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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

 
Characteristics of included studies [ordered by study ID]
Bellissimo-Rodrigues 2009

MethodsStudy design: RCT, 2 parallel groups

Location: Sao Paulo, Brazil

Number of centres: 1

Study period: March 2006 to February 2008

Funding source: Not stated


ParticipantsSetting: ICU in tertiary care hospital

Inclusion criteria: All patients admitted to ICU with expected stay > 48 hours. Not all participants received mechanical ventilation

Exclusion criteria: Previous chlorhexidine sensitivity, pregnancy, formal indication for chlorhexidine use, prescription of another oral topical medication

Number randomised: 200 (only 133 on ventilators)

Number evaluated: 194

Baseline characteristics:

-Intervention group: Age: median 62.5 (17-89) M/F: 47/51; APACHEII Score: median 17 (5-35)

-Control group: Age: median 54.0 (15-85) M/F: 51/45; APACHEII Score: median 19 (5-41)


InterventionsComparison: 0.12% chlorhexidine solution versus placebo

Experimental group (n = 64 on vent): 0.12% chlorhexidine solution applied orally 3 times daily. Oral hygiene was conducted by nurses specially trained in the protocol. 3 times daily after mechanical cleaning of the mouth by a nurse, 15 ml of study solution was applied and attempts made to distribute solution over all oral surfaces

Control group (n = 69 on vent): The same protocol was conducted with the placebo solution, which was identical in colour consistency smell and taste


Outcomes1. Respiratory tract infections (VAP for those on ventilators)

2. Respiratory tract infection-free survival time

3. Time from ICU admission to first RTI

4. Duration of mechanical ventilation

5. Length of ICU stay

6. Total mortality

7. Mortality due to RTI

8. Antibiotic use

9. Microbiological culture of endotracheal secretions

10. Adverse effects


NotesSample size calculation: "to have sufficient power to detect a 69% difference in incidence of VAP with α = 5% and β = 20% it was estimated that 96 patients per group were required"

Only 133/194 of patients evaluated received mechanical ventilation

Email sent 3 September 2012. Reply received


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"randomised" Method of sequence generation not described but undertaken by pharmacy

Allocation concealment (selection bias)Low risk"only the pharmacist knew which code numbers corresponded to which type of solution"

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blind

Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble blind

Incomplete outcome data (attrition bias)
All outcomes
Low risk6/200 patients were excluded from the analysis. 1 control patient needed to receive chlorhexidine treatment, and further 3 in control group and 2 in experimental group were excluded due to protocol violation. Unlikely to have introduced a bias

Selective reporting (reporting bias)Low riskAll planned outcomes reported

Other biasLow riskNo other sources of bias identified

Berry 2011

MethodsStudy design: Feasibility study – single blind parallel group RCT with 3 groups

Location: Australia

Number of centres: 1

Study period:

Funding source: Hospital


ParticipantsSetting: A 20-bed adult intensive care unit in a university hospital

Inclusion criteria: All intubated patients admitted to the unit were considered for inclusion in the study provided they met the following criteria: able to be randomised within 12 hours of intubation, aged over 15 years and next of kin able to give informed consent

Exclusion criteria: Patients were ineligible for study participation if they: required specific oral hygiene procedures in relation to maxillofacial trauma or dental trauma/surgery; had been in the ICU previously during the current period of hospitalisation; received irradiation or chemotherapy on admission to the ICU or in the preceding 6 weeks; or suffered an autoimmune disease. Informed consent was obtained for all subjects and agreement to participate could be withdrawn at any time

Number randomised: 225 (71, 76, 78 in Groups 1, 2, 3)

Number evaluated: 109 (33, 33, 43 in Groups 1, 2, 3)

Group 1 (chlorhexidine 0.2% aqueous) group: Age: 58.2±19.4; M/F: 35/36; APACHEII Score: 22.8±7.8

Group 2 (sodium bicarbonate mouthwash rinsed 2 hourly): Age: 60.4±17.5; M/F: 42/24; APACHEII Score: 22.0±7.5

Group 3 (sterile water rinsed 2 hourly): Age: 59.1±18.1; M/F: 44/34; APACHEII Score: 21.6±7.8


InterventionsComparison: Chlorhexidine 0.2% versus water versus sodium bicarbonate

Group 1: Twice daily irrigation with chlorhexidine 0.2% aqueous oral rinse with 2 hourly irrigation with sterile water

Group 2: Sodium bicarbonate mouthwash rinsed 2 hourly

Group 3: sterile water rinsed 2 hourly (used as the control in this review)

"All treatment options included a comprehensive cleaning of the mouth using a soft, pediatric toothbrush 3 times a day"


Outcomes3 outcome variables were reported:

1. Microbial colonisation of dental plaque (or gums in edentulous patients)

2. Incidence of VAP

3. Adverse events


NotesSample size calculation: Feasibility study to inform sample size calculation for main study


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"...randomisation into one of three groups according to a balanced randomisation table prepared by biostatistician"

Allocation concealment (selection bias)Low riskStudy packs were identical in outward appearance and allocation remained blinded until study pack opened by attending nurse

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskParticipants: Blinding not possible, but non-blinding of carers may have introduced a risk of bias

Blinding of outcome assessment (detection bias)
All outcomes
Low riskMicrobiologist and radiologists who assessed outcomes were blinded to allocated treatment

Incomplete outcome data (attrition bias)
All outcomes
High risk102/225 participants evaluated. High rate of attrition and reasons varied in each group. Death rate higher in Group B, breach of inclusion criteria more likely in Groups B &C

Selective reporting (reporting bias)Low riskPlanned outcomes reported

Other biasHigh riskStudy stopped early due to withdrawal of investigational product by regulator

Bopp 2006

MethodsStudy design: Pilot study, 2-arm RCT

Location: USA

Number of centres: 1

Study period: February to August 2002

Funding source: Grant from American Dental Hygienists' Association's Institute for Oral Health


ParticipantsSetting: Critical care unit

Inclusion criteria: Orally and nasally intubated patients entering critical care unit

Exclusion criteria: Taking metronidazole, history of allergy to chlorhexidine, sensitive to alcohol, risk for endocarditis, history of other serious illness (specified), those with pneumonia

Number randomised: 5

Number evaluated: 5

Baseline characteristics:

-Intervention group: Age: 40, range 28-52; M/F: 0/2

-Control group: Age: 73.7, range 62-81; M/F: 2/1


InterventionsComparison: 0.12% chlorhexidine + suction toothbrush versus suction swab + hydrogen peroxide

Experimental group (n = 2): Twice daily oral hygiene care with 0.12% chlorhexidine gluconate during intubation period plus oral cleaning with PlaqVac suction toothbrush

Control group (n = 3): Standard oral care 6 times daily using a suctioning soft foam swab and half strength hydrogen peroxide, plus oral lubricant


OutcomesMicrobial colonisation VAP, mortality


NotesSample size calculation: This was a pilot study. Data were not used in meta-analysis on advice of statistician

Email sent to contact author 14 November 2012, reply received 19 November 2012


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"...randomly assigned to either control or experimental treatment by the flip of a coin"

Allocation concealment (selection bias)High riskCoin toss was undertaken by researcher. No allocation concealment

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskBlinding not possible. Reply from contact author "they were not blinded"

Blinding of outcome assessment (detection bias)
All outcomes
High riskReply from contact author "they were not blinded"

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll randomised patients included in outcome evaluation

Selective reporting (reporting bias)Unclear riskVAP planned and reported in this pilot study. Microbial culture data not reported per person, and mortality is also reported

Other biasLow riskNo other sources of bias detected

Cabov 2010

MethodsStudy design: 2-parallel arm RCT

Location: Croatia

Number of centres: 1

Study period: March to December 2008

Funding source: Supported by Croatian Ministry of Science Education and Sports Grant number 065-1080057-0429


ParticipantsSetting: Surgical ICU in university hospital

Inclusion criteria: Aged > 18 years, medical condition suggesting hospitalisation in ICU > 3 days, eventual requirement for mechanical ventilation by oro or nasotracheal ventilation

Exclusion criteria:

Number randomised: 60. 40 of the 60 participants (17 and 23 in each group) were on mechanical ventilation

Number evaluated: 60

Baseline characteristics:

-Intervention group: Age: 57±16; M/F: 19/11

-Control group: Age: 52±19; M/F: 20/10


InterventionsComparison: Chlorhexidine gel versus placebo

Experimental group (n = 17): 3 times daily, following standard oral care comprising rinsing mouth with bicarbonate isotonic serum, followed by gently oropharyngeal sterile aspiration, patients received application of 0.2% chlorhexidine gel applied by nurses to dental gingival and oral surfaces using a sterile gloved finger

Control group (n = 23): Standard oral care, 3 times daily as above followed by administration of placebo gel

In both groups gel was left in place and oral cavity was not rinsed


OutcomesSimplified acute physiological score (SAPS), dental status, dental plaque, plaque culture, nosocomial infections, mortality


NotesSample size calculation: Not reported


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"...randomized into two groups using a computer-generated balanced randomization table"

Allocation concealment (selection bias)Unclear riskUnclear who conducted the allocation and whether it was concealed from the investigators

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blind

Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll randomised participants included in outcome evaluations

Selective reporting (reporting bias)Low riskAll planned outcomes reported

Other biasLow riskNo other sources of bias identified

Caruso 2009

MethodsStudy design: 2-arm RCT

Location: Brazil

Number of centres: 1

Study period: August 2001 to December 2004

Funding source: Not stated


ParticipantsSetting: Closed medical surgical ICU unit in oncologic hospital

Inclusion criteria: Patients aged > 18 years expected to need mechanical ventilation for > 72 hours through orotracheal or tracheotomy tube

Exclusion criteria: Previous mechanical ventilation within past month, mechanical ventilation for > 6 hours prior to study enrolment, contraindication to bronchoscopy and expected to die or stop treatment within 48 hours

Number randomised: 262

Number evaluated: 262

Baseline characteristics:

-Intervention group: Age: 65±14 years; M/F: 66/64

-Control group: Age: 63±6 years; M/F: 70/62


InterventionsComparison: Saline rinse versus usual care

Experimental group (n = 130): Instillation of 8 ml of isotonic saline prior to tracheal suctioning, which was conducted by respiratory therapists

Control group (n = 132): Tracheal suction alone with no saline instillation

Aspirations were carried out when 1 of the following occurred: visible airway secretion into endotracheal tube, discomfort or patient asynchrony, noisy breathing, increased peak expiratory pressures, or decreased tidal volume during ventilation attributed to airway secretion


Outcomes1. Incidence of VAP

2. Duration of ventilation in ICU

3. Length of stay in ICU

4. ICU mortality

5. Tracheal colonisation

6. Suctions per day, chest radiographs


NotesSample size calculation: Estimated that 130 patients per group required to give 80% power with alpha 5% to detect a decrease in VAP from 30% to 15%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"randomised" No details of method of sequence generation provided in report

Allocation concealment (selection bias)Unclear riskNot described

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskAttending physicians and nurses blinded to study group. Intervention carried out by respiratory therapists available on ICU 24/7

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessment conducted by physicians and nurses blinded to allocated treatment

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll randomised patients included in outcome evaluation

Selective reporting (reporting bias)Low riskAll planned outcomes reported in full

Other biasLow riskNo other sources of bias identified

Chen 2008

MethodsStudy design: A single centre RCT with 2 parallel groups

Location: China

Number of centres: 1 surgical ICU in provincial hospital

Study period: Not stated

Funding source: External


ParticipantsInclusion criteria: Admission into the ICU, orally intubated, receiving mechanical ventilation ≥ 7 days, without oral and lung disease

Exclusion criteria: Using hormone therapy, with diabetes

Number randomised: 120

Number evaluated: 120

Intervention group: n = 60; mean age: 42.0±9.0; M/F: 39/21

Control group: n = 60; mean age: 40.0±8.0; M/F: 45/15

Baseline characteristics were comparable


InterventionsComparison: Oral care + chlorhexidine rinse versus saline rinse

Intervention group: Oral cavity irrigated with 50 ml GSE rinse (chlorhexidine + extracts of grapefruit + FE enzyme) then aspirated off, 4 times a day, and routine oral nursing care was given once a day after the first irrigation

Control group: Oral irrigation with 50 ml saline, 4 times a day, without the combination of routine oral care


Outcomes3 outcome variables were reported:

1. Incidence of VAP after 7 days of mechanical ventilation

2. Incidence of oral inflammation (ulceration and herpes)

3. Change in bacteria colonisation: the throat swab cultures at baseline and after treatment


NotesGSE rinse: We are advised by reviewers from China that GSE rinse should be treated as chlorhexidine + 2 potentially active other antiseptics

Diagnosis of VAP was according to Chinese Society of Respiratory Diseases criteria

Information translated from Chinese paper by Shi Zongdao and colleagues


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskPatients were randomised into different groups according to a randomised number table

Allocation concealment (selection bias)Unclear riskNot mentioned

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskBlinding not described and not possible. Difference between intervention and control means carers would be aware of who was in each group

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskBlinding not described

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals

Selective reporting (reporting bias)Unclear riskInsufficient information on throat swab culture result (baseline and after treatment)

Other biasUnclear riskThe treatment group received co-intervention of routine oral nursing care once daily, but this was not done in the control group

DeRiso 1996

MethodsStudy design: Parallel group RCT

Location: Indiana USA

Number of centres: 1

Study period: Not stated

Funding source: The study was supported by a grant from the August Tomusk Foundation


ParticipantsSetting: Surgical ICU for post-operative cardiac surgery

Inclusion criteria: Patients undergoing cardiac surgery which required cardiopulmonary bypass

Exclusion criteria: Intra-operative death, pre-operative infection or intubation, pregnancy, heart and lung transplant recipients, known hypersensitivity to chlorhexidine

Number randomised: Unclear

Number evaluated: 353 (173 in chlorhexidine group and 180 in control)

Baseline characteristics:

-Intervention group: Age: 64.1±0.86; M/F: 119/54

-Control group: Age: 63.5±0.84; M/F: 123/57


InterventionsComparison: Chlorhexidine oral rinse versus placebo

Experimental group: 0.5 fl ounce (approx 15 ml) of 0.12% chlorhexidine (+ 11.6% ethanol (Proctor & Gamble)) mouthrinse used as oropharyngeal rinse and "rigorously applied" to buccal, pharyngeal, gingival tongue and tooth surfaces for 30 seconds twice daily

Control group: Placebo mouthrinse identical in appearance containing base solution and 3.2% ethanol (1/3 of concentration of active solution)

All patients also received the standard oral care of the ICU (systemic antibiotics, pressor agents and nutritional support as deemed necessary


Outcomes5 outcome variables were reported:

1. Nosocomial infection rates (upper & lower RTI, UTI, fungemias, line sepsis, wound & blood infection, other infection)

2. Non-prophylactic antibiotic use

3. Length of stay in hospital

4. Duration of intubation

5. Mortality


NotesSample size calculation: Not reported

Unclear duration of mechanical ventilation. Unable to contact author


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"..the pharmacy randomised the patients to either experimental or control group by means of computer driven random number generator"

Allocation concealment (selection bias)Low riskAllocation was performed in pharmacy and solutions wit identical appearance were dispensed for use in ICU

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blind. Quote: "…matching placebo…Both were packaged in 120-mL brown bottles and labelled 'Oral Rinse Solution: Peridex/Placebo Trial Solution' with a 1-week expiration date"

Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble blind

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNumber of patients originally randomised to treatment or control groups not stated

Selective reporting (reporting bias)Low riskPlanned outcomes reported (no data for length of stays, duration of ventilation)

Other biasLow riskNo other sources of bias identified

Feng 2012

MethodsStudy design: A single centre RCT with 3 parallel groups (2 groups included in this review)

Location: China

Number of centres: 1 ICU in a city hospital

Study period: February 2009 to January 2011

Funding source: Not stated


ParticipantsInclusion criteria: Entry ICU, with orotracheal intubation and ventilation

Exclusion criteria: Pulmonary infection, stomatitis or oral tumours before intubation, accompanied with ulcer of the digestive tract, malignant tumours of the body, taking steroids >3 days, diabetes

Number randomised: 204

Number evaluated: 204

Intervention group: 0.05% povidone iodine: n = 71; mean age: 43.7±8.1 years

Intervention group: 1/5000 furacilin: n = 65; mean age: 38.5±11.6 years

Control group: Saline n = 68; mean age: 40.3±8.5 years

Baseline characteristics: Not specified


InterventionsComparison: Povidone iodine + toothbrushing versus saline + toothbrushing

Group A (n = 71): Toothbrushing along the slits between the teeth with 0.05% povidone iodine by nurses, then the oropharyngeal cavity was rinsed with 50 ml of the solution and it was suctioned out completely. This procedure was repeated 4 times a day

Group B: Toothbrushing along the slits between the teeth with 1/5000 furacilin (antibiotic) by nurses. Excluded from this review

Control group (n = 68): Toothbrushing along the slits between the teeth with 0.9% saline by nurses, then the oropharyngeal cavity was rinsed with 50 ml of the saline and it was suctioned out completely. This procedure was repeated 4 times a day


Outcomes4 outcome variables were reported:

1. Incidence of VAP

2. Rates of oral ulcer and/or herpes

3. Oral cleaness - no odour, no foreign bodies and visually clean surfaces of tube and equipment

4. Throat swab culture


NotesDiagnosis of VAP was according to Chinese Society of Respiratory Diseases criteria


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Patients were divided into three groups according to randomisation principle"

Allocation concealment (selection bias)Unclear riskNot specified

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskBlinding not described and not possible for the carers who would be aware of who was in each group

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk Not specified

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll randomised participants included in the outcome evaluation

Selective reporting (reporting bias)Low riskThe results were fully reported

Other biasLow riskNo other sources of bias identified

Fields 2008

MethodsStudy design: Parallel group RCT

Location: Akron Ohio, USA

Number of centres: 1

Study period: October 2005 to March 2006

Funding source: Internal hospital funding


ParticipantsSetting: 24-bed stroke, neurological and medical ICU

Inclusion criteria: Any mechanically ventilated patient on the stroke/medical ICU intubated in the hospital for < 24 hours , no previous diagnosis of pneumonia

Exclusion criteria: Patients with prior tracheotomies, younger than 18 years, AIDS secondary to immunocompromised systems, edentulous patients

Number randomised: Not stated

Number evaluated: Not stated

Baseline characteristics: Not reported


InterventionsComparison: Toothbrushing 8 hourly versus usual care

Experimental group: Nurse brushed patient's teeth, tongue and hard palate for > 1 minute, then used toothette swab to swab patient's teeth tongue and hard palate for > 1 minute, then apply moisturiser to lips. Mouth and pharynx were suctioned as needed using catheter which was replaced every 24 hours. Oral assessment every 12 hours. Oral care kit #2 provided for each participant, with worksheet #2

Control group: Usual care (unspecified) which could include up to 2 toothbrushings daily and toothette mouthcare as needed. Nurses used oral care kit #1 and worksheet #1


Outcomes1. Incidence of VAP


NotesSample size calculation: "Desired sample size was 200 ventilator dependent patients or 2000 ventilator days"

Email sent to authors 3 September 2012 requesting numbers of patients treated. No reply received. Trial included in text as narrative only


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"..a plastic bin labelled 1-350, containing sealed envelopes which each had either worksheet #1 or #2, plus information about the trial to give to families". No mention of whether envelopes were sequentially numbered. Method of sequence generation not described

Allocation concealment (selection bias)Low riskAllocation contained in sealed envelopes

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot possible, both nurses and patients would have known allocated treatment

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskOutcome of VAP assessed by infection control nurse. Unclear whether this person was blinded to allocated treatment

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: The study neither reports the number of patients randomised nor the number analysed

Selective reporting (reporting bias)High riskComment: No numerical data were reported in this paper. VAP incidence was not reported by treatment group or with any measure of variance

Other biasUnclear riskInsufficient information in the trial report to produce confidence in the methodology of this trial

Fourrier 2000

MethodsStudy design: Single blind RCT

Location: Lille, France

Number of centres: 1

Study period: June 1997 to July 1998

Funding source: Not stated


ParticipantsSetting: Adult ICU

Inclusion criteria: Patients admitted to ICU aged > 18 years, medical condition likely to require ICU stay of 5 days, requiring mechanical ventilation by oro or nasopharyngeal intubation or tracheostomy

Exclusion criteria: Edentulous patients

Number randomised: 60

Number evaluated: 58

Baseline characteristics:

-Intervention group: Age: 51.2±15.2; M/F: 19/11; SAPS II Score: 37±15

-Control group: Age: 50.4±15.5; M/F: 19/11; SAPS II Score: 33±13


InterventionsComparison: Rinse + chlorhexidine gel versus rinse alone

Experimental group: After mouthrinsing and oropharyngeal aspiration, 0.2% chlorhexidine gel was applied to dental and gingival surfaces of the patient using glove protected finger. Intervention 3 times daily

Control group: Mouthrinsing with bicarbonate isotonic serum followed by gentle oropharyngeal aspiration 4 times daily during ICU stay

Patients were allowed to eat and drink freely


Outcomes1. Incidence of nosocomial infections

2. Dental status (DMFT/CAO)

3. Amount of dental plaque (Loe & Silness Index)

4. Plaque bacterial culture


NotesSample size calculation: Not reported

Investigators verified antibacterial activity of chlorhexidine gel in vitro prior to study

Unclear numbers on mechanical ventilation developing VAP. Email sent 14 November 2012


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"...patients were randomized into two groups according to a computer-generated balanced randomization table"

Allocation concealment (selection bias)Unclear riskInsufficient information was reported to determine whether or not the allocation of the sequence was concealed

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot possible as no placebo used

Blinding of outcome assessment (detection bias)
All outcomes
Low riskBacteriologist blinded to randomisation code, and evaluation of nosocomial infections done by hygienist nurse and physician not aware of the treatment given

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskUnclear how many patients are included in the evaluation of the outcomes

Selective reporting (reporting bias)Low riskPlanned outcome of nosocomial infection, dental plaque, and colonisation reported

Other biasLow riskGroups appear similar at baseline. No other sources of bias identified

Fourrier 2005

MethodsStudy design: A multicentre double-blind placebo-controlled study with 2 parallel groups

Location: France

Number of centres: 6 ICUs (3 in university hospitals & 3 in general hospitals)

Study period: January 2001 to September 2002

Funding source: Partial funding from Programme Hospitalier de Recherche Clinique PHRC (French Ministry of Health)


ParticipantsInclusion criteria: Age > 18 years and a medical condition suggesting an ICU stay at least 5 days and the requirement of mechanical ventilation by orotracheal or nasotracheal intubation. Only patients hospitalised for 48 hours before admission in the ICU could be included

Exclusion criteria: Patients with a tracheostomy tube at recruitment; completely edentulous; suffering from facial trauma; post-surgical and requiring specific oropharyngeal care; known allergy to chlorhexidine

Age group: Mean 61.0 SD 14.7, 61.1 years SD 14.9 in each group

Number randomised: 228

Number evaluated: 228 (ITT)

Intervention group: Age: 61.1±14.9; M/F: 73/41; SAPS II Score: 45.0±17.5

Control group: Age: 61.0±14.7; M/F: 83/31; SAPS II Score: 45.2±17.5


InterventionsComparison: Chlorhexidine gel versus placebo

Intervention (n = 114): After mouthrinsing and aspiration, plaque antiseptic decontamination of gingival and dental plaque with a 0.2% chlorhexidine gel provided by nurses at least 3 times a day during the entire ICU stay

Control (n = 114): A placebo gel, same usage as that of plaque antiseptic decontamination

"Toothbrushing was not allowed in the protocol"


OutcomesThe following variables were reported and compared:

1. Incidence of VAP

2. Incidence of VAP (%) per 1000 days of mechanical ventilation

3. Incidence of VAP (%) per 1000 days of intubation

5. Mortality from day 0 to day 28

6. ICU days (mean±SD)

7. Days of intubation (mean±SD)

8. Antibiotic days (mean±SD)


NotesSample size calculation: Calculation provided based on expected incidence of nosocomial infections of 30% in placebo group and 15% in treatment group. Planned interim analysis to determine effects of interventions, and study stopped based on pre-planned stopping rule after this interim analysis

Email sent to author 14 November 2012


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"...randomly assigned … block randomization stratified by site"

Allocation concealment (selection bias)Low risk"all randomization lists were held in sealed envelopes in the pharmacy departments of the 6 centres"

Blinding of participants and personnel (performance bias)
All outcomes
Low riskThe placebo gel was undistinguishable by colour, taste or odour with the tested agent. The investigators were unaware of patients assignments

Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskOnly 1 patient in intervention group was excluded and the reason was clearly explained. ITT analysis

Selective reporting (reporting bias)Low riskAll planned outcomes clearly defined and reported

Other biasLow riskNo other sources of bias identified. Although this study was stopped early interim analysis was planned in protocol and carried out appropriately

Grap 2004

MethodsStudy design: Multicentre RCT with 3 parallel groups

Location: USA

Number of centres: 1

Study period: Not stated

Funding source: AD Williams Foundation of Virginia Commonwealth University


ParticipantsInclusion criteria: ≥18 years, admitted to the ED, surgical trauma ICU or neuroscience ICU who required endotracheal intubation and were mechanically ventilated

Exclusion criteria: Edentulous persons

Age group: Mean 50.3 SD 16.0 range 20-87

Number randomised: 34

Number evaluated: Variable

Spray group: n = 11; swab group: n = 12; control group: n = 11. M/F: 24/10; mean APACHE III Score: 63.1±23.8


InterventionsComparison: Chlorhexidine spray versus chlorhexidine swab versus usual care

Spray group (n = 11): At early post-intubation a single oral application of 0.12% chlorhexidine gluconate was given in 20 sprays for about 2 ml of the agent

Swab group (n = 12): At early post-intubation a single oral application of 0.12% chlorhexidine gluconate was given by swabbing for about 2 ml of the agent

Control (n = 11): Usual care method but not described


Outcomes1. Change of mean CPIS from admission to the time of 48 hours

2. Number of the cases with positive cultures in the study period


NotesSample size calculation: Not reported but study was a pilot


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Randomized ….  using a block randomization scheme"

Allocation concealment (selection bias)Low risk"The block size varied so that the research assistants were not able to predict the next group assignment"

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot possible as no placebos used

Blinding of outcome assessment (detection bias)
All outcomes
Low riskData collectors and culture evaluators were blinded

Incomplete outcome data (attrition bias)
All outcomes
High riskOnly 12/34 participants had complete data at admission and at 48 hours for evaluation of VAP. Attrition mainly due to endotracheal extubation but numbers greater in both chlorhexidine groups compared to control

Selective reporting (reporting bias)High riskPlanned outcomes of negative oral cultures and CPIS (no variance estimates) reported in minority of participants. Unclear number of VAP, and no mortality data reported

Other biasLow riskNo other sources of bias identified

Grap 2011

MethodsStudy design: RCT

Location: Virginia USA

Number of centres: 2 units in same hospital, Level 1 trauma centre

Study period: Not stated

Funding source: Triservice Nursing research program grant TSNRP MDA-905-03-TS02


ParticipantsSetting: Surgical trauma ICU & neuroscience ICU

Inclusion criteria: Patients intubated within 12 hours of admission to trauma centre (intubation may have occurred in emergency department, in the field or in pre-hospital setting)

Exclusion criteria: Previous endotracheal tube placed in 48 hours prior to admission, clinical diagnosis of pneumonia on admission, burn injuries, edentulous persons

Number randomised: 152, 7 lost, enrolled sample 145 (71/74) (only 75 were still intubated after 48 hours)

Number evaluated: At 48 or 72 hours = 60 (36/24) (for VAP) 39 (21/18)

Baseline characteristics: Not reported for each randomised group in total

Those with 48/72 hour data:

-Experimental group: n = 36, M/F 27/9, APACHE II 70.69±30.14

-Control group: n = 24, M/F 11/13, APACHE II 60.46±23.45


InterventionsComparison: Chlorhexidine applied by swab versus usual care

Experimental group: 1 5 ml dose of chlorhexidine 0.12% applied to all areas of oral cavity by swab within 12 hours prior to intubation. All patients received usual oral comfort care (details not reported)

Control group: Usual oral comfort care as per usual practice


Outcomes1. Incidence of VAP

2. CPIS score

3. APACHE III

4. TRISS

5. Oral Health (DMFT)


NotesSample size calculation: Not reported (but pilot study published in 2004)

Email sent and reply received to clarify the data


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"The subjects were randomised to a treatment group or control group using a block randomisation scheme"

Allocation concealment (selection bias)Unclear riskNot described

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot possible because no placebo used

Blinding of outcome assessment (detection bias)
All outcomes
High riskNot mentioned and probably not done as researchers were nurses and likely to be involved in both delivery of interventions and assessment of outcomes

Incomplete outcome data (attrition bias)
All outcomes
High riskHuge attrition, and reasons for losses not described for each group. Conclusions based on 39/152 (26%) of those originally randomised to treatment or control

Selective reporting (reporting bias)High riskPrimary outcome planned was development of VAP but inclusion criteria used in this study meant that less than half those randomised were at risk of developing VAP

Other biasHigh riskStudy report notes statistically significant difference in gender and CPIS score between groups at baseline. No baseline characteristics data reported for each randomised group, and likely that important prognostic factors e.g. place of intubation, surgery, may have been different in each group

Hu 2009

MethodsStudy design: RCT

Location: Beijing, China

Number of centres: 1

Study period:

Funding source: No external funding


ParticipantsSetting: ICU in second affiliated hospital of PLA General Hospital

Inclusion criteria: Patients in ICU receiving mechanical ventilation

Exclusion criteria: Unclear

Number randomised: 47

Number evaluated: Unclear

Baseline characteristics: Not reported for each randomised group in total

Those with 48/72 hour data:

-Experimenal group: n = 25, M/F 16/9, age range 19-68

-Control group: n = 22, M/F 13/9, age range 22-60


InterventionsComparison: Saline swab + rinse versus saline swab

Experimental group: Lips, teeth, tongue and palate were swabbed with a saline saturated cotton ball and the oral cavity was rinsed with saline twice daily

Control group: Lips, teeth, tongue and palate were swabbed with saline saturated cotton ball twice daily


OutcomesVAP, mortality, days on ventilator, days in hospital, halitosis, ulceration


NotesInformation translated from Chinese paper by Shi Zongdao and colleagues. Unable to confirm outcome data with trial authors


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskEmail from author "the sequence was generated by using a random number table"

Allocation concealment (selection bias)Low riskEmail from author "allocation was concealed using opaque envelopes numbered with inclusion sequence"

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskPatients and carers were not blinded to interventions received

Blinding of outcome assessment (detection bias)
All outcomes
Low riskEmail from author "the outcome assessors were are group of nurses not involved with the interventions". Probably blinded to allocated treatment group

Incomplete outcome data (attrition bias)
All outcomes
High riskThe number of participants included in the outcome assessments at each time point is unclear. VAP reported as percentages only?

Selective reporting (reporting bias)High riskAll planned outcomes reported but as percentages only?

Other biasLow riskNo other sources of bias identified

Jacomo 2011

MethodsStudy design: Double-blind placebo-controlled RCT (NCT00829842)

Location: Sao Paulo, Brazil

Number of centres: 1

Study period: February 2006 to February 2008

Funding source: Not stated


ParticipantsSetting: Tertiary care hospital paediatric ICU

Inclusion criteria: Children with congenital heart disease undergoing cardiac surgery with or without cardiopulmonary bypass, admitted to paediatric ICU for post-operative care

Exclusion criteria: Pre-operative pneumonia, hypersensitivity to chlorhexidine, congenital or acquired immunodeficiency, refusal to participate

Number randomised: 164

Number evaluated: 160 (4 intra-operative deaths)

Baseline characteristics:

-Intervention group: Age: median12.2 (0-176 months); M/F: 42/45

-Control group: Age: median 10.8 (0-204 months); M/F: 35/38


InterventionsComparison: Chlorhexidine (gargle or swab) versus placebo

Experimental group: Oral hygiene with 0.12% chlorhexidine gluconate solution, administered pre-operatively and twice daily post-operatively. 0.3 ml/kg of body weight were used in children aged > 6 years, who gargled for 30 seconds avoiding ingestion. In younger children and intubated post-operative patients solution was applied to oral mucosa, gingival, tongue and tooth surfaces for 30 seconds with a spatula wrapped in gauze

Control group: Received the same treatment with placebo solution that looked and tasted the same

All patients received orotracheal intubation and prophylactic systemic antibiotics intravenously for 48 hours


Outcomes1. Incidence of nosocomial pneumonia

2. Incidence of VAP

3. Duration of intubation

4. Need for reintubation

5. Time to development of pneumonia

6. Length of paediatric ICU/hospital stay

7. 28-day mortality


NotesSample size calculation: Estimated that 160 participants would detect a reduction in 50% in incidence of nosocomial pneumonia (31% to 15.5%) with α = 0.05 & β = 0.20

NCT 00829842 at ClinicalTrials.gov


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"..randomized to the experimental or control groups by means of a list generated by a computerized system that uses a random number generator to produce customized sets of random numbers"

Allocation concealment (selection bias)Low risk"The randomisation list was held in the hospital pharmacy and all investigators were unaware of patients assignments"

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blind. Texture, colour, and flavour of placebo similar to active solution, placed in similar containers and labelled A or B

Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble blind. "..the diagnosis of nosocomial pneumonia was made independently by the PICU physicians and an infection control practitioner blinded to the patient's group"

Incomplete outcome data (attrition bias)
All outcomes
Low risk2 participants in each group died and were therefore excluded from pneumonia outcomes

Selective reporting (reporting bias)Unclear riskPlanned outcomes clearly reported but unclear how many trial participants were ventilated for at least 48 hours

Other biasLow riskNo other sources of bias identified

Koeman 2006

MethodsStudy design: A multicentre randomised double-blind placebo-controlled trial with 3 parallel groups

Location: 2 university hospitals and 3 general hospitals in the Netherlands

Number of centres: 5 hospitals (2 surgical and 5 mixed ICUs)

Study period: February 2001 to March 2003

Funding source: ZONMw Netherlands Organization for Health Research and Development (project number 2200.0046)


ParticipantsInclusion criteria: Consecutive adult patients (> 18 years of age) needing mechanical ventilation for at least 48 hours were included within 24 hours after intubation and start of mechanical ventilation

Exclusion criteria: A pre-admission immunocompromised status, pregnancy, and if the physical condition did not allow oral application of study medication

Age group:

Number randomised: 385

Number evaluated: 379

Group A: Chlorhexidine group: n = 127; mean age: 60.9±15.3; M/F: 71/57; APACHEII: 22.2±7.02

Group B: Chlorhexidine/COL group: n = 128; mean age: 62.4±19.1; M/F: 66/61; APACHEII: 23.7±7.38

Group C: Control group: n = 130; mean age: 62.1±15.9; M/F: 93/37; APACHEII: 21.8±7.43


InterventionsComparison: Chlorhexidine (in petroleum jelly) versus petroleum jelly alone

Group A: Chlorhexidine group (n = 127): Oral decontamination with chlorhexidine (2%) in Vaseline petroleum jelly

Group B: Chlorhexidine/COL group (n = 128): Oral decontamination with chlorhexidine plus colistin antibiotic chlorhexidine/colistin (CHX/COL 2%/2%) in Vaseline petroleum jelly

Group C: Control (n = 130): Oral decontamination with Vaseline petroleum jelly

Trial medication was administered 4 times daily, after removing remnants of the previous dose with a gauze moistened with saline. Approximately 2 cm of paste, approximately 0.5 g was put on a gloved fingertip and administered to each side of the buccal cavity


OutcomesThe following outcome variables were reported for each group:

1. Incidence of VAP

2. Incidence of early onset VAP

3. Days ventilated (mean±SD)

4. ICU stay (mean±SD)

5. Days in hospital after ICU discharge (mean±SD)

6. Changes of endotracheal colonisation through cultures in 3 time windows after ventilation, 1-3 days, 5-8 days and 9-12 days respectively


NotesSample size calculation: Reported in paper together with planned sequential analysis

Only Group A and Group C included in this review


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"...randomly assigned to one of three study groups by computerised randomisation schedule. Randomization was stratified by hospital"

Allocation concealment (selection bias)Low riskTrial medication (chlorhexidine 2% in petroleum jelly (Vaseline) FNA, chlorhexidine 2% with COL 2% in Vaseline FNA, and Vaseline FNA) was produced and labelled by the Department of Clinical Pharmacy of the University Hospital Maastricht. Experimental and placebo pastes were tasteless and of comparable smell and consistency

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blind, placebo controlled

Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble blind, placebo controlled

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe study was discontinued in 6 patients, 5 participants withdrew consent, 1 due to adverse event. Intention-to-treat analysis included all participants for primary outcome

Selective reporting (reporting bias)Low riskAll planned outcomes reported

Other biasLow riskUnlikely

Kusahara 2012

MethodsStudy design: Double-blind placebo-controlled RCT

Location: Sao Paulo Brazil

Number of centres: 1, tertiary care hospital affiliated with Federal University of Sao Paulo Brazil

Study period: 36 months dates not stated

Funding source: Funded by a grant from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (04-13361-2)


ParticipantsSetting: PICU

Inclusion criteria: Children admitted to PICU likely to require ventilation within 24 hours of admission

Exclusion criteria: Newborn, confirmed diagnosis of pneumonia at admission, known hypersensitivity to chlorhexidine, tracheostomy, duration of ventilation less than 48 hours, intubated for more than 24 hours prior to PICU admission

Number randomised: 96 (46/50)

Number evaluated: 96, at day 2 (44/45), at day 4 23/23

Baseline characteristics:

-Intervention group: Age: 12±49.75 months; M/F: 28/18

-Control group: Age: 34.5±58.8 months; M/F: 32/18


InterventionsToothbrushing + 0.12% chlorhexidine gel versus toothbrushing + placebo

Experimental group: Oral care with toothbrushing and oral gel containing chlorhexidine twice daily (08:00 & 20:00 hours). Mouth was divided into 4 quadrants and each brushed in a defined pattern. With child in lateral position, gel was applied directly to toothbrush, and all tooth surfaces (vestibular, lingual, occlusal and incisal) were cleaned and ventral surface of tongue was brushed posterior to anterior. Each quadrant was rinsed with water and excess fluid and debris was removed with continuous suction. Finally oral foam applicator was immersed in the gel and applied all over the gingival surfaces of the patient

Control group: Oral care with toothbrushing and placebo oral gel twice daily. With child in lateral position, gel was applied directly to toothbrush, and all tooth surfaces (vestibular, lingual, occlusal and incisal) were cleaned and ventral surface of tongue was brushed posterior to anterior. Each quadrant was rinsed with water and excess fluid and debris was removed with continual suction. Finally oral foam applicator was immersed in the gel and applied all over the gingival surfaces of the patient


Outcomes1. Incidence of VAP

2. Duration of ventilation in PICU

3. Length of stay in PICU

4. Hospital mortality

5. Tracheal colonisation with Gram +ve & -ve organisms


NotesSample size calculation: Reported that this was not done "due to the absence of previous research on this population"

Email correspondence with Prof Pedreira confirmed that Pedreira 2009 and Kusuhara 2012 both refer to the same study. NCT 01083407 & NCT0410682 at ClinicalTrials.gov


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"..randomised into two groups using a balanced randomisation table generated by True Epistat Program"

Allocation concealment (selection bias)Low riskBoth chlorhexidine and identical placebo gels were supplied by pharmacy in identical containers and only the pharmacist was aware of the gel type for each patient

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blind. Identical placebo used so that neither participants nor clinical staff were aware of allocated treatment

Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble blind. Only the pharmacist was aware of the gel type for each patient

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll randomised participants included in the outcome evaluation

Selective reporting (reporting bias)Low riskOne primary and 4 secondary outcomes reported in full

Other biasUnclear riskStatistically significant difference in mean age of children in each group. This may have introduced a bias

Long 2012

MethodsStudy design: A single centre RCT with 2 parallel groups

Location: China

Number of centres: 1 ICU in the university hospital

Study period: February 2010 to March 2012

Funding source: Program for masters degree


ParticipantsInclusion criteria: Patients admitted to ICU, with oral intubation, receiving mechanical ventilation ≥ 48 hours, age ≥ 18 years, patients or their relatives agreed to participate in the study

Exclusion criteria: Intubated in emergency e.g. after cardiac arrest, operations upon the oral cavity, trauma of the respiratory tract, with severe bleeding or coagulation disorders

Number randomised: 70

Number evaluated: 61 (the other 9 were death or ventilation < 48 hours)

Intervention group: Mean age: 60.06±10.71 years, M/F 20/11, APACHE 17.94±1.24

Control group: Mean age: 63.67±10.02 years, M/F 18/12, APACHE 18.23±0.57


InterventionsComparison: Povidone iodine + toothbrushing versus povidone iodine alone

Experimental group (n = 31): Modified oral nursing method: swab with 0.1% povidone iodine immediately before intubation, then toothbrushing and rinsing with 0.1 povidone iodine, 3 times a day

Control group (n = 30): Usual oral nursing method: swab with cotton balls soaked with 0.1% povidone iodine


Outcomes3 outcome variables were available:

1. Incidence of VAP

2. Mortality

3. Ventilation days


NotesMicrobial examinations for the aspirate secretions obtained from inferior respiratory tract every day after intubation were referred for diagnosis of VAP


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"...patients were randomly assigned into 2 groups, observing group and control group with 35 cases in each group"

Allocation concealment (selection bias)Unclear riskNot specified

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskBlinding not described and not possible for the carers who would be aware of who was in each group

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot specified

Incomplete outcome data (attrition bias)
All outcomes
Low risk9 randomised patients were excluded from analysis, numbers and reasons similar for each group

Selective reporting (reporting bias)Low riskPlanned outcomes reported

Other biasUnclear riskOnly the results of microbial examination of the aspirate secretions from the inferior respiratory tract as tool of VAP diagnosis may not be enough

Lorente 2012

MethodsStudy design: Parallel group RCT

Location: Tenerife, Spain

Number of centres: 1

Study period: August 2010 to August 2011

Funding source: Hospital funding


ParticipantsSetting: Medical/surgical ICU

Inclusion criteria: Consecutive patients undergoing invasive mechanical ventilation for at least 24 hours

Exclusion criteria: Edentulous, aged < 18 years, pregnant, HIV positive, white blood cells < 1000 cells/mm3, solid or haematological tumour, immunosuppressive therapy, mechanical ventilation duration less than 24 hours

Number randomised: 436 (217/219)

Number evaluated: 436

Baseline characteristics:

-Intervention group: Age: 61.0±15.6 years; M/F: 146/71

-Control group: Age: 60.4±16.6 years; M/F: 145/74


InterventionsToothbrushing + 0.12% chlorhexidine gel versus chlorhexidine alone

Experimental group (n = 217): Oral cleansing performed with 0.12% chlorhexidine impregnated gauze, and oral cavity injection, followed by manual brushing of the teeth with a brush impregnated with 0.12% chlorhexidine (tooth by tooth on the anterior and posterior surfaces, the gum line and the tongue for a period of 90 seconds)

Control group (n = 219): Oral cleansing performed with 0.12% chlorhexidine impregnated gauze, and oral cavity injection only

In both groups nurse performed oral care every 8 hours. First endotracheal cuff pressure was tested, oropharyngeal secretions were aspirated, then chlorhexidine impregnated gauze was used to cleanse the teeth tongue and mucosal surfaces, followed by injection of 10 ml 0.12% of chlorhexidine digluconate into oral cavity, and finally after 30 seconds the OParea was suctioned


Outcomes1. Incidence of VAP

2. Duration of ventilation

3. ICU mortality

4. Tracheal colonisation with Gram +ve & -ve organisms

5. Antibiotic exposure


NotesSample size calculation: Estimated that 218 patients per group required to give 80% power and alpha error of 5%, to show a reduction in VAP from 15% to 7.5%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"..a list of random numbers generated with Excel software (Microsoft, Seattle, WA)"

Allocation concealment (selection bias)Unclear riskNo information about allocation concealment

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot possible

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"The diagnosis of VAP was made by an expert panel, blinded to group assignment"

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll randomised patients are included in the outcome evaluations

Selective reporting (reporting bias)Low riskPlanned outcomes reported in full

Other biasLow riskNo other sources of bias identified

McCartt 2010

MethodsStudy design: 3-arm "quasi experimental" RCT

Location: Florida, USA

Number of centres: 1

Study period: Not stated

Funding source: Nursing dissertation


ParticipantsSetting: Medical/surgical ICU

Inclusion criteria: Patients aged > 18 years, anticipated to be orally intubated for at least 72 hours

Exclusion criteria: Admitting diagnosis of pneumonia, nasally intubated, expected to be extubated within 24 hours

Number randomised: 85

Number evaluated: Variable (70-80)

Baseline characteristics:

-Experimental group A: Age: 63 years; M/F: 11/18

-Experimental group B: Age: 60 years; M/F:16/15

-Control group: Age: 57 years; M/F: 11/14


InterventionsComparison: Toothbrushing + 0.12% chlorhexidine gel versus chlorhexidine alone

Experimental group (n = 29): Chlorhexidine gluconate spray 0.12% twice daily at 12-hour intervals

Experimental group (n = 31): Chlorhexidine gluconate spray + toothbrushing twice daily at 12-hour intervals

Control group (n = 25): Standard hygiene care with toothette swabs


Outcomes1. Oral pH

2. Oral cultures

3. Clinical Pulmonary Infection score

4. Oral assessment


NotesSample size calculation: Reported to have been done but unclear numbers per group required

Email sent to author 24 January 2013 - no reply received


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"..randomly assigned" "utilizing random tables generated by the Office of Research and Development in the Department of Nursing at the University of Florida"

Allocation concealment (selection bias)Unclear riskNot described

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot possible

Blinding of outcome assessment (detection bias)
All outcomes
High riskNot done

Incomplete outcome data (attrition bias)
All outcomes
High riskNumbers evaluated at 72 hours appear to be 69 (5, 7, 4 lost from groups A, B & C respectively) reasons not stated

Selective reporting (reporting bias)High riskStated purpose of the study was to determine whether there was a difference in VAP but this outcome was not reported

Other biasLow riskNo other sources of bias identified

Munro 2009

MethodsStudy design: A single centre RCT with 4 parallel groups

Location: 3 ICUs in large urban University Medical Centre, Virginia, USA

Number of centres: 3 (ICUs)

Study period: Not stated

Funding source: Grant NIH R01 NR07652


ParticipantsInclusion criteria: Critically ill adults (over 18) in 3 intensive care units were enrolled within 24 hours of intubation. All patients older than 18 years (n = 10913) in medical, surgical/trauma, and neuroscience ICUs were screened for inclusion

Exclusion criteria: Clinical diagnosis of pneumonia at the time of intubation, edentulous patients, patients who had a previous endotracheal intubation during the current hospital admission

Group 1: 26/18 M/F, age mean 46.1 (18.2)

Group 2: 28/21 M/F, age mean 47.1 (15.7)

Group 3: 28/20 M/F, age mean 47.3 (18.8)

Group 4: 37/14 M/F, age mean 46.8 (16.4)

Number randomised: 547 (but 355 subsequently excluded due to pneumonia at baseline)

Number evaluated: 192


InterventionsComparison: Chlorhexidine swab versus toothbrushing versus both versus usual care

Group 1: (n = 44) a 0.12% solution of chlorhexidine gluconate (chlorhexidine) 5 mL by oral swab twice daily (at 10 AM and 10 PM)

Group 2: (n = 49) toothbrushing (manual toothbrush) 3 times a day (at 9 AM, 2 PM, and 8 PM), detailed toothbrushing protocol followed quadrant by quadrant

Group 3: (n = 48) combination care (toothbrushing 3 times a day and chlorhexidine every 12 hours)

Group 4: (n = 51) control (usual care)


OutcomesVAP measured by CPIS score, also dichotomised at day 1, 3, 5, 7

Mortality (died during hospitalisation)


NotesMedian length of stay and stay in ICU were presented


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"A randomized controlled 2 × 2 factorial experimental design was used...Patients were randomly assigned to 1 of 4 treatments". "Patients were randomized to treatment within each ICU according to a permuted block design developed by the biostatistician (D.K.M.) before the start of the study"

Allocation concealment (selection bias)Low riskNot mentioned but probably done as allocation was made by statistician

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot possible

Blinding of outcome assessment (detection bias)
All outcomes
High riskNot described, and probably not done

Incomplete outcome data (attrition bias)
All outcomes
High risk355/547 (65%) of those originally randomised were excluded from the analysis at day 3 because they were found to have pneumonia at baseline

Selective reporting (reporting bias)Unclear riskVAP reported as percentages only and denominator unclear

Other biasLow riskNo other sources of bias identified

Needleman 2011

MethodsStudy design: Parallel group RCT

Location: London UK

Number of centres: 1

Study period: March 2007 to May 2009

Funding source: Partially funded by UK Department of Health NIHR Biomedical Research Centres funding scheme


ParticipantsSetting: Neurocritical care unit

Inclusion criteria: Admitted to hospital < 48 hours prior to neurocritical care unit admission, expected to survive > 48 hours, and expected to require endotracheal intubation for > 48 hours

Exclusion criteria: Edentulous, known adverse reaction to chlorhexidine, recent history of chest infection, received antibiotics within 3 months prior to study start

Number randomised: 46

Number evaluated: 44 - 28 (attrition over time)

Baseline characteristics:

-Intervention group: Age: 53.0±12.5; M/F: 14/9

-Control group: Age: 42.7±12.8; M/F: 13/10


InterventionsComparison: Chlorhexidine rinse + powered toothbrush versus chlorhexidine swab alone

Experimental group (n = 23): Oral hygiene using a powered toothbrush (Colgate Actibrush) plus 20 ml of chlorhexidine solution 4 times daily for 2 minutes per session Oropharyngeal suction was used to remove excess fluid or debris

Control group (n = 23): Oral hygiene using a sponge toothette plus 20 ml of chlorhexidine solution 4 times daily for 2 minutes per session. Oropharyngeal suction was used to remove excess fluid or debris


Outcomes1. Oral plaque colonisation with VAP-associated bacteria

2. Amount of dental plaque

Outcomes measured on days 1 (pre-oral hygiene), 3 and 5


NotesSample size calculation: Estimated that 16 patients per group would be required to detect a reduction from 63% to 10% in presence of VAP-associated pathogens, which would be clinically important


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Randomization sequence was computer generated using SPSS statistical software"

Allocation concealment (selection bias)Low riskRandomisation was "concealed from those recruiting patients in sequentially numbered sealed opaque envelopes", which were prepared by the statistician

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot possible because experimental and control interventions were so different

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"..oral hygiene assessment, microbial sampling, microbial assessment and data analysis were masked with regard to experimental group status"

Incomplete outcome data (attrition bias)
All outcomes
High riskLosses to follow-up were high, due to early tracheal extubation, death or transfer to another facility. Numbers for each cause not given and total numbers were high and different in each group (13/23 (57%) control and 5/23 (22%) experimental participants at day 5)

Selective reporting (reporting bias)Low riskPlanned outcomes reported in full

Other biasLow riskNo other sources of bias identified

Ozcaka 2012

MethodsStudy design: Double-blind placebo-controlled RCT

Location: Izmir, Turkey

Number of centres: 1

Study period: November 2007 to November 2009

Funding source: "The study was funded solely by the institutions of the authors"


ParticipantsSetting: Respiratory ICU

Inclusion criteria: Patients aged 18 or over, admitted to respiratory ICU expecting to require ventilation for > 48 hours

Exclusion criteria: Witnessed episode of aspiration, confirmed diagnosis of post-obstructive pneumonia, known hypersensitivity to chlorhexidine, diagnosed thrombocytopenia, pregnancy, oral mucositis, readmission to same ICU, expected survival < 1 week, edentulism

Number randomised: 66

Number evaluated: 61

Baseline characteristics:

-Intervention group: Age: 60.5±14.7 years

-Control group: Age: 56.0±18.2 years


InterventionsComparison: Chlorhexidine solution versus saline

Experimental group (n = 32): Oral mucosa was swabbed with 0.2% chlorhexidine on sponge pellets, 4 times daily. Excess rinse was suctioned from patient's mouth after 1 minute

Control group (n = 34): Oral mucosa was swabbed with saline on sponge pellets, 4 times daily. Excess rinse was suctioned from patient's mouth after 1 minute

Deep suctioning was performed in both groups every 6 hours and following position changes to remove pooled secretions from around the cuff of the endotracheal tube


Outcomes1. Incidence of VAP

2. Mortality

3. Duration of ventilation in ICU

4. Length of stay in ICU

5. Presence of potential respiratory pathogens in minibronchoalveolar lavage


NotesSample size calculation: Estimated that 28 participants per group would be required to give 81% power with alpha of 5%, to show a reduction in VAP from 70% to 30%

Email sent 22 January 2013 and reply received 29 January 2013


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"The randomisation prepared a set of subject identification (SID) numbers which had assigned treatment"

Comment: Description unclear, but involvement of statistician suggests this was well done

Allocation concealment (selection bias)Low risk"Study nurse obtained the SID number when the patient was enrolled"

Comment: Allocation was probably concealed and not able to be anticipated by investigators

Blinding of participants and personnel (performance bias)
All outcomes
Low risk"Assignment of treatment was blinded to patients and to all investigators, including periodontist, .... respiratory ICU physicians and outcome statisticians"

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"Assignment of treatment was blinded to patients and to all investigators, including periodontist, .... respiratory ICU physicians and outcome statisticians"

Incomplete outcome data (attrition bias)
All outcomes
Low risk66 patients randomised, 1 secondary exclusion from each group, and 2 and1 early deaths in chlorhexidine and control groups, respectively
Comment: Unlikely to have introduced a bias

Selective reporting (reporting bias)Low riskPlanned outcomes reported

Other biasLow riskNo other sources of bias identified

Panchabhai 2009

MethodsStudy design: Open-label RCT

Location: Mumbai India

Number of centres: 1

Study period: 8 months - dates not stated

Funding source: Not stated


ParticipantsSetting: ICU (mixed medical and surgical), tertiary care hospital

Inclusion criteria: All patients admitted to ICU during study period who signed consent

Exclusion criteria: Pregnant women, those with pneumonia at baseline, those for whom oral care was contraindicated, those with allergy to chlorhexidine

Number randomised: 512

Number evaluated: 471 (only 88/83 = 171 on mechanical ventilation)

Baseline characteristics (given for 471 who completed the trial only):

-Intervention group: Age: 35.2±15.9; M/F: 136/88; APACHEII Score: 12(9-17)

-Control group: Age: 36.9±16.2; M/F: 171/76; APACHEII Score: 14±(9-19)


InterventionsComparison: Chlorhexidine versus potassium permanganate

Experimental group (n = 250): Oral and pharyngeal suction of pooled secretions followed by swabbing of the oral cavity, teeth, palate, buccal spaces, posterior pharyngeal wall, and hypopharynx with normal saline.Then oropharyngeal cleansing, following the same procedure, twice daily with 0.2% chlorhexidine solution

Control group (n = 262): Oral and pharyngeal suction of pooled secretions followed by swabbing of the oral cavity, teeth, palate, buccal spaces, posterior pharyngeal wall, and hypopharynx with normal saline.Then oropharyngeal cleansing twice daily, following the same procedure, with 0.01% potassium permanganate solution

Non-intubated patients, rinsed with water, then rinsed and gargled with 10 ml of study solution. No eating/drinking for 1 hour post-intervention


Outcomes1. Incidence of nosocomial pneumonia

2. Day of development of pneumonia

3. Mortality (hospital)

4. Duration of ICU stay


NotesSample size calculation: "This study had a statistical power of 75% to detect a 50% reduction in the incidence of nosocomial pneumonia in the study group with 95% level of confidence. Assuming the incidence of pneumonia in the control group was 16%, 506 subjects were required"

Email sent to author 14 November 2012


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"..randomly assigned to treatment .... by concealed simple random sampling"

Comment: No details of sequence generation provided

Allocation concealment (selection bias)Unclear risk"..concealed simple randomisation"

Comment: Unclear whether allocation was concealed from researchers

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskOpen-label RCT

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOpen-label RCT but "two independent, blinded reviewers made the diagnosis of nosocomial pneumonia"

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk26/250 (10%) and 15/262 (5.7%) were excluded from the analysis in the chlorhexidine and control groups respectively. Reasons given were ICU stay < 48 hours, 14/250 versus 6/262, and protocol violation 12/250 and 9/262 respectively

Selective reporting (reporting bias)Low riskAll planned outcomes reported in full

Other biasUnclear riskBaseline parameters only reported for those who completed the study

Pobo 2009

MethodsStudy design: Prospective, single blind, randomised trial with parallel groups

Location: Spain

Number of centres: 1 ICU at a hospital

Study period: Not stated

Funding source: This work was supported by Fondo de Investigaciones Sanitarias (FISS 06/060), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (06/06/36), and the Agency for the Administration of University and Research Grants (2005/SGR/920)


ParticipantsInclusion criteria: Intubated adults without evidence of pulmonary infection, expected to remain ventilated for longer than 48 hours. Randomised within 12 hours of intubation

Exclusion criteria: Edentulous, suspicion of pneumonia at time of intubation or evidence of massive aspiration during intubation, tracheostomy (or expected within 48 hours), recent enrolment in other trials, pregnancy, and chlorhexidine allergy

Age group: Adults

Intervention group: n = 74; age: 55.3±17.9; M/F: 49/25; mean APACHEII Score: 18.8±7.1

Control group: n = 73; age: 52.6±17.2; M/F: 46/27; mean APACHEII Score: 18.7±7.3

Number randomised: 147 (74 in toothbrush group and 73 in standard care group)

Number evaluated: 147


InterventionsComparison: Powered toothbrush + standard oral care versus standard oral care alone

Group 1 (n = 74): Standard oral care plus toothbrush group: besides the standard oral care, toothbrushing was performed tooth by tooth, on anterior and posterior surfaces, and along the gumline, the tongue was also brushed. A powered toothbrush was used (Braun Oral B AdvancePower 450 TX, Braun GmbH). This procedure was repeated once every 8 hours
Group 2 (n = 73): Standard oral care: maintaining head elevation at 30 degrees. After aspiration of oropharyngeal secretions and adjustment of endotracheal cuff pressure, a gauze containing 20 ml of 0.12% chlorhexidine digluconate was applied to all the oral surfaces including tongue and mucosal surface, and 10 ml of 0.12% chlorhexidine digluconate was injected into oral cavity, being aspirated after 30 seconds, repeated every 8 hours


OutcomesThe following outcome variables were reported for each group:

1. Incidence of VAP

2. Incidence of suspected VAP per 1000 days of mechanical ventilation

3. Mean days of mechanical ventilation (mean±SD)

4. ICU length of stay (mean±SD)

5. Mortality


NotesIn the review, the standard oral care group was viewed as intervention with chlorhexidine and the other group was viewed as control with toothbrushing

Sample size calculation: Estimated that 200 patients per group would be required to show a 50% reduction in VAP with 80% power and alpha error of 5%. After 147 of planned 400 patients were randomised the study was stopped by the steering committee due to no difference in VAP between the groups

NCT 00842478 at ClinicalTrials.gov


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomisation by means of a computer generated list, stratified for antibiotic use at admission

Allocation concealment (selection bias)Low riskThe list was concealed in opaque sealed envelopes opened by the nurse within 12 hours of intubation

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskBlinding not possible. Participants unlikely to be aware of treatment, but carers were aware

Blinding of outcome assessment (detection bias)
All outcomes
Low riskInvestigators and attending physicians were blinded to assigned groups

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals. All randomised participants included in the analysis

Selective reporting (reporting bias)Low riskExpected outcomes reported including adverse events

Other biasHigh riskStudy stopped early after recruitment of 147 of planned 400 patients because no differences between groups were found and revised estimates indicated that 1500 patients would need to be recruited to show a difference. Numbers not feasible in this centre

Prendergast 2012

MethodsStudy design: Prospective, randomised trial with 2 parallel groups. NCT 00518752

Location: USA

Number of centres: 1 neuroscience ICU at a tertiary medical centre

Study period: August 2007 to August 2009

Funding source: Not stated


ParticipantsInclusion criteria: All patients aged at least 18 years admitted to neuroscience ICU, intubated within 24 hours of admission

Exclusion criteria: Pregnancy, edentulous, aged < 18 years, facial fractures or trauma affecting oral cavity, unstable cervical fractures, anticipated extubation within 24 hours, grim prognosis

Intervention group: n = 38; age: 54±17.8; M/F: 19/19

Control group: n = 40; age: 51±18.4; M/F: 23/17

Number randomised: 78 (38 in comprehensive group and 40 in standard care group)

Number evaluated: Variable (less than 11 patients/group)


InterventionsComparison: Powered toothbrush + comprehensive oral care versus manual toothbrush + standard oral care

Group 1 (n = 38): Tongue scraping using a low profile tongue scraper with posterior to anterior sweeping motion across the dorsal surface of the tongue. Then toothbrushing with Oral B vitality powered toothbrush + Biotene (non-foaming) toothpaste for 2 minutes, then a liberal application or Oral Balance gel. Care performed twice daily

Group 2 (n = 40): Standard oral care: using manual paediatric toothbrush, toothpaste with 1000 ppm fluoride with SLS and water-based inert lubricant (KY jelly). Care performed twice daily


OutcomesThe following outcome variables were reported for each group:

1. Oral and sputum cultures every 48 hours

2. Incidence of suspected VAP (day 2-6)

3. ICU length of stay (mean±SD)

4. Mortality


NotesSample size calculation: Not reported

NCT 00518752 at ClinicalTrials.gov


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"..randomized ... using a computer generated list maintained in a separate locked cabinet"

Allocation concealment (selection bias)Low risk"..list was maintained in a separate locked cabinet from enrolment forms to prevent manipulation of eligibility judgements"

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot possible

Blinding of outcome assessment (detection bias)
All outcomes
Low riskDiagnosis of VAP by examination of chest radiographs, by physicians blinded to allocated treatment (information in Prendergast dissertation)

Incomplete outcome data (attrition bias)
All outcomes
High riskUnclear how many were assessed at each time point but paper states that "less than 11 patients in each group at each time point"

Selective reporting (reporting bias)Low riskAll planned outcomes reported

Other biasLow riskNo other sources of bias identified

Roca Biosca 2011

MethodsStudy design: Single blind RCT

Location: Tarragona, Spain

Number of centres: 1

Study period: June 2006 to May 2009

Funding source: Grant from Health Investigation Fund (FISS 06/060)


ParticipantsSetting: ICU (14-bed)

Inclusion criteria: Adults aged > 18 years, requiring mechanical ventilation for at least 48 hours, no pneumonia at baseline, at least 2 premolars and 1 incisor, consenting to take part

Exclusion criteria: Edentulous, suspected pneumonia < 18 years, requiring < 48 mechanical ventilation, tracheotomy, moribund (death expected within 72 hours) allergic to chlorhexidine

Number randomised: 147

Number evaluated:

Baseline characteristics: Report states that there were no differences in gender, age, diagnosis, APACHE scores between the groups at baseline. No supporting data reported


InterventionsComparison: Powered toothbrush + standard oral care versus standard oral care alone

Experimental group: RASPALL - Standard oral hygiene protocol + powered toothbrush. Patient was elevated to 35 degrees, oropharyngeal secretions were aspirated, intubation cuff pressure checked, then teeth, tongue and oral cavity cleaned with swab soaked in 10 ml 0.12% chlorhexidine digluconate. Solution left for 30 seconds then excess was aspirated. All tooth surfaces then brushed using a powered toothbrush

Control group: Standard oral hygiene protocol alone as described for treatment group


Outcomes4 outcome variables planned:

1. Plaque index (Loe & Silness) days 1, 5 and 10

2. Plaque cultures

3. VAP (reported as NAV)

4. Halitosis


NotesSample size calculation: Not reported

Translated from Portuguese by Luisa Fernandez-Mauleffinch

Email to authors sent 14 November 2012


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Group assignment was done randomly by sealed envelope"
Method of sequence generation not described

Allocation concealment (selection bias)Low risk"Group assignment was done randomly by sealed envelope"

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot possible to blind patients or personnel

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskStudy described as single blind but unclear who was blinded. Microbiologist?

Incomplete outcome data (attrition bias)
All outcomes
High riskNumbers of patients included in outcome of plaque index were 74 and 73 at day 0, 60 and 57, at day 5 and 29 and 32 at day 10 for toothbrush and control groups respectively. Reasons for missing outcome data are extubation, need for tracheotomy, VAP, death or intubation for total of 28 days. No information as to numbers per group missing for each reason

Selective reporting (reporting bias)High riskPlanned outcomes of plaque index and microbiological culture reported but data for VAP and halitosis in each group not reported

Other biasUnclear riskInsufficient information in trial report to be clear about potential for other bias

Scannapieco 2009

MethodsStudy design: A randomised, double-blind, placebo-controlled clinical trial

Location: USA

Number of centres: 1 18-bed trauma ICU

Study period: March 2004 until November 2007

Funding source: USPH grant R01DE-14685 from the National Institute of Dental and Craniofacial Research


ParticipantsInclusion criteria: Those admitted to the ICU who were expected to be intubated and mechanically ventilated within 48 hours of admission

Exclusion criteria: A witnessed aspiration suspected with chemical pneumonitis; a confirmed diagnosis of post-obstructive pneumonia e.g. advanced lung cancer; a known hypersensitivity to chlorhexidine; absence of consent; a diagnosed thrombocytopenia (platelet count less than 40 and/or a INR above 2, or other coagulopathy); a do not intubate order; children under the age of 18 years; pregnant women; legal incarceration; transfer from another ICU; oral mucositis; immunosuppression either-HIV or drug-induced e.g. organ transplant patients or those on long term steroid therapy; and readmission to the ICU

Number randomised: 175

Number evaluated: 146

Intervention group (chlorhexidine 1): n = 47; mean age: 44.8±19.9; M/F: 43/15; mean APACHEII Score: 18.5±4.1

Intervention group (chlorhexidine 2): n = 50; mean age: 47.6±19.1; M/F: 44/14; mean APACHEII Score: 19.7±6.1

Control group: n = 49; mean age: 50.0±22.5; M/F: 36/23; mean APACHEII Score: 19.1±6.1


InterventionsComparison: Chlorhexidine twice per day + toothbrush versus chlorhexidine once per day + toothbrush versus placebo + toothbrush

Intervention group: Chlorhexidine (0.12% CHX gluconate) was applied using a rinse-saturated oral foam applicator (Sage Products, Cary, IL, USA) once a day (placebo at other time)

Intervention group: Chlorhexidine (0.12% CHX gluconate) was applied using a rinse-saturated oral foam applicator (Sage Products, Cary, IL, USA) twice a day (in the morning at about 8 AM and in the evening at about 8 PM)
Control group: Placebo was applied using a rinse-saturated oral foam applicator twice per day

All groups had routine oral care using a suction toothbrush (Sage Products, Cary, IL, USA) twice a day and as needed to brush teeth and the surface of the tongue or approximately 1 to 2 minutes, and applying suction at completion and as needed during the brushing


Outcomes1. Incidence of VAP (diagnosed as the presence of more than 104 CFU of pathogen/ml of bqBAL fluid)

2. Death

3. Days ventilated

4. Days in hospital

5. Antibiotic use


NotesSample size calculation: Estimated that 53 patients per arm would give 90% power to detect a 505 decrease in colonisation. For outcomes 2 to 5, the P values were for 3 group comparisons

NCT00123123 at ClinicalTrials.gov


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA web-based subject enrolment system which allocated randomised subject identification numbers

Allocation concealment (selection bias)Low riskThe oral topical treatment for each box was formulated and prepared by the hospital pharmacy. Sealed envelopes containing a random number were generated in blocks of 6 to provide concealment of patient assignment from the investigators

Blinding of participants and personnel (performance bias)
All outcomes
Low risk"Assignment of treatment was blinded to patients and all investigators including outcome assessors, statisticians and care providers"

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"Assignment of treatment was blinded to patients and all investigators including outcome assessors, statisticians and care providers"

Incomplete outcome data (attrition bias)
All outcomes
High risk175 subjects were randomised, microbiological baseline data were available for 146 subjects, 115 had full data at 48 hours. Greater than 20% drop-outs in all groups. ITT analysis used for 175 patients but unclear what imputation was used to account for losses

Selective reporting (reporting bias)Unclear riskPlanned microbiological outcomes were reported only in graphs with no data presented

Other biasHigh riskProblems with data analysis due to unclear denominator and imputations. Pre-study antibiotic exposure higher in control group

Sebastian 2012

MethodsStudy design: Double-blind stratified placebo-controlled RCT

Location: New Delhi, India

Number of centres: 1

Study period: November 2007 to April 2009

Funding source: Indian Council of Medical Research Grant. Chlorhexidine gel and placebo supplied by ICPA Health Products Limited


ParticipantsSetting: Paediatric ICU (6 beds)

Inclusion criteria: Patients aged 3 months to 15 years who required orotracheal or nasotracheal intubation and mechanical ventilation. Patients with pneumonia at baseline were also included as these made up 66% of patient population

Exclusion criteria: Patients mechanically ventilated for > 48 hours prior to paediatric ICU admission, those with tracheostomies, with inaccessible oral cavities, or with known hypersensitivity to chlorhexidine

Number randomised: 86 (41/45)

Number evaluated: 86

Baseline characteristics:

-Intervention group: Age: 13/41, 3-12 months; 28/41, 1 year to 15 years; M/F: 23/18

-Control group: Age: 15/45, 3-12 months; 30/45, 1 year to 15 years; M/F: 27/18


InterventionsComparison: Chlorhexidine gel versus placebo

Experimental group (n = 41): Oral cavity was suctioned to remove secretions then mucosal surfaces were cleaned with saline soaked gauze. Then 0.75 cm 1% chlorhexidine gel was applied to each side of the mouth using a standardised disposable applicator

Control group (n = 45): Oral cavity was suctioned to remove secretions then mucosal surfaces were cleaned with saline soaked gauze. Then 0.75 cm placebo gel was applied to each side of the mouth using a standardised disposable applicator

Care was repeated every 8 hours


Outcomes1. Incidence of VAP

2. Length of stay in ICU

3. Duration of hospital stay

4. Hospital mortality

5. Type and antibiotic sensitivity of organisms cultured


NotesSample size calculation: Estimated that 91 patients per group were required to give 80% power with alpha 5% to detect a reduction in VAP from 40% to 20%

NCT00597688 at ClinicalTrials.gov

This study included patients with pneumonia at baseline and used age appropriate CDC criteria to diagnose VAP


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskEligible participants were stratified into 1 of 4 groups based on age group and presence or pneumonia at baseline. Within each stratum patients were randomised to receive either chlorhexidine or placebo gel. "..the random sequence was generated for each stratum using STATA 9.0 in blocks of 6"

Allocation concealment (selection bias)Low riskNo details about how the allocation was communicated to the researchers, but allocation likely to have been concealed

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blind

Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll randomised participants included in the ITT analysis

Selective reporting (reporting bias)Low riskAll planned outcomes reported. Medians and IQRs (as reported) are the correct statistic for a skewed distribution but cannot be combined in meta-analysis

Other biasLow riskPaper states that "the funding agency did not have any role in the study design, data collection and analysis, decision to publish or preparation of the manuscript"

Seguin 2006

MethodsStudy design: 3-arm parallel RCT

Location: Rennes, France

Number of centres: 1

Study period: August 2001 to January 2003

Funding source: Not stated


ParticipantsSetting: Surgical ICU

Inclusion criteria: Adult patients (> 18 years) with closed head trauma admitted to ICU and expected to need mechanical ventilation for at least 2 days

Exclusion criteria: Admitted more than 12 hours after initial trauma, those with facial, thoracic, abdominal or spinal injuries, known history of reaction to iodine or of respiratory disease, chest infiltrates at admission or need for curative antibiotics

Number randomised: 110 (38/36/36)

Number evaluated: 98 (36/31/31)

Baseline characteristics:

-Iodine group: Age: 38±17 years; M/F: 28/10

-Saline group: Age: 38±16 years; M/F: 24/12

-Control group: Age: 41±18 years; M/F: 23/13


InterventionsComparison: Povidone Iodine versus saline versus usual care (no rinse)

Iodine group (n = 38): Nasopharynx and oropharynx rinsed 4 hourly with 20 ml of 10% povidone iodine aqueous solution (Betadine oral rinse solution) reconstituted in a 60 ml solution with sterile water, followed by aspiration of oropharyngeal secretions

Saline group (n = 36): Nasopharynx and oropharynx rinsed 4 hourly with 60 ml saline, followed by aspiration of oropharyngeal secretions

Control group (n = 36): Standard regimen without any installation but with aspiration of oropharyngeal secretions

For all patients the suction catheters were inserted as distally as possible. Procedures were reported on patients chart


Outcomes1. Incidence of VAP - early and late onset

2. Duration of ventilation in surgical ICU

3. Length of stay in surgical ICU

4. Surgical ICU mortality


NotesSample size calculation: Estimated that 30 patients in each group would provide 80% power with alpha error 5% to detect a reduction in VAP from 50% to 20%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Patients were randomly assigned to received one of three regimens according to computer-generated random number codes kept in sealed envelopes"

Allocation concealment (selection bias)Low risk"Patients were randomly assigned to received one of three regimens according to computer-generated random number codes kept in sealed envelopes"

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot possible

Blinding of outcome assessment (detection bias)
All outcomes
High riskOutcome assessors not blinded. Attempts were made to make the diagnosis of VAP as objective as possible using a clear set of criteria and VAP diagnosis was confirmed by positive bronchoalveolar lavage culture. However risk of detection bias remains

Incomplete outcome data (attrition bias)
All outcomes
Low risk12 randomised patients (11%) excluded from analysis. 6 patients (1/3/2 in each group) were withdrawn because unexpected recovery meant that they were not on mechanical ventilation for 48 hours and a further 6 patients (1/2/3) died. Unlikely to have introduced a bias

Selective reporting (reporting bias)Low riskPlanned outcomes reported in full

Other biasLow riskNo other sources of bias identified

Tantipong 2008

MethodsStudy design: A single centre RCT with 2 parallel groups

Location: Thailand

Number of centres: 1 tertiary care university hospital

Study period: January 2006 through March 2007

Funding source: Thailand Research Fund and Faculty of Medicine Siriraj Hospital


ParticipantsInclusion criteria: Eligible patients were adults aged ≧ 18 years who were hospitalised in intensive care units (a total of 36 beds) or general medical wards (a total of 240 beds) at Siriraj Hospital and who received mechanical ventilation

Exclusion criteria: Patients who had pneumonia at enrolment or who had a chlorhexidine allergy

Number randomised: 207

Number evaluated: 207 (110 patients received mechanical ventilation for > 48 hours)

Experimental group: n = 102; age: 56.5±20.1; M/F: 50/52; mean APACHEII Score: 16.7±7.9

Control group: n = 105; age: 60.3±19.1; M/F: 51/54; mean APACHEII Score: 18.2± 8.1

Patients' demographic characteristics between groups did not differ significantly


InterventionsComparison: Toothbrush + chlorhexidine versus toothbrush + placebo

Experimental group (n = 102): Received oral care 4 times per day with brushing the teeth, suctioning any oral secretions, and rubbing the oropharyngeal mucosa with 15 ml of a 2% chlorhexidine solution, until their endotracheal tubes were removed

Control group (n = 105): Underwent the same oral care procedure with normal saline solution


OutcomesThe following outcome variables were reported for each group:

1. Incidence of VAP

2. Number of cases of VAP per 1000 ventilator-days

3. Incidence of VAP for patients who received mechanical ventilation for more than 2 days

4. Overall mortality

5. Mean days of mechanical ventilation (mean±SD)

6. Rate of irritation of oral mucosa


NotesSample size calculation: Estimated that 108 patient per group required to give 80% power to detect a 50% decrease in VAP with 5% Type 1 error


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"..randomized..... by stratified randomization according to sex and hospital location of eligible patient"

Allocation concealment (selection bias)High riskNot mentioned and probably not done

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot blinded as chlorhexidine solution had different odour and taste from saline

Blinding of outcome assessment (detection bias)
All outcomes
Low riskThe assessors who determined whether a patient developed pneumonia were unaware of the patient's study group assignment

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskAll randomised participants included in outcome evaluation but only 53% of participants on ventilators for > 2 days and therefore at risk of VAP

Selective reporting (reporting bias)Unclear riskPlanned outcome VAP but not all participants at risk and information unclear. Mortality reported

Other biasUnclear riskOnly 60% of study participants received ventilation in ICU and only 53% of participants received mechanical ventilation for more than 48 hours. Likely that nursing care protocols were different in general medical wards compared to ICUs

Xu 2007

MethodsStudy design: Parallel group RCT

Location: Nanjing, China

Number of centres: 1

Study period: December 2004 to June 2006

Funding source: No external funding


ParticipantsSetting: ICU in drum tower hospital of Nanjing University

Inclusion criteria: Critically ill adult patients in ICU receiving mechanical ventilation

Exclusion criteria: Participants with severe oral diseases, mechanical ventilation for more than 24 hours prior to study entry, those who refused oral care protocol

Number randomised: 164

Number evaluated: 164

Baseline characteristics: Not reported for each randomised group


InterventionsComparison: Saline swab versus saline rinse versus both

Experimental group A (n = 58): Rinsing the oropharyngeal cavity with saline for 5-10 seconds, followed by suction aspiration, repeated 5-10 times twice daily for 7 days

Experimental group B (n = 62): Both wipe and rinse as above, twice daily for 7 days

Control group (n = 44): Usual care - wiping the oropharyngeal cavity with saline-soaked cotton ball twice daily for 7 days


OutcomesVAP, stomatitis, fungal infection


NotesDiagnosis of VAP was according to Chinese Society of Respiratory Diseases criteria

Information translated from Chinese paper by Shi Zongdao and colleagues


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"randomly allocated" but no details of sequence generation described

Allocation concealment (selection bias)Unclear riskNot described

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described, and probably not possible

Blinding of outcome assessment (detection bias)
All outcomes
High riskNot described and probably not done

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll randomised participants included in outcome evaluation

Selective reporting (reporting bias)Low riskPlanned outcomes reported

Other biasLow riskNo other sources of bias identified

Xu 2008

MethodsStudy design: Parallel group RCT

Location: Shandong, China

Number of centres: 1

Study period: No stated

Funding source: No external funding


ParticipantsSetting: ICU of the second hospital of Shandong University

Inclusion criteria: Adult patients entering ICU receiving mechanical ventilation expected to last > 48 hours

Exclusion criteria: Patients with pulmonary infections

Number randomised: 116

Number evaluated: 116

Baseline characteristics: Not reported for each randomised group


InterventionsComparison: Saline rinse versus saline swab

Experimental group (n = 64): Rinse of the oropharyngeal cavity with saline for 5-10 seconds, followed by suction aspiration and repeated 5-10 times, twice daily

Control group (n = 52): Standard oral care comprising scrubbing with a cotton ball soaked in saline, twice daily


OutcomesVAP, duration of ventilation (days)


NotesDiagnosis of VAP was according to Chinese Society of Respiratory Diseases criteria

Information translated from Chinese paper by Shi Zongdao and colleagues


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"randomly allocated" Method of sequence generation not described

Allocation concealment (selection bias)High riskNot mentioned and probably not done

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot mentioned and probably not possible

Blinding of outcome assessment (detection bias)
All outcomes
High riskNot mentioned and probably not done

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll randomised participants included in the outcome evaluation

Selective reporting (reporting bias)Low riskBoth outcomes listed in methods are reported in the results section

Other biasLow riskNo other sources of bias identified

Yao 2011

MethodsStudy design: Single blind pilot RCT (NCT 00604916)

Location: Taiwan

Number of centres: 1

Study period: March to November 2007

Funding source: Grants from Taiwan National Science Council and career development grant from National Health Research Institutes


ParticipantsSetting: Surgical ICU

Inclusion criteria: Intubated and ventilated post-operative patients expected to be in ICU > 48 hours and expected to require mechanical ventilation for 48-72 hours with nasal or endotracheal intubation

Exclusion criteria: Patients with pneumonia at baseline

Number randomised: 53

Number evaluated: 53 (VAP), day 3-4 50, day 7-8 42

Baseline characteristics:

-Intervention group: Age: 60.7±16.0; M/F: 17/11; APACHEII Score: 19.6± 5.2

-Control group: Age: 60.5±16.5; M/F: 17/8; APACHEII Score: 19.4± 4.4


InterventionsComparison: Oral care + toothbrushing twice per day versus usual oral care

Experimental group: Standardised oral care protocol twice daily for 15-20 minutes for 7 days from trained intervention nurse. Bed elevated 30 to 45 degrees, hypopharyngeal suctioning, mouth moistened with 5-10 ml purified water, buccal surfaces of teeth cleaned with powered toothbrush and lingual tooth surfaces and tongue, gums and mucosa massaged with soft paediatric toothbrush. Oral cavity then cleaned with toothette swab connected to a suction tube and rinsed with 50 ml water + hypopharyngeal suctioning

Control group: Received oral care protocol, twice daily for 10-15 minutes provided by same trained intervention nurse. Patients elevated, hypopharyngeal suctioning, lips moistened with toothette swab and water, then further hypopharyngeal suctioning


Outcomes1. Oral Assessment Guide (OAG Eilers et al 1988) score

2. Plaque score (Turesky-Gilmore-Glickman modification of Quigley-Hein plaque index with disclosing dye. Recorded 1 tooth from each quadrant (prioritising premolars and incisors) scores summed)

3. Duration of ventilation

4. Length of ICU stay

5. Incidence of VAP (defined as CPIS > 6)

4. Mortality (ICU)


NotesSample size calculation: Pilot study

NCT 00604916 at ClinicalTrials.gov

Email sent to author 14 November 2012. Reply received 12 December 2012


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"...randomized using a computer generated randomization table"

Allocation concealment (selection bias)Unclear riskNot mentioned in trial report

Comment: Unclear whether allocation was concealed from researchers prior to assignment

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskExperimental group received toothbrushing (both powered and manual) and control group did not, so blinding of participants and personnel not possible

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcomes assessed by 2 hygienists blinded to allocated treatment. VAP assessed by CPIS score

Incomplete outcome data (attrition bias)
All outcomes
Low riskVAP outcome assessed in all randomised participants. For oral health and plaque outcomes 8/28 (experimental) and 7/25 (control) patients lost (transferred to ward) and 2/28 patients in experimental group died

Selective reporting (reporting bias)Low riskPlanned outcomes reported, but denominators unclear for VAP and mortality. However this information was supplied by email from the authors

Other biasUnclear risk3/28 (11%) and 1/25 (4%) patients in experimental and control groups were edentulous. Unclear how the intervention and outcomes were applied in these participants

Zhao 2012

MethodsStudy design: A single centre RCT with 2 parallel groups

Location: China

Number of centres: 1 surgical ICU in city hospital

Study period: May 2010 to April 2011

Funding source: Not stated


ParticipantsInclusion criteria: Admission into the ICU, orally intubated, receiving mechanical ventilation

Exclusion criteria: Not specified

Number randomised: 324 (162 per group)

Number evaluated: 324

Age group: Mean 66.25±15.28

Baseline characteristics were comparable


InterventionsComparison: Yikou (triclosan) rinse versus saline

Experimental group: Oral cavity swab with 15 ml of Yikou gargle (triclosan is main ingredient), 4 times a day

Control group: Oral cavity swab with normal saline, 4 times a day

Secretions were aspirated using suction once daily and sent to lab for culture


Outcomes3 outcome variables were available:

1. Incidence of VAP in less than 4 days of ventilation and within 4 to 10 days of ventilation

2. Mechanical ventilation days

3. ICU stay days

4. Culture of the samples taking from oropharyngeal cavity and inferior respiratory tract (Table 3, detection rates of microbial pathogens before and after oral nursing care were listed)


NotesDiagnosis of VAP was mainly determined by microbial examination of the aspirate secretions from the inferior respiratory tract, which was performed every day


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"randomly divided into 2 groups"

Allocation concealment (selection bias)Unclear riskNot specified

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskBlinding not described and not possible for the carers who would be aware of who was in each group

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk Not specified

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe main results were all reported

Selective reporting (reporting bias)Low riskThe results were fully reported

Other biasUnclear riskOnly the results of microbial examination of the aspirate secretions from the inferior respiratory tract as tool of VAP diagnosis was mentioned and its diagnostic efficacy may not be enough

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Abusibeih 2010Quasi-randomised trial

Bordenave 2011Identified from ClinicalTrials.gov website as ongoing study but email from contact author on 8 November 2012 confirmed that this study did not proceed due to lack of funding

Chao 2009Not RCT

Epstein 1994The participants involved in the study were not critically ill

Fan 2012The ingredients of the mouthwash used in the trial were not reported, so we could not judge the mouthwash containing antibiotics or not

Ferozali 2007The target population was long term care residents, not critically ill patients in hospitals

Genuit 2001Not RCT

Guo 2007RCT, but patients had lung trauma (injury before receiving the oral nursing intervention)

Houston 2002Likely that less than 10% of study participants had mechanical ventilation for a minimum of 48 hours

Lai 1997RCT of critically ill patients, unclear how many were on mechanical ventilation, outcome candidiasis

Li 2011Participants allocated to groups by alternation (not RCT)

Li 2012The mouthwash Kouitai used in the trial contains both chlorhexidine and metronidazole, and the later is an antibiotic

Liang 2007The participants involved in the study did not use mechanical ventilation

Liwu 1990Clinical controlled trial, not an RCT

MacNaughton 2004Published as abstract only with interim analysis. Insufficient information in abstract to include this study in the systematic review and attempts to locate full publication or to contact the author unsuccessful

McCoy 2012Not RCT

Ogata 2004The target population was patients about to receive orotracheal intubation, they were not on mechanical ventilation. Study about gargling with povidone iodine before oral intubation to reduce the transport of bacteria into the trachea, not oral care intervention in critically ill patients to reduce VAP

Pawlak 2005Not RCT

Santos 2008Email reply from Dr Santos stated that "The nurse put the first admission on biotene and the second admission on cetylpyridium, the third admission on biotene and so on." Alternation as an allocation method is not truly random and therefore this study was excluded

Segers 2006The participants involved in the study did not use mechanical ventilation

Ueda 2004The target population was patients at nursing homes, not critically ill patients in hospitals

Wang 2006Quasi-randomised controlled trial

Wang 2012The interventions being tested in the experimental group includes elevation of the head of the bed, closed endotracheal suctioning in addition to oral nursing care, which is outside the scope of the review

Yin 2004RCT aiming to improve oral cleanliness. Unlikely that participants received mechanical ventilation

Zouka 2010Abstract only, insufficient information to include in review. Emailed contact author 6 November 2012 without response

 
Characteristics of studies awaiting assessment [ordered by study ID]
Anon 2012

Methods

Participants

InterventionsEB57 oral care-based programme for reducing VAP

Outcomes

NotesFull-text copy requested from library

Baradari 2012

MethodsDouble-blind RCT

Participants60 ICU patients "divided into 2 equal groups". Seems unlikely that they are receiving mechanical ventilation

InterventionsChlorhexidine versus herbal mouthrinse

Outcomes

NotesLanguage: Iranian - will require translation. Full-text copy requested from library

Seo 2011

Methods

Participants

InterventionsOral hygiene

Outcomes

NotesLanguage: Korean - will require translation. Full-text copy requested from library

Yun 2011

Methods

Participants

InterventionsToothbrushing

Outcomes

NotesLanguage: Korean - will require translation. Full-text copy requested from library

 
Characteristics of ongoing studies [ordered by study ID]
NCT 01657396

Trial name or titleImplementation and evaluation of revised protocols for oral hygiene for mechanically ventilated patients

MethodsRCT - 3-arm parallel group study

ParticipantsAdults in intensive care units in Alberta, Canada

InterventionsSAGE Q care (commercial package) versus SAGE Q care plus chlorhexidine versus standard oral hygiene care

OutcomesVAP, frequency of oral care procedures, OA score, duration of ICU and hospital stay, ICU and hospital mortality, antimicrobial utilisation, acquisition of antimicrobial resistant organisms

Starting dateJuly 2012 (currently recruiting)

Contact informationDr Dan Zuege (dan.zuege@albertahealthservices.ca )

Notes

 
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]

 
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

Toothbrushing (± chlorhexidine) versus no toothbrushing (± chlorhexidine) for critically ill patients to prevent ventilator-associated pneumonia (VAP)

Patient or population: Critically ill patients to prevent ventilator-associated pneumonia
Settings: Intensive care units (ICUs)
Intervention: Toothbrushing (± chlorhexidine)

Comparison: No toothbrushing (± chlorhexidine)

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

Assumed riskCorresponding risk

No toothbrushingToothbrushing

Incidence of VAP

Follow-up: mean 1 month
245 per 1000 1183 per 1000
(105 to 295)
OR 0.69
(0.36 to 1.29)
828
(4 studies)2
⊕⊕⊝⊝
low,3,4
5

Mortality
Follow-up: mean 1 month
277 per 1000 1245 per 1000
(192 to 307)
OR 0.85
(0.62 to 1.16)
828
(4 studies)
⊕⊕⊕⊝
moderate2

Duration of ventilation
Follow-up: mean 1 month
The mean duration of ventilation in the control groups ranged from 9.8 to 10 daysThe mean duration of ventilation in the intervention groups was
0.85 lower
(2.43 lower to 0.73 higher)
583
(2 studies)
⊕⊕⊕⊝
moderate 6

Duration of ICU stay
Follow-up: mean 1 month
The mean duration of ICU stay in the control groups ranged from 13 to 15 daysThe mean duration of ICU stay in the intervention groups was
1.82 lower
(3.95 lower to 0.32 higher)
583
(2 studies)
⊕⊕⊕⊝
moderate6

*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; 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 Assumed risk is based on the outcomes in the control groups of the included studies
2 3 studies compared toothbrushing + chlorhexidine with chlorhexidine alone and the fourth study compared toothbrushing with no toothbrushing (no chlorhexidine in either group)
32 studies at high risk of bias and 2 studies at unclear risk of bias
4Substantial heterogeneity (I2 = 64%). Meta-analysis of 3 studies with chlorhexidine in both groups shows no heterogeneity (I2 = 0%)
5A fifth study, which randomised 117 participants showed no difference between toothbrushing + chlorhexidine and chlorhexidine alone (OR 0.78, 95% CI 0.36 to 1.68, P = 0.56). This study was at high risk of bias, and there was insufficient information to include data from this study in the meta-analysis
6 1 study at high risk of bias and 1 study at unclear risk of bias
 
Table 1. Other outcome data from included studies

 ComparisonOutcomeDataEffect estimate (95% CI)

CHX versus placebo/control (Berry 2011)Microbial colonisationThere was no significant difference in comparison of change in microbial growth from day 1 to day 4 between CHX and control groups

Toothbrushing versus none (Bopp 2006)Incidence of VAP0/2 cases in toothbrushing group and 1/3 case in control group

Duration of ventilationMean 5.5 days (SD 0.3896) n = 2 in toothbrushing group and mean 5 days (SD 0.8051) n = 3

Duration of ICU stayMean 18 days (SD 1.6695) n = 2 in toothbrushing group and mean 10.3 days (SD 2.6971) n = 3

CHX versus placebo/control (Grap 2004)Microbial colonisationPositive cultures in 3/11 patients in CHX spray group, 3/12 patients in CHX swab group and 4/11 patients in control group over the study period

CHX versus placebo (Koeman 2006)Mortality

 
Hazard ratioHR 1.12 (0.72 to 1.17)

 

Oral microbial colonisation

 
Hazard ratio, Gram positive organisms

Hazard ratio, Gram negative organisms
HR 0.695 (0.606 to 0.796) (Gram positive)

HR 0.826 (0.719 to 0.950) (Gram negative)

CHX spray versus CHX spray + toothbrush versus usual care (McCartt 2010)Mean CPIS at 72 hours compared to baselineCHX spray: CPIS score at 72 hours mean 4.88 (SD 2.14) n = 24

CHX spray + toothbrush: CPIS score at 72 hours mean 5.00 (SD 1.84) n = 24

Usual care: CPIS score at 72 hours mean 5.19 (SD 1.56) n = 21
CHX spray versus usual care P = 0.58

CHX + toothbrushing versus usual care P = 0.71

Experimental groups combined versus usual care P = 0.57

Powered toothbrush + CHX versus CHX alone (Roca Biosca 2011)Plaque indexMean in toothbrush group 1.68 (n = 29) and mean in control group 1.91 (n = 32)
No estimates of variance but reported that P = 0.7 (no difference)

Incidence of VAPOdds ratio 0.78 (95% CI 0.36 to 1.68, P = 0.56)

CHX (once daily or twice daily) versus placebo (Scannapieco 2009)Plaque indexNo difference between the 3 groups (data presented graphically)

 CHX = chlorhexidine; CI = confidence interval; CPIS = Clinical Pulmonary Infection Score; HR = hazard ratio; ICU = intensive care unit; SD = standard deviation; VAP = ventilator-associated pneumonia