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, Louise Rose, Sarah Carbone, Ruxandra Pinto, Orla M Smith, Lisa Burry, Eddy Fan, Andre Carlos Kajdacsy-Balla Amaral, Victoria A McCredie, Damon C Scales, Brian H Cuthbertson, Craig M Dale, Louise Rose, Sarah Carbone, Ruxandra Pinto, Orla M Smith, Lisa Burry, Eddy Fan, Andre Carlos Kajdacsy-Balla Amaral, Victoria A McCredie, Damon C Scales, Brian H Cuthbertson

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.

Conflict of interest statement

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

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Figures

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

References

    1. Rello J, Afonso E, Lisboa T, Ricart M, Balsera B, Rovira A, Valles J, Diaz E, Investigators FP. A care bundle approach for prevention of ventilator-associated pneumonia. Clin Microbiol Infect. 2013;19:363–369. doi: 10.1111/j.1469-0691.2012.03808.x.
    1. Camporota L, Brett S. Care bundles: implementing evidence or common sense? Crit Care. 2011;15:159. doi: 10.1186/cc10232.
    1. Hua F, Xie H, Worthington HV, Furness S, Zhang Q, Li C. Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia. Cochrane Database Syst Rev. 2016;10(10):CD008367. doi: 10.1002/14651858.CD008367.pub3.
    1. Labeau SO, Van de Vyver K, Brusselaers N, Vogelaers D, Blot SI. Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis. Lancet Infect Dis. 2011;11:845–854. doi: 10.1016/S1473-3099(11)70127-X.
    1. Klompas M, Branson R, Eichenwald EC, Greene LR, Howell MD, Lee G, Magill SS, Maragakis LL, Priebe GP, Speck K, Yokoe DS, Berenholtz SM. Strategies to prevent ventilator-associated pneumonia in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35:915–936. doi: 10.1086/677144.
    1. Muscedere J, Sinuff T, Heyland DK, Dodek PM, Keenan SP, Wood G, Jiang X, Day AG, Laporta D, Klompas M. The clinical impact and preventability of ventilator-associated conditions in critically ill patients who are mechanically ventilated. Chest. 2013;144:1453–1460. doi: 10.1378/chest.13-0853.
    1. Klompas M, Speck K, Howell MD, Greene LR, Berenholtz SM. Reappraisal of routine oral care with chlorhexidine gluconate for patients receiving mechanical ventilation: systematic review and meta-analysis. JAMA Intern Med. 2014;174:751–761. doi: 10.1001/jamainternmed.2014.359.
    1. Price R, MacLennan G, Glen J. Selective digestive or oropharyngeal decontamination and topical oropharyngeal chlorhexidine for prevention of death in general intensive care: systematic review and network meta-analysis. BMJ. 2014;348:g2197. doi: 10.1136/bmj.g2197.
    1. Plantinga NL, Wittekamp BHJ, Leleu K, Depuydt P, Van den Abeele AM, Brun-Buisson C, Bonten MJM. Oral mucosal adverse events with chlorhexidine 2% mouthwash in ICU. Intensive Care Med. 2016;42:620–621. doi: 10.1007/s00134-016-4217-7.
    1. Cieplik F, Jakubovics NS, Buchalla W, Maisch T, Hellwig E, Al-Ahmad A. Resistance toward chlorhexidine in oral bacteria - is there cause for concern? Front Microbiol. 2019;10:587. doi: 10.3389/fmicb.2019.00587.
    1. Kampf G. Acquired resistance to chlorhexidine - is it time to establish an 'antiseptic stewardship' initiative? J Hosp Infect. 2016;94:213–227. doi: 10.1016/j.jhin.2016.08.018.
    1. 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. Crit Care. 2019;23:382. doi: 10.1186/s13054-019-2664-6.
    1. Niven DJ, Mrklas KJ, Holodinsky JK, Straus SE, Hemmelgarn BR, Jeffs LP, Stelfox HT. Towards understanding the de-adoption of low-value clinical practices: a scoping review. BMC Med. 2015;13:255–255. doi: 10.1186/s12916-015-0488-z.
    1. Lyu PF, Hockenberry JM, Gaydos LM, Howard DH, Buchman TG, Murphy DJ. Impact of a sequential intervention on albumin utilization in critical care. Crit Care Med. 2016;44(7):1307–1313. doi: 10.1097/CCM.0000000000001638.
    1. Norton WE, Chambers DA. Unpacking the complexities of de-implementing inappropriate health interventions. Implement Sci. 2020;15:2. doi: 10.1186/s13012-019-0960-9.
    1. Wittekamp BH, Plantinga NL. Less daily oral hygiene is more in the ICU: no. Intensive Care Med. 2021;47(3):331–333. doi: 10.1007/s00134-021-06359-5.
    1. Helfrich CD, Rose AJ, Hartmann CW, van Bodegom-Vos L, Graham ID, Wood SJ, Majerczyk BR, Good CB, Pogach LM, Ball SL, Au DH, Aron DC. How the dual process model of human cognition can inform efforts to de-implement ineffective and harmful clinical practices: a preliminary model of unlearning and substitution. J Eval Clin Pract. 2018;24:198–205. doi: 10.1111/jep.12855.
    1. Dale CM, Rose L, Carbone S, Smith OM, Burry L, Fan E, Amaral ACK, McCredie VA, Pinto R, Quinonez CR, Sutherland S, Scales DC, Cuthbertson BH. 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. Trials. 2019;20:603. doi: 10.1186/s13063-019-3673-0.
    1. Clinical Trials Ontario (2021) Streamlined research ethics review. . Accessed 01 Jan 2021
    1. Weijer C, Grimshaw JM, Eccles MP, McRae AD, White A, Brehaut JC, Taljaard M, Ottawa Ethics of Cluster Randomized Trials Consensus Group The Ottawa statement on the ethical design and conduct of cluster randomized trials. PLoS Med. 2012;9:e1001346–e1001346. doi: 10.1371/journal.pmed.1001346.
    1. Hemming K, Taljaard M, McKenzie JE, Hooper R, Copas A, Thompson JA, Dixon-Woods M, Aldcroft A, Doussau A, Grayling M, Kristunas C, Goldstein CE, Campbell MK, Girling A, Eldridge S, Campbell MJ, Lilford RJ, Weijer C, Forbes AB, Grimshaw JM. Reporting of stepped wedge cluster randomised trials: extension of the CONSORT 2010 statement with explanation and elaboration. BMJ. 2018;363:k1614. doi: 10.1136/bmj.k1614.
    1. Dale CM, Prendergast V, Gelinas C, Rose L. Validation of the critical-care pain observation tool (CPOT) for the detection of oral-pharyngeal pain in critically ill adults. J Crit Care. 2018;48:334–338. doi: 10.1016/j.jcrc.2018.09.024.
    1. Ames NJ, Sulima P, Yates JM, McCullagh L, Gollins SL, Soeken K, Wallen GR. Effects of systematic oral care in critically ill patients: a multicenter study. Am J Crit Care. 2011;20:e103–114. doi: 10.4037/ajcc2011359.
    1. Sinuff T, Muscedere J, Adhikari NK, Stelfox HT, Dodek P, Heyland DK, Rubenfeld GD, Cook DJ, Pinto R, Manoharan V, Currie J, Cahill N, Friedrich JO, Amaral A, Piquette D, Scales DC, Dhanani S, Garland A. Knowledge translation interventions for critically ill patients: a systematic review. Crit Care Med. 2013;41:2627–2640. doi: 10.1097/CCM.0b013e3182982b03.
    1. Klompas M, Berra L. Should ventilator-associated events become a quality indicator for ICUs? Respir Care. 2016;61:723–736. doi: 10.4187/respcare.04548.
    1. Centers for Disease Control (CDC) (2020) Ventilator-associated event (VAE). . Retrieved 20 Dec 2020
    1. Zhao T, Wu X, Zhang Q, Li C, Worthington HV. Hua F (2020) Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia. Cochrane Database Syst Rev. 2020;12(12):CD008367. doi: 10.1002/14651858.CD008367.pub4.
    1. Shiau HJ, Reynolds MA. Sex differences in destructive periodontal disease: exploring the biologic basis. J Periodontol. 2010;81:1505–1517. doi: 10.1902/jop.2010.100045.
    1. Terezakis E. The impact of hospitalization on oral health: a systematic review. J Clin Periodontol. 2011;38:628–636. doi: 10.1111/j.1600-051X.2011.01727.x.
    1. Dale CM, Smith O, Burry L, Rose L. Prevalence and predictors of difficulty accessing the mouths of intubated critically ill adults to deliver oral care: an observational study. Int J Nurs Stud. 2018;80:36–40. doi: 10.1016/j.ijnurstu.2017.12.009.
    1. 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. Intensive Care Med. 2018;44:1017–1026. doi: 10.1007/s00134-018-5171-3.
    1. Dennesen P, van der Ven A, Vlasveld M, Lokker L, Ramsay G, Kessels A, van den Keijbus P, van Nieuw AA, Veerman E. Inadequate salivary flow and poor oral mucosal status in intubated intensive care unit patients. Crit Care Med. 2003;31:781–786. doi: 10.1097/01.CCM.0000053646.04085.29.
    1. McNally E, Krisciunas GP, Langmore SE, Crimlisk JT, Pisegna JM, Massaro J. Oral care clinical trial to reduce non-intensive care unit, hospital-acquired pneumonia: lessons for future research. J Healthc Qual. 2019;41:1–9. doi: 10.1097/JHQ.0000000000000131.
    1. Ellingson K, Haas JP, Aiello AE, Kusek L, Maragakis LL, Olmsted RN, Perencevich E, Polgreen PM, Schweizer ML, Trexler P, VanAmringe M, Yokoe DS. Strategies to prevent healthcare-associated infections through hand hygiene. Infect Control Hosp Epidemiol. 2014;35:937–960. doi: 10.1086/651677.
    1. Ernst R CI (2014) Price indexes for clinical trial research: a feasibility study. In: Services DoIaM, editor. Washington, DC: U.S. Bureau of Labor Statistics
    1. Klompas M, Berra M. Should ventilator-associated events become a quality indicator for ICUs? Respir Care. 2016;61(6):723–736. doi: 10.4187/respcare.04548.
    1. Moore GF, Audrey S, Barker M, Bond L, Bonell C, Hardeman W, Moore L, O’Cathain A, Tinati T, Wight D, Baird J. Process evaluation of complex interventions: Medical Research Council guidance. BMJ. 2015;350:h1258. doi: 10.1136/bmj.h1258.
    1. Hemming K, Taljaard M. Sample size calculations for stepped wedge and cluster randomised trials: a unified approach. J Clin Epidemiol. 2016;69:137–146. doi: 10.1016/j.jclinepi.2015.08.015.
    1. Hemming K, Taljaard M. Reflection on modern methods: when is a stepped-wedge cluster randomized trial a good study design choice? Int J Epidemiol. 2020;49:1043–1052. doi: 10.1093/ije/dyaa077.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa