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Vol. 47. Núm. 1.
Páginas 55-56 (enero 2022)
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Vol. 47. Núm. 1.
Páginas 55-56 (enero 2022)
Letter to the Editor
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Antiseptic mouthwashes and mortality: look beyond chlorhexidine
Enjuagues bucales antisépticos y mortalidad: más allá de la clorhexidina
S. Blota,
Autor para correspondencia

Corresponding author.
, M. Deschepperb
a Department of Internal Medicine and Pediatrics, Ghent University, Campus UZ Gent, Ghent, Belgium
b Data Science Institute, Ghent University Hospital, Belgium
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Dear Editor:

Ventilator-associated pneumonia (VAP) remains a concern calling for optimal prevention strategies.1 In this regard, we read with interest the article by Vieira et al. concerning chlorhexidine oral care in ICU patients.2 The authors wonder whether there is still room for this practice in VAP prevention care bundles. Indeed, the scientific evidence supporting chlorhexidine mouthwashes is limited to cardiac-surgery patients. Additionally, Vieira’s question originates from the accumulating body of literature illustrating excess mortality in patients exposed to chlorhexidine mouthwashes.3 These observations have incited controversy because of the lack of a pathogenic mechanism explaining the mouthwash-mortality relationship. Initially, micro-aspiration of mouthwash solution has been proposed as a potential explanation because of chlorhexidine’s lung toxicity. However, the theoretical basis is small as it is based on, on one hand, an accidental case of massive aspiration of abundant amounts of the mouthwash solution, and, on the other hand, an experimental model exposing lungs of mice to chlorhexidine dosages way beyond what is used in daily practice. Moreover, in the hospital-wide cohort study by Deschepper and colleagues, the harmful impact of chlorhexidine mouthwashes appeared to be higher in non-critically ill and non-ventilated patients, thereby annihilating the micro-aspiration hypothesis.4

We recently suggested that a disturbance of the enterosalivary nitrate-nitrite-nitric oxide (NO) pathway may explain the increased mortality risk observed in patients exposed to chlorhexidine mouthwashes.5 NO is a key molecule in human physiology with an essential role in neurotransmission, mitochondrial respiration, the maintenance of vascular permeability and tonicity, the inhibition of leucocyte adhesion and platelet aggregation, and protection against anti-oxidants. An essential step in the nitrate-nitrite-NO pathway is the reduction of nitrate to nitrite. This process takes place in the oral cavity and is provided by facultative anaerobic bacteria located at the posterior surface of the tongue. Evidently, antiseptic mouthwashes eradicate these bacteria thereby interrupting the pathway. This may lead to a reduced bio-availability of NO, a condition that puts patients at risk for ischaemic heart events and sepsis as has been reported in literature (data summarized in Ref.5).

The combination of (i) the limited evidence that chlorhexidine mouthwashes reduce VAP risk, (ii) multiple studies indicating deleterious effects associated with chlorhexidine mouthwashes, and (iii) the presence of a plausible pathogenic mechanism, strengthens the call to abandon the use of chlorhexidine from our oral care routine.3 Albeit that so far no deleterious outcomes have been reported with other oral solutions, we believe it would be a mistake to replace chlorhexidine-based solutions by another type of antiseptic mouthwash. If an interruption of the nitrate-nitrite-NO pathway is indeed responsible for the increased mortality risk, the harmful effect is not chlorhexidine-specific. Therefore, all antiseptic mouthwashes are to be avoided, and not only chlorhexidine-based solutions. We propose a ‘back-to-basics approach’ with emphasis on mechanical cleaning (i.e., toothbrushing) rather than a chemical disinfection threatening that all-important oral microbiome.

We are eager to hear the thoughts of Vieira and colleagues about the nitrate-nitrite-NO theorem and, more importantly, about our recommendation to avoid all oral antiseptics rather than only chlorhexidine-based oral care solutions.

Conflict of interest statement

Both authors have no conflicts of interest to declare regarding the letter to the editor.

S. Blot, E. Ruppé, S. Harbarth, K. Asehnoune, G. Poulakou, C.-E. Luyt, et al.
Healthcare-associated infections in adult intensive care unit patients: changes in epidemiology, diagnosis, prevention and contributions of new technologies.
Intensive Crit Care Nurs., 70 (2022),
P.C. Vieira, R.B. de Oliveira, T.M. da Silva Mendonça.
Should oral chlorhexidine remain in ventilator-associated pneumonia prevention bundles?.
Med Intensiva (Engl Ed)., 46 (2022), pp. 259-268
S. Blot, S.O. Labeau, C.M. Dale.
Why it’s time to abandon antiseptic mouthwashes.
Intensive Crit Care Nurs., 70 (2022),
M. Deschepper, W. Waegeman, K. Eeckloo, D. Vogelaers, S. Blot.
Effects of chlorhexidine gluconate oral care on hospital mortality: a hospital-wide, observational cohort study.
Intensive Care Med., 44 (2018), pp. 1017-1026
S. Blot.
Antiseptic mouthwash, the nitrate-nitrite-nitric oxide pathway, and hospital mortality: a hypothesis generating review.
Intensive Care Med., 47 (2021), pp. 28-38
Medicina Intensiva
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