Skip to main content
Download PDF

Chlorhexidine is not effective at any concentration in preventing ventilator-associated pneumonia: a systematic review and network meta-analysis

Journal of Anesthesia, Analgesia and Critical Care volume 4, Article number: 30 (2024) Cite this article

Abstract

Introduction

Oral chlorhexidine has been widely used for ventilator-associated pneumonia prevention in the critical care setting; however, previous studies and evidence synthesis have generated inconsistent findings. Our study aims to investigate if different concentrations of oral chlorhexidine may be effective in preventing such complication in intensive care unit patients.

Methods

After pre-registration (Open Science Framework: 8CUKF), we conducted a network meta-analysis with the following PICOS: adult patients (age > 18 years old) undergoing invasive mechanical ventilation admitted in ICU (P); any concentration of chlorhexidine used for oral hygiene (I); placebo, sham intervention, usual care, or no intervention (C); rate of VAP (primary outcome), mechanical ventilation length, ICU length of stay (LOS), hospital LOS, mortality (secondary outcomes) (O); randomized controlled trials (S). We used the following database: PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and EMBASE without any limitation in publication date or language.

Results

Chlorhexidine did not demonstrate any significant advantage over the control group in preventing ventilator-associated pneumonia or reducing mortality, duration of mechanical ventilation, length of stay in the intensive care unit, or overall mortality.

Conclusions

Chlorhexidine oral decontamination does not reduce the rate of ventilator-associated pneumonia in critically ill adult patients and its routine use could not be recommended.

Trial registration

Registration number: Open Science Framework: 8CUKF.

Introduction

Hospital-acquired infections contribute to prolonging hospital stays, increasing patients’ morbidity and mortality, and inflating hospitalization costs [1, 2]. Patients admitted to intensive care units (ICUs) face an increased risk of acquiring such an infection that in some studies has been estimated to be around 30% [3].

Lower respiratory system is the most common site of infection in ICU patients [4].

Ventilator-associated pneumonia (VAP) is a distinct form of pneumonia occurring in patients undergoing invasive mechanical ventilation. Micro-organisms access the respiratory system through entry points, such as the endotracheal tube, or via leakage of secretions around the endotracheal cuff [5]. Numerous factors contribute to the development of VAP in critically ill patients, e.g., the aspiration of gastrointestinal microbes, compromised cough reflex, the inability to effectively clear secretions through the pharynx and mouth, and inadequate oral care [5].

The occurrence of VAP is associated with a mortality risk ranging from 1 to 10% [6]. One of the proposed strategies for VAP prophylaxis is the use of oral chlorhexidine washes to prevent the growth and aspiration of bacteria. Being simple and low-cost, the vast majority of ICUs have adopted daily oral care with chlorhexidine in their patients [7]. Despite the robust rationale, the assessment of oral antiseptics use as a preventive strategy for VAP has generated inconsistent findings in prior studies [8,9,10]. Moreover, a meta-analysis, overall including 16 randomized controlled trials and 3630 patients, did not support the use of chlorhexidine for the prevention of VAP in non-cardiac surgery patients [11]. However, this work did not consider the effect of the different concentrations of oral chlorhexidine employed in the included studies.

The objective of this network meta-analysis is to assess whether different concentrations of oral chlorhexidine may be effective in preventing VAP in ICU patients. Secondary outcomes were duration of invasive mechanical ventilation, ICU length of stay, and hospital length of stay and mortality.

Methods

The protocol for this network meta-analysis has been prospectively registered on Open Science Framework [12], and the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement guidelines was followed for the reporting of the present manuscript [13].

Eligibility criteria

Studies were considered to be eligible for inclusion using the following PICOS criteria: adult patients (age > 18 years old) undergoing invasive mechanical ventilation admitted in ICU (P); any concentration of chlorhexidine used for oral hygiene (I); placebo, sham intervention, usual care, or no intervention (C); rate of VAP (primary outcome), mechanical ventilation length, ICU length of stay (LOS), hospital LOS, mortality (secondary outcomes) (O); randomized controlled trials (S).

Search strategy

We performed a systematic search of the medical literature for the identification, screening, and inclusion of articles. We did not apply any restriction related to language or year of publication. We queried the following database from inception to May 17, 2023: PubMed, The Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and EMBASE.

Study selection

Three researchers (CL, AS, CP) independently screened titles and abstracts of the identified papers in order to select relevant manuscripts. Each citation was reviewed in full-text form if considered potentially relevant. All the references of the included literature were examined to retrieve further relevant studies. The search strategy for each database is available as supplementary material. After identifying those studies meeting inclusion criteria, two authors (VB, AB) manually reviewed and assessed each of the included studies.

Quality assessment and certainty of evidence assessment

Risk of bias was assessed independently by two members of the team not previously involved in the study selection phase (ADC, TP). The assessment was performed using the Risk of Bias (RoB) 2 Tool, expressing the overall risk of bias on a three-grade scale (“low risk of bias,” “high risk of bias,” or “some concerns”) [14]. In case of disagreements after discussion among assessors, a third researcher (PN) was consulted.

Statistical methods

Meta-analysis of data was performed using R version 4.1 (R Foundation for Statistical Computing, Vienna, Austria) and the package “netmeta.” The treatment effect for continuous outcomes was measured using mean difference (MD) with 95% confidence interval (CI). For dichotomous outcomes, we expressed the treatment effect as odds ratio (OR) with 95% CI. Availability of evidence, transitivity assumption, intra-network connectivity, and network coherence were considered to assess the feasibility of conducting a network meta-analysis [15]. To rank comparators, we conducted a ranking analysis using the frequentist analogue of the surface under the cumulative ranking curve (SUCRA) [16]. In case of data expressed as median and quartiles, we utilized Hozo’s method [17] to estimate the mean and standard deviation (SD). Additionally, we abstained from applying continuity correction to cases with zero events.

Sensitivity analysis

We decided to perform the following post hoc sensitivity analysis for the primary outcome: (a) excluding postoperative patients, (b) excluding high risk-of-bias studies, (c) excluding all comparators other than placebo/no intervention.

Heterogeneity and publication bias analysis

For assessment of study inconsistency and heterogeneity, the I2 and Tau2 statistics were used. Values of I2 were categorized as follows: low heterogeneity: I2 < 25%, moderate heterogeneity: I2 25 to 50%, or high heterogeneity: I2 > 50%) [18]. A random-effect model was preferred, regardless of heterogeneity. Publication bias was evaluated both by visual inspection of funnel plots or Egger’s test when more than ten studies were available for a specific outcome.

Results

Study characteristics

PRISMA flowchart of the included studies is depicted in Fig. 1. We selected 181 articles for full-text assessment. Of these, only 23 articles met our inclusion criteria [8,9,10, 19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38]. However, one study was excluded, as it presented a mixed intubated/not intubated cohort of patients, and the corresponding author was unable to provide us with the subset of intubated patients only [38]. Therefore, 22 articles (5314 patients) were eventually included for qualitative and quantitative analysis.

Fig. 1
figure 1

PRISMA flowchart

Full size image

Characteristics of the included studies are reported in Table 1. The identified chlorhexidine concentrations were as follows: 0.12% (nine studies) [8, 20, 22, 24,25,26,27,28, 33], 0.2% (eight studies) [9, 10, 21, 23, 29, 30, 36, 37], 2% (six studies) [19, 30,31,32, 34, 35]. Among these studies, only one performed a direct comparison among chlorhexidine concentrations, i.e., 0.2% vs 2.0% [30].

Table 1 Study characteristics
Full size table

Risk of bias assessment

The overall risk of bias assessment is summarized in Fig. 2 and detailed in Additional file 2. Six studies were evaluated to be at high risk of bias, thirteen studies to some concern, while the remaining studies were evaluated to be at low risk of bias.

Fig. 2
figure 2

Overall risk of bias assessment

Full size image

Outcomes

Results for all the outcomes are summarized in Table 2, and the SUCRA analysis is shown in Table 3. Publication bias was detected for no outcomes (Additional file 3).

Table 2 Study outcomes
Full size table
Table 3 Surface under the cumulative ranking curve analysis
Full size table

VAP

Twenty-one studies evaluated VAP in 6626 patients overall (367 patients assigned to the 2.0% concentration, 464 to the 0.2%, 2471 to the 0.12%, and 3324 assigned to the control group). None of the concentrations of chlorhexidine was associated with a statistically significant reduction in VAP, when compared to either non-chlorhexidine comparators or other chlorhexidine concentrations (Table 1). Heterogeneity was high (I2 66.8%, Tau2 0.39). The estimation of direct and indirect evidence is available as supplementary material (Additional file 4), while the graph describing the network among intervention is presented as Additional file 5. There was no evidence of publication bias at the funnel plot (Egger test p-value 0.635).

Mechanical ventilation duration

Twelve studies evaluated the mechanical ventilation duration and randomized 5379 patients (255 to the 2.0% concentration, 188 to the 0.2%, 2191 to the 0.12%, while 2745 were assigned to the control group). The utilization of chlorhexidine at any concentration was not found to reduce mechanical ventilation duration, in comparison with the control group. Heterogeneity was high (I2 56%; Tau2 1.23). No publication was detected at funnel plot (p-value 0.456).

ICU LOS

Ten studies reported results for ICU LOS, randomizing a total of 2040 patients (255 to the 2.0% concentration, 188 to the 0.2%, 594 to the 0.12%, and 1003 to the control group). We did not observe shorter ICU LOS in patients receiving any concentration of chlorhexidine, when compared to the control group. Heterogeneity was low (I2 21.7%, Tau2 1.02), and there were no signs of publication bias (p-value 0.457).

Hospital LOS

Analysis of seven studies, randomizing a total of 1834 patients (155 to the 2.0% concentration, 70 to the 0.2%, 695 to the 0.12%, while 914 to the control group), found only a statistically significant but clinically unimportant reduced LOS in 0.12% patients (− 0.60; CI − 0.72; − 0.47 days). In this analysis, there was low heterogeneity (I2 0%, Tau2 0) without publication bias at the visual inspection of the funnel plot.

Mortality

Fourteen studies reported data for this outcome, enrolling 5978 patients overall (185 in the 2.0% group, 347 in the 0.2% group, 2447 in the 0.12% group, while 2999 patients in the control group). No significant effect was detected for any of the intervention. Low heterogeneity was reported (I2 21.4%, Tau2 0.045) and no publication bias (p-value 0.490).

Sensitivity analysis

Results for the sensitivity analyses are reported in Table 4. Briefly, none of the subgroup analyses was able to determine the superiority of chlorhexidine at any concentration over controls.

Table 4 Sensitivity analysis for the primary outcome
Full size table

Discussion

This systematic review and network meta-analysis including 5314 adult patients from 21 RCTs found that no concentration of chlorhexidine was associated with reduced rate of VAP, in comparison either with other chlorhexidine concentrations or with no-chlorhexidine interventions. Moreover, compared to other chlorhexidine concentrations or no-chlorhexidine interventions, no concentration of chlorhexidine improved mechanical ventilation duration, LOS, and mortality.

Since the finding is that no concentration of chlorhexidine is effective in preventing VAP or any of the other investigated outcomes, our network meta-analysis contributes additional evidence to a previous pairwise meta-analysis, published in 2014 [11], already questioning the impact of chlorhexidine on preventing VAP in non-cardiac surgery patients.

Previous meta-analysis [39, 40] showed that certain mode of chlorhexidine delivery (solution but no gel or rinse) or frequency of use (4 times/die) could have an impact on VAP incidence; however, the paucity of mode of deliveries and frequency of administrations when subcategorized for chlorhexidine solutions prevented us to conduct such subgroups analysis. This remains for sure an interesting point for future research.

Moreover, 0.12% chlorhexidine concentration group is more represented (2590 patients), compared to the 0.2% (464 patients) and 2% (367 patients) groups. Therefore, expanding the sample size for the other groups might reveal significant benefits on the rate of VAP. However, higher chlorhexidine concentrations may increase the risk of oral lesions [40], selecting the growth of germs resistant to chlorhexidine [41, 42].

Over the years, there have been significant changes in guidelines regarding the use of chlorhexidine for preventing VAP in ventilated patients.

When examining the guidelines, it is essential to note that the “Zero-VAP” bundle (Spanish guidelines) [43] suggested the standard use of chlorhexidine to prevent VAP, recommending concentrations as high as 2%. However, not all the scientific societies agreed with such a recommendation. In fact, in the same year (2014), the SHEA/IDSA guidelines [44] categorized oral care with chlorhexidine under special approaches instead of basic practices due to potential risks and unclear benefits.

A more recent European guideline [45] does not provide a formal recommendation on the use of chlorhexidine for oral care in mechanically ventilated patients due to a lack of safety data and an unclear balance between the potential reduction in VAP and the potential increase in mortality. The latest update from SHEA [46] does not recommend the use of oral chlorhexidine as it may increase mortality rates. Our study aligns with the most recent guidelines and further strengthened these recommendations.

Our research has some limitations that warrants discussion. First, intransitivity may have arisen from the inclusion of studies published over a 26-year period. Over this period, there could have been substantial modifications to VAP prevention bundles, antimicrobial therapies, and other clinical practices, potentially impacting the research outcomes. Second, the main analysis on primary outcome showed high heterogeneity that was not explained by our subgroup analyses, reducing the overall confidence in our results. The among-studies heterogeneity in protocols for chlorhexidine oral decontamination and antimicrobial stewardship and outcome definitions may explain such finding. Third, we included all non-chlorhexidine interventions, i.e., placebo, sham intervention, usual care, and no intervention, in the same group.

Conclusion

Chlorhexidine oral decontamination does not reduce the rate of VAP in critically ill adult patients in the ICU, and we could not recommend its routine use. Nevertheless, further research is warranted, particularly investigating the potential benefits of chlorhexidine at higher concentrations.

Availability of data and materials

No datasets were generated or analysed during the current study.

Abbreviations

ICU:

Intensive care unit

LOS:

Length of stay

MD:

Mean difference

OR:

Odds ratio

SD:

Standard deviation

SUCRA:

Surface under the cumulative ranking curve

VAP:

Ventilator-associated pneumonia

References

  1. Melsen WG, Rovers MM, Groenwold RH et al (2013) Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies. Lancet Infect Dis 13:665–671. https://doi.org/10.1016/S1473-3099(13)70081-1

    Article  PubMed  Google Scholar 

  2. Emmerson AM, Enstone JE, Griffin M, Kelsey MC, Smyth ET (1996) The Second National Prevalence Survey of infection in hospitals–overview of the results. J Hosp Infect 32:175–190. https://doi.org/10.1016/s0195-6701(96)90144-1049

    Article  CAS  PubMed  Google Scholar 

  3. Aly NY, Al-Mousa HH, Asar Al, el SM, (2008) Nosocomial infections in a medical-surgical intensive care unit. Med Princ Pract 17:373–377. https://doi.org/10.1159/000141500

    Article  PubMed  Google Scholar 

  4. Farag AM, Tawfick MM, Abozeed MY, Shaban EA, Abo-Shadi MA (2020) Microbiological profile of ventilator-associated pneumonia among intensive care unit patients in tertiary Egyptian hospitals. J Infect Dev Ctries 14:153–161. https://doi.org/10.3855/jidc.12012

    Article  PubMed  Google Scholar 

  5. Wu D, Wu C, Zhang S, Zhong Y (2019) Risk factors of ventilator-associated pneumonia in critically iii patients. Front Pharmacol 10:482. https://doi.org/10.3389/fphar.2019.00482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Muscedere J, Sinuff T, Heyland DK et al (2013) The clinical impact and preventability of ventilator-associated conditions in critically ill patients who are mechanically ventilated. Chest 144:1453–1460. https://doi.org/10.1378/chest.13-0853

    Article  PubMed  Google Scholar 

  7. Small J, Campbell R, Paton L, Mackay A (2015) A survey of chlorhexidine oral care in Scottish intensive care units. ICMx 3(Suppl 1):A710. https://doi.org/10.1186/2197-425X-3-S1-A710

    Article  PubMed Central  Google Scholar 

  8. Segers P, Speekenbrink RGH, Ubbink DT, Van Ogtrop ML, De Mol BA (2006) Prevention of nosocomial infection in cardiac surgery by decontamination of the nasopharynx and oropharynx with chlorhexidine gluconate: a randomized controlled trial. JAMA 269:2460–2466. https://doi.org/10.1001/jama.296.20.2460

    Article  Google Scholar 

  9. Fourrier F, Dubois D, Pronnier P et al (2005) 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 33:1728–1735

    Article  PubMed  Google Scholar 

  10. Tantipong H, Morkchareonpong C, Jaiyindee S, Thamlikitkul, (2008) Randomized controlled trial and meta-analysis of oral decontamination with 2% chlorhexidine solution for the prevention of ventilator-associated pneumonia. Infect Control Hosp Epidemiol 29:131–136

    Article  PubMed  Google Scholar 

  11. Klompas M, Speck K, Howell MD, Greene LR, Berenholtz SM (2014) Reappraisal of routine oral care with chlorhexidine gluconate for patients receiving mechanical ventilation: systematic review and meta-analysis. JAMA Intern Med 174:751–761. https://doi.org/10.1001/jamainternmed.2014.359

    Article  CAS  PubMed  Google Scholar 

  12. De Cassai A (2023) Effectiveness of different concentrations of chlorhexidine for prevention of ventilator-associated pneumonia: a network meta-analysis. Open Science Framework. https://doi.org/10.17605/OSF.IO/8CUKF

  13. Liberati A, Altman DG, Tetzlaff J et al (2009) The PRISMA statement for reporting systematic reviews and meta - analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700. https://doi.org/10.1136/bmj.b2700

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sterne JAC, Savović J, Page MJ et al (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 366:l4898. https://doi.org/10.1136/bmj.l4898

    Article  PubMed  Google Scholar 

  15. Chaimani A, Caldwell DM, Li T, Higgins JPT, Salanti G (2022) Chapter 11: Undertaking network meta-analyses. In: Higgins JPT, Thomas J, Chandler J, et al., eds. Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane. Available from www.training.cochrane.org/handbook. Accessed 11 Apr 2023

  16. Rücker G, Schwarzer G (2015) Ranking treatments in frequentist network meta - analysis works without resampling methods. BMC Med Res Methodol 15:58. https://doi.org/10.1186/s12874-015-0060-8

    Article  PubMed  PubMed Central  Google Scholar 

  17. Hozo SP, Djulbegovic B, Hozo I (2005) Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 5:13. https://doi.org/10.1186/1471-2288-5-13

    Article  PubMed  PubMed Central  Google Scholar 

  18. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta - analyses. BMJ 327:557–560. https://doi.org/10.1136/bmj.327.7414.557

    Article  PubMed  PubMed Central  Google Scholar 

  19. Meinberg MC, Cheade Mde F, Miranda AL, Fachini MM, Lobo SM (2012) The use of 2% chlorhexidine gel and toothbrushing for oral hygiene of patients receiving mechanical ventilation: effects on ventilator-associated pneumonia. Rev Bras Ter Intensiva 24:369–374. https://doi.org/10.1590/s0103-507x2012000400013

    Article  PubMed  PubMed Central  Google Scholar 

  20. Scannapieco FA, Yu J, Raghavendran K et al (2009) A randomized trial of chlorhexidine gluconate on oral bacterial pathogens in mechanically ventilated patients. Crit Care 13:R117. https://doi.org/10.1186/cc7967

    Article  PubMed  PubMed Central  Google Scholar 

  21. Özçaka Ö, Başoğlu OK, Buduneli N, Taşbakan MS, Bacakoğlu F, Kinane DF (2012) Chlorhexidine decreases the risk of ventilator-associated pneumonia in intensive care unit patients: a randomized clinical trial. J Periodontal Res 47:584–592. https://doi.org/10.1111/j.1600-0765.2012.01470.x

    Article  CAS  PubMed  Google Scholar 

  22. De Riso AJ, II, Ladowski JS, Dillon TA, Justice JW, Peterson AC, (1996) 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 109:1556–1561

    Article  Google Scholar 

  23. Panchabhai TS, Dangayach NS, Krishnan A, Kothari VM, Karnad DR (2009) Oropharyngeal cleansing with 0.2% chlorhexidine for prevention of nosocomial pneumonia in critically ill patients: an open-label randomized trial with 0.01% potassium permanganate as control. Chest 135:1150–1156. https://doi.org/10.1378/chest.08-1321. (PMID: 19420193)

    Article  CAS  PubMed  Google Scholar 

  24. Bellissimo-Rodrigues F, Bellissimo-Rodrigues WT, Viana JM et al (2009) Effectiveness of oral rinse with chlorhexidine in preventing nosocomial respiratory tract infections among intensive care unit patients. Infect Control Hosp Epidemiol 30:952–958. https://doi.org/10.1086/605722

    Article  PubMed  Google Scholar 

  25. Dale CM, Rose L, Carbone S et al (2021) Effect of oral chlorhexidine de-adoption and implementation of an oral care bundle on mortality for mechanically ventilated patients in the intensive care unit (CHORAL): a multi-center stepped wedge cluster-randomized controlled trial. Intensive Care Med 47:1295–1302. https://doi.org/10.1007/s00134-021-06475-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Munro CL, Grap MJ, Jones DJ, McClish DK, Sessler CN (2009) Chlorhexidine, toothbrushing, and preventing ventilator-associated pneumonia in critically ill adults. Am J Crit Care 18:428–437. https://doi.org/10.4037/ajcc2009792. (quiz 438)

    Article  PubMed  PubMed Central  Google Scholar 

  27. Zarinfar N, Ghaznavi-Rad E, Mahmoodiyeh B, Reyhani A (2021) Comparison of three interventional approaches to prevent ventilator-associated pneumonia in intensive care units (ICUs): a clinical trial study. Qatar Med J 2021:21. https://doi.org/10.5339/qmj.2021.21

    Article  PubMed  PubMed Central  Google Scholar 

  28. Grap MJ, Munro CL, Hamilton VA, Elswick RK Jr, Sessler CN, Ward KR (2011) Early, single chlorhexidine application reduces ventilator-associated pneumonia in trauma patients. Heart Lung 40:e115–e122. https://doi.org/10.1016/j.hrtlng.2011.01.006

    Article  PubMed  Google Scholar 

  29. Jahanshir M, Nobahar M, Ghorbani R, Malek F (2023) Effect of clove mouthwash on the incidence of ventilator-associated pneumonia in intensive care unit patients: a comparative randomized triple-blind clinical trial. Clin Oral Investig 27:3589–3600. https://doi.org/10.1007/s00784-023-04972-w

    Article  PubMed  Google Scholar 

  30. Zand F, Zahed L, Mansouri P, Dehghanrad F, Bahrani M, Ghorbani M (2017) 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 40:318–322. https://doi.org/10.1016/j.jcrc.2017.02.029

    Article  CAS  PubMed  Google Scholar 

  31. Lin YJ, Xu L, Huang XZ et al (2015) Reduced occurrence of ventilator-associated pneumonia after cardiac surgery using preoperative 0.2% chlorhexidine oral rinse: results from a single-centre single-blinded randomized trial. J Hosp Infect 91:362–366. https://doi.org/10.1016/j.jhin.2015.08.018

    Article  CAS  PubMed  Google Scholar 

  32. Tuon FF, Gavrilko O, Almeida S et al (2017) 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 8:159–163. https://doi.org/10.1016/j.jgar.2016.12.007

    Article  PubMed  Google Scholar 

  33. Pobo A, Lisboa T, Rodriguez A et al (2009) A randomized trial of dental brushing for preventing ventilator-associated pneumonia. Chest 136:433–439. https://doi.org/10.1378/chest.09-0706

    Article  PubMed  Google Scholar 

  34. Meidani M, Khorvash F, Abbasi S, Cheshmavar M, Tavakoli H (2018) Oropharyngeal irrigation to prevent ventilator-associated-pneumonia: comparing potassium permangenate with chlorhexidine. Int J Prev Med 9:93. https://doi.org/10.4103/ijpvm.IJPVM_370_17.PMID:30450176;PMCID:PMC6202778

    Article  PubMed  PubMed Central  Google Scholar 

  35. Koeman M, van der Ven AJ, Hak E et al (2006) Oral decontamination with chlorhexidine reduces the incidence of ventilator-associated pneumonia. Am J Respir Crit Care Med 173:1348–1355. https://doi.org/10.1164/rccm.200505-820OC

    Article  CAS  PubMed  Google Scholar 

  36. Fourrier F, Cau-Pottier E, Boutigny H, Roussel-Delvallez M, Jourdain M, Chopin C (2000) Effects of dental plaque antiseptic decontamination on bacterial colonization and nosocomial infections in critically ill patients. Intensive Care Med 26:1239–1247. https://doi.org/10.1007/s001340000585

    Article  CAS  PubMed  Google Scholar 

  37. Berry AM, Davidson PM, Masters J, Rolls K, Ollerton R (2011) Effects of three approaches to standardized oral hygiene to reduce bacterial colonization and ventilator associated pneumonia in mechanically ventilated patients: a randomised control trial. Int J Nurs Stud 48:681–688. https://doi.org/10.1016/j.ijnurstu.2010.11.004

    Article  CAS  PubMed  Google Scholar 

  38. Cabov T, Macan D, Husedzinović I et al (2010) The impact of oral health and 0.2% chlorhexidine oral gel on the prevalence of nosocomial infections in surgical intensive-care patients: a randomized placebo-controlled study. Wien Klin Wochenschr 122:397–404. https://doi.org/10.1007/s00508-010-1397-y

    Article  CAS  PubMed  Google Scholar 

  39. Lee S, Lighvan NL, McCredie V et al (2019) Chlorhexidine-related mortality rate in critically ill subjects in intensive care units: a systematic review and meta-analysis. Respir Care 64:337–349. https://doi.org/10.4187/respcare.06434

    Article  PubMed  Google Scholar 

  40. Villar CC, Pannuti CM, Nery DM, Morillo CM, Carmona MJ, Romito GA (2016) Effectiveness of Intraoral chlorhexidine protocols in the prevention of ventilator-associated pneumonia: meta-analysis and systematic review. Respir Care 61:1245–1259. https://doi.org/10.4187/respcare.04610

    Article  PubMed  Google Scholar 

  41. Plantinga NL, Wittekamp BHJ, Leleu K et al (2016) Oral mucosal adverse events with chlorhexidine 2% mouthwash in ICU. Intensive Care Med 42:620–621. https://doi.org/10.1007/s00134-016-4217-7

    Article  PubMed  PubMed Central  Google Scholar 

  42. Cieplik F, Jakubovics NS, Buchalla W, Maisch T, Hellwig E, Al-Ahmad A (2019) Resistance toward chlorhexidine in oral bacteria - is there cause for concern? Front Microbiol 10:587. https://doi.org/10.3389/fmicb.2019.00587

    Article  PubMed  PubMed Central  Google Scholar 

  43. Alvarez Lerma F, Sanchez Garcia M, Lorente L et al (2014) Guidelines for the prevention of ventilator-associated pneumonia and their implementation. The Spanish “Zero-VAP” bundle. Med Intensiva 38:226–236. https://doi.org/10.1016/j.medin.2013.12.007

    Article  CAS  PubMed  Google Scholar 

  44. Klompas M, Branson R, Eichenwald EC et al (2014) Strategies to prevent ventilator-associated pneumonia in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol 35(Suppl 2):S133–154. https://doi.org/10.1017/s0899823x00193894

    Article  PubMed  Google Scholar 

  45. Torres A, Niederman MS, Chastre J et al (2017) International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociacion Latinoamericana del Torax (ALAT). Eur Respir J 50(3):1700582. https://doi.org/10.1183/13993003.00582-2017

    Article  CAS  PubMed  Google Scholar 

  46. Klompas M, Branson R, Cawcutt K et al (2022) Strategies to prevent ventilator-associated pneumonia, ventilator-associated events, and nonventilator hospital-acquired pneumonia in acute-care hospitals: 2022 Update. Infect Control Hosp Epidemiol 43:687–713. https://doi.org/10.1017/ice.2022.88

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

None

Funding

None.

Author information

Authors and Affiliations

  1. Sant’Antonio Anesthesia and Intensive Care Unit, University Hospital of Padua, Padua, Italy

    Alessandro De Cassai & Marina Munari

  2. UOC Anesthesia and Intensive Care Unit, University Hospital of Padova, Padua, Italy

    Tommaso Pettenuzzo, Annalisa Boscolo, Nicolò Sella & Paolo Navalesi

  3. Cardiac Surgery Intensive Care Unit, University Hospital of Padua, Padua, Italy

    Veronica Busetto

  4. Department of Medicine - DIMED, University of Padova, Padua, Italy

    Christian Legnaro, Chiara Pretto, Alessio Rotondi, Annalisa Boscolo & Paolo Navalesi

  5. Thoracic Surgery and Lung Transplant Unit - Department of Cardiac, Thoracic, Vascular Sciences, and Public Health, University of Padua, Padua, Italy

    Annalisa Boscolo

Authors
  1. Alessandro De Cassai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tommaso Pettenuzzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Veronica Busetto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christian Legnaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chiara Pretto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alessio Rotondi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Annalisa Boscolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nicolò Sella
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Marina Munari
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Paolo Navalesi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: Alessandro De Cassai; Methodology: Alessandro De Cassai, Tommaso Pettenuzzo; Formal analysis and investigation: Alessandro De Cassai; Writing - original draft preparation:Alessandro De Cassai Tommaso Pettenuzzo; Writing - review and editing: Alessandro De Cassai, Tommaso Pettenuzzo, Paolo Navalesi, Marina Munari, Veronica Busetto, Christian Legnaro, Chiara Pretto, Alessio Rotondi, Nicolò Sella; Funding acquisition: all the authors; Supervision: Paolo Navalesi and Marina Munari

Corresponding author

Correspondence to Alessandro De Cassai.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1.

Search strategy.

Additional file 2.

Risk of bias assessment.

Additional file 3.

Funnel plots.

Additional file 4.

Direct–indirect evidence for the main outcome.

Additional file 5.

Network graph.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

De Cassai, A., Pettenuzzo, T., Busetto, V. et al. Chlorhexidine is not effective at any concentration in preventing ventilator-associated pneumonia: a systematic review and network meta-analysis. J Anesth Analg Crit Care 4, 30 (2024). https://doi.org/10.1186/s44158-024-00166-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s44158-024-00166-2

Keywords

Journal of Anesthesia, Analgesia and Critical Care

ISSN: 2731-3786

Contact us