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

  1. Zongdao Shi1,
  2. Huixu Xie1,
  3. Ping Wang2,
  4. Qi Zhang3,
  5. Yan Wu4,
  6. E Chen5,
  7. Linda Ng6,
  8. Helen V Worthington7,
  9. Ian Needleman8,
  10. Susan Furness7,*

Editorial Group: Cochrane Oral Health Group

Published Online: 13 AUG 2013

Assessed as up-to-date: 14 JAN 2013

DOI: 10.1002/14651858.CD008367.pub2


How to Cite

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.

Author Information

  1. 1

    West China College of Stomatology, Sichuan University, Department of Oral and Maxillofacial Surgery, State Key Laboratory of Oral Diseases, Chengdu, Sichuan, China

  2. 2

    West China College of Stomatology, Sichuan University, Department of Dental Implantation, Chengdu, Sichuan, China

  3. 3

    West China College of Stomatology, Sichuan University, Department of Oral Implantology, State Key Laboratory of Oral Diseases, Chengdu, Sichuan, China

  4. 4

    Chongqing Medical University, Department of Orthodontics, Chongqing, China

  5. 5

    West China College of Stomatology, Sichuan University, Department of Paediatric Dentistry, Chengdu, Sichuan, China

  6. 6

    University of Queensland, School of Nursing and Midwifery, South Brisbane, Queensland, Australia

  7. 7

    School of Dentistry, The University of Manchester, Cochrane Oral Health Group, Manchester, UK

  8. 8

    UCL Eastman Dental Institute, Unit of Periodontology and International Centre for Evidence-Based Oral Healthcare, London, UK

*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.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 13 AUG 2013

SEARCH

 

Summary of findings    [Explanations]

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

 
Summary of findings for the main comparison. Chlorhexidine (mouthrinse or gel) versus placebo/usual care for critically ill patients to prevent ventilator-associated pneumonia

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

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Control (placebo or usual care)Chlorhexidine (mouthrinse or gel)

VAP
Follow-up: mean 1 month
242 per 1000160 per 1000
(130 to 197)
OR 0.60
(0.47 to 0.77)
2402
(17 studies)
⊕⊕⊕⊝
moderate1
This equates to an NNT of 15 (95% CI 10 to 34)

Mortality
Follow-up: mean 1 month
239 per 1000257 per 1000
(215 to 303)
OR 1.10
(0.87 to 1.38)
2111
(15 studies)
⊕⊕⊕⊝
moderate1

Duration of ventilation
Days of ventilation required
Follow-up: mean 1 month
The mean duration of ventilation in the control groups ranged from 7 to 18 daysThe mean duration of ventilation in the intervention groups was
0.09 higher
(0.84 lower to 1.01 higher)
933
(6 studies)
⊕⊕⊕⊝
moderate1

Duration of ICU stay
Follow-up: mean 1 month
The mean duration of ICU stay in the control groups ranged from 10 to 24 daysThe mean duration of ICU stay in the intervention groups was
0.21 higher
(1.48 lower to 1.89 higher)
833
(6 studies)
⊕⊕⊕⊝
moderate1

*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

 Summary of findings 2 Toothbrushing (± chlorhexidine) versus no toothbrushing (± chlorhexidine) for critically ill patients to prevent ventilator-associated pneumonia

 

Background

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Description of the condition

Patients in intensive care units in hospital frequently require mechanical ventilation because their ability to breathe unassisted is impaired due to trauma, or as the result of a medical condition or recent surgery. These critically 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 following 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 also 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 plaque increases, 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 patient'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 toothbrushing) for maximum impact (Marsh 2010).

One of the complications which may develop in ventilated patients 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 necessary 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-aspiration contributes to the development of nosocomial pneumonia (Azoulay 2006; Scannapieco 1992; Mojon 2002).

There is increasing evidence in the literature to suggest a link between 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 clinics (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 hospital-acquired pneumonia genetically matched those from dental plaque (El-Solh 2004).

Ventilator-associated pneumonia is a relatively common nosocomial 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 understanding of the risk factors and preventative measures improves. A recent study estimated that the attributable mortality of VAP to be 10% (Melsen 2011). Cohort 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 interventions 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 developing antibiotic resistant organisms (Panchabhai 2009). However overuse of antibiotics is associated with the development of multidrug 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 mechanical 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 toothpaste, to remove plaque and debris from the oral cavity. Oral hygiene 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, chlorhexidine, 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 prolonged mouth opening which may be exacerbated by the side effects of medications used in their treatment. In healthy 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 debris as well as replacing some of the functions of saliva, moistening and rinsing the mouth. Toothbrushing, with either a manual 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 load.

However, it is important that during oral hygiene care, the plaque and debris 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 maintained closed suction systems, together with an appropriately fitted cuff around the endotracheal tube are other important aspects of care of critically ill patients that are not part of this systematic review.

 

Why it is important to do this review

Other Cochrane systematic reviews have evaluated the use of topical antibiotic pastes applied to the oral cavity (selective oral decontamination D'Amico 2009), the use of probiotics (Hao 2011) and systemic antibiotics (Selim 2010) to prevent VAP. Other published 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 evidence (Berry 2007; Shi 2004). Clinical guidelines recommend the use of oral hygiene care but there is a lack of available evidence 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 interventions (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.

 

Objectives

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

To assess the effects of oral hygiene care on prevention of VAP in critically ill patients receiving mechanical ventilation in hospital settings.

 

Methods

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Criteria for considering studies for this review

 

Types of studies

We included in the review all randomised controlled trials (RCTs) of oral hygiene care interventions.

 

Types of participants

Critically ill patients in hospital settings receiving mechanical ventilation, 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 for 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 hygiene care was given during 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 mechanical ventilation only for the duration of the surgery, with no further 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 where the intervention 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 because these interventions are covered in another Cochrane review (D'Amico 2009). Trials of probiotics administered to prevent respiratory 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).

 

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. Oral 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.

 

Search methods for identification of studies

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 electronic databases:

  • Cochrane Oral Health Group's Trials Register (to 14 January 2013) (Appendix 1)
  • The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 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 Group 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 manually 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 collection 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. Multiple reports from a study were linked and the report with more complete follow-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 discussion. Attempts were made to contact study authors to obtain additional information as necessary.

 

Data extraction and management

Two review authors independently extracted data from the included studies into the pre-designed structured data extraction forms. Any disagreements were resolved by discussion. Contents of the data extraction included the following items.

(1) General characteristics of the study
Authors, year of publication, country where the study was performed, funding, language of publication, study duration, citation, 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 collected details of all experimental and control interventions, such as dosages for drugs used and routes of delivery, 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 from the interventions, quantity of pathogenic microorganisms from culture of oropharyngeal materials or tracheal aspirates, indices of the plaque, inflammation of the gum or periodontal tissues etc were collected. All outcome variables were specified in terms of definition, timing, units and scales.

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 studies, independently and in duplicate, using The Cochrane Collaboration's 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 concerning 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 randomisation 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 risk of attrition bias was assessed as high. Alternatively if the numbers of participants, and/or the reasons for exclusion were different 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 alter the magnitude of the effect 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 of biasInterpretationIn outcomeIn included studies

Low risk of biasPlausible bias unlikely to seriously alter the resultsLow risk of bias for all key domainsMost information is from studies at low risk of bias

Unclear risk of biasPlausible bias that raises some doubt about the resultsUnclear risk of bias for one or more key domainsMost information is from studies at low or unclear risk of bias

High risk of biasPlausible bias that seriously weakens confidence in the resultsHigh risk of bias for one or more key domainsThe proportion of information from studies at high risk of bias is sufficient to affect the interpretation of results



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 risk of bias domain (Figure 1), and (b) cross-tabulation of judgements by study and by domain (Figure 2).

 FigureFigure 1. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
 FigureFigure 2. Risk of bias summary graph: review authors' judgements about each risk of bias item for each included study

 

Measures of treatment effect

For dichotomous outcomes, we computed the effect measure the odds ratio (OR) together with the 95% confidence interval. For continuous outcomes, mean difference (MD) with 95% confidence 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 supply any missing data. Missing standard deviations were to be obtained using the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

 

Assessment of heterogeneity

To detect heterogeneity among studies in a meta-analysis, a Chi2 test with a 0.01 level of significance as the cut-off value was applied. The impact of statistical heterogeneity was quantified using the I2 statistic. The thresholds of I2 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 heterogeneity existed then it was investigated. We used subgroup analyses 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 reporting of research findings is influenced by the nature and direction 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 constructed a funnel plot. We planned to investigate the asymmetry in the funnel plot (indicating possible publication bias) by undertaking statistical analysis using the methods introduced by Egger 1997 (continuous outcome) and Rücker 2008 (dichotomous outcome) (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 differences 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 questionable 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    [Explanations]

The GRADE system for evaluating quality of the evidence of systematic 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.

 

Results

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Description of studies

 

Results of the search

After removal of duplicates, the electronic search strategies identified 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 authors to determine their eligibility, and from these 35 studies were identified which met the inclusion criteria for this review. One ongoing 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.

 FigureFigure 3. Study flow diagram

 

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), Thailand (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 treatment in 34 RCTs included in this review and the other trial did not state how many patients were included (Fields 2008). The criteria for inclusion in these studies generally specified no prior intubation, no clinically 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 included studies participants 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; Needleman 2011; 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. Toothbrushing 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).
  2. Powered toothbrushing versus manual toothbrushing (one study: Prendergast 2012).
  3. Other solutions (nine studies).
    1. Bicarbonate (Berry 2011).
    2. Povidone iodine (Feng 2012; Long 2012; Seguin 2006).
    3. 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 hydrogen peroxide (Bopp 2006), water/alcohol mixture (DeRiso 1996; Jacomo 2011), placebo gel (Fourrier 2005; Koeman 2006; 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 studies the intervention described as placebo may have had some antibacterial activity but this was considered to be negligible compared 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 pneumonia (VAP) defined as pneumonia developing in a person who has been on mechanical ventilation for at least 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 between the two arms of the study (Roca Biosca 2011) and in another 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 outcome had been on mechanical ventilation for at least 48 hours. One study reported 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 pneumonia were specified in 21 of the studies which reported the outcome 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 Pugin's 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 following: temperature greater than 38.5º C or less than 35º C, white blood cell count greater than 11,000/mm3 or less than 4000/mm3, 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 patients with new pulmonary infiltrates or opacities on the chest X-ray were pre-diagnosed VAP and lower tracheal mini-bronchoalveolar 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 ≥ 104 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 characteristics of bronchial secretions from mucoid to mucopurulent or purulent, (c) white cell count greater than 10,000/mm3, (d) positive culture of tracheal aspirate or positive culture of bronchoalveolar lavage fluid or both, or (e) arterial oxygen tension/inspiratory fraction of oxygen PaO2/FiO2 decreased over 30% within the period of ventilation.

The study by Hu 2009 reported the outcome of VAP based on clinical examination plus three criteria: 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 allocated 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 mortality either 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 reported we used these data, and where ICU mortality was not reported we used 30-day mortality.

 

Measures of secondary outcomes

 
Duration of ventilation

There were 15 studies which reported this outcome (Bellissimo-Rodrigues 2009; Caruso 2009; Fourrier 2000; Fourrier 2005; Hu 2009; Koeman 2006; Long 2012; Lorente 2012; Ozcaka 2012; Pobo 2009; Prendergast 2012; Scannapieco 2009; Seguin 2006; Xu 2008; Zhao 2012). The studies by Jacomo 2011 and Sebastian 2012 reported the median duration of ventilation and the range for each group, but these data could not be combined in a meta-analysis.

 
Duration of ICU stay

There were 14 studies reporting this outcome (Bellissimo-Rodrigues 2009; Bopp 2006; Caruso 2009; Fourrier 2000; Fourrier 2005; Koeman 2006; Kusahara 2012; Lorente 2012; Ozcaka 2012; Panchabhai 2009; Pobo 2009; Prendergast 2012; Seguin 2006; Zhao 2012). The studies by Jacomo 2011 and Sebastian 2012 reported the median ICU stay and the range for each group, but these data could not be combined in a meta-analysis.

 
Systemic antibiotic therapy

There were three studies which reported some measure of systemic antibiotic use. DeRiso 1996 reported the number of patients in each group who required treatment of an infection with systemic antibiotics during their ICU stay, and Fourrier 2005 and Scannapieco 2009 both reported the mean number of days of systemic antibiotic use in the intervention and control groups.

 
Microbial colonisation

Oropharyngeal colonisation is considered to be an important source in the pathogenesis of VAP and reducing bacterial colonisation may be a step towards prevention of VAP. Unfortunately only six studies (Cabov 2010; Feng 2012; Grap 2004; Kusahara 2012; Needleman 2011; Zhao 2012) reported data for the outcome of numbers of participants with microbial colonisation of plaque in each treatment group, and each study used a slightly different measure. Additionally, Fourrier 2005 reported the bacteria cultured from dental plaque only for the subgroup of participants who developed a nosocomial infection, and Scannapieco 2009 reported a graph of mean log of potential plaque respiratory pathogens in each group, but we were unable to use these measures in our meta-analysis.

 
Oral health indices

Plaque indices were mentioned as outcomes in five studies (Needleman 2011; Ozcaka 2012; Roca Biosca 2011; Scannapieco 2009; Yao 2011). Complete data for plaque indices were available in two studies (Needleman 2011; Ozcaka 2012), were supplied by the corresponding author in one study (Yao 2011), one study (Scannapieco 2009) reported this outcome in graphs only and the other study (Roca Biosca 2011) did not report any estimate of variance so these data could not be used in this review.

 
Adverse effects

Only two of the included studies (Bellissimo-Rodrigues 2009; Tantipong 2008) reported adverse effects of the interventions, four studies reported that there were no adverse effects (Berry 2011; Jacomo 2011; Ozcaka 2012; Sebastian 2012) and the remaining studies did not mention adverse effects in the reports.

 

Excluded studies

There were 25 excluded studies. Reasons are summarised below.

For further information see Characteristics of excluded studies.

 

Risk of bias in included studies

 

Allocation

 

Sequence generation

Twenty-six of the included studies described clearly a random method of sequence generation and were assessed at low risk of bias for this domain. The remaining nine studies (Caruso 2009; Feng 2012; Fields 2008; Long 2012; Panchabhai 2009; Roca Biosca 2011; Xu 2007; Xu 2008; Zhao 2012) stated that allocation was random but provided no further details and were therefore assessed at unclear risk of bias for this domain.

 

Allocation concealment

Allocation concealment was clearly described in 19 of the included studies and they were assessed at low risk of bias for this domain. In 13 studies (Cabov 2010; Caruso 2009; Chen 2008; Feng 2012; Fourrier 2000; Grap 2011; Long 2012; Lorente 2012; McCartt 2010; Panchabhai 2009; Xu 2007; Yao 2011; Zhao 2012) allocation concealment was not described in sufficient detail to determine risk of bias and these studies were assessed at unclear risk of bias. The remaining three studies (Bopp 2006; Tantipong 2008; Xu 2008) were assessed at high risk of bias because the allocation was not concealed from the researchers.

The risk of selection bias based on combined assessment of these two domains was high in three studies (Bopp 2006; Tantipong 2008; Xu 2008), unclear in 15 studies (Cabov 2010; Caruso 2009; Chen 2008; Feng 2012; Fields 2008; Fourrier 2000; Grap 2011; Long 2012; Lorente 2012; McCartt 2010; Panchabhai 2009; Roca Biosca 2011; Xu 2007; Yao 2011; Zhao 2012) and low in the remaining 17 studies.

 

Blinding

Ten studies (Bellissimo-Rodrigues 2009; Cabov 2010; DeRiso 1996; Fourrier 2005; Jacomo 2011; Koeman 2006; Kusahara 2012; Ozcaka 2012; Scannapieco 2009; Sebastian 2012) were described as double blind and were assessed at low risk of performance bias. In the remaining 25 studies blinding of the patients and their caregivers to the allocated treatment was not possible because the active and control treatments were so different, and no placebos were used. These studies were assessed at unclear risk of performance bias.

Blinding of outcome assessment was possible in all of the included studies and was described in 22 studies (Bellissimo-Rodrigues 2009; Berry 2011; Cabov 2010; Caruso 2009; DeRiso 1996; Fourrier 2000; Fourrier 2005; Grap 2004; Hu 2009; Jacomo 2011; Koeman 2006; Kusahara 2012; Lorente 2012; Needleman 2011; Ozcaka 2012; Panchabhai 2009; Pobo 2009; Prendergast 2012; Scannapieco 2009; Sebastian 2012; Tantipong 2008; Yao 2011) which were assessed as being at low risk of detection bias. Seven of the included studies (Bopp 2006; Grap 2011; McCartt 2010; Munro 2009; Seguin 2006; Xu 2007; Xu 2008) reported no blinding of outcome assessment and were assessed at high risk of detection bias. In the remaining six studies there was insufficient information provided and the risk of detection bias was assessed as unclear.

 

Incomplete outcome data

In the studies included in this review loss of participants during the course of the study is to be expected as these critically ill people leave the intensive care unit either because they recover and no longer require mechanical ventilation, or because they die from their illness. In 20 of the included studies (Bellissimo-Rodrigues 2009; Bopp 2006; Cabov 2010; Caruso 2009; Chen 2008; Feng 2012; Fourrier 2005; Jacomo 2011; Koeman 2006; Kusahara 2012; Long 2012; Lorente 2012; Ozcaka 2012; Pobo 2009; Sebastian 2012; Seguin 2006; Xu 2007; Xu 2008; Yao 2011; Zhao 2012) either all the randomised participants were included in the outcome, or the number of losses/withdrawals and the reasons given were similar in both arms of the study, and these studies were assessed at low risk of attrition bias.

Eleven of the included studies were assessed at high risk of attrition bias because the numbers and reasons for withdrawal/exclusion were different in each arm of the study, or because the number of participants withdrawn or excluded from the outcomes evaluation were high and insufficient information was provided (Berry 2011; Fields 2008; Grap 2004; Grap 2011; Hu 2009; McCartt 2010; Munro 2009; Needleman 2011; Prendergast 2012; Roca Biosca 2011; Scannapieco 2009). In the remaining four studies there was insufficient information available to determine the risk of attrition bias.

 

Selective reporting

Twenty-three of the included studies (Bellissimo-Rodrigues 2009; Berry 2011; Cabov 2010; Caruso 2009; DeRiso 1996; Feng 2012; Fourrier 2000; Fourrier 2005; Koeman 2006; Kusahara 2012; Long 2012; Lorente 2012; Needleman 2011; Ozcaka 2012; Panchabhai 2009; Pobo 2009; Prendergast 2012; Scannapieco 2009; Seguin 2006; Xu 2007; Xu 2008; Yao 2011; Zhao 2012) reported the outcomes specified in their methods section in full, or this information was supplied by trial authors, and these studies were assessed at low risk of reporting bias.

Four studies did not report all the outcomes specified in their methods sections (Grap 2004; Grap 2011; McCartt 2010; Roca Biosca 2011), one study reported outcomes as percentages, and the denominators for each arm were unclear (Hu 2009), and one study did not report the number of participants evaluated (Fields 2008). These six trials were assessed at high risk of reporting bias.

The remaining six trials (Bopp 2006; Chen 2008; Jacomo 2011; Munro 2009; Sebastian 2012; Tantipong 2008) were assessed at unclear risk of reporting bias because there was insufficient information reported to make a clear judgement.

 

Other potential sources of bias

Four studies were assessed at high risk of other bias. The study by Berry 2011 was stopped early due to withdrawal of one of the investigational products by a regulatory authority, and the study by Pobo 2009 was stopped after 37% of the planned 400 patients had been recruited because there appeared to be no difference between the study arms in the outcome of VAP. Grap 2011 did not report baseline data for each randomised treatment group but the trial report noted that there was a "statistically significant difference in gender and CPIS score between groups at baseline", and we considered that this difference was likely to have biased the results. In the study by Scannapieco 2009 the imputations used for the missing data were unclear and the pre-study exposure to systemic antibiotics was greater in the control group, so this study was assessed at high risk of other bias.

In nine studies (Chen 2008; Fields 2008; Kusahara 2012; Long 2012; Panchabhai 2009; Roca Biosca 2011; Tantipong 2008; Yao 2011; Zhao 2012) the risk of other bias was assessed as unclear. The reasons for this are as follows. The participants in the treatment group in the study by Chen 2008 received a co-intervention that was not given to the control group, and in both Fields 2008 and Roca Biosca 2011 the study reports contained insufficient information for us to be confident that study methodology was robust. In the study by Kusahara 2012, there was a statistically significant difference in the age of the children in each arm of the study and we are unclear whether this is associated with potential bias. Panchabhai 2009 reported baseline characteristics only for those participants completing the study, Tantipong 2008 included participants treated in different units of the hospital where care and co-interventions are likely to have been different, and in Yao 2011 there is no information as to how the edentulous participants in each arm were treated. Long 2012 and Zhao 2012 reported the criteria for VAP diagnosis as being positive culture of lower respiratory tract secretions, with no other criteria and it is unclear if this would have introduced a bias in these unblinded studies.

The remaining 22 studies were assessed at low risk of other bias.

 

Overall risk of bias

Overall just five of the included studies (14%) were assessed at low risk of bias (Bellissimo-Rodrigues 2009; Fourrier 2005; Koeman 2006; Ozcaka 2012; Sebastian 2012) for all domains and 13 studies (37%) were at unclear risk of bias for at least one domain. Nearly half of the included studies (17 studies, 49%) were at high risk of bias in at least one domain (Figure 1; Figure 2).

 

Effects of interventions

See:  Summary of findings for the main comparison Chlorhexidine (mouthrinse or gel) versus placebo/usual care for critically ill patients to prevent ventilator-associated pneumonia;  Summary of findings 2 Toothbrushing (± chlorhexidine) versus no toothbrushing (± chlorhexidine) for critically ill patients to prevent ventilator-associated pneumonia

 

Comparison 1: Chlorhexidine versus placebo/usual care (with or without toothbrushing)

Chlorhexidine antiseptic was evaluated in a total of 20 studies included in this review, but only 17 studies could be included in meta-analysis for VAP. One study was a very small pilot study (Bopp 2006, n = 5) and no usable outcome data could be extracted, another study (McCartt 2010) did not report outcome data in a form that could be used in a meta-analysis. The study by Scannapieco 2009 reported data in a graph only and stated that there was no difference between the two chlorhexidine groups and the control group in the outcome of VAP. Available data from these studies are recorded in Additional  Table 1.

Five of the 20 studies were assessed at high risk of bias (Bopp 2006; Grap 2004; Grap 2011; McCartt 2010; Munro 2009), four studies were at low risk of bias (Bellissimo-Rodrigues 2009; Fourrier 2005; Koeman 2006; Ozcaka 2012) and the remaining 11 studies were at unclear risk of bias.

These studies have been subgrouped according to whether chlorhexidine was administered as a liquid mouthrinse or a gel, and whether chlorhexidine was used in conjunction with toothbrushing or not.

 

Incidence of VAP

Overall the combined meta-analysis of 17 studies (two at high risk of bias, 11 at unclear risk of bias and four at low risk of bias) showed a reduction in VAP with use of chlorhexidine odds ratio (OR) 0.60, 95% confidence interval (CI) 0.47 to 0.77, P < 0.001, I2 = 21%) ( Analysis 1.1). The statistical heterogeneity observed in this estimate is not likely to be important.

Seven studies (with a total of 1037 participants) compared chlorhexidine solution (0.12% or 0.2%) with either placebo (six studies) or 'usual care' (Grap 2011) without toothbrushing. However, six studies report the use of a swab to either clean the mouth prior to chlorhexidine application, or to ensure that the chlorhexidine solution was applied to all oral surfaces. (In the study by Chen 2008 the mode of application is unclear.)

The meta-analysis showed a reduction in VAP in the chlorhexidine group (OR 0.60, 95% CI 0.38 to 0.94, P = 0.03, I2 = 41%) ( Analysis 1.1, Subgroup 1.1.1). This equates to a number needed to treat (NNT) of 15 (95% CI 10 to 34).

A further five studies (669 participants) compared chlorhexidine gel (0.2% or 2%) with placebo (no toothbrushing in either group) and the meta-analysis showed a similar reduction in VAP associated with chlorhexidine gel (OR 0.57, 95% CI 0.31 to 1.06, P = 0.08, I2 = 45%) ( Analysis 1.1, Subgroup 1.1.2).

Three studies (total 408 participants) compared chlorhexidine solution (2%, 0.12% or 0.2%) with placebo (with toothbrushing in both groups). The meta-analysis showed a reduction in VAP in the chlorhexidine group (OR 0.44, 95% CI 0.23 to 0.85, P = 0.01, I2 = 0%) ( Analysis 1.1, Subgroup 1.1.3).

A further study (Kusahara 2012, including 96 children) at unclear risk of bias compared chlorhexidine gel (0.12%) with placebo (with toothbrushing in both groups) and found no difference in the incidence of VAP ( Analysis 1.1, Subgroup 1.1.4).

Munro 2009 reported the results from some of the patients randomised into a study with a factorial design. This study showed a reduction in VAP which did not attain statistical significance (P = 0.06) associated with the use of chlorhexidine, where exposure to toothbrushing was equal in both groups ( Analysis 1.1, Subgroup 1.1.5).

The pilot study by Bopp 2006 also showed a reduction in VAP associated with chlorhexidine. McCartt 2010 did not report VAP as an outcome, but instead reported mean CPIS scores. While CPIS > 6 may generally be considered to indicate VAP, this study did not dichotomise the outcome data. Mean CPIS score showed no evidence of a difference between chlorhexidine alone, chlorhexidine + toothbrushing and usual care, perhaps because mean CPIS lacks sensitivity as an outcome measure (Additional  Table 1).

 

Mortality

The outcome of mortality was reported in 15 studies and overall the meta-analysis showed no evidence of a difference between chlorhexidine and placebo/usual care with minimal heterogeneity (OR 1.10, 95% CI 0.87 to 1.38, P = 0.44, I2 = 2%) ( Analysis 1.2).

Likewise there was no evidence of a difference in mortality in all of the subgroups (chlorhexidine mouthrinse with or without toothbrushing).

  • Chlorhexidine mouthrinse (no toothbrushing) compared to placebo/usual care (OR 1.16, 95% CI 0.72 to 1.88, P = 0.54, I2 = 36% ( Analysis 1.2, Subgroup 1.2.1).
  • Chlorhexidine gel (no toothbrushing) compared to placebo/usual care (OR 0.89, 95% CI 0.45 to 1.76, P = 0.73, I2 = 43%) ( Analysis 1.2, Subgroup 1.2.2).
  • Chlorhexidine mouthrinse plus toothbrushing versus toothbrushing alone (OR 1.09, 95% CI 0.72 to 1.64, P = 0.69, I2 = 0%) ( Analysis 1.2, Subgroup 1.2.3).
  • The single study (Kusahara 2012) of children receiving chlorhexidine gel + toothbrushing versus usual care (including toothbrushing) also showed no difference in the outcome of mortality ( Analysis 1.2, Subgroup 1.2.4).
  • Koeman 2006 comparing chlorhexidine gel with placebo showed no difference in mortality (Additional  Table 1).

 

Duration of ventilation

From the six studies which reported this outcome there is no evidence of a difference in the duration of ventilation between the groups receiving chlorhexidine solution compared to those receiving placebo/usual care (mean difference (MD) 0.09, 95% CI -0.84 to 1.01 days, P = 0.85, I2 = 24%) ( Analysis 1.3).

There was no evidence of a difference in duration of ventilation in any of the subgroups.

 

Duration of ICU stay

Likewise there was no evidence of a difference between the group receiving chlorhexidine rinse solution compared to placebo/usual care in the outcome of duration of ICU stay (six RCTs, MD 0.21 days, 95% CI -1.48 to 1.89, P = 0.81, I2 = 9%) and similarly there was no evidence of a difference in two subgroups ( Analysis 1.4, Subgroup 1.4.1;  Analysis 1.4, Subgroup 1.4.2) and insufficient evidence to determine whether or not there was a difference in  Analysis 1.4, Subgroup 1.4.3.

 

Duration of systemic antibiotic therapy

Two trials (total of 374 participants) reported this outcome and there was insufficient evidence to determine whether or not there is a difference in duration of use of systemic antibiotics between the chlorhexidine and control groups (MD 0.23 days, 95% CI -0.85 to 1.30, P = 0.68, I2 = 50%) with moderate heterogeneity probably due to the differences between the two studies in the mode of chlorhexidine used ( Analysis 1.5).

 

Microbial colonisation

There was also insufficient evidence to determine whether there is a difference between chlorhexidine and control groups in the outcome of positive microbiological cultures (three studies, OR 0.69, 95% CI 0.35 to 1.33, P = 0.26, I2 = 70%) ( Analysis 1.6). We combined the two chlorhexidine groups in the Grap 2004 study for the meta-analysis and the raw data are recorded in Additional  Table 1. Two studies of adults (Cabov 2010; Grap 2004) reported cultures from the mouth, and trachea respectively and the third study (Kusahara 2012) of children, reported oropharyngeal culture results. The clinical differences between these studies may explain some of the heterogeneity in the meta-analysis.

Another study (Berry 2011) where the data could not be incorporated into the meta-analysis showed no difference in positive cultures between the interventions compared (Additional  Table 1).

 

Oral health indices: plaque index

Two of the studies in this group (Ozcaka 2012; Scannapieco 2009) reported the outcome of plaque index but only Ozcaka 2012 reported numerical data. Neither study found a difference in plaque indices between the chlorhexidine and control groups ( Analysis 1.7, Additional  Table 1).

 

Adverse effects

Three studies in this group reported adverse effects. Bellissimo-Rodrigues 2009 reported that three patients in the chlorhexidine group and five in the placebo group found the taste unpleasant and Tantipong 2008 found mild reversible irritation of the oral mucosa in 10% of the chlorhexidine patients compared to 1% of the control group patients ( Analysis 1.8). Berry 2011 stated that there were no adverse effects in either group.

Adverse effects were not mentioned in the other studies in this group.

The outcomes of caregivers' preferences and cost were not reported.

 

Heterogeneity

There is moderate heterogeneity in two of the subgroups (Analysis 1.1, Subgroups 1.1.1 and 1.1.2) which is likely to be due to clinical differences between these studies, due to variability in the frequency, application method, volume and concentration of chlorhexidine solution. In Subgroup 1.1.1, six of the seven studies used a placebo control and the volume of chlorhexidine (either 0.12% or 0.2%) used varied between 10 and 50 ml administered either two, three or four times daily. One study (Grap 2011) used a single application by swab of a very small volume of chlorhexidine pre-operatively. One of the seven studies was on children aged from birth to 14 years (Jacomo 2011) and the others recruited adults. In Subgroup 1.1.2, there is also moderate heterogeneity which may be due to variations in the way the intervention was delivered. Three of the five studies in this subgroup (Cabov 2010; Fourrier 2000; Fourrier 2005) administered 0.2% chlorhexidine gel three times daily following rinsing of the mouth and aspiration of rinse. The other two studies (Koeman 2006; Sebastian 2012) used a gel with higher chlorhexidine concentration (2% and 1% respectively) and applied the gel using a swab.

 

Sensitivity analysis

For the primary outcome of VAP we conducted a sensitivity analysis excluding the studies at high risk of bias. The estimate remained very similar (OR 0.61, 95% CI 0.49 to 0.78, P < 0.001, I2 = 29%).

However a meta-analysis of the three studies of children (Jacomo 2011; Kusahara 2012; Sebastian 2012) (342 participants, aged from 3 months to 15 years) provided no evidence that chlorhexidine compared to placebo showed a difference in the outcomes of VAP (OR 1.07, 95% CI 0.65 to 1.77, P = 0.79, I2 = 0%) or mortality (OR 0.73, 95% CI 0.41 to 1.30, P = 0.28, I2 = 0%) (Analyses not shown).

 

Publication bias

Each of the subgroups in this comparison contained a small number of studies and therefore it was not appropriate to produce a funnel plot to investigate possible publication bias.

 

Comparison 2: Toothbrushing versus no toothbrushing

The eight studies included in this comparison (Bopp 2006; Fields 2008; Lorente 2012; Munro 2009; Needleman 2011; Pobo 2009; Roca Biosca 2011; Yao 2011) all had toothbrushing as part of the intervention, versus no toothbrushing in the control group. Six of these studies were at high risk of bias and two studies (Lorente 2012; Yao 2011) had an unclear risk of bias. Three studies used a powered toothbrush (Pobo 2009; Roca Biosca 2011; Yao 2011 ) and five used a manual toothbrush. One study (Bopp 2006) was a very small pilot study (n = 5) and the data from this study are recorded in Additional  Table 1, and the study by Fields 2008 reported no numerical data at all. The study by Roca Biosca 2011 did not report data for each arm of the study and we were not able to obtain these data from the authors. Available data from this study are recorded in Additional  Table 1.

 

Incidence of VAP

One small study (Yao 2011, 53 participants), at high risk of bias, compared usual care plus the addition of twice daily toothbrushing with a powered toothbrush, to usual care alone, and found a reduction in VAP. The usual care intervention comprised patient's bed being elevated 30 to 45 degrees, hypopharyngeal suctioning, lips moistened with 'toothette' swab and water, then further hypopharyngeal suctioning. A second study with 147 participants, also assessed at high risk of bias (Pobo 2009), compared powered toothbrushing plus usual care including chlorhexidine , with usual care alone and found no difference in the outcome of VAP. The combined estimate from these studies showed no difference in the incidence of VAP (OR 0.35, 95% CI 0.06 to 1.97, P = 0.23, I2 = 81%) ( Analysis 2.1, Subgroup 2.1.1) with the heterogeneity likely due to the additional exposure to chlorhexidine in both groups of only one of the studies.

In Lorente 2012 where the intervention group received toothbrushing with a manual toothbrush as well as chlorhexidine, compared to chlorhexidine alone in the control group, there was no evidence of a difference in the incidence of VAP between the intervention and control groups.

A study with a factorial design (Munro 2009) compared toothbrushing with no toothbrushing (equal exposure to chlorhexidine in both arms), and reported no difference in the development of VAP ( Analysis 2.1, Subgroup 2.1.3).

Bopp 2006 was a very small pilot study (n = 5) of toothbrushing versus none, and the data are reported in Additional  Table 1. There were no numerical outcome data in the study by Fields 2008; the report makes the statement that "the VAP rate dropped to zero within a week of beginning the every 8 hours toothbrushing regimen in the intervention group." This rate of zero incidence of VAP was reportedly sustained for 6 months. Roca Biosca 2011 recruited 117 participants and reported a summary estimate for the outcome of VAP and found no difference between powered toothbrushing and no toothbrushing (Additional  Table 1).

The combined meta-analysis of four studies (Lorente 2012; Munro 2009; Pobo 2009; Yao 2011) shows no evidence of a difference in the incidence of VAP due to toothbrushing (OR 0.69, 95% CI 0.36 to 1.29, P = 0.24 , I2 = 64%) with substantial statistical heterogeneity likely to be explained by the differences in exposure to chlorhexidine between the studies ( Analysis 2.1).

 

Mortality

Four studies (Lorente 2012; Munro 2009; Pobo 2009; Yao 2011) evaluated the effect of toothbrushing as an addition to oral care, on the outcome of mortality. The comparisons were slightly different in each trial but the overall meta-analysis found no evidence of a difference between intervention and control groups without heterogeneity (OR 0.85, 95% CI 0.62 to 1.16, P = 0.31, I2 = 0%) ( Analysis 2.2).

 

Duration of ventilation

Meta-analysis of two trials (total 583 participants) reported the outcome of mean duration of mechanical ventilation, and showed no difference associated with toothbrushing (MD -0.85 days, 95% CI -2.43 to 0.73 days, P = 0.29, I2 = 0%) ( Analysis 2.3).

The data from Bopp 2006 are reported in Additional  Table 1.

 

Duration of ICU stay

Meta-analysis of two trials (total 583 participants) which reported the outcome of mean duration of ICU stay found no evidence of a difference between the groups (MD -1.82, 95%CI -3.95 to 0.32, P = 0.10, I2 = 0%,  Analysis 2.4). The data from Bopp 2006 are reported in Additional  Table 1.

 

Duration of systemic antibiotic therapy

This outcome was not reported by any of the studies in this group.

 

Microbial colonisation

One small study (Needleman 2011, n = 28) reported the number of patients per group with colonisation of plaque by VAP-associated pathogens and found no difference between the intervention and control groups ( Analysis 2.5).

 

Oral health indices: plaque score

Two studies (Needleman 2011; Yao 2011) also reported the outcome of plaque score in each group after 5 days or 7-8 days respectively. Each study used a different scale so these data were combined for meta-analysis using standardised mean difference (SMD) and showed evidence of reduced plaque in the toothbrushing group (SMD -1.20, 95% CI -1.70 to -0.70, P < 0.001, I2 = 0%) ( Analysis 2.6).

Roca Biosca 2011 reported plaque scores, without any estimates of variance. The trial report also stated that there was no difference between the groups (Additional  Table 1).

 

Adverse effects

Pobo 2009 reported that there were no adverse effects reported in either arm of the study and none of the other studies in this comparison mentioned adverse effects.

The outcomes of caregivers' preferences and cost were not reported.

 

Comparison 3: Powered toothbrushing versus manual toothbrushing

One small study of 78 participants (Prendergast 2012), assessed at high risk of bias, compared the use of a powered toothbrush as a component of 'comprehensive oral care' with a control group receiving manual toothbrushing and standard oral care.

In this study there was no difference between the intervention and control groups with regard to the outcomes of incidence of VAP, mortality or mean duration of ventilation or ICU stay ( Analysis 3.1;  Analysis 3.2;  Analysis 3.3;  Analysis 3.4). There were no adverse effects mentioned in this study. The outcomes of oral health indices, microbiological cultures, systemic antibiotic therapy, caregivers' preferences for oral hygiene care or cost were not reported in the study.

 

Comparison 4: Other oral care solutions

Nine studies (Berry 2011; Caruso 2009; Feng 2012; Hu 2009; Long 2012; Seguin 2006; Xu 2007; Xu 2008; Zhao 2012) with a combined total of 1457 participants randomised to treatments, and all at high risk of bias, evaluated the effects of other solutions with a potential antiseptic effect on the outcomes of VAP, mortality and duration of ventilation.

 

Incidence of VAP

Two studies (Feng 2012; Seguin 2006) compared povidone iodine rinse with a saline rinse and showed evidence of a reduction in VAP (OR 0.35, 95% CI 0.19 to 0.65, P < 0.001, I2 = 53%). The heterogeneity in this estimate could be due to the additional intervention of toothbrushing in both groups in Feng 2012.

Seguin 2006 also compared povidone iodine rinse with usual care (suction alone with no rinse) and found a reduction in VAP. The result of this study has not been replicated so should be interpreted with caution.

Long 2012 compared povidone iodine rinse plus toothbrushing with povidone iodine rinse alone and found a reduction in VAP. The result of this study has not been replicated so should be interpreted with caution.

Two small studies with a total of 83 participants (Xu 2007; Xu 2008), both at high risk of bias, which compared a saline rinse with a saline soaked swab found no difference in incidence of VAP (OR 0.65, 95% CI 0.37 to 1.14, P = 0.13, I2 = 41%).

The studies by Hu 2009 and Xu 2007, both at high risk of bias, compared both saline rinse plus swab, with a saline soaked swab alone (usual care) and found some very weak evidence (from total of 40 participants) that the combined rinse plus swab reduced the incidence of VAP (OR 0.30, 95% CI 0.14 to 0.63, P = 0.002, I2 = 0%).

Two studies (Caruso 2009; Seguin 2006), both at high risk of bias, compared a saline rinse with usual care (no rinse) and found a reduction in VAP (OR 0.50, 95% CI 0.29 to 0.88, P = 0.02, I2 = 39%). While this result should be interpreted cautiously due to the high risk of bias, there appears to be some evidence that the use of a saline rinse prior to aspiration of secretions was associated with reduction of ventilator-associated pneumonia.

A single study (Berry 2011), at high risk of bias, compared bicarbonate rinse plus toothbrushing with a water rinse plus toothbrushing and found no difference in the incidence of VAP.

Another single study (Zhao 2012) compared triclosan rinse with saline rinse and found no difference in the outcome of VAP over the duration of the study ( Analysis 4.1, Subgroup 4.1.8). The results of this study have not been replicated so should be interpreted with caution.

A single 3-arm study compared povidone iodine, furacilin and usual care (Feng 2012) and found both antiseptics combined with toothbrushing were more effective than usual care ( Analysis 4.1, Subgroup 4.1.1 and  Analysis 4.1, Subgroup 4.1.10) with little difference between the two antiseptic solutions ( Analysis 4.1, Subgroup 4.1.9).

 

Mortality

There was only a single study at high risk of bias in each of five subgroups reporting mortality ( Analysis 4.2, Subgroups 4.2.1, 4.2.2, 4.2.3, 4.2.4 and 4.2.6), providing insufficient evidence to determine whether or not there is a difference in mortality. Two studies comparing saline rinse with usual care with no rinse (Caruso 2009; Seguin 2006) showed no difference in mortality (OR 1.20, 95% CI 0.77 to 1.87, P = 0.43, I2 = 0%) ( Analysis 4.2, Subgroup 4.2.5). There is no evidence of a difference in mortality for any of the comparisons reported.

 

Duration of ventilation and duration of ICU stay

These outcomes were evaluated by single studies within each subgroup, providing insufficient evidence to determine whether or not there is a difference between the various interventions and controls.

Saline rinse versus usual care (with no rinse) was evaluated by two studies (Caruso 2009; Seguin 2006) and there was no evidence of a difference in either duration of ventilation (MD -0.40 days, 95% CI -2.55 to 1.75, P = 0.72, I2 = 0%) or duration of ICU stay (MD -1.17 days, 95% CI -3.95 to 1.60, P = 0.41, I2 = 32%).

 

Microbial colonisation

One study (Feng 2012) reported a reduction in positive cultures in the povidone iodine group but the results of this study have not been replicated so should be interpreted with caution.

None of these nine studies reported the outcomes of duration of systemic antibiotic therapy, adverse effects, caregivers' preferences for oral hygiene care or cost.

 

Discussion

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Summary of main results

Thirty-five randomised controlled trials are included in this review and these studies evaluate four main groups of interventions, in the oral hygiene care of critically ill patients receiving mechanical ventilation in intensive care units.

  • Chlorhexidine antiseptic versus placebo/usual care (with or without toothbrushing)

There is moderate quality evidence from 17 RCTs that the use of chlorhexidine (either as a mouthrinse or a gel) reduces the odds of developing VAP (OR 0.60, 95% CI 0.47 to 0.77, P < 0.001, I2 = 21%) ( Summary of findings for the main comparison), with an NNT of 15 (95% CI 10 to 34). There is no evidence that use of chlorhexidine is associated with a difference in mortality (15 studies), duration of mechanical ventilation (six studies) or duration of ICU stay (six studies) (moderate quality evidence). There is insufficient evidence to determine the effect of chlorhexidine on the other secondary outcomes of this review.

From the three studies of children there was no evidence of a difference between chlorhexidine and placebo for the outcomes of VAP and mortality (moderate quality evidence).

  • Toothbrushing versus no toothbrushing (with or without chlorhexidine)

Based on four RCTs (low quality evidence) we found no evidence of a difference between oral care with chlorhexidine plus toothbrushing and oral care with chlorhexidine alone with regard to the outcome of VAP (OR 0.69, 95% CI 0.36 to 1.29, P = 0.24 , I2 = 64%). There is no evidence of a difference between toothbrushing or no toothbrushing for the outcomes of mortality (OR 0.85, 95% CI 0.62 to 1.16, P = 0.31, I2 = 0%), duration of ventilation (MD -0.85 days, 95% CI -2.43 to 0.73, P = 0.29, I2 = 0%) or duration of ICU stay (MD -1.82 days, 95% CI -3.95 to 0.32 days, P = 0.10, I2 = 0%) (moderate quality evidence).

  • Oral care with powered toothbrush versus oral care with manual toothbrush

From the single study in this comparison there is insufficient evidence to determine the effects of powered versus manual toothbrushing on the outcomes of VAP, mortality, duration of mechanical ventilation or duration of ICU stay.

  • Oral care with other solutions

The studies in this comparison were at high overall risk of bias and made different comparisons. There is some weak evidence that povidone iodine rinse is more effective than saline in reducing VAP (OR 0.35, 95% CI 0.19 to 0.65, P = 0.0009, I2 = 53%) (two studies, 206 participants, high risk of bias). We found no evidence of a difference between a saline swab and a saline rinse with regard to the reduction of VAP (OR 0.65, 95% CI 0.37 to 1.14, P = 0.13, I2 = 41%) (two studies, 83 participants, high risk of bias), and very weak evidence that use of both a saline swab and a saline rinse may be more effective than a saline swab alone (OR 0.30, 95% CI 0.14 to 0.63, P = 0.002, I2 = 0%) (two studies, 40 participants, high risk of bias). There is insufficient evidence to clearly determine the effectiveness of any of the oral care solutions for any of the outcomes evaluated.

 

Overall completeness and applicability of evidence

In this review we have included studies which compared active oral hygiene care interventions with either placebo or usual care. We recognise that the use of a placebo is a better control comparison in research studies because it enables the masking of caregivers as to which patients are in the active or control group, thus eliminating some possible performance bias. However, we chose to include pragmatic studies where 'usual care' was the control comparator, despite recognising that in many instances 'usual care' was not specified and may have varied between patients and between individual caregivers. Likewise in some of the included studies, the precise details of what was involved in the oral hygiene care intervention were poorly described making it difficult to determine the similarity in oral hygiene care practices between studies.

We also recognise that participation in a research study is likely to have a positive effect on the performance of 'usual care' improving both the quality of care and compliance with routine practice - a Hawthorne effect (McCarney 2007). The combination of a 'usual care' control group, the absence of caregiver blinding in most cases, and the Hawthorne effect of being part of a study may have reduced the observed difference in effect between the active and control interventions in these studies. Two of the studies noted that care was recorded in patient notes but none of the studies included in this review reported compliance with oral hygiene care protocols.

Another area of variability between the studies (and possibly also between studies and usual practice) is the diagnosis of VAP, which is at least partly subjective and may be made based on variable diagnostic criteria. Most studies (26/35) stated the criteria used to diagnose VAP, and the two most common were some version of the clinical pulmonary infection score (CPIS) based on Pugin's criteria (Cook 1998; Pugin 1991) (16 studies) and Centers for Disease Control (CDC) criteria as described in Horan 2008 (six studies). Four studies conducted in China (Chen 2008; Feng 2012; Xu 2007; Xu 2008) used Chinese Society of Respiratory Diseases (CSRD) criteria for diagnosis of VAP. In two studies some of the study participants had pneumonia at baseline (Munro 2009; Sebastian 2012).

Although this review found evidence that the use of chlorhexidine as part of oral care reduces the incidence of VAP, there was no evidence of a reduction in mortality. There is some debate in the literature about the attributable mortality of VAP, but a recent survival analysis of nearly 4500 patients found that ICU mortality attributable to VAP was about 1% on day 30 (Bekaert 2011), which might explain our findings.

This review has not found evidence that oral care including both toothbrushing and chlorhexidine is different from oral care with chlorhexidine alone in reducing VAP. Only one of the trials of toothbrushing which reported the outcome of VAP also reported plaque levels as an indicator of the effectiveness of the toothbrushing carried out in this trial (Yao 2011). This small trial (53 participants), which was assessed at high risk of bias, did not use chlorhexidine in either group, and found a reduction in both plaque and VAP in the powered toothbrushing group compared to the no toothbrushing group. Three other trials of toothbrushing in our meta-analysis (Lorente 2012 (manual), Munro 2009 (manual), Pobo 2009 (powered toothbrush)), with a combined total of 775 participants included exposure to chlorhexidine in both intervention and control groups. Assessed at unclear, high and high risk of bias respectively, meta-analysis of these three trials showed no evidence of a difference in the outcome of VAP. A further study (Roca Biosca 2011), included in this review and also at high risk of bias, was not able to be included in the meta-analysis, but also found no difference between oral care with chlorhexidine and toothbrushing and oral care with chlorhexidine alone. All five of these studies describe the toothbrushing intervention in detail, and note that nurses delivering the intervention received specific training. While the presence of ventilator tubes in the mouths of trial participants makes effective toothbrushing difficult, despite this, it seems likely that the toothbrushing intervention was carried out thoroughly within these trials.

Earlier cohort studies noted that patients in ICU who developed VAP were likely to have increased length of stay in the ICU (Apostolopoulou 2003; Cook 1998). However, this Cochrane review has not evaluated duration of ICU stay in patients who develop VAP. The studies in this review report mean length of ICU stay and the standard deviation for each arm of the study. These are combined in meta-analysis based on an assumption the duration of ICU stay in each arm of each trial follows an approximately normal distribution. In fact the distribution of duration of stay in ICU is likely to be skewed and the means are likely to be a poor indicator of the effect of oral hygiene care on duration of ICU stay.

This systematic review has not looked at the outcome of cost of interventions. However, it is likely that the additional cost of using an antiseptic mouthrinse or gel is low in comparison with the cost of the antibiotics used to treat VAP. One study (Jacomo 2011) reported the cost of the chlorhexidine gluconate solution per patient was USD 3.15. Reducing the incidence of VAP using relatively inexpensive additions to usual care is likely to be a cost effective, as well as avoiding additional morbidity for the patient.

It is interesting that only mild adverse reactions of chlorhexidine were reported in three of the 20 studies which evaluated chlorhexidine. In over 2000 participants included in these studies there was no report of hypersensitivity to chlorhexidine.

Three of the included studies evaluated chlorhexidine in children aged from a few months to 15 years. These studies found no evidence of a difference in VAP associated with including chlorhexidine in oral hygiene care. The reason(s) for this are unclear.

 

Quality of the evidence

All the included studies were prospective, randomised controlled trials but only five of the included studies (14%) were assessed at low risk of bias (Bellissimo-Rodrigues 2009; Fourrier 2005; Koeman 2006; Ozcaka 2012; Sebastian 2012) for all domains, 13 studies (37%) were at unclear risk of bias for at least one domain. Nearly half of the included studies (17 studies, 49%) were at high risk of bias in at least one domain.

 

Potential biases in the review process

In order to reduce the risk of publication bias we conducted a broad search, for both published and unpublished studies, and there were no restrictions on language. We searched the reference lists of included studies and contacted many of the authors of the included studies in order to obtain information that was not included in the published reports. We also searched the reference lists of other published reviews of oral hygiene care for critically ill patients.

We have made a number of changes to the methods of this review since the publication of the protocol (see Differences between protocol and review). Some of these changes were clarifications, and some were to take account of other Cochrane reviews published or in preparation, to avoid unnecessary duplication of effort. We acknowledge that post hoc changes to the review methods may introduce a risk of bias into this review.

 

Agreements and disagreements with other studies or reviews

A recent meta-analysis by Pineda 2006 found that the use of chlorhexidine for oral decontamination did not reduce the incidence of nosocomial pneumonia. However this meta-analysis included only four studies and the outcome was nosocomial pneumonia rather than VAP. A recent review by Labeau 2011 included 14 studies of either chlorhexidine or povidone iodine antiseptics and found that the use of antiseptics as part of oral hygiene care reduced the incidence of VAP by approximately one third. Our review confirmed these findings.

Two published meta-analyses (Alhazzani 2013; Gu 2012) of toothbrushing to reduce VAP included four trials and found no evidence of a difference in incidence of VAP, again possibly due to low statistical power. Our review has similar conclusions.

 

Authors' conclusions

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

 

Implications for practice

Effective oral hygiene care is important for ventilated patients in intensive care to reduce ventilator-associated pneumonia. There is evidence from this review that oral hygiene care incorporating chlorhexidine mouthrinse or gel, is effective in reducing the development of ventilator-associated pneumonia in adult patients in intensive care. The definition of oral hygiene care varied among the studies included in this review but common elements include cleaning of the teeth and gums with a swab or gauze, removing secretions using suction and rinsing the mouth.

 
Implications for research

Although the included studies provided some evidence of the benefits of oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia, incomplete reporting of studies is a major limitation. More consistent use of the CONSORT statement for reporting of randomised controlled clinical trials would increase the value of research.

  1. Detailed reporting of methods, such as generation of allocation sequence, allocation concealment, and numbers and reasons for withdrawals and exclusions.
  2. Use of a placebo where possible to enable blinding.
  3. Full reporting of methods used to diagnose ventilator-associated pneumonia.
  4. Reporting of adverse effects of interventions.

Further trials of oral hygiene care (including use of manual or powered toothbrushes, or swabs) should report both measures of effectiveness of plaque removal and prevention of ventilator-associated pneumonia.

 

Acknowledgements

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Thanks to Anne Littlewood, Trials Search Co-ordinator of Cochrane Oral Health Group for refining search strategies, providing searching results from the databases of CINAHL via EBSCO, LILACS and OpenSIGLE; to Luisa Fernandez-Mauleffinch, Philip Riley, and Anne-Marie Glenny for kind help in developing and refining this review. Our thanks to Ruth Floate for preparing the plain language summary. Our thanks to Luisa Fernandez-Mauleffinch for translation of Santos 2008 from Portuguese and Roca Biosca 2011 from Spanish, and to Phil Riley for assisting with the data extraction and risk of bias assessment. Our thanks to Mervyn Singer for his assistance in clarifying the details of the criteria for including studies in this review. Our thanks to Tina Poklepovic for her help in obtaining additional data for one of the included studies (Cabov 2010).

 

Data and analyses

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
Download statistical data

 
Comparison 1. Chlorhexidine versus placebo/usual care

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Incidence of VAP172402Odds Ratio (M-H, Random, 95% CI)0.60 [0.47, 0.77]

    1.1 Chlorhexidine solution versus placebo (no t'brushing in either group)
71037Odds Ratio (M-H, Random, 95% CI)0.60 [0.38, 0.94]

    1.2 Chlorhexidine gel versus placebo (no t'brushing in either group)
5669Odds Ratio (M-H, Random, 95% CI)0.57 [0.31, 1.06]

    1.3 Chlorhexidine solution versus placebo (t'brushing both groups)
3408Odds Ratio (M-H, Random, 95% CI)0.44 [0.23, 0.85]

    1.4 Chlorhexidine gel versus placebo (t'brushing both groups)
196Odds Ratio (M-H, Random, 95% CI)1.03 [0.44, 2.42]

    1.5 Chlorhexidine solution versus usual care (some t'brushing in each group)
1192Odds Ratio (M-H, Random, 95% CI)0.58 [0.32, 1.02]

 2 Mortality142111Odds Ratio (M-H, Random, 95% CI)1.10 [0.87, 1.38]

    2.1 Chlorhexidine solution versus placebo (no t'brushing in either group)
6973Odds Ratio (M-H, Random, 95% CI)1.16 [0.72, 1.88]

    2.2 Chlorhexidine gel versus placebo (no t'brushing in either group)
4414Odds Ratio (M-H, Random, 95% CI)0.89 [0.45, 1.76]

    2.3 Chlorhexidine solution versus placebo (t'brushing both groups)
4628Odds Ratio (M-H, Random, 95% CI)1.09 [0.72, 1.64]

    2.4 Chlorhexidine gel versus placebo (t'brushing both groups)
196Odds Ratio (M-H, Random, 95% CI)0.67 [0.24, 1.81]

 3 Duration of ventilation6933Mean Difference (IV, Random, 95% CI)0.09 [-0.84, 1.01]

    3.1 Chlorhexidine solution versus placebo (no t'brushing in either group)
3316Mean Difference (IV, Random, 95% CI)-2.74 [-0.63, 0.63]

    3.2 Chlorhexidine gel versus placebo (no t'brushing in either group)
3543Mean Difference (IV, Random, 95% CI)1.26 [-0.78, 3.30]

    3.3 Chlorhexidine solution versus placebo (t'brushing both groups)
174Mean Difference (IV, Random, 95% CI)-1.30 [-4.20, 1.60]

 4 Duration of ICU stay6833Mean Difference (IV, Random, 95% CI)0.21 [-1.48, 1.89]

    4.1 Chlorhexidine solution versus placebo (no t'brushing in either group)
2194Mean Difference (IV, Random, 95% CI)-1.22 [-4.07, 1.62]

    4.2 Chlorhexidine gel versus placebo (no t'brushing in either group)
3543Mean Difference (IV, Random, 95% CI)0.53 [-1.56, 2.61]

    4.3 Chlorhexidine gel versus placebo (t'brushing both groups)
196Mean Difference (IV, Random, 95% CI)5.0 [-2.20, 12.20]

 5 Duration of systemic antibiotic therapy2374Mean Difference (IV, Fixed, 95% CI)0.23 [-0.85, 1.30]

    5.1 Chlorhexidine gel versus placebo (no t'brushing in either group)
1228Mean Difference (IV, Fixed, 95% CI)-1.18 [-3.41, 1.05]

    5.2 Chlorhexidine solution versus placebo (t'brushing both groups)
1146Mean Difference (IV, Fixed, 95% CI)0.65 [-0.58, 1.88]

 6 Positive cultures3170Odds Ratio (M-H, Fixed, 95% CI)0.69 [0.35, 1.33]

    6.1 Chlorhexidine solution versus placebo (no t'brushing in either group)
134Odds Ratio (M-H, Fixed, 95% CI)0.62 [0.13, 2.88]

    6.2 Chlorhexidine gel versus placebo (no t'brushing in either group)
140Odds Ratio (M-H, Fixed, 95% CI)0.15 [0.03, 0.63]

    6.3 Chlorhexidine gel versus placebo (t'brushing both groups)
196Odds Ratio (M-H, Fixed, 95% CI)1.40 [0.55, 3.53]

 7 Plaque index1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 8 Adverse effects2401Odds Ratio (M-H, Fixed, 95% CI)2.22 [0.84, 5.90]

    8.1 Unpleasant taste
1194Odds Ratio (M-H, Fixed, 95% CI)0.57 [0.13, 2.47]

    8.2 Reversible mild irritation of oral mucosa
1207Odds Ratio (M-H, Fixed, 95% CI)11.30 [1.42, 90.01]

 
Comparison 2. Toothbrushing versus no toothbrushing

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Incidence of VAP4828Odds Ratio (M-H, Random, 95% CI)0.69 [0.36, 1.29]

    1.1 Powered toothbrush + usual care (± CHX) versus usual care (± CHX)
2200Odds Ratio (M-H, Random, 95% CI)0.35 [0.06, 1.97]

    1.2 Toothbrush + CHX versus CHX alone
1436Odds Ratio (M-H, Random, 95% CI)0.87 [0.47, 1.62]

    1.3 Toothbrush (+some CHX) versus no toothbrush (+some CHX)
1192Odds Ratio (M-H, Random, 95% CI)1.09 [0.62, 1.92]

 2 Mortality4828Odds Ratio (M-H, Random, 95% CI)0.85 [0.62, 1.16]

    2.1 Powered toothbrush+ usual care versus usual care
2200Odds Ratio (M-H, Random, 95% CI)1.32 [0.14, 12.90]

    2.2 Toothbrush + CHX versus CHX alone
2528Odds Ratio (M-H, Random, 95% CI)0.86 [0.59, 1.25]

    2.3 Toothbrush alone versus no treatment
1100Odds Ratio (M-H, Random, 95% CI)1.20 [0.44, 3.25]

 3 Duration of ventilation2Mean Difference (IV, Fixed, 95% CI)Subtotals only

    3.1 Toothbrush + CHX versus CHX alone
2583Mean Difference (IV, Fixed, 95% CI)-0.85 [-2.43, 0.73]

 4 Duration of ICU stay2Mean Difference (IV, Fixed, 95% CI)Subtotals only

    4.1 Toothbrush + CHX versus CHX alone
2583Mean Difference (IV, Fixed, 95% CI)-1.82 [-3.95, 0.32]

 5 Colonisation with VAP associated organisms (Day 5)1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    5.1 versus CHX alone
128Risk Ratio (M-H, Fixed, 95% CI)0.82 [0.40, 1.68]

 6 Plaque score276Std. Mean Difference (IV, Fixed, 95% CI)-1.20 [-1.70, -0.70]

    6.1 Powered toothbrush versus usual care
276Std. Mean Difference (IV, Fixed, 95% CI)-1.20 [-1.70, -0.70]

 
Comparison 3. Powered toothbrush versus manual toothbrush

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Incidence of VAP1Odds Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Powered t'brush + comp oral care versus manual t'brush + std oral care
178Odds Ratio (M-H, Fixed, 95% CI)0.8 [0.28, 2.31]

 2 Mortality1Odds Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Powered t'brush + comp oral care versus manual t'brush + std oral care
178Odds Ratio (M-H, Fixed, 95% CI)1.06 [0.14, 7.90]

 3 Duration of ventilation1Mean Difference (IV, Fixed, 95% CI)Subtotals only

    3.1 Powered t'brush + comp oral care versus manual t'brush + std oral care
178Mean Difference (IV, Fixed, 95% CI)0.0 [-1.78, 1.78]

 4 Duration of ICU stay1Mean Difference (IV, Fixed, 95% CI)Subtotals only

    4.1 Powered t'brush + comp oral care versus manual t'brush + std oral care
178Mean Difference (IV, Fixed, 95% CI)-2.0 [-5.93, 1.93]

 
Comparison 4. Other oral care solutions

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Incidence of VAP9Odds Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Povidone iodine versus saline
2206Odds Ratio (M-H, Fixed, 95% CI)0.35 [0.19, 0.65]

    1.2 Povidone iodine versus usual care
167Odds Ratio (M-H, Fixed, 95% CI)0.13 [0.03, 0.50]

    1.3 Povidone iodine (+ t'brush) versus povidone iodine alone
161Odds Ratio (M-H, Fixed, 95% CI)0.26 [0.07, 0.93]

    1.4 Saline rinse versus saline swab
2218Odds Ratio (M-H, Fixed, 95% CI)0.65 [0.37, 1.14]

    1.5 Saline rinse + swab versus saline swab (usual care)
2153Odds Ratio (M-H, Fixed, 95% CI)0.30 [0.14, 0.63]

    1.6 Saline rinse versus usual care
2324Odds Ratio (M-H, Fixed, 95% CI)0.50 [0.29, 0.88]

    1.7 Bicarbonate rinse versus water
1154Odds Ratio (M-H, Fixed, 95% CI)1.03 [0.25, 4.27]

    1.8 Triclosan rinse versus saline
1324Odds Ratio (M-H, Fixed, 95% CI)0.80 [0.52, 1.24]

    1.9 Furacilin versus povidone iodine
1136Odds Ratio (M-H, Fixed, 95% CI)0.41 [0.17, 1.03]

    1.10 Furacilin versus saline
1133Odds Ratio (M-H, Fixed, 95% CI)0.19 [0.08, 0.46]

 2 Mortality5Odds Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Povidone iodine versus saline
167Odds Ratio (M-H, Fixed, 95% CI)0.42 [0.13, 1.33]

    2.2 Povidone iodine versus usual care
167Odds Ratio (M-H, Fixed, 95% CI)0.83 [0.24, 2.91]

    2.3 Povidone iodine (+ t'brush) versus povidone iodine alone
161Odds Ratio (M-H, Fixed, 95% CI)0.54 [0.12, 2.47]

    2.4 Saline rinse + swab versus saline swab (usual care)
147Odds Ratio (M-H, Fixed, 95% CI)0.29 [0.06, 1.31]

    2.5 Saline rinse versus usual care
2324Odds Ratio (M-H, Fixed, 95% CI)1.20 [0.77, 1.87]

    2.6 Bicarbonate rinse versus water
1154Odds Ratio (M-H, Fixed, 95% CI)3.82 [1.18, 12.30]

 3 Duration of ventilation6Mean Difference (IV, Fixed, 95% CI)Subtotals only

    3.1 Povidone iodine versus saline
167Mean Difference (IV, Fixed, 95% CI)-1.0 [-4.36, 2.36]

    3.2 Povidone iodine versus usual care
167Mean Difference (IV, Fixed, 95% CI)-3.0 [-7.67, 1.67]

    3.3 Povidone iodine (+ t'brush) versus povidone iodine alone
161Mean Difference (IV, Fixed, 95% CI)0.13 [-0.78, 1.04]

    3.4 Saline versus usual care
2324Mean Difference (IV, Fixed, 95% CI)-0.40 [-2.55, 1.75]

    3.5 Saline rinse + swab versus saline swab
147Mean Difference (IV, Fixed, 95% CI)-3.91 [-5.85, -1.97]

    3.6 Saline rinse versus saline swab
1116Mean Difference (IV, Fixed, 95% CI)-10.80 [-15.88, -5.72]

    3.7 Triclosan rinse versus saline
1324Mean Difference (IV, Fixed, 95% CI)-5.24 [-5.64, -4.84]

 4 Duration of ICU stay3Mean Difference (IV, Fixed, 95% CI)Subtotals only

    4.1 Povidone iodine versus saline
167Mean Difference (IV, Fixed, 95% CI)1.0 [-5.23, 7.23]

    4.2 Povidone iodine versus usual care
167Mean Difference (IV, Fixed, 95% CI)-4.0 [-10.99, 2.99]

    4.3 Saline versus usual care
2324Mean Difference (IV, Fixed, 95% CI)-1.17 [-3.95, 1.60]

    4.4 Triclosan rinse versus saline
1324Mean Difference (IV, Fixed, 95% CI)-4.97 [-5.55, -4.39]

 5 Positive cultures1Odds Ratio (M-H, Fixed, 95% CI)Subtotals only

    5.1 Povidone iodine versus saline
1139Odds Ratio (M-H, Fixed, 95% CI)0.45 [0.21, 0.97]

 

Appendices

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Appendix 1. Cochrane Oral Health Group's Trials Register search strategy

#1 ((critical* AND ill*):ti,ab) AND (INREGISTER)
#2 ((depend* and patient*):ti,ab) AND (INREGISTER)
#3 (("critical care" or " intensive care" or ICU or CCU):ti,ab) AND (INREGISTER)
#4 ((intubat* or ventilat*):ti,ab) AND (INREGISTER)
#5 ((#1 or #2 or #3 or #4)) AND (INREGISTER)
#6 ((pneumonia or "nosocomial infect*" or VAP):ti,ab) AND (INREGISTER)
#7 (#5 and #6) AND (INREGISTER)

 

Appendix 2. Cochrane Central Register of Controlled Trials (CENTRAL) search strategy

#1        MeSH descriptor Critical illness this term only
#2        (critical* in All Text near/6 ill* in All Text) 
#3        (depend* in All Text near/6 patient* in All Text) 
#4        MeSH descriptor Critical care this term only 
#5        (intensive-care in All Text or "intensive care" in All Text or critical-care in All Text or "critical care" in All Text) 
#6        ICU in Title, Abstract or Keywords
#7        ((intubat* in All Text near/5 patient* in All Text) or (ventilat* in All Text near/5 patient* in All Text)) 
#8        (#1 or #2 or #3 or #4 or #5 or #6 or #7) 
#9        (VAP in Title, Abstract or Keywords or VAP in Title, Abstract or Keywords)  
#10      "nosocomial infection*" in Title, Abstract or Keywords
#11      MeSH descriptor Pneumonia, Ventilator-Associated this term only 
#12      pneumonia in All Text
#13      (#9 or #10 or #11 or #12) 
#14      MeSH descriptor Oral health this term only 
#15      MeSH descriptor Oral hygiene explode all trees 
#16      MeSH descriptor Dentifrices explode all trees 
#17      MeSH descriptor Mouthwashes explode all trees 
#18      MeSH descriptor Periodontal diseases explode all trees 
#19      periodont* in All Text
#20      ("oral care" in All Text or "oral health" in All Text or oral-health in All Text or "mouth care" in All Text or "oral hygien*" in All Text or oral-hygien* in All Text or "dental hygien*" in All Text or decontaminat* in All Text)
#21      (mouthwash* in All Text or mouth-wash* in All Text or mouth-rins* in All Text or mouthrins* in All Text or "oral rins*" in All Text or oral-rins* in All Text or "artificial saliva" in All Text or "saliva substitut*" in All Text or ( (denture* in All Text near/6 clean* in All Text) or toothpaste* in All Text) or dentifrice* in All Text)
#22      (#14 or #15 or #16 or #17 or #18 or #19 or #20 or #21)
#23      (#8 and #13) 
#24      (#22 and #23) 

 

Appendix 3. MEDLINE via OVID search strategy

1.  CRITICAL ILLNESS/
2.  (critical$ adj5 ill$).mp.
3.  (depend$ adj5 patient$).mp.
4.  INTENSIVE CARE/
5.  ("intensive care" or intensive-care or "critical care" or critical-care).mp.
6.  ICU.mp. or CCU.ti,ab.
7.  ((intubat$ or ventilat$) adj5 patient$).mp.
8.  or/1-7
9.  PNEUMONIA, VENTILATOR-ASSOCIATED/
10. pneumonia.ti,ab.
11. VAP.ti,ab.
12. "nosocomial infection".mp.
13. or/9-12
14. exp ORAL HYGIENE/
15. exp DENTIFRICES/
16. MOUTHWASHES/
17. ANTI-INFECTIVE AGENTS, LOCAL/
18. Cetylpyridinium/
19. Chlorhexidine/
20. Povidone-Iodine/
21. ("oral care" or "mouth care" or "oral hygien$" or oral-hygien$ or "dental hygien$").ti,ab.
22. (mouthwash$ or mouth-wash$ or mouth-rins$ or mouthrins$ or "oral rins$" or oral-rins$ or toothpaste$ or dentifrice$ or toothbrush$ or chlorhexidine$ or betadine$ or triclosan$ or cepacol or Corsodyl or Peridex or Hibident or Prexidine or Parodex or Chlorexil or Peridont or Eludril or Perioxidin or Chlorohex or Savacol or Periogard or Chlorhexamed or Nolvasan or Sebidin or Tubulicid or hibitane).mp.
23. (antiseptic$ or antiinfect$ or "local microbicide$" or "topical microbicide$").mp.
24. or/14-23
25. 8 and 13 and 24

 

Appendix 4. EMBASE via OVID search strategy

1.  CRITICAL ILLNESS/
2.  (critical$ adj5 ill$).mp.
3. (depend$ adj5 patient$).mp.
4.  INTENSIVE CARE/
5.  ("intensive care" or intensive-care or "critical care" or critical-care).mp.
6.  (ICU or CCU).ti,ab.
7.  ((intubat$ or ventilat$) adj5 patient$).mp.
8. or/1-7
9.  PNEUMONIA, VENTILATOR-ASSOCIATED/
10. pneumonia.ti,ab.
11. VAP.ti,ab.
12. "nosocomial infection".mp.
13. or/9-12
14. exp ORAL HYGIENE/
15. exp DENTIFRICES/
16. MOUTHWASHES/
17. ANTI-INFECTIVE AGENTS, LOCAL/
18. Cetylpyridinium/
19. Chlorhexidine/
20. Povidone-Iodine/
21. ("oral care" or "mouth care" or "oral hygien$" or oral-hygien$ or "dental hygien$").ti,ab.
22. (mouthwash$ or mouth-wash$ or mouth-rins$ or mouthrins$ or "oral rins$" or oral-rins$ or toothpaste$ or dentifrice$ or toothbrush$ or chlorhexidine$ or betadine$ or triclosan$ or cepacol or Corsodyl or Peridex or Hibident or Prexidine or Parodex or Chlorexil or Peridont or Eludril or Perioxidin or Chlorohex or Savacol or Periogard or Chlorhexamed or Nolvasan or Sebidin or Tubulicid or hibitane).mp.
23. (antiseptic$ or antiinfect$ or "local microbicide$" or "topical microbicide$").mp.
24. or/14-23
25. 8 and 13 and 24

The above subject search was linked to the Cochrane Oral Health Group filter for EMBASE via OVID:

1. random$.ti,ab.
2. factorial$.ti,ab.
3. (crossover$ or cross over$ or cross-over$).ti,ab.
4. placebo$.ti,ab.
5. (doubl$ adj blind$).ti,ab.
6. (singl$ adj blind$).ti,ab.
7. assign$.ti,ab.
8. allocat$.ti,ab.
9. volunteer$.ti,ab.
10. CROSSOVER PROCEDURE.sh.
11. DOUBLE-BLIND PROCEDURE.sh.
12. RANDOMIZED CONTROLLED TRIAL.sh.
13. SINGLE BLIND PROCEDURE.sh.
14. or/1-13
15. ANIMAL/ or NONHUMAN/ or ANIMAL EXPERIMENT/
16. HUMAN/
17. 16 and 15
18. 15 not 17
19. 14 not 18

 

Appendix 5. CINAHL via EBSCO search strategy

S25      S14 and S24 

S24      S15 or S16 or S17 or S18 or S19 or S20 or S21 or S22 or S23       

S23      (antiseptic* or antiinfect* or "local microbicide*" or "topical microbicide*") 

S22      (mouthwash* or mouth-wash* or mouth-rins* or mouthrins* or "oral rins*" or oral-rins* or toothpaste* or dentifrice* or toothbrush* or chlorhexidine* or betadine* or triclosan* or cepacol or Corsodyl or Peridex or Hibident or Prexidine or Parodex or Chlorexil or Peridont or Eludril or Perioxidin or Chlorohex or Savacol or Periogard or Chlorhexamed or Nolvasan or Sebidin or Tubulicid or hibitane)          

S21      ("oral care" or "mouth care" or "oral hygien*" or oral-hygien* or "dental hygien*")   

S20      (MH Povidone-Iodine)           

S19      (MH Chlorhexidine)   

S18      (MH "Antiinfective Agents, Local")    

S17      MH MOUTHWASHES          

S16      (MH "DENTIFRICES+")        

S15      (MH "Oral Hygiene+")           

S14      S8 AND S13 

S13      S9 or S10 or S11 or S12       

S12      TI pneumonia or AB pneumonia        

S11      MH PNEUMONIA, VENTILATOR-ASSOCIATED 

S10      TI "nosocomial infection" and AB "nosocomial infection"     

S9        TI VAP or AB VAP     

S8        S1 or S2 or S3 or S4 or S5 or S6 or S7        

S7        ((intubat* N5 patient*) or (ventilat* N5 patient*))       

S6        TI ICU or AB ICU or TI CCU or AB CCU     

S5        (intensive-care or "intensive care" or critical-care or "critical care")             

S4        MH CRITICAL CARE            

S3        (depend* N6 patient*)            

S2        (critical* N6 ill*)          

S1        MH CRITICAL ILLNESS 

 

Appendix 6. LILACS via BIREME Virtual Health Library search strategy

(Mh Critical illness or "Enfermedad Crítica" or "Estado Terminal" or "critical illness$" or Mh Intensive care or "Cuidados Intensivos" or "Terapia Intensiva" or "critical care" or "intensive care" or "ICU" or "CCU" or intubate$ or ventilate$) [Words] and (Mh Pneumonia, Ventilator-Associated or "Neumonia Asociada al Ventilador" or "Pneumonia Associada à Ventilação Mecânica" or (ventilator AND pneumonia)) [Words] and (Mh Oral hygiene or "oral hygiene" or "Higiene Bucal" or "oral care" or "mouth care" or mouthwash$ or mouthrins$ or toothpaste$ or dentifrice$ or chlorhexidine or betadine or triclosan or Clorhexidina or Clorexidina or "Antisépticos Bucales" or "Antissépticos Bucais" or "Cepillado Dental" or "Escovação Dentária" or antiseptic$ or antiinfective$)

 

Appendix 7. Chinese Biomedical Literature Database search strategy

#1   缺省[智能]:危重 -限定:1978-2012

#2   缺省:ICU -限定:1978-2012

#3   缺省:VAP -限定:1978-2012

#4   缺省:插管 -限定:1978-2012

#5   #4 or #3 or #2 or #1

#6   缺省:口腔护理

#7   缺省[智能]:口腔清洁

#8   缺省:口腔卫生

#9   缺省[智能]:刷牙

#10   #9 or #8 or #7 or #6

#11   #10 and #5

#12   缺省[智能]:随机

#13   缺省:随机对照

#14   #13 or #12

#15  #14 and #11

 

Appendix 8. China National Knowledge Infrastructure search strategy

#1        数据库:中国期刊全文数据库 检索条件:((题名=VAP) 或者 (摘要=ICU) 或者 (题名=危重))并且(摘要=呼吸机相关性肺炎) 或者 (摘要=插管) (模糊匹配);2003-2012;全部期刊;时间排序; 单库检索

#2        数据库:中国期刊全文数据库 检索条件: (题名=口腔护理) 或者 (摘要=口腔去污染) 或者 (题名=口腔清洁) 或者 (摘要=刷牙) 或者 (主题=口腔卫生) (模糊匹配);时间排序; 单库检索(结果中检索) 

#3        数据库:中国期刊全文数据库 检索条件: (题名=随机对照) 或者 (摘要=随机) 或者 (题名=随机对照实验) 或者 (摘要=随机分配) 或者 (主题=随机隐藏) (模糊匹配);时间排序; 单库检索(结果中检索)

 

Appendix 9. Wan Fang Database search strategy

1.         ((全部字段 =(模糊匹配) "危重") ) ;按相关度排序       

2.         ((全部字段 =(模糊匹配) "ICU") ) ;按相关度排序                                

3.         ((全部字段 =(模糊匹配) "VAP") ) ;按相关度排序

4.         ((全部字段 =(模糊匹配) "口腔") ) ;按相关度排序

5.         ((全部字段 =(模糊匹配) "刷牙") ) ;按相关度排序

6.         ((全部字段 =(模糊匹配) "去污染") ) ;按相关度排序                            

7.         ((全部字段 =(模糊匹配) "洗必泰") ) ;按相关度排序

8.         ((全部字段 =(模糊匹配) "口腔冲洗") ) ;按相关度排序

9.         ((全部字段 =(模糊匹配) "危重") ) 或 ((全部字段 =(模糊匹配) "ICU") ) 或 ((全部字段 =(模糊匹配) "VAP") )

10.       ((全部字段 =(模糊匹配) "口腔") ) 或 ((全部字段 =(模糊匹配) "刷牙") ) 或 ((全部字段 =(模糊匹配) "去污染") ) 或 ((全部字段 =(模糊匹配) "洗必泰") ) 或 ((全部字段 =(模糊匹配) "口腔冲洗") )

11.       ( ((全部字段 =(模糊匹配) "口腔") ) 或 ((全部字段 =(模糊匹配) "刷牙") ) 或 ((全部字段 =(模糊匹配) "去污染") ) 或 ((全部字段 =(模糊匹配) "洗必泰") ) 或 ((全部字段 =(模糊匹配) "口腔冲洗") ) ) 与 ( ((全部字段 =(模糊匹配) "口腔") ) 或 ((全部字段 =(模糊匹配) "刷牙") ) 或 ((全部字段 =(模糊匹配) "去污染") ) 或 ((全部字段 =(模糊匹配) "洗必泰") ) 或 ((全部字段 =(模糊匹配) "口腔冲洗") ) 与 ((全部字段 =(模糊匹配) "危重") ) 或 ((全部字段 =(模糊匹配) "ICU") ) 或 ((全部字段 =(模糊匹配) "VAP") ) )

 

Appendix 10. OpenGrey search strategy

"oral health" or "oral hygiene" or "oral care" or "mouth care" or "dental hygiene" or mouthwash* or mouth-wash or mouthrinse* or mouth-rinse* or "artificial saliva" or "saliva substitute*" or toothpaste* or dentifrice* or periodontic* or periodontal

 AND 

"critical care" or "intensive care" or ICU or "critical illness" or intubated or ventilated

 

Appendix 11. ClinicalTrials.gov search strategy

ventilator and pneumonia and "oral hygiene"

 

What's new

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Last assessed as up-to-date: 14 January 2013.


DateEventDescription

27 November 2013AmendedMinor typographical error.



 

Contributions of authors

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Zongdao Shi and Huixu Xie: As joint first authors, conceiving, designing and co-ordinating the protocol, preparing a draft of the review.

Sue Furness: Contact author, updating background, revising inclusion criteria, screening search results, extracting data, assessing risk of bias, conducting meta-analysis and revising the text of the review.

Helen Worthington: Screening search results, extracting data, assessing risk of bias, conducting meta-analysis.

Ian Needleman: Updating background and revising inclusion criteria, extracting data, assessing risk of bias, contributing to the discussion section.

Ping Wang, Huixu Xie, Qi Zhang: Undertaking searches, screening search results, appraising risk of bias, extracting data.

E Chen and Yan Wu, Ian Needleman: Appraising quality of those papers for which Xie and Wang disagreed, participating in the discussion prior to preparation of the first draft.

Linda Ng: Electronic and handsearching for nursing journal articles.

 

Declarations of interest

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Ian Needleman is the first author of one of the studies included in this review. The assessment of risk of bias and the data extraction of this study was undertaken by two other review authors.

None known.

 

Sources of support

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Internal sources

  • West China College of Stomatology of Sichuan University and the Chinese Cochrane Center, China.
    This review was supported by the West China College of Stomatology, Sichuan University academically and in manpower resource; statistical analysis was supported by the Chinese Cochrane Center
  • The University of Manchester, UK.
  • Manchester Academic Health Sciences Centre (MAHSC), UK.
    The Cochrane Oral Health Group is supported by MAHSC and the NIHR Manchester Biomedical Research Centre

 

External sources

  • Cochrane Oral Health Group Global Alliance, UK.
    All reviews in the Cochrane Oral Health Group are supported by Global Alliance member organisations (British Orthodontic Society, UK; British Society of Paediatric Dentistry, UK; Canadian Dental Hygienists Association, Canada; National Center for Dental Hygiene Research & Practice, USA and New York University College of Dentistry, USA) providing funding for the editorial process (http://ohg.cochrane.org/)
  • CMB funding SR0510, Project of Development of Systematic Review supported by Chinese Medical Board of New York, USA.
  • National Institute for Health Research (NIHR), UK.
    CRG funding acknowledgement:
    The NIHR is the largest single funder of the Cochrane Oral Health Group
    Disclaimer:
    The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR, NHS or the Department of Health

 

Differences between protocol and review

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Clarifications were made to the criteria for studies eligible to be included in this review.

  • Participants in trials should not have a respiratory infection at baseline.
  • The interventions to be included in this review must include an oral hygiene care component. Trials where the intervention 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.
  • Minimum duration of mechanical ventilation of 48 hours, in order for the diagnosis of nosocomial pneumonia, diagnosed either during period of ventilation or within 48 hours of extubation, to be considered ventilator-associated pneumonia.
  • Outcome of mortality defined as either all cause ICU mortality or where this was not available, all cause 30-day mortality. We considered that the effect of the underlying condition(s) on mortality would be similar in each randomised treatment group during this period.
  • In order to avoid duplication, trials where the intervention was selective decontamination of the digestive tract with antibiotics were excluded as these interventions are included in another Cochrane review (D'Amico 2009).
  • Likewise trials where the intervention was probiotics were excluded as these interventions are included in another Cochrane review (Hao 2011).

The text in the methods section of this review about the risk of bias assessment has been updated in line with the latest version of the Cochrane Hanbook for Systematic Reviews of Interventions and additional details about the process followed have been added.

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
Bellissimo-Rodrigues 2009 {published data only}
  • Bellissimo-Rodrigues F, Bellissimo-Rodrigues WT, Viana JM, Teixeira GC, Nicolini E, Auxiliadora-Martins M, et al. Effectiveness of oral rinse with chlorhexidine in preventing nosocomial respiratory tract infections among intensive care unit patients. Infection Control & Hospital Epidemiology 2009;30(10):952-8.
Berry 2011 {published data only}
  • Berry AM, Davidson PM, Masters J, Rolls K, Ollerton R. Effects of three approaches to standardized oral hygiene to reduce bacterial colonization and ventilator associated pneumonia in mechanically ventilated patients: A randomised control trial. International Journal of Nursing Studies 2011;48(6):681-8.
Bopp 2006 {published data only}
  • Bopp M, Darby M, Loftin KC, Broscious S. Effects of daily oral care with 0.12% chlorhexidine gluconate and a standard oral care protocol on the development of nosocomial pneumonia in intubated patients: a pilot study. Journal of Dental Hygiene 2006;80(3):9.
Cabov 2010 {published and unpublished data}
  • Cabov T, Macan D, Husedzinovic I, Skrlin-Subic J, Bosnjak D, Sestan-Crnek S, et al. The impact of oral health and 0.2% chlorhexidine oral gel on the prevalence of nosocomial infections in surgical intensive-care patients: a randomized placebo-controlled study. Wiener Klinische Wochenschrift 2010;122(13-14):397-404.
Caruso 2009 {published data only}
  • Caruso P, Denari S, Ruiz SAL, Demarzo SE, Deheinzelin D. Saline instillation before tracheal suctioning decreases the incidence of ventilator-associated pneumonia. Critical Care Medicine 2009;37(1):32-8.
Chen 2008 {published data only}
  • Chen QL, Ye XF, Jiang YZ, Yan MQ. Application of new oral care method to orotracheal intubation. Fujian Medical Journal 2008;30(5):155-7.
DeRiso 1996 {published data only}
  • DeRiso AJ 2nd, Ladowski JS, Dillon TA, Justice JW, Peterson AC. Chlorhexidine gluconate 0.12% oral rinse reduces the incidence of total nosocomial respiratory infection and nonprophylactic systemic antibiotic use in patients undergoing heart surgery. Chest 1996;109(6):1556-61.
Feng 2012 {published data only}
  • Feng S,  Sun X,  Chen Y. Application of different mouthwashes in oral nursing for patients with orotracheal intubation. China Medicine and Pharmacy 2012;8(2):100-1.
Fields 2008 {published data only}
  • Fields LB. Oral care intervention to reduce incidence of ventilator-associated pneumonia in the neurologic intensive care unit. Journal of Neuroscience Nursing 2008;40(5):291-8.
Fourrier 2000 {published data only}
  • Fourrier F, Cau-Pottier E, Boutigny H, Roussel-Delvallez M, Jourdain M, Chopin C. Effects of dental plaque antiseptic decontamination on bacterial colonization and nosocomial infections in critically ill patients. Intensive Care Medicine 2000;26(9):1239-47.
Fourrier 2005 {published data only}
  • Fourrier F, Dubois D, Pronnier P, Herbecq P, Leroy O, Desmettre T, et al. Effect of gingival and dental plaque antiseptic decontamination on nosocomial infections acquired in the intensive care unit: a double-blind placebo-controlled multicenter study. Critical Care Medicine 2005;33(8):1728-35.
Grap 2004 {published data only}
  • Grap MJ, Munro CL, Elswick RK Jr, Sessler CN, Ward KR. Duration of action of a single, early oral application of chlorhexidine on oral microbial flora in mechanically ventilated patients: a pilot study. Heart & Lung 2004;33(2):83-91.
Grap 2011 {published data only}
  • Grap MJ, Munro CL, Hamilton VA, Elswick RK Jr, Sessler CN, Ward KR. Early, single chlorhexidine application reduces ventilator-associated pneumonia in trauma patients. Heart & Lung 2011;40(5):e115-22.
Hu 2009 {published data only}
  • Hu X, Chen X. Application of improved oral nursing method to orotracheal intubation. Chinese Journal of Misdiagnostics 2009;9(17):4058-9.
Jacomo 2011 {published data only}
  • Jacomo AD, Carmona F, Matsuno AK, Manso PH, Carlotti AP. Effect of oral hygiene with 0.12% chlorhexidine gluconate on the incidence of nosocomial pneumonia in children undergoing cardiac surgery. Infection Control & Hospital Epidemiology 2011;32(6):591-6.
Koeman 2006 {published data only}
  • Koeman M, van der Ven AJ, Hak E, Joore HC, Kaasjager K, de Smet AG, et al. Oral decontamination with chlorhexidine reduces the incidence of ventilator-associated pneumonia. American Journal of Respiratory & Critical Care Medicine 2006;173(12):1348-55.
  • Koeman M, van der Ven AJ, Hak E, Joore JC, Kaasjager HA, de Smet AM, et al. Less ventilator-associated pneumonia after oral decontamination with chlorhexidine; a randomised trial. Nederlands Tijdschrift voor Geneeskunde 2008;152(13):752-9.
Kusahara 2012 {published data only}
  • Kusahara DM, Peterlini MA, Pedreira ML. Oral care with 0.12% chlorhexidine for the prevention of ventilator-associated pneumonia in critically ill children: Randomised, controlled and double blind trial. International Journal of Nursing Studies 2012;49(11):1354-63.
  • Kusahara DM, Peterlini MAS, Pedreira MLG. Randomized, controlled and double blinded trial of oral decontamination with 0.12% chlorhexidine for the prevention of ventilator-associated pneumonia in children. Pediatric Critical Care Medicine 2011;12(3, Suppl 1):A16.
  • Pedreira MLG, Kusahara DM, de Carvalho WB, Nunez SC, Peterlini MAS. Oral care interventions and oropharyngeal colonization in children receiving mechanical ventilation. American Journal of Critical Care 2009;18(4):319-29.
Long 2012 {published data only}
  • Long Y, Mou G, Zuo Y, lv F, Feng Q, Du J. Effect of modified oral nursing method on the patients with orotracheal intubation. Journal of Nurses Training 2012;27(24):2290-3.
Lorente 2012 {published data only}
  • Lorente L, Lecuona M, Jimenez A, Palmero S, Pastor E, Lafuente N, et al. Ventilator-associated pneumonia with or without toothbrushing: a randomized controlled trial. European Journal of Clinical Microbiology and Infectious Diseases 2012;31(10):2621-9.
McCartt 2010 {published data only}
  • McCartt PAM. Effect of Chlorhexidine Oral Spray versus Mechanical Toothbrushing and Chlorhexindine Rinse in Decreasing Ventilator Associated Pneumonia in Critically Ill Adults [PhD thesis]. Gainesville, Florida, USA: University of Florida, 2010:91.
Munro 2009 {published data only}
  • Munro C, Grap M, Sessler C, McClish D. Effect of oral care interventions on dental plaque in mechanically ventilated ICU adults. American Journal of Critical Care 2007;16(3):309.
  • Munro CL, Grap MJ, Jones DJ, McClish DK, Sessler CN. Chlorhexidine, toothbrushing, and preventing ventilator-associated pneumonia in critically ill adults. American Journal of Critical Care 2009;18(5):428-37.
Needleman 2011 {published data only}
Ozcaka 2012 {published data only}
Panchabhai 2009 {published data only}
  • Panchabhai TS, Dangayach NS, Krishnan A, Kothari VM, Karnad DR. Oropharyngeal cleansing with 0.2% chlorhexidine for prevention of nosocomial pneumonia in critically ill patients: an open-label randomized trial with 0.01% potassium permanganate as control. Chest 2009;135(5):1150-6.
Pobo 2009 {published data only}
  • Pobo A, Lisboa T, Rodriguez A, Sole R, Magret M, Trefler S, et al. A randomized trial of dental brushing for preventing ventilator-associated pneumonia. Chest 2009;136(2):433-9.
Prendergast 2012 {published data only}
  • Prendergast V. Safety and efficacy of oral care for intubated neuroscience intensive care patients. Doctoral Dissertation Series 2012-3. Lund, Sweden: Lund University, 2012:1-86.
  • Prendergast V, Hagell P, Hallberg IR. Electric versus manual tooth brushing among neuroscience ICU patients: is it safe?. Neurocritical Care 2011;14(2):281-6.
  • Prendergast V, Hallberg IR, Jakobsson U, Renvert S, Moran A, Gonzalez O. Comparison of oropharyngeal and respiratory nosocomial bacteria between two methods of oral care: A randomized controlled trial. Journal of Neuroscience and Neurosurgical Nursing 2012;1(1):10-18.
  • Prendergast V, Jakobsson U, Renvert S, Hallberg IR. Effects of a standard versus comprehensive oral care protocol among intubated neuroscience ICU patients: results of a randomized controlled trial. Journal of Neuroscience Nursing 2012;44(3):134-46.
Roca Biosca 2011 {published data only}
  • Roca Biosca A, Anguera Saperas L, García Grau N, Rubio Rico L, Velasco Guillén MC. Prevention of mechanical ventilator-associated pneumonia: a comparison of two different oral hygiene methods. Enfermería Intensiva 2011;22(3):104-11.
Scannapieco 2009 {published data only}
  • Scannapieco FA, Yu J, Raghavendran K, Vacanti A, Owens SI, Wood K, et al. A randomized trial of chlorhexidine gluconate on oral bacterial pathogens in mechanically ventilated patients. Critical Care 2009;13(4):R117.
Sebastian 2012 {published data only}
  • Sebastian MR, Lodha R, Kapil A, Kabra SK. Oral mucosal decontamination with chlorhexidine for the prevention of ventilator-associated pneumonia in children - a randomized, controlled trial. Pediatric Critical Care Medicine 2012;13:e305-10.
Seguin 2006 {published data only}
  • Seguin P, Tanguy M, Laviolle B, Tirel O, Malledant Y. Effect of oropharyngeal decontamination by povidone-iodine on ventilator-associated pneumonia in patients with head trauma. Critical Care Medicine 2006;34(5):1514-9.
Tantipong 2008 {published data only}
  • Silvestri L, van Saene HK, Milanese M, Zei E, Blazic M. Prevention of ventilator-associated pneumonia by use of oral chlorhexidine. Infection Control & Hospital Epidemiology 2009;30(1):101-3.
  • Tantipong H, Morkchareonpong C, Jaiyindee S, Thamlikitkul V. Randomized controlled trial and meta-analysis of oral decontamination with 2% chlorhexidine solution for the prevention of ventilator-associated pneumonia. Infection Control & Hospital Epidemiology 2008;29(2):131-6.
Xu 2007 {published data only}
  • Xu J, Feng B, He L, Shen H, Chen XY. Influence of different oral nursing methods on ventilator-associated pneumonia and oral infection in the patients undergoing mechanical ventilation. Journal of Nursing Science 2007;7(22):56-7.
Xu 2008 {published data only}
  • Xu HL. Application of improved oral nursing method to the prevention of ventilator-associated pneumonia. Journal of Qilu Nursing 2008;14(19):15-6.
Yao 2011 {published data only}
  • Yao L, Chang C, Wang C, Chen C. Effect of an oral care protocol in preventing ventilator associated pneumonia in ICU patients. Critical Care 2008;12(Suppl 2):Abs No P48.
  • Yao LY, Chang CK, Maa SH, Wang C, Chen CC. Brushing teeth with purified water to reduce ventilator-associated pneumonia. Journal of Nursing Research 2011;19(4):289-97.
Zhao 2012 {published data only}
  • Zhao Y. Research on application of Yikou gargle in prevention of ventilation associated pneumonia. Chinese Journal of Nosocomiology 2012;23(22):5232-3.

References to studies excluded from this review

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
Abusibeih 2010 {published data only}
Bordenave 2011 {published data only}
  • Bordenave C. Evaluation of the effectiveness of a protocol of intensification of mouth care (teeth brushing and chlorhexidine 0.12%) on the colonisation of tracheal aspirations in intubated and ventilated patients in intensive care. Recherche en Soins Infirmiers 2011;(106):92-8.
Chao 2009 {published data only}
Epstein 1994 {published data only}
Fan 2012 {published data only}
  • Fan T. The effect of a modified oral nursing care method on prevention of ventilator associated pneumonia. Nursing Practice and Research 2012;9(12):99-100.
Ferozali 2007 {published data only}
  • Ferozali F, Johnson G, Cavagnaro A. Health benefits and reductions in bacteria from enhanced oral care . Special Care in Dentistry 2007;27(5):168-76.
Genuit 2001 {published data only}
  • Genuit T, Bochicchio G, Napolitano LM, McCarter RJ, Roghman MC. Prophylactic chlorhexidine oral rinse decreases ventilator-associated pneumonia in surgical ICU patients. Surgical Infections 2001;2(1):5-18.
Guo 2007 {published data only}
  • Guo MJ. Study on the new oral nursing for the patient of acute lung brain-storm through tracheal. Chinese Journal of Modern Nursing 2007;13(26):2537-8.
Houston 2002 {published data only}
  • Houston S, Hougland P, Anderson JJ, LaRocco M, Kennedy V, Gentry LO. Effectiveness of 0.12% chlorhexidine gluconate oral rinse in reducing prevalence of nosocomial pneumonia in patients undergoing heart surgery. American Journal of Critical Care 2002;11(6):567-70.
Lai 1997 {published data only}
  • Lai M, Huang H. Toothpaste mouth care for critically ill patients. Journal of Nursing Science 1997;12(2):106-7.
Li 2011 {published data only}
  • Li W, Ma X, Peng Y, Cao J, Loo WTY, Hao L, et al. Application of a Nano-antimicrobial film to prevent ventilator-associated pneumonia: A pilot study. African Journal of Biotechnology 2011;10(10):1926-31.
Li 2012 {published data only}
  • Li S, Zhang H, Zhang B. Application of different oral nursing methods to prevent ventilation associated pneumonia. Practical Clinical Medicine 2012;13(5):92-3.
Liang 2007 {published data only}
  • Liang YL, Lu LQ, Liang JT. Oral cavity nursing study in endotracheal intubation with the Baihu decoction. Journal of Nurses Training 2007;1(22):79-80.
Liwu 1990 {published data only}
  • Liwu A. Oral hygiene in intubated patients. The Australian Journal of Advanced Nursing 1990;7(2):4-7.
MacNaughton 2004 {published data only}
  • MacNaughton PD, Bailey J, Donlin N, Branfield P, Williams A, Rowswell H. A randomised controlled trial assessing the efficacy of oral chlorhexidine in ventilated patients (029). Intensive Care Medicine 2004;30(Suppl):S12.
McCoy 2012 {published data only}
  • McCoy T, Fields W, Kent N. Evaluation of emergency department evidence-based practices to prevent the incidence of ventilator-acquired pneumonia. Journal of Nursing Care Quality 2012;27(1):83-8.
Ogata 2004 {published data only}
  • Ogata J, Minami K, Miyamoto H, Horishita T, Ogawa M, Sata T, et al. Gargling with povidone-iodine reduces the transport of bacteria during oral intubation. Canadian Journal of Anaesthesia 2004;51(9):932-6.
Pawlak 2005 {published data only}
  • Pawlak D, Semar R, Cantos K. Improving frequency of oral care in the medical intensive care unit. American Journal of Infection Control 2005;33(5):E147.
Santos 2008 {published data only}
  • Santos PSdS, Mello WR, Wakim RCS, Paschoal MÂG. Use of oral rinse with enzymatic system in patients totally dependent in the intensive care unit [Uso de solução bucal com sistema enzimático em pacientes totalmente dependentes de cuidados em unidade de terapia intensiva]. Revista Brasileira de Terapia Intensiva 2008;20(2):154-9.
Segers 2006 {published data only}
  • Segers P, Speekenbrink RG, Ubbink DT, van Ogtrop ML, de Mol BA. Prevention of nosocomial infection in cardiac surgery by decontamination of the nasopharynx and oropharynx with chlorhexidine gluconate: a randomized controlled trial. JAMA 2006;296(20):2460-6.
Ueda 2004 {published data only}
  • Ueda K, Yamada Y, Toyosato A, Nomura S, Saitho E. Effects of functional training of dysphagia to prevent pneumonia for patients on tube feeding. Gerodontology 2004;21(2):108-11.
Wang 2006 {published data only}
  • Wang MM. The improvement of oral care in ICU intubated patients. Journal of Mudanjiang Medical College 2006;27(5):80-1.
Wang 2012 {published data only}
  • Wang YX, He LY, Gao MR, Wang ZW, Li XY. Application of oral nursing care bundle to prevent VAP for critically surgically ill patients. Chinese Archives of General Surgery 2012;6(5):448-50.
Yin 2004 {published data only}
  • Yin XR, Liao Y. The improvement of the oral care for patients with orotracheal intubation. West China Medical Journal 2004;19(3):482.
Zouka 2010 {published data only}
  • Zouka M, Soultati I, Hari H, Pourzitaki C, Paroutsidou G, Thomaidou E, et al. Oral dental hygiene and ventilator-associated pneumonia prevention in an ICU setting: Comparison between two methods (preliminary data of a randomised prospective study). Intensive Care Medicine 2010;36:S103.

References to studies awaiting assessment

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
Anon 2012 {published data only}
  • Anon. EB57 Development of an oral care-based programme for prevention of ventilator-associated pneumonia. Critical Care Nurse 2012;32(2):e34.
Baradari 2012 {published data only}
  • Baradari AG, Khezri HD, Arabi S. Comparison of antibacterial effects of oral rinses chlorhexidine and herbal mouth wash in patients admitted to intensive care unit. Bratislavske Lekarske Listy 2012;113(9):556-60.
Seo 2011 {published data only}
  • Seo H-K, Choi E-H, Kim J-H. The effect of oral hygiene for ventilator-associated pneumonia (VAP) incidence. Journal of Korean Critical Care Nursing 2011;4(2):1.
Yun 2011 {published data only}
  • Yun H-Y, Lee E-S, Kim J-Y, Kim H-S, Kim K-A, Kim E-S, et al. Effect of tooth-brushing on oral health and ventilator-associated pneumonia of critically ill patients. Journal of Korean Critical Care Nursing 2011;4(2):1.

Additional references

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
Alhazzani 2013
  • Alhazzani W, Smith O, Muscedere J, Medd J, Cook D. Toothbrushing for critically ill mechanically ventilated patients: a systematic review and meta-analysis of randomized trials evaluating ventilator-associated pneumonia. Critical Care Medicine 2013;41(2):646-55.
Apostolopoulou 2003
  • Apostolopoulou E, Bakakos P, Katostaras T, Gregorakos L. Incidence and risk factors for ventilator-associated pneumonia in 4 multidisciplinary intensive care units in Athens. Respiratory Care 2003;48(7):681-8.
ATS Guideline 2005
  • American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. American Journal of J Respiratory and Critical Care Medicine 2005;171(4):388-416.
Azarpazhooh 2006
Azoulay 2006
  • Azoulay E, Timsit JF, Tafflet M, de Lassence A, Darmon M, Zahar JR, et al. Candida colonization of the respiratory tract and subsequent pseudomonas ventilator-associated pneumonia. Chest 2006;129(1):110-7.
Bekaert 2011
  • Bekaert M, Timsit JF, Vansteelandt S, Depuydt P, Vésin A, Garrouste-Orgeas M, et al. Attributable mortality of ventilator-associated pneumonia: a reappraisal using causal analysis. American Journal of Respiratory and Critical Care Medicine 2011;184(10):1133-9.
Berry 2007
  • Berry AM, Davidson PM, Masters J, Rolls K. Systematic literature review of oral hygiene practices for intensive care patients receiving mechanical ventilation. American Journal of Critical Care 2007;16(6):552-62.
Cook 1998
  • Cook DJ, Walter SD, Cook RJ, Griffith LE, Guyatt GH, Leasa D, et al. Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients. Annals of Internal Medicine 1998;29(6):433-46.
D'Amico 2009
Edwards 2009
  • Edwards JR, Peterson KD, Mu Y, Banerjee S, Allen-Bridson K, Morrell G, et al. National Healthcare Safety Network (NHSN) report: data summary for 2006 through 2008, issued December 2009. American Journal of Infection Control 2009;37(10):783-805.
El-Solh 2004
  • El-Solh AA, Pietrantoni C, Bhat A, Okada M, Zambon J, Aquilina A, et al. Colonization of dental plaques: a reservoir of respiratory pathogens for hospital-acquired pneumonia in institutionalized elders. Chest 2004;126(5):1575-82.
Estes 1995
Fourrier 1998
  • Fourrier F, Duvivier B, Boutigny H, Roussel-Delvallez M, Chopin C. Colonization of dental plaque: a source of nosocomial infections in intensive care unit patients. Critical Care Medicine 1998;26(2):301-8.
Garrouste-Orgeas 1997
  • Garrouste-Orgeas M, Chevret S, Arlet G, Marie O, Rouveau M, Popoff N, et al. Oropharyngeal or gastric colonization and nosocomial pneumonia in adult intensive care unit patients. A prospective study based on genomic DNA analysis. American Journal of Respiratory and Critical Care Medicine 1997;156(5):1647-55.
Gu 2012
  • Gu WJ, Gong YZ, Pan L, Ni YX, Liu JC. Impact of oral care with versus without toothbrushing on the prevention of ventilator-associated pneumonia: a systematic review and meta-analysis of randomized controlled trials. Critical Care 2012;16:R190.
Guyatt 2008
  • Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924-6.
Hao 2011
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Horan 2008
  • Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. American Journal of Infection Control 2008;36(5):309-32.
Labeau 2011
  • Labeau SO, Van de Vyver K, Brusselaers N, Vogelaers D, Blot SI. Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis. The Lancet Infectious Diseases 2011;11(11):845-54.
Marsh 2010
  • Marsh PD. Microbiology of dental plaque biofilms and their role in oral health and caries. Dental Clinics of North America 2010;54(3):441-54.
McCarney 2007
Melsen 2011
  • Melsen WG, Rovers MM, Koeman M, Bonten MJ. Estimating the attributable mortality of ventilator-associated pneumonia from randomized prevention studies. Critical Care Medicine 2011;39(12):2736-42.
Mojon 2002
  • Mojon P. Oral health and respiratory infection. Journal of the Canadian Dental Association 2002;68(6):340-6.
Muscedere 2008
  • Muscedere J, Dodek P, Keenan S, Fowler R, Cook D, Heyland D. Comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia: prevention. Journal of Critical Care 2008;23(1):126-37.
Pineda 2006
Pugin 1991
  • Pugin J, Auckenthaler R, Mili N, Janssens JP, Lew PD, Suter PM. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic 'blind' bronchoalveolar lavage fluid. American Review of Respiratory Disease 1991;143(5 Pt 1):1121-9.
Scannapieco 1992
Schulz 2002
Selim 2010
  • Selim AG, Balalis G, Bhaskar B, van Driel ML. Antibiotics for ventilator-associated pneumonia. Cochrane Database of Systematic Reviews 2010, Issue 4. [DOI: 10.1002/14651858.CD004267]
Shi 2004
  • Shi ZD, Yu JR, Luo R, He Y, Liu XC, Chen E. Effect of oral nursing care: a systematic review. Chinese Journal of Evidence Based Medicine 2004;4(12):837-46, 858.
Tablan 2004
  • Tablan OC, Anderson L, Besser R, Bridges C, Hajjeh R. Guidelines for preventing healthcare-associated pneumonia: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee. Morbidity & Mortality Weekly Report. Recommendations & Reports 2004;55 (RR-3):1-36.
Terezakis 2011
Terpenning 2005
Treloar 1995
  • Treloar DM, Stechmiller JK. Use of a clinical assessment tool for orally intubated patients. American Journal of Critical Care 1995;4(5):355-60.
Whittaker 1996
Zanatta 2011
  • Zanatta FB, Bergoli AD, Werle SB, Antoniazzi RP. Biofilm removal and gingival abrasion with medium and soft toothbrushes. Oral Health and Preventive Dentistry 2011;9(2):177-83.