Chlorhexidine: Friend or Foe?

Meghan MacKenzie, BSc (Pharm), ACPR, PharmD

Karen Webb-Anderson, RN, BSc, BScN, CCN(c), MN

Cynthia Isenor, RN, MScN

Objectives

• Review the culprit for this discussion, ventilator associated pneumonia (VAP), and the bundle approach to prevention

• Review the evidence related to the use of chlorohexidine gluconate (CHG) for the prevention of VAP

• Share experiences of how to change well engrained clinical practices, such as the VAP bundle

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Ventilator Associated Pneumonia• Intubated patient is at risk of inoculation of lower respiratory

tract

• Sources: – oropharynx, subglottic, sinuses and GI tract

• Access: – ETT / cuff

• Host: – Immunosuppressed, Co-morbidities, Weak or absent cough

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Ventilator Associated Pneumonia

• Reported rates of 10-20% ventilated patients

incidence in Canadian ICUs 10.6 / 1000 ventilator days

• Associated mortality and morbidity

in Canada, responsible for approx. 230 deaths / yr

• Significant healthcare costs

estimated cost per pneumonia $11,500 /

$46 million per annum in Canada

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VAP rates • How do we measure how we are doing?• Rate is dependent on the definition• Determining a single comparative rate or benchmark is

challenging given:– the variation of case definitions – the variation of ICU-type – the variation of associated risk factors

Practically: • ICU clinicians ‘don’t believe’ the rates, as we often treat sick

patients on speculation

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Examples of Local DataNSHA HAI Surveillance Quarterly Report

Q1 FY 2018-19

3A and 5.2 ICU 2017

Q1 Q2 Q3 Q4

3A # of VAPs 2 1 1 0

Rate/1000 vent days 4.4 2.6 3.0 0.0

5.2 # of VAPs 0 2 3 1

Rate/1000 vent days 0.0 3.3 5.0 1.8

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‘Bundles’

• Evidence-based practices grouped together to support uptake / consistent practice

• Synergy of interventions• Common practice in ICU

– Compliance is becoming a minimum expectation

• Most VAP bundle studies analyze a ‘fixed package’ vs disaggregating the contributions of each component

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Bundle Components for VAP Prevention

Safer Healthcare Now! / Canadian Patient Safety Institute website:

Five key components for the VAP bundle:• Elevate the head of the bed to 45° when possible; otherwise, attempt to maintain the head of the

bed at more than 30°• Evaluate readiness for extubation daily• Use endotracheal tubes with subglottic secretion drainage• Conduct oral care and decontamination with chlorhexidine• Initiate safe enteral nutrition within 24–48 hours of ICU admissionAdditional evidence-based components of care:• Hand hygiene• Practices that promote patient mobility and autonomy• Venous thromboembolism prophylaxis

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Bundle Components for VAP PreventionCanadian Patient Safety Institute website:

Five key components for the VAP bundle:• Elevate the head of the bed to 45° when possible; otherwise, attempt to maintain the head of the bed at

more than 30°• Evaluate readiness for extubation daily• Use endotracheal tubes with subglottic secretion drainage• Conduct oral care and decontamination with chlorhexidine• Initiate safe enteral nutrition within 24–48 hours of ICU admissionAdditional evidence-based components of care:• Hand hygiene• Practices that promote patient mobility and autonomy• Venous thromboembolism prophylaxis

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Accreditation Canada StandardsUp to Version 11:

“The Safer Healthcare Now! Ventilator-Associated Pneumonia (VAP) bundle is implemented for all clients on ventilators, in partnership with the client and family.”

Version 12 – present

High-Priority Criteria: “Interventions that cover prevention and treatment of ventilator-associated pneumonia are implemented for all clients who are intubated/trecheostomized and mechanically ventilated.

Guidelines for the Criteria: CPSI provides the following prevention strategies: elevation of the head of the bed, daily assessment of readiness for extubation, use of oral versus nasal tubes to access the trachea or stomach, and the use of subglottic aspiration endotracheal tubes to drain subglottic secretions.

10Note absence of

‘decontamination with chlorhexidine’

• But what if a well-engrained bundle has a component with conflicting evidence?

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SUMMARY OF EVIDENCE FOR CHG

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JAMA Intern Med. 2014;174(5):751-761.

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Klompas M et al; 201416 RCTs, n= 3630

P Adult patients receiving mechanical ventilation

I Chlorhexidine

C Placebo

O VAPMortalityDuration of mechanical ventilation ICU and Hospital LOS Antibiotics

JAMA Intern Med. 2014;174(5):751-761. 14

CHLORHEXIDINE NO CHLORHEXIDINE RISK RATIO 95% CI

Cardiac surgery patients

5.6% (52/928) 10% (92/940) 0.56 (0.41-0.77)

Non-Cardiac surgery patients

17% (155/905) 22% (185/857) 0.78 (0.60-1.02)

Total

11% (207/1833) 15% (277/1797) 0.73 (0.58-0.92)

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Klompas M et al; 2014: VAP

JAMA Intern Med. 2014;174(5):751-761.

CHLORHEXIDINE NO CHLORHEXIDINE RISK RATIO 95% CI

Cardiac surgery patients

1.7% (16/928) 2% (19/940) 0.88 (0.25-3.14)

Non-Cardiac surgery patients

38% (267/709) 35% (228/657) 1.13 (0.99-1.29)

Total

17% 15% 1.13 (0.99-1.28)

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Klompas M et al; 2014: Mortality

JAMA Intern Med. 2014;174(5):751-761.

Klompas M et al; 2014

Cardiac Surgery

Intervention Comparator

0.12% solution BID Identical placebo

0.12% solution BID Listerine

0.12% solution QID + 0.12% nasal gel Identical placebo

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Klompas M et al; 2014

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Non-Cardiac Surgery

Intervention Comparator

0.2% gel TID placebo gel

0.2% solution BID Identical placebo

0.2% gel TID Placebo gel

0.12% solution BID Half strength hydrogen peroxide

2% in petroleum jelly QID Vaseline

0.2% solution BID Normal Saline

2% solution QID Normal Saline

0.12% solution TID Identical Placebo

0.2% solution BID 0.01% potassium permangate

0.12% solution QID and BID Identical placebo

0.2% solution BID Sterile water

2% gel QID Placebo gel

0.2% solution QID Normal saline

Klompas M et al; 2014: Interpretation

• No difference found in VAP when looking only at non cardiac surgery patients– Patient representation for chlorhexidine 0.12% is low– VAP in cardiac surgery patients with the intervention we

currently use– ? can this benefit be extrapolated to medical/surgical ICU

Bottom line • There may be a benefit in terms of VAP, but it has not been

elucidated• There is no difference in mortality

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20Cochrane Database of Systematic Reviews 2016, Issue 10. Art. No.: CD008367.

Hau F et al; 2016Meta-analysis 18 RCTs, n=2451, 86% adults

P Critically ill adults and children receiving mechanical ventilation

I Chlorhexidine rinse or gel

C Placebo or usual care

O VAPMortality Duration of mechanical ventilation ICU LOS

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Hau F et al; 2016

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Hau F et al; 2016: Interpretation

• Clinical heterogeneity is high

• Evidence deemed high quality by Cochrane

• Intervention of exposure to chlorhexidine–incidence of VAP

• RR 0.75, 95% CI 0.62 to 0.91, P=0.004

– No difference in mortality observed• RR 1.09, 95% CI 0.96 to 1.23, P = 0.20

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24BMJ 2014;348:g2197

Price R et al; 2014

Meta-analysis 11 RCTs n=2618

P Adult general ICU patients (Cardiac surgery patients were excluded)

I Chlorhexidine in any formulation

C Standard of care or placebo

O Mortality

25BMJ 2014;348:g2197

Price R et al; 2014

26BMJ 2014;348:g2197

Price R et al; 2014

27BMJ 2014;348:g2197

• Increased odds of mortality when chlorhexidineused in adult ICU patients

Summary Study Results

Klompas 2014 No difference in VAP rates among non-cardiac surgery patientsNo difference in mortality

Hau 2016 Decrease in VAP when adults, children, cardiac surgery, surgical and medical ICU patients are pooled No difference in mortality

Price 2014 Increased odds of mortality when chlorhexidine used in adult ICU patients

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Retrospective, single center, observational cohort, 11,138 patients. Increased odds of death in patients not ventilated and not admitted to ICUs.

Uncertain rationale for harm

• Aspiration of chlorhexidine, leading to acute lung injury/ARDS

• Adverse effects on oral mucosa

• Allergic reactions

• Contribute to increasing antimicrobial resistance

30Intensive Care Med (2018) 44:1153–1155

Recommendations

European Guidelines for the management of HAP/VAPEur Respir J 2017; 50: 1700582

Panel decided not to make a recommendation on the use of CHG, until more safety data available

Intensive Care Society, bundle of interventions for prevention of VAPJournal of the Intensive Care Society 2016, Vol. 17(3) 238–243

Does not recommend the use of CHG in non-cardiac surgery patients

CADTHChlorhexidine for Oral Care: A Review of Clinical Effectiveness and Guidelines. Ottawa: CADTH; 2019 Jan

• CHG was effective for the prevention of VAP in cardiothoracic ICUs

• The evidence is un-clear in non-cardiac surgery patients• Chlorhexidine was associated with a high risk of mortality

in non- cardiac surgery patients

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CHORAL study

• Objective:

– Evaluate the de-adoption of oral chlorhexidine and the introduction of oral care practices on selected outcomes in critically ill mechanically ventilated adults

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Nova Scotia Health Authority

• Decision

– Removal of chlorhexidine from mouth care process in the Central Zone ICUs

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What Now?

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Practice Change

Current Practice

Structural

• CHG has been built into routine Admission Order Sets

Culture of Best-Practice

• Over years, has the focus on extensive education and auditing of components

Changing PracticeStructural

• Removal of CHG from Order Sets

Changing Culture of Practice

• Requires re-education & explanation as challenging a well-established practice

• Offer a new strategy – importance of mouth care without CHG

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Discussion An important facilitator of change in healthcare is what others are doing, how they interpret the same evidence within the Canadian context• Recent conversation in national

Critical Care Email group suggest lots still using CHG, with a few exceptions (practice shared from Alberta no CHG unless Cardiac Surgery)

• CACCN publication (fall 2018) – ICU Nurses in Quebec indicated the quality of mouth care provided is low and varied

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Discussion Has there been discussion of the potential risk of CHG in your units?

How are you weighing the risks to adjust practice?

What does mouth care look like in your ventilated patients?

Have you experienced a similar well-engrained practice, promoted as a ‘bundle’ component, being called into question?

What is the responsibility of organizations to ‘unbundle’ practices?

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