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Meta-Analysis
. 2020 Dec 24;12(12):CD008367.
doi: 10.1002/14651858.CD008367.pub4.

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

Tingting Zhao #  1 , Xinyu Wu #  1 , Qi Zhang  2 , Chunjie Li  3 , Helen V Worthington  4 , Fang Hua  1   5   6
Affiliations
Meta-Analysis

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

Tingting Zhao et al. Cochrane Database Syst Rev. .

Abstract

Background: Ventilator-associated pneumonia (VAP) is defined as pneumonia developing in people who have received mechanical ventilation for at least 48 hours. VAP is a potentially serious complication in these patients who are already critically ill. Oral hygiene care (OHC), using either a mouthrinse, gel, swab, toothbrush, or combination, together with suction of secretions, may reduce the risk of VAP in these patients.

Objectives: To assess the effects of oral hygiene care (OHC) on incidence of ventilator-associated pneumonia in critically ill patients receiving mechanical ventilation in hospital intensive care units (ICUs).

Search methods: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 25 February 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2020, Issue 1), MEDLINE Ovid (1946 to 25 February 2020), Embase Ovid (1980 to 25 February 2020), LILACS BIREME Virtual Health Library (1982 to 25 February 2020) and CINAHL EBSCO (1937 to 25 February 2020). We also searched the VIP Database (January 2012 to 8 March 2020). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.

Selection criteria: We included randomised controlled trials (RCTs) evaluating the effects of OHC (mouthrinse, gel, swab, toothbrush or combination) in critically ill patients receiving mechanical ventilation for at least 48 hours.

Data collection and analysis: At least two review authors independently assessed search results, extracted data and assessed risk of bias in included studies. We contacted study authors for additional information. We reported risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, using the random-effects model of meta-analysis when data from four or more trials were combined.

Main results: We included 40 RCTs (5675 participants), which were conducted in various countries including China, USA, Brazil and Iran. We categorised these RCTs into five main comparisons: chlorhexidine (CHX) mouthrinse or gel versus placebo/usual care; CHX mouthrinse versus other oral care agents; toothbrushing (± antiseptics) versus no toothbrushing (± antiseptics); powered versus manual toothbrushing; and comparisons of other oral care agents used in OHC (other oral care agents versus placebo/usual care, or head-to-head comparisons between other oral care agents). We assessed the overall risk of bias as high in 31 trials and low in two, with the rest being unclear. Moderate-certainty evidence from 13 RCTs (1206 participants, 92% adults) shows that CHX mouthrinse or gel, as part of OHC, probably reduces the incidence of VAP compared to placebo or usual care from 26% to about 18% (RR 0.67, 95% confidence intervals (CI) 0.47 to 0.97; P = 0.03; I2 = 66%). This is equivalent to a number needed to treat for an additional beneficial outcome (NNTB) of 12 (95% CI 7 to 128), i.e. providing OHC including CHX for 12 ventilated patients in intensive care would prevent one patient developing VAP. There was no evidence of a difference between interventions for the outcomes of mortality (RR 1.03, 95% CI 0.80 to 1.33; P = 0.86, I2 = 0%; 9 RCTs, 944 participants; moderate-certainty evidence), duration of mechanical ventilation (MD -1.10 days, 95% CI -3.20 to 1.00 days; P = 0.30, I2 = 74%; 4 RCTs, 594 participants; very low-certainty evidence) or duration of intensive care unit (ICU) stay (MD -0.89 days, 95% CI -3.59 to 1.82 days; P = 0.52, I2 = 69%; 5 RCTs, 627 participants; low-certainty evidence). Most studies did not mention adverse effects. One study reported adverse effects, which were mild, with similar frequency in CHX and control groups and one study reported there were no adverse effects. Toothbrushing (± antiseptics) may reduce the incidence of VAP (RR 0.61, 95% CI 0.41 to 0.91; P = 0.01, I2 = 40%; 5 RCTs, 910 participants; low-certainty evidence) compared to OHC without toothbrushing (± antiseptics). There is also some evidence that toothbrushing may reduce the duration of ICU stay (MD -1.89 days, 95% CI -3.52 to -0.27 days; P = 0.02, I2 = 0%; 3 RCTs, 749 participants), but this is very low certainty. Low-certainty evidence did not show a reduction in mortality (RR 0.84, 95% CI 0.67 to 1.05; P = 0.12, I2 = 0%; 5 RCTs, 910 participants) or duration of mechanical ventilation (MD -0.43, 95% CI -1.17 to 0.30; P = 0.25, I2 = 46%; 4 RCTs, 810 participants).

Authors' conclusions: Chlorhexidine mouthwash or gel, as part of OHC, probably reduces the incidence of developing ventilator-associated pneumonia (VAP) in critically ill patients from 26% to about 18%, when compared to placebo or usual care. We did not find a difference in mortality, duration of mechanical ventilation or duration of stay in the intensive care unit, although the evidence was low certainty. OHC including both antiseptics and toothbrushing may be more effective than OHC with antiseptics alone to reduce the incidence of VAP and the length of ICU stay, but, again, the evidence is low certainty. There is insufficient evidence to determine whether any of the interventions evaluated in the studies are associated with adverse effects.

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Conflict of interest statement

Tingting Zhao: none known Xinyu Wu: none known Qi Zhang: none known Chunjie Li: none known Helen V Worthington: none known. I am an Editor with Cochrane Oral Health. Fang Hua: none known. I am an Editor with Cochrane Oral Health.

Figures

1
1
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
2
2
Risk of bias summary graph: review authors' judgements about each risk of bias item for each included study
3
3
Study flow diagram
1.1
1.1. Analysis
Comparison 1: Chlorhexidine versus placebo/usual care, Outcome 1: Incidence of VAP
1.2
1.2. Analysis
Comparison 1: Chlorhexidine versus placebo/usual care, Outcome 2: Mortality
1.3
1.3. Analysis
Comparison 1: Chlorhexidine versus placebo/usual care, Outcome 3: Duration of ventilation (days)
1.4
1.4. Analysis
Comparison 1: Chlorhexidine versus placebo/usual care, Outcome 4: Duration of ICU stay (days)
1.5
1.5. Analysis
Comparison 1: Chlorhexidine versus placebo/usual care, Outcome 5: Duration of systemic antibiotic therapy (days)
1.6
1.6. Analysis
Comparison 1: Chlorhexidine versus placebo/usual care, Outcome 6: Number of participants treated with systemic antibiotics
1.7
1.7. Analysis
Comparison 1: Chlorhexidine versus placebo/usual care, Outcome 7: Plaque index
1.8
1.8. Analysis
Comparison 1: Chlorhexidine versus placebo/usual care, Outcome 8: Adverse effects
2.1
2.1. Analysis
Comparison 2: Chlorhexidine versus other oral care agents, Outcome 1: Incidence of VAP
2.2
2.2. Analysis
Comparison 2: Chlorhexidine versus other oral care agents, Outcome 2: Mortality
2.3
2.3. Analysis
Comparison 2: Chlorhexidine versus other oral care agents, Outcome 3: Number of participants treated with systemic antibiotics
3.1
3.1. Analysis
Comparison 3: Toothbrushing versus no toothbrushing, Outcome 1: Incidence of VAP
3.2
3.2. Analysis
Comparison 3: Toothbrushing versus no toothbrushing, Outcome 2: Mortality
3.3
3.3. Analysis
Comparison 3: Toothbrushing versus no toothbrushing, Outcome 3: Duration of ventilation (days)
3.4
3.4. Analysis
Comparison 3: Toothbrushing versus no toothbrushing, Outcome 4: Duration of ICU stay (days)
3.5
3.5. Analysis
Comparison 3: Toothbrushing versus no toothbrushing, Outcome 5: Plaque score
4.1
4.1. Analysis
Comparison 4: Powered toothbrush versus manual toothbrush, Outcome 1: Incidence of VAP
4.2
4.2. Analysis
Comparison 4: Powered toothbrush versus manual toothbrush, Outcome 2: Mortality
4.3
4.3. Analysis
Comparison 4: Powered toothbrush versus manual toothbrush, Outcome 3: Duration of ventilation (days)
4.4
4.4. Analysis
Comparison 4: Powered toothbrush versus manual toothbrush, Outcome 4: Duration of ICU stay (days)
5.1
5.1. Analysis
Comparison 5: Other oral care agents, Outcome 1: Incidence of VAP
5.2
5.2. Analysis
Comparison 5: Other oral care agents, Outcome 2: Mortality
5.3
5.3. Analysis
Comparison 5: Other oral care agents, Outcome 3: Duration of ventilation (days)
5.4
5.4. Analysis
Comparison 5: Other oral care agents, Outcome 4: Duration of ICU stay (days)
5.5
5.5. Analysis
Comparison 5: Other oral care agents, Outcome 5: Number of participants treated with systemic antibiotics
5.6
5.6. Analysis
Comparison 5: Other oral care agents, Outcome 6: Adverse effects
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Haghighi 2017 {published data only}
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Jafari 2007 {published data only}
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Kusahara 2012b {published data only}
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Lai 1997 {published data only}
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Li 2011 {published data only}
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Li 2012 {published data only}
    1. 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}
    1. 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.
Liao 2015 {published data only}
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Liwu 1990 {published data only}
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Maury 2015 {published data only}
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    1. 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.
McCoy 2012 {published data only}
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Munro 2015 {published data only}
    1. Munro CL, Grap MJ, Sessler CN, Elswick RK Jr, Mangar D, Karlnoski-Everall R, et al. Preintubation application of oral chlorhexidine does not provide additional benefit in prevention of early-onset ventilator-associated pneumonia. Chest 2015;147(2):328-34. - PMC - PubMed
Nasiriani 2016 {published data only}
    1. Nasiriani K, Torki F, Jarahzadeh MH, Rashidi Maybodi F. The effect of brushing with a soft toothbrush and distilled water on the incidence of ventilator-associated pneumonia in the intensive care unit. Tanaffos 2016;15:101-7. [1735-0344: (Print) // 1735-0344 (Linking)] - PMC - PubMed
NCT01657396 {unpublished data only}
    1. NCT01657396. Implementation and evaluaion of revised protocols for oral hygiene for mechanically ventilated patients [Implementation and evaluation of revised protocols for oral hygiene for mechanically ventilated patients in Alberta Health Services Calgary Region - a pilot project.]. www.clinicaltrials.gov/ct2/show/NCT01657396?term=01657396&draw=1&amp... (first received 6 August 2012).
Needleman 2011 {published data only}
    1. Needleman IG, Hirsch NP, Leemans M, Moles DR, Wilson M, Ready DR, et al. Randomized controlled trial of toothbrushing to reduce ventilator-associated pneumonia pathogens and dental plaque in a critical care unit. Journal of Clinical Periodontology 2011;38(3):246-52. - PubMed
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    1. 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. - PubMed
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Pelucchi 2013 {published data only}
    1. Pelucchi G, Ciucur M, Giacovelli M, Lucchini A, Luongo M. Oral hygiene [L'igiene del cavo orale]. SCENARIO: Official Italian Journal of ANIARTI 2013;30:23-34.
Pivkina 2014 {published data only}
    1. Pivkina AI, Gusarov VG, Zhivotneva IV, Bodunova GE. Oral care in ventilated patients - can we improve it? Intensive Care Medicine 2014;40:S28.
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    1. Santos PS, Mello WR, Wakim RCS, Paschoal MG. 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. - PubMed
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Tsai 2017 {published data only}
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    1. 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.
Wang 2016 {published data only}
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References to studies awaiting assessment

Chacko 2017 {published data only}
    1. Chacko R, Rajan A, Lionel P, Thilagavathi M, Yadav B, Premkumar J. Oral decontamination techniques and ventilator-associated pneumonia. British Journal of Nursing 2017;26:594-9. - PubMed
Hashemi 2018 {published data only}
    1. Hashemi ST, Alikiaii B, Ali Fallah-Medvari M, Karimi F, Fallah-Medvari A. Comparison of effects of chlorhexidine mouthwash versus stop-snoring mouthwash in prevention of ventilator-associated pneumonia. Journal of Isfahan Medical School 2018;36:227-32.
Hashemi 2019 {published data only}
    1. Hashemi ST, Alikiaii B, Fallah Medvari MA, Karimi F, Fallah Medvari A. Comparison of effects of chlorhexidine mouthwash with herbal cinnamol mouthwash on prevention of ventilator associated pneumonia. Medical Journal of Tabriz University of Medical Sciences and Health Services 2020;41(6):91-7.
IRCT20110427006318N12 {published data only}
    1. IRCT20110427006318N12. Effect of propolis mouthwash on incidence of pneumonia in hospitalized patient in critical care unit [Effect of propolis mouthwash on incidence of ventilator-associated pneumonia in hospitalized patient in critical care unit]. www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20110427006318N12 (first received 2 April 2019).
IRCT2013050813278N1 {published data only}
    1. IRCT2013050813278N1. The effect of oral care on pulmonary infection in intensive care unit [Comparison of two methods of oral care on oral health and the prevention of ventilator-associated pneumonia in mechanically ventilated patients in intensive care unit]. www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT2013050813278N1 (first received 25 May 2013).
IRCT201512115363N8 {published data only}
    1. IRCT201512115363N8. Effect of damask rose extract in the prevention of ventilator-associated pneumonia [Clinical trial to compare the effect of damask rose extract and chlorhexidine in prevention of ventilator-associated pneumonia in critically ill patients]. www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT201512115363N8 (first received 4 December 2016).
IRCT2016052828134N1 {published data only}
    1. IRCT2016052828134N1. Effects of botanical mouthwash of aloe vera on ventilator associated pneumonia of patients having endotracheal tube hospitalized in the intensive care unit. www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT2016052828134N1 (first received 21 June 2016).
IRCT2017022032676N1 {published data only}
    1. IRCT2017022032676N1. Comparing the effect of persica and chlorhexidine on the prevention of ventilator associated pneumonia in patient admitted in ICU [Effect of persica and chlorhexidine on the prevention of ventilator associated pneumonia]. www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT2017022032676N1 (first received 22 April 2017).
IRCT2017050727819N4 {published data only}
    1. IRCT2017050727819N4. The effects of mouthwash on prevention of pneumonia [The comparison of the effects of orthodentol and chlorhexidine mouthwash on prevention of ventilator associated pneumonia in mechanically ventilated patients]. www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT2017050727819N4 (first received 26 June 2017).
IRCT20171225038053N1 {published data only}
    1. IRCT20171225038053N1. Effect of two methods mouth wash (chlorhexidine and chlorhexidine combined with hydrogen peroxide solution) on frequency of oral plaques and ventilator-associated pneumonia in patients undergoing mechanical ventilation [Comparison of the effect of two methods mouth wash (chlorhexidine and chlorhexidine combined with hydrogen peroxide solution) on frequency of oral plaques and ventilator-associated pneumonia in patients undergoing mechanical ventilation in the intensive care unit of Imam Khomeini Educational Center, Urmia, 2017-18]. www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20171225038053N1 (first received 9 September 2018).
IRCT20180520039739N2 {published data only}
    1. IRCT20180520039739N2. Evaluation of effect of chlorhexidine on prevention of ventilator associated pneumonia [Comparison of the effect of Chlorhexidine mouthwash with Dine mouthwash on prevention of ventilator-associated pneumonia in pediatric intensive care unit]. www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20180520039739N2 (first received 26 November 2018).
IRCT20191012045066N1 {published data only}
    1. IRCT20191012045066N1. The effects of oral care program on oropharyngeal complications and the occurrence of ventilator associated pneumonia [Evaluation and comparison of the effects of three oral care programs on oropharyngeal complications and the occurrence of ventilator associated pneumonia in patients undergoing mechanical ventilation]. www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20191012045066N1 (first received 7 November 2019).
Jamshidi 2016 {published data only}
    1. Jamshidi MR, Qatreh Samany F, Goli Farhood G, Qodrati S, Falakaflaki B. Evaluating the effect of chlorhexidine and tooth brushing in preventing the ventilator associated pneumonia. Journal of Zanjan University of Medical Sciences and Health Services 2016;24(105):9-17.
Mehrabadi 2015 {published data only}
    1. Gholami Mehrabadi M, Khosravi SH, Rezaie K, Malekianzadeh B, Ghorbanpour M, Moslemi A, et al. The effect of Echinacea mouthwash on ventilator associated pneumonia in patients in intensive care units. Medical-Surgical Nursing Journal 2015;4(3):13-20.

References to ongoing studies

RBR‐7p6568 {published data only}
    1. RBR-7p6568. Oral hygiene in critically ill patients [Oral hygiene in critically ill patients - a randomized controlled trial]. www.who.int/trialsearch/Trial2.aspx?TrialID=RBR-7p6568 (first received 8 October 2019).
TCTR20190530003 {published data only}
    1. TCTR20190530003. Efficacy of moraceae with chlorhexidine mouthwash on microbial flora of critically ill intubated patients [Efficacy of moraceae with chlorhexidine mouthwash on microbial flora of critically ill intubated patients: a randomized controlled pilot study]. www.who.int/trialsearch/Trial2.aspx?TrialID=TCTR20190530003 (first received 29 May 2019). - PMC - PubMed

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