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Preventing Ventilator-Associated Pneumonia: Review of the Evidence Michael Klompas MD, MPH, FIDSA, FSHEA Harvard Medical School, Harvard Pilgrim Health Care Institute, and Brigham and Women’s Hospital, Boston, MA Hong Kong Symposium on Prevention of Healthcare-associated Infections in Hospitals and Community Institutions January 19, 2019

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Page 1: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Michael Klompas MD, MPH, FIDSA, FSHEA Harvard Medical School, Harvard Pilgrim Health Care Institute,

and Brigham and Women’s Hospital, Boston, MA

Hong Kong Symposium on Prevention of Healthcare-associated Infections in Hospitals and Community Institutions

January 19, 2019

Page 2: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Disclosures

o Grant funding o Centers for Disease Control and Prevention o Massachusetts Department of Public Health

o Royalties o UpToDate

Page 3: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Ventilator-associated pneumonia

o Affects ~5-10% of ventilated patients o Increases ICU length of stay by ~4-7 days o Increases hospital length of stay by ~14 days o Crude mortality rate 30-50% o Attributable mortality 8-12% o Adds ~$10,000 to $40,000 to cost of hospital stay

Safdar et al, Crit Care Med 2005; 33:2184 Tejerina et al, J Crit Care 2006; 21:56

Muscedere et al, J Crit Care 2008;23:5-10 Eber et al, Arch Intern Med 2010;170:347-353

Nguile-Makao et al, Intensive Care Med 2010;36:781-9 Melsen et al, Lancet Infect Dis 2013;13:665-671

Kollef et al., Infection Control Hosp Epidemiol 2012;33:250-256 Ohannessian et al. Crit Care Med 2018;46:1093-1098

Page 4: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

from doctorrw.blogspot.com

Page 5: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Recommendations on Prevention of Ventilator-Associated Pneumonia

Page 6: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

0

50

100

150

200

1990 1995 2000 2005 2010 2015

Count of VAP Prevention Publications by Year PubMed, 1990-2018

Page 7: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Potential Strategies to Prevent VAP

1. Avoid intubation

2. Minimize sedation

3. Daily interruption of sedation

4. Spontaneous breathing trials

5. Early mobility

6. Head of bed elevation

7. Trendelenburg position

8. Subglottic secretion drainage

9. Maintain ETT cuff pressure

10. Tapered endotracheal cuffs

11. Ultrathin polyurethane cuffs

12. Avoid inhalers

13. Closed suctioning systems

14. Avoid patient transport

15. Tight glycemic control

16. Improve hand hygiene

17. Regular oral care

18. Toothbrushing / scaling

19. Oral care with chlorhexidine

20. Oral decontamination

21. Digestive decontamination

22. Use probiotics

23. Early enteral feeding

24. Acidify gastric contents

25. Avoid gastric distention

26. Silver-coated ETT tubes

27. Mucous shaver

28. Early tracheostomy

29. Change vent circuits only when soiled

30. Saline instillation prior to suctioning

31. Non-invasive positive pressure ventilation

32. High flow O2 by nasal cannula

33. Prophylactic antibiotics

34. Even to negative fluid balance

35. Minimize blood tranfusions

36. Avoid paralytics

37. Conduct VAP surveillance

38. Educate staff

39. Provide feedback to staff on rates and processes

40. Bundle interventions

Page 8: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Strategic Framework to Prevent VAP

Minimize aspiration of secretions around endotracheal tube cuff

Reduce colonization of the aerodigestive tract

Minimize contamination of equipment

Avoid intubation if possible

Minimize duration of intubation

• High flow O2 by nasal cannula • Non-invasive positive pressure ventilation

• Minimize sedation • Spontaneous awakening trials

• Spontaneous breathing trials • Early mobility

• Head of bed elevation • Subglottic secretion drainage

• Maintain cuff pressure • Novel cuff materials & shapes

• Regular oral care • Oral antiseptics

• Probiotics • Oral / digestive decontamination

• Silver-coated endotracheal tubes • Mucous shaver

• Change vent circuits only when soiled

Page 9: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

How do we choose from this list?

What works?

What should we prioritize?

Page 10: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

The VAP Prevention Paradox

VAP Rates

Vent

Days

ICU

Days

Hospital

Days Death

Oral care with chlorhexidine

Silver-coated endotracheal tubes

Subglottic secretion drainage

Head-of-bed elevation

Critical Care 2009;13:315

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Many strategies lower VAP rates but have no impact on other outcomes!

Why the mismatch?

Page 12: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

VAP diagnosis is subjective

VAP diagnosis is non-specific

Many VAP studies are under-powered

Reasons for the Prevention Paradox

The case of oral care with chlorhexidine

The case of silver-coated ETTs & subglottic secretion drainage

The case of head of bed elevation

Page 13: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

VAP diagnosis is subjective

VAP diagnosis is non-specific

Many VAP studies are under-powered

Reasons for the Prevention Paradox

The case of oral care with chlorhexidine

The case of silver-coated ETTs & subglottic secretion drainage

The case of head of bed elevation

Page 14: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Oral Care with Chlorhexidine Meta-analysis of Randomized Studies: lower VAP rates

Lower VAP Rates Risk Ratio 0.72 (0.55-0.94)

Lancet Infectious Dis 2011;11:845

Page 15: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Does this patient have VAP?

Page 16: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

from downloads.lww.com/wolterskluwer_vitalstream_com/sample-content/9780781788786_Craven/samples/mod09/topic9a/text.html

Are there more secretions today?

Page 17: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Interobserver Agreement in VAP Diagnosis

7

IP 1 (11 VAPs)

IP 2 (20 VAPs)

3

3 0

1 7

5

IP 3 (15 VAPs)

Am J Infection Control 2010:38:237

Kappa = 0.40

50 ventilated patients with respiratory deterioration

Page 18: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

VAP Prevention Studies are at High Risk for Bias

Especially Open Label studies

Page 19: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Open Label vs Double Blind Studies

Open Label Randomized Controlled Trials:

Double-Blind Randomized Controlled Trials:

JAMA Internal Med 2014;174:751

Lower VAP Rates! RR 0.61 (0.35-1.04)

No Difference! RR 0.88 (0.66-1.16)

Page 20: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Need to look at objective outcomes

Page 21: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Duration of Mechanical Ventilation

No Difference! Mean Difference 0.01 days (-1.12 to 1.14)

Randomized trials of oral care with chlorhexidine vs control solution

JAMA Internal Med 2014;174:751-761

Page 22: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

ICU Length of Stay

No Difference! Mean Difference -0.10 days (-0.25 to 0.05)

Randomized trials of oral care with chlorhexidine vs control solution

JAMA Internal Med 2014;174:751-761

Page 23: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Mortality

Trend to Higher Mortality! RR 1.13 (0.99 to 1.28)

JAMA Internal Med 2014;174:751-761

Page 24: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Second Meta-Analysis of RCTs: Significantly Higher Mortality

Mortality Mortality

BMJ 2014;348:g2197

Odds Ratio 1.25 (1.05-1.50)

Page 25: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Independent Signal

Retrospective cohort analysis 5,539 patients on mechanical ventilation

Spontaneous breathing trials

Spontaneous awakening trials

Head of bed elevation

Stress ulcer prophylaxis

Thromboprophylaxis

Oral care with chlorhexidine

0.2 2.0 1.0

Hazard Ratios for Ventilator Death

Lower Mortality

Higher Mortality

5.0 0.5

JAMA Internal Med 2016;176:1277-1283

adjusted for comorbidities, severity of illness, contraindications, etc.

Page 26: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

But what’s the mechanism?

Page 27: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Oral Ulcers Associated with 2% Chlorhexidine

Bleeding Ulcer White Plaques

Intensive Care Med 2016;42:620-621

Page 28: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Oral Ulcers Associated with 2% Chlorhexidine

Bleeding Mouth Dry Tongue, Apthous Lesions

Intensive Care Med 2016;42:620-621

Page 29: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Case Reports of Allergies and Anaphylaxis

9% of perioperative allergic reactions attributed to chlorhexidine

Case reports of anaphylaxis

Allergy 2014;69(10):1390-1396 Acta Anaesthesiol Scand 2001;45:1290-1294

Page 30: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Case Reports of ARDS following Aspiration

Vet Hum Toxicol 2002;44:89-91

Page 31: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Aspiration of Oral Antiseptics and ARDS

0%

5%

10%

15%

20%

Providone-Iodine Placebo

% P

atie

nts

wit

h A

RD

S

ARDS

Randomized controlled trial of providone-iodine vs placebo to prevent VAP

Crit Care Med 2014;42:1-8

Page 32: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Chlorhexidine Instillation into Rat Lungs

Human and Experimental Toxicology 2011;30:1795-1803

After 24 hours

After 7 days

Control 0.02% CHG 0.20% CHG

Page 33: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

VAP diagnosis is subjective

VAP diagnosis is non-specific

Many VAP studies are under-powered

Reasons for the Prevention Paradox

The case of oral care with chlorhexidine

The case of silver-coated ETTs & subglottic secretion drainage

The case of head of bed elevation

Page 34: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Accuracy of clinical diagnosis of VAP

80%

100% Se

nsit

ivit

y /

P

osit

ive

Pre

dict

ive

Val

ue

60%

40%

20%

0% Positive

Predictive Value

Tejerina et al., J Critical Care 2010;25:62

Sensitivity

Loose definition: Infiltrate and 2 of temp / wbc / purulence

Strict definition: Infiltrate and 3 of temp / wbc / purulence

Relative to 253 autopsies

Page 35: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Accuracy of BAL cultures Relative to histology

80%

100% Se

nsit

ivit

y /

P

osit

ive

Pre

dict

ive

Val

ue

60%

40%

20%

0% Positive

Predictive Value

Kirtland, Chest 1997;112:445 Fabregas, Thorax 1999;54:867

Chastre, Am Rev Respir Dis 1984;130:924 Torres, Am J Resp Crit Care Med 1994;149:324

Marquette, Am J Resp Crit Care Med 1995;151:1878 Papazian, Am J Resp Crit Care Med 1995;152:1982

Sensitivity

Page 36: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Circularity Between VAP Preventive Practices and the VAP Definition

VAP Definition Fever

Leukocytosis Purulent Secretions

Positive cultures

Oral care with CHG Silver Coated ETT

Subglottic secretion drainage Semi-recumbent position etc.

positive cultures and/or

secretions

Page 37: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

This means that even studies with Double Blinding &

Objective Diagnostic Criteria are still at risk of bias

Page 38: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Silver-Coated Endotracheal Tubes

o Randomized controlled trial of 2,003 patients to silver coated vs conventional endotracheal tubes

o VAP defined as present if quantitative BAL fluid culture with >104 colony forming units/mL

36% fewer VAPs in patients randomized to

silver-coated endotracheal tubes

JAMA 2008;300:805-813

Page 39: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Silver-Coated Endotracheal Tubes

VAP Counts Included:

Normal flora Candida species Enterococcus, &

Coagulase-Negative Staphylococci

JAMA 2008;300:805-813

Page 40: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Silver Coated Endotracheal Tubes

0

1

2

3

4

5

6

7

8

VAP Rates Mortality Vent Days ICU Days

36% decrease no difference! no difference! no difference!

20%

30%

10%

0%

JAMA 2008;300:805-813

Control ETT Silver Coated ETT N=2,003

Page 41: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Subglottic Secretion Drainage

Risk Ratio 0.58 (0.51- 0.67)

Crit Care Med 2016;44:830-840

Meta-Analysis of randomized trials: Significantly Lower VAP Rates

Page 42: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Subglottic Secretion Drainage

Crit Care Med 2016;44:830-840

Meta-Analysis of randomized trials: No Impact on Ventilator Days or ICU Days

Ventilator Days

ICU Days

No difference!

No difference!

Page 43: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

VAP diagnosis is subjective

VAP diagnosis is non-specific

Many VAP studies are under-powered

Reasons for the Prevention Paradox

The case of oral care with chlorhexidine

The case of silver-coated ETTs & subglottic secretion drainage

The case of head of bed elevation

Page 44: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Preventive Practices in U.S. Hospitals

0%

25%

50%

75%

100%

Semi-recumbent position Oral care with an antiseptic Subglottic secretion drainage

Per

cent

of

Hos

pita

ls

2005 2009 2013

Random samples of ~600 U.S. acute care hospitals, 2005-2013

BMJ Quality Safety 2015;24:385-392

Page 45: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Reducing the risk of ventilator-acquired pneumonia through head of bed elevation

Nursing Crit Care 2007;12:287

N=221

N=86

N=30

Head of Bed Elevation Studies

Page 46: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

0%

10%

20%

30%

Drakulovic et al.,Lancet 1999

0%

20%

40%

60%

Keeley et al,Nursing Crit Care 2007

Supine Semi-recumbent

Head-of-Bed Elevation and VAP Rates

P=.02

N=221

NS

N=86

NS

N=30

0%

10%

20%

30%

van Nieuwenhoven,Crit Care Med 2006

VA

P

Page 47: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Semi-recumbent vs Supine Position

Lower VAP Rates

Cochrane Review 2016;1:CD009946

64% decrease in VAP risk ratio

Page 48: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Semi-recumbent vs Supine Position …no difference in mortality or duration of mechanical ventilation

Cochrane Review 2016;1:CD009946

Mortality

Vent days

Page 49: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Maybe Head Down is Better than Head Up?

Intensive Care Med 2017;43:1572-1581

Cumulative Risk for VAP

Head Up

Head Down

394 patients randomized to lateral Trendelenburg vs semi-recumbent position

Page 50: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Maybe Head Down is Better than Head Up?

Intensive Care Med 2017;43:1572-1581

394 patients randomized to lateral Trendelenburg vs semi-recumbent position

o VAP o 0.5% vs 4.0% (P=.04)

o Antibiotic Utilization o No difference

o 28-day mortality o No difference

o Adverse Events o 6 in lateral Trendelenburg group vs 0 in semi-recumbent

o Oxygen desaturation, hemodynamic instability, intracranial hemorrhage, brachial plexus injury

o Trial stopped early

Page 51: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Joint Commission Journal on Quality and Patient Safety 2005;31:243-248

Page 52: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Elevate the head of the bed

Daily sedative interruptions

Spontaneous breathing trials

Stress ulcer prophylaxis

DVT prophylaxis

Oral care with chlorhexidine

The Classic Ventilator Bundle

Page 53: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Bundles Associated with Lower VAP Rates

0

10

20

VA

Ps

per

1000

Ven

t-D

ays

Before Bundle Implementation After Bundle Implementation

Page 54: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

0

5

10

15

20

25

Pre-Bundle Post-Bundle

VA

Ps

per

1000

ven

tila

tor-

days

Better Care?

Some combination of the above?

Stricter Surveillance?

How do we interpret a drop in VAP rates?

Am J Infect Control 2012;40:408-410

Change in case mix?

Less colonization vs less VAP?

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U.S. National VAP Rates Cases Reported to CDC by Hospitals, 2004-2012

0

2

4

6

8

10

12

2003 2005 2007 2009 2011 2013

VA

Ps

per

1000

ven

t-da

ys

Source: CDC NNIS and NHSN

SICUs

MICUs

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U.S. National VAP Rates, 2005-2013

JAMA 2016;316:2427-2429

VA

P c

ases

per

100

pat

ient

s

Centers for Medicare and Medicaid Services Audits

Page 57: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

“Given the uncertainty surrounding the accuracy and reproducibility of VAP diagnoses … we prioritize VAP interventions that have been shown to

improve objective outcomes, such as duration of mechanical ventilation, intensive care or hospital length of stay, mortality, and/or costs in randomized

controlled trials.”

Infection Control Hospital Epidemiol 2014;8:915

Page 58: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Infection Control Hospital Epidemiol 2014;8:915

Basic Practices Special Practices

Interventions that improve objective outcomes and confer little risk of harm

Interventions that improve objective outcomes but confer some risk of harm

Interventions that decrease VAP rates but insufficient data available on their impact on objective outcomes

Interventions that are outcome neutral but cost saving

Page 59: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Infection Control Hospital Epidemiol 2014;8:915

Basic Practices Special Practices

Interventions that improve objective outcomes and confer little risk of harm

Interventions that improve objective outcomes but confer some risk of harm

Interventions that decrease VAP rates but insufficient data available on their impact on objective outcomes

Interventions that are outcome neutral but cost saving

Page 60: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Basic Practices: Improve Objective Outcomes, Little Risk of Harm

o Use non-invasive positive pressure ventilation in selected populations

o Manage patients without sedation whenever possible

o Interrupt sedation daily

o Assess readiness to extubate daily

o Perform spontaneous breathing trials with sedatives turned off

o Facilitate early mobility

Page 61: Preventing Ventilator-Associated Pneumonia: Review of the ...icidportal.ha.org.hk/Home/File?path=/Training Calendar...Preventing Ventilator-Associated Pneumonia: Review of the Evidence

Non-Invasive Positive Pressure Ventilation

Randomized trials of non-invasive ventilation for acute hypercapnic respiratory failure due to COPD exacerbations

Relative Risk for Death 0.54 (95% CI 0.38-0.76)

Cochrane Review 2017;7:CD004104

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Lighter Sedation: Lower Mortality, Fewer Vent Days

Crit Care Med 2018;46:471-479

Mortality

Ventilator Days

Lower Mortality

Fewer Vent Days

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Lancet 2008;371:126-34

0

5

10

15

20

Vent Days ICU Days Hospital Days

Day

s

Daily SBT Alone Daily SBT + SAT

-2 days

-3.8 days

-4.3 days

Paired Sedative Interruptions & Breathing Trials

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Early mobility

o May encourage & facilitate less sedation

o May help prevent delirium

o These benefits may by synergistic with other ventilator bundle components such as spontaneous awakening and breathing trials.

o Data on outcomes are mixed. Some studies show less time to extubation while others do not.

http://69.36.35.38/images/CHESTPhysician/CritCareCom0610Fig2.jpg

Thorax 2018;73:213-221 JAMA 2016;315:2694-2702 Lancet 2016;388:1377–88 Crit Care Med 2013;41:717

Lancet 2009;373:1874 Arch Phys Med Rehabil 2010;91:536

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Early Mobility Hospital Death

Days Alive and Out of Hospital to 180 days

No impact on hospital death rates…

…but more days alive and out of hospital

Intensive Care Med 2017;43:171-183

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Ventilator Bundle Compliance and Death

Spontaneous breathing trials

Spontaneous awakening trials

Head of bed elevation

Thromboprophylaxis

Stress ulcer prophylaxis

Oral care with chlorhexidine

0.2 2.0 1.0

Hazard Ratios for Ventilator Death

Lower Mortality Higher Mortality

5.0 0.5

Retrospective analysis of 5,539 patients on mechanical ventilation

adjusted for comorbidities, severity of illness, contraindications, etc.

JAMA Internal Med 2016;176:1277-1283

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Ventilator Bundle Compliance and Time to Extubation Alive

Thromboprophylaxis

Spontaneous breathing trials

Spontaneous awakening trials

Head of bed elevation

Stress ulcer prophylaxis

Oral care with chlorhexidine

0.2 2.0 1.0

Hazard Ratios for Extubation Alive

Later Extubation Earlier Extubation

5.0 0.5

Retrospective analysis of 5,539 patients on mechanical ventilation

adjusted for comorbidities, severity of illness, contraindications, etc.

JAMA Internal Med 2016;176:1277-1283

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Infection Control Hospital Epidemiol 2014;8:915

Basic Practices Special Practices

Interventions that improve objective outcomes and confer little risk of harm

Interventions that improve objective outcomes but confer some risk of harm

Interventions that decrease VAP rates but insufficient data available on their impact on objective outcomes

Interventions that are outcome neutral but cost saving

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Basic Practices: Outcome Neutral but Cost Saving

Change ventilator circuits only when visibly soiled or malfunctioning

Am Rev Respir Dis 1991;143:738 Ann Intern Med 1995;123:168

Infect Control Hosp Epidemiol 1996;17:14 Infect Control Hosp Epidemiol 2004;25:1077

Multiple RCTs

No impact on VAP rates

No impact on duration of mechanical ventilation, ICU length of stay, or mortality

BUT … cost saving!

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Infection Control Hospital Epidemiol 2014;8:915

Basic Practices Special Practices

Interventions that improve objective outcomes and confer little risk of harm

Interventions that improve objective outcomes but confer some risk of harm

Interventions that decrease VAP rates but insufficient data available on their impact on objective outcomes

Interventions that are outcome neutral but cost saving

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Special Practice: Better Outcomes but Possible Risks

Selective oral & digestive decontamination

www.ukenglish.org.uk/idiom-of-the-week-elephant-in-the-room

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Selective Oral & Digestive Decontamination

Oropharyngeal antibiotic paste applied 4x/day

o Tobramycin

o Colistin

o Amphotericin B

Designed to target Staph aureus, aerobic gram negatives, and yeast

Clin Microbiol Infect 2018;24:505-513

Selective Oral Decontamination

Oropharyngeal paste applied 4x/day

o Same antibiotics as SOD

Plus…

Antibiotic suspension via NG tube

o Same antibiotics as SOD

Plus…

4-day course of intravenous cefotaxime

Selective Digestive Decontamination

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Selective Oral & Digestive Decontamination

Digestive Decontamination vs Control

Oral Decontamination vs Control

Digestive vs Oral Decontamination

Mortality Odds Ratio 0.82 (95% CI 0.72-0.93)

Mortality Odds Ratio 0.84 (95% CI 0.73-0.97)

Mortality Odds Ratio 0.90 (95% CI 0.82-0.97)

Individual patient level meta-analysis of randomized trials, N=16,528 patients

N=5,304

N=3,921

N=12,967

Clin Microbiol Infect 2018;24:505-513

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Impact on Antibiotic Resistance Meta-analysis of 9 trials of digestive decontamination that included data on resistance rates

Aminoglycoside resistance: OR 0.73 (0.51-1.05)

Fluoroquinolone resistance: OR 0.52 (0.16-1.68)

Cephalosporin resistance: OR 0.33 (0.20-0.52)

Lancet Infect Dis 2013;13:328

Odds Ratio 0.73 (0.51-1.05)

Odds Ratio 0.52 (0.16-1.68)

Odds Ratio 0.33 (0.20-0.52)

Odds Ratio

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How can it be that giving antibiotics to everyone leads to less resistance???

Fewer infections overall in the digestive decontamination group

Fewer infections = fewer resistant infections

Fewer infections leads to less overall antibiotic usage

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Is the effect sustained?

Months

Cefotaxime resistance rates in respiratory isolates amongst 8 Dutch ICUs for 24 months following introduction of selective digestive decontamination versus the preceding 33 months

J Antimicrob Chemother 2014;69:797

No apparent sustained change in resistance rates over time

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Does SDD generalize to high resistance settings?

ICU-Acquired Gram Negative Bacteremia 28 Day Mortality

2% CHG SOD SDD* 2% CHG SOD SDD*

Cluster randomized trial of usual care vs 2% CHG oral care vs selective oral decontamination vs selective digestive decontamination* in 13 ICUs with high baseline rates of antibiotic utilization and resistant organisms

1.0

1.5

0.75

0.5

Adj

uste

d H

azar

d /

Odd

s R

atio

JAMA 2018;320:2087-2098 *SDD included oral antibiotic paste and gastric suspension but no intravenous antibiotics

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Infection Control Hospital Epidemiol 2014;8:915

Basic Practices Special Practices

Interventions that improve objective outcomes and confer little risk of harm

Interventions that improve objective outcomes but confer some risk of harm

Interventions that decrease VAP rates but insufficient data available on their impact on objective outcomes

Interventions that are outcome neutral but cost saving

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Special Practices: Lower VAP Rates, Insufficient Data on Other Outcomes

o Probiotics

o Automated control of endotracheal tube cuff pressures

o Saline instillation before tracheal suctioning

o Mechanical toothbrushing

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Probiotics

Ventilator-associated pneumonia

Risk Ratio for VAP 0.73 (95% 0.60-0.89)

Frontiers in Pharmacology 2017;8:717

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Probiotics

Overall Mortality

Trend towards lower mortality!

Frontiers in Pharmacology 2017;8:717

Parallel non-significant trends towards fewer ventilator days and shorter ICU length-of-stay

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Generally Not Recommended

o Oral chlorhexidine

o Stress ulcer prophylaxis

o Tapered endotracheal tubes

o Subglottic secretion drainage

o Silver-coated endotracheal tubes

o Monitoring residual gastric volumes

o Early parenteral nutrition

o Kinetic beds

o Prone positioning

No impact on VAP and/or objective outcomes

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Stress Ulcer Prophylaxis Randomized controlled trials of ulcer prophylaxis vs placebo in patients getting enteral nutrition

Less pneumonia with SUP

More pneumonia with SUP

Antacid Placebo

OR 1.53 (95% CI 1.04-2.27)

Higher risk for VAP!

Ventilator-associated pneumonia

Critical Care 2018;22:20

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Stress Ulcer Prophylaxis Randomized trials of stress ulcer prophylaxis vs placebo in patients getting enteral nutrition

Less bleeding with SUP

More bleeding with SUP

Antacid Placebo

No clear decrease in bleeding!

Gastrointestinal Bleeding

Critical Care 2018;22:20

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Stress Ulcer Prophylaxis

-20

0

20

40

GI bleeding Pneumonia

Ris

k D

iffe

renc

e pe

r 10

00 P

atie

nts

plac

ebo

sucr

alfa

te

H2

blo

cker

s

PP

Is

plac

ebo

sucr

alfa

te

H2

blo

cker

s

PP

Is

Intensive Care Med 2018;44:1-11

Network meta-analysis of 57 randomized controlled trials, N=7,293

*

*

*

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Tapered vs Conical Endotracheal Tube Cuffs

Crit Care Med 2018;46:316–323 Intensive Care Med 2017;43:1562-1571

Anesth Pain Med 2017;12:275-280

Animal studies suggest that a tapered cuff may better protect against seepage of secretions around the endotracheal tube cuff

No Impact on VAP Rates !

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What’s missing?

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0

0.5

1

1.5

2

2.5

2nd 3rd 4th

Adj

uste

d O

dds

of D

eath

Cumulative Fluid Balance and Risk of Death International survey of 1,808 patients with sepsis admitted to an intensive care unit

Reference

Fluid Balance Quartile at 72h From Admission

Crit Care Med 2017:45:386-394

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Depletive Fluid Management and VAP Randomized controlled trial of depletive fluid management during ventilator weaning

(smaller volume infusions, more diuresis), N=304

0%

5%

10%

15%

20%

VAP VAE0

1

2

3

4

Days to ExtubationVAP VAE Days to Extubation

Usual Care Depletive Fluid Management

Chest 2014;146:58-65

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Summary

o Many interventions proposed to prevent VAP

o Many reported to lower VAP rates but few have been associated with improvements in objective outcomes.

o Possible reasons for the VAP Prevention Paradox • VAP diagnosis is subjective (observer bias may favor lower VAP rates)

• VAP signs are non-specific (interventions may decrease colonization more than infection)

• Lack of power

o Implication: need to look at objective outcomes for corollary evidence of benefit when evaluating prevention studies

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My Recommendations

o Avoid intubation if possible (use non-invasive strategies)

o Elevate the head of the bed

o Provide oral care without chlorhexidine

o Minimize sedation

o Paired daily spontaneous awakening and breathing trials

o Early mobility

o Thromboprophylaxis

o Conservative fluid management

o +/- Selective digestive decontamination

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Thank You!

[email protected]