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Antiseptic mouthwash, the nitrate–nitrite–nitric oxide pathway, and hospital mortality : a hypothesis generating review

Stijn Blot (UGent)
(2021) INTENSIVE CARE MEDICINE. 47(1). p.28-38
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Organization
Abstract
Meta-analyses and several large cohort studies have demonstrated that antiseptic mouthwashes are associated with mortality in hospitalized patients. A clear pathogenic mechanism is lacking, leading to controversy and a reluctance to abandon or limit the use of antiseptic mouthwashes. Here, we generate the hypothesis that a disturbance in nitric oxide homeostasis by antiseptic mouthwashes may be responsible for the observed increase in mortality risk. Nitric oxide is essential in multiple physiological processes, and a reduction in nitric oxide bioavailability is associated with the occurrence or worsening of pathologies, such as atherosclerosis, diabetes, and sepsis. Oral facultative anaerobic bacteria are essential for the enterosalivary nitrate-nitrite-nitric oxide pathway due to their capacity to reduce nitrate to nitrite. Nitrate originates from dietary sources or from the active uptake by salivary glands of circulating nitrate, which is then excreted in the saliva. Because antiseptic mouthwashes eradicate the oral bacterial flora, this nitric oxide-generating pathway is abolished, which may result in nitric oxide-deficient conditions potentially leading to life-threatening complications such as ischaemic heart events or sepsis.
Keywords
Critical Care and Intensive Care Medicine, Antiseptic mouthwash, Chlorhexidine, Oral care, Mortality, Nitric oxide, Enterosalivary pathway, Nitrate-nitrite-NO pathway, CRITICALLY-ILL PATIENTS, VENTILATOR-ASSOCIATED PNEUMONIA, BLOOD-PRESSURE, DIETARY NITRATE, ISCHEMIA-REPERFUSION, CHLORHEXIDINE GLUCONATE, ATTRIBUTABLE MORTALITY, SALIVARY NITRITE, ORAL MICROBIOME, REACTIVE OXYGEN

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MLA
Blot, Stijn. “Antiseptic Mouthwash, the Nitrate–Nitrite–Nitric Oxide Pathway, and Hospital Mortality : A Hypothesis Generating Review.” INTENSIVE CARE MEDICINE, vol. 47, no. 1, 2021, pp. 28–38, doi:10.1007/s00134-020-06276-z.
APA
Blot, S. (2021). Antiseptic mouthwash, the nitrate–nitrite–nitric oxide pathway, and hospital mortality : a hypothesis generating review. INTENSIVE CARE MEDICINE, 47(1), 28–38. https://doi.org/10.1007/s00134-020-06276-z
Chicago author-date
Blot, Stijn. 2021. “Antiseptic Mouthwash, the Nitrate–Nitrite–Nitric Oxide Pathway, and Hospital Mortality : A Hypothesis Generating Review.” INTENSIVE CARE MEDICINE 47 (1): 28–38. https://doi.org/10.1007/s00134-020-06276-z.
Chicago author-date (all authors)
Blot, Stijn. 2021. “Antiseptic Mouthwash, the Nitrate–Nitrite–Nitric Oxide Pathway, and Hospital Mortality : A Hypothesis Generating Review.” INTENSIVE CARE MEDICINE 47 (1): 28–38. doi:10.1007/s00134-020-06276-z.
Vancouver
1.
Blot S. Antiseptic mouthwash, the nitrate–nitrite–nitric oxide pathway, and hospital mortality : a hypothesis generating review. INTENSIVE CARE MEDICINE. 2021;47(1):28–38.
IEEE
[1]
S. Blot, “Antiseptic mouthwash, the nitrate–nitrite–nitric oxide pathway, and hospital mortality : a hypothesis generating review,” INTENSIVE CARE MEDICINE, vol. 47, no. 1, pp. 28–38, 2021.
@article{8699567,
  abstract     = {{Meta-analyses and several large cohort studies have demonstrated that antiseptic mouthwashes are associated with mortality in hospitalized patients. A clear pathogenic mechanism is lacking, leading to controversy and a reluctance to abandon or limit the use of antiseptic mouthwashes. Here, we generate the hypothesis that a disturbance in nitric oxide homeostasis by antiseptic mouthwashes may be responsible for the observed increase in mortality risk. Nitric oxide is essential in multiple physiological processes, and a reduction in nitric oxide bioavailability is associated with the occurrence or worsening of pathologies, such as atherosclerosis, diabetes, and sepsis. Oral facultative anaerobic bacteria are essential for the enterosalivary nitrate-nitrite-nitric oxide pathway due to their capacity to reduce nitrate to nitrite. Nitrate originates from dietary sources or from the active uptake by salivary glands of circulating nitrate, which is then excreted in the saliva. Because antiseptic mouthwashes eradicate the oral bacterial flora, this nitric oxide-generating pathway is abolished, which may result in nitric oxide-deficient conditions potentially leading to life-threatening complications such as ischaemic heart events or sepsis.}},
  author       = {{Blot, Stijn}},
  issn         = {{0342-4642}},
  journal      = {{INTENSIVE CARE MEDICINE}},
  keywords     = {{Critical Care and Intensive Care Medicine,Antiseptic mouthwash,Chlorhexidine,Oral care,Mortality,Nitric oxide,Enterosalivary pathway,Nitrate-nitrite-NO pathway,CRITICALLY-ILL PATIENTS,VENTILATOR-ASSOCIATED PNEUMONIA,BLOOD-PRESSURE,DIETARY NITRATE,ISCHEMIA-REPERFUSION,CHLORHEXIDINE GLUCONATE,ATTRIBUTABLE MORTALITY,SALIVARY NITRITE,ORAL MICROBIOME,REACTIVE OXYGEN}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{28--38}},
  title        = {{Antiseptic mouthwash, the nitrate–nitrite–nitric oxide pathway, and hospital mortality : a hypothesis generating review}},
  url          = {{http://dx.doi.org/10.1007/s00134-020-06276-z}},
  volume       = {{47}},
  year         = {{2021}},
}

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