Protocol for a multi-centered, stepped wedge, cluster randomized controlled trial of the de-adoption of oral chlorhexidine prophylaxis and implementation of an oral care bundle for mechanically ventilated critically ill patients: the CHORAL study

Abstract

BackgroundRoutine application of chlorhexidine oral rinse is recommended to reduce risk of ventilator-associated pneumonia (VAP) in mechanically ventilated patients. Recent reappraisal of the evidence from two meta-analyses suggests chlorhexidine may cause excess mortality in non-cardiac surgery patients and does not reduce VAP. Mechanisms for possible excess mortality are unclear. The CHORAL study will evaluate the impact of de-adopting chlorhexidine and implementing an oral care bundle (excluding chlorhexidine) on mortality, infection-related ventilator-associated complications (IVACs), and oral health status.MethodsThe CHORAL study is a stepped wedge, cluster randomized controlled trial in six academic intensive care units (ICUs) in Toronto, Canada. Clusters (ICU) will be randomly allocated to six sequential steps over a 14-month period to de-adopt oral chlorhexidine and implement a standardized oral care bundle (oral assessment, tooth brushing, moisturization, and secretion removal). On study commencement, all clusters begin with a control period in which the standard of care is oral chlorhexidine. Clusters then begin crossover from control to intervention every 2 months according to the randomization schedule. Participants include all mechanically ventilated adults eligible to receive the standardized oral care bundle. The primary outcome is ICU mortality; secondary outcomes are IVACs and oral health status. We will determine demographics, antibiotic usage, mortality, and IVAC rates from a validated local ICU clinical registry. With six clusters and 50 ventilated patients on average each month per cluster, we estimate that 4200 patients provide 80% power after accounting for intracluster correlation to detect an absolute reduction in mortality of 5.5%. We will analyze our primary outcome of mortality using a generalized linear mixed model adjusting for time to account for secular trends. We will conduct a process evaluation to determine intervention fidelity and to inform interpretation of the trial results.DiscussionThe CHORAL study will inform understanding of the effectiveness of de-adoption of oral chlorhexidine and implementation of a standardized oral care bundle for decreasing ICU mortality and IVAC rates while improving oral health status. Our process evaluation will inform clinicians and decision makers about intervention delivery to support future de-adoption if justified by trial results.Trial registrationClinicalTrials.gov, NCT03382730. Registered on December 26, 2017.Electronic supplementary materialThe online version of this article (10.1186/s13063-019-3673-0) contains supplementary material, which is available to authorized users.

Ventilator-associated pneumonia in adults: a narrative review

“…More concerningly, some meta-analyses and observational studies have reported that oral care with chlorhexidine may increase mortality rates, perhaps because some patients may aspirate some of the antiseptic triggering acute lung injury [91,95,99,100,111,112]. A cluster randomized de-adoption study is currently underway to better characterize the safety and effectiveness of oral chlorhexidine for ventilated patients [113].…”

Less daily oral hygiene is more in the ICU: no

“…And third, the vehiculum and method of application may also matter; a solution may be more easy to micro-aspirate than a gel or toothpaste and each may contain different other components. These side notes require additional research and until results of future studies such as the CHORAL study are available [ 12 ], the potential beneficial effects of CHX come with potential detrimental effects. As a result, the European Society of Intensive Care Medicine refrained from a recommendation concerning CHX use in the most recent VAP guideline [ 13 ].…”

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

“…stroke patients) cannot be ruled out as a trigger for pulmonary complications. The absence of an explanatory pathogenic mechanism has led to controversy in clinical practice and the consideration of alternatives [30][31][32][33][34][35].…”