, Lydon TJ. Delirium: A
Symptom of How Hospital Care Is Failing Older Persons
and a Window to Improve Quality of Hospital Care. The
American Journal of Medicine 1999;106(5):565573.
McCusker 2003a
McCusker J, Cole MG, Dendukuri N, Belzile E. Does
delirium increase hospital stay?. Journal of the American
Inouye 1999c
Inouye SK. Predisposing and precipitating factors for
delirium in hospitalized older patients. Dementia &
Geriatric Cognitive Disorders 1999;10(5):393400.
McCusker 2003b
McCusker J, Cole M, Dendukuri N, Han L, Belzile E. The
course of delirium in older medical inpatients: a prospective
study. J Gen Intern Med 2003;18(9):696704.
Inouye 2000a
Inouye SK, Bogardus ST, Jr, Baker DI, Leo-Summers L,
Cooney LM, Jr. The Hospital Elder Life Program: a model
of care to prevent cognitive and functional decline in older
hospitalized patients. Journal of the American Geriatrics
Society 2000;48(12):1697706.
Milbrandt 2004
Milbrandt EB, Deppen S, Harrison PL, Shintani AK,
Speroff T, Stiles RA, et al.Costs associated with delirium in
mechanically ventilated patients. Critical Care Medicine
2004;32(4):955962.
Inouye 2000b
Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP,
Horwitz RI. Clarifying confusion: the confusion assessment
method. A new method for detection of delirium. Annals of
Inouye 2003
Inouye SK, Bogardus Jr ST, Williams CS, Leo-Summers
L, Agostini JV. The role of adherence on the effectiveness
McCusker 2002
McCusker J, Cole M, Abrahamowicz M, Primeau F, Belzile
E. Delirium predicts 12-month mortality. Archives of
Milisen 2005
Milisen K, Lemiengre J, Braes T, Foreman MD.
Multicomponent intervention strategies for managing
delirium in hospitalized older people: systematic review.
Journal of Advanced Nursing 2005;52(1):7990.
Moller 1998
Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen
H, Canet J, et al.Long-term postoperative cognitive
dysfunction in the elderly ISPOCD1 study. ISPOCD

14
investigators. International Study of Post-Operative

Cognitive Dysfunction. Lancet 1998;351(9106):85761.
Rizzo 2001
Rizzo JA, Bogardus ST, Jr, Leo-Summers L, Williams
CS, Acampora D, Inouye SK. Multicomponent targeted
patients: what is the economic value?. Medical Care 2001;
39(7):74052.
Roberts 2004
Roberts B. Screening for delirium in an adult intensive care
unit. Intensive Crit Care Nurs 2004;20(4):20613.
Rockwood 1999
Rockwood K. Educational interventions in delirium.
Dementia & Geriatric Cognitive Disorders 1999;10(5):
4269.
Santos 2004
Santos FS, Velasco IT, Fraguas R, Jr. Risk factors for
delirium in the elderly after coronary artery bypass graft
surgery. Int Psychogeriatr 2004;16(2):17593.
Siddiqi 2006
Siddiqi N, House AO, Holmes JD. Occurrence and
outcome of delirium in medical in-patients: a systematic
literature review. Age Ageing 2006;35:350364.
Stevens 1998
Stevens LE, de Moore GM, Simpson JM. Delirium in
hospital: does it increase length of stay?. Australian & New
Zealand Journal of Psychiatry 1998;32(6):8058.
Trzepacz 1988
Trzepacz PT, Baker RW, Greenhouse J. A symptom rating
scale for delirium. Psychiatry Res 1988;23(1):8997.
Trzepacz 1996
Trzepacz PT. Delirium. Advances in diagnosis,
pathophysiology, and treatment. Psychiatric Clinics of North
America 1996;19(3):42948.
Trzepacz 2001
Trzepacz PT, Mittal D, Torres R, Kanary K, Norton J,
Jimerson N. Validation of the Delirium Rating Scale-
revised-98: comparison with the delirium rating scale and

the cognitive test for delirium. Journal of Neuropsychiatry &
Clinical Neurosciences 2001;13(2):22942.
Uldall 1997
Uldall KK, Berghuis JP. Delirium in AIDS patients:
recognition and medication factors. AIDS Patient Care &
Stds 1997;11(6):43541.
Weber 2004
Weber JB, Coverdale JH, Kunik ME. Delirium: Current
trends in prevention and treatment. Internal Medicine
Journal 2004;34(3):115121.
Wengel 1998
Wengel SP, Roccaforte WH, Burke WJ. Donepezil improves
symptoms of delirium in dementia: implications for future
research. Journal of Geriatric Psychiatry & Neurology 1998;
11(3):15961.
WHO 1992
World Health Organisation. International classification of
diseases, 10th revision. Geneva: World Health Organisation,
1992.
Williams-Russo 1992
Williams-Russo P, Urquhart BL, Sharrock NE, Charlson
ME. Post-operative delirium: Predictors and prognosis
in elderly orthopedic patients. Journal of the American
Young 2003
Young LJ, George J. Do guidelines improve the process and
outcomes of care in delirium?. Age and Ageing 2003;32(5):
5258.
References to other published versions of this review

Siddiqi 2007
Siddiqi N, Stockdale R, Britton AM, Holmes J.
Interventions for preventing delirium in hospitalised
patients. Cochrane Database of Systematic Reviews 2007,
Issue 2. [DOI: 10.1002/14651858.CD005563.pub2]
Indicates the major publication for the study

15
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]

Aizawa 2002
Methods
Randomisation: Allocation immediately after surgery but method not described

Power calculation: No and small number in study
Blinding of participants: No
Outcomes assessments blind: Yes
Informed consent: Yes
Delirium diagnostic criteria: DSM IV
Outcomes Measurement: Twice daily screening interview after surgery by one psychiatrist for 7 consecutive days
Intention to treat analysis: No
Drop outs from protocol: 2 from intervention group
Incomplete follow up: 2/42 - excluded after randomisation and no data presented on these
Proportion of participants reported in final analysis: 95%
Study duration: 29 months
Participants
Number in study: 42
Japan
One surgical department
Post resection of gastric or colorectal cancer
Age: More than 70 yrs and less than 86 yrs; mean age 75.9 and 76.2 yrs in intervention and control groups respectively
Co-morbidity: Not given
Dementia: Not mentioned specifically but mental disorders excluded (although method not described)
Delirium at enrollment: As for dementia, not mentioned specifically
Exclusions: Liver, renal or respiratory dysfunction, mental disorders, visual impairment, resection of other organs,
emergency surgery
Interventions
Delirium Free Protocol (DFP): Post surgery, Diazepam 0.1 mg/kg IM at 20.00, Flunitrazepam 0.04 mg/kg IV and
Pethidine 1mg/kg IV infusions 20.00-04.00 for 3 nights
Controls: Treatment as usual. No placebo
Outcomes
1. Incident delirium in 7 days postop

2. Behavioural disturbance in 7 days postop
3. Length of admission
Notes
Intervention used likely to sedate (morning lethargy due to DFP in 8/20), and perhaps interfere with assessment for
delirium
Very specific study population, limiting generalisability
Funding Source: Not given

16
Berggren 1987
Methods
Randomisation: Method not described

Power calculation: No
Blinding of participants: No, not possible because of the type of interventions
Delirium diagnostic criteria: DSM III
Outcomes Measurement: Modified Organic Brain Syndrome Scale (OBS) by 2 researchers with good (over 90%)
inter-rater reliability. Assessments on postop day 1 and 7
Intention to treat analysis: Yes
Drop outs from protocol: 0
Incomplete follow up: 0
Participants
Number in study: 57
Sweden
Orthopaedic wards of one University hospital
Patients requiring surgery for femoral neck fracture
Age range: 65-86 yrs; mean age 78 and 77 yrs respectively in epidural and halothane groups respectively
Co-morbidity (number): Ischaemic heart disease(29), hypertension(13), diabetes(9), cerebrovascular disease(6), respiratory disease(5), depression(10), parkinsons(5), severely impaired hearing(11), severe visual impairment(10)
Dementia: Not mentioned specifically but would in effect be excluded by exclusion criteria
Delirium at enrollment: Not excluded specifically, but lucidity requirement for inclusion
Exclusions: Score more than 6/36 on 12 item disorientation subscale of OBS assessed within 3 hours of admission
Interventions
Epidural anaesthesia
Comparison with Halothane anaesthesia
Outcomes
1. Incident delirium on postop day 1 or 7

3. Physical morbidity
Notes
Funding source: Swedish Medical Council; King Gustav V Birthday Foundation; Umea University Research Foundation

17
Diaz 2001
Methods
Randomisation: Method not described

Power calculation: Yes, indicates needed to enrol 88 patients, but results for 81 reported
Blinding of participants: Yes
Delirium diagnostic criteria: American Psychiatric Association 1987
Outcomes Measurement: Abbreviated Mental Test Score (AMT) and Confusion Assessment Method (CAM) preop,
immediately postop, and on day 1, 2 and 3 postop. Training and number of assessors not described
Intention to treat analysis: No. Details of 7 subjects who dropped out not given
Drop outs from protocol: 7
Incomplete follow up: 7/88
Study duration: Not given
Participants
Number in study: 88
Chile
Multicentre, Orthopaedic or Trauma departments
Patients requiring surgery for hip fracture
Anaesthetic risk ASA I, II or III
Surgery under regional anaesthesia
Age: Over 70 yrs; mean 79.45 and 79.97 yrs in intervention and controls respectively
Comorbidity: Specific conditions not described. Present in 28/35 in Intervention group and 39/46 in Control group
Dementia: Excluded
Delirium at enrollment: Excluded using MiniMental State Examination (MMSE), AMT, CAM
Exclusions: Organic brain disorder, major cerebrovascular disease, anaesthetic risk ASA IV
Interventions
Citicoline 400 mg orally 8 hrly, given between 24 hrs before and 4 days after surgery.
Controls: Placebo matched for colour, consistency and flavour
Authors state that if anticholinergics and benzodiazepines were being used they were stopped, and anaemia and
haemodynamic variables corrected in both groups
Outcomes
1. Incident delirium immediately, day 1, day 2 and day 3 post op

2. Cognitive status
Notes
Study underpowered, as incidence of delirium much lower than the 20% used in power calculation
Funding Source: Not given

18
Kalisvaart 2005
Methods
Randomisation: Adequate concealed allocation

Power calculation: No but discussion states study under powered
Delirium diagnostic criteria: DSM IV and CAM
Outcomes Measurement: Daily Delirium Rating Scale Revised 98 (DRS-R-98), MMSE, Digit span by trained
assessors
Drop outs from protocol: 48, 20 in intervention group and 28 controls
Incomplete follow up: 11/ 212 in intervention group and 24/218 controls
Participants
Number in study: 430

Netherlands
2 surgical and 3 orthopaedic wards in 1 Teaching hospital
Admitted for acute or elective hip surgery
At intermediate or high risk of delirium (presence of 1 or more delirium risk factors)
Age: More than 70 yrs; mean 78.71 and 79.57 yrs in intervention and control groups respectively
Dementia: Not given Delirium at enrollment: Excluded, but method not described
Exclusions: Haloperidol allergy, prolonged QTc interval, use of cholinesterase inhibitors or levodopa, parkinsonism,
epilepsy, inability to participate in interviews, delay in surgery more than 72 hrs from admission
Interventions
Haloperidol 0.5 mg orally three times daily on admission until 3 days post op
Controls: Placebo tablets identical in appearance
Proactive geriatric consultation offered to all patients in both groups
If delirium occurred, patients treated with haloperidol or lorazepam (or both) 3 times daily in increasing doses
depending on symptoms
Outcomes
1. Incident delirium post op

2. Duration of delirium
3. Delirium severity
5. Withdrawal from protocol
6. Adverse effects
Notes
Funding source: Medical Center Alkmaar

19
Liptzin 2005
Methods
Randomisation: By research pharmacist but method not described

Power calculation: Yes, but used a higher estimate of delirium incidence than in study
Delirium diagnostic criteria: DSM IV
Outcomes Measurement: Delirium Symptom Interview (DSI) and CAM daily pre and postop, and postop daily
medical records review by experienced research assistant; Delirium presence determined from this information at day
7 and 14 postop
Intention to treat analysis: No
Drop outs from protocol: 11 in intervention group and 11 controls
Incomplete follow up: 10/90
Participants
Number in study: 90
USA
One academic medical centre
Scheduled for elective admission for hip or knee arthroplasty
Age Range: 52-90 yrs; mean 67.2 and 69.4 yrs respectively
Dementia: Not given Delirium at enrollment: Not assessed
Exclusions: Gastro-oesophageal reflux disease, sick sinus syndrome, using donepezil or intolerant to it, non-English
speaking
Interventions
Donepezil 5 mg once daily for 14 days before and after surgery, doubled to 10 mg if developed any symptoms of
delirium
Placebo identical in appearance
Outcomes
1. Incident delirium postop

2. Duration of delirium
4. Withdrawal from protocol
Notes
Funding source: Unrestricted research grant from Pfizer

20
Marcantonio 2001
Methods
Randomisation: Adequate concealed allocation

Power calculation: Yes. Study adequately powered for bivariate analyses but not for the multivariate or stratified
analyses.
Blinding of participants: No, not possible given nature of intervention
Informed consent: Yes, or proxy assent if unable to consent
Delirium diagnostic criteria: CAM
Outcomes Measurement: Daily interviews from enrollment to discharge to complete MMSE, DSI, CAM, (MDAS)
by trained assessors
Drop outs from protocol 0
Incomplete follow up: 0
Study duration: Not given
Participants
Number in study: 126

USA
1 academic tertiary centre orthopaedic department
Admitted for primary surgical repair of hip fracture
At intermediate or high risk of delirium (presence of 1 or more delirium risk factors)
Age: 65 yrs or over; mean 78 and 80 yrs in intervention and controls respectively
Co-morbidity: High (Charlson index >/= 4) in 39% and 33% of intervention and control groups respectively
Dementia: 37% in intervention group and 51% in controls Delirium at enrollment: Assessed but not excluded
Exclusions: Metatstatic cancer or comorbid illness reducing life expectancy to less than 6 months; Unable to obtain
consent (or proxy assent) within 24 hrs of surgery, or 48 hrs of admission
Interventions
Proactive consultation by Consultant Geriatrician, with daily visits starting preop or within 24 hrs post op for duration
of admission. Protocol based targeted recommendations over and above what was already being done by team, limited
to 5 at initial visit and 3 at follow-up visits
Controls: Usual care, consisting of management by orthopaedic team and consultation by internal medicine or
geriatrics on reactive rather than proactive basis
Outcomes
1. Delirium incidence- total cumulative during admission

2. Delirium duration
3. Severity- cumulative incidence of severe delirium during admission
5. Institutionalisation at discharge
Notes
Funding source: Older Americans Independence Center; Charles Farnworth Trust;

Delirium examined but not reported at intake, making interpretation of results for primary outcome of cumulative
delirium incidence difficult

21
Characteristics of excluded studies [ordered by study ID]
Study
Reason for exclusion
Baldwin 2004
The intervention was not designed to prevent delirium. Cognitive impairment rather than delirium was used as
an outcome measure
Budd 1974
A validated method for diagnosis of delirium was not used.
Cerchietti 2000
Not a delirium prevention study.
Cole 2002
Culp 2003
Randomisation not used and participants were long term care residents
Inouye 1993a
Not original research- review article.
Inouye 1999
Randomisation not used.
Kaneko 1999
A validated method for delirium diagnosis was not used. Although DSM IIIR diagnostic criteria used, data
obtained from retrospective chart review
Landefeld 1995
Outcomes examined did not include delirium.
Lundstrom 2005
Mentes 2003
Milisen 2001
Before and after study.
Naughton 2005
Tabet 2005
Tokita 2001
Delirium diagnosis relied on retrospective records review.
Wanich 1992
Wong 2005
Randomisation not used. Before and after study.

22
Characteristics of ongoing studies [ordered by study ID]

Boustani 2005a
Trial name or title
Donepezil in the Prevention of Post-Operative Cognitive Decline
Methods
Participants
30 adults aged 65 and older who have a baseline mild cognitive impairment (MCI) and are undergoing
elective hip or knee replacement
Interventions
Donepezil or a matching placebo for 3-6 weeks, starting 4 weeks preoperatively
Outcomes
Primary Outcomes: Changes in the International Study of Post-Operative Cognitive Decline (ISPOCD) and
the CogHealth computerized battery tests at 1 week and 12 weeks after surgery.
Secondary Outcomes: Delirium status measured by the CAM and the MDAS daily during the post-operative
period; Global Cognitive status assessed using the MMSE; Length of Stay in the hospital post-operatively;
Discharge site; Adverse effects
Starting date
February 2005
Contact information
smunger@regenstrief.org
Notes
Boustani 2005b
Trial name or title
Enhancing Care for Hospitalized Older Adults with Cognitive Impairment
Methods
Participants
400 patients with cognitive impairment who have been hospitalized in a medical ward
Interventions
A cognitive screening program coupled with a Computerized Decision Support System or usual care
Outcomes
Primary Outcomes: Use of potentially inappropriate medications, urinary catheter or physical restraints, and
length of time in initiating a referral order, as recorded in the electronic medical record; Total number of
hospital acquired complications recorded in the medical record that may be related to Cognitive Impairment
(CI)
Secondary Outcomes: Length and cost of hospital stay from discharge records and billing system
Starting date
July 2006
Contact information
smunger@regenstrief.org
Notes

23
Boustani 2005c
Trial name or title
Donepezil in Preventing Delirium in Hospitalized Elderly
Methods
Participants
30 adults aged 65 or older who are undergoing hip fracture surgery
Interventions
Donepezil or a matching placebo within 24 hours prior to surgery and for 4 days after surgery
Outcomes
Primary Outcomes: Postoperative cumulative incident cases of delirium, as defined by the CAM administered
at baseline prior to surgery and daily until discharge; delirium severity as measured by the MDAS
Secondary Outcomes: Cognitive Status as measured by the MMSE; behavioral status using the Rating Scale
for Aggressive Behavior in the Elderly (RAGE); length of stay in hospital postoperatively; discharge site;
adverse effects; use of psychotropic medications
Starting date
July 2004
Contact information
ClinicalTrials.gov identifier NCT00182884 smunger@regenstrief.org
Notes
Diehl 2005
Trial name or title
Prevention of Postoperative Delirium with Donepezil
Methods
Participants
Cognitively healthy, elective hip or knee replacement patients aged 70 or over
Interventions
Donepezil or matching placebo before (over 5-7 days), during and after (over 7 days) surgery
Outcomes
Primary Outcomes: Incidence of delirium

Secondary Outcomes: Cognitive performance
Starting date
January 2006
Contact information
janine.diehl@lrz.tum.de
Notes
Ely 2004a
Trial name or title
A Randomized, Double-blind Trial in Ventilated ICU Patients Comparing Treatment with an Alpha2 Agonist
versus a Gamma Aminobutyric Acid (GABA)-Agonist to Determine Delirium Rates, Efficacy of Sedation,
Analgesia and Discharge Cognitive Status
Methods

24
Ely 2004a
(Continued)
Participants
100 adult mechanically ventilated patients
Interventions
A sedation strategy of dexmedetomidine fentanyl versus lorazepam fentanyl,
Outcomes
Primary Outcomes: Delirium

Secondary Outcomes: Efficacy of sedation
Starting date
August 2004
Contact information
wes.ely@vanderbilt.edu
Notes
Ely 2004b
Trial name or title
Delirium in the ICU: a Prospective, Randomized, Trial of Placebo vs Haloperidol vs Ziprasidone
Methods
Participants
102 adult mechanically ventilated patients
Interventions
Placebo or Haloperidol or Ziprasidone
Outcomes
Primary Outcomes: Incidence and duration of delirium

Secondary Outcomes: Severity of neuropsychological dysfunction at hospital discharge
Starting date
December 2004
Contact information
wes.ely@vanderbilt.edu
Notes
Harari 2005
Trial name or title
Proactive intervention to improve post-operative outcomes in at risk older people undergoing surgery: a
randomised controlled trial
Methods
Participants
Patients at risk of post-operative complications aged 65 or over awaiting major surgery
Interventions
Proactive multidisciplinary geriatric intervention or usual care
Outcomes
Primary outcome: hospital bed-days Secondary: 30-day re-admission, delirium, other medical complications,
mortality, function, anxiety, depression, resource use

25
Harari 2005
(Continued)
Starting date
January 2003
Contact information
danielle.harari@gstt.sthames.nhs.uk
Notes
Steiner 2005
Trial name or title
Rivastigmine for the Prevention of Postoperative Delirium in Patients Undergoing Cardiac Surgery
Methods
Participants
120 patients aged 65 or more undergoing cardiac surgery with use of extracorporeal circulation
Interventions
Rivastigmine (oral solution), starting on the evening preceding the operation and for the first seven days
postoperatively or placebo
Outcomes
Primary Outcomes: Development of postoperative delirium within 7 days after cardiac surgery
Secondary Outcomes: Severity of delirium occurring within 7 days after cardiac surgery; Length of stay
(intensive care and hospital); Amount of drugs used for rescue therapy of delirium
Starting date
January 2006
Contact information
lsteiner@uhbs.ch
Notes
van der Burg 2005
Trial name or title
Post-Operative Haloperidol Versus Placebo for Prevention of Post-Operative Delirium After Acute Hip
Surgery
Methods
Participants
206 patients aged 75 yrs and older undergoing surgery for hip fracture
Interventions
Post-operative haloperidol or placebo
Outcomes
Primary Outcomes: Incidence of post-operative delirium

Secondary Outcomes: Length of stay.; Mortality.; ADL dependence at 3 months
Starting date
November 2005
Contact information
Boke Linso Sjirk Borger van der Burg, MD boudewijn.borgervanderburg@gmail.com
Notes
26
DATA AND ANALYSES
Comparison 1. Post surgery administration of DFP v Usual care
Outcome or subgroup title

1 Incidence of delirium in first 7
days after surgery
2 Behavioural disturbance in 1st 7
days after surgery
3 Length of admission
No. of
studies
No. of
participants
40
Risk Ratio (M-H, Fixed, 95% CI)
0.14 [0.02, 1.06]
40
0.2 [0.03, 1.56]
40
Mean Difference (IV, Fixed, 95% CI)
-4.30 [-12.51, 3.91]
Statistical method
Effect size
Comparison 2. Epidural anaesthesia v Halothane anaesthesia

1 Incident delirium on day 1 or
day 7 post surgery
2 Physical morbidity
2.1 Stroke
2.2 Urinary Tract Infection
2.3 Decubitus ullcer
No. of
studies
No. of
participants
57
1.32 [0.73, 2.39]
1
1
1
1
57
57
57

Subtotals only
7.24 [0.39, 134.12]
1.33 [0.57, 3.09]
0.62 [0.16, 2.36]
Statistical method
Effect size
Comparison 3. Prophylactic citocoline v Placebo

1 Incident delirium
1.1 Incident delirium
immediately post surgery
1.2 Incident delirium day 1
post surgery
post surgery
post surgery
2 MMSE score post surgery
No. of
studies
No. of
participants
1
1
81

Subtotals only
0.56 [0.16, 2.02]
81
0.66 [0.22, 2.01]
81
0.99 [0.24, 4.12]
81
1.31 [0.28, 6.12]
Other data
No numeric data
Statistical method

Effect size
27
Comparison 4. Prophylactic haloperidol v Placebo

1 Incident delirium post surgery
2 Delirium duration
3 Delirium severity
4 Length of admission
5 Withdrawal from protocol
6 Adverse effects
No. of
studies
No. of
participants
1
1
430
430
1
1
1
430
430
430
Statistical method
Other data
Effect size
0.91 [0.59, 1.42]
-6.44 [-7.64, -5.24]
No numeric data
-5.5 [-8.17, -2.83]
0.73 [0.43, 1.26]
0.39 [0.10, 1.43]
Comparison 5. Prophylactic donepezil v Placebo

1 Delirium incidence after surgery
4 Withdrawal from protocol
No. of
studies
No. of
participants
1
1
80
80
Statistical method
Effect size
1.20 [0.48, 3.00]
1.05 [0.52, 2.14]
Comparison 6. Proactive geriatric consultation v Usual care

1 Cumulative delirium incidence
1.1 Cumulative delirium
incidence in all patients
1.2 Cumulative delirium
incidence in dementia
sub-group
2 Delirium duration
3 Severity- cumulative incidence
of severe delirium
4 Institutionalisation at discharge
5 Cognitive statusdelirium
prevalence at discharge
No. of
studies
No. of
participants
1
1
126
Odds Ratio (M-H, Fixed, 95% CI)

Subtotals only
0.48 [0.23, 0.98]
50
0.73 [0.22, 2.38]
1
1
126
126

-0.20 [-0.95, 0.55]

0.40 [0.18, 0.89]
1
1
126
126

1.05 [0.93, 1.18]

0.69 [0.30, 1.57]
Statistical method

Effect size
28
Analysis 1.1. Comparison 1 Post surgery administration of DFP v Usual care, Outcome 1 Incidence of
delirium in first 7 days after surgery.
Review:
Comparison: 1 Post surgery administration of DFP v Usual care

Outcome: 1 Incidence of delirium in first 7 days after surgery
Study or subgroup
Treatment
Control
n/N
n/N
Risk Ratio
Weight
Aizawa 2002
1/20
7/20
100.0 %
0.14 [ 0.02, 1.06 ]
Total (95% CI)
20
20
100.0 %
0.14 [ 0.02, 1.06 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI
Total events: 1 (Treatment), 7 (Control)

Heterogeneity: not applicable
Test for overall effect: Z = 1.91 (P = 0.057)
0.001 0.01 0.1
Favours treatment
10 100 1000
Favours control
Analysis 1.2. Comparison 1 Post surgery administration of DFP v Usual care, Outcome 2 Behavioural
disturbance in 1st 7 days after surgery.
Review:

Outcome: 2 Behavioural disturbance in 1st 7 days after surgery
Study or subgroup
Treatment
Control
n/N
n/N
Risk Ratio
Weight
Aizawa 2002
1/20
5/20
100.0 %
0.20 [ 0.03, 1.56 ]
Total (95% CI)
20
20
100.0 %
0.20 [ 0.03, 1.56 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

0.1 0.2
0.5
Favours treatment
10
Favours control

29
Analysis 1.3. Comparison 1 Post surgery administration of DFP v Usual care, Outcome 3 Length of
admission.
Review:

Outcome: 3 Length of admission
Study or subgroup
Treatment
Control
Mean Difference
Mean(SD)
Mean(SD)
Aizawa 2002
20
25.6 (9.4)
20
29.9 (16.2)
Total (95% CI)
20
Weight
Mean Difference
100.0 %
-4.30 [ -12.51, 3.91 ]
100.0 %
-4.30 [ -12.51, 3.91 ]
IV,Fixed,95% CI
IV,Fixed,95% CI
20

Test for subgroup differences: Not applicable
-10
-5
Favours treatment
10
Favours control
Analysis 2.1. Comparison 2 Epidural anaesthesia v Halothane anaesthesia, Outcome 1 Incident delirium on
day 1 or day 7 post surgery.
Review:
Comparison: 2 Epidural anaesthesia v Halothane anaesthesia

Outcome: 1 Incident delirium on day 1 or day 7 post surgery
Study or subgroup
Berggren 1987
Total (95% CI)
Epidural
Halothane
n/N
n/N
Risk Ratio
Weight
14/28
11/29
100.0 %
1.32 [ 0.73, 2.39 ]
28
29
100.0 %
1.32 [ 0.73, 2.39 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI
Total events: 14 (Epidural), 11 (Halothane)

0.1 0.2
0.5
Favours treatment
10
Favours control

30
Analysis 2.2. Comparison 2 Epidural anaesthesia v Halothane anaesthesia, Outcome 2 Physical morbidity.
Review:
Comparison: 2 Epidural anaesthesia v Halothane anaesthesia

Outcome: 2 Physical morbidity
Study or subgroup
Epidural
Halothane
n/N
n/N
Risk Ratio
Weight
3/28
0/29
100.0 %
7.24 [ 0.39, 134.12 ]
28
29
100.0 %
7.24 [ 0.39, 134.12 ]
9/28
7/29
100.0 %
1.33 [ 0.57, 3.09 ]
28
29
100.0 %
1.33 [ 0.57, 3.09 ]
3/28
5/29
100.0 %
0.62 [ 0.16, 2.36 ]
28
29
100.0 %
0.62 [ 0.16, 2.36 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI
1 Stroke
Berggren 1987
Subtotal (95% CI)

2 Urinary Tract Infection
Berggren 1987
Subtotal (95% CI)

3 Decubitus ullcer
Berggren 1987
Subtotal (95% CI)

0.1 0.2
0.5
Favours treatment
10
Favours control

31
Analysis 3.1. Comparison 3 Prophylactic citocoline v Placebo, Outcome 1 Incident delirium.

Review:
Comparison: 3 Prophylactic citocoline v Placebo

Outcome: 1 Incident delirium
Study or subgroup
Treatment
Control
n/N
n/N
Risk Ratio
Weight
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI
1 Incident delirium immediately post surgery

Diaz 2001
3/35
7/46
100.0 %
0.56 [ 0.16, 2.02 ]
35
46
100.0 %
0.56 [ 0.16, 2.02 ]
4/35
8/46
100.0 %
0.66 [ 0.22, 2.01 ]
35
46
100.0 %
0.66 [ 0.22, 2.01 ]
3/35
4/46
100.0 %
0.99 [ 0.24, 4.12 ]
35
46
100.0 %
0.99 [ 0.24, 4.12 ]
3/35
3/46
100.0 %
1.31 [ 0.28, 6.12 ]
35
46
100.0 %
1.31 [ 0.28, 6.12 ]
Subtotal (95% CI)

2 Incident delirium day 1 post surgery
Diaz 2001
Subtotal (95% CI)

Diaz 2001
Subtotal (95% CI)

Diaz 2001
Subtotal (95% CI)

0.1 0.2
0.5
Favours treatment
10
Favours control
Analysis 3.2. Comparison 3 Prophylactic citocoline v Placebo, Outcome 2 MMSE score post surgery.
MMSE score post surgery
Study
Int (mean score)
Int SD
Control (mean score)
Controls SD
P-value
Diaz 2001
23.48
6.0
24.95
4.9
0.2, not significant;

32
Analysis 4.1. Comparison 4 Prophylactic haloperidol v Placebo, Outcome 1 Incident delirium post surgery.
Review:
Comparison: 4 Prophylactic haloperidol v Placebo

Outcome: 1 Incident delirium post surgery
Study or subgroup
Treatment
Control
n/N
n/N
32/212
36/218
100.0 %
0.91 [ 0.59, 1.42 ]
212
218
100.0 %
0.91 [ 0.59, 1.42 ]
Kalisvaart 2005
Total (95% CI)
Risk Ratio
Weight
Risk Ratio
M-H,Fixed,95% CI
M-H,Fixed,95% CI

0.1 0.2
0.5
Favours treatment
10
Favours control
Analysis 4.2. Comparison 4 Prophylactic haloperidol v Placebo, Outcome 2 Delirium duration.

Review:

Outcome: 2 Delirium duration
Study or subgroup
Treatment
Control
Mean Difference
Mean(SD)
Mean(SD)
Kalisvaart 2005
212
5.41 (4.91)
218
11.85 (7.56)
Total (95% CI)
212
Weight
Mean Difference
100.0 %
-6.44 [ -7.64, -5.24 ]
100.0 %
-6.44 [ -7.64, -5.24 ]
IV,Fixed,95% CI
IV,Fixed,95% CI
218

Test for overall effect: Z = 10.50 (P < 0.00001)
-10
-5
Favours treatment
10
Favours control
Analysis 4.3. Comparison 4 Prophylactic haloperidol v Placebo, Outcome 3 Delirium severity.

Delirium severity
Study
Int max DRS score
Int. SD
Ctrls max DRS score
Controls SD
Mean difference
Kalisvaart 2005
14.4
3.5
18.4
4.4
4.0, [95% CI 1.4, 2.3] P< 0.001)

33
Analysis 4.4. Comparison 4 Prophylactic haloperidol v Placebo, Outcome 4 Length of admission.

Review:

Outcome: 4 Length of admission
Study or subgroup
Treatment
Control
Mean Difference
Mean(SD)
Mean(SD)
Kalisvaart 2005
212
17.1 (11.1)
218
22.6 (16.7)
Total (95% CI)
212
Weight
Mean Difference
100.0 %
-5.50 [ -8.17, -2.83 ]
100.0 %
-5.50 [ -8.17, -2.83 ]
IV,Fixed,95% CI
IV,Fixed,95% CI
218

-10
-5
Favours treatment
10
Favours control
Analysis 4.5. Comparison 4 Prophylactic haloperidol v Placebo, Outcome 5 Withdrawal from protocol.
Review:

Outcome: 5 Withdrawal from protocol
Study or subgroup
Kalisvaart 2005
Total (95% CI)
Treatment
Control
n/N
n/N
Risk Ratio
Weight
20/212
28/218
100.0 %
0.73 [ 0.43, 1.26 ]
212
218
100.0 %
0.73 [ 0.43, 1.26 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

0.1 0.2
0.5
Favours treatment
10
Favours control

34
Analysis 4.6. Comparison 4 Prophylactic haloperidol v Placebo, Outcome 6 Adverse effects.

Review:

Outcome: 6 Adverse effects
Study or subgroup
Treatment
Control
n/N
n/N
Risk Ratio
Weight
Kalisvaart 2005
3/212
8/218
100.0 %
0.39 [ 0.10, 1.43 ]
Total (95% CI)
212
218
100.0 %
0.39 [ 0.10, 1.43 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

0.1 0.2
0.5
Favours treatment
10
Favours control
Analysis 5.1. Comparison 5 Prophylactic donepezil v Placebo, Outcome 1 Delirium incidence after surgery.
Review:
Comparison: 5 Prophylactic donepezil v Placebo

Outcome: 1 Delirium incidence after surgery
Study or subgroup
Liptzin 2005
Total (95% CI)
Treatment
Control
n/N
n/N
Risk Ratio
Weight
8/39
7/41
100.0 %
1.20 [ 0.48, 3.00 ]
39
41
100.0 %
1.20 [ 0.48, 3.00 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

0.1 0.2
0.5
Favours treatment
10
Favours control

35
Analysis 5.4. Comparison 5 Prophylactic donepezil v Placebo, Outcome 4 Withdrawal from protocol.
Review:
Comparison: 5 Prophylactic donepezil v Placebo

Outcome: 4 Withdrawal from protocol
Study or subgroup
Liptzin 2005
Total (95% CI)
Treatment
Control
n/N
n/N
Risk Ratio
Weight
11/39
11/41
100.0 %
1.05 [ 0.52, 2.14 ]
39
41
100.0 %
1.05 [ 0.52, 2.14 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

0.1 0.2
0.5
Favours treatment
10
Favours control
Analysis 6.1. Comparison 6 Proactive geriatric consultation v Usual care, Outcome 1 Cumulative delirium
incidence.
Review:
Comparison: 6 Proactive geriatric consultation v Usual care

Outcome: 1 Cumulative delirium incidence
Study or subgroup
Treatment
Control
Odds Ratio
n/N
n/N
M-H,Fixed,95% CI
Weight
Odds Ratio
M-H,Fixed,95% CI
1 Cumulative delirium incidence in all patients

Marcantonio 2001
20/62
32/64
100.0 %
0.48 [ 0.23, 0.98 ]
62
64
100.0 %
0.48 [ 0.23, 0.98 ]
13/21
20/29
100.0 %
0.73 [ 0.22, 2.38 ]
21
29
100.0 %
0.73 [ 0.22, 2.38 ]
Subtotal (95% CI)


2 Cumulative delirium incidence in dementia sub-group
Marcantonio 2001
Subtotal (95% CI)

0.1 0.2
0.5
Favours treatment
10
Favours control

36
Analysis 6.2. Comparison 6 Proactive geriatric consultation v Usual care, Outcome 2 Delirium duration.
Review:

Outcome: 2 Delirium duration
Study or subgroup
Treatment
Marcantonio 2001
Total (95% CI)
Control
Mean Difference
Mean(SD)
Mean(SD)
62
2.9 (2)
64
3.1 (2.3)
62
Weight
IV,Fixed,95% CI
Mean Difference
IV,Fixed,95% CI
64
100.0 %
-0.20 [ -0.95, 0.55 ]
100.0 %
-0.20 [ -0.95, 0.55 ]

-10
-5
Favours treatment
10
Favours control
Analysis 6.3. Comparison 6 Proactive geriatric consultation v Usual care, Outcome 3 Severity- cumulative
incidence of severe delirium.
Review:

Outcome: 3 Severity- cumulative incidence of severe delirium
Study or subgroup
Marcantonio 2001
Total (95% CI)
Treatment
Control
n/N
n/N
Risk Ratio
Weight
7/62
18/64
100.0 %
0.40 [ 0.18, 0.89 ]
62
64
100.0 %
0.40 [ 0.18, 0.89 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

0.1 0.2
0.5
Favours treatment
10
Favours control

37
Analysis 6.4. Comparison 6 Proactive geriatric consultation v Usual care, Outcome 4 Institutionalisation at
discharge.
Review:

Outcome: 4 Institutionalisation at discharge
Study or subgroup
Marcantonio 2001
Total (95% CI)
Treatment
Control
n/N
n/N
Risk Ratio
Weight
57/62
56/64
100.0 %
1.05 [ 0.93, 1.18 ]
62
64
100.0 %
1.05 [ 0.93, 1.18 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

0.1 0.2
0.5
Favours treatment
10
Favours control
Analysis 6.5. Comparison 6 Proactive geriatric consultation v Usual care, Outcome 5 Cognitive statusdelirium prevalence at discharge.
Review:

Outcome: 5 Cognitive statusdelirium prevalence at discharge
Study or subgroup
Marcantonio 2001
Total (95% CI)
Treatment
Control
n/N
n/N
Risk Ratio
Weight
8/62
12/64
100.0 %
0.69 [ 0.30, 1.57 ]
62
64
100.0 %
0.69 [ 0.30, 1.57 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

0.1 0.2
0.5
Favours treatment
10
Favours control

38
ADDITIONAL TABLES
Table 1. Quality Assessment Tool (Adapted from US Preventive Services Task Force)
Validity Criteria
Met
Partially Met
Unmet/Unknown
Initial assembly of comparable

groups (includes concealment
of treatment allocation and potential confounders distributed
equally among groups)
Maintenance
of comparable groups (includes
attrition, crossovers, adherence,
contamination)
Clear definition of interventions
All important outcomes considered and predefined
Outcome measurements equal,
reliable, and valid (includes
masking of outcome assessment)
No important differential loss
to follow-up or overall high loss
to follow-up (trials should have
losses less than 25%, unless due
to death)
Intention-to-treat analysis
Table 2. Study Quality Assessment
Study
Quality Assessment
Aizawa 2002
Berggren 1987
Diaz 2001
Kalisvaart 2005
Liptzin 2005

39
Table 2. Study Quality Assessment
Marcantonio 2001
(Continued)
WHATS NEW
Last assessed as up-to-date: 11 January 2007.
Date
Event
Description
3 November 2008
Amended
Converted to new review format.
HISTORY
Protocol first published: Issue 4, 2005
Review first published: Issue 2, 2007
Date
Event
Description
12 January 2007
New citation required and conclusions have changed
Substantive amendment
CONTRIBUTIONS OF AUTHORS
Najma Siddiqi: All correspondence; drafting of protocol versions; searching for trials; selection of trials; extraction of data and critical
review of studies; entry of data; interpretation of data analyses; updating review
Rachel Stockdale: Drafting of protocol versions; searching for trials; selection of trials; extraction of data and critical review of studies;
entry of data; interpretation of data analyses
Annette Britton: Extraction of data and critical review of studies
John Holmes: Arbiter in selection of trials and interpretation of data analyses
Contact Editors: Leon Flicker and Lon Schneider
Consumer Editor: Duncan Forsyth
This review has been peer reviewed anonimously by two peer reviewers

40
DECLARATIONS OF INTEREST
None
SOURCES OF SUPPORT
Internal sources
University of Leeds, UK.
Leeds Mental Health NHS Teaching Trust, UK.
Leeds Teaching Hospitals NHS Trust, UK.
External sources
No sources of support supplied
INDEX TERMS
Medical Subject Headings (MeSH)
Hospitalization;
Anesthesia, Epidural; Anesthetics, Inhalation; Cytidine Diphosphate Choline [administration & dosage]; Delirium
[ prevention & control]; Halothane; Indans [administration & dosage]; Nootropic Agents [administration & dosage]; Piperidines
[administration & dosage]
MeSH check words

Humans

41

Cochrane SCA Sindrome Confusional Agudo

Enviado por

Dados do documento

Título original

Direitos autorais

Formatos disponíveis

Compartilhar este documento

Compartilhar ou incorporar documento

Opções de compartilhamento

Você considera este documento útil?

Este conteúdo é inapropriado?

Direitos autorais:

Formatos disponíveis

Cochrane SCA Sindrome Confusional Agudo

Enviado por

Direitos autorais:

Formatos disponíveis

Interventions for preventing delirium in hospitalised patients

Interventions for preventing delirium in hospitalised patients (Review)

Interventions for preventing delirium in hospitalised patients (Review)

Interventions for preventing delirium in hospitalised patients

PLAIN LANGUAGE SUMMARY

core features of delirium have been clarified in the DSM-IV (APA

Interventions for preventing delirium in hospitalised patients (Review)

(Francis 1990), and 7 to 9.6% in elderly patients presenting

Prevention of delirium is obviously desirable for both patients and

Criteria for considering studies for this review

Interventions for preventing delirium in hospitalised patients (Review)

We also included adverse events, although this was not specified

Search methods for identification of studies

Interventions for preventing delirium in hospitalised patients (Review)

1.Delirium/ all subheadings

14 delirium-tremens/ all subheadings

Interventions for preventing delirium in hospitalised patients (Review)

6.(toxic next psychosis)

Data collection and analysis

Interventions for preventing delirium in hospitalised patients (Review)

Alzheimers disease, might also be helpful in delirium (Gleason

Risk of bias in included studies

Interventions for preventing delirium in hospitalised patients (Review)

precluded this (Aizawa 2002; Berggren 1987; Marcantonio 2001).

a) Incident delirium in the 7 days after surgery was significantly

Interventions for preventing delirium in hospitalised patients (Review)

and control groups (RR 0.91 [95% CI 0.59, 1.42]).

b) Delirium duration. There was little difference between the two

Interventions for preventing delirium in hospitalised patients (Review)

delirium incidence following surgery under epidural or halothane

Interventions for preventing delirium in hospitalised patients (Review)

Implications for research

References to studies included in this review

References to studies excluded from this review

Interventions for preventing delirium in hospitalised patients (Review)

Inouye 1993a {published data only}

elderly hip-fracture patients. Journal of the American

References to ongoing studies

Interventions for preventing delirium in hospitalised patients (Review)

randomised controlled trial.. National Research Register

Interventions for preventing delirium in hospitalised patients (Review)

of nonpharmacologic interventions: Evidence from the

Interventions for preventing delirium in hospitalised patients (Review)

investigators. International Study of Post-Operative

revised-98: comparison with the delirium rating scale and

References to other published versions of this review

Indicates the major publication for the study

Interventions for preventing delirium in hospitalised patients (Review)

Characteristics of included studies [ordered by study ID]

Randomisation: Allocation immediately after surgery but method not described

1. Incident delirium in 7 days postop

Interventions for preventing delirium in hospitalised patients (Review)

Randomisation: Method not described

1. Incident delirium on postop day 1 or 7

Interventions for preventing delirium in hospitalised patients (Review)

Randomisation: Method not described

1. Incident delirium immediately, day 1, day 2 and day 3 post op

Interventions for preventing delirium in hospitalised patients (Review)

Randomisation: Adequate concealed allocation

Number in study: 430

1. Incident delirium post op

Funding source: Medical Center Alkmaar

Interventions for preventing delirium in hospitalised patients (Review)