guidelines on oral hygiene for improving surgical …

1

GUIDELINES ON ORAL HYGIENE FOR IMPROVING SURGICAL OUTCOMES Philippine Surgical Infection Society

Summary of Evidence 1. Oral hygiene offers benefits in terms of lower rates of nosocomial infection,

nosocomial pneumonia, ventilator-associated pneumonia and surgical site infection, shorter ICU stay, less ventilator days and lower oral colony counts. Overall harm-benefit ratio is in favor of oral hygiene. (level 1a, moderate certainty)

2. Several oral care agents have shown benefits in improving surgical outcomes. Among them are chlorhexidine mouthwash/rinse (level 1a, moderate to high

certainty), povidone iodine mouthwash/rinse (level 1a, moderate certainty), oral topical antibiotics (level 1a, moderate to high certainty), essential oil-based oral agent (level 1b, moderate certainty), hexetidine (level 1b, low certainty), and oral topical probiotics (level 1b, low certainty).

3. Toothbrushing was associated with a tendency to improve surgical outcomes but

did not reach statistical significance. (level 1a, moderate certainty) 4. Apart from toothbrushing, no comparative trial has been conducted to

demonstrate benefit of other specific oral hygiene care method/technique in terms of surgical outcomes. Instead, oral hygiene care bundles including oral rinsing or gargling, cleaning of the tongue and other oral mucosal surfaces, and dental flossing were used and considered good practice. (level 4, no certainty).

5. Dentist-delivered oral hygiene treatment was superior to ICU nurse delivered care

in the prevention of respiratory infections. (level 1b, low to moderate certainty) 6. Once and twice a day delivery of oral hygiene yielded similar outcomes. (level 1b,

moderate certainty) 7. No trial evidence is available on the optimum duration of oral hygiene provision.

Provision of oral care during the patient’s hospital stay is considered best practice. (level 4, no certainty)

EXECUTIVE SUMMARY

2

Recommendations 1. Implement an oral hygiene program among surgical patients. (Strong)

1.a. Patients who are scheduled to undergo cardiothoracic surgery should receive oral hygiene care perioperatively. (Strong)

1.b. Patients who are scheduled to undergo oropharyngeal surgery should receive oral hygiene care perioperatively. (Strong)

1.c. Surgical patients who are critically ill and on mechanical ventilation should receive oral hygiene care. (Strong)

1.d. Consider a perioperative oral hygiene program for surgical patients who will undergo general anesthesia. (Strong)

1.e. Consider a perioperative oral hygiene program for surgical patients who will receive anesthesia other than general anesthesia (eg. regional, intravenous, local, etc.). (Weak)

2. Include the use of oral hygiene care agents in the oral hygiene program for surgical patients. (Strong)

2.a. Use chlorhexidine mouthwash and consider povidone iodine mouthwash, essential

oil-based mouthwash, hexetidine, and oral topical probiotics as alternative oral care agents for surgical patients. (Strong)

2.b Consider topical antibiotics as an alternative oral hygiene care agent for surgical patients, but with serious consideration on its impact on antimicrobial resistance. (Weak)

3. Include toothbrushing in the oral care program for surgical patients, whenever feasible.(Strong)

4. Consider including the following maneuvers in oral hygiene programs for surgical patients:(Weak)

• oral rinsing or gargling

• removal of tongue coating

• cleaning of tongue and mucosal surface with a sponge or brush

• mechanical cleansing of the oral cavity with spatula wrapped in gauze

• dental flossing

5.a. Provide an oral hygiene program that can be delivered / implemented by trained nurses to surgical patients. (Weak)

5.b. Refer surgical patients to the dentist for further oral health care, when appropriate. (Weak)

6. Provide oral hygiene care at least once a day to surgical patients. (Strong)

7.a. Implement an oral hygiene program for operative surgical patients at least one day preoperatively and until hospital discharge. (Weak)

7.b. Implement an oral hygiene program for critically ill and mechanically ventilated patients at the time of intubation until hospital discharge. (Weak)

3

Introduction

Nosocomial infections such as surgical site infections (SSI) and postoperative pneumonia significantly contribute to a patient’s morbidity and mortality. They increase length of hospital stay and the need for medications, leading to additional health care costs and use of health care resources (Rabello, 2018).. Nosocomial respiratory infections account for approximately 10-15% of all hospital acquired infections, with 20-50% mortality among affected patients (Pedersen 2016).

Of the proposed mechanisms that can lead to nosocomial infections among surgical patients, of particular interest is the swallowing and aspiration of pathogenic microorganisms in the oral cavity (Nobuhara et al., 2018). Oral secretions are also contaminated by dental plaque colonized with respiratory pathogens (Nicolosi et al., 2014).

Previous research has assessed the effect of oral hygiene management on nosocomial infections and postoperative complications. A systematic review evaluating perioperative systemic oral hygiene among patients undergoing elective thoracic surgery found that all studies pointed to a reduction in the number of postoperative infections as a result of systemic decontamination of the nasopharynx and/or oropharynx (Pedersen 2016). Studies in other populations have found that oral hygiene management has been effective in preventing infectious diseases and postoperative complications. Perioperative oral hygiene management reduced SSI risk after colorectal surgery and subsequently shortened hospital stays, and that perioral management should commence as soon as surgery is contemplated (Nobuhara 2018). Conversely, another study concluded that lack of preoperative oral management was significantly associated with SSI (OR=10.17, P=0.035) (Hasegawa 2018).

There are no current standard definitions of oral hygiene management in a surgical context. Oral hygiene measures include, but are not limited to, the following: mechanical aids to remove plaque and debris from the oral cavity (eg. Toothbrushing, swabbing with water), topical or chemical disinfection to reduce colonization (eg. mouthrinse, sprays, liquids, or gels), a combination of mechanical and topical disinfection (eg. Swabbing with antiseptic, toothbrushing with antibacterial toothpaste, or daily toothbrushing plus antiseptic rinse), and professional dental care (eg. Aided toothbrushing, suctioning to remove excess fluid). These measures have no specified duration or frequency and can be administered by patients, caregivers and health care professionals (Liu 2018).

Currently few guidelines exist internationally or nationally that offer evidence-based recommendations on pre- or peri-operative oral hygiene in surgical settings. In 2004, the Center of Disease Control in the USA recommended the use of chlorhexidine at a concentration of 0.12% among patients undergoing cardiovascular surgery for the prevention of pneumonia during the pre-operative period (CDC 2004). Based on the

GUIDELINES ON ORAL HYGIENE FOR IMPROVING SURGICAL OUTCOMES EXECUTIVE SUMMARY

4

findings of the systematic review of the effect of perioperative oral hygiene on respiratory tract infections after elective thoracic surgery, a Danish Clinical Guideline was published recommending patients should initiate systematic oral hygiene 2 days before scheduled surgery. A before-and-after quality improvement study that evaluated the implementation of the guideline in a Danish institution found that the need for postoperative antibiotics was reduced from 12.6% to 7.7% of patients in a Department of Thoracic Surgery (Pedersen 2015; Pedersen 2019).

On September 15, 2020, the Philippine Surgical Infection Society initiated the development of a set of evidence-based recommendations on oral hygiene for improving surgical outcomes for adoption in the Philippines. Here, the methods, results and recommendations are presented.

Systematic review methods Identification of guideline scope and key clinical questions An online survey was conducted of the board members of the Philippine Surgical Infection Society and the members of the Philippine College of Surgeons Surgical Infection Committee on the scope of the guideline recommendations and key clinical questions. The survey yielded 6 clinical questions which informed the systematic search and review of the scientific evidence to support the recommendations:

1. Does oral hygiene improve outcomes for surgical patients? 2. What solutions/oral agents are effective in improving outcomes for surgical

patients? 3. Among the different agents, which is the best? 4. What methods/ techniques of oral hygiene are effective in improving

outcomes for surgical patients? 5. What is the optimal frequency for the provision of oral hygiene? 6. What is the optimal duration of the intervention?

Literature search Medline and Cochrane bibliographic databases were searched for relevant publications, with no time restriction. The following search terms were used: oral hygiene, oral care, oral health, mouthwash, mouthrinse, nosocomial infection, nosocomial pneumonia, respiratory infection, and surgical site infection. The search was limited to randomized, controlled trials and reviews. Selection of studies

5

Following removal of duplicates, two review authors screened the titles and abstracts of study records identified by the searches for potential eligibility. The full-text of selected records were retrieved and screened independently by two review authors using a standardized form, linking together multiple records of the same study in the process. At both screening stages, disagreements were resolved by discussion or consultation with a third review author. The reference lists of published systematic reviews were searched for additional studies. Trials were eligible for inclusion if they included surgical cases (whether operative or non-operative cases usually attended to by surgeons such as trauma patients), compared oral hygiene programs using various agents and techniques individually or in combination with placebo or usual care or other oral hygiene programs, and if they reported any of the following: nosocomial infection, nosocomial pneumonia, ventilator-associated pneumonia, SSI, mortality, ICU admission, ventilator days, adverse events, or oral colony count. Data extraction and analysis

Two review authors independently extracted outcome data. Study characteristics were extracted by one review author and reviewed for accuracy by a second review author. Any disagreements were resolved by discussion or by consulting a third review author. Data extracted and included in the 'characteristics of included studies' table were: study design; year of publication, inclusion criteria, exclusion criteria, number of participants for each treatment group, description of interventions, co –interventions and outcomes.

Where data were available from more than one study reporting the same comparison and outcome, these data were pooled and meta-analysis performed. For studies with multiple publications, only the most up-to-date or complete data for each outcome were utilized. A fixed effects model was used to calculate pooled estimates of treatment effect and 95% confidence intervals. Where there was clinical or methodological heterogeneity a random effects model was used.

Measures of treatment effect were expressed as risk ratios for dichotomous outcomes and mean differences for continuous outcomes. If studies used different scales to assess the same continuous outcome, the standardized mean difference was used instead of the mean difference.

Where no data could be pooled, results of individual studies were reported narratively. Assessment of risk of bias

6

The risk of bias of each included study was assessed independently by two review authors. Any disagreements were resolved by discussion or by consulting a third review author. Risk of bias was assessed by using the recommended tool in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins et al., 2011). This includes the assessment of: random sequence generation; allocation concealment; blinding of participants and personnel; blinding of outcome assessment; incomplete outcome data; selective reporting; and other sources of bias, such as funding source.

Assessment of the certainty of the evidence The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of evidence related to the outcomes as listed above (Guyatt 2008). The grade approach assesses evidence to be of high certainty, moderate certainty, low certainty or very low certainty. Certainty was downgraded by one level for serious (or by two for very serious) risk of bias, indirectness of evidence, inconsistency, imprecision or potential publication bias.

Systematic review summary results Of the 3,171 citations identified in the searches of bibliographical databases, after removal of duplicates, title and abstract screening and assessment of full text articles, 88 articles were included in the guidelines review. The Preferred Reporting Items for Systematic Review and Meta-analyses flow diagram of the study selection process is shown in Figure 1.

Figure 1. PRISMA Flow Diagram of Study Selection Overall, 29 systematic reviews and 59 RCTs were included. All were published in English. , 20 were in surgical populations, 18 were mixed, and 21 from the medical or unknown group. Thirty three trials assessed the effectiveness of chlorhexidine versus

7

placebo, 5 trials the effectiveness of povidone iodine versus placebo, 7 trials the effectiveness of topical antibiotics versus placebo, 1 trial the effectiveness of essential oils versus placebo, 3 trials the effectiveness of agents versus placebo, 6 trials one agent versus another agent, 1 trial compared dosing / frequency of chlorhexidine, and 9 trials comparing one maneuver (eg. toothbrushing) with none / sham. Outcomes assessed were nosocomial infection, nosocomial pneumonia, ventilator-associated pneumonia, surgical site infection, mortality, ventilator days, ICU days, and adverse events. The characteristics of the included RCTs are further detailed in Appendix 1. Appendix 2 lists the systematic reviews used as further references for the studies. Twenty meta-analyses were performed and associated forest plots generated from pooling of the extracted RCT data, and the results of single trials where no data could be pooled for meta-analysis were reported narratively. The collated evidence for each of the six key clinical questions was used to develop provisional recommendations, which would then be accepted, rejected or modified through a consensus process. A full report of the systematic review presenting these results in detail is published separately. In this report of the recommendations, Evidence Summaries are presented with each key clinical question in the Guideline Recommendation section.

Consensus methods The collated evidence for each of the six key clinical questions and the provisional recommendations were circulated to the member of the Guideline Development Panel. The panel comprised 14 representatives from 10 specialty surgical societies and societies concerned with infection control. The panel members are listed in Appendix 3. On November 14, 2020, the panel was convened for a consensus meeting to decide on the recommendations of the guidelines. At the meeting, the evidence for each clinical question was presented and the provisional recommendation discussed. Each provisional recommendation could be accepted, rejected or modified. Modification could involve changing a single provisional recommendation into more than one recommendation. A modified Delphi technique was used to arrive at a decision regarding the wording and strength of each recommendation. Consideration of the strength of each recommendation took into account availability of evidence, magnitude and certainty of the evidence, harms and benefits, and patient preference. While no patient representative attended the consensus meeting, panel members were asked to take into account their understanding of patient preferences.

8

The target consensus level for the final acceptance of a recommendation was 95% agreement. Discussion and modification of each recommendation continued until this was achieved through repeated votes. During the consensus meeting, 19 recommendations were finalized relating to five of the six key clinical questions. For one of the key clinical questions there was insufficient evidence to make any recommendation. Of 11 provisional recommendations relating to the 6 clinical questions disseminated to the expert panel prior to the consensus meeting, nine were ultimately included. Of these, only three recommendations were retained verbatim and reached consensus on the first vote for both wording and the strength of recommendation (recommendations 1, 2a, and 5a). The remaining six were revised after one vote and reached consensus on the second vote. During the course of discussions, ten additional recommendations were included and consensus was reached for wording and strength on the first vote after they were proposed. Several of these arose as modifications of the 11 originally proposed recommendations (for example, creating separate recommendations for patients undergoing cardiothoracic and oropharyngeal surgery instead of one recommendation for both). The full recommendations are presented in the next section along with summaries of the evidence considered and the panel’s discussions. The technical working group obtained commitment from the consensus panel members for their respective organizations to adopt and disseminate the guidelines among their members for implementation. The Philippine Surgical Infection Society will formally endorse these guidelines to the Philippine College of Surgeons for adoption and dissemination. The guidelines will then be presented to the public in the PCS annual convention and other scientific fora. Finally, an abbreviated version of the guidelines will be produced for posting on websites and dissemination on social media.

Funding Support and Declaration of Conflicts of Interest The Philippine Surgical Infection Society, through a research grant from J&J Philippines, commissioned the conduct of a systematic review on oral hygiene for improving surgical outcomes and sponsored the development of this Guideline. The individual declaration of conflict of interest for the members of the Technical Working Group and the members of the Consensus Panel Members are presented in Appendix 3.

Commented [CJ[1]: Johnson & Johnson Philippines Inc. (JJPI)

9

GUIDELINE RECOMMENDATIONS

Clinical Question: Does oral hygiene improve outcomes for surgical patients?

Evidence Summary: Twenty nine systematic reviews and 59 RCTs involving various oral hygiene programs for surgical patients and critically ill patients are fairly consistent in concluding that oral hygiene offers benefits in terms of nosocomial infection, nosocomial pneumonia, ventilator-associated pneumonia and surgical site infection. Shorter ICU stay and less ventilator days were also demonstrated. No significant benefit has been found in terms of mortality. Significantly higher adverse event rates were noted with oral hygiene compared to placebo or usual care, but these were mostly minor (eg. mild reversible irritation of the oral mucosa, burning sensation, local urticaria, bleeding gums, and tooth discoloration). The most serious oral hygiene-related adverse event was aspiration of mouthwash or oral content with the potential to increase the risk of nosocomial pneumonia, but this was very rare. Overall, the harm-benefit ratio is in favor of oral hygiene. Level of Evidence: 1a, moderate certainty Panel Discussion: The Panel agreed that oral hygiene is beneficial and should be given to all surgical patients. Acknowledging the limited evidence available on the magnitude of benefit to all types of operative cases, rather than lowering the strength of recommendation for this subgroup of patients, it was agreed upon that for those who will undergo (or have a risk of conversion to) general anesthesia (ie. endotracheal intubation specifically), separate recommendations should be given according to the type of anesthesia.

Recommendation 1: Implement an oral hygiene program among surgical patients. Strength of Recommendation: Strong

Recommendation 1a: Patients who are scheduled to undergo cardiothoracic surgery should receive oral hygiene care perioperatively.

Strength of Recommendation: Strong

Recommendation 1b: Patients who are scheduled to undergo oropharyngeal surgery should receive oral hygiene care perioperatively.


10

Recommendation 1c: Surgical patients who are critically ill and on mechanical ventilation should receive oral hygiene care.


Recommendation 1d: Consider a perioperative oral hygiene program for surgical patients who will undergo (or have a risk of conversion to) general anesthesia.


Recommendation 1e: Consider a perioperative oral hygiene program for surgical patients who will receive anesthesia other than general anesthesia (eg. regional, intravenous, local, etc.).

Strength of Recommendation: Weak

Clinical Question: What solutions/oral agents are effective in improving outcomes for surgical patients?

The following agents were used in oral hygiene programs among surgical patients in clinical trials considered in the evidence review:

a. Chlorhexidine rinse/swab b. Povidone iodine rinse / swab c. Topical antibiotics d. Essential oils (including Listerine) e. Hexetidine f. Topical probiotics

Evidence Summary A. Chlorhexidine Mouthwash

Meta-analysis of 28 RCTs comparing chlorhexidine–based oral hygiene programs and placebo or usual care reported that they are beneficial in terms of lowering the risk of nosocomial infections, nosocomial pneumonia and ventilator-associated pneumonia as well as shortening ICU stay. There was insufficient evidence to demonstrate a significant benefit with the use of chlorhexidine in terms of SSI rates, mortality, and ventilator days. There was a tendency for more adverse events associated with chlorhexidine but the difference did not reach statistical significance.

Nosocomial Infection: RR 0.64 (95%CI 0.54, 0.76)* Nosocomial Pneumonia: RR 0.78 (95% CI 0.68, 0.89)* Ventilator-associated Pneumonia: RR 0.73 (95%CI 0.65, 0.83)*

11

SSI: RR 0.62 (95%CI 0.23, 1.71) ICU Stay: MD -0.83 (95%CI -1.35,-0.30)* Ventilator Days: MD-0.05 (95%CI -0.14, 0.04) Mortality: RR 1.08 (95%CI 0.95,1.22) Adverse Event: RR 2.25(95%CI 0.31, 16.55) Colony count: 1 RCT showed that chlorhexidine was stronger in reducing

anaerobic than aerobic bacteria (1865 times decrease vs 13 times decrease after 5 mins washing) but also exhibited lower absolute intra-oral bacterial counts after application of chlorhexidine. (Kosutic 2009) Of the 9 RCTs that studied bacterial colonization, 6 reported a decrease in cultures positive for Gram-positive bacteria in the chlorhexidine group vs placebo group while cultures positive for Gram-negative bacteria were similar in proportions in the two groups.

* Indicates statistical significance

Level of evidence: 1a, moderate to high certainty B. Povidone iodine Mouthwash

Meta-analysis of 4 RCTs comparing povidone-iodine-based oral hygiene programs versus placebo or usual care reported that they are beneficial in terms of shorter ventilator days. However, there was insufficient evidence to demonstrate a significant benefit in terms of lowering the risk of ventilator-associated pneumonia, mortality, and shortening ICU stay with the use of oral povidone iodine.

Ventilator-associated Pneumonia: RR 0.61 (95%CI 0.30, 1.26) ICU Days: MD -0.35 (95%CI -3.90, 3.21) Ventilator Days: MD -1.19(95%CI -1.99, -0.40)* Mortality: RR 1.04 (95%CI 0.74, 1.46) Colony count: 3 RCTs reported a significant reduction in aerobic and

anaerobic oral cavity bacterial counts. 1 RCT showed a decreased cuff contamination level (15.8 + 12.6%, p<0.001) in the povidone iodine group vs placebo group. (Takeyasu 2014)

* Indicates statistical significance One small trial reported that none of the patients in the povidone iodine arm developed SSI while 3 of 30 patients (10%) in the control group developed SSI. RR 0.14 (95%CI 0.01, 2.65) (Kosutic 2009) No trial data is available on the effect of povidone iodine oral care on nosocomial infection and nosocomial pneumonia. Level of evidence: 1a, moderate certainty

12

C. Oral topical antibiotics Meta-analysis of 5 RCTs comparing topical antibiotic–based oral hygiene programs and placebo or usual care reported a tendency towards a lower risk of ventilator-associated pneumonia as well as shorter ICU stay and ventilator days with the use of topical antibiotics but the differences did not reach statistical significance. Topical antibiotic-based oral care did not lower the risk for death.

Ventilator-associated Pneumonia: RR 0.65 (95%CI 0.42, 1.02) ICU Stay: MD -2.4 (95%CI -5.62, 0.83) Ventilator days: MD -4.02 (-9.43, 1.4) Mortality: RR 0.98 (95%CI 0.81, 1.18) Colony count: 1 RCT reported a significant reduction in aerobic and

anaerobic oral cavity counts using 1% cetrimide solution vs placebo. (Kosutic 2009). In another RCT, the use of methylcellulose sodium carboxy paste containing 2% polymyxin E, 2% tobramycin and 2% amphotericin B showed significantly less acquired lower respiratory tract and intra-abdominal infections compared to the control group. Acquired infections caused by Gram-positive (28 vs 45) and Gram-negative (6 vs 40) bacteria were isolated less in the study group than in the control group (Kerver 1988).

One small trial showed significant benefit in lowering the risk of nosocomial pneumonia (RR 0.38 (95%CI 0.18, 0.83)), but not for surgical site infection (RR 0.36 (95%CI 0.05, 2.87)), associated with the use of topical antibiotic oral gel (Kerver 1988).

Level of evidence: 1a, moderate to high certainty Note: Currently, no oral topical antibiotic is available locally. Panel Discussion: The issue of antimicrobial resistance was raised as an additional issue of harm in the use of topical antibiotics. This resulted in the downgrading of the strength of recommendation, despite the evidence of benefit.

D. Essential oil- based mouth wash (Listerine)

No clinical trial that investigated the effectiveness of essential oils mouthwashes in surgical patients has been identified in the literature.

One 3-armed trial compared Listerine mouthwash with sodium bicarbonate mouthwash and sterile water among critically ill patients. No significant differences in ventilator-associated pneumonia rates (4.7% vs 4.4%, RR 1.07, 95%CI 0.41, 2.78), ventilator days, ICU stay, adverse event rates, or systemic antibiotic use were observed across all treatment groups (Berry 2013). One randomized trial compared chlorhexidine and phenolic mixture (Listerine) among patients who underwent aortocoronary bypass. Incidence of nosocomial pneumonia did not differ significantly between the two groups (4/279 vs 9/291, p

13

= 0.21), nor did the incidence of positive culture growth (52/270 vs 44/291, p =0.19). Mortality rates were also similar between the two groups (6/270 vs 3/291). Colony culture studies showed more growth in the chlorhexidine group than in the Listerine group (19.26% vs 15.12%) although the difference was not statistically significant (p=0.19) (Houston 2002). All other available information on essential oils was limited to normal healthy patients or on patients with dental conditions. A systematic review of 26 trials provided evidence of anti-plaque and anti-gingivitis effects of essential-oil-containing mouth rinse as an adjunct to daily oral health regimen (Alshehri,2018) Level of evidence: 1b, moderate certainty

E. Hexetidine

No clinical trial has been identified in the literature that investigated the effectiveness of hexetidine mouthwashes in surgical patients. One small randomized trial compared chlorhexidine and hexetidine among critically-ill patients. The study reported similar incidences of VAP in both groups. It was observed that though there was a tendency for a faster recovery (decline in Clinical Pulmonary Infection Score) among patients who received chlorhexidine, both group scores showed parallel improvement overtime (Zouka 2010) Level of evidence: 1b, low certainty

F. Oral topical probiotics

One small randomized trial compared oral care using application of chlorhexidine with that using probiotic bacterium Lactobacillus planterum 299 among mechanically ventilated patients. No difference was found between the two groups in terms of ventilator days, length of stay in the ICU, and in-hospital mortality rates (Klarin 2018). Level of evidence: 1b, low certainty

Note: Currently, no oral topical antibiotic is available locally.

Recommendation 2 : Include the use of oral hygiene care agents in the oral hygiene program for surgical patients. Strength of Recommendation: Strong

Recommendation 2a : Use chlorhexidine mouthwash and consider povidone iodine mouthwash, essential oil-based mouthwash, hexetidine, and oral topical probiotics as alternative oral care agents for surgical patients. Strength of Recommendation: Strong

Commented [CJ[2]: Please see recommended text

14

Recommendation 2b : Consider topical antibiotics as an alternative oral hygiene care agent for surgical patients, but with serious consideration on its impact on antimicrobial resistance. Strength of Recommendation: Weak

Clinical Question: Among the different agents, which is the best?

Evidence Summary There is limited trial evidence directly comparing one agent with another. Only two trials were identified, one comparing chlorhexidine and phenolic mixture / essential oils and another comparing chlorhexidine and hexetidine (see above). No clear difference was established in the effectiveness of the different agents. Level of Evidence: 1b. low certainty

No recommendation regarding the best oral hygiene agent could be made due to limited evidence.

Clinical Question: What methods/ techniques of oral hygiene are effective in improving outcomes for surgical patients?

The available trials using oral hygiene evaluated the following practices: - Oral rinse (with or without agent) - Removal of dental plaque with toothbrush - Brushing of the teeth, gingiva, tongue and palate - Interdental brushing - Dental flossing - Tooth polishing - Removal of tongue coating / cleaning of tongue and mucosal surface with a

sponge brush or wet tissue - Gargling - Irrigation of the oral cavity and oropharynx - Removal of calculus - Atraumatic restorative treatment of caries - Mechanical cleansing of the oral cavity with a spatula wrapped in gauze - Topical application of the agent

15

There is limited trial evidence that directly investigated the benefit of these practices individually.

16

A. Toothbrushing Evidence Summary Four trials compared oral hygiene care, which includes toothbrushing and care without toothbrushing. Pooled analysis of the data did not show sufficient evidence of a significant difference in ventilator-associated pneumonia rates, ICU stay, and ventilator days, although with some tendency to favor toothbrushing. There was no difference in the mortality rates between the two groups.

Ventilator-associated pneumonia: RR 0.69 (95%CI 0.44, 1.09) ICU stay: MD -1.6 (95%CI 3.4, 0.21) Ventilator days: MD -0.93 (-2.71, 0.86) Mortality: RR 0.96 (95%CI 0.75, 1.22)

Level of evidence: 1a, moderate certainty

Recommendation 3: Include toothbrushing in the oral care program for surgical patients, whenever feasible. Strength of recommendation: Weak

B. Other oral hygiene care techniques and practices. Evidence Summary There is limited trial evidence that directly investigated the individual benefit of specific practices / techniques. Level of evidence: 4, no certainty

Recommendation 4 : Consider including the following maneuvers in oral hygiene programs for surgical patients:

o oral rinsing or gargling o removal of tongue coating o cleaning of tongue and mucosal surface with a sponge or brush o mechanical cleansing of the oral cavity with spatula wrapped in gauze o dental flossing

Strength of Recommendation: Weak

C. Oral hygiene program delivered by different health practitioners Evidence Summary No trial compared the delivery of the same oral hygiene program by different types of health practitioner.

17

One small trial compared the effect of the addition of oral care provided by dental health practitioners with the care provided ICU nurses alone. The additional procedures include toothbrushing, tongue scraping, removal of calculus, atraumatic restorative treatment of caries, and teeth extraction. The dentist-delivered treatment was superior to ICU nurse delivered care in the prevention of VAP and lower respiratory tract infections (8/127 or 6.3% vs 18/127 or 14.17%). No significant difference was reported in the other surgical outcomes (mortality, ventilator days and ICU days) (Bellissimo-Rodrigues 2014). Level of Evidence: 1b, low to moderate certainty Panel Discussions: Despite superiority of dentist-delivered oral care, the feasibility of such in our setting is uncertain. Hence the panel agreed not to recommend such type of care while acknowledging the evidence. As an alternative, referral for dental care postoperatively or after discharge, when appropriate, was recommended.

Recommendation 5a: Provide an oral hygiene program that can be delivered / implemented by trained nurses to surgical patients. Strength of recommendation: Weak

Recommendation 5b: Refer surgical patients to the dentist for further oral health care, when appropriate. Strength of recommendation: Weak

Clinical Question: What is the optimal frequency for the provision of oral hygiene?

Evidence Summary There is very limited evidence on the relative effectiveness of different frequencies of oral hygiene provision on surgical outcomes. One 3-arm trial compared chlorhexidine-containing rinse twice a day and once a day among critically-ill trauma patients in two of the treatment groups. Similar rates of nosocomial pneumonia (7/50 vs 7/50), ventilator-associated pneumonia (7/50 vs 7/57) and mortality (8/47 vs 8/50) were observed. Level of evidence: 1b, moderate certainty

Recommendation 6: Provide oral hygiene care at least once a day to surgical patients.

Strength of recommendation: Strong

18

Clinical Question: What is the optimal duration of the intervention?

Evidence Summary Included trials used different durations of oral hygiene programs. No trial compared different durations of provision of oral hygiene care. In trials involving elective surgical patients, oral hygiene programs started from one to five days prior to the surgery. Some continued the care until one to two days postoperatively. Trials involving critically ill mechanically ventilated patients, the oral hygiene programs would continue until extubation or discharge from the ICU. Level of evidence: 4, no certainty Panel Discussions: Despite the absence of clinical trial evidence, the panel agreed to provide recommendations on the time frame of implementing an oral hygiene program.

Recommendation 7a:

Implement an oral hygiene program for operative surgical patients at least one day preoperatively and until hospital discharge. Strength of Recommendation: Weak Recommendation 7b: Implement an oral hygiene program for critically ill and mechanically ventilated patients at the time of intubation until hospital discharge. Strength of Recommendation: Weak

19

References Background and Methodology 1. CDC Centers for Disease Control and Prevention. Guidelines for Preventing Health-Care-Associated Pneumonia. Morbidity and Mortality Weekly Report. March 26, 2004: 53(RR03);1-36 2. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924-926. doi:10.1136/bmj.39489.470347.AD

3. Hasegawa T, Takeda D, Tanaka M, et al. Effects of preoperative dental examination and oral hygiene instruction on surgical site infection after hepatectomy: a retrospective study [published online ahead of print, 2020 May 18]. Support Care Cancer. 2020;10.1007/s00520-020-05525-7. doi:10.1007/s00520-020-05525-7 4. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.1 (updated September 2020). Cochrane, 2020. Available from www.training.cochrane.org/handbook. 5. Liu C, Cao Y, Lin J, et al. Oral care measures for preventing nursing home-acquired pneumonia. Cochrane Database Syst Rev. 2018;9(9):CD012416. Published 2018 Sep 27. doi:10.1002/14651858.CD012416.pub2 6. Nicolosi, L., del Carmen Rubio, M., Martinez, C., Gonzalez, N. and Cruz, M., 2013. Effect of Oral Hygiene and 0.12% Chlorhexidine Gluconate Oral Rinse in Preventing Ventilator-Associated Pneumonia After Cardiovascular Surgery. Respiratory Care, 59(4), pp.504-509. 7. Nobuhara, H., Yanamoto, S., Funahara, M., Matsugu, Y., Hayashida, S., Soutome, S., Kawakita, A., Ikeda, S., Itamoto, T. and Umeda, M., 2018. Effect of perioperative oral management on the prevention of surgical site infection after colorectal cancer surgery. Medicine, 97(40), p.e12545. 8. Pedersen PU, Haakonsen SJ, Madsen I, et al. Clinical guideline: systematic perioperative oral hygiene in reduction of postoperative infections after elective thoracic surgery in adults. Center of clinical guidelines, 2015 9. Pedersen PU, Larsen P, Håkonsen SJ. The effectiveness of systematic perioperative oral hygiene in reduction of postoperative respiratory tract infections after elective thoracic surgery in adults: a systematic review. JBI Database System Rev Implement Rep. 2016;14(1):140-173. doi:10.11124/jbisrir-2016-2180 10. Pedersen PU, Tracey A, Sindby JE, Bjerrum M. Preoperative oral hygiene recommendation before open-heart surgery: patients' adherence and reduction of

20

infections: a quality improvement study. BMJ Open Qual. 2019;8(2):e000512. Published 2019 Apr 3. doi:10.1136/bmjoq-2018-000512 11. Rabello F, Araújo VE, Magalhães S. Effectiveness of oral chlorhexidine for the prevention of nosocomial pneumonia and ventilator-associated pneumonia in intensive care units: Overview of systematic reviews. Int J Dent Hyg. 2018;16(4):441-449. doi:10.1111/idh.12336 Systematic Reviews 1. Alshehri FA. The use of mouthwash containing essential oils (Listerine) to improve oral health: A systematic review. Saudi Dent J. 2018;30:2-6. doi:https://doi.org/10.1016/j.sdentj.2017.12.004 2. Andrews T, Steen C. A review of oral preventative strategies to reduce ventilator-associated pneumonia. Nurs Crit Care. 2013;18(3):116-122. doi:10.1111/nicc.12002 3. Balamurugan E, Kanimozhi A KG. Effectiveness of chlorhexidine oral decontamination in reducing the incidence of ventilator associated pneumonia: A meta-analysis. Br J Med Pract. 2012;5(1). 4. Bardia A, Blitz D, Dai F, et al. Preoperative chlorhexidine mouthwash to reduce pneumonia after cardiac surgery: A systematic review and meta-analysis. J Thorac Cardiovasc Surg. 2019;158(4):1094-1100. doi:10.1016/j.jtcvs.2019.01.014 5. Buckley MS, Dzierba AL, Smithburger PL, McAllen KJ, Jordan CJ, Kane-Gill SL. Chlorhexidine for the prevention of ventilator associated pneumonia in critically ill adults. J Infect Prev. 2013;14(5):162-169. doi:10.1177/1757177413490814 6. Chan EY, Ruest A, Meade MO, Cook DJ. Oral decontamination for prevention of pneumonia in mechanically ventilated adults: Systematic review and meta-analysis. Br Med J. 2007;334(7599):889-893. doi:10.1136/bmj.39136.528160.BE 7. Chlebicki MP, Safdar N. Topical chlorhexidine for prevention of ventilator-associated pneumonia: A meta-analysis. Crit Care Med. 2007;35(2):595-602. doi:10.1097/01.CCM.0000253395.70708.AC 8. Coppadoro A, Bittner E, Berra L. Novel preventive strategies for ventilator-associated pneumonia. Crit Care. 2012;16(2):210. Published 2012 Dec 12. doi:10.1186/cc11225 9. Cotoia A, Spadaro S, Gambetti G, Koulenti D, Cinnella G. Pathogenesis-Targeted Preventive Strategies for Multidrug Resistant Ventilator-Associated Pneumonia: A Narrative Review. Microorganisms. 2020;8(6):821. Published 2020 May 30. doi:10.3390/microorganisms8060821 10. Cotti E, Arrica M, Di Lenarda A, et al. The perioperative dental screening and management of patients undergoing cardiothoracic, vascular surgery and other

21

cardiovascular invasive procedures: A systematic review. Eur J Prev Cardiol. 2017;24(4):409-425. doi:10.1177/2047487316682348 11. Hoshijima H, Kuratani N, Takeuchi R, et al. Effects of oral hygiene using chlorhexidine on preventing ventilator-associated pneumonia in critical-care settings: A meta-analysis of randomized controlled trials. J Dent Sci. 2013;8(4):348-357. doi:10.1016/j.jds.2012.11.004 12. Hua F, Xie H, Worthington HV, Furness S, Zhang Q, Li C. Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia. Cochrane Database Syst Rev. 2016;10(10):CD008367. doi:10.1002/14651858.CD008367.pub3 13. Klompas M. Oropharyngeal Decontamination with Antiseptics to Prevent Ventilator-Associated Pneumonia: Rethinking the Benefits of Chlorhexidine. Semin Respir Crit Care Med. 2017;38(3):381-390. doi:10.1055/s-0037-1602584 14. Labeau SO, van de Vyver K, Brusselaers N, Vogelaers D, Blot SI. Prevention of ventilator-associated pneumonia with oral antiseptics: A systematic review and meta-analysis. Lancet Infect Dis. 2011;11(11):845-854. doi:10.1016/S1473-3099(11)70127-X 15. Li J, Xie D, Li A, Yue J. Oral topical decontamination for preventing ventilator-associated pneumonia: A systematic review and meta-analysis of randomized controlled trials. J Hosp Infect. 2013;84(4):283-293. doi:10.1016/j.jhin.2013.04.012 16. Pedersen PU, Larsen P, Håkonsen SJ. The effectiveness of systematic perioperative oral hygiene in reduction of postoperative respiratory tract infections after elective thoracic surgery in adults: a systematic review. JBI Database System Rev Implement Rep. 2016;14(1):140-173. doi:10.11124/jbisrir-2016-2180 17. Pineda LA, Saliba RG, El Solh AA. Effect of oral decontamination with chlorhexidine on the incidence of nosocomial pneumonia: a meta-analysis. Crit Care. 2006;10(1):R35. doi:10.1186/cc4837 18. Plantinga NL, de Smet AMGA, Oostdijk EAN, et al. Selective digestive and oropharyngeal decontamination in medical and surgical ICU patients: individual patient data meta-analysis. Clin Microbiol Infect. 2018;24(5):505-513. doi:10.1016/j.cmi.2017.08.019 19. Pop-Vicas AE, Abad C, Baubie K, Osman F, Heise C, Safdar N. Colorectal bundles for surgical site infection prevention: A systematic review and meta-analysis [published online ahead of print, 2020 May 11]. Infect Control Hosp Epidemiol. 2020;1-8. doi:10.1017/ice.2020.112 20. Price R, MacLennan G, Glen J. Selective digestive or oropharyngeal decontamination and topical oropharyngeal chlorhexidine for prevention of death in

22

general intensive care: Systematic review and network meta-analysis. BMJ. 2014;348(March):1-15. doi:10.1136/bmj.g2197 21. Rabello F, Araújo VE, Magalhães S. Effectiveness of oral chlorhexidine for the prevention of nosocomial pneumonia and ventilator-associated pneumonia in intensive care units: Overview of systematic reviews. Int J Dent Hyg. 2018;16(4):441-449. doi:10.1111/idh.12336 22. Roberts N, Moule P. Chlorhexidine and tooth-brushing as prevention strategies in reducing ventilator-associated pneumonia rates. Nurs Crit Care. 2011;16(6):295-302. doi:10.1111/j.1478-5153.2011.00465.x 23. Silvestri L, Weir I, Gregori D, et al. Effectiveness of oral chlorhexidine on nosocomial pneumonia, causative micro-organisms and mortality in critically ill patients: a systematic review and meta-analysis. Minerva Anestesiol. 2014;80(7):805-820. 24. Silvestri L, Weir WI, Gregori D, et al. Impact of Oral Chlorhexidine on Bloodstream Infection in Critically Ill Patients: Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Cardiothorac Vasc Anesth. 2017;31(6):2236-2244. doi:10.1053/j.jvca.2016.11.005 25. Snyders O, Khondowe O, Bell J. Oral chlorhexidine in the prevention of ventilator-associated pneumonia in critically ill adults in the ICU: A systematic review. South African J Crit Care. 2011;27(2):48-56. doi:10.7196/SAJCC.123 26. Spreadborough P, Lort S, Pasquali S, et al. A systematic review and meta-analysis of perioperative oral decontamination in patients undergoing major elective surgery. Perioper Med (Lond). 2016;5:6. Published 2016 Mar 22. doi:10.1186/s13741-016-0030-7 27. Vilela MC arolin. N, Ferreira GZ ann., Santos PS érgi. da S, Rezende NP ep. M de. Oral care and nosocomial pneumonia: a systematic review. Einstein (Sao Paulo). 2015;13(2):290-296. doi:10.1590/S1679-45082015RW2980 28. Zhang TT, Tang SS, Fu LJ. The effectiveness of different concentrations of chlorhexidine for prevention of ventilator-associated pneumonia: a meta-analysis. J Clin Nurs. 2014;23(11-12):1461-1475. doi:10.1111/jocn.12312 29. Zhao D, Song J, Gao X, et al. Selective oropharyngeal decontamination versus selective digestive decontamination in critically ill patients: A meta-analysis of randomized controlled trials. Drug Des Devel Ther. 2015;9:3617-3624. doi:10.2147/DDDT.S84587

23

Randomized Control Trials 1. Abele-Horn M, Dauber A, Bauernfeind A, Russwurm W, Seyfarth-Metzger I, Gleich P, Ruckdeschel G. Decrease in nosocomial pneumonia in ventilated patients by selective oropharyngeal decontamination (SOD). Intensive Care Med. 1997 Feb;23(2):187-95. doi: 10.1007/s001340050314. PMID: 9069004. 2. Amora-Silva BF, Ribeiro SC, Vieira CL, et al. Clinical efficacy of new α-bisabolol mouthwashes in postoperative complications of maxillofacial surgeries: a randomized, controlled, triple-blind clinical trial. Clin Oral Investig. 2019;23(2):577-584. doi:10.1007/s00784-018-2464-4 3. Bellissimo-Rodrigues F, Bellissimo-Rodrigues WT, Viana JM, Teixeira GC, Nicolini E, Auxiliadora-Martins M, Passos AD, Martinez EZ, Basile-Filho A, Martinez R. Effectiveness of oral rinse with chlorhexidine in preventing nosocomial respiratory tract infections among intensive care unit patients. Infect Control Hosp Epidemiol. 2009 Oct;30(10):952-8. doi: 10.1086/605722. PMID: 19743899. 4. Bellissimo-Rodrigues WT, Menegueti MG, Gaspar GG, Nicolini EA, Auxiliadora-Martins M, Basile-Filho A, Martinez R, Bellissimo-Rodrigues F. Effectiveness of a dental care intervention in the prevention of lower respiratory tract nosocomial infections among intensive care patients: a randomized clinical trial. Infect Control Hosp Epidemiol. 2014 Nov;35(11):1342-8. doi: 10.1086/678427. Epub 2014 Oct 2. PMID: 25333428. 5. Bergmans DC, Bonten MJ, Gaillard CA, Paling JC, van der Geest S, van Tiel FH, Beysens AJ, de Leeuw PW, Stobberingh EE. Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med. 2001 Aug 1;164(3):382-8. doi: 10.1164/ajrccm.164.3.2005003. PMID: 11500337. 6. Berry AM, Davidson PM, Masters J, Rolls K, Ollerton R. Effects of three approaches to standardized oral hygiene to reduce bacterial colonization and ventilator associated pneumonia in mechanically ventilated patients: A randomised control trial. International Journal of Nursing Studies 2011;48(6):681-8 7. Berry AM. A comparison of Listerine and sodium bicarbonate oral cleansing solutions on dental plaque colonisation and incidence of ventilator associated pneumonia in mechanically ventilated patienst: a randomised control trial. Intensive and critical care nursing 2013;29(5):275-81 8. Bopp M, Darby M, Loftin KC, Broscious S. Effects of daily oral care with 0.12% chlorhexidine gluconate and a standard oral care protocol on the development of nosocomial pneumonia in intubated patients: a pilot study. J Dent Hyg. 2006 Summer;80(3):9. Epub 2006 Jul 1. PMID: 16953990. 9. Cabov T, Macan D, Husedzinović I, et al. The impact of oral health and 0.2% chlorhexidine oral gel on the prevalence of nosocomial infections in surgical intensive-

24

care patients: a randomized placebo-controlled study. Wien Klin Wochenschr. 2010;122(13-14):397-404. doi:10.1007/s00508-010-1397-y 10. Chen QL, Ye XF, Jiang YZ, Yan MQ. Application of new oral care method to orotracheal intubation. Fujian Medical Journal 2008;30(5):155-7 11. Chua JVDE, Sison CMC, Berba RP. The efficacy of povidone-iodine oral rinse in preventing ventilator-associated pneumonia: a randomized, double-blind, placebo-controlled (VAPOR) trial: preliminary report. Philipp J Microbiol Infect Dis 2004; 33:153-161 12. D'Journo XB, Falcoz PE, Alifano M, Le Rochais JP, D'Annoville T, Massard G, Regnard JF, Icard P, Marty-Ane C, Trousse D, Doddoli C, Orsini B, Edouard S, Million M, Lesavre N, Loundou A, Baumstarck K, Peyron F, Honoré S, Dizier S, Charvet A, Leone M, Raoult D, Papazian L, Thomas PA. Oropharyngeal and nasopharyngeal decontamination with chlorhexidine gluconate in lung cancer surgery: a randomized clinical trial. Intensive Care Med. 2018 May;44(5):578-587. doi: 10.1007/s00134-018-5156-2. Epub 2018 Apr 18. PMID: 29671041. 13. DeRiso AJ 2nd, Ladowski JS, Dillon TA, Justice JW, Peterson AC. Chlorhexidine gluconate 0.12% oral rinse reduces the incidence of total nosocomial respiratory infection and nonprophylactic systemic antibiotic use in patients undergoing heart surgery. Chest. 1996 Jun;109(6):1556-61. doi: 10.1378/chest.109.6.1556. PMID: 8769511. 14. Feng S, Sun X, Chen Y. Application of different mouthwashes in oral nursing for patients with orotracheal intubation. China Medicine and Pharmacy 2012;8(2):100-1. 15. Fourrier F, Cau-Pottier E, Boutigny H, Roussel-Delvallez M, Jourdain M, Chopin C. Effects of dental plaque antiseptic decontamination on bacterial colonization and nosocomial infections in critically ill patients. Intensive Care Med. 2000;26(9):1239-1247. doi:10.1007/s001340000585 16. Fourrier F, Dubois D, Pronnier P, et al. Effect of gingival and dental plaque antiseptic decontamination on nosocomial infections acquired in the intensive care unit: a double-blind placebo-controlled multicenter study. Crit Care Med. 2005;33(8):1728-1735. doi:10.1097/01.ccm.0000171537.03493.b0 17. Grap MJ, Munro CL, Hamilton VA, Elswick RK, Sessler CN, Ward KR. Early, single chlorhexidine application reduces ventilator-associated pneumonia in trauma patients. Hear Lung J Acute Crit Care. 2011;40(5):e115-e122. doi:10.1016/j.hrtlng.2011.01.006 18. Houston S, Hougland P, Anderson JJ, LaRocco M, Kennedy V, Gentry LO. Effectiveness of 0.12% chlorhexidine gluconate oral rinse in reducing prevalence of nosocomial pneumonia in patients undergoing heart surgery. Am J Crit Care. 2002 Nov;11(6):567-70. PMID: 12425407.

25

19. Jácomo AD, Carmona F, Matsuno AK, Manso PH, Carlotti AP. Effect of oral hygiene with 0.12% chlorhexidine gluconate on the incidence of nosocomial pneumonia in children undergoing cardiac surgery. Infect Control Hosp Epidemiol. 2011 Jun;32(6):591-6. doi: 10.1086/660018. PMID: 21558772. 20. Jones TR, Kaulbach H, Nichter L, Edlich RF, Cantrell RW. Efficacy of an antibiotic mouthwash in contaminated head and neck surgery. Am J Surg. 1989;158(4):324-327. doi:10.1016/0002-9610(89)90126-8 21. Kerver AJ, Rommes JH, Mevissen-Verhage EA, Hulstaert PF, Vos A, Verhoef J, Wittebol P. Prevention of colonization and infection in critically ill patients: a prospective randomized study. Crit Care Med. 1988 Nov;16(11):1087-93. doi: 10.1097/00003246-198811000-00001. PMID: 3168500. 22. Klarin B, Adolfsson A, Torstensson A, Larsson A. Can probiotics be an alternative to chlorhexidine for oral care in the mechanically ventilated patient? A multicentre, prospective, randomised controlled open trial. Crit Care. 2018 Oct 28;22(1):272. doi: 10.1186/s13054-018-2209-4. PMID: 30368249; PMCID: PMC6204275. 23. Koeman M, van der Ven AJ, Hak E, et al. Oral decontamination with chlorhexidine reduces the incidence of ventilator-associated pneumonia. Am J Respir Crit Care Med. 2006;173(12):1348-1355. doi:10.1164/rccm.200505-820OC 24. Kollef M, Pittet D, Sánchez García M, Chastre J, Fagon JY, Bonten M, Hyzy R, Fleming TR, Fuchs H, Bellm L, Mercat A, Mañez R, Martínez A, Eggimann P, Daguerre M, Luyt CE; Prevention of Pneumonia Study (POPS-1) Trial Group. A randomized double-blind trial of iseganan in prevention of ventilator-associated pneumonia. Am J Respir Crit Care Med. 2006 Jan 1;173(1):91-7. doi: 10.1164/rccm.200504-656OC. Epub 2005 Sep 28. PMID: 16192451. 25. Kosutic D, Uglesic V, Perkovic D, Persic Z, Solman L, Lupi-Ferandin S, Knezevic P, Sokler K, Knezevic G. Preoperative antiseptics in clean/contaminated maxillofacial and oral surgery: prospective randomized study. Int J Oral Maxillofac Surg. 2009 Feb;38(2):160-5. doi: 10.1016/j.ijom.2008.11.023. Epub 2009 Jan 22. PMID: 19167188. 26. Kusahara DM, Peterlini MA, Pedreira ML. Oral care with 0.12% chlorhexidine for the prevention of ventilator-associated pneumonia in critically ill children: randomised, controlled and double blind trial. Int J Nurs Stud. 2012;49(11):1354-1363. doi:10.1016/j.ijnurstu.2012.06.005 27. Laggner AN, Tryba M, Georgopoulos A, Lenz K, Grimm G, Graninger W, Schneeweiss B, Druml W. Oropharyngeal decontamination with gentamicin for long-term ventilated patients on stress ulcer prophylaxis with sucralfate? Wien Klin Wochenschr. 1994;106(1):15-9. PMID: 8135026.

26

28. Liu X, Xiu Z-X & Li L.The clinical application of chlorhexidine in the oral care of mechanically ventilated patients. Journal of Clinical Nursing (China) 2008; 7, 74, 44 29. Long Y, MouG, Zuo Y, lv F, Feng Q, Du J. Effect of modified oral nursing method on the patients with orotracheal intubation. J Nurses Train 2012;27(24):2290-3 30. Lorente L, Lecuona M, Jiménez A, et al. Ventilator-associated pneumonia with or without toothbrushing: A randomized controlled trial. Eur J Clin Microbiol Infect Dis. 2012;31(10):2621-2629. doi:10.1007/s10096-012-1605-y 31. MacNaughton P, Bailey J, Donlin N. , Intensive Care Med, A randomized controlled trial assessing efficacy of oral chlorhexidine in ventilated patients: European Society of Intensive Care Medicine 2004;30( suppl): S5–S18 32. Meinberg MC, Cheade Mde F, Miranda AL, Fachini MM, Lobo SM. The use of 2% chlorhexidine gel and toothbrushing for oral hygiene of patients receiving mechanical ventilation: effects on ventilator-associated pneumonia. Uso de clorexidina 2% gel e escovação mecânica na higiene bucal de pacientes sob ventilação mecânica: efeitos na pneumonia associada a ventilador. Rev Bras Ter Intensiva. 2012;24(4):369-374. doi:10.1590/s0103-507x2012000400013 33. Mo ZD, Li XL, KeMo ZD, Li XL, Ke JY, Wu JP, Chen XW. Analysis of risk factors in ventilator-associated pneumonia and preventive effect of oral care. Chinese Journal of Nosocomiology 2016;26(3):698-699, 705 34. Munro CL, Grap MJ, Jones DJ, McClish DK, Sessler CN. Chlorhexidine, toothbrushing, and preventing ventilator-associated pneumonia in critically ill adults. Am J Crit Care 2009;18 (5):428-37. doi: 10.4037/ajcc2009792. 35. Nicolosi LN, del Carmen Rubio M, Martinez CD, Gonzalez NN, Cruz ME. Effect of oral hygiene and 0.12% chlorhexidine gluconate oral rinse in preventing pneumonia after cardiovascular surgery. Respir Care 2-9014;59:504 36. Nie HM & Lv CM. The effect of chlorhexidine tooth brushing on prevention of ventilator-related pneum-nia. Contemporary Nurses Specialist (China), 2011; 1, 95–96 37. Okuda M, Kaneko Y, Ichinohe T, Ishihara K, Okuda K. Reduction of potential respiratory pathogens by oral hygienic treatment in patients undergoing endotracheal anesthesia. J Anesth. 2003;17(2):84-91. doi:10.1007/s005400300022 38. Özçaka Ö, Başoğlu OK, Buduneli N, Taşbakan MS, Bacakoğlu F, Kinane DF. Chlorhexidine decreases the risk of ventilator-associated pneumonia in intensive care unit patients: a randomized clinical trial. J Periodontal Res. 2012 Oct;47(5):584-92. doi: 10.1111/j.1600-0765.2012.01470.x. Epub 2012 Feb 29. PMID: 22376026. 39. Panchabhai TS, Dangayach NS, Krishnan A, Kothari VM, Karnad DR. Oropharyngeal cleansing with 0.2% chlorhexidine for prevention of nosocomial pneumonia in

27

critically ill patients: an open-label randomized trial with 0.01% potassium permanganate as control. Chest. 2009 May;135(5):1150-1156. doi: 10.1378/chest.08-1321. PMID: 19420193. 40. Pobo A, Lisboa T, Rodriguez A, et al. A randomized trial of dental brushing for preventing ventilator-associated pneumonia. Chest. 2009;136(2):433-439. doi:10.1378/chest.09-0706 41. Rios F, Maskin B, Sanez, Valiente A, Galante A, Cazes, Camaero P, Aguliar L, Peluffo G, Bendetti F, Hidalgo J, Lloria M, and Apeztegulia C. Prevention of ventilator associated pneumonia (VAP) by oral decontamination (OD): prospective, randomized, double-blind, placebo controlled study. American Thoracic Society 2005 International Conference; May 20 25; San Diego, California 2005;C95. 42. Rujipong P, Lekutai S, Pinyopasakul W, Rungruanghiranya S. The effect of using an oral care clinical nursing practice guideline on oral hygiene status and ventilator-associated pneumonia in intubated patients. J Nurs Sci 2009;27(Sup- pl 2):57-63 43. Sato M, Yoshihara A, Miyazaki H. Preliminary study on the effect of oral care on recovery from surgery in elderly patients [published correction appears in J Oral Rehabil. 2007 Jan;34(1):77]. J Oral Rehabil. 2006;33(11):820-826. doi:10.1111/j.1365-2842.2006.01634.x 44. Scannapieco FA, Yu J, Raghavendran K, et al. A randomized trial of chlorhexidine gluconate on oral bacterial pathogens in mechanically ventilated patients. Crit Care. 2009;13(4):1-12. doi:10.1186/cc7967 45. Sebastian MR, Lodha R, Kapil A, Kabra SK. Oral mucosal decontamination with chlorhexidine for the prevention of ventilator-associated pneumonia in children - a randomized, controlled trial. Pediatr Crit Care Med. 2012;13(5):e305-e310. doi:10.1097/PCC.0b013e31824ea119 46. Segers P, Speekenbrink RG, Ubbink DT, van Ogtrop ML, de Mol BA. Prevention of nosocomial infection in cardiac surgery by decontamination of the nasopharynx and oropharynx with chlorhexidine gluconate: a randomized controlled trial. JAMA. 2006 Nov 22;296(20):2460-6. doi: 10.1001/jama.296.20.2460. PMID: 17119142. 47. Seguin P, Tanguy M, Laviolle B, Tirel O, Mallédant Y. Effect of oropharyngeal decontamination by povidone-iodine on ventilator-associated pneumonia in patients with head trauma. Crit Care Med. 2006;34(5):1514-1519. doi:10.1097/01.CCM.0000214516.73076.82 48. Seguin P, Laviolle B, Dahyot-Fizelier C, et al. Effect of oropharyngeal povidone-iodine preventive oral care on ventilator-associated pneumonia in severely brain-injured or cerebral hemorrhage patients: a multicenter, randomized controlled trial. Crit Care Med. 2014;42(1):1-8. doi:10.1097/CCM.0b013e3182a2770f

28

49. Takeyasu Y, Yamane GY, Tonogi M, Watanabe Y, Nishikubo S, Serita R, Imura K. Ventilator-associated pneumonia risk decreased by use of oral moisture gel in oral health care. Bull Tokyo Dent Coll. 2014;55(2):95-102. doi: 10.2209/tdcpublication.55.95. PMID: 24965954. 50. Tang J, Chen SL, Deng JL. Efficacy of mouth cavity irrigation in prevention of ventilator-associated pneumonia. Chinese Journal of Nosocomiology 2013;23(17):4119-21 51. Tantipong H, Morkchareonpong C, Jaiyindee S, Thamlikitkul V. Randomized controlled trial and meta-analysis of oral decontamination with 2% chlorhexidine solution for the prevention of ventilator-associated pneumonia. Infect Control Hosp Epidemiol. 2008;29(2):131-136. doi:10.1086/526438 52. Tuon FF, Gavrilko O, Almeida S, Sumi ER, Alberto T, Rocha JL, Rosa EA. Prospective, randomised, controlled study evaluating early modification of oral microbiota following admission to the intensive care unit and oral hygiene with chlorhexidine. J Glob Antimicrob Resist. 2017 Mar;8:159-163. doi: 10.1016/j.jgar.2016.12.007. Epub 2017 Feb 20. PMID: 28216018. 53. Xu HL. Application of improved oral nursing method to the prevention of ventilator‐associated pneumonia. Journal of Qilu Nursing 2008;14(19):15‐6. 54. Yao L-Y, Chang C-K, Maa S-H, Wang C, Chen CC-H. Brushing teeth with purified water to reduce ventilator-associated pneumonia. J Nurs Res. 2011;19(4):289-297. doi:10.1097/JNR.0b013e318236d05f 55. Zaiton H, Elshamy K, Elesawy F, Sultan M. Effect of implementing an oral care protocol in minimizing rate of ventilator-associated pneumonia among mechanically ventilated patients at Mansoura emergency hospital. J Am Sci 2012;8:503-14 56. Zand F, Zahed L, Mansouri P, Dehghanrad F, Bahrani M, Ghorbani M. The effects of oral rinse with 0.2% and 2% chlorhexidine on oropharyngeal colonization and ventilator associated pneumonia in adults' intensive care units. J Crit Care. 2017 Aug;40:318-322. doi: 10.1016/j.jcrc.2017.02.029. Epub 2017 Mar 1. PMID: 28320561. 57. Zhou W, Wang SL, & Zhang P-W. (2009). Oral chlorhexidine on ventilator-associated pneumonia. Journal of Hospital Infection, 19, 1383-1384. 58. Zhu L. (2011). Application of chlorhexidine oral care to prevent ventilator-associated pneumonia. Guide to Chinese Medicine 9, 142-143. 59. Zouka M, Soultati I, Hari H, Pourzitaki C, Paroutsidou G, Thomaidou E, et al. Oral dental hygiene and ventilator‐associated pneumonia prevention in an ICU setting: Comparison between two methods (preliminary data of a randomised prospective study). Intensive Care Medicine 2010;36:S103

30

Appendix 1 : Characteristics of Included Randomized Controlled Trials

Quality Assessment (Risk of Bias) Green = Low risk, Yellow = Uncertain, Red = High Risk D1 : Randomization, D2 : Allocation Concealment, D3 : Blinding of participants and personnel, D4 : Blinding on outcome assessment, D5 : Completeness of followup, D6 : Other sources of bias

STUDY ID

POPULATION INTERVENTION

CONTROL

OUTCOMES

QUALITY ASSESSMENT (RoB) COMMENTS Inclusion Exclusion D1 D2 D3 D4 D5 D6

Abele-Horn 1997

N = 67 Intubation within 24 h of admission, expected time on a ventilator more than 4 days, and the interval between intubation and first microbial cultureless than 36 h. Anesthesiology ICU

Patients transferred from other hospitals and patients with obvious infections, prior antibiotic therapy, adult respiratory distress syndrome, leucopenia, or myelosuppression at the time of admission.

2% amphotericin B, 2% tobramycin, 2% polymyxin E Oropharyngeal decontamination 4 times a day, administered as pre-mixed paste (2% amphotericin B, 2 % tobramycin, and 2 % polymyxin E) to the palpate and to the lower lip.

Usually did not receive any antibiotics. If they had had surgery, they got one dose of perioperative prophylaxis: mezlocillin and metronidazole for abdominal surgery and cefazolin for orthopedics, bone, or head surgery. If infections were suspected, caused by unknown bacteria,initial therapy was begun with a combination of penicillins of cephalosporins and an aminoglycoside.

Vent days, ICU days

31

STUDY ID


CONTROL

OUTCOMES


Amora-Silva 2019

N = 30 Patients aged between 18 and 100 years, in the immediate preoperative period of oral and maxillofacial surgery performed at the Fortaleza’s Holly House of Mercy (Santa Casa da Misericordia de Fortaleza) - SCMF, under general anesthesia, consisting of open reduction and internal fixation (ORIF) of maxillofacial fractures with involvement of the oral cavity Not intubated

Patients undergoing maxillofacial surgery performed elsewhere, patients who have not had a fractured dentate region, who have not been submitted to ORIF, or who have no intraoral soft tissue sutures or injuries; patients under 18 or over 100 years of age; carriers of immunodeficiency, diabetes, or hematological disorders; edentulous patients; and/or with allergy to the components of the tested mouthwashes.

0.5% BISA (alpha bisabolol) mouthwash Test group 1: 0.5% BISA mouthwash 0.12% CHX + 0.5% BISA mouthwash Test group 2: 0.12% CHX + 0.5% BISA mouthwash Self administered

0.12% chlorhexidine 0.12% CHX mouthwash Self administered

Colony count

Bellissimo-Rodrigues 2009

N = 194 All patients admitted to ICU (adult clinical and surgical patients) with expected stay > 48 hours. respiratory failure 71%, compromised mental status 37%, shock 37%, surgery 14%

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

0.12% chlorhexidine 0.12% chlorhexidine solution applied orally 3 times daily; By patients if conscious, by nurses if unconscious / ventilated

Placebo solution, which was identical in colour, consistency, smell and taste By patients if conscious, by nurses if unconscious / ventilated

NP, VAP, Mort, Vent days, ICU days

32

STUDY ID


CONTROL

OUTCOMES


Bellissimo-Rodrigues 2014

N = 254 All adult patients admitted to a single general ICU if they had a perspective of staying at least 2 consecutive days.

Excluded were pregnant patients and those with blood dyscrasia

Toothbrushing Dental care by a dental surgeon 4-5x a week and oral hygiene protocol including toothbrushing, tongue scraping, removal of calculus, atraumatic restorative treatment of caries, teeth extraction, and oral topical application of CHX

0.12% or 2% chlorhexidine Routine oral hygiene protocol 3x a day by ICU nurse including mechanical cleansing of oral cavity with spatula wrapped in gauze followed by topical application of CHX 0.12% or 2% based on level of consciousness

VAP, Mort, Vent days

Bergmans 2001 N = 226 Mixed medical / surgical age >16 years intubated within 24 h of admission and who needed mechanical ventila-tion with an expected duration of 2 d

Not specified Orabase with gentamicin, colistin, and vancomycin Orabase with gentamicin, colistin, and vancomycin QID until extubation, death, limited to 21 days

Placebo in ICU with patients receiving topical antimicrobial prophylaxis Placebo in ICU with no topical antimicrobial prophylaxis

VAP, Mort, Vent days, ICU days

33

STUDY ID


CONTROL

OUTCOMES


Berry 2011 N = 109 The 20 bed surgical-medical ICU provides mechanical ventilation to over 800 adult patients annually trauma 25%, cardiac disease 20%, respiratory failure 40%, neurosurgery 35%, surgery 21% able to be randomised within 12 h of intubation, aged over 15 years and next of kin able to give informed consent

Required specific oral hygiene procedures in relation to facio-maxillary or dental trauma/surgery; had been in the ICU previously during the current period of hospitalization; received irradiation or chemotherapy on admission to the ICU or in the preceding 6 weeks; or suffered an autoimmune disease.

0.2% CHX solution oral rinse BID+ sterile water oral rinse two hourly 0.2% CHX solution oral rinse BID+ sterile water oral rinse two hourly Sodium bicarbonate mouthwash rinsed two hourly Administered by ICU nurses

Sterile water oral rinse two hourly Administered by ICU nurses

NP, VAP, Mort

Berry 2013 N = 398 All patients admitted to the medicalsurgical 20 bed adult ICU were assessed for inclusion in the study able to be randomised within 12 hours of intubation, aged over 15 years and next of kin able to give informed consent

Required specific oral hygiene procedures following facio-maxillary or dental trauma/surgery; had received irradiation or chemotherapy on admission to the ICU or in the preceding 6 weeks; diagnosed with autoimmune disease; had previous ICU admission during current period of hospitalisation

6.5g sodium bicarbonate mouth wash in 1 l of sterile water, 20 ml every 2 hours Listerine mouthwash, 20 ml instilled twice a day and sterile water every 2 hours for remaining time Administered by nurses

Sterile water mouth rinses, 20 ml every two hours. Administered by nurses

VAP

34

STUDY ID


CONTROL

OUTCOMES


Bopp 2006 N = 5 Orally and nasally intubated patients entering critical care unit

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

0.12% chlorhexidine Twice daily oral hygiene care with 0.12% chlorhexidine gluconate during intubation period plus oral cleaning with PlaqVac suction toothbrush Administered by critical care nursing staff

Standard oral care 6 times daily using a suctioning soR foam swab and half strength hydrogen peroxide, plus oral lubricant Administered by critical care nursing staff

NP, VAP, ICU stay

Small sample size of only 5 subjects (3 control, 2 treatment)

Cabov 2010 N = 60 Non-edentulous patients admitted to the ICU, aged >18 years, medical condition suggesting hospitalization in the ICU for at least 3 days, and eventual requirement for MV by oro or nasotracheal intubation

Not specified 0.2% chlorhexidine 0.2% CHX gel applied over dental, gingival, and oral surfaces after standard oral care (mouth rinsing using bicarbonate isotonic serum followed by aspiration) Administered by nurses

Placebo dental gel (same color, taste, and odor as CHX gel) Administered by nurses

NI, NP, VAP, ICU days, Mort, Colony count

35

STUDY ID


CONTROL

OUTCOMES


Chen 2008 N = 120 Admission into the ICU, orally intubated, receiving mechanical ventilation > 7 days, without oral and lung disease

Using hormone therapy; with diabetes

Chlorhexidine concentration not specified Oral cavity irrigated with 50 ml GSE rinse (chlorhexidine + extracts of grapefruit + FE enzyme) then aspirated oG, 4 times a day, and routine oral nursing care was given once a day after the first irrigation

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

VAP Treatment group received co-intervention of routine oral nursing care OD, but this was not done in the control group

Chua 2004 N = 42 Medical, surgical, neurological, neurosurgical, and central ICUs Medical 57%, surgical 12%, neurosurgical 21%

Not specified 1% povidone iodine 1% povidone iodine given as buccal swab TID

Placebo Mort, Vent days

36

STUDY ID


CONTROL

OUTCOMES


D’Journo 2018 N = 450 Adults older than 18 years and scheduled for major anatomical pulmonary resection surgery (anatomical segmentectomy, lobectomy, or pneumonectomy) for suspected primary lung cancer or pulmonary metastasis

Noninclusion criteria were age < 18 years, lower respiratory tract infection, emergency lung resection surgery, tracheostomy, impaired swallowing, need for noninvasive ventilation (NIV) before surgery, documented hypersensitivity to CHG, previous head and neck cancer, previous thoracic surgery, and oral assessment guide score ≥ 9

0.12% chlorhexidine gluconate and 4% chlorhexidine gluconate Chlorhexidine gluconate (CHG) 0.12% rinse solution for oropharyngeal decontamination and 4% CHG soap for nasopharyngeal decontamination.

Placebo of same color, taste, and smell

NI, NP, SSI, AEs, Mort

Deriso 1996 N = 353 Patients >18 years old who underwent cardiac surgery (CABG, valvular surgery, combined CABG and valvular surgery, septal surgery, cardiac tumor excision); Cardiac surgical ICU

Intraoperative death, preoperative infection or intubation, pregnancy, heart and lung transplant recipients, and known hypersensitivity to CHX

0.12% chlorhexidine 0.12% chx gluconate oral rinse preoperatively + two times a day until ICU discharge

Placebo of same color, taste, and smell

NI, NP, SSI, ICU days, Mort, Colony count

37

STUDY ID


CONTROL

OUTCOMES


Feng 2012 N = 136 Entry ICU, with orotracheal intubation and ventilation

Pulmonary infection, stomatitis or oral tumours before intubation, accompanied by ulcer of the digestive tract, malignant tumours of the body, taking

steroids ＞ 3 days,

diabetes

1/5000 furacillin Toothbrushing along the slits between the teeth with 1/5000 furacilin (antibiotic) by nurses 0.05% povidone iodine 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 4x a day

Toothbrushing + 0.9% saline 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

VAP

Fourrier 2000 N = 60 Medical or surgical ICU, >18 years old, anticipated stay in ICU 5 days, mechanical ventilation condition suggesting an ICU stay of 5 days

Edentulous patients

0.2% chlorhexidine 0.2% chx gel three times a day until ICU discharge Administered by nurses

Standard oral care (mouth rinsing with bicarbonate isotonic Administered by nurses

NP, VAP, ICU days, Mort, Vent days, Colony count

38

STUDY ID


CONTROL

OUTCOMES


Fourrier 2005 N = 228 60% medical ICU, 40% surgical ICU; >18 years old, anticipated stay in ICU 5 days, mechanical ventilation with ICU stay of 5 days; hospitalized for 48 hours before admission to ICU

Completely edentulous; suffering from facial trauma; postsurgical and requiring specific oropharyngeal care; and known allergy to chlorhexidine

0.2% chlorhexidine 0.2% CHX gel TID for max 28 days Administered by nurses

Placebo, same color, taste and smell Administered by nurses


Grap 2011 N = 39 Trauma ICU NSICU 38%, STICU 62%

Not specified 0.12% chlorhexidine Sterile application of 5 mL of 0.12% CHX solution OD

Standard oral care without CHX

NP, VAP, ICU days, Vent days

Houston 2002 N = 561 Patients who underwent aortocoronary bypass graft and/or valve surgery requiring cardiopulmonary bypass; Cardiac surgery ICU

Those who died during surgery, were pregnant, had preop respiratory infection documented in medical record or as reported by the patient

0.12% chlorhexidine 15 mL of 0.12% chx gluconate oral rinse preoperatively + two times a day for 10 days or until extubation, tracheostomy, death, or diagnosis

Solution of a phenolic mixture

NP, VAP, Mort, Colony count

39

STUDY ID


CONTROL

OUTCOMES


Jacomo 2011 N = 160 All children with congenital heart disease undergoing cardiac surgery with or without cardiopulmonary bypass consecutively admitted in the PICU in the postoperative period

Not specified 0.12% chlorhexidine 0.12% CHX gluconate alcoholic solution preoperatively and BID post operatively Administered by trained nurse or same physician (ADNJ)

Placebo solution same texture, color, flavor preoperatively and postoperatively

NP, VAP, Mort, ICU days, Vent days

Jones 1989 N = 12 Patients undergoing elective head and neck operations with planned entrance into the upper aerodigestive tract No mention of intubation or mechanical ventilation

Procedures that were intraoral and did not involve the soft tissues of the neck, upper aerodigestive tract not accessible to a topical mouthwash, such as the nasopharynx, nasal cavity, and sinuses white blood cell count of less than 3,500 cells/mm3, antibiotic administration within 5 days of the procedure, history of allergic or hypersensitivity reactions to the oral or parenteral antibiotics, a serum creatine level greater than 2 mg/dl, and a serum total bilirubin level greater than 2 mg/dl.

500mg neomycin, 500mg erythromycin Antibiotic mouthwash 30-ml dose of antibiotic mouthwash contained 500 mg of neomycin, 500 mg of erythromycin base, and wintergreen flavoring) Four doses of the mouthwash were given over a 12- hour interval, the last dose being given on call to the operating room. Patients instructed to swish then swallow

Placebo (similar volume of normal saline solution flavored with wintergreen Patients instructed to swish then swallow

Colony count Small sample size (7 experimental intervention, 5 placebo)

40

STUDY ID


CONTROL

OUTCOMES


Kerver 1988 N = 149 Patients admitted to the surgical ICU who required ICU care for >5 days Mechanically ventilated

Not specified Methylcellulose sodiumcarboxy paste containing 2% polymyxin E, 2% tobramycin and 2% amphotericin B

Placebo

NP, SSI, Mort, Colony count

Klarin 2018 N = 137 > 18, critically ill with an anticipated need for mechanical ventilation of at least 24 h; endotracheal intubation and mechanical ventilation initiated within 24 h before inclusion; and no standard oral care had been performed. Mixed Population ( liver transplant, Px undergoing Major surgery)

Not moribund; not having pneumonia as admission diagnosis; no fractures in the facial skeleton or the base of the skull; no oral ulcers; not immune deficient; not a carrier of HIV or viral hepatitis; not being tracheotomised

Lp299 Gauze swabs soaked in carbonated bottled water, after which Lp299 was applied to the mucosal surface of the oral cavity

Toothbrush + 1mg/ml chlorhexidine Toothbrush + all mucosal surfaces swabbed with moistened 1mg/ml CHX solution

VAP, Colony count, Vent days, ICU days

41

STUDY ID


CONTROL

OUTCOMES


Koeman 2006 N = 257 2 mixed and 2 surgical ICUs Trauma 10%, surgery 15%, cardiovascular 10%, pulmonary 34% Consecutive adult patients (18 yr of age) needing mechanical ventilation for at least 48 h were included within 24 h after intubation and start of mechanical ventilation

Preadmission immunocompromised status; pregnancy, and the inapplicable physical condition

2% chlorhexidine CHX 2% in petroleum jelly [Vaseline]FNA, CHX 2% with COL 2% in Vaseline FNA, and Vaseline FNA QID Approximately 2 cm of paste, approximately 0.5 g, was put on a gloved fingertip and administered to each side of the buccal cavity Administered by nurses

Placebo, same taste, smell, and consistency Administered by nurses


42

STUDY ID


CONTROL

OUTCOMES


Kollef 2006 N = 709 83% Non trauma, 27% trauma Mechanically ventilated 18 yr of age or older, orally/nasally intubated, randomized within 24 h of intubation and expected to remain mechanically ventilated for at least 48 h after the first dose of study medication, estimated to survive for at least 21 d, and not expected to be transferred to another institution during the 21-d study period.

Current diagnosis of pneumonia; an absolute neutrophil count less than 1,000/mm3; HIV infection with a last known CD4 count of less than 500/mm3; organ transplantation immunosuppressive therapy; current hematologic malignancy, cystic fibrosis, severe craniofacial trauma or other medical condition expected to require imminent tracheostomy, patient or patient’s family or physician not in favor of aggressive medical management, advanced directive to withhold life-sustaining treatment, morbid state or expected to survive less than 21 d because of an advanced comorbid medical condition, participation in a clinical trial of any unlicensed drug or device within 30 d before the first dose of study drug, or concurrent participation in a clinical trial of any unlicensed drug or device.

9mg iseganan Iseganan 3ml (9mg) six times daily until 14 days. Discontinued if patient develops VAP or was extubated

Placebo VAP, Mort

43

STUDY ID


CONTROL

OUTCOMES


Kosutic 2009 N = 60 Only patients with exclusively elective intra-oral surgical procedures under local or general anesthesia were included in the study. No mention if mechanically ventilated

Intraoperative death, preoperative infection or intubation, pregnancy, heart and lung transplant recipients, and known hypersensitivity to CHX

1% cetrimide solution 1% povidone iodine 0.12% chlorhexidine gluconate 0.12% chx gluconate oral rinse preoperatively + two times a day until ICU discharge

0.9% NaCl SSI, Colony count

Kusahara 2012 N = 96 Medical-surgical PICU children who were mechanically ventilated in a nine bed PICU at a 700-bed tertiary care hospital all who were likely to require intubation and mechanical ventilation within 24 h of admission

Newborn status, confirmed diagnosis of pneumonia at admission, known hypersensitivity to chlorhexidine, absence of parental consent, children with tracheostomies, duration of mechanical ventilation less than 48 h or children who had received tracheal intubation for more than 24 h prior to PICU admission

0.12% chlorhexidine 0.12% CHX gel BID with teeth brushing Administered by PICU nursing team

Placebo gel same color and odor twice daily with teeth brushing Administered by PICU nursing team

NP, VAP, Mort

Laggner 1994 N = 67 General ICU

Not specified Gentamicin gel QID until extubation

Placebo VAP, Mort, Vent days

Liu 2008 N = 60 General ICU

Not specified 0.12% chlorhexidine 0.12% CHX BID

Saline for routine care

VAP

44

STUDY ID


CONTROL

OUTCOMES


Long 2012 N = 61 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

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

0.1% povidone iodine + toothbrushing 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

0.1% povidone iodine Usual oral nursing method: swab with cotton balls soaked with 0.1% povidone iodine

VAP, Mort

Lorente 2012 N = 216 Medical-surgical ICU Consecutive patients undergoing invasive mechanical ventilation for at least 24 hours

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

0.12% chlorhexidine + toothbrushing 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)

0.12% chlorhexidine Oral cleansing performed with 0.12% chlorhexidine impregnated gauze, and oral cavity injection only

VAP, Mort, Vent days, Colony count

45

STUDY ID


CONTROL

OUTCOMES


Macnaughton 2004

N = 179 Medical-surgical ICU, patients needing mechanical ventilation >48 hours

Treatment of infection on admission to ICU, CHX hypersensitivity

0.2% chlorhexidine 0.2% CHX mouthwash BID administered by nurse

Placebo of identical appearance and smell administered by nurse

NP, VAP

Meinberg 2012 N = 52 Surgical ICU; > 18 years old, mechanical ventilation < 24 hours after admission, and expected to require ventilation for more than 72 hours.

Aspiration pneumonia, tracheostomy, pregnancy, and immunosuppression.

2% chlorhexidine + toothbrushing Toothbrushing plus chlorhexidine gel 2% 4 times daily Performed by nursing team

Placebo + toothbrushing Toothbrushing plus placebo gel 4 times daily Performed by nursing team

VAP, Mort, Vent days, ICU days

Study terminated for unclear reason related to “futility”

Mo 2016 N = 210 Department of Cardio-Thoracic Surgery mechanical ventilation > 48 hours

Patients with pulmonary infections or oral diseases

Saline Rinse with saline for 10 minutes each time, 4 times per day

Saline swab Swab with saline 4 times per day

Mort

46

STUDY ID


CONTROL

OUTCOMES


Munro 2009 N = 192 Critically ill adults (> 18) in 3 intensive care units enrolled within 24 hours of intubation. Patients receiving mechanical ventilation enrolled within 24 hours of intubation; older than 18 years in medical, surgical/trauma, and neuroscience ICUs

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

Usual care provided by study personnel

VAP, Mort, ICU stay

47

STUDY ID


CONTROL

OUTCOMES


Nicolosi 2014 N = 300 Scheduled for CVS [surgery] requiring sternotomy Coronary bypass, bypass with pump, valve replacement, combined, thoracic aortic surgery, mechanically ventilated

Requiring emergency surgery, died within 48 hours after surgery, with infection before surgery, received antibiotic therapy during 30 days before surgery, receiving immunosuppressives, hypersensitive to chlorhexidine gluconate, totally edentulous

0.12% chlorhexidine toothbrushing using modified Bass technique and dental floss, rinsing afterwards with 0.12% chlorhexidine gluconate every 12 hours for 3 days

Usual care (which includes mupirocin ointment and 3rd generation cephalosporin)

NI, NP, SSI, Mort, Vent days

Nie and Lv 2009

N = 200 General ICU

Pre-intubation Respiratory tract infection, coagulation abnormalities, palsy and swallowing dysfunction The MV time <48 hours, edentulous, orotracheal intubation recently

0.12% chlorhexidine Tooth brushing with 0.12% CHX, rinse with sterile water and moisturise lips with paraffin oil BID

Saline VAP

Okuda 2003 N = 32 Patients classified as ASA I or II who were scheduled to undergo oral surgery requiring endotracheal intubation

Not specified Oral cleansing with 200 ml of 0.5% povidone iodine including brushing of teeth using an electric toothbrush, scrubbing the periodontium, buccal mucosa, and tongue. Oral rinsing with 50ml of 0.5% povidone-iodine twice a day after surgery.

No oral cleansing Colony count

48

STUDY ID


CONTROL

OUTCOMES


Ozcaka 2012 N = 61 Respiratory ICU, dentate patients Intubated and mechanically ventilated

Chemical pneumonitis; postobstructive pneumonia; hypersensitivity to CHX; thrombocytopenia; pregnancy; oral mucositis; readmission survival expectation <1 week and edentulism

0.2% chlorhexidine 0.2% CHX swab QID Performed by ICU nurse staff

Normal saline QID Performed by ICU nurse staff

NP, VAP, Mort, Vent days, Colony count

Panchabai 2009

N = 471 Patients admitted to the Medical-Neuro ICU

Pregnant women, patients with pneumonia (community acquired or nosocomial) on hospital admission, and patients in whom oral care was contraindicated or who had a history of allergy to chlorhexidine

0.2% chlorhexidine 10mL of 0.2% CHX gluconate solution oral cleansing BID twice-daily oropharyngeal cleansing with a 0.2% chlorhexidine gluconate solution (Unilab Chemicals and Pharmaceuticals Ltd; Mumbai, India)

0.01 potassium permanganate solution BID oropharyngeal cleansing with 0.01% potassium permanganate solution twice daily in accordance with the standard protocol being followed in the ICU.


49

STUDY ID


CONTROL

OUTCOMES


Pobo 2009 N = 147 Intubated adults without evidence of pulmonary infection, expected to remain ventilated for > 48 hours

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

0.12% chlorhexidine Group 2 (n = 73): Standard oral care: maintaining head elevation at 30°. After aspiration of oropharyngeal secretions and adjustment of endotracheal cuG 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 Performed by nurses

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 Performed by nurses

VAP, SSI, Mort, Vent days

Possible confounding use of antibiotics - 28/73 and 25/74 in control and experimental groups receiving antibiotics at time of admission

50

STUDY ID


CONTROL

OUTCOMES


Rios 2005 N = 96 Medical or surgical (including trauma)

Not specified Polymyxin B + gentamicin gel Polymyxin B and gentamicin gel TID until 14 hours after extubation

Placebo


Rujipong 2009 N = 24 Critically ill patients with oral endotracheal intubation aged at least 15 years old, admitted into ICUs and general ward 1) No previous diagnosis of pneumonia; (2) intubated for more than 48 hours

(1) Cannot be placed in semi-fowler position; (2) must not have burns > 20% of total body surface; (3) Be re-intubated; (4) No teeth; (5) ulceration in oral cavity; (6) history of allergy to chlorhexidine mouth wash.

0.12% chlorhexidine Oral care based on the clinical nursing practice guideline toothbrushing with 0.12% chlorhexidine mouthwash for 15 minutes twice a day Performed by researcher

Routine oral care by using of cotton swabs with 0.004% chloroxylenol for 15 minutes twice a day. Performed by researcher

NP

51

STUDY ID


CONTROL

OUTCOMES


Sato 2006 N = 30 age >60 years, undergoing gastrointestinal surgery

Not specified Toothbrushing + 0.02% povidone iodine + cephem antibiotics oral care once daily from baseline (day of surgery) to day 5, included gargling with 0.02% povidone iodine, tooth brushing, denture cleaning using a special brush and tongue dorsum cleaning using a tongue brush. with cephem antibiotics

0.02% povidone iodine + cephem antibiotics gargling with 0.02% povidone iodine with cephem antibiotics

Colony count

Scannapieco 2009

N = 99 Trauma ICU Expected to be intubated and mechanically ventilated within 48 hours of admission

Chemical pneumonitis; post obstructive pneumonia; hypersensitivity to CHX; thrombocytopenia; pregnant; oral mucositis;

0.12% chlorhexidine Oral 0.12% CHX (3 ml CHX gluconate 20% added to 200ml of distilled water; 5 ml essence of peppermint with 5 ml 95% ethanol, and 15 ml glycerin) using a rinse-saturated oral foam applicator BID in group 1, OD in group 2; by ICU staff nurses

Placebo contained all ingredients, except for CHX, which was substituted with distilled water. Performed by ICU staff nurses

NP, Mort, Vent days

More use of antibiotics pre-study in control group

52

STUDY ID


CONTROL

OUTCOMES


Sebastian 2012 N = 86 Medical PICU aged 3 months to 15 years who required orotracheal or nasotracheal intubation and mechanical ventilation

Mechanically ventilated for over 24 hours prior to PICU admission, with tracheostomies, with inaccessible oral cavities, and with known hypersensitivity to chlorhexidine

1% chlorhexidine 0.5g of 1% CHX gel every 8 hours Administered by nursing staff

Placebo gel same appearance, consistency, taste and smell applied every 8 hours Administered by nursing staff


Segers 2006 N = 954 Patients older than 18 years old who were scheduled to undergo sternotomy for cardiothoracic surgery; Non emergent cardiac surgeries Participants in the study did not use mechanical ventilation

Emergency procedures, preoperative infection or use of antimicrobials or both, hypersensitivity to chlorhexidine gluconate, absence of written informed consent, treatment with an alternative prophylactic regimen like selective decontamination of the digestive tract

0.12% chlorhexidine 0.12% CHX gluconate oral rinse and nasal gel QID until extubation Applied by nurse using sponge if patient unable

Placebo, same color, taste and smell Applied by nurse using sponge if patient unable

NI, NP, VAP, SSI, ICU days, Mort, Vent days, Colony count

53

STUDY ID


CONTROL

OUTCOMES


Seguin 2006 N = 67 Surgical ICU Adults (> 18 years) with closed head trauma admitted to ICU and expected to need mechanical ventilation for at least 2 days

Admitted > 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

10% povidone iodine Povidone iodine 10% 20ml reconstituted with 60ml sterile water to nasopharynx and oropharynx 6 times daily until extubation

Control A: Nasopharynx and oropharynx rinsed 4-hourly with 60 ml saline, followed by aspiration of oropharyngeal secretions Control B: Standard regimen without any instillation but with aspiration of oropharyngeal secretions Administered by nurses


Seguin 2014 N = 150 > 18 years, closed traumatic brain injury (Glasgow Coma Score m 8), expected mechanical ventilation i 48 hours. Protocol amended to include patients with cerebral haemorrhage.

Patients in whom oral care procedure could not be performed within 12 hours after intubation, or had tetraplegia, facial trauma, pulmonary contusion involving > 1 lobe, aspiration pneumonia, current curative antimicrobial therapy, known allergy to povidone-iodine, pregnancy

10% Betadine oral antiseptic solution 20 mL of povidone iodine (10%) using a 60 mL syringe (final concentration 3.3%). injected in the buccal and pharyngeal cavities; suctioned every 4 hours; continued until extubation or until day 30. Administered by nurses

Placebo administered by nurses

VAP, Mort

54

STUDY ID


CONTROL

OUTCOMES


Takeyasu 2014 N = 168 Patients on mechanical ventilation with oral intubation for more than 10 hours in the ICU at Tokyo Dental College Ichikawa General Hospital

Not specified 1% povidone iodine Oral healthcare according to protocol using 30cc of 1% povidone-iodine solution / 2-fold diluted oxydol

Oral moisture gel Oral moisture gel Performed by a nurse trained by a dentist or a dental hygienist.

VAP, Vent days, Colony count

Exclusion criteria not mentioned, VAP not defined, unorthodox method for determining colony count

Tang 2013 N = 60 Adult ICU All patients admitted to the ICU with receipt of mechanical ventilation of at least 48 hours were assessed for inclusion in the study.

Unclear Saline Rinse oral cavity with saline

Saline swab Saline swab with saline cotton ball

Mort, Vent days

Tantipong 2008 N = 207 Medical and surgical ICUs and medical ward Medical 12%, surgical 50%, general medical wards 38%

Patients who had pneumonia at enrolment or who had a CHX allergy

2% chlorhexidine Brushing the teeth, suctioning any oral secretions, rubbing the oropharyngeal mucosa with 15 mL of 2% CHX solution QID

Oral care with normal saline

NP, VAP, AEs, Mort, Colony count

Only 60% of study participants received ventilation in ICU and only 53% of participants received MV for >48 hours

55

STUDY ID


CONTROL

OUTCOMES


Tuon 2017 N = 16 Hospital admission followed by MV, Age >18 years, Patients identified as high probability of MV for >48h, Permanent teeth (anterior and posterior) Mechanically ventilated

Failure to provide written informed consent, hospitalization >24 hours, recent use of antibiotics (<1 week), recent admission to another hospital or emergency room, suspected infection in the upper or lower respiratory, and less than four culture samples

2% chlorhexidine 15 ml of 2% CHX digluconate

0.9% NaCl

VAP

Xu 2008 N = 116 ICU of the second hospital of Shandong University Adults entering ICU receiving mechanical ventilation expected to last > 48 hours

Patients with pulmonary infections

Saline Rinse of the oropharyngeal cavity with saline for 5 - 10 seconds, followed by suction aspiration and repeated 5 - 10 times, twice daily

Saline soaked cotton ball Standard oral care comprising scrubbing with a cotton ball soaked in saline, twice daily

Vent days

Yao 2011 N = 53 Surgical ICU Expected length of ICU stay over 2 days, expected to receive mechanical ventilation for at least 48-72 hours with oral or nasal-tracheal intubation Mechanically ventilated

Patients already presented with pneumonia were excluded.

Toothbrushing + oral care protocol : head of bed elevated at 45 degrees, oral cavity moisturized by 10ml purified water, electric and soft toothbrush, toothette swab, hypopaharyngeal suctioning by trained nurse

Twice daily mock oral care by trained nurse


56

STUDY ID


CONTROL

OUTCOMES


Zaiton 2012 N = 80 Surgical ICU Mechanically ventilated patients, with oral endotracheal intubations; patients' aged were18 years and above, with no previous diagnosis or signs and symptoms of pneumonia and intubated for more than three day.

Nasal intubations, tracheotomies, ulceration or trauma in oral cavity, bleeding tendency and documented history of hematological disorders, oral surgeries, patients who cannot place in semi-fowler position, history of allergy to chlorhexidine mouth wash, patients who receive therapy for infection in the oral cavity, and reintubated patients

Chlorhexidine concentration not specified 15 mL CHX diluted in 50 mL of water every 12 hours by the researcher

Routine oral care with normal saline 0.9% OD by ICU nurses

NP, VAP, Vent days, ICU days

Zand 2017 N = 114 Patients aged 18 and above having a tracheal tube, being under mechanical ventilation for at least 48H Mechanically ventilated

Pneumonia on admission, hx of allergy to CHX, inflammation of the oral mucosa or trauma to the mouth, immune disorders caused by medications or illness, suffering from burn damages, pregnant, not admitted to ICU for the first time

0.2% chlorhexidine 0.2% CHX twice daily performed by researcher

2% chlorhexidine 2% CHX twice daily performed by researcher

VAP, AEs, Vent days

Zhou 2009 N = 99 ICU & CCU

Not specified 0.5% chlorhexidine 0.5% CHX QID according to the oral care process

Placebo VAP

57

STUDY ID


CONTROL

OUTCOMES


Zhu 2011 N = 93 ICU, CCU Mechanical ventilation >48 hours; no pneumonia related symptoms at admission

Not specified 2% chlorhexidine 2% CHX according to the oral care process TID

Saline VAP

Zouka 2010 N = 27 Medical-surgical ICU

Not specified 0.12 chlorhexidine 0.12% CHX solution in saline (3:1)

Hexetidine 0.1% solution

NP, VAP

58

Appendix 2 : Systematic and Narrative Reviews Considered in the Guidelines

Study ID General Topic No. of Trials

Alsheri 2018 Listerine to improve oral health 26

Andrews 2013

Oral decontamination and mechanical hygiene to reduce incidence of VAP

6 SR, 4 RCTs

Balamurugan 2012

CHX oral decontamination to reduce VAP 9

Bardia 2019 Preoperative CHX mouthwash to reduce pneumonia after cardiac surgery

5

Buckley 2013 CHX for the prevention of VAP 7

Chan 2007 Effect of oral decontaminaton on incidence of pneumonia and mortality in adults requiring mechanical ventilation in an ICU

11

Chlebicki 2007

Efficacy of topical CHX applied to oropharynx vs placebo / standard of care for prevention of VAP

7

Cotoia 2020 Nonantibiotic strategies to reduce VAP, including oral hygiene with CHX and selective oral decontamination

20

Cotti 2017 Preoperative dental treatment among cardiothoracic / vascular surgery patients

44

Hoshijima 2013

Effect of oral hygiene using CHX to prevent VAP in critical care settings

9

Hua 2016 Oral hygiene care (including different solutions, mechanical methods, etc.) to prevent VAP

38

Klompas 2017 Oropharyngeal decontamination with antiseptics such as CHX to prevent VAP

16

Kola 2007 Efficacy of oral chlorhexidine in preventing lower respiratory tract infection

7

Labeau 2011 Prevention of VAP using oral antiseptics 14

Li 2013 Oral topical antiseptics to prevent VAP 16

Pedersen 2016

Perioperative oral hygiene effect on reducing respiratory tract infections after elective thoracic surgery

6

Pineda 2006 Effect of oral decontamination using CHX on nosocomial pneumonia

4

Plantinga 2017

Selective digestive and oropharyngeal decontamination in medical and surgical ICU patients

6

Pop-Vicas 2020

Colorectal bundle (including oral care) for SSI prevention

40

Price 2014 Selective digestive or oropharyngeal decontamination and topical oropharyngeal CHX for prevention of death in general intensive care

29

59

Study ID General Topic No. of Trials

Rabello 2018 Effectiveness of oral CHX for the prevention of nosocomial pneumonia and VAP in ICUs

16

Roberts 2011 CHX and toothbrushing as prevention strategies in reducing VAP

8

Silvestri 2004 Effectiveness of oral CHX on nosocomial pneumonia, causative micro-organisms, and mortality in critically ill patients

22

Silvestri 2017 Impact of CHX on bloodstream infection in critically ill patients

5

Snyders 2011 Oral CHX in the prevention of VAP in critically ill ICU patients

7

Spredborough 2016

Perioperative oral decontamination in patients undergoing major elective surgery

4

Vilela 2015 Effect of oral care using CHX and other methods on nosocomial pneumonia

14

Zhang 2014 Effectiveness of different CHX concentrations on prevention of VAP

18

Zhao 2020 Selective oropharyngeal decontamination vs selective digestive decontamination in critically ill patients

4

60

Appendix 3 Technical Working Group and Consensus Panel Participants

Technical Working Group Dr. Marie Carmela Lapitan, Lead systematic reviewer and project lead - recipient of a research grant on surgical site infection from J&J in 2016

Dr. Joshua Vincent Baroña, systematic reviewer and project staff - no declared conflict of interest

Dr. Giselle Celine Cerrillo-Villanueva, systematic reviewer and project staff - no declared conflict of interest

Dr. Maria Carmela Uy, systematic reviewer and project staff - no declared conflict of interest

Dr. Brian S. Buckley, technical writer - no declared conflict of interest

Ms. Jenneth Cruz, project manager - no declared conflict of interest

Consensus Panel Participants (in alphabetical order) Dr. Robert Bandolon, Philippine Society of Colon and Rectal Surgeons - no declared conflict of interest

Dr. Arvin Briones, Philippine Society of Ultrasound for Surgery - no declared conflict of interest

Dr. Arturo P. Castro, Philippine Urological Association - no declared conflict of interest

Ms. Victoria I. Ching, Philippine Hospital Infection Control Society - no declared conflict of interest

Mr. Ricardo Corado, Philippine Hospital Infection Control Nurses Association, Inc - no declared conflict of interest

Dr. Maria Margarita Lat-Luna, Philippine Academy of Ophthalmology - no declared conflict of interest

Dr. Ida Marie Lim, Philippine Society of General Surgeons - no declared conflict of interest

Dr. Jeannette Marie Matsuo, Philippine Academy of Head and Neck Surgery, Inc - no declared conflict of interest

Dr. Renato Montenegro, Philippine College of Surgeons Committee on Surgical Infection - no declared conflict of interest

Mr. Gabriel Naig, Operating Room Nurses Association of the Philippines - no declared conflict of interest

Dr. Esther Saguil, Philippine Surgical Infection Society - commissioned to prepare a module on Hexetidine gargle by J&J Phils

Dr. Jose Antonio Salud, Philippine College of Surgeons - no declared conflict of interest

Dr. Karl Matthew C. Sy Su, Philippine Society of Anesthesiologists - no declared conflict of interest

Dr. Carmenchu Villavicencio, Philippine Society of Microbiology and Infectious Diseases, Inc - no declared conflict of interest

Ms. Jane Ethel Yraola, Operating Room Nurses Association of the Philippines - no declared conflict of interest

Commented [CJ[3]: Johnson & Johnson Philippines Inc.

Commented [CJ[4]: Johnson & Johnson Philippines Inc.

guidelines on oral hygiene for improving surgical …

Documents