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Systematic Review
Revised

The effect of non-pharmacologic strategies on prevention or management of intensive care unit delirium: a systematic review

[version 3; peer review: 2 approved]
* Equal contributors
PUBLISHED 24 Jun 2022
Author details Author details
OPEN PEER REVIEW
REVIEWER STATUS

Abstract

Background: Post-operative delirium is a common complication among adult patients in the intensive care unit. Current literature does not support the use of pharmacologic measures to manage this condition, and several studies explore the potential for the use of non-pharmacologic methods such as early mobility plans or environmental modifications. The aim of this systematic review is to examine and report on recently available literature evaluating the relationship between non-pharmacologic management strategies and the reduction of delirium in the intensive care unit.
Methods: Six major research databases were systematically searched for articles analyzing the efficacy of non-pharmacologic delirium interventions in the past five years. Search results were restricted to adult human patients aged 18 years or older in the intensive care unit setting, excluding terminally ill subjects and withdrawal-related delirium. Following title, abstract, and full text review, 27 articles fulfilled the inclusion criteria and are included in this report.
Results: The 27 reviewed articles consist of 12 interventions with a single-component investigational approach, and 15 with multi-component bundled protocols. Delirium incidence was the most commonly assessed outcome followed by duration. Family visitation was the most effective individual intervention while mobility interventions were the least effective. Two of the three family studies significantly reduced delirium incidence, while one in five mobility studies did the same. Multi-component bundle approaches were the most effective of all; of the reviewed studies, eight of 11 bundles significantly improved delirium incidence and seven of eight bundles decreased the duration of delirium.
Conclusions: Multi-component, bundled interventions were more effective at managing intensive care unit delirium than those utilizing an approach with a single interventional element. Although better management of this condition suggests a decrease in resource burden and improvement in patient outcomes, comparative research should be performed to identify the importance of specific bundle elements.

Keywords

critical care, delirium, intensive care, non-pharmacologic, systematic review

Revised Amendments from Version 2

This revision addressed additional limitations and future directions of our review topic (non-pharmacologic delirium strategies in critically ill adult patients). Segments were added to the discussion section regarding: the distinction between different etiologies of ICU delirium, expanding patient populations, and underlying differences among sub-populations of patients with ICU delirium. We also updated author affiliations and funding to their current status.

See the authors' detailed response to the review by Claudia D. Spies, Fatima Yürek and Alawi Luetz
See the authors' detailed response to the review by Elizabeth Mahanna-Gabrielli

Introduction

Delirium is a multifactorial, acute, confusional state characterized by the disturbance of consciousness and cognition; it is particularly common in the intensive care unit (ICU) with incidence ranging from 19 to 87% with especially high rates in mechanically ventilated patients13. ICU delirium is associated with adverse outcomes including increased mortality, prolonged mechanical ventilation and hospitalization, increased risk of cognitive dysfunction after discharge, and increased cost of care47.

While the pathophysiology of delirium is not well understood, there are multiple factors associated with an increased risk for developing delirium including age, neurologic or psychological disorders, polypharmacy, medications, and sensory impairment811. Modifiable environmental risk factors including immobilization, use of restraints, isolation, and levels of environmental light and sound are also considered risk factors for the development of delirium in the ICU8,12.

The morbidity associated with delirium as well as the multitude of delirium risk factors present in the ICU make delirium prevention and management strategies essential. These strategies have included pharmacological, non-pharmacological, and multicomponent interventions with the aim of decreasing the incidence and duration of delirium. Research into pharmacological interventions has focused on haloperidol and dexmedetomidine, though there has also been limited research into the effects of ramelteon, melatonin, and ziprasidone1316. Despite continued research, current literature does not support the use of anti-psychotic agents, benzodiazepines, or melatonin in the management of delirium13,17.

Given the lack of evidence supporting pharmacological measures, further research into the efficacy of non-pharmacologic interventions such as early mobilization, environmental modifications, or management bundles is crucial. The implementation of effective delirium management shows promise in decreasing morbidity, mortality, length of stay, and resource burden in the ICU setting. In terms of the PICOS framework (Population, Interventions, Comparisons, Outcomes, Study Design)18, our systematic review aims to address the effects of any non-pharmacologic prevention or management strategy on the incidence, prevalence, duration, or severity of delirium in critically ill adult patients compared to control patients, with no restrictions on study design.

Methods

Search strategy and data extraction

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in this review and included as Reporting guidelines19,20. The electronic databases of PubMed, Embase, Cochrane Central, Web of Science, The Cumulative Index to Nursing and Allied Health Literature (CINAHL), and ClinicalTrials.gov were systematically searched on May 15, 2019 for articles concerning non-pharmacologic treatments for delirium in the ICU. Search terms were tailored to each database in order to best utilize the individual subject headings, keywords, and medical subject headings (MeSH) terms included in the individual databases. A full list of search terms is shown in the Extended data20.

In addition to our search terms, search results were restricted to articles published in English within five years of the date of the search (Jan 1, 2014 to May 15, 2019). After retrieving articles within a ten year window as outlined in Extended Data20, the authors decided to further reduce the range to within five years. This date range was chosen in order to provide a review of the most recent developments in this field of research. After search results were compiled and duplicates were removed, a total of 5234 articles were selected for title and abstract review. Four authors (JSC, HH, MMR, RB) screened the titles and abstracts and retrieved articles for eligibility, resulting in 113 articles selected for full text review. Three authors (JSC, HH, JL) then independently reviewed the full text of eligible articles, completed data extraction worksheets adapted from the Cochrane Review Group’s Data Extraction Form (https://dplp.cochrane.org/data-extraction-forms), and assessed the articles for risk of bias using the Cochrane risk of bias tool21. Elements of the data extraction worksheet included study design and setting, participant characteristics, details of the intervention and control groups, diagnostic tools, and patient outcomes (Extended data, Supplementary Table 1)20. Any disagreements were resolved by thoroughly discussing any points of concern. During the full text review 86 articles were removed because they failed to meet our inclusion criteria resulting in a total of 27 included articles (Figure 1).

a316d56d-274d-43fc-9d43-687ecc9f6023_figure1.gif

Figure 1. PRISMA Record Screening Flow Chart.

Inclusion and exclusion criteria

Our review addresses non-pharmacological management strategies for delirium in the ICU. Included articles were those investigating non-pharmacologic interventions and their impact on delirium incidence, prevalence, duration, or severity in an adult (≥ 18 years) intensive care unit setting. Articles were excluded if they focused on non-human subjects, pediatrics, terminally ill subjects, withdrawal related delirium, case reports, or where no full-text article was available (abstract only). There were no restrictions on study design. Studies solely investigating delirium-free-coma-free days were excluded since it is not possible to review as a delirium-specific result. One multi-center study was excluded as both the frequency and method of assessment for delirium were not specified for all study centers, making it difficult to reliably compare the results with other trials22. Another study was excluded because neither the screening process nor the cohort were described other than total number of patients enrolled, and there were no exclusion criteria noted to infer any characteristics of the selected population23.

Risk of bias assessment

In addition to data extraction using the Cochrane Review Group’s Data Extraction Form, a risk of bias assessment was performed by all authors on all included randomized controlled trials (RCTs) and randomized pilot studies. A risk of bias worksheet was developed by modifying Cochrane’s Risk of Bias Tool and articles were ranked as having a low, high, or unclear risk of bias21. Disagreements were settled by discussion between the authors. A total of eleven included studies underwent this assessment. Details of the risk of bias assessment categories can be found in the Extended data, Supplementary Table 220.

Results

After searching the literature, 27 articles are included in our systematic review2450 (Figure 1). Study details of each reviewed trial are located in Table 1. The 27 included studies provide results on many distinct outcomes; however, only the delirium-related outcomes of incidence, prevalence, duration, and severity were reviewed (Table 2Table 5). Outcomes combining delirium and coma into the same statistic were excluded, as no delirium-specific results could be assessed outright. An overall summary of delirium outcomes can be found in Table 2.

Table 1. Study summary.

StudyDesignPopulation, nPatient
characteristics
Notable exclusion
criteria
Intervention
characteristics
Control
characteristics
Method(s) of
assessment &
frequency
Pharmacologic
aspect?
Álvarez et al.
2017
RCT, pilotn=140Non-intubated
patients ≥60 years
old, hospitalized
within 24 hours
in the ICU for
postsurgical
observation or for
acute or chronic
decompensated
illness
Severe
communication
disorders; delirium
before ICU admission;
cognitive decline
(defined with score
>3.3 in the IQCODE
and >6 points in the
Spanish version of
FAQ)
Early and intensive OT

Details: two 40 minute
sessions per day (one
in the morning and one
in the evening) for 5
consecutive days

Components: polysensory
stimulation; body
positioning; cognitive
stimulation; BADLs;
stimulation of upper
extremities; family
engagement
Standard non-
pharmacological
prevention

Components:
reorientation
twice daily; early
mobilization 3
times daily; sight
and hearing aids;
environmental
management
(minimize physical
restraints; clock
and calendar);
sleep protocols;
caution with use
of medications
with the potential
to cause delirium
CAM: duration
& incidence of
delirium (twice
daily for 5
consecutive days)

DRS: severity of
delirium
Yes: avoidance
of nighttime
medications,
anticholinergic
drugs, and
benzodiazepines
Arbabi et al.
2018
quasi-
experimental
n=148Patients >18
years admitted to
general ICU
History of cognitive
disorders such as
dementia; alcohol
abuse; impaired
consciousness; history
of psychiatric drugs;
must not interrupt the
admission drug use
Multicomponent bundle

Components: staff
education; educational
posters; environmental
changes: clock, calendar,
family visits, appropriate
lighting, eye & ear aids,
light alarms instead of
audio alarms, staff-patient
interaction, hydration,
early mobility
Usual care, details
not specified.
CAM-ICU (twice
daily, once in
morning and
once in evening)
Yes: staff
educated on
pharmacologic
delirium
treatments
Balas et al.
2014
pre-post,
prospective
cohort study
n=296Patients ≥19 years
old admitted to
medical or surgical
critical care service
No LAR present to
provide consent
within 48 hours of
ICU admission; those
who failed the safety
screening or did not
receive clearance
from their physician
ABCDE bundle

Components: (A) sedation
awakening trial; (B)
spontaneous breathing
trial; (C) interdisciplinary
coordination; (D)
delirium monitoring &
management; (E) early
mobility
Usual care, details
not specified.
CAM-ICU (every 8
hours)
None.
Bounds et al.
2016
retrospective
study
n=159Patients ≥18 years
old and have
stayed in the ICU
>24 hours
Intracranial pressure
increased >50% from
first ICU measure
for hospitalization;
quadriplegia; GCS
score < 8 without use
of sedatives; comfort
measures only as
documented in the
medical record as a
medical order for life-
sustaining treatment
and/or palliative care;
cardiopulmonary
arrest resulting in
death.
ABCDE bundle

Components: (A)
sedation awakening
trial; (B) spontaneous
breathing trial; (C)
choice of medication
& interdisciplinary
coordination; (D)
delirium prevention &
management; (E) early
mobility
Usual care, details
not specified.
ICDSC (twice
daily at 05:00 and
17:00)
Yes: medication
management
Bryczkowski
et al. 2014
pre-post,
prospective
intervention
cohort study
n=123All patients
>50 years old
consecutively
admitted to the
SICU for ≥24 h
Diagnosed with
moderate to severe
TBI, defined as a
head AIS score of
≥3; transfer from jail
or in police custody;
history of dementia;
patients whose
delirium statuses
were recorded as
“unobtainable” or
undocumented
during their time in
the SICU
Multicomponent bundle

Components: protocol
to lighten sedation;
limit medications
associated with delirium;
sleep protocol: limit
unnecessary PM care,
lower lights and volume,
massage, music, quiet
time therapy; staff-
patient-family education
program
Usual care, details
not specified.
CAM-ICU (at
least every 12
hours, additional
measurements
after changes to
routine, i.e. after a
visit to radiology)
Yes: medication
management
Campbell 2014evidence-based
project
n=58Patients ≥18 years
old, admitted
to or in the ICU
and placed on
mechanical
ventilation for at
least 48 hours
Primary diagnosis
of stroke with coma,
or myocardial
infarction with coma;
pregnant; history
of developmental
disability or dementia;
receiving therapeutic
hypothermia; those
dependent in
activities of daily living
prior to admission;
actively dying
Early mobility protocol

Details: introduction
of progressive mobility
exercises following
successful interruption of
sedation and awakening
Usual care, details
not specified.
CAM-ICU (once
daily at 08:00)
None.
Chai 2017pre-post, quasi-
experimental QI
project
n=301Any patient
>18 years old
admitted to a
comprehensive
mixed-ICU
(medical, surgical,
cardiac, neurology)
No exclusion criteria.ABCDEF bundle

Components:
(A) assessment/
management of pain; (B)
spontaneous awakening
& breathing trials; (C)
choice of sedation; (D)
delirium monitoring
& management; (E)
early mobility; (F) family
engagement
Details not
specified.
CAM-ICU (at least
once per shift)
Yes: pain
management
and choice of
sedation
Damshens
et al. 2018
RCTn=80Any patient >15
years old admitted
to ICU trauma
service
History of cognitive
impairment,
depression, taking
psychotropic drugs,
drug abuse, and
alcohol abuse;
patients with visual
or hearing loss; ICU
admission for <48
hours
Music therapy

Details: two 45 minute
sessions per day (once
in morning and once at
night); music tracks were
mainly instrumental and
selected by a music expert
Details not
specified.
CAM-ICU (at least
once per shift)
None.
Eghbali-Babadi
et al. 2017
RCTn=68Non-intubated
ICU patients 18–70
years old after
elective open
heart surgery,
with immediate
family available for
intervention
History of addiction
to drugs, alcohol, and
cigarette smoking;
presence of delirium,
consciousness
level disorder, or
mental disease
before surgery;
history of blindness
or deafness; family
history for surgery*;
death; post-surgery
acute complications
Family visitation

Details: additional
30–40 minute morning
visitation session by an
approved, study-educated
immediate family member

Components: visual
and hearing aids; hand
holding; reorientation;
presence of meaningful
personal items;
encouragement to
express feelings and
regain independence
Visitation
by hospital
regulations,
and visits were
recorded.
CAM-ICU (twice
daily, once in
evening and once
in morning after
family visit)
None.
Fallahpoor
et al. (2016)
action research
study
n=100Patients >18 years
old admitted to
ICU after elective
CABG surgery
Blindness or
deafness; history of
mental illness, CVA,
or kidney failure;
return to operating
room; bleeding or
tamponade; requiring
balloon pump or
mitral valve repair;
death
3-part management
program:

Before surgery: effective
patient communication;
identify and control
delirium risk factors; staff
and patient education;

During surgery: identify
delirium risk factors;
stabilize hemodynamics;
time management;

After surgery: identify
delirium risk factors;
optimize environment;
reorientation; effective
communication;
psychological & medical
support; physical stability
& activity; safety; sleep
and sensory experiences
Details not
specified.
CAM-ICU (every 8
hours)
Not specified.
Giraud et al.
2016
RCT, pilot time-
cluster
n=223ICU patients ≥70
years old after
elective or urgent
cardiac surgery
Severe visual
impairment
preventing self-
recognition in a
mirror; physical or
communication
barriers impeding
intervention; severe
mental disability;
history of psychiatric
illness requiring prior
hospitalization
Structured mirror usage

Details: use of and
education on using
mirrors to support
mental status, attention,
physical mobilization, and
multisensory feedback
and integration; use on
awakening, change in
mental status, and during
nursing procedures and
activity therapies

Mirror details: (a) 23x41
cm personal mirror for
viewing of the face; (b)
160x50 cm posture
mirror to provide visual,
proprioceptive feedback
Current standard
post-surgical ICU
care, including
no prescriptions
around the use
of mirrors, and
allowing control
patients who
brought a mirror
from home to use
it per their normal
habits.
CAM-ICU (twice
daily)
None.
Guo et al. 2016RCTn=160Oral cancer
patients aged
65–80 years
scheduled for
tumor resection
surgery
History of CNS
disorders or mental
illness; MMSE score
<24 or dementia of
various etiologies;
history of endocrine
and metabolic
disorders; recent use
of glucocorticoids;
alcohol or drug
dependence;
secondary surgery
or severe infectious
complications;
illiteracy or language
barriers; severe
hearing or visual
impairment; projected
SICU stay ≤ 48 hours
Multicomponent
non-pharmacologic
intervention:

Components: cognitive
prehabilitation; post-
operative reorientation;
eye & ear aids; additional
communication avenues
for verbally impaired
patients; decreased
environmental noise;
improved sleep protocols;
eye masks & earplugs;
limited restraint &
catheter use; music
therapy; immediate nasal
feeding if able
Usual care
consisted of
standard hospital
services provided
by physicians,
nurses, and
support staff
(e.g., physical
therapists,
pharmacists, and
dietitians).
CAM-ICU (twice
daily, once in
morning and
once in evening)
None.
Hamzehpour
et al. 2017
RCTn=100ICU patients >18
years old
GCS ≤ 7; history of
mental illness; death;
ICU stay <24 hours;
sedative injection
Roy adaptation model

Components: delirium
education; fluid and
electrolyte balance;
nutrition protocol;
sleep protocol; activity
and mobility protocol;
monitoring of excretion,
oxygen, circulatory, and
endocrine condition
Routine care:
performing
physician orders;
daily assessment
of consciousness;
systematic patient
evaluation
NEECHAM
confusion scale
(twice daily, once
in morning and
once in evening)
Not specified.
Karadas &
Ozdemir 2016
RCTn=94Patients ≥65 years
old with an ICU
stay of at least 24
hours
Presence of delirium
before the procedure;
amputated extremity;
invasive mechanical
ventilation;
procedures limiting
mobility; RASS score
of -4 and -5; advanced
osteoporosis; terminal
illness; known
cognitive disorders
(dementia and
psychosis); increased
intracranial pressure;
active gastrointestinal
system bleeding;
arrhythmia; active
myocardial ischemia
ROM exercises

Details: 10 repetitions per
exercise for approximately
30 min once daily; if
patient did not tolerate
the intervention, it ceased
& continued the next day

Components: passive,
assisted-active, or active
ROM exercises performed
on the four extremities in
the supine position
Usual care, details
not specified.
CAM-ICU (once
daily)
None.
Khan et al.
(2014)
pre-post,
implementation
study
n=702Mechanically
ventilated ICU
patients ≥ 18 years
old
Hearing impaired;
legally blind;
admitted with
alcohol intoxication;
prisoners; diagnosed
as having an Axis 1
Psychiatric disorder
‘Wake Up and Breathe'
protocol

Components: daily
sedation interruption &
spontaneous awakening
trial, followed by
spontaneous breathing
trial depending on the
patient’s response to the
former
Continuous
analgesic
and sedative
infusions based
on physicians'
discretion.
CAM-ICU (twice
daily)
Yes: sedation
management
Kram et al.
(2015)
pre-post,
implementation
study
n=83All adult patients
admitted to the
ICU
Safety screening
failures; patients
without clearance
from their attending
surgeon; physicians
could write an order
out of any bundle
component they
believed was not in
the patient’s best
interest
ABCDE bundle

Components: (A & B)
spontaneous awakening
and breathing trials;
(C) interdisciplinary
coordination; (D)
delirium screening &
management; (E) early
mobility
Details not
specified.
ICDSC (twice
daily at 05:00 and
17:00)
Yes: sedation
management
Lisann-
Goldman et al.
2017
mixed-methods
pilot study
n=25Patients ≥40
years old, with
planned ICU
admission after
elective cardiac
surgery with
cardiopulmonary
bypass, and a
MMSE score of ≥24
Intracranial or
emergency surgery;
severe visual or
auditory disorder
or handicaps;
illiteracy or minimal
reading or writing
ability; presence of a
major, uncontrolled
psychiatric condition;
severe cognitive
impairment
Mindfulness exercises

Pre-operative: discussion
exercises with the
study PI; listen to audio
discussing Langerian
mindfulness (8 minutes
48 seconds)

Post-operative: discussion
exercises with the study
PI, twice daily in the
morning and afternoon
Preoperative:
Engaged in
discussion
related to cardiac
surgery and
then listened to
audio describing
the step-by-
step process
of undergoing
cardiac surgery
(8 minutes 34
seconds)

Post-operative:
neutral
conversation
on the same twice
daily schedule
CAM-ICU (twice
daily)
None.
Mailhot et al.
2017
randomized pilot
study
n=30All patients
admitted to the
surgery ICU or
surgery unit
with: (1) post-
surgical delirium
confirmed by a
DSM-V medical
diagnosis; (2)
undergoing either
CABG or heart
valve surgery; and
(3) has a family
caregiver available
for scheduled
bedside visits
Planned transfer
to another hospital
less than 3 days
after delirium
onset; preoperative
diagnosis of cognitive
impairment;
irreversible
postoperative
cognitive damage
Family caregiver

Details: an approved,
study-educated family
member applied
bedside strategies
to aid the patient in
reorientation, observe
and communicate signs
of delirium with nursing
staff, and present family
memories
Both groups
received usual
care, including
pharmacological
and non-
pharmacological
interventions
suggested in best
practice guidelines
described in the
Registered Nurses’
Association of
Ontario guidelines
(RNAO, 2016).
CAM-ICU (once
daily)

DI (once positive
delirium result is
recorded)

DSM-V (confirm
delirium
diagnosis once
positive ICDSC
result is recorded)

ICDSC (once daily)
Yes: use of
pharmacological
interventions in
usual care; usual
care is applied
to both study
groups.
Moon & Lee
2015
RCT, single-blindn=123Patients ≥18 years
old on day of ICU
admission with ICU
stay of ≥48 hours
Persistent RASS
score of -4 or -5;
severe visual and
auditory problems;
serious psychiatric or
neurologic diagnosis;
score of ≤23 on
the MMSE-Korean;
admission to the
isolation ward due
to infection; death or
discharge on day of
admission; inability
to conduct CAM-ICU
when in a very violent
status & RASS +3 or
+4
Multicomponent bundle

Components: cognitive
assessment &
reorientation; sensory
aids; indirect night
lighting; consistent care
staff; items from home;
minimize bed relocation;
address & manage
delirium risk factors
early; nutritional, fluid,
electrolyte balance; early
ambulation; increased
awareness of drugs
associated with delirious
side effects; early
infection detection; limit
catheter use; monitor for
hypoxemia; pain control
Typical nursing
care included
regular checking
of consciousness
and orientation
without
attempting
to (1) reorient
the patient; (2)
communicate
using nonverbal
communication
skills; (3) provide
visual or hearing
aids; (4) assign
the same nurse
in charge
throughout stay;
(5) minimize
bed movement;
or (6) carefully
use particular
medications (e.g.,
anticholinergic
agents and
opiates)
CAM-ICU
(frequency not
specified)
Yes: careful
use of drugs
associated with
delirious side
effects; pain
control
Munro et al.
2017
RCT, prospectiven=30Patients >18 years
old within 24 hours
of ICU admission
Anticipation of
imminent patient
death; medical
contraindication to
the intervention (i.e.
psychiatric auditory
hallucinations, or
profound deafness);
inability to speak
either English or
Spanish
Automated reorientation
messages

Details: reorientation
script recorded by either
a family member or a
bilingual female unknown
to the subject; played
8x from 09:00-16:00
stating the subject’s
preferred name & that
the message is recorded;
the following details
were randomly ordered
to prevent repetition:
information about ICU
environment, expected
visual and auditory
stimuli, availability of staff
& family
Usual care, details
not specified.
CAM-ICU (twice
daily)
None.
Parry et al.
2014
case-matched
control study
n=16Patients ≥18 years
old admitted to
the ICU with a
diagnosis of sepsis,
mechanically-
ventilated for >48
hours, and in ICU
for ≥4 days
Physical limitations
(presence of external
fixator, pacemaker,
defibrillator, open
wound or skin
abrasions); obesity
(BMI>40, too heavy
for cycling machine);
anticipation of
imminent patient
death
Functional electrical
stimulation (FES) cycling

Details: supine, motorized
cycle ergometer attached
to a current-controlled
stimulator(20-60 min
once daily 5x a week);
stimulation occurred at
specific times, based on
normal activation patterns
regulated by the bicycle
software & causing
visible muscle contraction
(quadriceps, hamstrings,
gluteals, calves)
Usual care
following
institutional
protocols for
resuscitation
& sepsis
management,
routine
physiotherapy
once subject was
considered awake
using De Jonghe
5-point criteria
CAM-ICU (once
daily)
None.
Pun et al. 2019prospective,
multicenter
cohort study
via national QI
collaborative
n=10840Any adult patient
admitted to
medical, surgical,
cardiac, or
neurologic ICU
for at least 2
consecutive 24-
hour days
Death or ICU
discharge within
24 hours of ICU
admission, active life
support withdrawal
and/or comfort-care
measures within
24 hours of ICU
admission
ABCDEF bundle

Components: (A)
assess/prevent/manage
pain; (B) spontaneous
awakening & breathing
trials; (C) choice of
analgesia/sedation; (D)
delirium monitoring
& management; (E)
early mobility; (F) family
engagement
NA: analytic
comparison
is between
complete bundle
performance and
partial bundle
performance
CAM-ICU or
ICDSC (≥2 times
daily)
Yes: pain
management
and choice
of analgesia/
sedation
Rivosecchi
et al. 2016
pre-post,
prospective
observational QI
project
n=483Any patient
admitted to the
medical ICU
Any amount of
time admitted to
an ICU (internal or
external) before
MICU admission;
documented
history of cognitive
impairment; already
admitted to MICU
when study period
began; MICU stay ≤24
hours; presented
to the MICU delirious;
no recorded ICDSC
measurements
M.O.R.E. bundle + staff
education

Components: (M) music;
(O) opening/closing of
blinds; (R) reorientation/
cognitive stimulation; (E)
eye/ear care
Daily bedside
multidisciplinary
rounds, sedation
algorithms,
mobilization
protocols, and
every 4-hour
delirium screening
using the ICDSC.
ICDSC (every 4
hours)
Yes: sedation
algorithms
Rosa et al.
2017
pre-post study,
prospective
n=286any patient ≥18
years old admitted
to the ICU
Patients with aphasia,
pre-existing delirium,
exclusively palliative
treatment at ICU
admission, expected
ICU stay <24 hours,
those who remained
unarousable ≥48
hours (RASS –4 or –5),
and those readmitted
to the ICU after
enrollment in the
study.
Extended visitation hours

Details: two or fewer
visitors at a time, for
12 hours/day (09:00-
21:00); families allowed
to participate in
multidisciplinary bedside
rounds; no time limit
for terminal patients,
conflicts, or delirium
Regular visitation
schedule

Details: two or
fewer family
visitors at a time
for 4.5 hours
per day, broken
up into three
visitation blocks
(09:00-11:00,
16:00-17:30,
21:00-22:00);
no time limit for
terminal patients,
conflicts, or
delirium
CAM-ICU (twice
daily, once every
12 hours)
None.
Simons et al.
2016
RCTn=734any patient ≥18
years old admitted
to the ICU
An expected ICU
stay of <24 hours;
anticipated life
expectancy <48
hours; severe hearing
or visual impairment;
severe mental
impairment
Dynamic Lighting
Application (DLA)

Details: gradual exposure
to blueish-white light from
07:00-11:30 and 13:30-
16:00 (peak 1700 lux,
4300 K); from 11:30-13:30
the light was dimmed to
300 lux, 3000 K.
The control group
was consistently
exposed to 300 lux, 3000 K
lighting.
CAM-ICU (at least
3 times daily)

non-ICU patients:
DOS scale,
consultation
with geriatrician,
treatment with
pharmacological
agents for
suspected
delirium
(frequency not
specified)
None.
Sullinger et al.
2017
pre-post study,
retrospective,
observational
n=89critically ill patients
≥18 years old with
acute delirium in
an open surgical-
trauma ICU
Missing or
incomplete CAM-
ICU assessments;
pregnancy; history
of dementia,
schizophrenia,
bipolar disease or
a prolonged QTc at
baseline (>500 ms
regardless of gender).
Management bundle +
nursing education

Components: non-pharm
interventions (replacing
vision/hearing aids,
healing arts consult
[massage therapy,
craniosacral therapy,
therapeutic touch, music
therapy], mobility plan
[repositioning, sitting,
ambulation], light and
blinds adjustment,
revised quiet hours
[13:00- 15:00 and 22:00-
04:00], earplugs, family
presence); initiate anti-
psychotic medications
if non-pharmacologic
therapies fail
Details not
specified.
CAM-ICU (twice
daily, once per 12-
hour shift)
Yes: initiate
anti-psychotic
medications
if non-
pharmacologic
therapies fail
Zhang et al.
2017
pre-post study,
prospective
n=278any patient
≥18 years old
admitted to the
cardiothoracic ICU
after CABG
ICU stay of ≤24 hours;
history of mental
disease or delirium
at admission; patient
could not awaken
from surgery within
the first 24 hours
after surgery
Management bundle

Components: delirium
risk factor screening &
modification (pain control,
early catheter removal,
reorientation, increased
family visits, minimizing
care-related interruptions,
comfortable nursing,
monitoring for sleeping
difficulties)
Details not
specified.
CAM-ICU:
delirium (not
specified)

DSR-R-98: severity
(when a positive
CAM-ICU is
recorded)
Yes: medication
management

Abbreviations: BADLs: basic activities of daily living; CABG: coronary artery bypass graft; CAM: Confusion Assessment Method; CNS: central nervous system; CVA: cerebrovascular accident; DI: Delirium Index; DOS scale: Delirium Observation Screening scale; DRS/DRS-R-98: Delirium Rating Scale-Revised-98; DSM-V: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition; FAQ: Functional Activity Questionnaire; GCS: Glasgow Coma Score; ICDSC: Intensive Care Delirium Screening Checklist; ICU: intensive care unit; IQCODE: Informant Questionnaire on Cognitive Decline in the Elderly; LOS: length of stay; MMSE: Mini-Mental State Examination; OT: occupational therapy; QI: quality improvement; RASS: Richmond Agitation-Sedation Scale; RCT: randomized controlled trial; SICU: surgical ICU.

* exclusion criteria of 'family history for surgery': cannot confirm whether for elective open heart surgery, or surgery in general.

Table 2. Summary of delirium outcomes.

Individual interventionsIncidencePrevalenceDurationSeverity
automated reorientation44----yes*--
dynamic lighting48n.s.--n.s.--
family, caregiver42NA--NAn.s.
family, RVM vs EVM47yes------
family, additional structured visit32yes------
mindfulness exercises41NA------
mirrors34n.s.--n.s.--
mobility, early and intensive OT24yes--yesn.s.
mobility, early29n.s.--n.s.--
mobility, ROM exercises38n.s.--n.s.--
mobility, FES45n.s.--yes--
music therapy31n.s.------
Bundled interventionsIncidencePrevalenceDurationSeverity
ABCDE26--yesyes*--
ABCDE27--yesyes--
ABCDE40--NA----
ABCDEF30yes------
ABCDEF37yes------
M.O.R.E.46yes--yes--
multicomponent25yes--yes--
multicomponent28n.s.--yes--
multicomponent43n.s.------
multicomponent49----yes--
multicomponent non-pharmacologic35yes*--yes--
post-CABG delirium management33yes------
risk factor screening & target modification50yes--n.s.n.s.
Roy adaptation model36yes*----yes*
'Wake Up and Breathe' protocol39n.s.n.s.----

Legend: n.s., not significant, p>0.05; yes, significant, p<0.05; NA, not analyzed for significance; --, not measured in this study; yes*, some measured time-points are significant.

Table 3. Results on incidence and prevalence of delirium.

Incidence
InterventionNumber of patients
enrolled
Group ResultsStatistical Results
ABCDEF bundle30b n=351
(CG n=151; IG n=150)
Day
08:00–11:00
CG 77 (51%)
IG 16 (10.7%)
χ2(1) = 57.32   p <.001*
Night
20:00–23:00
CG 89 (58.9%)
IG 27 (18%)
χ2(1) = 53.25 p <.001*
ABCDEF bundle, complete vs
partial performance37i
n=10840Not reported AOR 0.60 (0.49–0.72)
p < 0.0001
Dynamic lighting48c n=734
(CG n=373; IG n=361)
CG 123 (33%)
IG 137 (38%)
OR 1.24 (0.92, 1.68)
p=0.16
Family, additional structured
visit32c
n=68
(CG n=34; IG n=34)
Day 2
10:00
CG 8 (23.53%)
IG 4 (11.76%)
χ2=3.98 p=0.04*
Day 2
17:00
CG 11 (32.35%)
IG 4 (11.76%)
χ2=8.38 p<0.05*
Day 3
10:00
CG 7 (20.58%)
IG 3 (8.83%)
χ2=4.12 p=0.03*
Family, caregiver42an=30
(CG n=14; IG n=16)
CG 71.4%
IG 43.8%
NA
Family, restricted visitation vs
extended visitation47c
n=286
(CG n=141; IG n=145)
CG 29 (20.5%)
IG 14 (9.6%)
RR 0.50 (0.26, 0.95)
p=0.03*
Mindfulness exercises41dn=25
(CG n=13; IG n=12)
CG 0 (0%)
IG 0 (0%)
NA
Mirrors34cn=223
(CG n=108; IG n=115)
CG 17 (16%)
IG 20 (17%)
OR 1.15 (0.54, 2.43)
p=0.705
Mobility, early & intensive
OT24c
n=140
(CG n=70; IG n=70)
CG 14 (20%)
IG 2 (3%)
p=0.001*
Mobility, early mobility29cn=58
(CG n=27; IG n=31)
CG 24 (89%)
IG 29 (93.5%)
χ2(1, N=38) = 0.398
p=0.53
Mobility, FES cycling therapy45cn=16
(CG n=8; IG n=8)
CG 7 (87%)
IG 2 (25%)
p>0.05
Mobility, ROM exercises38cn=94
(CG n=47; IG n=47)
CG 10 (21.3%)
IG 4 (8.5%)
χ2=3.02 p>0.05
M.O.R.E. bundle + nursing
education46e
n=483
(CG n=230; IG n=253)
CG 36 (15.7%)
IG 24 (9.4%)
p=0.04*
Multicomponent bundle (staff
education & environmental
changes)25c
n=148
(CG n=69; IG n=79)
CG 50 (72.46%)
IG 30 (37.97%)
p=0.01*
Multicomponent bundle +
education28c
n=123
(CG n=57; IG n=66)
CG 27 (47%)
IG 38 (58%)
p=0.26
Multicomponent bundle43cn=121
(CG n=63; IG n=60)
CG 21 (33.3%)
IG 12 (20.0%)
p=0.10
Multicomponent, non-
pharmacologic bundle35c
n=160
(CG n=79; IG n=81)
Day 1CG 13 (16.25%)
IG 4 (7.50%)
p=0.035*
Day 2CG 9 (11.25%)
IG 5 (6.25%)
p=0.374
Day 3CG 4 (5.00%)
IG 1 (1.25%)
p=0.364
TotalCG 25 (31.25%)
IG 10 (15.00%)
p=0.006*
Music therapy31cn= 80
(CG n=40; IG n= 40)
CG 16 (40%)
IG 15 (37.5%)
χ2=0.053 p>0.818
Post-CABG delirium
management bundle33b,c
n=100
(CG n=50; IG n=50)
Overall
incidence
CG 34 (68%)
IG 19 (38%)
p=0.001*
-30% change
Patients
with
‘x’ number
of
delirious
events
0CG 16 (32%)
IG 31 (62%)
1–3CG 24 (48%)
IG 12 (24%)
4–7CG 8 (16%)
IG 5 (10%)
8+CG 2 (4%)
IG 2 (4%)
OverallNAp=0.008
Risk factor screening & target
modification50c
n=278
(CG n=137; IG n=141)
CG 41 (29.93%
IG 19 (13.48%)
χ2=11.112 p=0.001*
Roy adaptation model36fn=100
(CG n=50; IG n=50)
Days 1–6
(AM & PM)
See full reference text.p>0.05
Day 7 AMCG 31 (68.9%)
IG 15 (36.6%)
p<0.008*
Day 7 PMCG 30 (61.9%)
IG 20 (42.9%)
p<0.05*
'Wake Up and Breathe'
protocol39g
n=702
(CG n=262; IG n=440)
CG 14 (23.0%)
IG 33 (19.6%)
AOR 0.718
(0.326,1.578)
p=0.40
Prevalence
InterventionNumber of patients
enrolled
Group ResultsStatistical Results
ABCDE bundle26cn=296
(CG n=146; IG n=150)
CG 91 (62.3%)
IG 73 (48.7%)
p=0.03*
ABCDE bundle27en=159
(CG n=80; IG n=79)
CG 38%
IG 23%
p=0.01*
ABCDE bundle40en=83
(CG n=47; IG n=36)
CG NA
IG 7 (19%)
NA
‘Wake Up and Breathe’
protocol39h
n=702
(CG n=262; IG n=440)
CG 94 (66.7%)
IG 167 (55.3%)
AOR 0.650 (0.413, 1.022)
p=0.06

Abbreviations: AOR: adjusted odds ratio; CABG: coronary artery bypass graft; CG: control group; FES: functional electrical stimulation; IG: intervention group; FES: functional electrical stimulation; NA: not analyzed; OR: odds ratio; OT: occupational therapy; ROM: range of motion; RR: relative risk.

Legend: a = Percent of patients with at least one positive CAM-ICU screening; b = Number of recorded delirium events; c = Number of patients with at least one positive CAM-ICU screening; d = Number of patients with at least one positive CAM-ICU screening, patients with RASS -4 or -5 counted as ‘not delirious’; e = Number or percent of patients with at least one positive ICDSC screening; f = Number of patients with at least one NEECHAM score of < 25; g = Number of patients with a positive CAM-ICU after an initial negative result; h = Number of patients with any CAM-ICU positive result; i = not reported; * = significant difference, p<0.05; † = 95% confidence interval; ‡ = contradictory numbers reported, see referenced text.

Table 4. Results on duration of delirium.

Duration
InterventionNumber of patients
enrolled
Duration measurementGroup ResultsStatistical Results
ABCDE bundle26n=296
(CG n=146; IG n=150)
duration in days
median (IQR)
CG 3 (1, 6)
IG 2 (1, 4)
p=0.52
% ICU days spent delirious
median (IQR)
CG 50% (30, 64.3)
IG 33.3% (18.8, 50)
p=0.003*
ABCDE bundle27number of days a patient
had positive ICDSC score
mean ± SD (range)
CG 3.8 ± 2.9 (1.0, 14.0)
IG 1.72 ± 0.8 (1.0, 4.0)
p<0.001*
Automated
reorientation44
n=30
(CG n=10; UG n=10; FG
n=10)
delirium-free days
mean (SD)
CG 1.6 (1.13)
UG 1.6 (1.07)
FG 1.9 (0.99)
p=0.0437*
days of delirium
mean (SD)
CG 0.9 (1.28)
UG 0.6 (0.84)
FG 0.3 (0.48)
p>0.05
Dynamic lighting48n=734
(CG n=373; IG n=361)
duration in hours
median (IQR)
CG 2 (1, 5)
IG 2 (2, 5)
p=0.87
Family, caregiver42n=30
(CG n=14; IG n=16)
duration in days
mean (SD)
CG 4.14 (4.04)
IG 1.94 (1.34)
--
Mirrors34n=223
(CG n=108; IG n=115)
duration in days
median (IQR [range])
CG 2 (1, 8 [1, 3])
IG 1 (1, 3 [1, 25])
RR 0.66 (0.26, 1.70)
p=0.393
proportion of ICU stay
mean (SD)
CG 0.65 (0.29)
IG 0.54 (0.30)
Co-eff -0.10 (-0.67, 0.47)
p=0.729
Mobility, early &
intensive OT24
n=140
(CG n=70; IG n=70)
ratio of delirium duration to
exposure time
CG IRR 6.66 (5.23, 8.3)
IG IRR 0.15 (0.12, 0.19)
CG p=0.000*
IG p=0.000*
Mobility, early29n=58
(CG n=27; IG n=31)
duration in days
mean ± SD (range)
CG 2.70 ± 2.18 (0, 9)
IG 3.58 ± 2.68 (0, 9)
p=0.18
Mobility, FES45n=16
(CG n=8; IG n=8)
duration in days
median (IQR)
CG 6.0 (3.3, 13.3)
IG 0.0 (0.0, 3.0)
p=0.042*
Mobility, ROM
exercises38
n=94
(CG n=47; IG n=47)
duration in hours
median (range)
CG 38 (9, 120)
IG 15 (3, 144)
Z= -0.997 p>0.05
M.O.R.E. bundle46n=483
(CG n=230; IG n=253)
duration in hours
median (IQR)
CG 20 (9.5, 37) 16.1% of
ICU LOS
IG 16 (8, 24) 9.6% of
ICU LOS
p<0.001*
Multicomponent
bundle (staff education
& environmental
changes)25
n=148
(CG n=69; IG n=79)
% of days with delirium
mean ± SD
CG 35.84 ± 39.31
IG 26.18 ± 35.38
p=0.001*
Multicomponent bundle
+ education28
n=123
(CG n=57; IG n=66)
delirium-free days out of 30
mean (range)
CG 24 (22, 26)
IG 27 (25, 28)
p=0.002*
Multicomponent non-
pharmacologic bundle35
n=160
(CG n=79; IG n=81)
duration in hours
mean ± SD
CG 60.2 ± 15.8
IG 28.1 ± 8.6
p<0.001*
Multicomponent bundle
+ nursing education49
n=89
(CG n=38; IG n=51)
number of delirious days
mean ± SD
CG 8.2 ± 5.7
IG 4.5 ± 4.4
p<0.001*
Risk factor screening &
target modification50
n=278
(CG n=137; IG n=141)
duration in days, from first
positive CAM-ICU to recovery
(2 consecutive days with
negative CAM-ICU)
all durations (1–5 days),
both groups
p=0.876

Abbreviations: CG: control group; FES: functional electrical stimulation; FG: family voice group; IG: intervention group; IQR: interquartile range; IRR: incidence risk ratio; OT: occupational therapy; ROM: range of motion; RR: relative risk; SD: standard deviation; UG: unknown voice group.

Legend: * = significant, p<0.05; † = 95% confidence interval.

Table 5. Results on severity of delirium.

Severity
InterventionNumber of patients
enrolled
MeasurementGroup ResultsStatistical
Results
Family, caregiver42n=30
(CG n=14; IG n=16)
DI
mean (SD)
Overall
(Days 1–3)
NAp=0.27
Day 1CG 2.07 (4.05)
IG 10.56 (3.5)
NA
Day 2CG 8 (6.34)
IG 5.38 (5.45)
NA
Day 3CG 5.5 (7)
IG 3.43 (4.96)
NA
Mobility, early & intensive
OT24
n=140
(CG n=70; IG n=70)
DRS
mean (range)
CG 10 (8, 13)
IG 9 (6, 12)
p=0.7
Risk factor screening &
target modification50
n=278
(CG n=137; IG n=141)
DRS-R-98
Number (%)
Overall (Results from
all 3 severity groups)
NAZ= -0.792
p=0.428
MildCG 10 (7.30)
IG 7 (4.96)
NA
ModerateCG 21 (15.33)
IG 8 (5.67)
NA
SevereCG 10 (7.30)
IG 4 (2.84)
NA
Roy adaptation model36n=100
(CG n=50; IG n=50)
NEECHAM
Confusion Scale
Day 1–3, AM & PM
(6 time points)
See full
reference text.
p>0.05
Day 4–7, AM & PM
(8 time points)
See full
reference text.
p≤0.028*
(range p=0.000
to p=0.028)

Abbreviations: DI: Delirium Index; DRS: Delirium Rating Scale; DRS-R-98: Delirium Rating Scale-Revised-98; NA: not analyzed; OT: occupational therapy.

Legend: * = significant difference, p<0.05; † = confidence interval not specified.

Of these 27 articles, 24 assessed incidence and/or prevalence within their cohorts2443,4548,50, 16 assessed for duration2428,34,35,38,42,4446,4850, and four for severity24,36,42,50. Additionally, 12 focused on the effect of single interventions24,29,31,32,34,38,41,42,44,45,47,48 while 15 considered bundled, multicomponent interventions2528,30,33,3537,39,40,43,46,49,50. Individual interventions included mobility protocols, distinct family visiting policies, dynamic lighting, music therapy, automated reorientation messages, mindfulness exercises, and the structured use of mirrors in recovery. These individual interventions also comprised multiple components of the bundled interventions. A summary of study details can be found in Table 1.

Measurements for incidence, prevalence, and duration were based upon multiple methods of delirium screening, including the Confusion Assessment Method (CAM), CAM-ICU, Intensive Care Delirium Screening Checklist (ICDSC), and Neelon and Champagne (NEECHAM) scales. Incidence and prevalence were similarly defined in all studies except for one, and are recorded separately in Table 3; only one study looked at both incidence and prevalence39. Severity was assessed by using the Delirium Index (DI), the Delirium Rating Scale (DRS), the Revised Delirium Rating Scale (DRS-R-98), and NEECHAM scale (Table 5).

Of the 27 included studies, 11 were RCTs or randomized pilot studies24,31,32,3436,38,4244,48, eight were pre-post prospective studies26,28,39,40,46,47,49,50, and two were quasi-experimental25,30. The remaining six were a case-matched control study, an evidence based protocol, a mixed-methods pilot study, a prospective multicenter cohort study, a retrospective cohort study, and an action research study27,29,33,37,41,45.

Risk of bias assessment

The ten RCTs and the randomized pilot study underwent a risk of bias assessment performed by all authors. Risks of bias fell into five major groups (selection bias, performance bias, detection bias, attrition bias, and reporting bias), and based on a study’s scores in each of these groups it was labeled as having an overall high, low, or unclear risk of bias. Four were considered low risk of bias24,34,42,48, two had a high risk of bias32,44, and five had an unclear risk of bias31,35,36,38,43. The most common source of bias was performance bias due to the impossibility of blinding participants or personnel to certain treatments. Common sources of unclear and high risk of bias included the methods of randomization and allocation concealment, as well as how missing data was handled.

Individual interventions

Early mobility. The effect of early mobility protocols on delirium was the most commonly studied individual intervention. Four of the studies included in our review individually assessed the efficacy of early mobility24,29,38,45 in treating and preventing delirium; of these, two were RCTs24,38, one was an evidence-based project29, and one was a case-matched control study45. They assessed delirium through CAM24 and CAM-ICU29,38,45.

The pilot RCT performed by Álvarez et al. investigated the effect of early mobilization through early and intensive occupational therapy (OT), including polysensory stimulation, body positioning, cognitive stimulation exercises, basic activities of daily living, upper extremity motor exercises, and family involvement, on non-intubated, elderly patients (≥ 60) in addition to the study center’s standard, non-pharmacological delirium prevention care24. Delirium associated outcomes included incidence, duration, and severity; they found significant differences in incidence and duration of delirium, with both p-values ≤ 0.001, but no significant difference in severity (Table 3Table 5).

Another RCT by Karadas and Ozdemir assessed the effect of range of motion (ROM) exercises on delirium in elderly ICU patients (≥ 65 years)38. Interventional care included ROM exercises for 30 minutes daily after establishing the patient’s ability to complete 10 repetitions on each of the four extremities while lying in bed. They reported no statistically significant differences between cohorts for delirium associated outcomes (Table 3 & Table 4).

Campbell addressed early mobilization in mechanically ventilated ICU patients with an evidence-based project29. They measured the effect of a tiered protocol of ROM exercises, bed mobility exercises, seated balance activities, transfer activities (such as bed to chair), standing exercises, and ambulation on delirium incidence and duration but found neither to be significant (Table 3 & Table 4).

The effectiveness of functional electrical stimulation (FES) to promote mobility and recovery in mechanically ventilated patients with sepsis was evaluated by Parry et al. in a case-matched control study45. The intervention included use of a motorized cycle ergometer to directly stimulate four major lower limb muscles (quadriceps, hamstrings, gluteals, and calves) five times weekly for 20–60 minutes a session dependent on the individual patient’s tolerance. While delirium incidence was not significantly affected (Table 3), the median days of delirium differed between arms (6.0 in control and 0.0 in intervention) (Table 4).

Family involvement. Of the 12 studies in our review which focused on individual interventions, three studied the effect of family involvement on delirium in adult ICU patients. One was a randomized pilot study42, one an RCT32, and one was a pre-post study47. All three studies utilized CAM-ICU in their assessment of delirium.

Mailhot et al. constructed a randomized pilot study to explore the effect of a family caregiver (FC) assisting with delirium management after being ‘mentored’ (MENTOR_D) by nurses in the ‘MENTOR_D’ intervention42. They assessed the efficacy of this intervention on all delirious, adult coronary artery bypass graft (CABG) patients admitted to the surgical ICU by measuring the outcomes of duration, occurrence, and severity of delirium over three days42. This intervention enrolled 14 patient-nurse (control) care dyads and 16 patient-FC care dyads, which had the FC apply bedside strategies to aid the patient in reorientation. In addition to reorientation, the FC was asked to observe and communicate signs of delirium with nursing staff, present family memories, and speak clearly and simply. Delirium duration and occurrence on post-operative Day 2 improved clinically between groups (duration, mean days from 4.14 to 1.94; occurrence, from 71.40% to 43.80%); however, this result was not assessed for statistical significance and the severity result was not found to be significant (Table 3Table 5).

The RCT performed by Eghbali-Babadi et al. investigated a modified family visitation policy, implementing an additional 30–40 minute special visit by an approved family member, and its effect on delirium incidence in non-intubated adults aged 18–70 after elective open heart surgery32. They found a statistically significant reduction in delirium incidence in the intervention group with a p-values of 0.04, <0.05, and 0.03 at three different time points (Table 3).

Rosa et al. also measured the effect of a modified family visitation policy on delirium incidence, although their population was less restrictive and included any adult ICU patient47. Their pre-post study included the extension of visitation hours from 4.5 hours per day over three visitation blocks to 12 hours per day between 09:00–21:00. This resulted in a statistically significant difference in delirium incidence, improving from 20.5% to 9.6% (Table 3).

Environmental approaches (lighting, music therapy, automated reorientation). Three RCTs assessed the impact of environmental factors on delirium in the ICU, assessed by CAM-ICU, through manipulation of light48, music therapy31, or automated reorientation44.

In Simons et al.’s dynamic lighting application RCT, adult ICU patients were exposed to variations in high intensity, blueish-white lighting while delirium incidence and duration were measured48. The intervention group was exposed to a peak of 1700 lux (brightness)/4300 K (color temperature) from 09:00–11:30 and 13:30–16:00, and a daytime minimum of 300 lux/3000 K from 11:30–13:30; the control group was exposed solely to 300 lux/3000 K (Table 1). Neither the cumulative incidence of ICU-acquired delirium nor the duration were significantly affected, and the trial was ended early after the intervention was deemed futile (Table 3 & Table 4).

In another RCT, Damshens et al. introduced therapeutic music selected by a music expert, twice a day for 45 minutes to assess the effect on delirium incidence in adults admitted to ICU trauma service31. Patients in the control group received conventional care for the duration of their admission. There was no resultant change to delirium incidence between the two groups (Table 3).

Munro et al. developed a novel patient reorientation strategy in an RCT, which utilized bilingual (Spanish or English) messages pre-recorded by either family members or females unknown to the adult ICU subjects44. The recordings included an introduction with the patient’s name and location, with several additional randomly ordered statements in order to reorient the patient to their unfamiliar surroundings and reason for hospitalization. All three arms (two intervention groups and one control group) were compared and it was found that the family voice group had a significant improvement in delirium free days (p= 0.0437) but not mean days of delirium (Table 4).

Self-involvement approaches (mirror usage, mindfulness exercises). The remaining two studies on the effect of individual interventions assessed the impact of self-involvement approaches, including mirror usage34 and mindfulness exercises41, on ICU delirium measured by CAM-ICU. One study was a pilot RCT34, while the other was a mixed-methods pilot study41.

In a pilot time-cluster RCT, Giraud et al. tested the effect of introducing structured mirror usage into post-operative recovery in elderly ICU patients (≥70 years) after cardiac surgery34. Mirror usage was standardized by developing a protocol for nurses and physiotherapists, aiming to use both small, personal mirrors as well as larger posture mirrors in order to help the patient with reorientation and self-awareness, enhance multisensory feedback on minor procedures, and augment passive and active physical therapies. The control cohort received usual care, including allowing control patients who brought a mirror from home to use it per their normal habits. After comparing the usual care group with the mirrors group, no significant improvement was found in delirium incidence, ICU days with delirium, or the proportion of the total ICU length of stay that the patient spent delirious (Table 3 & Table 4).

The mixed-methods study by Lisann-Goldman et al. had subjects who were 40 years of age or older participate in Langerian mindfulness discussion exercises both prior to and after elective cardiac surgery with cardiopulmonary bypass41. In addition to discussion exercises, patients listened to an audio file before surgery. This audio file walked them through techniques on how to re-assess one’s situation and improve their outlook by taking emotional control of the situation, encouraging the patients to focus on the process of change and allowing oneself to accept new ideas and remain confident about the unknown. The discussion exercises continued post-operatively twice daily. In contrast, the ‘informational control’ group went through normal pre-operative discussions followed by an audio file describing the process of cardiac surgery. They found that no subject developed delirium in either the interventional or the ‘informational control’ group so the effectiveness of the treatment could not be assessed.

Bundled protocols

‘Wake Up and Breathe’ protocol. Khan et al. designed a ‘Wake Up and Breathe’ protocol in a pre-post interventional study to assess for any change in delirium and sedation in mechanically ventilated, adult ICU patients39. They modified elements of the Awakening and Breathing Controlled trial (ABC) to implement a spontaneous awakening trial and daily sedation vacation followed by a spontaneous breathing trial, depending on the patient’s response51. Delirium was assessed by CAM-ICU, and both the incidence and prevalence of delirium were analyzed, with the study finding no significant change in either measured outcome (Table 3).

ABCDE(F) bundles. Five of the 15 studies which examined delirium bundles studied the effectiveness of ABCDE(F) bundle protocols on reducing delirium. ABCDE(F) bundles have multiple components including: spontaneous awakening (A) and breathing (B) trials, interdisciplinary coordination of sedatives and medications (C), delirium screening and management (D), early mobilization (E), and family engagement and involvement (F)52. Of these five studies, two were pre-post studies26,40, one was a prospective multicenter cohort study37, one was a quasi-experimental quality improvement project30, and one was a retrospective cohort study27. Three measured delirium outcomes using CAM-ICU26,30,40, one utilized ICDSC27, and one multicenter study used either CAM-ICU or ICDSC37.

Balas et al. assessed the impact of an ABCDE bundle on adult ICU patients, evaluating the prevalence and duration of delirium in both total days and percent of ICU days spent delirious, with a pre-post study26. The prevalence and percent of ICU days spent delirious were improved in the post period with p-values of 0.03 and 0.003 respectively (Table 3 & Table 4). However, the overall duration of delirium was not significantly different (Table 4).

The retrospective assessment of an ABCDE bundle by Bounds et al. evaluated its effect on delirium prevalence and duration in an adult ICU population27. Both the prevalence and duration were significantly decreased in the ABCDE bundle group (p= 0.01 and 0.001 respectively; (Table 3 & Table 4).

Kram et al. also looked at a similar patient cohort, all adult patients 18 or older admitted to the ICU, in a pre-post ABCDE bundle study with a smaller subject population (Kram, n=83; Balas, n=296; Bounds, n=159)40. They assessed the effectiveness of the ABCDE bundle on delirium by measuring delirium prevalence and comparing it to a control based on literature values. The measured delirium prevalence of 19% (Table 3) fell outside their cited literature values of 20–80%.

Chai initiated an ABCDEF bundle in a mixed ICU setting and analyzed delirium incidence in the adult patients in a pre-post, quasi-experimental quality improvement project30. Delirium incidence was compared between morning and night occurrences (morning 08:00–11:00; night 20:00–23:00); both showed significant improvement in the intervention group with a p-value <0.001 for both morning and evening measurements (Table 3).

A prospective cohort study performed by Pun et al. through a national quality improvement initiative compared complete ABCDEF bundle performance with proportional ABCDEF bundle performance in adult ICU patients with an ICU stay of at least 48 consecutive hours37. Complete bundle performance was defined as a patient-day where 100% of the eligible bundle elements were performed, whereas proportional performance was anything less37. Their study was comprehensive, including 10,840 patients for delirium outcome analysis across 68 ICUs in the United States and Puerto Rico37. When comparing the incidence of delirium between patients with complete and proportional ABCDEF bundle performance, they found that patients with complete performance were significantly less likely to develop delirium (Table 3)37. In an additional analysis, Pun et al. found a dose-dependent reduction of delirium incidence when the more eligible ABCDEF bundle elements were performed (p < 0.0001)37. It is worth noting that this study had a high rate of ‘missingness’ for delirium data and the analysis team chose not to perform multiple imputations37.

Other bundled protocols. The remaining nine bundle studies developed new, unique bundles. They included four pre-post studies28,46,49,50, three RCTs35,36,43, one quasi-experimental study25, and one action research study33. Seven assessed delirium incidence and duration using CAM-ICU25,28,33,35,43,49,50, one used NEECHAM36, and one used ICDSC46.

A quasi-experimental study designed by Arbabi et al. developed a multi-component delirium management bundle comprised of staff education and environmental and non-pharmacologic care changes25. They measured the effectiveness of their bundle by assessing delirium incidence and duration in all adult patients admitted to the general ICU, finding a significant difference in both outcomes (p = 0.01 and 0.001 respectively; Table 3 & Table 4).

Bryczkowski et al. assessed the effectiveness of their bundle, which included a staff-patient-family education program, medication management strategies, and non-pharmacological sleep enhancement protocols, on delirium incidence and delirium free days in patients over the age of 50 years28. The research team found no significant improvement in delirium incidence (Table 3), although the average total number of delirium-free days out of 30 changed significantly from 24 to 27 between groups (p=0.002; Table 4).

Another bundle study developed by Fallahpoor et al. focused specifically on adults admitted to the ICU after elective CABG in an action research study. Their post-CABG delirium management bundle was assessed in an action research study and had three elements focusing on pre-, intra-, and post-operative methods to identify delirium risk factors, optimize time spent in surgery, and introduce staff education and post-operative environmental changes33. Delirium related outcomes included the incidence ratio and total number of recorded delirium events, with significant differences found in both (p=0.001 and 0.008 respectively; Table 3).

In the RCT conducted by Guo et al., the effect of a bundle consisting of cognitive prehabilitation, post-operative cognitive stimulation activities, environmental changes, music therapy, and non-pharmacologic care changes on delirium incidence and duration after oral tumor resection in patients aged 65–80 years was studied35. The incidence of delirium improved significantly overall, but was only significantly different on post-operative day one compared to days two and three (p=0.035, p=0.374, p=0.364 respectively; Table 3); the duration of delirium also differed significantly (p< 0.001; Table 4).

Hamzehpour et al. designed an RCT and implemented the Roy adaptation nursing model for all adult ICU patients, which focuses on balance of nutrition, electrolytes, and fluids while promoting activity, sleep hygiene, and monitoring of circulation and endocrine function36. Their primary delirium-specific outcomes were incidence and severity, and they analyzed both outcomes for two time points (morning & night) for seven days. Their research only showed significant improvements to incidence on day seven, both morning and night (p<0.008 and p<0.05; Table 3), but delirium severity, assessed with NEECHAM, improved through the morning of day four to the night of day seven at all measured time points (every time point, p≤0.028; Table 5).

Moon and Lee implemented a bundle which included early cognitive assessments and reorientation, sensory aids, environmental changes, consistent care staff and location, familiar items from home, nursing care changes, and early mobility as part of an RCT aimed at assessing delirium incidence in adult ICU patients with at least a 48 hour stay43. Their study did not show a significant difference between the intervention and the control group who received usual care (Table 3).

In a pre-post, observational quality improvement project, Rivosecchi et al. combined staff education with a non-pharmacologic bundle to look at incidence and duration of delirium in any adult patient aged 18 or older admitted to the medical ICU46. Their M.O.R.E. bundle included (M)usic, (O)pening blinds, (R)eorientation and cognitive stimulation, and (E)ye and ear care. Both delirium incidence and duration were significantly impacted, with incidence decreasing from 15.7% to 9.4% and a reduction in duration from 16.1% of the ICU stay to 9.6% (p = 0.04 and <0.001 respectively; Table 3, Table 4).

Sullinger et al. enrolled adult surgical-trauma ICU patients with acute delirium in a pre-post retrospective study, tailoring their bundle to incorporate staff education with sensory aids, healing arts techniques, mobility, environmental changes, and family presence49. Their bundle also included the initiation of anti-psychotic medications if non-pharmacologic tactics failed. The only specifically delirium related outcome was the number of days spent delirious, resulting in a significant decrease from 8.2 to 4.5 median days (Table 4).

Any patient 18 years or older admitted to a cardiothoracic ICU after CABG surgery was analyzed for incidence, duration, and severity of delirium by Zhang et al. in a prospective pre-post study50. Their delirium bundle targeted risk factor screening and modifications, including increased family visits, reorientation, and changes to nursing care. The only significant improvement was to incidence of delirium which dropped from 29.93% to 13.48% (Table 3), while the intervention had no impact on duration or severity (Table 4 & Table 5).

Discussion

Summary of findings

Our review included 27 trials that evaluated the effect of various non-pharmacological treatment and management protocols on delirium in an ICU setting. Assessment of the efficacy of these protocols in the last five years was most commonly done by considering incidence and/or prevalence. A total of 25 studies assessed for the effects of these protocols on incidence and/or prevalence, with 11 studying individual approaches and 14 studying bundles. Of these 25 trials, 11 reported significant improvements overall2427,30,32,33,37,46,47,50, nine found no significant improvement28,29,31,34,38,39,43,45,48, and two only found significant change at certain time points35,36; the remaining three did not analyze for statistical significance of their results4042. The 11 effective interventions for incidence and/or prevalence were primarily bundled protocols (eight trials)2527,30,33,37,46,50, followed by family approaches (two trials)32,47, and early and intensive OT (one trial)24. The two studies with time point dependent changes were both bundles, one non-pharmacologic35 and the other introduced the Roy adaptation nursing model36. The multicomponent non-pharmacologic bundle found improvements in incidence both overall and on day one, while the Roy adaptation trial only saw a change in incidence on day seven in both the morning and the evening. Three studies did not analyze for statistical significance4042; however, the family caregiver intervention saw an overall reduction in the percent of subjects who developed delirium from 71.40% to 43.80%42. The study on mindfulness exercises had no subjects in either investigational group develop delirium41, and an ABCDE bundle reported a post-bundle incidence of 19% but stated there was no pre-bundle data with which to compare40. No other studies that looked at delirium incidence were effective.

In addition to incidence and prevalence, another common outcome was a change in the duration of delirium. Sixteen of the reviewed studies evaluated the duration of delirium, eight focusing on individual interventions and eight introducing bundled protocols. Of these 16 studies, eight found significant changes overall24,25,27,28,35,45,46,49, two had significant improvements at select time points26,44, and five did not have significant results29,34,38,48,50; the one remaining study did not assess for statistical significance42. Six of the eight successful trials were bundles and both of the two effective individual therapies were mobility-focused (early and intensive OT, and FES)24,45. Only four studies looked at delirium severity24,36,42,50 with only one finding any significant results, and only finding them at select time-points (Roy Adaptation Model)36.

The pilot RCT performed by Alvarez et al. utilized a unique method for assessing the performance of their intervention. In addition to assessing delirium incidence, they measured the ratio of delirium duration to the amount of time exposed to the treatment (IRR)24. They found that IRR decreased as the time exposed to treatment increased to a significant degree (p= 0.000). This ratio could be explained in three ways. Either the duration of delirium stayed the same as the time exposed to treatment increased, the duration of delirium increased slower than the time exposed increased, or the duration of delirium decreased while the time of exposure increased. However, the last explanation is impossible, due to the duration of delirium being a sum overtime which could not decrease, such that the result must be explained by either a small increase or no increase in the duration of delirium. If the decrease in the IRR is explained by smaller and smaller increases to delirium duration it is likely that the IRR results from either the trend of patients slowly becoming healthier over time, or the conjunction of that with the intervention. However, if the IRR is explained by the delirium duration ceasing to increase, then once it stops the treatment may still be effective, but it is not becoming more effective over time and plateaus in effectiveness.

Implications of results and application to practice

The reviewed studies focused on individual interventions that had a wide range of limitations and were, on the whole, less effective than bundled protocols in the treatment and management of delirium. Many of these studies had limited reliability due to small or extremely small sample sizes29,41,44,45. Additionally, even when results were significant, they often had limited applications to practice due to the prevalence of restricted populations. Three of the individual intervention studies limited their study cohort to elderly adults15,24,38, a population which is at an increased risk of delirium. It is unclear whether these results would apply to younger patients. Studied populations were also commonly narrowed to either exclusively intubated patients45, non-intubated patients24,32 or patients with a particular illness34,42,45. Another possible limitation was in the questionable reliability of delirium assessment criteria. This is mentioned by Campbell who stated that 35% of CAM-ICU were incorrectly labeled as ‘unable to assess’29. The question of reliability was also raised in Lisann-Goldman et al.. This study could not assess the effectiveness of their intervention as no patients developed delirium41. However, this could be explained by the fact that fully sedated patients were considered ‘not delirious’ since CAM-ICU could not be performed. The authors also noted that since it often takes weeks or months to fully integrate new behavioral thought techniques, a study focused on changing thought patterns in days would not entirely reflect the full benefit if any were present41.

Eight of the individual intervention studies were RCTs. This type of study introduces the possibility of additional limitations due to the nature of its design. Two of these RCTs had a high risk of bias32,44 due to a failure to blind patients and personnel, as well as blinding of the outcome assessment and improper allocation concealment. The question of blinding raises another possible limitation of many of these studies, namely the possibility of the Hawthorne effect in patients who knew that they were being observed and receiving an intervention for the treatment/prevention of delirium.

The 15 studies which investigated bundled protocols had, overall, larger sample sizes, fewer cohorts with limited populations, and indicated better reliability in their delirium assessment than the studies which focused on individual interventions. The smallest sample size was 83 patients40; however, this study did not split the sample into multiple cohorts and all patients received the intervention. One study had a sample size of 8949, and all other studies had a sample size of at least 100 patients. A total of five studies restricted their studied population beyond adult ICU patients28,33,35,39,50. Two of these limited their population by age28,35; however, Bryczkowski et al., despite limiting their population by age, included any patients greater than 50 years old, younger than the age when delirium risk is noted to increase53,54. One study limited its population to mechanically ventilated patients39, two considered only patients undergoing CABG33,50, and one studied patients after oral tumor resection35. These population restrictions could limit the generalizability and applicability of the interventions; however, this risk is reduced since bundles were often investigated in multiple studies with similar results.

Only three of the bundle studies were RCTs35,36,43. Each of these RCTs had an unclear risk of bias with the most common risk being the inability to blind participants and personnel. The impossibility of blinding in delirium intervention studies makes RCTs a questionable approach. Eight of the bundle studies, recognizing blinding as an impossibility, chose to conduct pre-post prospective studies rather than RCTs26,28,30,39,40,46,49,50. These studies carried a lower risk of introducing bias to their studies and avoided crossover between arms. The pre-post study performed by Kram et al. had the major limitation of not including a pre cohort and only comparing the results of their intervention with literature values40. Additionally, while they found their measured delirium prevalence to fall outside their included literature values (19%), this prevalence falls within the values provided by the current literature (19- 87%)2. Chai’s pre-post study had a delirium assessment with questionable reliability. While all other studies assessed delirium whenever the Richmond Agitation-Sedation Scale (RASS) was ≥ -3, they reported that patients were unable to be assessed whenever RASS was < -2, resulting in a greater proportion of patients not assessed for delirium30.

In sum, multicomponent, bundled approaches were more successful at improving delirium outcomes compared to individual techniques; however, the effective individual tactic of family engagement was included as a component in the effective bundles. Although a majority of the reviewed bundles were effective, it is difficult to compare results as the trials had large differences in study design, enrollment numbers, and delirium assessment measures.

Given the findings of this systematic review, further research is warranted in order to confirm these results and apply them to other patient populations. For example, patients in non-ICU hospital wards would likely be more capable of mobility or visitation interventional components that in turn increase their sense of independence, wellbeing, and recovery support compared to critically ill persons. Due to the nature of these differences, it is worth considering tangential application of ICU delirium prevention and management interventions dependent on a patient’s level of care and health stability. An additional consideration for future research is to ascertain the level of effectiveness of individual intervention components against differently aged patient subpopulations. It is possible that certain interventional elements may be more effective for older versus younger critically ill adults at risk for ICU delirium due to differences in underlying risk factors and etiologies.

Strengths and limitations

The strengths of our systematic review include thorough search terms and the methodology to assess a vast majority of recent literature in this field.

One limitation of this systematic review is that we only focused on trials within the past five years which excluded some well-cited early studies on delirium. We also did not evaluate other listed outcomes which could provide additional insight into any change in delirium status. Since the condition can be transient and delirium screenings are not performed as frequently throughout the ICU day as other measurements, outcomes such as restraint use or amount of prescribed sedatives or anti-psychotic medications would be beneficial to assess in this setting. While the decision to omit exclusion criteria on study design allowed for assessment of a broader range of trials, it was difficult to compare outcomes when multiple differing designs and measurement tools were used. Although the CAM-ICU was widely used, some studies used alternative tools and there was no standardized way of defining or measuring delirium duration or severity. A different measurement tool was used to evaluate severity in each of the four studies reviewing this outcome, and duration was defined in a multitude of fashions. Combining this realization with the fact that some studies focused on highly specific subpopulations suggests that some trials may need to be replicated in a standardized fashion to account for any differences in methodology or subjective assessments.

Additionally, this review did not clearly delineate between patients with post-operative ICU delirium and those who developed nonsurgical-related ICU delirium. This distinction is imperative, as the risk factors and appropriate treatment approaches may differ for these patient groups. It would be of future benefit to determine such differences, and which interventional components or bundles are best designed for each etiology.

Conclusions

Many ICU delirium treatment and management protocols were developed and tested within the last five years in a variety of study designs. Few trials on individual interventions had positive effects on delirium incidence and duration, but multicomponent bundles were found to be more effective overall while incorporating the effective individual intervention of family engagement. Based on the results of bundle studies, the implementation of multi-component protocols in ICUs can reduce ICU delirium, thereby reducing cost of care, improving overall outcomes, and limiting time spent mechanically ventilated, medicated, or admitted. Despite these results, further research is needed on individual interventions in order to improve specific elements of multicomponent bundles by adding or removing ineffective therapies. Additional research is also warranted to evaluate for any positive effects in more generalized hospital populations.

Data availability

Underlying data

All data underlying the results are available as part of the article and no additional source data are required.

Extended data

OSF: The Effect of Non-Pharmacologic Strategies on Prevention or Management of Intensive Care Unit Delirium: A Systematic Review. https://doi.org/10.17605/OSF.IO/Y7NQ620.

Registration DOI: 10.17605/OSF.IO/C3RHF

This project contains the following extended data:

  • Supplementary Appendix 2 – Database search terms

  • Supplementary Table 1 – Data extraction form

  • Supplementary Table 2 – Risk of bias assessment

Data are available under the terms of the ‘Creative Commons Zero "No rights reserved" data waiver’ (CC0 1.0 Public domain dedication).

Reporting guidelines

OSF: PRISMA checklist for ‘The Effect of Non-Pharmacologic Strategies on Prevention or Management of Intensive Care Unit Delirium: A Systematic Review’. https://doi.org/10.17605/OSF.IO/Y7NQ620

Registration DOI: 10.17605/OSF.IO/C3RHF

Data are available under the terms of the ‘Creative Commons Zero "No rights reserved" data waiver’ (CC0 1.0 Public domain dedication).

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Cupka JS, Hashemighouchani H, Lipori J et al. The effect of non-pharmacologic strategies on prevention or management of intensive care unit delirium: a systematic review [version 3; peer review: 2 approved]. F1000Research 2022, 9:1178 (https://doi.org/10.12688/f1000research.25769.3)
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Reviewer Report 06 Sep 2022
Claudia D. Spies, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin, Berlin, Germany 
Henning Krampe, Charité - Universitätsmedizin Berlin, Berlin, Germany 
Fatima Yürek, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin, Berlin, Germany 
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We would like to thank the authors for the thorough response to our review, as well as for addressing all relevant concerns. The authors did a very good job with the revision, so that the manuscript has improved very much. ... Continue reading
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Spies CD, Krampe H and Yürek F. Reviewer Report For: The effect of non-pharmacologic strategies on prevention or management of intensive care unit delirium: a systematic review [version 3; peer review: 2 approved]. F1000Research 2022, 9:1178 (https://doi.org/10.5256/f1000research.134761.r142132)
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Reviewer Report 18 May 2022
Claudia D. Spies, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin, Berlin, Germany 
Fatima Yürek, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin, Berlin, Germany 
Alawi Luetz, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin, Berlin, Germany 
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Major issues:
  1. The evaluations do not clearly differentiate between ICU delirium in critically ill patients and postoperative delirium in the ICU. The risk factors for critically ill patients with acute organ failure requiring ICU treatment and
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Spies CD, Yürek F and Luetz A. Reviewer Report For: The effect of non-pharmacologic strategies on prevention or management of intensive care unit delirium: a systematic review [version 3; peer review: 2 approved]. F1000Research 2022, 9:1178 (https://doi.org/10.5256/f1000research.30705.r74838)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
  • Author Response 24 Jun 2022
    Azra Bihorac, Department of Medicine, University of Florida, Gainesville, 32608, USA
    24 Jun 2022
    Author Response
    Response to Major Issue #1:  Thank you so much for pointing this out – this distinction is imperative. We added a brief segment to the limitations portion of our discussion ... Continue reading
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  • Author Response 24 Jun 2022
    Azra Bihorac, Department of Medicine, University of Florida, Gainesville, 32608, USA
    24 Jun 2022
    Author Response
    Response to Major Issue #1:  Thank you so much for pointing this out – this distinction is imperative. We added a brief segment to the limitations portion of our discussion ... Continue reading
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Reviewer Report 05 Nov 2020
Elizabeth Mahanna-Gabrielli, Department of Anesthesiology, Perioperative and Pain Medicine, University of Miami Miller School of Medicine, Miami, FL, USA 
Approved
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This manuscript is a systematic review of the effect of non-pharmacologic strategies on prevention or management of delirium in the ICU. The manuscript is comprehensive, well written, and follows appropriate PICOS framework and PRISMA guidelines for a systematic review.
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Mahanna-Gabrielli E. Reviewer Report For: The effect of non-pharmacologic strategies on prevention or management of intensive care unit delirium: a systematic review [version 3; peer review: 2 approved]. F1000Research 2022, 9:1178 (https://doi.org/10.5256/f1000research.28439.r73595)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
  • Author Response (F1000Research Advisory Board Member) 24 Sep 2021
    Azra Bihorac, Department of Medicine, University of Florida, Gainesville, 32608, USA
    24 Sep 2021
    Author Response F1000Research Advisory Board Member
    1. Could the authors clarify if the date range was 5 years from the date of search (Jan 1, 2014 to May 15, 2019) as stated in the manuscript?
    ... Continue reading
COMMENTS ON THIS REPORT
  • Author Response (F1000Research Advisory Board Member) 24 Sep 2021
    Azra Bihorac, Department of Medicine, University of Florida, Gainesville, 32608, USA
    24 Sep 2021
    Author Response F1000Research Advisory Board Member
    1. Could the authors clarify if the date range was 5 years from the date of search (Jan 1, 2014 to May 15, 2019) as stated in the manuscript?
    ... Continue reading

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Alongside their report, reviewers assign a status to the article:
Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions
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