Impact of non-pharmacological interventions on prevention and treatment of delirium in critically ill patients: protocol for a systematic review of quantitative and qualitative research
Bannon et al. Systematic Reviews
Impact of non-pharmacological interventions on prevention and treatment of delirium in critically ill patients: protocol for a systematic review of quantitative and qualitative research
Leona Bannon 0 3
Jennifer McGaughey 2
Mike Clarke 1
Daniel Francis McAuley 0 3
Bronagh Blackwood 0 3
0 Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast , 97 Lisburn Road, Belfast BT9 7BL , Northern Ireland
1 Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast , Belfast BT12 6BJ , Northern Ireland
2 School of Nursing and Midwifery, Queen's University Belfast , 97 Lisburn Road, Belfast BT9 7BL , Northern Ireland
3 Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast , 97 Lisburn Road, Belfast BT9 7BL , Northern Ireland
Background: Critically ill patients have an increased risk of developing delirium during their intensive care stay. To date, pharmacological interventions have not been shown to be effective for delirium management but non-pharmacological interventions have shown some promise. The aim of this systematic review is to identify effective non-pharmacological interventions for reducing the incidence or the duration of delirium in critically ill patients. Methods: We will search MEDLINE, EMBASE, CINAHL, Web of Science, AMED, psycINFO and the Cochrane Library. We will include studies of critically ill adults and children. We will include randomised trials and controlled trials which measure the effectiveness of one or more non-pharmacological interventions in reducing incidence or duration of delirium in critically ill patients. We will also include qualitative studies that provide an insight into patients and their families' experiences of delirium and non-pharmacological interventions. Two independent reviewers will assess studies for eligibility, extract data and appraise quality. We will conduct meta-analyses if possible or present results narratively. Qualitative studies will also be reviewed by two independent reviewers, and a specially designed quality assessment tool incorporating the CASP framework and the POPAY framework will be used to assess quality. Discussion: Although non-pharmacological interventions have been studied in populations outside of intensive care units and multicomponent interventions have successfully reduced incidence and duration of delirium, no systematic review of non-pharmacological interventions specifically targeting delirium in critically ill patients have been undertaken to date. This systematic review will provide evidence for the development of a multicomponent intervention for delirium management of critically ill patients that can be tested in a subsequent multicentre randomised trial. Systematic review registration: PROSPERO CRD42015016625
Delirium; ICU syndrome; Critical illness; Intensive care unit; Non-pharmacological interventions
Description of the condition
Survivors of critical illness frequently experience
‘malfunction of the cognitive processes in the brain’, known
as delirium [
]. The American Psychiatric Association
] defines delirium as ‘a global disturbance of
consciousness characterised by fluctuating mental status,
inattention, and disorganised thinking’ which develops over a
short period of time and tends to fluctuate throughout the
course of the day (p. 127). Delirium is not a disease but a
syndrome with a wide spectrum of possible aetiologies [
Critically ill patients have an increased risk of developing
delirium during their hospital stay. This often results from
sepsis and disturbances in inflammation and coagulation
pathways leading to microvascular thrombosis [
addition, critical illness disrupts circadian rhythm and
sleep patterns and along with sedatives such as
benzodiazepines that are commonly used to treat delirium in septic
patients, can impair immunity and contribute to
The incidence of delirium is difficult to determine. In
the United Kingdom (UK), studies find a 65 % incidence
of delirium in mechanically ventilated intensive care unit
(ICU) patients [
] and international studies have
demonstrated incidence from 25 to 87 % in critically ill patients
]. In a recent point prevalence survey of nine ICUs
in the UK, the incidence of delirium was 29 % in adult
ICU patients. This study also confirmed that delirium
screening practices in the UK remain inconsistent, which
may account for the low incidence rates found .
Other reasons for a broad range in incidence figures
could be differences in incidence in subspecialty ICUs,
populations with variable severity of illness and
underrecognition of the syndrome [
Delirium is potentially modifiable depending on the
individual patients’ circumstances. In recent years, the
need to introduce validated screening programmes in
the ICU has been recognised [
]. In the absence of a
valid screening tool, delirium can go unnoticed in up to
70 % of patients [
]. The gold standard for diagnosis
of delirium is the DSM-IV criteria applied by a trained
psychiatrist, but this method is often not feasible in the
hospital setting as psychiatric services are not available
around the clock. As a result, multiple delirium
detection tools have been developed and validated against
DSM-IV criteria for use in the ICU. The Confusion
Assessment Method for the Intensive Care Unit
(CAMICU) and the Intensive Care Delirium Screening Checklist
(ICDSC) are the most commonly used tools [
cardinal feature of delirium, inattention [
], is included in
both CAM-ICU and ICDSC tools.
Delirium screening and awareness of the associated
risk factors are mutually dependent for the successful
management of delirium. Van den Boogaard [
developed a delirium prediction model for intensive care
patients based on ten risk factors including age, Apache II
score, admission group, coma, infection, metabolic
acidosis, use of sedatives and morphine, urea concentration
and urgent admission. Many of these risk factors are
irreversible, but others, such as use of sedatives and
morphine, could potentially be modified.
Risk factors for delirium can be divided into three
categories, acute illness, host factors including age or chronic
health problems and iatrogenic or environmental factors
]. The iatrogenic or environmental factors include
immobilisation, sensory deprivation, sleep deprivation and
social isolation [
]. Sleep deprivation can be caused
by high levels of background noise, absence of natural
light, patient care activities, mechanical ventilation,
medication, pain, anxiety and stress [
]. These factors have
been found to disrupt normal sleep-wake cycles causing
sleep deprivation and increasing the risk of delirium [
Disrupted sleep in the ICU has been identified as a
modifiable precipitating risk factor for delirium [
In addition to sleep disruption, mechanically ventilated
patients often experience prolonged bed rest and heavy
sedation during their ICU stay and this can lead to
complications such as ICU weakness or delirium [
introduction of physical and occupational therapy in the
earliest days of critical illness has been shown to prevent
sedative-related immobility and reduce incidence of
Patients often wake in ICU in unfamiliar surroundings
with no recollection of the previous days or even weeks,
and this can be extremely confusing for them. Staff need
to focus on helping patients adjust to their new
environment with regular communication. Education and
orientation programmes have shown benefit for delirium
management in ICU by increasing awareness of the
condition and helping staff cater for patients
psychological needs [
]. Targeting these risk factors might
help manage the negative outcomes that are associated
Patients who experience delirium during critical illness
can experience short (during ICU and hospital stay) and
long-term (after hospital discharge) sequelae. Studies have
shown that short-term outcomes for patients who develop
delirium while in ICU are associated with prolonged
duration of mechanical ventilation, ICU admission and
hospital stay [
7, 16, 28, 29
]. Evidence suggests that for every
extra day patients test positive for delirium, it increases
the risk of a prolonged hospital stay by 20 % . Similarly,
Salluh et al. [
] in their systematic review and
metaanalysis of outcomes of delirium in critically ill patients
found that patients with delirium had an increased mean
length of stay (approximately 1 day longer) and increased
mean duration of mechanical ventilation (almost 2 days
longer than patients without delirium), even after
adjusting for variables such as age, sex and Apache II
scores. Prolonged duration of delirium increases the risk
of these negative consequences [
]. Several studies
have also identified a link between delirium and
inhospital mortality [
5, 12, 16, 26, 28, 33, 34
]. These findings
suggest that an increased duration of mechanical
ventilation, ICU admission and hospital stay often contribute to
long-term negative outcomes such as increased mortality
Some critically ill patients have been followed up to
1-year post ICU to study long-term effects of critical
illness. These studies found that delirium is an
independent risk factor for a threefold higher likelihood
of death within 6 months of critical illness even after
adjusting for covariates such as severity of illness,
coma and use of sedatives [
]. Pisani et al. 
found that the number of positive delirium days in
ICU was significantly associated with time to death in
the year following critical illness. Delirium in critical
illness can also predict a tenfold higher likelihood of
cognitive impairment at 1 year [
]. Studies show that
up to six out of every ten patients that survive critical
illness struggle with significant cognitive impairment
for months to years after their critical illness has resolved.
This has significant implications on their quality of life
and health care costs and leads to institutionalisation [
In addition, delirium is a significant predictor of functional
decline and inability to carry out activities of daily living,
at both hospital discharge and 3-month follow-up [
These negative outcomes incur increased costs and more
importantly result in long-term persistent cognitive
deficits such as dementia [
] which can significantly
impact on a patient’s ability to return to their normal lives.
A longer duration of delirium in ICU is associated
with worse outcomes, so removal or reversal of the
underlying cause of delirium remains a top priority for
successful management of the condition [
]. There has
been limited success with pharmacological therapies,
results are inconsistent and therapies can be expensive
]. This lack of evidence on pharmacological therapies
for prevention and treatment of delirium is highlighted
in the 2013 pain, agitation and delirium (PAD)
guidelines of the American College of Critical Care Medicine
]. Prophylactic antipsychotics and dexmedetomidine
have been shown to reduce the prevalence of delirium in
critically ill patients. However, no single pharmacologic
intervention to prevent or treat delirium has been
routinely able to improve mortality rates or hospital
length of stay [
4, 34, 39–45
The American College of Critical Care Medicine’s
pain, agitation and delirium guidelines recommend
nonpharmacological interventions such as early mobilisation
]. Recently published NICE guidelines [
recommend a number of non-pharmacological interventions
to prevent delirium such as ensuring adequate fluid
intake, encouraging exercise or range of motion exercise,
introducing cognitively stimulating activities and
providing appropriate lighting and clear signage. However, it is
worth noting these recommendations are based largely
on studies in non-ICU patients (older adults, acute
]. Although this strategy has not been tested
on critically ill patients, these non-pharmacological
interventions might also benefit ICU patients, but these
patients are exposed to many more risk factors for
delirium and therefore the proven effectiveness of these
interventions in other patients may not be generalizable to
them. Therefore, further research into the use of these
interventions in an ICU population is needed.
Description of the intervention
A non-pharmacological intervention is any non-drug
intervention. Research in other patient populations is
informative for ICU clinicians despite the lack of direct
evidence from the ICU setting [
]. Interventions are
aimed at targeting risk factors associated with delirium
in ICU such as immobilisation, sensory deprivation,
sleep deprivation and social isolation and aimed to
reduce incidence and/or severity of delirium in critically ill
patients. Interventions are not limited to but may include
earplugs, eye masks, noise control strategies, pharmacy
medication review, music therapy, physical therapy,
cognitively stimulating activities, family presence, bright light
therapy, education and orientation programmes.
How the intervention might work
It is hypothesised that a multicomponent
nonpharmacological intervention may reduce incidence
and severity of delirium by targeting known risk factors
such as sensory deprivation, sleep deprivation and
immobilisation in critically ill patients. In other patient
populations, multicomponent interventions have been successful
by targeting modifiable risk factors. For example, Inouye
et al., [
] investigated a risk factor targeted protocol for
prevention of delirium in an acutely ill elderly population.
The protocol targeted sleep deprivation, disorientation,
immobility, dehydration and visual and hearing
impairments. It successfully achieved a 40 % risk reduction in
incidence of delirium in the intervention group. Martinez
et al., [
] halved delirium incidence in an acute hospital
setting by introducing a delirium prevention protocol
delivered by families. Family members were educated about
the signs and symptoms of delirium, orientation with
familiar objects and photographs and providing hearing aids
and eyeglasses. Similarly, Marcantonio et al., [
an 18 % absolute reduction in the incidence of delirium by
introducing a protocol which involved a geriatric
consultation early in the surgical hip fracture patient’s admission.
The protocol aimed to reduce potentially deliriogenic
medications, provide adequate pain relief, control blood
pressure, prevent hypoxemia and ensure presence of
hearing aids and eyeglasses if needed.
Some single intervention studies of non-pharmacological
interventions have also shown promise in the ICU setting,
including early mobilisation, earplugs and orientation
programmes for patients [
22, 26, 27
Why is it important to do this review?
Delirium has a high prevalence in ICU and is associated
with serious negative outcomes and increased costs. Each
delirium incident increases ICU costs 1.3-fold and hospital
costs 1.4-fold [
]. Pharmacological interventions are
costly and have not shown significant benefit for delirium
prevention to date whereas non-pharmacological
interventions such as physical therapy, ear plugs and
orientation are likely to be less expensive and have shown
promise in delirium management in ICU [
22, 26, 27
Additionally, a recently published Cochrane Review on
non-pharmacological interventions for sleep promotion in
critically ill patients found that the use of earplugs and/or
eye masks may have beneficial effects on sleep and
delirium incidence but recommended further research due to
the poor quality of the studies [
]. There is a growing
need and interest in non-pharmacological interventions,
and a systematic review of the literature specifically
addressing delirium in critically ill patients would help guide
ICU staff in delirium management [
]. In addition to
providing guidance for staff, the findings would be useful
for developing an intervention for future evaluation. This
systematic review is both unique and important for
two major reasons. First, it will summarise the current
evidence and provide an effect estimation for
nonpharmacological interventions for delirium targeted at
critically ill patients. Secondly, it will synthesise qualitative
data from staff, ICU survivors and families’ views on
interventions to inform the development and acceptability
of non-pharmacological interventions. An understanding
of these factors is important for determining the success
of the interventions. These interventions are complex, and
quantitative studies often do not provide details on factors
that can influence the success of the interventions such as
workload or implementation process. However, a
knowledge of these factors could help ensure the development
of a successful intervention.
What are the effects of the 11 non-pharmacological
interventions named below*, (which could feasibly be
delivered within the current roles of the multidisciplinary
team in intensive care), on delirium prevention and
treatment in Intensive care units?
* (1) earplugs, (2) noise reduction, (3) eye masks, (4)
lighting control, (5) education, (6) orientation, (7)
cognitive therapy, (8) bright light therapy, (9) music
therapy, (10) physical therapy or exercise and (11)
pharmacy protocol or review.
1. What are ICU survivors and their family members
perceptions of non-pharmacological interventions
for delirium in ICU?
2. What are clinical staff ’s perceptions on acceptability
and sustainability of non-pharmacological
interventions for delirium in ICU?
This protocol was written in accordance to the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses
Protocols (PRISMA-P) checklist (Additional file 1) [
Types of studies
We will include both quantitative and qualitative studies.
The quantitative studies will include clinical trials
(randomised trials and other clinical controlled trials
including controlled before/after studies and interrupted time
series) that evaluate non-pharmacological interventions
for reducing incidence and duration of delirium for
critically ill patients regardless of age. We will exclude cohort
studies, case studies and reports.
The qualitative studies will include studies that use
observation, interviews and focus groups that are grounded
in phenomenology, ethnography, grounded theory, action
research and descriptive research.
Types of participants
Critically ill patients in the intensive or high dependency
unit requiring vasopressors, oxygen therapy, invasive or
non-invasive ventilation will be eligible for this review.
Both adult and paediatric participants will be included in
this review although these will be analysed separately.
We will exclude studies of interventions delivered after
ICU/high dependency unit (HDU) discharge.
In qualitative studies, the types of participants will be
ICU survivors, their families and clinical staff from the
ICU environment who have experience caring for patients
Types of intervention(s) and comparators for quantitative studies
We will include studies of non-pharmacological
interventions that could be reasonably undertaken by clinicians in
the UK NHS, including but not limited to earplugs, noise
reduction strategies, eye masks, lighting control, education,
orientation, cognitive therapy, bright light therapy,
medication review, music therapy and physical therapy.
Interventions can include behavioural, cognitive, psychological and
physical training interventions. Studies may examine one
or a combination of interventions. We will include studies
that compare non-pharmacological interventions with
either different non-pharmacological interventions,
pharmacological interventions (sedatives and antipsychotics) or
with no delirium targeted intervention.
We will exclude studies that require trained
professionals to deliver the intervention such as acupuncturists
or massage therapists that could not reasonably be
delivered within the current roles of the multidisciplinary
team in ICU.
Types of outcome measures for quantitative studies
1. Primary outcomes
The primary outcome is the incidence and/or duration
of delirium. Delirium must be measured by any delirium
screening tool that has been validated against DSM-IV
criteria for delirium [
] such as the Confusion Assessment
Method for the ICU (CAM-ICU), the Intensive Care
Delirium Screening Checklist (ICDSC) or the Neelon and
Champagne Confusion Scale (Neecham).
2. Secondary outcomes
any adverse event reported by the authors
mortality as reported by the authors
subjective sleep quality (measures) as reported by
participants to authors
cognitive function (measures) as reported by the
quality of life measured by a validated tool
Qualitative phenomena of interest
The perception and experiences of ICU survivors, their
families and ICU clinical staff are the main qualitative
phenomena of interest. As each group has unique
perceptions and experiences, the phenomenon of interest
will vary. Non-pharmacological interventions are
complex, and there are several factors that can influence the
success of these interventions in ICU. For clinical staff,
their perception of the acceptability and sustainability of
non-pharmacological interventions for delirium would
include phenomenon related to user friendliness and
impact on workload, and their views on how the
interventions and process of implementation worked and did not
work as applicable are the phenomena of interest. For
ICU survivors, the phenomena of interest are memories
of non-pharmacological interventions, their views on
value and worth of these interventions, views on how
they impacted their ICU delirium and views on overall
acceptability of these interventions. For families, the
phenomena of interest are their degree of involvement
with non-pharmacological interventions, i.e. were they
involved in education on delirium or orientating their
relatives, satisfaction regarding their involvement, their
views on how the interventions worked and their
satisfaction and views on acceptability and value of the
interventions. A deep understanding of these factors is crucial for
interpreting the study findings. Quantitative studies do
not provide information on how these factors can
influence the success of the interventions; however, a
knowledge of these factors could help decipher the reasons why
an intervention was or was not successful.
We will search the Cochrane library, MEDLINE (via OVID
SP 1966 to present) (Additional file 2), EMBASE (via
OVID SP, 1974 to present), CINAHL (via EBSCO, 1981 to
present), PsycINFO, (via OVIDSP, 1967 to present), AMED
(Allied and Complementary Medicine Database) (via
EBSCO host, 1985 to present) and ISI Web of Science
(1950 to present). Additional information will be sought
from searches of grey literature databases (Opengrey) and
NHS databases (NHS Evidence and NICE Guidelines).
Various synonyms for delirium will be searched to
include ICU syndrome, acute encephalopathy, cognitive
failure, acute brain syndrome, acute confusional state,
reversible dementia, ICU psychosis, altered mental state,
pseudosenility, toxic encephalopathy, septic
encephalopathy, transient organic brain syndrome and acute brain
failure. Synonyms for non-pharmacological interventions
will include earplugs or ear protective devices, eye masks,
relaxation therapy, cognitively stimulating activities, sound
masking, orientation programmes, education, bright light
therapy, sleep promotion, noise reduction or control,
lighting control, therapeutic touch, family presence,
exercise or physical therapy, music, behavioural or cognitive
therapy, medication review and pharmacological services
or protocol or guidelines. Synonyms for critical illness will
include critically ill, intensive or critical care and intensive
care or critical care unit.
We will attempt to identify ongoing and closed but
unpublished studies by searching the major clinical trials
registries such as the metaRegister of Controlled Trials
(mRCT) (www.isrctn.com/page/mrct), ClinicalTrials.gov
(https://clinicaltrials.gov/) and the World Health
Organisation (WHO) International Clinical Trials Registry Platform
(ICTRP) (http://apps.who.int/trialsearch/). We will also
search the reference lists of any identified RCTs and contact
primary authors for missing or additional data.
Selection of studies
One authors (LB) will examine the titles retrieved and
exclude any titles that are irrelevant. Two authors (LB,
JMcG) will independently examine the abstracts
identified from the search. We will retrieve and evaluate the
full text of potentially relevant studies. Two authors
(LB, JMcG) will independently assess their eligibility
according to the review’s eligibility criteria and resolve
any disagreements by discussion. A third author (BB)
will settle any disagreements. Where appropriate, LB will
contact study authors by telephone or email to clarify
study eligibility. We will record reasons for study
exclusion in the table ‘Characteristics of excluded studies’.
Data extraction will be independently undertaken by two
authors (LB, JMcG).
The data extraction form will be divided into sections
to include randomised studies,
non-randomised/observational studies and qualitative studies. Data will be
extracted from each quantitative study using a data
extraction form which will include general study
information, study characteristics, participant’s
characteristics, intervention and settings, complications and
outcome data/results. Data will be extracted from
each qualitative study on study setting, population,
phenomena of interest, study design, methods, finding
Assessment of risk of bias in included quantitative studies
All included studies will be assessed for internal validity
and risk of bias using domain-based evaluation as
described in the Cochrane Handbook for Systematic
Reviews of Interventions, version 5.1.0, chapter 8 [
Cochrane risk of bias form will be used to evaluate each
included study. Each study will be assessed as low, high
or uncertain risk for the adequacy of sequence generation,
allocation concealment, blinding, incomplete outcome
data, selective outcome reporting and other bias. Two
authors will critically appraise included studies using this
tool (LB, JMcG). The Newcastle Ottawa Scale [
] will be
used to assess risk of bias in non-randomised studies such
as controlled before and after studies and intermittent
time series studies.
For qualitative studies, quality assessment will be judged
using a tool adapted from the Critical Appraisal Skills
Programme (CASP) [
] framework and Popay [
framework for critical appraisal of qualitative studies and
previously used in Jordan et al., [
] (included in
Additional file 3). Using this approach, studies were defined
as high, moderate or low quality studies as follows; high:
criteria was clearly applied and described or
communicated from primary author; moderate: criteria not
reported clearly and unable to communicate with primary
author and finally, low: criteria not applied or applied
Data analysis—quantitative studies
Measures of treatment effect
We will use changes in scores from validated delirium
screening tools, such as CAM-ICU (Confusion Assessment
Method for the Intensive Care Unit), NEElon and
CHAMpagne confusion scale (NEECHAM) or ICDSC (Intensive
Care Delirium Screening Checklist) to evaluate
intervention effect. In the event that change scores are not
available, we will use final value data.
Effect measures for dichotomous outcomes
Where possible, the treatment effect for dichotomous
outcomes will be expressed as a risk ratio (RR) with
95 % confidence intervals (CIs).
Effect measures for continuous outcomes
The treatment effect for continuous outcomes will be
displayed as a mean difference with 95 % CI. Where
continuous outcomes are measured using difference scales,
the treatment effect will be expressed as a standardised
mean difference (SMD) with 95 % CI if the results of
studies are combined.
Effect measures for ordinal outcomes and measurement scales
If performing meta-analysis, we will analyse longer
ordinal scales as continuous data and we will combine
adjacent categories and make them into dichotomous
data for shorter ordinal scales. Where ordinal scales are
summarised using methods for dichotomous data, we
will use risk ratios, odds ratios or risk difference to
describe the intervention effect. When ordinal scales are
summarised using methods for continuous data, we will
calculate mean difference or standardised mean difference
to estimate the intervention effect.
Unit of analysis issues
When alternative measurement scales are used, we will
contact the study authors to obtain their participant
level data and try to convert the results to standardised
units. If a study with more than two intervention groups
is included in meta-analysis, we will try to combine
relevant groups to create a single pairwise comparison. For
cluster randomised trials, we will use the appropriate
unit of analysis.
Dealing with missing data
Wherever possible, we will contact the original authors
to request missing data. If more than 20 % of the data
are missing from a study, we will exclude the study from
the meta-analysis and perform an available case analysis
on remaining studies. If possible, we will estimate
missing statistics (such as standard error or confidence
Assessment of heterogeneity
We will assess heterogeneity of each trial and the
intervention effects by compiling ad examining forest plots.
We will first explore clinical heterogeneity by assessing
clinical and methodological characteristics of the included
studies (for example trial design and quality, participant’s
characteristics, intervention or outcome measurements).
We will only attempt to incorporate data into a
metaanalysis if there is negligible clinical heterogeneity among
the selected studies.
We will use chi2 test (P < 0.1, significant heterogeneity)
to assess statistical heterogeneity [
]. If the chi2 test is
significant, we will use the I2 statistic to measure
inconsistency across the studies. I2 greater than 50 % indicates
significant heterogeneity. We will use a fixed-effect model
if the studies are homogenous.
Assessment of reporting biases
We will attempt to obtain and include data from
unpublished trials through grey literature searches to reduce
the risk of publication bias. We will use funnel plot
analysis to assess publication bias when there are greater
than ten studies included in the meta-analysis. In
interpreting funnel plots, we will explore other reasons for
asymmetry such as selection bias, methodological quality
and heterogeneity; artefactual and chance.
Subgroup analysis and investigation of heterogeneity
If sufficient studies are available, we will perform separate
analysis on paediatric patients, patients receiving
mechanical ventilation versus no mechanical ventilation and
studies of interventions aimed at prevention or treatment
We will test how robust the evidence is by performing
sensitivity analysis according to the risk of bias arising
from sequence generation and allocation concealment
(adequate or unclear or inadequate). We will compare
fixed-effect model results to random-effects model
results. If necessary, we will undertake sensitivity analysis to
examine the effects of excluding study subgroups.
Summary of findings tables
For quantitative studies, we will use the principles of the
GRADE system [
] to assess the quality of the body of
evidence associated with specific outcomes reported in
the trials. We will include the following outcomes:
incidence of delirium, duration of delirium, mortality,
quality of life, adverse events and cognitive outcomes in
our review and generate a summary of findings (SoF)
table using the GRADE software.
Data synthesis for qualitative studies
A thematic synthesis approach will be undertaken [
Coding and thematic development will be conducted
manually in three rigorous stages. In the first stage, two
reviewers (LB, JMcG) will independently code and
arrange the data into themes that involves a continual
process of attributing codes to small sections of meaning
within the text, moving back and forward across studies
and constantly comparing data and codes. In the second
stage, the reviewers will work collaboratively, to group
codes into logical and meaningful clusters analytical
themes relating to the aims of the review will be
developed. These will deliver evidence-based
recommendations for patient-centred interventions that consider the
needs of staff and patients. The third stage will involve
assessment of the Confidence in the Evidence from
Reviews of Qualitative research (CERQual) [
] which will
be used to provide an assessment of confidence for
individual review findings from qualitative evidence synthesis;
the themes will be summarised in the form of a qualitative
findings table. This table is similar to the ‘Summary of
findings’ tables used in Cochrane reviews of effectiveness.
The four components of the CERQual are the
methodological limitations of the qualitative studies contributing to
a review finding, the relevance to the review question of
the studies contributing to a review finding, the coherence
of the review finding and the adequacy of data supporting
a review finding. There are four levels for assessment of
confidence high, moderate, low and very low [
confidence indicates a high likelihood that the review
finding is a reasonable representation of the phenomena
of interest, moderate confidence indicates it is likely that
the review is a reasonable representation of the
phenomenon of interest, low confidence indicates it is possible
that the review finding is a reasonable representation of
the phenomenon of interest and very low confidence
indicates that it is not clear whether the review
finding is a reasonable representation of the phenomenon
of interest [
This systematic review will synthesise research evidence
on the effect of non-pharmacological interventions in all
critically ill patients. To our knowledge, this synthesis
has not been carried out in the ICU population.
Nonpharmacological interventions have been studied in
populations outside of intensive care units, and
multicomponent interventions have successfully reduced
incidence and duration of delirium. The NICE guidelines
] are largely based on studies of non-pharmacological
intervention in non-ICU populations [
the publication of these studies, interest in
nonpharmacological interventions has increased significantly.
This systematic review is important as it provides an
update on non-pharmacological interventions for delirium
targeted at critically ill patients, and it is also unique as it
will provide qualitative data on ICU staff, ICU survivors
and their families’ views on interventions to inform the
development of the multicomponent bundle.
This systematic review has been registered with
PROSPERO, an international prospective register of
systematic reviews (http://www.crd.york.ac.uk/prospero/
Additional file 1: Preferred Reporting Items for Systematic Review and
Meta-Analysis Protocols (PRISMA-P) 2015 checklist. Recommended items
to address in a SR protocol. (PDF 147 kb)
Additional file 2: MEDLINE search strategy. A list of the keywords used
in the MEDLINE search strategy to identify papers for assessment for
systematic review. (DOCX 13 kb)
Additional file 3: Data extraction form. Data extraction form with
section for randomised controlled trials, observational studies and
qualitative studies to assess quality and risk of bias. (DOCX 73 kb)
CAM-ICU: Confusion Assessment Method for the Intensive Care Unit;
CASP: Critical Appraisal Skills Programme; GRADE: Grading of
Recommendations Assessment, Development and Evaluation; HDU: high
dependency unit; ICDSC: Intensive Care Delirium Screening Checklist;
ICU: intensive care unit; PRISMA: Preferred Reporting Items for Systematic
Reviews and Meta-Analyses; SoF: summary of findings; UK: United Kingdom.
LB has attended study days sponsored by Orion pharmaceuticals.
LB and DM conceived the idea for this review. LB drafted the protocol under
the supervision of BB, DM, JMcG and MC. All authors read and approved the
final manuscript. Neither the funding body, sponsor nor institution had any
involvement in the development of this protocol.
We thank Patricia Watt and Richard Fallis, subject librarians at Queen’s University
Belfast Medical Library and the Belfast Health and Social Care Trust.
This work is being conducted as part of a Doctoral Research Fellowship
awarded to LB, funded by the Public Health Agency in Northern Ireland,
Research and Development Division.
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