Objective Outcomes

Michael Klompas MD, MPH, FRCPC, FIDSA

Harvard Medical School, Harvard Pilgrim Health Care Institute, and

Brigham and Women’s Hospital, Boston, USA

CUSP for Mechanically Ventilated Patients

October 7, 2014

What are they?

Why do they matter?

Disclosures

Grant funding from the US Centers for Disease Control and Prevention

Honoraria from Premier Healthcare Alliance for lectures on VAP surveillance

Ventilator-associated pneumonia

Affects ~5-10% of ventilated patients

Increases ICU length of stay by ~4-7 days

Increases hospital length of stay by ~14 days

Crude mortality rate 30-50%

Attributable mortality 8-12%

Adds ~$10-50,000 to cost of hospital stay

CMS 1533-P, 2007Safdar 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;170:347-353Nguile-Makao et al, Intensive Care Med 2010;36:781-9

Beyersmann et al, Infect Control Hosp Epidemiol 2006;27:493

Diagnostic Criteria for VAP

High Temp

Low Temp

High WBC

Low WBC

Low P:F Ratio

Increased vent settings

Purulent secretions

Gram stain neutrophils

New AntibioticStart

Infiltrate

CDC Old Definition ✓ ✓ ✓ ✓ ✓ ✓ ✓CDC New Definition ✓ ✓ ✓ ✓ ✓ ✓ ✓HELICS Criteria ✓ ✓ ✓ ✓ ✓ACCP Criteria ✓ ✓ ✓ ✓ ✓Clinical Pulmonary Infection Score ✓ ✓ ✓ ✓ ✓ ✓ ✓Johanson’s Criteria ✓ ✓ ✓ ✓

Ego et al. Chest 2014;ePub ahead of print

Impact of Diagnostic Criteria on VAP Prevalence

CDC Old

Criter

ia

CDC New

Crit

eria

HELICS

ACCPCPIS

Joha

nson

0

10

20

30

40

Nu

mb

er o

f V

AP

sProspective surveillance, 1824 patients, Tertiary Med-Surg Unit, Belgium

Ego et al. Chest 2014;ePub ahead of print

All VAP Signs Subjective, Non-Specific, or Both

The core clinical signs associated with VAP:

• Radiographic opacities• Fever• Abnormal white blood cell count• Impaired oxygenation• Increased pulmonary secretions

Interobserver agreement in VAP surveillance

7

IP 1 (11 VAPs)

IP 2(20 VAPs)3

30

1 7

5

IP 3 (15 VAPs)

Klompas, AJIC 2010:38:237Kappa = 0.40

50 ventilated patients with respiratory deterioration

6 Case Vignettes Presented to 43 Surveyors

0

1

2

3

4

5

6

Survey Respondents

Nu

mb

er o

f V

AP

s

Crit Care Med 2014;42:497

Accuracy of clinical diagnosis of VAPRelative to 253 autopsies

80%

100%

Sen

sit

ivit

y /

P

osit

ive P

red

icti

ve V

alu

e

60%

40%

20%

0%PositivePredictiv

eValue

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

Accuracy of quantitative BAL culturesRelative to histology

80%

100%

Sen

sit

ivit

y /

P

osit

ive P

red

icti

ve V

alu

e

60%

40%

20%

0%PositivePredictiv

eValue

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

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

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

Sensitivity

Implications for prevention

from doctorrw.blogspot.com

The VAP Prevention Paradox

VAPRate

s

Vent

LOS

ICULOS

Hospital

LOS

Death

Regular oral care with chlorhexidine

Silver-coated endotracheal tubes

Head-of-bed elevation

Crit Care 2009;13:315

VAP diagnosis is subjective

VAP diagnosis is non-specific

Many VAP studies under-powered

Reasons for the Prevention Paradox

The case of chlorhexidine

The case of silver-coated ETTs

The case of head of bed elevation

VAP diagnosis is subjective

VAP diagnosis is non-specific

Many VAP studies under-powered

Reasons for the Prevention Paradox

The case of chlorhexidine

The case of silver-coated ETTs

The case of head of bed elevation

Oral CHG in Non-Cardiac Surgery Patients

Open Label Studies: RR 0.61 (0.35-1.04)

Double-Blind Studies: RR 0.88 (0.66-1.16)

JAMA Internal Med 2014;174:751

Routine Oral Care with Chlorhexidine

Impact on mean duration of mechanical ventilation:

NONE

Impact on ICU length-of-stay

NONE

Impact on mortality

POSSIBLE INCREASE!!! RR 1.13 (0.99 to 1.28)

JAMA Internal Med 2014;174:751

VAP diagnosis is subjective

VAP diagnosis is non-specific

Many VAP studies under-powered

Reasons for the Prevention Paradox

The case of chlorhexidine

The case of silver-coated ETTs

The case of head of bed elevation

Silver-Coated Endotracheal TubesVAP Rates and Outcomes

VAP Incidence

VA

Ps p

er

100 P

ati

en

ts

4.0

5.0

3.0

2.0

1.0

0

8.0

10.0

6.0

2.0

0

4.0

Conventional ETTs

Silver coated ETTs

Len

gth

s o

f S

tay (

days)

Ventdays

ICUdays

Hospital

days

6.0 12.0

JAMA 2008;300:805

Silver-coated endotracheal tubesMicrobiological Outcomes

VAP Counts Included: yeast, normal flora, coag-neg Staph, & Enterococcus

VAP diagnosis is subjective

VAP diagnosis is non-specific

Many VAP studies under-powered

Reasons for the Prevention Paradox

The case of chlorhexidine

The case of silver-coated ETTs

The case of head of bed elevation

Reducing the risk of ventilator-acquired pneumonia through head of bed elevation Nursing Crit Care 2007;12:287

N=221

N=86

N=30

78% in VAP, P=.04

71% in VAP, P>.10

46% in VAP, P>.10

Semi-recumbent position and ICU Days

-2 -1 +1 +20

Drakulovic, Lancet 1999(difference in means)

van Nieuwenhoven, CCM 2006(difference in medians)

Keeley, Nursing Crit Care 2007(not reported)

Difference in ICU Length of Stay

Favors Semi-Recumbent

Position

Favors SupinePosition

???All studies

Critical Care Medicine 2013;41:2467-2475

Ventilator-associated conditions (VAC)

DatePEEP(min)

FiO2(min)

Jan 1 10 100

Jan 2 5 50

Jan 3 5 40

Jan 4 5 40

Jan 5 8 60

Jan 6 8 50

Jan 7 8 40

Jan 8 5 40

Jan 9 5 40

VAC

Rise in daily minimum PEEP ≥3cm or FiO2 ≥20 sustained ≥2 days after ≥2 days of stable or improving daily minimum PEEP or FiO2

http://www.cdc.gov/nhsn/VAE-calculator

Impact of VAEs on length-of-stayControlled for time to VAE, age, sex, unit, comorbidities, severity of illness. All comparisons are to patients without VAE (control).

Hospital Days

Ventilator Days

0 5 10 15 20 25 30 35

ControlVAC ***

IVAC ***Possible VAP ***Probable VAP ***

ControlVAC ***

IVAC ***Possible VAP ***Probable VAP ***

Days

Infect Control Hosp Epidemiol 2014;5:502-510

Impact of VAEs on mortality

Odds Ratio or Hazard Ratio1 10520.

5

USA – 3 centersPLoS ONE 2011;6:e18062

USA – 8 centersCrit Care Med 2012;40:3154

Canada – 11 centersChest 2013;144:1453

Netherlands – 2 centersAm J Resp Crit Care Med 2014;189:947

USA – 2 centersCrit Care Med 2014;ePub

USA – 1 centerInfect Control Hosp Epidemiol 2014;5:502

VAE VAP

Canadian Critical Care Trials Group ABATE StudyEnhanced care for vented patients, 11 ICUs, 1330 patients

Muscedere et al. Chest 2013;144:1453-1460

Baseline 6 months 15 months 24 months0

4

8

12

16VAC Rate (trend P=.05)

VA

Cs

per

100

pat

ien

ts

Conservative Fluid Management

• 304 patients randomized to daily BNP levels versus usual care

• Patients randomized to daily BNP levels• More diuretics, negative fluid balance• Less time to extubation• 50% fewer VAEs

P=.02

Dessap et al. Chest 2014; ePub ahead of print

Daily BNPs

Usual Care

0% 2% 4% 6% 8% 10% 12% 14% 16% 18% 20%

Incidence of VAEs

The VAP Prevention Paradox

VAPRate

s

Vent

LOS

ICULOS

Hospital

LOS

Death VAEs

Regular oral care with chlorhexidine ?Silver-coated endotracheal tubes ?Head-of-bed elevation ?

Crit Care 2009;13:315

The Upshot

VAP rates are unreliable outcomes

VAE rates likely reliable but still very new. Unclear how best practices will impact them.

If we want to know whether a prevention measure really works or not, we have to look at objective outcomes such as:

duration of mechanical ventilation

ICU length-of-stay

hospital length-of-stay

mortality

Minimize sedationGreater sedation associated with longer ventilator and ICU stays. Increases risk for pneumonia and other infections.

RCT data from Denmark showing that vented patients can be adequately managed with NO sedation

Spontaneous awakening trials associated with less overall sedative use and earlier extubation

http://ppcdrugs.com/en/products/alphabetical/midazolam-1mg-5ml/

NEJM 1996;335:1864-9 NEJM 2000;342:1471-7Lancet 2008;371:126-134 Lancet 2010;375:475-80

Paired daily sedative interruptions and spontaneous breathing trials

Spontaneous breathing trials associated with earlier extubation

Patients are more likely to pass spontaneous breathing trials if they’re awake for the trial

RCT data showing that pairing SATs with SBTs speeds extubation by ~3 days and shortens ICU and hospital LOS by ~4 days compared to SBTs alone

Lancet 2008;371:126-134NEJM 1996;335:1864-9

Wake Up and Breathe

Early mobility – Wake Up & Walk!

Early mobilization assocaited with less time to extubation and shorter ICU stays

May also help prevent atelectasis & delirium

As with improved sedative management and weaning protocols, less time on vent means less time at risk for VAEs

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

Lord et al., Crit Care Med 2013;41:717Schweickert et al., Lancet 2009;373:1874

Needham et al., Arch Phys Med Rehabil 2010;91:536

Low tidal volume ventilation

Higher tidal volumes associated with acute lung injury

Randomized controlled trial data showing that lower tidal volumes protect against acute lung injury in patients without ARDS and lower mortality rates in patients with ARDS

Determann, Critical care 2010;14(1):R1ARDSnet, NEJM 2000;342:1301-1308

http://page2anesthesiology.org/2012/less-rather-than-more-volume-is-better-when-ventilating-patients-after-cardiac-surgery/

Summary

VAP diagnosis is subjective and non-specific

Inconsistent association between VAP and patient outcomes

Many interventions purportedly lower VAP rates but no impact on patient outcomes: “the VAP Prevention Paradox”.

Makes VAP an unreliable outcome

VAEs more objective and consistently predict adverse outcomes… but the definitions are still very new, very little data so far on how prevention strategies impact VAE rates

Implication: need to look at objective outcomes if we want to be sure that CUSP 4 MVP is helping our patients

Michael Klompas (mklompas@partners.org)

Thank you!

Am J Resp Crit Care Med 2014;8:947Chest 2014;ePub ahead of print