Donald Dumfords Senior Talk

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Donald Dumfords Senior Talk
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Ventilator-Associated Pneumonia (VAP)
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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

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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.
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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
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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 pneumonia in critically ill
patients.
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VAP at UH cases/1000 ventilator days
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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 pneumonia in critically ill
patients.
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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 pneumonia in critically ill
patients.
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Hazard rate for ventilator-associated pneumonia
during the stay in the intensive care unit
Cook, D. J. et. al. Ann Intern Med
1998129433-440
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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 ratio5.09)
• Trauma (risk ratio5.0)
• Respiratory disease (risk ratio2.79)
• CNS disease (risk ratio3.4)

Cook et al. Incidence of and risk factors for
ventilator-associated pneumonia in critically ill
patients.
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Who gets VAP? (Risk factors)

• Increased risk with . . .
• Witnessed aspiration (Risk ratio3.25)
• Administration of paralyzing agent (risk
  ratio1.57)
• Decreased risk with . . .
• Exposure to antibiotics (Risk ratio0.37)
• Risk ratio0.94 per antibiotic prescribed
• At day 50.3
• At day 100.43
• At day 150.62
• At day 200.89

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

• Morbidity, Mortality and Cost

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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 review 2 Rello et al. Epidemiology
and outcomes of ventilator-associated pneumonia
in a large US database
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Increased mortality

• Attributable mortality rates ranging from
  5.8-13.51
• 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

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Etiology

• AKA- the Bugs

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Etiology

• Early vs. Late VAP1
• Early onset Pneumonia develops within 96 hours
  (4 days) of patients admission to the ICU or
  intubation for mechanical ventilation
• Late onset Pneumonia develops after 96 hours (4
  days) of patients 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-associat
  ed pneumonia.

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The Bugs

• Figure 1 from Park

Park DR. The microbiology of ventilator-associated
pneumonia.
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The Bugs
Park DR. The microbiology of ventilator-associated
pneumonia.
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Etiology- select risk factors for pathogens
Park DR. The microbiology of ventilator-associated
pneumonia.
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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.
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Treatment
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Treatment
American Thoracic Society, Infectious Diseases
Society of America. Guidelines for the management
of adults with hospital-acquired,
ventilator-associated, and healthcare-associated
pneumonia.
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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.
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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.
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Pathogenesis
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Pathogenesis
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Pathogenesis
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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

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Oropharyngeal colonization

• Scannapieco et al showed a transition in the
  colonization of dental plaques in patients in the
  ICU
• Control25 subjects presenting to preventive
  dentistry clinic
• Study group34 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
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Colonization of oropharynx

Medical
ICU (N34) Dentistry Clinic (N25)
Scannapieco et al. Colonization of dental plaque
by respiratory pathogens in medical intensive
care patients
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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
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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
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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.
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Pathogenesis- Through the tube

• Condensate in tubing
• Development of ETT biofilm

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Condensate

• Condensate in ventilator tubing becomes rapidly
  contaminated with bacteria from patients
  oropharynx
• Craven et al showed that 33 of inspiratory
  circuits were colonized within 2 hours and 80
  within 24 hours

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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.

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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

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

• Around the tube
• Through the tube
• Less tube

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Around the tube

• Oral decontamination and selective
  decontamination of the digestive tract
• Aspiraton of subglottic secretions including
  continuous aspiration of subglottic secretions
• Semi-recumbent positioning
• Sucralfate for stress ulcer prophylaxis

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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

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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

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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

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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.
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Dezfulian C, Shojanic K, Collard HR, Kim HM,
Matthay MA, Saint S. Subglottic secretion
drainage for preventing ventilator-associated
pneumonia.
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Drainage of subglottic secretions
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Continuous aspiration of subglottic secretions
(CASS)
Kollef et al. A randomized clinical trial of
continuous aspiration of Subglottic secretions
in cardiac surgery patients
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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

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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.
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Via the tube

• Ventilator circuit changes
• Condensate
• Silver-lined ET tubes

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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
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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 incidence24.5
• Control group incidence28.8
• Cost of ventilator circuit changes
• 7410 control group
• 330 for study group

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

• Heat-moisture exchanger
• Theoretical advantageprevents bacterial
  colonization of tubing
• Studies Mixed results
• Disadvantageincreases dead space and resistance
  to breathing
• Heated wire to elevate temp of inspired air
• AdvantageDecreases condensate formation
• DisadvantageBlockage of ET tube by dried
  secretions

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

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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

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Silver-lined ET tube

• NASCENT study- prospective, randomized,
  single-blind, controlled study
• Relative risk reduction of VAP35.9
• Delayed incidence of VAP
• No significant reduction in mortality

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Through the tube and around the tube

• Inhaled prophylactic antibiotics

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Inhaled prophylactic antibiotics

• Current controversial and more studies needed
• Major concern is development of antibiotic
  resistance
• No mortality benefit

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Less tube

• Nurse implemented sedation protocol

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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)

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UH bundle

• Head of bed elevated above 30 degrees
• Oral care q4H
• Suctioning q4H
• Stress ulcer prophylaxis

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References

• 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.
• 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 36309-32.
• 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.
• 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.
• Park DR. The microbiology of ventilator-associated
  pneumonia. Resp care 2005 50 742-65.

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References

• 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.
• 2003 Guidelines for preventing health-care
  associated pneumonia. Recommendations of CDC and
  the healthcare infection control practices
  advisory committee. CDC.gov.
• Kollef MH, Skubas NJ, Sundt TM. A randomized
  clinical trial of continous aspiration of
  subglottic secretions in cardiac surgery
  patients. Chest 1999 1161339-46.
• 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.
• 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.
• 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.

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References

• 12) 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 11811-18.
• 17) Adair CG et al. Implications of endotracheal
  tube biofilm for ventilator-associated pneumonia.
  Intensive Care Med 1999 25 1072-76.

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Thank you

• Any questions?