Randomized Controlled Trial

. 2021 Nov;47(11):1295-1302.

doi: 10.1007/s00134-021-06475-2. Epub 2021 Oct 5.

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

Craig M Dale^{1

2

3}, Louise Rose^{4

5}, Sarah Carbone¹, Ruxandra Pinto⁶, Orla M Smith^{1

7

8}, Lisa Burry^{5

9

10}, Eddy Fan^{5

11}, Andre Carlos Kajdacsy-Balla Amaral^{3

5

6}, Victoria A McCredie^{5

11

12}, Damon C Scales^{3

5

6}, Brian H Cuthbertson^{13

14

15

16}

Affiliations

¹ Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, 155 College Street, Suite 130, Toronto, ON, M5T 1P8, Canada.
² Trauma, Emergency and Critical Care, Sunnybrook Health Sciences Centre, Toronto, Canada.
³ Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
⁴ Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King's College London, 57 Waterloo Road, Room 1.1.3, London, SE1 8WA, UK.
⁵ Interdepartmental Division of Critical Care Medicine, Faculty of Medicine, University of Toronto, Toronto, Canada.
⁶ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
⁷ Department of Critical Care, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
⁸ Li Ka Shing Knowledge Institute, Toronto, Canada.
⁹ Department of Pharmacy, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
¹⁰ Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.
¹¹ Department of Medicine, University Health Network and Sinai Health System, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada.
¹² Krembil Research Institute, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada.
¹³ Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada. Brian.Cuthbertson@sunnybrook.ca.
¹⁴ Interdepartmental Division of Critical Care Medicine, Faculty of Medicine, University of Toronto, Toronto, Canada. Brian.Cuthbertson@sunnybrook.ca.
¹⁵ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada. Brian.Cuthbertson@sunnybrook.ca.
¹⁶ Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Canada. Brian.Cuthbertson@sunnybrook.ca.

PMID: 34609548
PMCID: PMC8490143
DOI: 10.1007/s00134-021-06475-2

Randomized Controlled Trial

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

Craig M Dale et al. Intensive Care Med. 2021 Nov.

. 2021 Nov;47(11):1295-1302.

doi: 10.1007/s00134-021-06475-2. Epub 2021 Oct 5.

Authors

Affiliations

¹ Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, 155 College Street, Suite 130, Toronto, ON, M5T 1P8, Canada.
² Trauma, Emergency and Critical Care, Sunnybrook Health Sciences Centre, Toronto, Canada.
³ Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
⁴ Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King's College London, 57 Waterloo Road, Room 1.1.3, London, SE1 8WA, UK.
⁵ Interdepartmental Division of Critical Care Medicine, Faculty of Medicine, University of Toronto, Toronto, Canada.
⁶ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
⁷ Department of Critical Care, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
⁸ Li Ka Shing Knowledge Institute, Toronto, Canada.
⁹ Department of Pharmacy, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
¹⁰ Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.
¹¹ Department of Medicine, University Health Network and Sinai Health System, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada.
¹² Krembil Research Institute, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada.
¹³ Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada. Brian.Cuthbertson@sunnybrook.ca.
¹⁴ Interdepartmental Division of Critical Care Medicine, Faculty of Medicine, University of Toronto, Toronto, Canada. Brian.Cuthbertson@sunnybrook.ca.
¹⁵ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada. Brian.Cuthbertson@sunnybrook.ca.
¹⁶ Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Canada. Brian.Cuthbertson@sunnybrook.ca.

PMID: 34609548
PMCID: PMC8490143
DOI: 10.1007/s00134-021-06475-2

Abstract

Purpose: Oral chlorhexidine is used widely for mechanically ventilated patients to prevent pneumonia, but recent studies show an association with excess mortality. We examined whether de-adoption of chlorhexidine and parallel implementation of a standardized oral care bundle reduces intensive care unit (ICU) mortality in mechanically ventilated patients.

Methods: A stepped wedge cluster-randomized controlled trial with concurrent process evaluation in 6 ICUs in Toronto, Canada. Clusters were randomized to de-adopt chlorhexidine and implement a standardized oral care bundle at 2-month intervals. The primary outcome was ICU mortality. Secondary outcomes were time to infection-related ventilator-associated complications (IVACs), oral procedural pain and oral health dysfunction. An exploratory post hoc analysis examined time to extubation in survivors.

Results: A total of 3260 patients were enrolled; 1560 control, 1700 intervention. ICU mortality for the intervention and control periods were 399 (23.5%) and 330 (21.2%), respectively (adjusted odds ratio [aOR], 1.13; 95% confidence interval [CI] 0.82 to 1.54; P = 0.46). Time to IVACs (adjusted hazard ratio [aHR], 1.06; 95% CI 0.44 to 2.57; P = 0.90), time to extubation (aHR 1.03; 95% CI 0.85 to 1.23; P = 0.79) (survivors) and oral procedural pain (aOR, 0.62; 95% CI 0.34 to 1.10; P = 0.10) were similar between control and intervention periods. However, oral health dysfunction scores (- 0.96; 95% CI - 1.75 to - 0.17; P = 0.02) improved in the intervention period.

Conclusion: Among mechanically ventilated ICU patients, no benefit was observed for de-adoption of chlorhexidine and implementation of an oral care bundle on ICU mortality, IVACs, oral procedural pain, or time to extubation. The intervention may improve oral health.

Trial registration: ClinicalTrials.gov NCT03382730.

Keywords: Chlorhexidine; Critical care; De-adoption; Oral health; Randomized controlled trial; Respiration, artificial.

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Conflict of interest statement

The authors have no conflicts of interest to report in the conduct of this research.

Figures

**Fig. 1**
Stepped wedge allocation of patients and hospitals to control and intervention phases according to stepped wedge design

See this image and copyright information in PMC

Comment in

De-adoption of chlorhexidine oral care and ICU mortality.
Blot S, Deschepper M, Labeau S. Blot S, et al. Intensive Care Med. 2022 May;48(5):624-625. doi: 10.1007/s00134-022-06621-4. Epub 2022 Jan 17. Intensive Care Med. 2022. PMID: 35037992 No abstract available.
De-adoption of chlorhexidine oral care and ICU mortality. Authors' reply.
Dale C, Cuthbertson B. Dale C, et al. Intensive Care Med. 2022 May;48(5):626-627. doi: 10.1007/s00134-022-06649-6. Epub 2022 Feb 16. Intensive Care Med. 2022. PMID: 35174399 No abstract available.

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De-adoption of chlorhexidine oral care and ICU mortality. Authors' reply.
Dale C, Cuthbertson B. Dale C, et al. Intensive Care Med. 2022 May;48(5):626-627. doi: 10.1007/s00134-022-06649-6. Epub 2022 Feb 16. Intensive Care Med. 2022. PMID: 35174399 No abstract available.
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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

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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

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