Article

Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia

Department of Oral and Maxillofacial Surgery, State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, China, 610041.
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 08/2013; 8(8):CD008367. DOI: 10.1002/14651858.CD008367.pub2
Source: PubMed

ABSTRACT

Ventilator-associated pneumonia (VAP) is defined as pneumonia developing in persons who have received mechanical ventilation for at least 48 hours. VAP is a potentially serious complication in these patients who are already critically ill. Oral hygiene care (OHC), using either a mouthrinse, gel, toothbrush, or combination, together with aspiration of secretions may reduce the risk of VAP in these patients.
To assess the effects of OHC on the incidence of VAP in critically ill patients receiving mechanical ventilation in intensive care units (ICUs) in hospitals.
We searched the Cochrane Oral Health Group's Trials Register (to 14 January 2013), CENTRAL (The Cochrane Library 2012, Issue 12), MEDLINE (OVID) (1946 to 14 January 2013), EMBASE (OVID) (1980 to 14 January 2013), LILACS (BIREME) (1982 to 14 January 2013), CINAHL (EBSCO) (1980 to 14 January 2013), Chinese Biomedical Literature Database (1978 to 14 January 2013), China National Knowledge Infrastructure (1994 to 14 January 2013), Wan Fang Database (January 1984 to 14 January 2013), OpenGrey and ClinicalTrials.gov (to 14 January 2013). There were no restrictions regarding language or date of publication.
We included randomised controlled trials (RCTs) evaluating the effects of OHC (mouthrinse, swab, toothbrush or combination) in critically ill patients receiving mechanical ventilation.
Two review authors independently assessed all search results, extracted data and undertook risk of bias. We contacted study authors for additional information. Trials with similar interventions and outcomes were pooled reporting odds ratios (OR) for dichotomous outcomes and mean differences (MD) for continuous outcomes using random-effects models unless there were fewer than four studies.
Thirty-five RCTs (5374 participants) were included. Five trials (14%) were assessed at low risk of bias, 17 studies (49%) were at high risk of bias, and 13 studies (37%) were assessed at unclear risk of bias in at least one domain. There were four main comparisons: chlorhexidine (CHX mouthrinse or gel) versus placebo/usual care, toothbrushing versus no toothbrushing, powered versus manual toothbrushing and comparisons of oral care solutions.There is moderate quality evidence from 17 RCTs (2402 participants, two at high, 11 at unclear and four at low risk of bias) that CHX mouthrinse or gel, as part of OHC, compared to placebo or usual care is associated with a reduction in VAP (OR 0.60, 95% confidence intervals (CI) 0.47 to 0.77, P < 0.001, I(2) = 21%). This is equivalent to a number needed to treat (NNT) of 15 (95% CI 10 to 34) indicating that for every 15 ventilated patients in intensive care receiving OHC including chlorhexidine, one outcome of VAP will be prevented. There is no evidence of a difference between CHX and placebo/usual care in the outcomes of mortality (OR 1.10, 95% CI 0.87 to 1.38, P = 0.44, I(2) = 2%, 15 RCTs, moderate quality evidence), duration of mechanical ventilation (MD 0.09, 95% CI -0.84 to 1.01 days, P = 0.85, I(2) = 24%, six RCTs, moderate quality evidence), or duration of ICU stay (MD -0.21, 95% CI -1.48 to 1.89 days, P = 0.81, I(2) = 9%, six RCTs, moderate quality evidence). There was insufficient evidence to determine whether there is a difference between CHX and placebo/usual care in the outcomes of duration of use of systemic antibiotics, oral health indices, microbiological cultures, caregivers preferences or cost. Only three studies reported any adverse effects, and these were mild with similar frequency in CHX and control groups.From three trials of children aged from 0 to 15 years (342 participants, moderate quality evidence) there is no evidence of a difference between OHC with CHX and placebo for the outcomes of VAP (OR 1.07, 95% CI 0.65 to 1.77, P = 0.79, I(2) = 0%), or mortality (OR 0.73, 95% CI 0.41 to 1.30, P = 0.28, I(2) = 0%), and insufficient evidence to determine the effect on the outcomes of duration of ventilation, duration of ICU stay, use of systemic antibiotics, plaque index, microbiological cultures or adverse effects, in children.Based on four RCTs (828 participants, low quality evidence) there is no evidence of a difference between OHC including toothbrushing (± CHX) compared to OHC without toothbrushing (± CHX) for the outcome of VAP (OR 0.69, 95% CI 0.36 to 1.29, P = 0.24 , I(2) = 64%) and no evidence of a difference for mortality (OR 0.85, 95% CI 0.62 to 1.16, P = 0.31, I(2) = 0%, four RCTs, moderate quality evidence). There is insufficient evidence to determine whether there is a difference due to toothbrushing for the outcomes of duration of mechanical ventilation, duration of ICU stay, use of systemic antibiotics, oral health indices, microbiological cultures, adverse effects, caregivers preferences or cost.Only one trial compared use of a powered toothbrush with a manual toothbrush providing insufficient evidence to determine the effect on any of the outcomes of this review.A range of other oral care solutions were compared. There is some weak evidence that povidone iodine mouthrinse is more effective than saline in reducing VAP (OR 0.35, 95% CI 0.19 to 0.65, P = 0.0009, I(2) = 53%) (two studies, 206 participants, high risk of bias). Due to the variation in comparisons and outcomes among the trials in this group there is insufficient evidence concerning the effects of other oral care solutions on the outcomes of this review.
Effective OHC is important for ventilated patients in intensive care. OHC that includes either chlorhexidine mouthwash or gel is associated with a 40% reduction in the odds of developing ventilator-associated pneumonia in critically ill adults. However, there is no evidence of a difference in the outcomes of mortality, duration of mechanical ventilation or duration of ICU stay. There is no evidence that OHC including both CHX and toothbrushing is different from OHC with CHX alone, and some weak evidence to suggest that povidone iodine mouthrinse is more effective than saline in reducing VAP. There is insufficient evidence to determine whether powered toothbrushing or other oral care solutions are effective in reducing VAP.

Full-text

Available from: Helen V Worthington
Oral hygiene care for critically ill patients to prevent
ve ntilator-associated pneumonia (Review)
Shi Z, Xie H, Wang P, Zhang Q, Wu Y, Chen E, Ng L, Worthington HV, Needleman I, Furness
S
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochran e Library
2013, Issue 8
http://www.thecochranelibrary.com
Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 1
T A B L E O F C O N T E N T S
1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . . . . . . . . . . . . . . . . . . .
6BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
12RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
23ADDITIONAL SUMMARY OF FINDINGS . . . . . . . . . . . . . . . . . . . . . . . . . .
26DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
28AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
28ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
28REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
33CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
90DATA AND ANA LYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Chlorhexidine versus placebo/usual care, Outcome 1 Incidence of VAP. . . . . . . 94
Analysis 1.2. Comparison 1 Chlorhexidine versus placebo/usual care, Outcome 2 Mortality. . . . . . . . . . 96
Analysis 1.3. Comparison 1 Chlorhexidine versus placebo/usual care, Outcome 3 Duration of ventilation. . . . . 98
Analysis 1.4. Comparison 1 Chlorhexidine versus placebo/usual care, Outcome 4 Duration of ICU stay. . . . . . 99
Analysis 1.5. Comparison 1 Chlorhexidine versus placebo/usual care, Outcome 5 Duration of systemic antibiotic
therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
Analysis 1.6. Comparison 1 Chlorhexidine versus placebo/usual care, Outcome 6 Positive cultures. . . . . . . . 101
Analysis 1.7. Comparison 1 Chlorhexidine versus placebo/usual care, Outcome 7 Plaque index. . . . . . . . . 102
Analysis 1.8. Comparison 1 Chlorhexidine versus placebo/usual care, Outcome 8 Adverse effects. . . . . . . . 102
Analysis 2.1. Comparison 2 Toothbrushing versus no toothbrushing, Outcome 1 Incidence of VAP. . . . . . . 103
Analysis 2.2. Comparison 2 Toothbrushing versus no toothbrushing, Outcome 2 Mortality. . . . . . . . . . 104
Analysis 2.3. Comparison 2 Toothbrushing versus no toothbrushing, Outcome 3 Duration of ventilation. . . . . 106
Analysis 2.4. Comparison 2 Toothbrushing versus no toothbrushing, Outcome 4 Duration of ICU stay. . . . . . 106
Analysis 2.5. Comparison 2 Toothbrushing versus no toothbrushing, O utcome 5 Colonisation with VAP associated
organisms (Day 5). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Analysis 2.6. Comparison 2 Toothbrushing versus no toothbrushing, Outcome 6 Plaque score. . . . . . . . . 108
Analysis 3.1. Comparison 3 Powered toothbrush versus manual toothbrush, Outcome 1 Incidence of VAP. . . . . 109
Analysis 3.2. Comparison 3 Powered toothbrush versus manual toothbrush, Outcome 2 Mortality. . . . . . . . 109
Analysis 3.3. Comparison 3 Powered toothbrush versus manual toothbrush, Outcome 3 Duration of ventilation. . . 110
Analysis 3.4. Comparison 3 Powered toothbrush versus manual toothbrush, Outcome 4 Duration of ICU stay. . . 110
Analysis 4.1. Comparison 4 Other oral care solutions, Outcome 1 Incidence of VAP. . . . . . . . . . . . 111
Analysis 4.2. Comparison 4 Other oral care solutions, Outcome 2 Mortality. . . . . . . . . . . . . . . 113
Analysis 4.3. Comparison 4 Other oral care solutions, Outcome 3 Duration of ventilation. . . . . . . . . . 114
Analysis 4.4. Comparison 4 Other oral care solutions, Outcome 4 Duration of ICU stay. . . . . . . . . . . 116
Analysis 4.5. Comparison 4 Other oral care solutions, Outcome 5 Positive cultures. . . . . . . . . . . . . 117
117ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
118APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
123CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
123DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
124SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
124DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .
iOral hygiene care for critically ill patients to prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 2
[Intervention Review]
Oral hygiene ca re for critically ill pa tie nts to prevent
ve ntilator-associated pneumonia
Zongdao Shi
1
, Huixu Xie
1
, Ping Wang
2
, Qi Zhang
3
, Yan Wu
4
, E Chen
5
, Linda Ng
6
, Helen V Worthington
7
, Ian Needleman
8
, Susan
Furness
7
1
Department of Oral and Maxillofacial Surgery, State Key Laboratory of O r al Diseases, West China College of Stomatology, Sichuan
University, Chengdu, China.
2
Department of Dental Implantation, West China College of Stomatology, Sichuan University, Chengdu,
China.
3
Department of Oral Implantology, State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan
University, Chengdu, China.
4
Department of Orthodontics, Chongqing Medical University, Chongqing, China.
5
Department of
Paediatric Dentistry, West China College of Stomatology, Sichuan University, Chengdu, China.
6
School of Nursing and Midwifery,
University of Queensland, South Brisbane, Australia.
7
Cochrane Oral Health Group, School of Dentistry, The University of Manchester,
Manchester, UK.
8
Unit of Per iodontology and International Centre for Evidence-Based Oral Healthcare, UCL Eastman Dental
Institute, London, UK
Contact address: Susan Furness, Cochrane Oral Health Group, School of Dentistry, The University of Manchester, Coupland III
Building, Oxford Road, Manchester, M13 9PL, UK.
Susan.Furness@manchester.ac.uk. suefurness@gmail.com.
Editorial group: Cochrane Oral Health Group.
Publication status and date: New, published in Issue 8, 2013.
Review content assessed as up-to-date: 14 January 2013.
Citation: Shi Z, Xie H, Wang P, Zhang Q, Wu Y, Chen E, Ng L, Worthington HV, Needleman I, Furness S. Oral hygiene care
for critically ill patients to prevent ventilator-associated pneumonia. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No. :
CD008367. DOI: 10.1002/14651858.CD008367.pub2.
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
A B S T R A C T
Background
Ventilator-associated pneumonia (VAP) is defined as pneumonia developing in persons who have received mechanical ventilation for
at least 48 hours. VAP is a potentially serious complication in the se patients who are already critically ill. Oral hygiene care (OHC),
using either a mouthrinse, gel, toothbrush, or combination, together with aspiration of secretions may reduce the risk of VAP in these
patients.
Objectives
To assess the effects of OHC on the incidence of VAP in cr iticall y ill patients receiving mechanical ventilation in intensive care units
(ICUs) in hospitals.
Search methods
We searched the Cochrane Oral Health Groups Trials Register (to 14 January 2013), CENTRAL (The Cochrane Library 2012, Issue
12), MEDLINE (OVID) (1946 to 14 January 2013), EMBASE (OVID) (1980 to 14 January 2013), LILACS (BIREME) (1982 to
14 January 2013), CINAHL (EBSCO) (1980 to 14 January 2013), Chinese Biomedical Literature Database (1978 to 14 January
2013), China National Knowledge Infrastructure (1994 to 14 January 2013), Wan Fang Database (January 1984 to 14 January 2013),
OpenGrey and ClinicalTr ials.gov (to 14 January 2013). There were no restrictions regarding language or date of publication.
Selection criteria
We included randomised controlled trials (RCTs) evaluating the effects of OHC (mouthrinse, swab, toothbrush or combination) in
critically ill patients receiving mechanical ventilation.
1Oral hygiene care for critically ill patients t o prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 3
Data collection and analysis
Two review authors independently assessed all search results, extracted data and undertook risk of bias. We contacted study authors
for additional information. Trials with similar interventions and outcomes were pooled reporting odds ratios (OR) for dichotomous
outcomes and mean differences (MD) for continuous outcomes using random-effects models unless there were fewer than four studies.
Main results
Thirty-five RCTs (5374 participants) were included. Five trials (14%) were assessed at low risk of bias, 17 studies (49%) were at high
risk of bias, and 13 studies (37%) were assessed at unclear risk of bias in at least one domain. There were four main comparisons:
chlorhexidine (CHX mouthrinse or gel) versus placebo/usual care, toothbrushing versus no toothbrushing, powered versus manual
toothbrushing and comparisons of oral care solutions.
There is moderate quality evidence from 17 RCTs (2402 participants, two at high, 11 at unclear and four at low risk of bias) that CHX
mouthrinse or gel, as part of OHC, compared to placebo or usual care is associated with a reduction in VAP (OR 0.60, 95% confidence
intervals (CI) 0.47 to 0.77, P < 0.001, I
2
= 21%). This is equivalent to a number needed to treat (NN T) of 15 (95% CI 10 to 34)
indicating that for every 15 ventilated patients in intensive care receiving OHC including chlorhexidine, one outcome of VAP will be
prevented. There is no evidence of a difference between CHX and placebo/usual care in the outcomes of mortality (OR 1.10, 95% CI
0.87 to 1.38, P = 0.44, I
2
= 2%, 15 RCTs, moderate quality evidence), duration of mechanical ventilation (MD 0.09, 95% CI -0.84 to
1.01 days, P = 0.85, I
2
= 24%, six RCTs, moderate quality evidence), or duration of ICU stay (MD -0.21, 95% CI -1.48 to 1.89 days,
P = 0.81, I
2
= 9%, six RCTs, moderate quality evidence). There was insufficient evidence to determine whether there is a difference
between CHX and placebo/usual care in the outcomes of duration of use of systemic antibiotics, oral health indices, microbiological
cultures, caregivers preferences or cost. O nl y three studies reported any adverse effects, and these were mild with similar frequency in
CHX and control groups.
From three trials of children aged from 0 to 15 years (342 participants, moderate quality evidence) there is no evidence of a difference
between OHC with CHX and placebo for the outcomes of VA P (OR 1.07, 95% CI 0.65 to 1.77, P = 0.79, I
2
= 0%), or mortality
(OR 0.73, 95% CI 0.41 to 1.30, P = 0.28, I
2
= 0%), and insufficient evidence to dete rmine the e ffect on the outcomes of duration of
ventilation, duration of ICU stay, use of systemic antibiotics, plaque index, microbiological cultures or adverse effects, in children.
Based on four RCTs (828 participants, low quality evidence) there is no evidence of a difference between OHC including toothbrushing
CHX) compared to OHC without toothbrushing CHX) for the outcome of VAP (OR 0.69, 95% CI 0.36 to 1.29, P = 0.24 , I
2
= 64%) and no evidence of a difference for mortality (OR 0.85, 95% CI 0.62 to 1.16, P = 0.31, I
2
= 0%, four RCTs, moderate quality
evidence). There is insufficient evidence to determine wheth er there is a difference due to toothbrushing for the outcomes of duration
of mechanical ventilation, duration of ICU stay, use of systemic antibiotics, oral health indices, microbiological cultures, adverse effects,
caregivers preferences or cost.
Only one trial compared use of a powered toothbrush with a manual toothbrush pr oviding insufficient evidence to determine the effect
on any of the outcomes of this review.
A range of other oral care solutions were compared. There is some weak evidence that povidone iodine mouthrinse is more effective
than saline in reducing VAP (OR 0.35, 95% CI 0.19 to 0.65, P = 0.0009, I
2
= 53%) (two studies, 206 participants, high risk of bias).
Due to the variation in comparisons and outcomes among the trials in this group there is insufficient evidence concerning the effects
of other oral care solutions on the outcomes of this review.
Authors conclusions
Effective OHC is important for ventilated patients in intensive care. OHC that includes eith er chlorhexidine mouthwash or gel is
associated with a 40% reduction in th e odds of developing ventilator-associated pneumonia in critically ill adults. However, there is no
evidence of a difference in the outcomes of mortality, duration of mechanical ventilation or duration of ICU stay. There is no evidence
that OHC including both CHX and toothbrushing is different from OHC with CHX alone, and some weak evidence to suggest that
povidone iodine mouthrinse is more effective than saline in reducing VAP. There is insufficient evidence to determine whether powered
toothbrushing or other oral care solutions are effective in reducing VAP.
P L A I N L A N G U A G E S U M M A R Y
Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia
2Oral hygiene care for critically ill patients t o prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 4
Review question
To assess the effects of oral hygiene care on the incidence of ventilator-associated pneumonia (VAP) in critically ill patients receiving
mechanical ventilation in intensive care units (ICUs) in hospitals (e xcluding the use of antibiotics). The aim was to summarise all the
available appropriate research in order to facilitate the provision of evidence-based care for these vulnerable patients.
Trials were grouped into four main comparisons.
1. Chlorhexidine antiseptic mouthrinse or gel compared to placebo (treatment without the active ingredient chlorhexidine) or usual
care, (with or without toothbrushing).
2. Toothbrushing compared with no toothbrushing, (with or without chlorhexidine).
3. Powered compared with manual toothbrushing.
4. Oral care with other solutions.
Background
Critically ill people, who may be unconscious or sedated while they are treated in intensive care units often need to have machines
to help them breathe (ventilators). The use of these machines for more than 48 hours may result in VAP. VAP is a potentially serious
complication in these patients who are already critically ill.
Keeping the teeth and the mouth clean, preventing the build-up of plaque on the teeth, or secretions in the mouth may help reduce the
risk of developing VAP. Oral hygiene care, using a mouthrinse, gel, toothbrush, or combination, together with aspiration of secretions
may reduce the risk of VAP in these patients.
Study characteristics
This review of existing studies was carried out by the Cochrane Oral Health Group and the evidence is current up to 14 January 2013.
Thirty-five separate research studies were included but only a minority (14%) of the studies were well conducted and described.
All of the studies took place in intensive care units in hospitals. In total there were 5374 participants randomly allocated to treatment.
Participants were critically ill and required assistance from nursing staff for their oral hygiene care. In three of th e included studies
participants were children and in the remaining studies only adults participated. Participants had been hospitalised as medical, surgical
or trauma patients. In 13 studies it was not clear which of these three categories the participants belonged to.
Key results
Effective oral hygiene care is important for ventilated patients in intensive care. We found evidence that chlorhexidine either as a
mouthrinse or a gel reduces the odds of VAP in adults by about 40%. So for example for every 15 people on ventilators in intensive
care, the use of oral hygiene care including chlorhexidine will prevent one person developing VAP. However, we found no evidence that
chlorhexidine makes a difference to the numbers of patients who die in ICU, to the number of days of mechanical ventilation or the
number of days in ICU.
The three studies of children (aged birth to 15 years) showed no evidence of a difference in VAP between the use of chlorhexidine
mouthrinse or gel and placebo in children.
Four studies showed no evidence of a difference between toothbrushing (with or without chlorhexidine) and oral care without tooth-
brushing (with or without chlorhexidine) in the risk of developing VAP. Two studies showed some evidence of a reduction in VAP with
povidone iodine antiseptic mouthrinse.
There was not enough research information available to provide evidence of the effects of other mouth care rinses such as water, saline
or triclosan.
Only two of the included studies reported any adverse effects of the interventions (mild oral irritation (one study) and unpleasant taste
(both chlorhexidine and placebo)), four studies reported that there were no adverse effects and the remaining studies do not mention
adverse effects in the reports.
Quality of the evidence
The evidence presented is of moderate quality. Only 14% of the studies were well conducted and described.
3Oral hygiene care for critically ill patients t o prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 5
S U M M A R Y O F F I N D I N G S F O R T H E M A I N C O M P A R I S O N [Explanation]
Chlorhexidine (mouthrinse or gel) versus placebo/usual care for critically ill patients to prevent ventilator-associated pneumonia (VAP)
Patient or population: Critically ill patients receiving mechanical ventilation
Settings: Intensive care unit (ICU)
Intervention: Chlorhexidine (mouthrinse or gel)
Comparison: Placebo or usual care
Outcomes Illustrative comparative risks* (95% CI) Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed risk Corresponding risk
Control (placebo or
usual care)
Chlorhexidine
(mouthrinse or gel)
VAP
Follow-up: mean 1 month
242 per 1000 160 per 1000
(130 to 197)
OR 0.60
(0.47 to 0.77)
2402
(17 studies)
⊕⊕⊕
moderate
1
This equates to an NNT of
15 (95% CI 10 to 34)
Mortality
Follow-up: mean 1 month
239 per 1000 257 per 1000
(215 to 303)
OR 1.10
(0.87 to 1.38)
2111
(15 studies)
⊕⊕⊕
moderate
1
Duration of ventilation
Days of ventilation re-
quired
Follow-up: mean 1 month
The mean duration of
ventilation in the control
groups ranged from 7 to
18 days
The mean duration of ven-
tilation in the intervention
groups was
0.09 higher
(0.84 lower to 1.01
higher)
933
(6 studies)
⊕⊕⊕
moderate
1
Duration of ICU stay
Follow-up: mean 1 month
The mean duration of ICU
stay in the control groups
ranged from 10 to 24
days
The mean duration of ICU
stay in the intervention
groups was
0.21 higher
(1.48 lower to 1.89
higher)
833
(6 studies)
⊕⊕⊕
moderate
1
4Oral hygiene care for critically ill patients t o prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 6
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the
assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)
CI: confidence interval; NNT: number needed to treat; OR: odds ratio
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate
Very low quality: We are very uncertain about the estimate
1
2 studies at high risk of bias, 11 at unclear risk of bias and 4 at low risk of bias
2
Assumed risk is based on the outcomes in the control groups of the included studies
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
5Oral hygiene care for critically ill patients t o prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 7
B A C K G R O U N D
Description of the condition
Patients in intensive care units in hospital frequently require me-
chanical ventilation because their ability to breathe unassisted is
impaired due to trauma, or as the result of a medical condition
or recent surgery. The se cr iticall y ill patients are also dependent
on hospital staff to meet their needs for nutrition and hygiene,
including oral hygiene.
Overall the research suggests that oral health deteriorates follow-
ing admission to a critical care unit (
Terezakis 2011). Intubation
and critical illness reduce oral immunity, may be associated with
mechanical injury of the mouth or respiratory tract, increase the
likelihood of dry mouth and the presence of the endotracheal
tube may al so make access for oral care more difficult (
Alhazzani
2013
; Labeau 2011). Dental plaque accumulates rapidly in the
mouths of critically ill patients and as the amount of pl aque in-
creases, colonisation by microbial pathogens is likely (
Fourrier
1998; Scannapieco 1992). Plaque colonisation may be exacerbated
in the absence of adequate oral hygiene care and by the drying of
the oral cavity due to prolonged mouth opening which reduces
the buffering and cleansing effects of saliva. In addition, the pa-
tient’s normal defence mechanisms for resisting infection may be
impaired (
Alhazzani 2013; Terpenning 2005). Dental plaque is
a complex biofilm which, once formed, is relatively resistant to
chemical control, requiring mechanical disruption (such as tooth-
brushing) for maximum impact (
Marsh 2010).
One of the complications which may develop in ventilated pa-
tients is ventilator-associated pneumonia (VAP). VAP is generally
defined as a pneumonia developing in a patient who has received
mechanical ventilation for at least 48 hours (
ATS Guideline 2005).
It is thought that the endotracheal tube, which delivers the neces-
sary oxygen to the patient, may also act as a conduit for pathogenic
bacteria which multiply in the oral cavity and move down the tube
into the lungs. Micro-aspiration of pharyngeal secretions may also
occur around an imperfect seal of the cuff of the endotracheal tube
in a ventilated patient. Several studies have shown that micro-aspi-
ration contributes to the development of nosocomial pneumonia
(
Azoulay 2006; Scannapieco 1992; Mojon 2002).
There is increasing evidence in the literature to suggest a link be-
tween colonisation of dental plaque with respiratory pathogens
and VAP (
Azarpazhooh 2006; Estes 1995; Fourrier 1998;
Garrouste-Orgeas 1997; Scannapieco 1992). Scannapieco et al
conducted a survey where 65% of 34 patients in intensive care
units (ICUs) were found to have respiratory pathogen colonisation
in the plaque or oral mucosa or both, compared with only 16%
of 25 patients in dental cl inics (
Scannapieco 1992). Treloar and
co-workers reported that 37.5% of oropharyngeal cultures taken
from orally intubated patients had the same pathogens as sputum
specimens (
Treloar 1995). In another study, pathogens from the
respiratory tract of patients with h ospital-acquired pneumonia ge-
netically matched those from dental plaque (
El-Solh 2004).
Ventilator-associated pneumonia is a relatively common nosoco-
mial infection in critically ill patients, with a reported prevalence
ranging between 6% and 52% (
Apostolopoulou 2003; Edwards
2009
) with some indications that incidence is decreasing as under-
standing of the risk factors and preventative measures improves.
A recent study estimated that the attributable mortality of VAP
to be 10% (
Melsen 2011). Cohor t studies (Apostolopoulou 2003;
Cook 1998) have found that duration of ICU stay is increased in
patients who develop VAP but it is unclear whether this is cause
or effect.
Antibiotics, administered either intraorally as topical pastes or
systemically have been used to prevent VAP and these interven-
tions are evaluated in other Cochrane systematic reviews (
D’Amico
2009
; Selim 2010). Topical antibiotic pastes have been shown to
be effective but are not widely used because of the risk of devel-
oping antibiotic resistant organisms (
Panchabhai 2009). However
overuse of antibiotics is associated with the development of mul-
tidrug resistant pathogens and therefore there is merit in using
other approaches for preventing infections such as VAP.
Description of the intervention
This systematic review evaluates various types of oral hygiene care
as a means of reducing the incidence of VAP in critically ill patients
receiving me chanical ventilation. Oral hygiene care is promoted
in clinical guidelines as a means of reducing the incidence of VAP
but the evidence base is limited (Tablan 2004).
Oral hygiene care includes the use of mouthrinses (water, saline,
antiseptics) applied either as sprays, liquids or with a swab, with
or without toothbrushing (either manual or powered) and tooth-
paste, to remove plaque and debris from the oral cavity. Oral hy-
giene care also involves suction to remove excess fluid, toothpaste
and debris and may be followed by the application of an antiseptic
gel. Antiseptics are broadly defined to include saline, chlorhex-
idine, povidone iodine, cetylpyridium and possibly others, (but
exclude antibiotics).
How the intervention might work
Patients on mechanical ventilation often have a very dry mouth
due to pr ol onged mouth opening which may be exacerbated by
the side effects of medications used in their treatment. In he althy
individuals, saliva functions to maintain oral health through its
lubricating, antibacterial and buffering properties (
Labeau 2011)
but patients on ventilators lack sufficient saliva for this to occur,
and the usual stimuli for saliva production are absent.
Routine oral hygiene care is designed to remove plaque and de-
bris as well as replacing some of the functions of saliva, moist-
ening and rinsing the mouth. Toothbrushing, with either a man-
6Oral hygiene care for critically ill patients t o prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 8
ual or powered toothbrush, removes plaque from teeth and gums
and disrupts the biofilm within which plaque bacteria multiply
(
Whittaker 1996; Zanatta 2011). It is hypothesised that using an
antiseptic, such as chlorhexidine gluconate or povidone-iodine, as
either a rinse or a gel may further reduce the bacterial load or delay
a subsequent increase in bacterial l oad.
However, it is important that during oral hygiene care, the plaque
and de bris are removed from the oral cavity with care in order to
avoid aspiration of contaminated fluids into the respiratory tract.
Raising the head of the bed, and careful use of appropriately main-
tained closed suction systems, together with an appropriately fit-
ted cuff around the endotracheal tube are other important aspects
of care of critically ill patients that are not part of th is systematic
review.
Why it is im portant to do thi s review
Other Cochrane systematic reviews have evaluated the use of top-
ical antibiotic pastes applied to the oral cavity (selective oral de-
contamination
D’Amico 2009), the use of probiotics (Hao 2011)
and systemic antibiotics (
Selim 2010) to prevent VAP. Other pub-
lished reviews have evaluated aspects of oral hygiene care, such as
toothbrushing (
Alhazzani 2013) or use of chlorhexidine (Pineda
2006), and broader reviews have noted the lack of available ev-
idence (
Berry 2007; Shi 2004). Clinical guidelines recommend
the use of oral hygiene care but there is a lack of available evi-
dence as a basis for specifying the essential components of such
care (
Muscedere 2008; Tablan 2004). The goal of this Cochrane
systematic review was to evaluate all oral hygiene care interven-
tions (excluding the use of antibiotics) used in ICU for patients
on ventilators to determine the effects of oral hygiene care on the
development of VAP. We planned to summarise all the available
research in order to facilitate the provision of evidence-based care
for these vulnerable patients.
O B J E C T I V E S
To assess the effects of oral hygiene care on prevention of VAP in
critically ill patients receiving mechanical ventilation in hospital
settings.
M E T H O D S
Criteria for consid eri ng studies for this review
Types of studies
We included in th e review all randomised controlled trials (RCTs)
of oral hygiene care interventions.
Types of participants
Critically ill patients in hospital se ttings receiving mechanical ven-
tilation, without ventilator-associated pneumonia or respiratory
infection at baseline. Trials where only some of the participants
were receiving mechanical ventilation were included if
the outcome of ventilator-associated pneumonia was
reported,
data f or those who had been treated with mechanical
ventilation for a minimum of 48 hours and then developed
nosocomial pneumonia were available.
Trials where participants were undergoing a surgical procedure
that involved mechanical ventilation (e.g. cardiac surgery) were
only included in this review if the oral h ygiene care was given dur-
ing the period of mechanical ventilation which had a minimum
duration of 48 hours. Trials where pre-operative patients received
a single dose of antibacterial rinse or gargle, and received mechan-
ical ventilation only for the duration of the surgery, with no fur-
ther mechanical ventilation and oral hygiene care during the post-
operative period were excluded.
Types of interventions
Intervention group: received clearly defined oral care
procedures such as nurse-assisted toothbrushing, oral and
pharyngeal cavity rinse, decontamination of oropharyngeal
cavities with antiseptics.
Control group: received no treatment, placebo, ’usual care’
or a different specific oral hygiene care procedure.
Trials whe re the inter vention being evaluated was a type of suction
system or variation of method, timing, or place where mechanical
ventilation was introduced (e.g. emergency room or ICU) were
excluded.
We excluded trials of selective decontamination using topical
antibiotics administered to the oral cavity or oropharynx be-
cause these interventions are covered in another Cochrane review
(
D’Amico 2009). Trials of probiotics administered to prevent res-
piratory infections were also excluded as these are covered in a
separate review (
Hao 2011).
Types of outcome measures
Primary outcomes
1. Incidence of VAP (defined as pneumonia developing in a
patient who has received mechanical ventilation for at least 48
hours).
2. Mortality (either ICU mortality if these data were available,
or 30-day mortality).
7Oral hygiene care for critically ill patients t o prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 9
Secondary outcomes
1. Duration of mechanical ventilation or ICU stay or both.
2. Systemic antibiotic use.
3. Colonisation of dental plaque, saliva, oropharyngeal
mucosa or endotracheal aspirates by VAP-associated organisms.
4. Or al health indices such as gingival index, plaque index,
bleeding index, periodontal index etc.
5. Adverse effects of the interventions.
6. Caregivers preferences for oral hygiene care.
7. Economic data.
Searc h meth ods for identification of studi es
For the identification of studies included or considered for this
review, we developed detailed search strategies for each database
searched. These were based on the search strategy developed for
MEDLINE (OVID) but revised appropriately for each database.
Electronic searches
We searched the following el ectronic databases:
Cochrane Oral Health Groups Trials Register (to 14
January 2013) (
Appendix 1)
The Cochrane Central Register of Controlled Trials
(CENTRAL) (The Cochrane Li b rary 2012, Issue 12) (
Appendix
2)
MEDLINE via OVID (1946 to 14 January 2013)
(
Appendix 3)
EMBASE via OVID (1980 to 14 January 2013) (
Appendix
4
)
CINAHL via EBSCO (1980 to 14 January 2013)
(
Appendix 5)
LILACS via BIREME Virtual Health Library (1982 to 14
January 2013) (
Appendix 6)
Chinese Biomedical Literature Database (1978 to 14
January 2013) (
Appendix 7)
China National Knowledge Infrastructure (1994 to 14
January 2013) (
Appendix 8)
Wan Fang Database (1984 to 14 January 2013) (
Appendix
9
)
OpenGrey (1980 to 14 January 2013) (
Appendix 10)
ClinicalTrials.gov (14 January 2013) (Appendix 11).
The search strategy used a combination of controlled vocabulary
and free text terms, details of the MEDLINE search are provided in
Appendix 3. The search of EMBASE was linked with the Cochrane
Oral Health Gr oup filter for identifying RCTs (Appendix 4). All
relevant publications were included irrespective of language.
Searching other resources
All the references lists of the included studies were checked man-
ually to identify any additional studies.
We contacted the first author of the included studies, other experts
in the field and manufacturers of oral hygiene products to request
unpublished relevant information.
Data c ollection and analysis
Selection of studies
Two review authors independently examined the title and abstract
of each article obtained from the searches. If they disagreed with
the inclusion of any study, there was group discussion with other
members of the review team until consensus was achieved. Mul-
tiple reports from a study were linked and the report with more
complete foll ow-up data was the primary source of data.
Full-text copies of potentially relevant reports were obtained and
examined in detail to determine whether the study fulfilled the
eligibility criteria. Any queries were once again resolved by dis-
cussion. Attempts were made to contact study authors to obtain
additional information as necessary.
Data extraction and management
Two review authors independently extracted data f r om the in-
cluded studies into the pre-designed structured data extraction
forms. Any disagreements were resolved by discussion. Contents
of the data extraction included the foll owing items.
(1) General characteristics of the study
Authors, year of publication, country where the study was per-
formed, funding, language of publication, study duration, cita-
tion, contact details for the authors and identifier.
(2) Specific trial characteristics
Basic study design characteristics: sequence generation, allocation
sequence concealment, blinding, incomplete outcome data and
selective outcome reporting etc were collected and presented in
the table of ’Characteristics of included studies’. Verbatim quotes
on the first three issues from original reports were adopted.
Participants: total number, setting, age, sex, country, ethnicity,
socio-demographic details (e.g. education level), diagnostic criteria
of VAP and the presence of co-morbid conditions.
Interventions: we coll ected details of all experimental and control
interventions, such as dosages for dr ugs used and routes of deliv-
ery, format for oral hygiene care, timing and duration of the oral
care procedures. In addition, information on any co-interventions
administered were also collected.
Outcomes: incidence of VAP or other respiratory diseases and
mortality (directly and indirectly attributable), adverse outcomes
resulting fr om the interventions, quantity of pathogenic microor-
ganisms from culture of oropharyngeal materials or tracheal aspi-
rates, indices of the plaque, inflammation of the gum or periodon-
tal tissues etc were collected. All outcome variables were specified
in terms of definition, timing, units and scales.
8Oral hygiene care for critically ill patients t o prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 10
Other results: we also collected summary statistics, sample size,
key conclusions, comments and any explanations provided for
unexpected findings by the study authors. The lead authors of
included studies were contacted if there were issues to be clarified.
Assessment of risk of bias in included studies
Two review authors assessed the risk of bias of all included stud-
ies, independently and in duplicate, using The Cochrane Collab-
orations domain-based, two-part tool as described in Chapter 8
of the Cochrane Handbook for Systematic Reviews of Interventions (
Higgins 2011). Study authors were contacted for clarification or
missing information where necessary. Any disagreements concern-
ing risk of bias were resolved by discussion. A ’Risk of bias table
was completed for each included study. For each domain of risk
of bias, we described what was reported to have happened in the
study in order to provide a rationale for the second part, which
involved assigning a judgement of Low risk’ of bias, ’High risk
of bias, or ’Unclear risk of bias.
For each included study, we assessed the following seven domains
of risk of bias.
Random sequence generation (selection bias): use of simple
randomisation (e.g. random number table, computer-generated
randomisation, central randomisation by a specialised unit),
restricted randomisation (e.g. random permuted blocks),
stratified r andomisation and minimisation were assessed as low
risk of bias. Other forms of simple randomisation such as
repeated coin tossing, throwing dice or dealing cards were also
considered as low risk of bias (
Schulz 2002). Where a study
report used the phrase randomised’ or random allocation but
with no further information we assessed it as unclear for this
domain.
Allocation concealment (selection bias): use of centralised/
remote allocation, pharmacy-controlled randomisation and
sequentially numbered, sealed, opaque envelopes were assessed as
low risk of bias. If a study report did not mention allocation
concealment we assessed it as unclear for this domain.
Blinding of participants and personnel (performance bias):
participants in included studies were in intensive care and on
mechanical ventilation and were therefore unlikely to be aware of
the treatment group to which they were assigned. Where no
placebo was used, caregivers would be aware of the assigned
intervention and it is unclear whether this would introduce a risk
of performance bias. If a study was described as double blind,
and a placebo was used we assumed that caregivers and outcome
assessors were blinded to the allocated treatment. If blinding was
not mentioned, and if no placebo was used we assumed that no
blinding of caregivers occurred and we assessed this domain as at
unclear risk of bias.
Blinding of outcome assessment (detection bias): if
outcome assessor blinding was not mentioned in the trial report
we assessed this domain as at unclear risk of bias.
Incomplete outcome data (attrition bias): where the overall
rate of attrition was high the r isk of attrition bias was assessed as
high. Alte r natively if the numbers of participants, and/or the
reasons for exclusion were diff erent in each arm of the study, risk
of attrition bias was assessed as high. If numbers of participants
randomised or evaluated in each arm of the study were not
reported we assessed this domain as unclear.
Selective reporting (reporting bias): if the study did not
report outcomes stated in the methods section, or reported
outcomes without estimates of variance, we assessed this as at
high risk of reporting bias.
Other bias: any other potential source of bias which might
feasibly alte r the magnitude of the e ffect estimate e.g. baseline
imbalance between study arms in important prognostic factors
(e.g. clinical pulmonary infection scores (CPIS), antibiotic
exposure), early stopping of the trial, or co-interventions or
differences in other treatment between study arms. Other
potential sources of bias were described and risk of bias assessed.
We summarised the risk of bias as follows.
Risk o f bias Interpretation In outcome In included studies
Low risk of bias Plausible bias unlikely to seriously
alter the results
Low risk of bias for al l key domains Most information is from studies at
low risk of bias
Unclear risk of bias Plausible bias that raises some
doubt about the results
Unclear risk of bias for one or more
key domains
Most information is from studies at
low or unclear risk of bias
High risk of bias Plausible bias that seriously weak-
ens confidence in the results
High risk of bias for one or more
key domains
The proportion of information
from studies at high risk of bias is
sufficient to affe ct the interpreta-
tion of results
9Oral hygiene care for critically ill patients t o prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 11
We presented the risk of bias graphically by: (a) proportion of
studies with each judgement (’Low risk’, ’High risk’, and ’Unclear
risk of bias) for each r isk of bias domain (
Figure 1), and (b) cross-
tabulation of judgements by study and by domain (
Figure 2).
Figure 1. Risk of bias graph: review authors’ judgements about each risk of bias item presented as
percentages across all included studies
10Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 12
Figure 2. Risk of bias summary graph: review autho rs’ judgements about each risk of bias item for each
included study
11Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 13
Measures of treatment effect
For dichotomous outcomes, we computed the effe ct measure the
odds ratio (OR) together with the 95% confidence interval. For
continuous outcomes, mean difference (MD) with 95% confi-
dence interval was used to estimate the summary effect.
Unit of analysis issues
The unit of analysis was the patient. The indices of plaque and
gingivitis were measured as mean values for the patients. Episodes
of care were also related back to individual patients.
Dealing with missing data
We contacted the lead author of studies requesting that they sup-
ply any missing data. Missing standard deviations were to be ob-
tained using the methods outlined in the Cochrane Han dbook for
Systematic Reviews of Interventions (Higgins 2011).
Assessment of heterogeneity
To detect heter ogeneity among studies in a meta-analysis, a Chi
2
test with a 0.01 le vel of significance as the cut-off v alue was applied.
The impact of statistical heterogeneity was quantified using the
I
2
statistic. The thresholds of I
2
recommended by the Cochrane
Handbook for Systematic Reviews of Interventions (
Higgins 2011)
0% to 40%: might not be important;
30% to 60%: may represent moderate heterogeneity;
50% to 90%: may represent substantial heterogeneity;
75% to 100%: considerable heterogeneity
were used for interpretation of the results. If considerable hetero-
geneity existed th en it was investigated. We used subgroup analy-
ses to investigate possible differences between the studies.
Assessment of reporting biases
Only a proportion of research projects conducted are ultimately
published in an indexed journal and become easily identifiable for
inclusion in systematic reviews. Reporting biases arise when the re-
porting of research findings is influenced by the nature and direc-
tion of the findings of the research. We investigated and attempted
to minimise potential reporting biases including publication bias,
time lag bias, multiple (duplicate) publication bias and language
bias in this review.
Where there were more than 10 studies in one outcome we con-
structed a funnel plot. We planned to investigate the asymmetry
in the funnel plot (indicating possible publication bias) by under-
taking statistical analysis using the methods introduced by
Egger
1997 (continuous outcome) and Rücker 2008 (dichotomous out-
come) (such analysis would have been done in STATA 11.0).
Data synthesis
Meta-analyses were undertaken for the similar comparisons and
same outcomes across studies. We decided to use random-effects
models providing there were four or more trials in any one meta-
analysis. If different scales were used, standardised mean differ-
ences were calculated.
Subgroup analysis and investigation of heterogeneity
One subgroup analysis was proposed a priori when discussing how
to structure the data comparisons. It was decided to undertake a
subgroup analysis for whether the patients teeth were cleaned or
not as it was hypothesised that antiseptics would be less effective
if toothbrushing was not used to disrupt dental plaque biofilm.
Sensitivity analysis
To determine whether the intervention effects of oral hygiene care
were robust, sensitivity analyses were planned to determine the
effect of those factors, such as exclusion of some studies with ques-
tionable diagnostic criteria for VAP, excluding studies with high
risk of bias, or changing assumptions about missing data on the
estimates of effect.
If the results did not change substantially in sensitivity analyses,
then the conclusion would have been regarded as stable with a
higher degree of certainty. Where sensitivity analyses identified
particular factors that greatly influenced the conclusions of the
review, the plausible causes of the uncertainties would have been
explored, and the results would be interpreted with caution.
Summary of findings
The GRADE system for evaluating quality of the evidence of sys-
tematic reviews (
Guyatt 2008; Higgins 2011) was adopted using
the software GRADEprofiler. The quality of the body of evidence
was assessed with reference to the overall risk of bias of the included
studies, the directness of the evidence, the inconsistency of the
results, the precision of the estimates, and the risk of publication
bias. The quality of the body of evidence was classified into four
categories: high, moderate, low and very low.
R E S U L T S
12Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 14
Description of studies
Results of the search
After removal of duplicates, the electronic search strategies iden-
tified 774 records from English language databases and 234 from
Chinese language databases, which were screened by at least two
review authors against the inclusion criteria for this review. Of
these 937 were discarded and full-text copies of 71 references were
requested. These papers were assessed by at least two review au-
thors to determine the ir eligibility, and from these 35 studies were
identified which met the inclusion criteria for this review. One on-
going study was identified and a further four studies are awaiting
classification because we have not yet obtained full-text copies or
they require translation or both.
The flow diagram is shown in
Figure 3.
13Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 15
Figure 3. Study flow diagram
14Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 16
Included studies
We included 35 RCTs in this review.
Setting
Nine of the included studies were conducted in the USA (
Bopp
2006
; DeRiso 1996; Fields 2008; Grap 2004; Grap 2011; McCartt
2010
; Munro 2009; Prendergast 2012; Scannapieco 2009), seven
in China (
Chen 2008; Feng 2012; Hu 2009; Long 2012; Xu 2007;
Xu 2008; Zhao 2012), four in Brazil (Bellissimo-Rodrigues 2009;
Caruso 2009; Jacomo 2011; Kusahara 2012), three in each of
France (
Fourrier 2000; Fourrier 2005; Seguin 2006) and Spain
(
Lorente 2012; Pobo 2009; Roca Biosca 2011), two in India
(
Panchabhai 2009; Sebastian 2012), and one in each of Australia
(
Berry 2011), Croatia (Cabov 2010), Taiwan(Yao 2011), Thai-
land (
Tantipong 2008), Turkey (Ozcaka 2012), the Netherlands
(Koeman 2006), and the United Kingdom (Needleman 2011).
All of the studies took place in intensive care units in hospitals.
Most of the studies were two-arm parallel group RCTs, but six
studies had three arms (
Berry 2011; Grap 2004; McCartt 2010;
Scannapieco 2009; Seguin 2006; Xu 2007) and one study had
four arms (
Munro 2009).
Participants
In total there were 5374 participants randomly allocated to treat-
ment in 34 RCTs included in this review and the other trial did
not state how many patients were included (
Fields 2008). The cri-
teria for inclusion in these studies generally specified no prior in-
tubation, no cl inically apparent pneumonia at baseline (except for
Sebastian 2012, where most of the children admitted to ICU had
pneumonia already and criteria of the Centers for Disease Control
(CDC) were strictly applied to diagnose subsequent VAP) and an
expected requirement for mechanical ventilation for a minimum
of 48 hours. Participants were critically ill and required assistance
from nursing staff for their oral hygiene care. In three of the in-
cluded studies par ticipants were children (
Jacomo 2011; Kusahara
2012
; Sebastian 2012) and in the remaining studies only adults
participated.
In four studies (
Koeman 2006; McCartt 2010; Munro 2009;
Panchabhai 2009) participants were either medical or surgical
patients, in another four studies participants were described as
trauma patients (
Grap 2011; Prendergast 2012; Scannapieco
2009
; Seguin 2006), six studies recruited surgical patients only
(
Chen 2008; DeRiso 1996; Jacomo 2011; Kusahara 2012; Yao
2011
; Zhao 2012), eight studies recruited medical patients
only (
Cabov 2010; Fields 2008; Fourrier 2000; Fourrier 2005;
Needleman2011; Ozcaka 2012; Sebastian 2012; Tantipong 2008)
and in the remaining 13 studies it was not clearly stated whether
participants were medical, surgical or trauma cases.
Classification of the interventions
The interventions in the included studies were in three broad
groups.
Chlorhexidine.
Chlorhexidine solution (applied as mouthrinse, spray
or on a swab).
Chlorhexidine gel.
Toothbrushing.
Powered.
Manual.
Other solutions.
Saline.
Bicarbonate.
Povidone iodine.
Triclosan.
These interventions were used either singly or in combinations.
We evaluated the following comparisons.
1. Chlorhexidine versus placebo/usual care with or without
toothbrushing (20 studies:
Bellissimo-Rodrigues 2009; Berry
2011
; Bopp 2006; Cabov 2010; Chen 2008; DeRiso 1996;
Fourrier 2000; Fourrier 2005; Grap 2004; Grap 2011; Jacomo
2011
; Koeman 2006; Kusahara 2012; McCartt 2010; Munro
2009
; Ozcaka 2012; Panchabhai 2009; Scannapieco 2009;
Sebastian 2012; Tantipong 2008).
2. Toothbr ushing versus no toothbrushing (in addition to
usual care) (eight studies:
Bopp 2006; Fields 2008; Lorente
2012; Munro 2009; Needleman 2011; Pobo 2009; Roca Biosca
2011
; Yao 2011).
3. Powered toothbrushing versus manual toothbrushing (one
study:
Prendergast 2012).
4. Other solutions (nine studies).
i) Saline (
Caruso 2009; Hu 2009; Seguin 2006; Xu
2007; Xu 2008).
ii) Bicarbonate (
Berry 2011).
iii) Povidone iodine (
Feng 2012; Long 2012; Seguin
2006
).
iv) Triclosan (
Zhao 2012).
Three studies (
Berry 2011; Bopp 2006; Munro 2009) are included
in two comparisons.
Placebos used included saline (
Chen 2008; Feng 2012; Hu 2009;
Ozcaka 2012; Seguin 2006; Tantipong 2008; Xu 2007; Xu 2008),
potassium permanganate (
Panchabhai 2009), half-strength hy-
drogen peroxide (
Bopp 2006), water/alcohol mixture (DeRiso
1996
; Jacomo 2011), placebo gel (Fourrier 2005; Koeman 2006;
15Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 17
Kusahara 2012;Sebastian 2012), base solution (Scannapieco 2009)
or water (
Berry 2011). In one trial the nature of the placebo was
not specified (
Bellissimo-Rodrigues 2009). In some of these stud-
ies the intervention described as placebo may have had some an-
tibacterial activity but this was considered to be negligible com-
pared to the active intervention.
In nine studies the control group received usual/standard care (
Caruso 2009; Fields 2008; Fourrier 2000; Grap 2004; Grap 2011;
McCartt 2010; Munro 2009; Seguin 2006; Yao 2011) (for specific
details see
Characteristics of included studies), and in four studies
there was a head to head comparison between two potentially
active interventions (
Needleman 2011; Pobo 2009; Prendergast
2012; Roca Biosca 2011).
Measures of primary outcomes
Incidence of VAP
The primary outcome of our review is ventilator-associated pneu-
monia (VAP) defined as pneumonia developing in a person who
has been on mechanical ventilation for at l east 48 hours. VAP was
fully reported by 28 of the included studies (
Bellissimo-Rodrigues
2009
; Berry 2011; Bopp 2006; Cabov 2010; Caruso 2009; Chen
2008
; DeRiso 1996; Feng 2012; Fourrier 2005; Grap 2011;
Hu 2009; Jacomo 2011; Koeman 2006; Kusahara 2012; Long
2012; Lorente 2012; Ozcaka 2012; Panchabhai 2009; Pobo 2009;
Prendergast 2012; Scannapieco 2009; Sebastian 2012; Seguin
2006
; Tantipong 2008; Xu 2007; Xu 2008; Yao 2011; Zhao 2012),
one study reported only that there was no difference in VAP be-
tween the two arms of the study (
Roca Biosca 2011) and in an-
other study it was reported that the VAP rate dropped to zero in
the intervention group but the control group event rate was not
reported (
Fields 2008 ). Two studies (Fourrier 2000; Hu 2009)
reported the outcome of nosocomial pneumonia but it was not
clear in the trial reports whether all those who developed this out-
come had been on mechanical ventilation for at least 48 hours.
One study repor ted mean CPIS score per group but did not record
cases of VAP (
McCartt 2010). We sought clarification from the
trial authors but to date no further data have been received.
Diagnostic criteria for the outcome of ventilator-associated pneu-
monia were specified in 21 of the studies which reported the out-
come of VAP (60%). Sixteen studies (
Berry 2011; Cabov 2010;
Caruso 2009; Fourrier 2000; Fourrier 2005; Grap 2004; Grap
2011; Koeman 2006; Kusahara 2012; McCartt 2010; Munro
2009
; Pobo 2009; Scannapieco 2009; Seguin 2006; Tantipong
2008
; Yao 2011) used Pugins criteria (Cook 1998; Pugin 1991)
which form the basis of the CPIS score, based on the presence of
an infiltrate on chest radiograph, plus two or more of the follow-
ing: temperature greater than 38.5º C or less than 35º C, white
blood cell count greater than 11,000/mm
3
or less than 4000/mm
3
, mucopurulent or purulent bronchial secretions, or more than
20% increase in fraction of inspired oxygen required to maintain
saturation above 92%. In
Ozcaka 2012 no specific criteria were
reported, but communication from the author confirmed that pa-
tients with new pulmonary infiltrates or opacities on the chest X-
ray were pre-diagnosed VAP and lower tracheal mini-bronchoalve-
olar lavage (mini-BAL) samples were taken and then subjects were
diagnosed according to CPIS criteria. Patients who had a score
6 and the presence of 10
4
colony-forming units/mL of a target
potential respiratory bacterial pathogen (PRP) in mini-BAL were
diagnosed VAP.
A further six studies (Bellissimo-Rodrigues 2009; DeRiso 1996;
Fields 2008; Jacomo 2011; Panchabhai 2009; Sebastian 2012)
used the CDC criteria as described in Horan 2008.
Four studies (
Chen 2008; Feng 2012; Xu 2007; Xu 2008) used the
criteria of the Chinese Society of Respiratory Diseases: presence
of new infiltrates on chest radiographs developed after 48 hours
of mechanical ventilation with any two of the following items: (a)
temperature greater than 38º C, (b) change in ch aracteristics of
bronchial secretions from mucoid to mucopurulent or purulent,
(c) white cell count greater than 10,000/mm
3
, (d) positive culture
of tracheal aspirate or positive culture of bronchoalveolar lavage
fluid or both, or (e) arterial oxygen tension/inspiratory fraction
of oxygen PaO
2
/FiO
2
decreased over 30% within the period of
ventilation.
The study by
Hu 2009 reported the outcome of VAP based on
clinical examination plus three criter ia: chest radiograph, white
cell count and culture of the aspirate from lower respiratory tract
(but no precise parameters were specified). In
Lorente 2012 the
diagnosis of VAP was made by an expert panel blinded to the al -
located intervention but the diagnostic criteria were not specified.
The study by
Prendergast 2012 had a single diagnostic criteria of a
new or worsening pulmonary infiltrate on chest radiograph. Two
studies used positive culture from the lower respiratory tract as
criteria for diagnosis of VAP (
Long 2012; Zhao 2012).
In the remaining two studies with the outcome of VAP, diagnostic
criteria were not reported (
Bopp 2006; Roca Biosca 2011) and the
study by
Needleman 2011 did not report the outcome of VAP.
Mortality
Twenty included studies reported the outcome of mor tality ei-
ther as ICU mortality or 30-day mortality (
Bellissimo-Rodrigues
2009
; Berry 2011; Cabov 2010; Caruso 2009; Fourrier 2000;
Fourrier 2005; Jacomo 2011; Kusahara 2012; Long 2012; Lorente
2012
; Munro 2009; Ozcaka 2012; Panchabhai 2009; Pobo 2009;
Prendergast 2012; Scannapieco 2009; Sebastian 2012; Seguin
2006; Tantipong 2008; Yao 2011). Where ICU mortality was re-
ported we used these data, and where ICU mortality was not re-
ported we used 30-day mortality.
Measures of secondary outcomes
16Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.