BIS monitoring versus clinical assessment for sedation in mechanically ventilated adult patients in the intensive care unit and its impact on clinical outcomes and resource utilization

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the effects of Bispectral Index monitoring (BIS) compared with clinical sedation assessment on mortality, duration of mechanical ventilation, intensive care unit (ICU) and hospital length of stay (LOS), ventilator-associated pneumonia, adverse events, amount of sedative agents used, cost and longer-term functional outcomes and quality of life as reported by study authors for mechanically ventilated adult study participants in the ICU.

Background

Description of the condition

A significant proportion of the patients admitted to an intensive care unit (ICU) undergo mechanical ventilation (Esteban 2002; Metnitz 2009). It is common practice to administer sedative and analgesic drugs, to these patients, to improve their comfort and their interaction with the ventilator. Different sedative and analgesic drugs are used for this purpose (Gommers 2008; Patel 2012). Careful titration of analgesia and sedation is important to prevent pain and discomfort in this population of patients, but oversedation has been associated with increased mortality and morbidity (Kollef 1998; Kress 2000). Optimizing sedation practice may reduce mortality, and may reduce duration of mechanical ventilation and ICU length of stay resulting in reduced cost and improved resource utilization (Jackson 2010). The recommended strategy to titrate sedation is to use scales or scores based on clinical criteria (Jacobi 2002). Many sedation tools have been developed, but not all have been validated and tested in clinical practice (Barr 2013). There is variability in the specific domains (e.g. consciousness, cognition, and comprehension) they assess (Sessler 2008) and in their implementation (about 88% of units use a sedation scale, with variability in the sedation scale used) (Martin 2007; Reschreiter 2008; Soliman 2001). Furthermore, these scales provide a subjective assessment of patient sedation, and their usefulness in patients undergoing muscle relaxation or who require deep sedation is limited.

Description of the intervention

With the aim to overcome the restraints of the subjective sedation scales, many techniques and devices [e.g. Bispectral Index (BIS), State Entropy (SE), Auditory evoked potentials (AEPs), Narcotrend Index (NI), Patient State Index (PSI)] have been developed with the purpose of providing an objective measurement of patients' sedation (Carrasco 2000). The Bispectral Index (BIS) is possibly the most studied and adapted.

BIS brain monitors are a family of monitoring devices based on the processing of an electroencephalographic signal.

The device uses three or four electrodes applied to the patient's forehead. The electrodes record the raw electroencephalogram (EEG) signal and process it through a proprietary algorithm, producing a dimensionless number, ranging from zero to 100, where 90 to100 indicates a state of wakefulness and zero represents absence of brain electrical activity. BIS monitoring is available in different hardware and software versions (LeBlanc 2006). The set up and maintenance cost of BIS monitoring is quite high. The monitor cost is around US $6,500.00 and a sensor which includes four electrodes costs around US $25.00 per set (Sedation Equipment & Supplies 2014), but this cost may be offset by a reduction in the usage of sedative drugs. In one study BIS monitored titration of sedatives in ICU patients resulted in 18% reduction in cost over two months period (about US $150.00 per patient) mainly as a result of reduction in lorazepam, midazolam and propofol usage (Kaplan 2000).

BIS is quite well established for monitoring anaesthesia depth (Punjasawadwong 2007), but there are differences in patient characteristics in critical care compared to anaesthesia. Critical care patient's brain may be abnormal. Delirium and neurological impairment are extremely common in the intensive care setting (Singhal 2014).  Sepsis is often characterized by an acute brain dysfunction (Sonneville 2013). There are several other conditions which can also cause encephalopathy in critical care patients (Fugate 2013; Hu 2013; Ma 2013; Stevens 2008; Ziaja 2013). Effect of hypoglycaemia, temperature, EMG activity and drugs like catecholamines on BIS scores might vary (LeBlanc 2006 ; Barr 2013). Also there are already well established validated clinical sedation scores available in critical care, hence it is not clear if BIS monitoring in critically ill patients is equally as effective as in anaesthesia.

How the intervention might work

Significant under-sedation occurs using subjective analysis of sedation in ICU (Kaplan 2000). BIS monitoring has been reported as better than clinical assessment for ICU patients undergoing short-term mechanical ventilation in terms of reduction in use of amount of sedatives and time to wakefulness (Zhao 2011). It has also been reported that BIS can reliably differentiate inadequate from adequate sedation (Karamchandani 2010); helps in faster emergence and improved recovery from sedation; and reduces recall phenomenon thereby reducing the post traumatic stress disorder (Kaplan 2000). When compared with four commonly used subjective clinical scales [Ramsay sedation scale (RSS), Richmond agitation sedation scale (RASS), Sedation agitation scale (SAS), Adaptation to Intensive care Environment scale], BIS showed significant correlation with all the scales (Yaman 2012). In another study comparing BIS with Richmond agitation sedation scale (RASS) in mechanically ventilated critically ill patients, BIS correlated well with RASS (Karamchandani 2010). With the production of an objective measurement in the form of a dimensionless number, BIS might be able to overcome some of the limitations of the subjective clinical sedation scales and provide a more reliable and consistent guidance for the titration of sedation in ICU.

Why it is important to do this review

Benefits of BIS monitoring in anaesthetized patients has been confirmed by a Cochrane review (Punjasawadwong 2007). Although several studies have evaluated the use of BIS monitoring in the ICU, no systematic review has been undertaken to establish its benefit for intensive care patients.  Use of BIS in intensive care has many advantages. Using BIS to guide sedative administration would allow optimization of drug delivery to the needs of the individual patients in order to avoid unnecessary deep or light sedation. Compared to clinical assessment BIS can distinguish between lightly and deeply sedated patients (Dewhurst 2000). It has a special role in critically ill brain injured patients with or without sedation (Deogaonkar 2004). It has also been reported to reduce consumption of sedative drugs (Kaplan 2000). All this may lead to reduced duration of mechanical ventilation, ICU length of stay, hospital length of stay and ultimately result in cost saving. By undertaking a well-conducted systematic review we aim to answer the question does the use of BIS monitoring as compared to clinical assessment of sedation leads to improvement in clinical outcomes and resource utilisation?

Objectives

To assess the effects of Bispectral Index monitoring (BIS) compared with clinical sedation assessment on mortality, duration of mechanical ventilation, intensive care unit (ICU) and hospital length of stay (LOS), ventilator-associated pneumonia, adverse events, amount of sedative agents used, cost and longer-term functional outcomes and quality of life as reported by study authors for mechanically ventilated adult study participants in the ICU.

Methods

Criteria for considering studies for this review

Types of studies

We will include all randomized controlled trials (RCTs) comparing BIS monitoring versus clinical assessment for the management of sedation in mechanically ventilated critically ill adult study participants, regardless of language and publication status.

We will include cluster-randomized trials but will not include non-randomized or quasi-randomized trials because of significant risk of bias.

We will also exclude cross-over trials because this methodology is not suitable for investigating the intervention topic of our study.

Types of participants

We will include all adult patients (18 years of age or older) undergoing mechanical ventilation in an ICU for longer than 24 hours, irrespective of the admission diagnosis.

Types of interventions

The intervention group will comprise all participants whose sedation was managed by a strategy based on BIS monitoring with or without the use of a protocol to titrate sedation level. The control group will include all participants whose sedation was managed by any clinical method (using clinical judgement or a specific clinical sedation scoring tool) with or without the use of a titration protocol.

Types of outcome measures

Primary outcomes
  1. Intensive care unit (ICU) length of stay (LOS), measured in days.

Secondary outcomes
  1. Duration of mechanical ventilation, measured in days.

  2. Any-cause mortality.

  3. Incidence of ventilator-associated pneumonia (VAP).

  4. Incidence of adverse events (e.g. self-extubation, unplanned disconnection of indwelling catheters).

  5. Hospital LOS in days.

  6. Number of sedative agents used.

  7. Cost.

  8. Longer-term functional outcomes as reported by study authors.

  9. Quality of life as reported by study authors.

Search methods for identification of studies

Electronic searches

BIS was introduced by Aspect Medical Systems, Inc. (Norwood, Massachusetts, USA) for the first time in 1994. We will search the current issue of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid SP, from 1994 to date), EMBASE (Ovid SP, from 1994 to date) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCOhost, from 1994 to date).

We will apply with relevant databases (MEDLINE and EMBASE) the sensitivity-maximizing strategy described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

We will adopt our MEDLINE search strategy (see Appendix 2) in searching all other databases.

We will search clinicaltrials.gov, controlled-trials.com and other national and regional registries for ongoing trials.

We will impose no language restriction.

Searching other resources

In addition to searches of electronic databases, we will:

  1. search OpenGrey for Information on grey literature;

  2. screen the reference lists of all eligible trials and relevant reviews;

  3. undertake cited reference searching using SciSearch;

  4. identify relevant studies published in dissertations or theses by searching ProQuest Dissertations and Theses database; and

  5. contact experts in the field and the manufacturer of the device.

Data collection and analysis

Selection of studies

Results of the searches described above will be merged using a reference management software, and all duplicates will be removed.

Two review authors (RS, AB) will independently examine titles and abstracts of identified studies to remove obviously irrelevant reports. We (RS, AB) will not be blinded to any details of the published study. After this first screening process, we (RS, AB) will compare our results and will resolve disagreements by discussion. In cases of inability to reach a consensus, we will consult a third review author (RJ).

Once we (RS, AB) have produced a list of potentially relevant studies, we will assign a unique identification number to each study and will retrieve the full text.

The same two review authors will independently assess studies for potential inclusion in the review by using the Cochrane Anaesthesia Review Group (CARG) Study Selection and Data Extraction form (Appendix 2). We will independently note the reasons for exclusion.

We will resolve disagreements in study selection by discussion. In cases of inability to reach a consensus, we will consult a third review author (RJ). If we require more information, we will contact the corresponding author of the relevant study to request needed details.

We will compile a list of all eligible studies, along with a list of excluded studies.

Data extraction and management

Two review authors (RS, AB) will extract data independently according to the predetermined criteria provided on the CARG Study Selection and Data Extraction form (Appendix 2). If any relevant data are missing, we will contact the first author or corresponding author of the study to obtain this information.

We (RS, AB) will resolve disagreements by discussion. If we are unable to reach an agreement, we will consult with a third review author (RJ) .

The following information about study context will be collected.

  1. Country where the study was conducted.

  2. Number of beds in the hospital.

  3. Number of beds in the ICU.

  4. Number of admissions to the ICU per year.

  5. Nurse-to-patient ratio.

  6. Type of ICU (medical, surgical, cardiac, neurological, trauma, burn).

  7. Type of sedation used in both groups, as well as dose and total amount given.

  8. Whether paralytics were used in both groups.

  9. Confounders: drugs (e.g. catecholamines, aminophylline), electromyography (EMG), sleep, temperature, hypoglycaemia, excessive muscle movement, etc.

  10. Diagnosis.

  11. Severity of illness scoring.

Assessment of risk of bias in included studies

Two review authors (RS, SS) will independently assess risk of bias using the Cochrane risk of bias tool (Higgins 2011). We will judge the quality of studies on the basis of risk of bias in the following domains.

  1. Selection bias.

    1. Random sequence generation.

    2. Allocation concealment.

  2. Detection bias.

    1. Blinding of outcome assessors.

    2. Blinding of personnel.

  3. Attrition bias.

    1. Incomplete outcome data.

  4. Reporting bias.

    1. Selective reporting.

  5. Other bias.

We will classify studies as low risk, high risk or unclear risk of bias for the above domains using information available from the studies and, when possible, provided by study authors. We will consider a study as having low risk of bias if all domains (except blinding of personnel, as blinding is not possible because of the nature of the study) are assessed as adequate. We will consider a study as having high risk of bias if one or more domains (except blinding of personnel) are assessed as inadequate and as having an unclear risk if insufficient detail of what happened in the study is reported. Primary analysis will be restricted to studies at low risk of bias. We will perform a sensitivity analysis excluding studies assessed as having high risk of bias. Cases of disagreement about classification of risks will be resolved by discussion amongst the two review authors (RS, SS). If agreement cannot be reached, we will consult with a third review author (MH).

We will include a 'Risk of bias' table as part of the 'Table of characteristics of included studies,' a 'Risk of bias summary' figure and a 'Risk of bias' graph, which will detail all judgements made for all studies included in the review. For the 'Risk of bias' table, we will provide a text box that includes a description of the design, conduct or observations that underline the judgement.

Measures of treatment effect

We will undertake analysis using RevMan 5.2 software.

For continuous outcomes, we will present the treatment effect as a mean difference (MD). For dichotomous outcomes, we will present the treatment effect as a risk ratio (RR). Effect estimates will be presented along with 95% confidence intervals (CIs).

Unit of analysis issues

We will include in our review only RCTs with a parallel-group design. The issue of repeated measures is not relevant for the outcomes under investigation.

It is possible that the review will include cluster-randomized studies. If the review should include these studies, we will perform a sensitivity analysis that excludes cluster-randomized studies to determine the impact of including them in the analysis.

Dealing with missing data

We will perform quantitative analysis on an intention-to-treat (ITT) basis and will contact the study authors to request missing data.

Assessment of heterogeneity

We will not perform meta-analysis if we suspect important clinical heterogeneity on examination of the included studies. We will use the Chi2statistic to test statistical heterogeneity between studies and will consider a P value ≤ 0.10 as indicating significant heterogeneity; we will use the I2 statistic to assess the magnitude of heterogeneity (Higgins 2002). We will consider I2 > 50% to indicate problematic heterogeneity between studies and will carefully consider the value of any pooled analysis. We will use a random-effects model analysis if I2 is greater than 30%. We will use a fixed-effect model of analysis to determine the best estimate of the intervention effect. If the two do not coincide, we will not consider the random-effects estimate as the actual intervention effect in the population under study. We will construct forest plots to summarize findings from the included studies.

Assessment of reporting biases

A comprehensive electronic search and a search of other sources such as trial registries will be undertaken as described above to minimize the effects of publication bias. If 10 or more studies are identified, funnel plots of effect estimates against their standard errors (on a reversed scale) will be created using RevMan 5.2. We will include a triangular 95% confidence interval based on a fixed-effect meta-analysis in the plot to identify asymmetry. We will construct a contour-enhanced funnel plot to differentiate asymmetry due to publication bias from that due to other factors. We will conduct sensitivity analyses to explore the robustness of the meta-analysis in terms of conclusions related to the causes of funnel plot asymmetry.

Data synthesis

We will quantitatively review the included data and will combine the data by intervention, outcome and population using the statistical software of The Cochrane Collaboration (RevMan 5.2). We will synthesize the data only in the absence of important clinical or statistical heterogeneity, and we will express pooled estimates of the mean difference for continuous variables and risk ratios for proportions, as described above.

We will use the inverse-variance fixed-effect method of meta-analysis for continuous variables. For duration of mechanical ventilation, the mean difference may be estimated from the median difference when necessary. As the number of studies is expected to be small, we will use the Mantel-Haenszel fixed-effect method of meta-analysis for dichotomous outcomes.

If cluster-randomized studies are identified, we will determine whether the results have been correctly analysed by using an appropriate method such as a multi-level model, variance component analysis or generalized estimating equations (GEEs). If this is done, we will include in the meta-analysis the effect estimates from these studies and their standard errors.

If substantial heterogeneity is present, and if sufficient studies are available, we will also perform a random effects meta-analysis.

We will present the results in the form of a forest plot.

Subgroup analysis and investigation of heterogeneity

When appropriate, with obvious clinical or statistical (I2 > 50%) heterogeneity, we will consider subgroup analysis based on participants with neurological injury, including:

  1. head injury;

  2. cardiopulmonary bypass; and

  3. use of neuromuscular blocking agents

whenever the data indicate heterogeneity on that basis.

Sensitivity analysis

We will perform sensitivity analyses to explore the consistency of effect size measures in studies with low risk of bias versus those with high risk of bias.

Summary of findings

We will present study findings in a standard 'Summary of findings' (SoF) table, which will include a list of all important outcomes; a measure of the typical burden of these outcomes; the absolute and relative magnitude of effect; the numbers of participants and studies addressing each outcome and a grade for the overall quality of the body of evidence for each outcome. Space will be provided for comments.

We will use the principles of the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) system (Guyatt 2008) to assess the quality of the body of evidence associated with specific outcomes (ICU LOS, duration of mechanical ventilation, any-cause mortality, incidence of VAP, incidence of adverse events (e.g. self-extubation, unplanned disconnection of indwelling catheters), hospital LOS, amount of sedative agents used, cost and longer-term functional outcomes and quality of life as reported by study authors)and will construct the SoF table using GRADE software. The GRADE approach appraises the quality of a body of evidence according to the extent to which one can be confident that an estimate of effect or association reflects the item being assessed. The quality of the body of evidence considers within-study risk of bias (methodological quality), directness of the evidence, heterogeneity of the data, precision of effect estimates and risk of publication bias.

Acknowledgements

We thank Michael O'Connor and Yodying Punjasawadwong (peer reviewers), Nathan Pace (statistical editor) and Bronagh Blackwood (content editor) for help and support in preparing this protocol.

Appendices

Appendix 1. Search strategy for CENTRAL

#1 MeSH descriptor: [Electroencephalography] explode all trees
#2 (EEG or BIS or electroence*):ti,ab or (brain near monitor*) or bispectral index:ti,ab
#3 #1 or #2
#4 MeSH descriptor: [Intensive Care] explode all trees
#5 MeSH descriptor: [Intensive Care Units] explode all trees
#6 MeSH descriptor: [Critical Care] explode all trees
#7 MeSH descriptor: [Respiration, Artificial] explode all trees
#8 MeSH descriptor: [Ventilators, Mechanical] explode all trees
#9 MeSH descriptor: [Propofol] explode all trees
#10 MeSH descriptor: [Conscious Sedation] explode all trees
#11 ((intensive or critical) near (care or unit*)):ti,ab or sedat*:ti,ab or (ventilat* near (mechanical* or intub*)):ti,ab
#12 #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11
#13 #3 and #12
#14 (child* not (adult* and child*))
#15 #13 not #14

Appendix 2. MEDLINE (Ovid SP) search strategy

1. exp Electroencephalography/ or (EEG or BIS or electroence*).ti,ab. or (brain adj3 monitor*).mp. or bispectral index.mp.
2. Intensive Care/ or Intensive Care Units/ or Critical Care/ or (ICU or ITU or ((intensive or critical) adj3 (care or unit*))).ti,ab. or Respiration, Artificial/ or Ventilators, Mechanical/ or Propofol/ or Conscious Sedation/ or sedat*.ti,ab. or (ventilat* adj3 (mechanical* or intub*)).mp.
3. ((randomized controlled trial or controlled clinical trial).pt. or randomized.ab. or placebo.ab. or clinical trials as topic.sh. or randomly.ab. or trial.ti.) not (animals not (humans and animals)).sh.
4. (child* not (adult* and child*)).af.
5. (1 and 2 and 3) not 4

Appendix 3. EMBASE (Ovid SP) search strategy

1. exp electroencephalography/ or (EEG or BIS or electroence*).ti,ab. or (brain adj3 monitor*).ti,ab. or bispectral index.ti,ab.
2. intensive care/ or intensive care unit/ or (ICU or ITU or ((intensive or critical) adj3 (care or unit*))).ti,ab. or artificial ventilation/ or mechanical ventilator/ or propofol/ or conscious sedation/ or sedat*.ti,ab. or (ventilat* adj3 (mechanical* or intub*)).ti,ab.
3. (placebo.sh. or controlled study.ab. or random*.ti,ab. or trial*.ti,ab. or ((singl* or doubl* or trebl* or tripl*) adj3 (blind* or mask*)).ti,ab.) not (animals not (humans and animals)).sh.
4. (child* not (adult* and child*)).af.
5. (1 and 2 and 3) not 4

Appendix 4. CINAHL (EBSCOhost) search strategy

S1 (MH "Electroencephalography") OR ( (EEG or BIS or electroence*) or (brain N3 monitor*) or bispectral index )
S2 AB ( ((intensive or critical) N3 (care or unit*)) or sedat* or (ventilat* N3 (mechanical* or intub*)) ) OR ( (MH "Critical Care") OR (MH "Intensive Care Units") OR (MH "Respiration, Artificial") OR (MH "Ventilators, Mechanical") OR (MH "Propofol") OR (MH "Conscious Sedation") )
S3 (random* or ((clinical or controlled) N3 trial*) or placebo* or prospective* or crossover or multicenter) or ((blind* or mask*) N3 (single or double or triple or treble))
S4 (child* not (adult* and child*))
S5 (S1 or S2 or S3) not S4

Appendix 5. CARG study selection and data extraction form

 

Review title or ID
     

 

Study ID (surname of first author and year first full report of study was published e.g. Smith 2001)
     

 

Report IDs of other reports of this study (e.g. duplicate publications, follow-up studies)
     

 

Notes:       

 

 

 

1.    General information

 

Date form completed (dd/mm/yyyy)     
Name/ID of person extracting data

     

 

Report title

(title of paper/abstract/report that data are extracted from)

     

 

Report ID

(ID for this paper/abstract/report)

     

 

Reference details

   

 

 

Report author contact details

     

 

Publication type

(e.g. full report, abstract, letter)

     

 

Study funding sources

(including role of funders)

     

 

Possible conflicts of interest

(for study authors)

     

 

Notes:    

 

 

  

First author Journal/Conference proceedings, etc. Year

 

 

   

  

2.    Study eligibility

 

Study characteristics

Eligibility criteria

(insert eligibility criteria for each characteristic as defined in the Protocol)

YesNoUnclear

Location in text

(pg & ¶/fig/table)

Type of studyRandomized controlled trial        

Controlled clinical trial

 

         
Cluster-randomized trials  

Participants

 

     

Adult patients (18 years of age or older) undergoing mechanical ventilation in an intensive care unit for longer than 24 hours

 

 

        
Types of intervention

 

BIS monitoring used                

     

 

                

      

 

Sedation protocol used

   
Clinical method used to assess levels of sedation (clinical judgement or specific clinical sedation scoring tool) in the control arm with or without use of a titration protocol   
Types of outcome measuresIntensive care unit (ICU) length of stay 

 

                  

      
Duration of mechanical ventilation  

 

                  

  
Longer-term functional outcomes as reported by study authors                      
INCLUDE  EXCLUDE  

Reason for exclusion

 

    
Notes:          

 

                                                                     

Do not proceed if any of the above answers are ‘No.’ If study is to be included in ‘Excluded studies’ section of the review, record below the information to be inserted into ‘Table of excluded studies.’
 

 

DO NOT PROCEED IF STUDY EXCLUDED FROM REVIEW

3.    Population and setting

 

 

Description

(include comparative information for each group (i.e. intervention and controls) if available)

Location in text

(pg & ¶/fig/table)

Population description

(from which study participants are drawn)

          
Country where the study was conducted    

Setting

(including location and social context)

          
Number of beds in the hospital          
Number of beds in the ICU          
Percentage of ventilated beds          
Nurse-to-patient ratio    
Number of patients admitted to ICU each year          

Type of ICU

 

   Surgical

   Medical

   Cardiac

   Trauma

   Neurological

   Burn

   Other, specify:      

     
Inclusion criteria          
Exclusion criteria          
Method/s of recruitment of participants          

Informed consent obtained

 

             

Yes      No     Unclear

          
Notes:         

 

4.    Methods

 

 

Descriptions as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Aim of study          
Design (e.g. parallel, cross-over, cluster)          
Single-centre/Multi-centre  

Unit of allocation

(by individuals, clusters/groups or body parts)

          
Start date

     

 

     
End date 

     

 

     

Total study duration

 

          

Severity of illness scoring system used

 

   APACHE

   SAPS

   SOFA

   AIS

   ISS

   TISS

   MPM

   MODS

   Other, specify:       

 
Diagnosis  

Sedatives used

(name, dosage, range, number and % of patients receiving this drug)

  
Administration of sedatives

   Continuous

   Bolus

 
Total number of sedative agents used with unit of measurement    
Paralytics used in both groups

 

Yes No Unclear

 
Method of sedation assessment used for control group

   Sedation and agitation scale (SAS)

   Visual analogue scale (VAS)

   Train of Four (TOF) in patient on paralysis

   Richmond Agitation and Sedation Scale (RASS)

   Observer's assessment of agitation and sedation

   Ramsey sedation scale

   Modified Ramsey sedation scale

   Cook

   Motor activity assessment scale (MAAS)

   Vancouver interactive and calmness scale

   Adaptation to intensive care environment

   Minnesota Sedation and Assessment Tool

   Score of the UK Intensive Care Society

   Sheffield

   Bloomsbury

   Local scoring system

   Other, specify:

 
Ethical approval needed/obtained for study

             

Yes      No     Unclear

          
Notes:        

 

5.     Risk of bias assessment

See Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions.

 

Domain

Risk of bias

 

Support for judgement

 

Location in text

(pg & ¶/fig/table)

Low riskHigh riskUnclear risk

Random sequence generation

(selection bias)

             

Allocation concealment

(selection bias)  

             

Blinding of participants and personnel

(performance bias)

   

Outcome group: all/     

     

     
(if required)   

Outcome group:      

     

     

Blinding of outcome assessors

(detection bias)

   

Outcome group: all/     

     

     
(if required)   

Outcome group:      

     

     

Incomplete outcome data

(attrition bias)

 

             

Selective outcome reporting?

(reporting bias)

             

Other bias 

 

             

Notes:         

 

 

 

Intention-to-treat

An intention-to-treat analysis is one in which all participants in a trial are analysed according to the intervention to which they were allocated, whether or not they received it .

All participants entering trial 
15% or fewer excluded 
More than 15% excluded 
Not analysed as ‘intention-to-treat’ 
Unclear 

Were withdrawals described?    Yes           No       Not clear 

Discuss if appropriate…………………………………………………………………………………………

6.     Participants

Provide overall data and, if available, comparative data for each intervention and comparison group.

 

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Total no. randomly assigned

(or total population at start of study for NRCTs)

          

Clusters

(if applicable, no., type, no. people per cluster)

          
Baseline imbalances          

Withdrawals and exclusions

(if not provided below by outcome)

          
Age (mean, median, range, etc.)          
Sex (number/%, etc.)          
Race/Ethnicity          
Severity of illness          
Diagnosis  
Co-morbidities          
Past history of delirium or dementia  
Other treatment received (additional to study intervention)          

Discharge destination

 

   Home

   Rehabilitation facility

   Skilled nursing facility (nursing home)

   Long-term acute care hospital

   Other, specify:      

     
Other relevant sociodemographics           
Subgroups measured           
Subgroups reported           
Notes:         

 

7.     Intervention groups

Copy and paste table for each intervention and comparison group.

 

Intervention group 1

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Group name

 

          

No. randomly assigned to group

(specify whether no. people or clusters)

          
Theoretical basis (include key references)          
Description (include sufficient detail for replication, e.g. content, dose, components)          
BIS version  
BIS mean, range, etc.  
BIS measurement at each sedation score and correlation  
Hours on BIS  

Confounders that may effect BIS reading

(aminophylline, catecholamines, ketamine, electrical/non-electrical EMG interference, hypoglycaemia, sleep, sound, temperature, excessive muscle movement)

  
Duration of treatment period          
Timing (e.g. frequency, duration of each episode)          
Delivery (e.g. mechanism, medium, intensity, fidelity)          

Providers

(e.g. no., profession, training, ethnicity etc., if relevant)

          
Co-interventions           
Economic variables
(i.e. intervention cost, changes in other costs as result of intervention)
          

Resource requirements to replicate intervention

(e.g. staff numbers, cold chain, equipment)

          
Notes:         

 

8.    Outcomes

 

 

Outcomes relevant to your review

(copy and paste from ‘Types of outcome measures’)

  Reported in paper (circle)
Intensive care unit (ICU) length of stayYes / No
Duration of mechanical ventilationYes / No
Any-cause mortalityYes / No
Incidence of ventilator-associated pneumoniaYes / No
Incidence of adverse events (self-extubation, unplanned disconnection of indwelling catheters, etc.)Yes / No
Hospital length of stayYes / No
Quality of lifeYes / No
Longer-term functional outcomes as reported by study authorsYes / No
CostYes / No
Total amount of sedative agents usedYes / No

 

Intensive care unit (ICU) length of stay

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Outcome name

 

          
Time points measured          
Time points reported          
Outcome definition (with diagnostic criteria if relevant)          
Person measuring/reporting          

Unit of measurement

(if relevant)  

          
Scales: upper and lower limits (indicate whether high  or low score is good)          
Is outcome/tool validated?

             

Yes      No     Unclear

          
Imputation of missing data
(e.g. assumptions made for ITT analysis)
          

Assumed risk estimate

(e.g. baseline or population risk noted in Background)

          
Power          

Notes:        

 

 

                            

 

Duration of mechanical ventilation

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Outcome name               
Time points measured          
Time points reported          
Outcome definition (with diagnostic criteria if relevant)          
Person measuring/reporting          

Unit of measurement

(if relevant)  

          
Scales: upper and lower limits (indicate whether high  or low score is good)          
Is outcome/tool validated?

            

Yes      No     Unclear

          
Imputation of missing data
(e.g. assumptions made for ITT analysis)
          

Assumed risk estimate

(e.g. baseline or population risk noted in Background)

          
Power          

Notes:       

 

 

Any-cause mortality

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Outcome name           
Time points measured          
Time points reported          
Outcome definition (with diagnostic criteria if relevant)          
Person measuring/reporting          

Unit of measurement

(if relevant)  

          
Scales: upper and lower limits (indicate whether high  or low score is good)          
Is outcome/tool validated?

             

Yes      No     Unclear

          
Imputation of missing data
(e.g. assumptions made for ITT analysis)
          

Assumed risk estimate

(e.g. baseline or population risk noted in Background)

          
Power          

Notes:       

 

 

Incidence of ventilator-associated pneumonia

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Outcome name           
Time points measured          
Time points reported          
Outcome definition (with diagnostic criteria if relevant)          
Person measuring/reporting          

Unit of measurement

(if relevant)  

          
Scales: upper and lower limits (indicate whether high or low score is good)          
Is outcome/tool validated?

             

Yes      No     Unclear

          
Imputation of missing data
(e.g. assumptions made for ITT analysis)
          

Assumed risk estimate

(e.g. baseline or population risk noted in Background)

          
Power          

Notes:       

 

 

Incidence of adverse events (e.g. self-extubation, unplanned disconnection of indwelling catheters)

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Outcome name           
Time points measured          
Time points reported          
Outcome definition (with diagnostic criteria if relevant)          
Person measuring/reporting          

Unit of measurement

(if relevant)

 

          
Scales: upper and lower limits (indicate whether high or low score is good)          
Is outcome/tool validated?

             

Yes      No     Unclear

          
Imputation of missing data
(e.g. assumptions made for ITT analysis)
          

Assumed risk estimate

(e.g. baseline or population risk noted in Background)

          
Power          

Notes:     

 

 

Hospital length of stay

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Outcome name           
Time points measured          
Time points reported          
Outcome definition (with diagnostic criteria if relevant)          
Person measuring/reporting          

Unit of measurement

(if relevant)  

          
Scales: upper and lower limits (indicate whether high or low score is good)          
Is outcome/tool validated?

             

Yes      No     Unclear

          
Imputation of missing data
(e.g. assumptions made for ITT analysis)
          

Assumed risk estimate

(e.g. baseline or population risk noted in Background)

          
Power          
Notes:        

 

Amount of sedative agents used

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Outcome name           
Time points measured          
Time points reported          
Outcome definition (with diagnostic criteria if relevant)          
Person measuring/reporting          

Unit of measurement

(if relevant)  

          
Scales: upper and lower limits (indicate whether high or low score is good)          
Is outcome/tool validated?

             

Yes      No     Unclear

          
Imputation of missing data
(e.g. assumptions made for ITT analysis)
          

Assumed risk estimate

(e.g. baseline or population risk noted in Background)

          
Power          
Notes:       

 

Cost

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Outcome name           
Time points measured          
Time points reported          
Outcome definition (with diagnostic criteria if relevant)          
Person measuring/reporting          

Unit of measurement

(if relevant)  

          
Scales: upper and lower limits (indicate whether high  or low score is good)          
Is outcome/tool validated?

             

Yes      No     Unclear

          
Imputation of missing data
(e.g. assumptions made for ITT analysis)
          

Assumed risk estimate

(e.g. baseline or population risk noted in Background)

          
Power          

Notes:       

 

 

Longer-term functional outcomes, as reported by study authors

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Outcome name           
Time points measured          
Time points reported          
Outcome definition (with diagnostic criteria if relevant)          
Person measuring/reporting          

Unit of measurement

(if relevant)  

          
Scales: upper and lower limits (indicate whether high or low score is good)          
Is outcome/tool validated?

             

Yes      No     Unclear

          
Imputation of missing data
(e.g. assumptions made for ITT analysis)
          

Assumed risk estimate

(e.g. baseline or population risk noted in Background)

          
Power          

Notes:     

  

 

 

Quality of life

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Outcome name           
Time points measured          
Time points reported          
Outcome definition (with diagnostic criteria if relevant)          
Person measuring/reporting          

Unit of measurement

(if relevant)  

          
Scales: upper and lower limits (indicate whether high or low score is good)          
Is outcome/tool validated?

             

Yes      No     Unclear

          
Imputation of missing data
(e.g. assumptions made for ITT analysis)
          

Assumed risk estimate

(e.g. baseline or population risk noted in Background)

          
Power          

Notes:      

 

 

 

9.    Results

 

Intensive care unit (ICU) length of stay

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Time point
(specify whether from start or end of intervention)
          
Post intervention or change from baseline?          
Results Intervention Control 
MeanSD (or other variance)No. participantsMeanSD (or other variance)No. participants     
                              
Overall result (comparison)     
Mean differenceStandard error95% confidence interval
               
No. missing participants and reasons               
No. participants moved from other group and reasons               
Any other results reported           

Unit of analysis

(individuals, clusters/groups or body parts)

          
Statistical methods used and appropriateness of these methods (e.g. adjustment for correlation)          
Reanalysis required? (specify)

             

Yes      No     Unclear

          
Reanalysis possible?

             

Yes      No     Unclear

          
Reanalysed results          

Notes:         

 

 

 

 

 

Duration of mechanical ventilation

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Time point
(specify whether from start or end of intervention)
          
Post intervention or change from baseline?          
Results Intervention Control 
MedianIQR (or other variance)No. participantsMedianIQR (or other variance)No. participants     
                              
Overall result (comparison)     
Mean or median differenceStandard error (or other variance)95% confidence interval
               
No. missing participants and reasons               
No. participants moved from other group and reasons               
Any other results reported           

Unit of analysis

(individuals, clusters/groups or body parts)

          
Statistical methods used and appropriateness of these methods (e.g. adjustment for correlation)          
Reanalysis required? (specify)

             

Yes      No     Unclear

          
Reanalysis possible?

             

Yes      No     Unclear

          
Reanalysed results          

Notes:       

  

 

 

Any-cause mortality

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Time point
(specify whether from start or end of intervention)
          
Results Intervention Control     
RiskNumber of participantsRiskNumber of participants
                    
Overall result (comparison)
Risk ratio (relative risk)Standard error (or other variance)95% confidence interval
               
No. participantsInterventionControl 
          
No. missing participants and reasons               
No. participants moved from other group and reasons               
Any other results reported          
Unit of analysis (by individuals, clusters/groups or body parts)          
Statistical methods used and appropriateness of these methods          
Reanalysis required? (specify)

             

Yes      No     Unclear

          
Reanalysis possible?

             

Yes      No     Unclear

          
Reanalysed results          

Notes:         

 

 

 

Incidence of ventilator-associated pneumonia

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Time point
(specify whether from start or end of intervention)
          
Results Intervention Control     
Risk Number of participants Risk Number of participants
                    
Overall result (comparison)
Risk ratio (relative risk)SE (or other variance)95% confidence interval
               
No. participantsInterventionControl 
          
No. missing participants and reasons               
No. participants moved from other group and reasons               
Any other results reported          
Unit of analysis (by individuals, clusters/groups or body parts)          
Statistical methods used and appropriateness of these methods          
Reanalysis required? (specify)

             

Yes      No     Unclear

          
Reanalysis possible?

             

Yes      No     Unclear

          
Reanalysed results          

Notes:         

 

 

Incidence of adverse events (e.g. self-extubation, unplanned disconnection of indwelling catheters)

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Time point
(specify whether from start or end of intervention)
          
Results Intervention Control     
RiskNumber of participantsRiskNumber of participants
                    
Overall result (comparison)
Risk ratio (relative risk)Standard error (or other variance)95% confidence interval
               
No. participantsInterventionControl 
          
No. missing participants and reasons               
No. participants moved from other group and reasons               
Any other results reported          
Unit of analysis (by individuals, clusters/groups or body parts)          
Statistical methods used and appropriateness of these methods          
Reanalysis required? (specify)

             

Yes      No     Unclear

          
Reanalysis possible?

             

Yes      No     Unclear

          
Reanalysed results          

Notes:         

 

 

Hospital length of stay

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Time point
(specify whether from start or end of intervention)
          
Post intervention or change from baseline?          
Results Intervention Control 
MeanSD (or other variance)No. participantsMeanSD (or other variance)No. participants     
                              
Overall result (comparison)     
Mean differenceStandard error95% confidence interval
               
No. missing participants and reasons               
No. participants moved from other group and reasons               

Any other results reported

 

          

Unit of analysis

(individuals, clusters/groups or body parts)

          
Statistical methods used and appropriateness of these methods (e.g. adjustment for correlation)          
Reanalysis required? (specify)

             

Yes      No     Unclear

          
Reanalysis possible?

             

Yes      No     Unclear

          
Reanalysed results          

Notes:       

  

 

 

Amount of sedatives used

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Time point
(specify whether from start or end of intervention)
          
Post intervention or change from baseline?          
Results Intervention Control 
MeanSD (or other variance)No. participantsMeanSD (or other variance)No. participants     
                              
Overall result (comparison)     
Mean differenceStandard error95% confidence interval
               
No. missing participants and reasons               
No. participants moved from other group and reasons               

Any other results reported

 

          

Unit of analysis

(individuals, clusters/groups or body parts)

          
Statistical methods used and appropriateness of these methods (e.g. adjustment for correlation)          
Reanalysis required? (specify)

             

Yes      No     Unclear

          
Reanalysis possible?

             

Yes      No     Unclear

          
Reanalysed results          

Notes:         

 

 

 

 

Cost

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Time point
(specify whether from start or end of intervention)
          
Post intervention or change from baseline?          
Results Intervention Comparison 
MeanSD (or other variance)No. participantsMeanSD (or other variance)No. participants     
                              
Overall result (comparison)     
Mean differenceStandard error95% confidence interval
               
No. missing participants and reasons               
No. participants moved from other group and reasons               

Any other results reported

 

          

Unit of analysis

(individuals, clusters/groups or body parts)

          
Statistical methods used and appropriateness of these methods (e.g. adjustment for correlation)          
Reanalysis required? (specify)

             

Yes      No     Unclear

          
Reanalysis possible?

             

Yes      No     Unclear

          
Reanalysed results          

Notes:       

  

 

 

Longer-term functional outcomes, as reported by study authors

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Time point
(specify whether from start or end of intervention)
          
Post intervention or change from baseline?          
Results Intervention Control 
Mean or medianSD (or other variance)No. participantsMean or medianSD (or other variance)No. participants     
                              
Overall result (comparison)     
Mean differenceStandard error95% confidence interval
               
No. missing participants and reasons               
No. participants moved from other group and reasons               

Any other results reported

 

          

Unit of analysis

(individuals, clusters/groups or body parts)

          
Statistical methods used and appropriateness of these methods (e.g. adjustment for correlation)          
Reanalysis required? (specify)

            

Yes      No     Unclear

          
Reanalysis possible?

             

Yes      No     Unclear

          
Reanalysed results          
Notes:          

 

Quality of life

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Comparison          
Outcome          
Subgroup          
Time point
(specify whether from start or end of intervention)
          
Post intervention or change from baseline?          
Results Intervention Control 
MeanSD (or other variance)No. participantsMeanSD (or other variance)No. participants     
                              
Overall result (comparison)     
Mean differenceStandard error95% confidence interval
               
No. missing participants and reasons               
No. participants moved from other group and reasons               

Any other results reported

 

          

Unit of analysis

(individuals, clusters/groups or body parts)

          
Statistical methods used and appropriateness of these methods (e.g. adjustment for correlation)          
Reanalysis required? (specify)

             

Yes      No     Unclear

          
Reanalysis possible?

             

Yes      No     Unclear

          
Reanalysed results          

Notes:      

  

 

 

 

Other outcomes

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Correlation with propofol, morphine and midazolam dose  

 

10. Applicability

 

Have important populations been excluded from the study? (consider disadvantaged populations and possible differences in the intervention effect)

             

Yes      No     Unclear

     
Is the intervention likely to be aimed at disadvantaged groups? (e.g. lower socioeconomic groups)

             

Yes      No     Unclear

     

Does the study directly address the review question?

(any issues of partial or indirect applicability)

             

Yes      No     Unclear

     

Notes:       

 

 

11. Other information

 

References to trial

 

Check other references identified in searches. If further references to this trial are identified, link the papers now and list below. All references to a trial should be linked under one Study ID in RevMan.

 

Code each paper Author(s) Journal/Conference proceedings, etc. Year
A Paper listed above  
B Further papers  
    

 

 

 

Description as stated in report/paper

 

Location in text

(pg & ¶/fig/table)

Key conclusions of study authors           
References to other relevant studies           
Correspondence required for further study information (from whom, what and when)     

Notes:      

  

 

 

Other information that you feel is relevant to the results

Indicate whether any data were obtained from the primary author; and whether results were estimated from graphs, etc., or were calculated by you using a formula (this should be stated and the formula given). In general, if results not reported in paper(s) are obtained, this should be made clear here to be cited in the review.

  

 

 

 

References to other trials

 

Did this report include any references to published reports of potentially eligible trials not already identified for this review?
First author Journal/Conference Year of publication
   
Did this report include any references to unpublished data from potentially eligible trials not already identified for this review? If yes, give list contact name and details
  

 

 

Contributions of authors

Rajesh M Shetty (RS), Antonio Bellini (AB), Dhuleep Wijayatilake (DW), Mark A Hamilton (MH), Rajesh Jain (RJ), Gonzalo De La Cerda (GC), Sarah Stowell (SS), Sunil Karanth (SK)

Conceiving of the review: RS.

Co-ordinating the review: RS, AB.

Undertaking manual searches: RS, AB, GC, RJ, SK.

Screening search results: RS, AB, DW, GC, RJ.

Organizing retrieval of papers: RS, AB, RJ.

Screening retrieved papers against inclusion criteria: RS, AB, RJ, SK.

Appraising quality of papers: RS, AB, SS.

Abstracting data from papers: RS, AB, SS, SK.

Writing to authors of papers for additional information: RS, DW.

Providing additional data about papers: RS, AB, RJ.

Obtaining and screening data on unpublished studies: RS, AB.

Managing data for the review: RS, AB, SS, SK.

Entering data into Review Manager (RevMan 5.2): RS, AB, SS.

Calculating RevMan statistical data: RS, AB, GC, SS.

Performing other statistical analysis not using RevMan: RS, AB, SS.

Interpreting data: RS, AB, SS.

Making statistical inferences: RS, AB, SS.

Writing the review: RS, AB, DW.

Securing funding for the review: RS, DW.

Performing previous work that served as the foundation of the present study: RS.

Serving as guarantor for the review (one author): RS.

Taking responsibility for reading and checking the review before submission: RS, AB, DW, MH.

Declarations of interest

Rajesh M Shetty: none known.

Antonio Bellini: none known.

Dhuleep Wijayatilake: none known.

Mark A Hamilton: none known.

Rajesh Jain: none known.

Gonzalo De La Cerda: none known.

Sarah Stowell: none known.

Sunil Karanth: none known.

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • Own funding from authors, UK.

Ancillary