1. 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?

2. Disclosures Grant funding from the US Centers for Disease Control and Prevention Honoraria from Premier Healthcare Alliance for lectures on VAP surveillance

3. 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, 2007 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 Beyersmann et al, Infect Control Hosp Epidemiol 2006;27:493

4. 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 Antibiotic Start 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

5. Impact of Diagnostic Criteria on VAP Prevalence Prospective surveillance, 1824 patients, Tertiary Med-Surg Unit, Belgium Ego et al. Chest 2014;ePub ahead of print

6. 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

8. Interobserver agreement in VAP surveillance 7 IP 1 (11 VAPs) IP 2 (20 VAPs) 3 3 0 1 7 5 IP 3 (15 VAPs) Klompas, AJIC 2010:38:237 Kappa = 0.40 50 ventilated patients with respiratory deterioration

9. 6 Case Vignettes Presented to 43 Surveyors Crit Care Med 2014;42:497

10. Accuracy of clinical diagnosis of VAP Relative to 253 autopsies 80% 100% Sensitivity / Positive Predictive Value 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

11. Accuracy of quantitative BAL cultures Relative to histology 80% 100% Sensitivity / Positive Predictive Value 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

12. Implications for prevention

13. from doctorrw.blogspot.com

14. The VAP Prevention Paradox VAP Rates Vent LOS ICU LOS Hospital LOS Death Regular oral care with chlorhexidine Silver-coated endotracheal tubes Head-of-bed elevation Crit Care 2009;13:315

15. 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

16. 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

17. 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

18. 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

19. 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

20. Silver-Coated Endotracheal Tubes VAP Rates and Outcomes VAP Incidence VAPs per 100 Patients 4.0 5.0 3.0 2.0 1.0 0 8.0 10.0 6.0 2.0 0 4.0 Conventional ETTsSilver coated ETTs Lengths of Stay (days) Vent days ICU days Hospital days 6.0 12.0 JAMA 2008;300:805

21. Silver-coated endotracheal tubes Microbiological Outcomes VAP Counts Included: yeast, normal flora, coag-neg Staph, & Enterococcus

22. 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

23. 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

24. Semi-recumbent position and ICU Days -2 +1 +2 0 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 Supine Position ??? All studies

25. Critical Care Medicine 2013;41:2467-2475

26. Ventilator -associated conditions (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

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

28. Impact of VAEs on length-of-stay Controlled for time to VAE, age, sex, unit, comorbidities, severity of illness. All comparisons are to patients without VAE (control). Control VAC *** IVAC *** Possible VAP *** Probable VAP *** Control VAC *** IVAC *** Possible VAP *** Probable VAP *** Days Infect Control Hosp Epidemiol 2014;5:502-510

29. Impact of VAEs on mortality Odds Ratio or Hazard Ratio 110520.5 USA – 3 centers PLoS ONE 2011;6:e18062 USA – 8 centers Crit Care Med 2012;40:3154 Canada – 11 centers Chest 2013;144:1453 Netherlands – 2 centers Am J Resp Crit Care Med 2014;189:947 USA – 2 centers Crit Care Med 2014;ePub USA – 1 center Infect Control Hosp Epidemiol 2014;5:502 VAEVAP

30. Canadian Critical Care Trials Group ABATE Study Enhanced care for vented patients, 11 ICUs, 1330 patients Muscedere et al. Chest 2013;144:1453-1460

31. 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

32. The VAP Prevention Paradox VAP Rates Vent LOS ICU LOS Hospital LOS DeathVAEs Regular oral care with chlorhexidine ? Silver-coated endotracheal tubes ? Head-of-bed elevation ? Crit Care 2009;13:315

33. 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

34. Minimize sedation Greater 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/alphabetic al/midazolam-1mg-5ml/ NEJM 1996;335:1864-9NEJM 2000;342:1471-7 Lancet 2008;371:126-134Lancet 2010;375:475-80

35. 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;371:126-134 NEJM 1996;335:1864-9 Wake Up and Breathe

36. 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/Crit CareCom0610Fig2.jpg Lord et al., Crit Care Med 2013;41:717 Schweickert et al., Lancet 2009;373:1874 Needham et al., Arch Phys Med Rehabil 2010;91:536

37. 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):R1 ARDSnet, NEJM 2000;342:1301-1308 http://page2anesthesiology.org/2012/less-rather-than-more- volume-is-better-when-ventilating-patients-after-cardiac-surgery/

38. 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

39. Michael Klompas (mklompas@partners.org) Thank you!

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