Intensive Care Medicine

, Volume 42, Issue 4, pp 620–621 | Cite as

Oral mucosal adverse events with chlorhexidine 2 % mouthwash in ICU

  • Nienke L. Plantinga
  • Bastiaan H. J. Wittekamp
  • Kris Leleu
  • Pieter Depuydt
  • Anne-Marie Van den Abeele
  • Christian Brun-Buisson
  • Marc J. M. Bonten
Open Access


Chlorhexidine Oral Lesion Oral Care Oral Mucosal Lesion Chlorhexidine Digluconate 
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Dear Editor,

Oral care using a chlorhexidine solution is commonly used as an infection prevention measure in European ICUs [1]. The preventive effects of different decontamination strategies, one of which is mouthwash with chlorhexidine digluconate 2 % (CHX 2 %), on the incidence of ICU-acquired bacteremia with multidrug-resistant bacteria is being investigated in a multicenter cluster-randomized study in 13 ICUs in six European countries [ NCT02208154] (see Supplementary Material for detailed methods). An unexpected high incidence of oral mucosal lesions was observed in ICU patients receiving CHX 2 %.

Oral mucosal lesions, including erosive lesions, ulcerations, white/yellow plaque formation, and bleeding mucosa were observed in 29 of 295 patients (9.8 %) that had received CHX 2 % in the first two hospitals testing this intervention (Supplementary Table S1, Pictures 1–4). The median time to onset of oral lesions was 8.0 days (IQR 4.5–11.0) in the 24 patients in whom duration of exposure could be ascertained. CHX 2 % was discontinued prematurely in 16/29 cases and oral mucosal lesions disappeared after cessation of CHX 2 % in all patients.

Patient characteristics were comparable for the baseline (n = 310) and CHX 2 % periods (n = 295; Supplementary Table S2) for the two ICUs. During the baseline period CHX 0.20 and 0.12 % were used for oral care in hospitals A and B, respectively, without evidence of oral lesions in any patient. All other procedures related to oral care remained identical in each hospital during both periods.

Amongst the CHX 2 % treated patients, occurrence of side effects was associated with male gender, APACHE II score, length of stay in the ICU, and duration of mechanical ventilation, suggesting a dose-response relationship, with increasing risks of oral mucosal lesions for the more severely ill patients, undergoing mechanical ventilation, and receiving CHX 2 % for longer periods (Table 1). This hypothesis is supported by the localization of the lesions in the oral cavity; most lesions occurred where stasis of the mouthwash might have occurred—despite suctioning after administration—such as below the tongue and in the buccal pockets.
Table 1

Baseline characteristics of CHX 2 % treated patients with and without adverse events


Adverse events (N = 29)

No adverse events (N = 266)

Pearson Chi square/indep. t test

Male gender

23 (79.3 %)

161 (60.5 %)

P = 0.047

Admission type


P = 0.155


13 (44.8 %)

153 (57.5 %)



5 (17.2 %)

20 (7.5 %)



11 (37.9 %)

93 (35.0 %)


Acute illness (y/n)

24 (82.8 %)

198 (74.4 %)

P = 0.324

Antibiotic at ICU admission (y/n)

11/29 (37.9 %)

123/259 (47.5 %)

P = 0.328

Age, mean (SD)

60.4 (13.3)

60.1 (15.7)

P = 0.921

APACHE II, mean (SD)

26.7 (8.0)

19.6 (8.6)

P < 0.0005

ICU-LOS, median (IQR)

28 (21–41.5)

10.5 (6–19)

P < 0.0005 (LN)

Geometric mean (SD)

27.2 (1.8)

10.6 (2.2)

Length of MV, median (IQR)

19 (14.5–28.5)

6 (3–11)

P < 0.0005 (LN)

Geometric mean (SD)

18.8 (1.8)

6.2 (2.3)

SD standard deviation, IQR interquartile range, LOS length of stay, LN log-transformed variable, MV mechanical ventilation, N number of patients

Mechanical stress during application of CHX 2 % may have played a role in hospital A, where the solution was initially applied using Kocher’s forceps with gauzes and where the incidence seemed to have reduced after changing to application using a syringe. Hospital B had applied CHX 2 % with a gauze wrapped around a gloved finger.

In 12 patients symptoms predominantly consisted of pronounced white plaques at the tongue and other localizations in the mouth, in some resembling Candida infection (Supplementary Picture 3). Yet, the incidence rate ratio between prior respiratory tract colonization with Candida spp. (monitored twice weekly as part of the study protocol and in clinical cultures) and the occurrence of side effects was 0.94 (95 % confidence interval 0.09–1.79, Supplementary Table S3). An association with herpes reactivation could not be determined as reactivation was investigated in five affected patients only (Supplementary Table S1).

The study safety committee recommended to replace CHX 2 % mouthwash by a CHX 1 % oral gel in the remaining hospitals. Since then CHX 1 % was withdrawn for reasons of intolerance in 2 of 419 (0.5 %) patients in four hospitals, after 12 and 30 days of use.

On the basis of these findings, we recommend against the use of 2 % chlorhexidine digluconate mouthwash in ICU patients.


Compliance with ethical standards

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Supplementary material

134_2016_4217_MOESM1_ESM.docx (192 kb)
Supplementary material 1 (DOCX 192 kb)


  1. 1.
    Rello J, Koulenti D, Blot S, Sierra R, Diaz E, De Waele JJ, Macor A, Agbaht K, Rodriguez A (2007) Oral care practices in intensive care units: a survey of 59 European ICUs. Intensive Care Med 33:1066–1070CrossRefPubMedGoogle Scholar

Copyright information

© The Author(s) 2016

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as appropriate credit is given to the original author(s) and the source, a link is provided to the Creative Commons license and any changes made are indicated.

Authors and Affiliations

  • Nienke L. Plantinga
    • 1
  • Bastiaan H. J. Wittekamp
    • 1
  • Kris Leleu
    • 2
  • Pieter Depuydt
    • 3
  • Anne-Marie Van den Abeele
    • 4
  • Christian Brun-Buisson
    • 5
  • Marc J. M. Bonten
    • 1
    • 6
  1. 1.Julius Center for Health Sciences and Primary CareUniversity Medical Center UtrechtUtrechtThe Netherlands
  2. 2.Department of Intensive CareAZ St. Lucas HospitalGhentBelgium
  3. 3.Department of Intensive CareGhent University HospitalGhentBelgium
  4. 4.Clinical Microbiology LaboratoryAZ St. Lucas HospitalGhentBelgium
  5. 5.Medical ICU and Infection Control UnitHopitaux Universitaires Henri Mondor and Université Paris-Est CréteilCréteilFrance
  6. 6.Department of Medical MicrobiologyUniversity Medical Center UtrechtUtrechtThe Netherlands

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