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Donald Dumford’s Senior Talk

Ventilator-Associated Pneumonia (VAP)

Overview

• Morbidity, mortality and cost associated with VAP

• Who gets VAP? Risk factors that increase likelihood of developing VAP

• Etiology: The bugs

• Treatment: The drugs

• How VAP develops (Pathogenesis)

• Measures to prevent VAP

Definition- “Know thy enemy”

Pneumonia that develops in someone who has been intubated

-Typically in studies, patients are only included if intubated greater than 48 hours

-Early onset= less than 4 days-Late onset= greater than 4 days

Endotracheal intubation increases risk of developing pneumonia by 6 to 21 fold

Accounts for 90% of infections in mechanically ventilated patients

American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.

CDC definition of pneumonia

Horan TC, Andrus M, Dudreck MA. CDC/NHSN surveillance definition of health-care associated infection and criteria for specific types of infection in the acute care setting

Prevalence of VAP

• Occurs in 10-20% of those receiving mechanical ventilation for greater than 48 hours

• Rate= 14.8 cases per 1000 ventilator days

Cook et al. Incidence of and risk factors for ventilator-associated pneumoniain critically ill patients.

VAP at UH# cases/1000 ventilator days

0

5

10

15

20

25

30

2004 2005 2006 2007 2008

Total

CTICU

SICU

MICU

CICU

NSU

When does VAP occur?

• Cook et al showed . . .– 40.1% developed before day 5– 41.2% developed between days 6 and 10– 11.3% developed between days 11-15– 2.8% developed between days 16 and 20– 4.5% developed after day 21

Cook et al. Incidence of and risk factors for ventilator-associated pneumoniain critically ill patients.

Time frame of intubation and risk

• Risk of pneumonia at intubation days– 3.3% per day at day 5– 2.3% per day at day 10– 1.3% per day at day 15

Cook et al. Incidence of and risk factors for ventilator-associated pneumoniain critically ill patients.

Cook, D. J. et. al. Ann Intern Med 1998;129:433-440

Hazard rate for ventilator-associated pneumonia during the stay in the intensive care unit

Who gets VAP? (Risk factors)

• Study of 1014 patients receiving mechanical ventilation for 48 hours or more and free of pneumonia at admission to ICU

• Increased risk associated with admitting diagnosis of :– Burns (risk ratio=5.09)– Trauma (risk ratio=5.0)– Respiratory disease (risk ratio=2.79)– CNS disease (risk ratio=3.4)

Cook et al. Incidence of and risk factors for ventilator-associated pneumoniain critically ill patients.

Who gets VAP? (Risk factors)

• Increased risk with . . .– Witnessed aspiration (Risk ratio=3.25)– Administration of paralyzing agent (risk ratio=1.57)

• Decreased risk with . . .– Exposure to antibiotics (Risk ratio=0.37)– Risk ratio=0.94 per antibiotic prescribed

• At day 5=0.3• At day 10=0.43• At day 15=0.62• At day 20=0.89

Cook et al. Incidence of and risk factors for ventilator-associated pneumoniain critically ill patients.

VAP

Morbidity, Mortality and Cost

Length of stay and cost

• Remember that Medicare is no longer reimbursing for nosocomial infections

• VAP increased length of stay in the ICU by 5-7 days (mean of 6.1 days)1,2

• Increase in cost– Increase of $10,000-$40,000 per patient 1,2

1 Safdar N et al. Clinical and economic consequences of ventilator-associated pneumonia: a systematic review2 Rello et al. Epidemiology and outcomes of ventilator-associated pneumonia in a large US database

Increased mortality

• Attributable mortality rates ranging from 5.8-13.5%1

• In systematic review by Safdar et al, patients with VAP found to be twice as likely to die as those without VAP (Pooled odds ratio 2.03)2

1 CDC.gov. Guidelines for preventing health-care-associated pneumonia, 2003.

2 Safdar N et al. Clincial and economic consequences of ventilator-associated pneumonia: a systematic review

Etiology

AKA- the Bugs

Etiology

• Early vs. Late VAP1

– Early onset= Pneumonia develops within 96 hours (4 days) of patient’s admission to the ICU or intubation for mechanical ventilation

– Late onset= Pneumonia develops after 96 hours (4 days) of patient’s admission to the ICU or intubation for mechanical ventilation

– Very early onset= within 48 hours after intubation2

1 CDC.gov. Guidelines for preventing health-care-associated pneumonia, 2003.

2 Park DR. The microbiology of ventilator-associated pneumonia.

The Bugs

• Figure 1 from Park

Park DR. The microbiology of ventilator-associated pneumonia.

The Bugs

Park DR. The microbiology of ventilator-associated pneumonia.

Etiology- select risk factors for pathogens

Streptococcus pneumoniae Smoking, COPD, absence of antibiotic therapy

Haemophilus influenzae Smoking, COPD, absence of antibiotic therapy

MSSA Younger age, Traumatic coma, Neurosurgery

MRSA COPD, steroid therapy, longer duration of MV, prior antibiotics

Pseudomonas aeruginosa COPD, steroid therapy, longer duration of MV, prior antibiotics

Acinetobacter species ARDS, head trauma, neurosurgery, gross aspiration, prior cephalosporin therapy

Park DR. The microbiology of ventilator-associated pneumonia.

Risks for MDR

American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.

Treatment

Treatment

American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.

Treatment- Early onset VAP with no risk factors, any disease severity

American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.

Treatment- Late onset or risk factors for MDR or all disease severity

American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.

Pathogenesis

PathogenesisNormal host defense mechanisms

Anatomy of airways

Cough reflex

Mucus

Mucociliary clearance

Alveolar macrophages

Leukocytes

Immunoglobulins

Complement

Lactoferrin

Basement membrane

Pathogenesis

Which of these is altered in the intubated patients?

Anatomy of airways

Cough reflex

Mucus

Mucociliary clearance

Pathogenesis

• Where do the bacteria come from?– Tracheal colonization- via oropharyngeal

colonization or GI colonization– Ventilator system

• How do they get into the lung?– Breakdown of normal host defenses– Two main routes

• Through the tube• Around the tube- microaspiration around ETT cuff

Oropharyngeal colonization• Scannapieco et al showed a transition in

the colonization of dental plaques in patients in the ICU

• Control=25 subjects presenting to preventive dentistry clinic

• Study group=34 noncardiac patients admitted to medical ICU at VA hospital (sampled within 12 hours of admission and every third day)

Scannapieco et al. Colonization of dental plaque by respiratory pathogens in medical intensive care patients

Colonization of oropharynx

Medical ICU (N=34) Dentistry Clinic (N=25)

Species Plaque Mucosa Plaque Mucosa

S. aureus 2 5 0 1

P. aeruginosa 8 7 0 0

K. pneumoniae 2 5 0 0

S. marcescens 3 4 0 0

E. aerogenes 0 0 0 1

E. cloacae 1 1 0 0

E. asburiae 0 0 0 1

P. mirabilis 1 0 0 0

E. coli 0 1 0 0

C. diversus 1 1 0 0

A. calcoaceticus 0 1 0 0

Pasteurella spp. 0 0 1 0

Total 18 24 1 3

Scannapieco et al. Colonization of dental plaque by respiratory pathogens in medical intensive care patients

GI colonization

• Increased gastric pH leads to bacterial overgrowth

• Reflux can then lead to colonization of oropharynx

• Use of antacids and H2 blockers associated with GI colonization

Safdar et al. The pathogenesis of ventilator-associated pneumonia: its relevance to developing effective strategies for prevention

Supine patients• Studies using radioactive labeling of gastric

contents showed that radioactive counts were higher in larynx of supine patients

• One of the studies showed the same organisms in stomach, pharynx and endobronchial samples1

• Drakulovic et al. studied rate of VAP and found it to be higher in supine compared to semi-recumbent patients2

1 Hess DR. Patient positioning and ventilator-associated pneumonia

2 Drakulovic et al. Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial

Tracheal colonization

• Cendrero et al:• 25 patients of 110 studied developed VAP• In these 25 patients, 22 had their trachea

colonized 3.63 days prior to diagnosis of VAP

• 17 of the 22 had oropharyngeal colonization prior to trachea

• Only 7 had prior colonization of the stomach

Cendrero JAC et al. Role of different routes of tracheal colonization in the development of pneumonia in patients receiving mechanical ventilation.

Pathogenesis- Through the tube

1) Condensate in tubing

2) Development of ETT biofilm

Condensate

• Condensate in ventilator tubing becomes rapidly contaminated with bacteria from patient’s oropharynx

• Craven et al showed that 33% of inspiratory circuits were colonized within 2 hours and 80% within 24 hours

ET tube biofilm

• Exopolysaccharide outer layer with quiescent bacteria within– Difficult for bacteria to penetrate outer layer

and bacteria within resistant to bactericidal effects of bacteria

• Adair et al study– “Microorganisms of high pathogenic potential

were isolated from all ETs collected from patients with VAP compared with 30% of ETs from the control group.”

ET tube biofilm

• Furthermore . . .– Study group of VAP patients- 70% found to

have tracheal isolates identical to biofilm isolates

– Control group without VAP- no matching isolates

Difficult to kill biofilm organismsComparison of MBC of antibiotics for tracheal isolates vs.

biofilm isolates

Organism Tobramycin Cefotaxime Cefuroxime

P. aeruginosa-Tracheal-ET

256>1024

32>1024

>1024>1024

Enterobacteriaceae-Tracheal-ET

4>1024

128256

32512

S. aureus-Tracheal-ET

18>1024

16128

16>1024

Prevention

Preventive strategies

1) Around the tube

2) Through the tube

3) Less tube

Around the tube

1) Oral decontamination and selective decontamination of the digestive tract

2) Aspiraton of subglottic secretions including continuous aspiration of subglottic secretions

3) Semi-recumbent positioning

4) Sucralfate for stress ulcer prophylaxis

Oral decontamination- 2 meta-analyses

• Chlebicki and Safdar investigating the use of chlorhexidine in intubated patients– From Chlebicki and Safdar- relative risk

reduction of 30%– Effect most substantial for cardiac surgery

patients– Concluded by research team that

chlorhexidine likely delays rather than prevents VAP

Oral decontamination

• Chan et al. investigated antibiotics and antiseptics– Antibiotics were not found to be beneficial– Antiseptics were found to be beneficial in 6

out of 7 studies• Chlorhexidine studied in 6, five of which showed

benefit

– Note that mortality, ICU stay and duration of mechanical ventilation were not statistically significant

SDD- selective decontamination of the digestive tract

• Multiple studies showing effectiveness• Big concern is antibiotic resistance• Most recently- NEJM January 2009

– Study of 13 intensive care units in Netherlands showed statistically significant reduction of mortality of 3.5% in patients receiving SDD

– Same study showed that patients receiving SOD (selective oropharyngeal decontamination) had decrease of 2.9%

Subglottic secretion drainage

• Meta-analysis of Dezfulian et al showed risk ratio of 0.51 for development of VAP

• Also found that those receiving secretion developed VAP 3.1 days later than control

• Study groups also averaged 1.8 less days of VAP

Dezfulian C, Shojanic K, Collard HR, Kim HM, Matthay MA, Saint S. Subglottic secretion drainage for preventing ventilator-associated pneumonia.

Dezfulian C, Shojanic K, Collard HR, Kim HM, Matthay MA, Saint S. Subglottic secretion drainage for preventing ventilator-associated pneumonia.

Drainage of subglottic secretions

Continuous aspiration of subglottic secretions (CASS)

Kollef et al. A randomized clinical trial of continuous aspiration of Subglottic secretions in cardiac surgery patients

Semi-recumbent positioning

• Reduces episodes of aspiration

• As mentioned previously, study by Drakulovic et al showed lower rates of VAP in patients in semi-recumbent position

• Recommended by CDC and ATS/IDSA guidelines

Stress Ulcer Prophylaxis

• Sucralfate vs. PPI– In recent studies there was no VAP benefit in

those receiving sucralfate and these patients also had higher incidence of GI bleed

CDC.gov. Guidelines for preventing health-care-associated pneumonia, 2003.

Via the tube

1) Ventilator circuit changes

2) Condensate

3) Silver-lined ET tubes

Ventilator circuit management

• Craven and colleagues showed that ventilator circuit change every 24 hours compared to 48 hours increased VAP incidence

• Several later studies showed that circuit changes could be used safely for greater than 48 hours

Kollef et al. Mechanical ventilation with or without 7-day circuit changes

Ventilator circuit management• 1999 study by Kollef et al. • Randomized clinical trial looking at circuit

change every 7 days vs. no routine circuit change

• Study group incidence=24.5%• Control group incidence=28.8%• Cost of ventilator circuit changes

– $7410 control group– $330 for study group

Kollef et al. Mechanical ventilation with or without 7-day circuit changes

Condensate management• Heat-moisture exchanger

– Theoretical advantage=prevents bacterial colonization of tubing

– Studies= Mixed results– Disadvantage=increases dead space and resistance

to breathing

• Heated wire to elevate temp of inspired air– Advantage=Decreases condensate formation– Disadvantage=Blockage of ET tube by dried

secretions

CDC.gov. Guidelines for preventing health-care-associated pneumonia, 2003.

Condensate management

• Nurse and provider education regarding management of tubes with patient position change or manipulation of bed to ensure that condensate in tubing does not flow towards patient

Silver-lined ET tube

• Broad-spectrum antimicrobial activity in vitro

• Reduces bacterial adhesion to devices in vitro

• Blocks biofilm formation on the device in animal models

• Dog model- decreased severity of lung colonization

Silver-lined ET tube

• NASCENT study- prospective, randomized, single-blind, controlled study

• Relative risk reduction of VAP=35.9%

• Delayed incidence of VAP

• No significant reduction in mortality

Through the tube and around the tube

Inhaled prophylactic antibiotics

Inhaled prophylactic antibiotics

• Current controversial and more studies needed

• Major concern is development of antibiotic resistance

• No mortality benefit

Less tube

1) Nurse implemented sedation protocol

Sedation protocol implementation

• 2007 study by Quenot et al.

• Control phase without nurse-implemented sedation protocol followed by study phase with nurse-implemented sedation protocol

• Study phase had significantly shorter duration of MV (4.2 days) and lower incidence of VAP (6% vs. 15%)

UH bundle

• Head of bed elevated above 30 degrees

• Oral care q4H

• Suctioning q4H

• Stress ulcer prophylaxis

References1) American Thoracic Society, Infectious Diseases Society of America.

Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416.

2) Horan TC, Andrus M, Dudreck MA. CDC/NHSN surveillance definition of health-care associated infection and criteria for specific types of infection in the acute care setting. Am J Infect Control 2008; 36:309-32.

3) Cook DJ, Walter SD, Cook RJ, Griffith LE, Guyatt GH, Leasa D, Jaeschke RZ, Crun-Buisson. Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients. Ann Intern Med 1998; 129: 433-440.

4) Safdar N, Dezfulian C, Collard HR, Saint S. Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med 2005; 33: 2184-93.

5) Park DR. The microbiology of ventilator-associated pneumonia. Resp care 2005; 50: 742-65.

References6) Rello J, Ollendorf DA, Oster G, Vera-Llonch M, Bellm L, Redman R,

Kollef MH. Epidemiology and outcomes of ventilator-associated pneumonia in large US database. Chest 2002; 122: 2115-2121.

7) 2003 Guidelines for preventing health-care associated pneumonia. Recommendations of CDC and the healthcare infection control practices advisory committee. CDC.gov.

8) Kollef MH, Skubas NJ, Sundt TM. A randomized clinical trial of continous aspiration of subglottic secretions in cardiac surgery patients. Chest 1999; 116:1339-46.

9) Safdar N, Crnich CJ, Maki DG. The pathogenesis of ventilator-associated pneumonia: its relevance to developing effective strategies for prevention. Resp Care 2005; 50: 729-41.

10) Scannapieco FA, Steward EM, Mylotte JM. Colonization of dental plaque by respiratory pathogens in medical intensive care patients. Crit Care Med 1992; 20: 740-5.

11) Kollef MH, Afessa B, Anzuesto A, et al. Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: the NASCENT randomized trial. JAMA 2008; 300: 805-813.

References12) Drakulovic MB, Torres A, Bauer TT, Nicolas JM, Nogue S, Ferrer M.

Supine body position as risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial. The Lancet 1999; 354: 1851-58.

13) Hess DR. Patient positioning and ventilator-associated pneumonia. Resp Care 2005; 50: 892-99.

14) Cendrero JAC, Sole-Violan J, Benitez AB, Catalan JN, Fernandez JA, Santana PS, de Castro FR. Role of different routes of tracheal colonization in the development of pneumonia in patients receiving mechanical ventilation. Chest 1999; 116: 462-70.

15) Collard HR, Saint S, Matthay MA. Prevention of ventilator-associated pneumonia: an evidence-based systematic review. Ann Int Med 2003; 138: 495-501

16) Dezfulian C, Shojanic K, Collard HR, Kim HM, Matthay MA, Saint S. Subglottic secretion drainage for preventing ventilator-associated pneumonia. Am J Med 2005; 118:11-18.

17) Adair CG et al. Implications of endotracheal tube biofilm for ventilator-associated pneumonia. Intensive Care Med 1999; 25: 1072-76.

Thank you

Any questions?