To: The use of 2% chlorhexidine gel and toothbrushing for oral hygiene of patients receiving mechanical ventilation: effects on ventilator-associated pneumonia

To the Editor

An article titled “The use of 2% chlorhexidine gel and tooth brushing for oral hygiene of patients receiving mechanical ventilation: effects on ventilator-associated pneumonia” was published in Rev Bras Ter Intensiva (2012; 24(4):369-74).⁽¹⁾ While the researchers terminated the study due to the futility of the applied method, the unrealistic results of the study inspired us to write this letter. The mentioned paper had the following fundamental scientific and technical problems:

• Chlorhexidine belongs to the family of N1, N5-substituted biguanides. At physiological pH, it can serve as an antiseptic for the maintenance of oral hygiene. Moreover, the application of 0.12% chlorhexidine solution is necessary for the healing and regeneration of oral tissues.⁽²⁾ In addition, the antibacterial effects of oral rinses containing 0.1% chlorhexidine solution have been well documented by several clinical studies.⁽³⁾ The bactericidal effects of chlorhexidine salts are attributed to the dissociation and release of the positively charged chlorhexidine cation. The released cation will then bind to negatively charged bacterial cell walls. Therefore, while chlorhexidine has antiseptic properties at low concentrations (≤0.12%), at high concentrations (>0.15%), it is a disinfectant capable of causing cellular disruption and cell death.⁽⁴⁾ Unfortunately, the esteemed authors did not clarify the type and potency of the applied chlorhexidine compound.

• Based on the available data, due to the cationic nature of chlorhexidine, its efficacy as a potent disinfectant is reduced in the presence of serum, blood, pus, soaps, and other anionic compounds. However, the authors did not consider such effects in gel preparation.⁽⁵⁾

• The sample size and statistical methods applied were inadequate. Additionally, the methodology was not comprehensively discussed. The authors did not appear to have benefitted from the numerous valuable and relevant reports published in this regard.

• In the study in question, the patients were divided into two groups: placebo and intervention. Ideally, there should have been an extra control group that received neither placebo nor the intervention.

• The authors determined that the incidences of ventilator-associated pneumonia (VAP) were 45.8% in the placebo group and 64.3% in the intervention group. However, the incidence of VAP in the absence of placebo/intervention was not determined. Although increased bacterial growth in the oral cavity due to the presence of organic substances in the gel might have been responsible for the mentioned incidences, the exact reasons could not be clarified. If the researchers had designed the study correctly by examining three groups (intervention, placebo, and control), they would have been able to compare the results among all groups and would understand the reasons underlying the failure of their approach.

• Although 1% chlorhexidine has been shown to exert antiseptic effects, the authors used a 2% chlorhexidine gel for no particular reason. It is possible that the basic materials present during gel preparation might have contained anionic components that could affect the intrinsic cationic activity of chlorhexidine. In fact, changing the gel formulation could have led to different results. Previous research has indicated that natural extracts of Morinda citrifolia and Aloe vera as well as papain extracts exhibited different activities.⁽⁶⁾

The destructive effects of chlorhexidine on the oral mucosa might have been responsible for the higher infection rates in the intervention group compared to the placebo group. In other words, the gel might have facilitated bacterial growth by destroying one of the most important defensive barriers. Furthermore, reactions between chlorhexidine and the gel components might have accelerated bacterial growth by providing nutrition.

Nevertheless, from an oral hygiene standpoint, chlorhexidine is considered crucial for preventing pneumonia and mouth infections. Therefore, studies in this field must focus on both the advantages and disadvantages of this oral antiseptic. Such evaluations will not only enhance medical team members’ and researchers’ understanding of the existing facts but also lay the ground for future research.

Ramezan Ali Ataee

Department of Medical Microbiology, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, IR of Iran