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Dental care and hospital mortality in ICU patients

      Dear Editor,
      Maintaining oral health in critically ill patients is important, as poor oral hygiene is associated with unfavorable outcomes such as pneumonia. However, cleaning the oral cavity in critically ill patients, especially those on mechanical ventilation, is a particular challenge as there is a lack of scientific basis regarding the appropriate technique, frequency of care, and preferred supplies and products.
      • Rello J
      • Koulenti D
      • Blot S
      • et al.
      Oral care practices in intensive care units: a survey of 59 European ICUs.
      • Unahalekhaka A
      • Butpan P
      • Wongsaen R
      • Phunpae P
      • Preechasuth K
      Contamination of antimicrobial-resistant bacteria on toothbrushes used with mechanically ventilated patients: a cross sectional study.
      • Izadi M
      • Bagheri M
      • Bahrami Far A
      • Sureda A
      • Soodmand M
      Effect of ozonated water and chlorhexidine mouthwash on oral health in critically ill patients on mechanical ventilation: a double-blind randomised clinical trial.
      In this regard we read with interest the article by Ribeiro and colleagues and applaud their repeated efforts to explore and stress the importance of thorough dental care in critically ill patients.
      • Ribeiro ILA
      • Bellissimo-Rodrigues WT
      • Mussolin MG
      • et al.
      Impact of a dental care intervention on the hospital mortality of critically ill patients admitted to intensive care units: a quasi-experimental study [e-pub ahead of print].
      By means of a quasi-experimental study with interrupted time-series, the authors assessed the impact of thrice weekly dental care in intensive care unit (ICU) patients compared with standard oral care by nurses mainly based on chlorhexidine mouthwashes. Pre-intervention mortality rates ranged from 32% to 36% and in the intervention period, a drop to 28% was observed (P = .015). The authors hypothesized that the reduction in mortality could be explained by diminished periodontal inflammation leading to a decreased likelihood of primary bloodstream infection, ischemic myocardial infarction, and stroke. Unfortunately, data to support this explanation were not collected.
      Alternatively, Ribeiro et al. assume that the reduced use of chlorhexidine mouthwashes may have contributed to the decreased mortality rate. In recent years the safety of chlorhexidine oral care has been repeatedly questioned. Chlorhexidine mouthwashes have been associated with an increased risk of mortality in meta-analysis of randomized trials as in large cohort studies executed either in ICUs or hospital-wide.
      • Parreco J
      • Soe-Lin H
      • Byerly S
      • et al.
      Multi-center outcomes of chlorhexidine oral decontamination in intensive care units.
      • Deschepper M
      • Waegeman W
      • Eeckloo K
      • Vogelaers D
      • Blot S.
      Effects of chlorhexidine gluconate oral care on hospital mortality: a hospital-wide, observational cohort study.
      • Price R
      • MacLennan G
      • Glen J
      • Collaboration SuDDICU
      Selective digestive or oropharyngeal decontamination and topical oropharyngeal chlorhexidine for prevention of death in general intensive care: systematic review and network meta-analysis.
      • Klompas M
      • Li L
      • Kleinman K
      • Szumita PM
      • Massaro AF.
      Associations between ventilator bundle components and outcomes.
      These observations led to a plea for prudent use of antiseptic mouthwashes
      • Blot S
      • Labeau SO
      • Dale CM.
      Why it's time to abandon antiseptic mouthwashes.
      and initiatives to safely de-adopt the practice from the daily routine.
      • Dale CM
      • Rose L
      • Carbone S
      • et al.
      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.
      However, the exact pathogenic mechanism remains unclear. At first it was assumed that micro aspiration of chlorhexidine in intubated patients triggered pulmonary complications. Indeed, in endotracheally intubated patients micro aspiration of subglottic secretions along the cuff is nearly unavoidable as any change in patient position causes deviations in cuff pressure and the manipulations associated with oral care may, at least theoretically, trigger microaspiration.
      • Lizy C
      • Swinnen W
      • Labeau S
      • et al.
      Cuff pressure of endotracheal tubes after changes in body position in critically ill patients treated with mechanical ventilation.
      ,
      • Griton M
      • Naud N
      • Gruson D
      • Bedel A
      • Boyer A
      The risk of microaspiration during oral care in mechanically ventilated patients: A randomised cross-over study comparing two different suction protocols.
      However, as the link between chlorhexidine oral care and mortality was also observed in non-ICU patients
      • Deschepper M
      • Waegeman W
      • Eeckloo K
      • Vogelaers D
      • Blot S.
      Effects of chlorhexidine gluconate oral care on hospital mortality: a hospital-wide, observational cohort study.
      , this hypothesis appeared unlikely. Ribeiro and colleagues assume that the increased mortality may be triggered by oral mucositis as they reported in a previous study in which they assessed the value of additional dental care in ICU patients receiving chlorhexidine-based oral care.
      • Bellissimo-Rodrigues WT
      • Menegueti MG
      • de Macedo LD
      • Basile-Filho A
      • Martinez R
      • Bellissimo-Rodrigues F
      Oral mucositis as a pathway for fatal outcome among critically ill patients exposed to chlorhexidine: post hoc analysis of a randomized clinical trial.
      Oral mucositis induced by chlorhexidine mouthwashes appeared associated with increased mortality (adjusted OR 6.1, 95% CI 2.0-19.1). We believe however, that their analysis includes a bias since higher chlorhexidine concentrations were applied in patients with greater disease severity (2% vs 0.12%), constituting an inherent trigger for mucositis.
      • Plantinga NL
      • Wittekamp BHJ
      • Leleu K
      • et al.
      Oral mucosal adverse events with chlorhexidine 2% mouthwash in ICU.
      Additionally, adjustments for severity of disease were based on admission data while patients may have acquired oral mucositis later in the ICU course.
      We believe that the mortality associated with chlorhexidine oral care is caused by a disturbance of the nitric oxide (NO) homeostasis.
      • Blot S
      Antiseptic mouthwash, the nitrate-nitrite-nitric oxide pathway, and hospital mortality: a hypothesis generating review.
      NO is a key-messenger molecule in multiple physiological processes such as, among more, relaxation and permeability of the microcirculation and inhibition of platelet aggregation.
      • Hollenberg SM
      • Cinel I.
      Bench-to-bedside review: nitric oxide in critical illness–update 2008.
      The oral microbiome has an essential role in the provision of NO by reducing nitrate to nitrite. By eradicating the oral bacterial flora, antiseptic mouthwashes interrupt the nitrate-nitrite-NO pathway resulting in a state of deficient NO bioavailability. As such, antiseptic mouthwash leads to a condition of suboptimal NO bioavailability, which put patients at risk for ischemic heart events and sepsis. This pathogenic mechanism is supported by Steitieh and Amin, who reported resolution of angor pectoris after cessation of chlorhexidine oral care and Parreco et al. who observed significantly higher rates of ICU-acquired sepsis in patients exposed to chlorhexidine mouthwashes.
      • Parreco J
      • Soe-Lin H
      • Byerly S
      • et al.
      Multi-center outcomes of chlorhexidine oral decontamination in intensive care units.
      ,
      • Steitieh D
      • Amin N.
      Angina pectoris worsened by mouthwash.
      When it comes to infection prevention and control, it is important to recognize that the interruption of the nitrate-nitrite-NO pathway by eradicating oral bacteria is evident with all broad-spectrum oral antiseptics, and not exclusively with chlorhexidine.
      • Blot S
      Antiseptic mouthwash, the nitrate-nitrite-nitric oxide pathway, and hospital mortality: a hypothesis generating review.
      Therefore, we recommend being cautious with antiseptic mouthwashes in general and to restrict this practice to evidence-based indications as described in the dental care protocol described by Ribeiro and colleagues.

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