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TRAUMA-ICU NURSING
EDUCATIONAL SERIES
VAP:
what, how, and why ?
Bradley J. Phillips, M.D.
Critical Care Medicine
Boston Medical Center
Boston University School of Medicine
Nosocomial Pneumonia
Leading cause of death from hospitalacquired
infections, with an associated
mortality rate of 30 %.
VAP is a sub-type of nosocomial pneumonia
specifically referring to a bacterial source
Kollef. NEJM 1999
“VAP”
defined as parenchymal lung infection
occurring more than 48 hrs after the initiation
of mechanical ventilation
Morehead & Pinto.
Arch Int Med 2000
VAP: a framework

(1)
Early-onset VAP
occurs within 48 – 72 hrs after tracheal intubation
 often from aspiration during the intubation process
 usually due to antibiotic-sensitive bacteria

 Oxacillin-sensitive
Staph aureus
 Haemophilus influenzae
 Strep pneumoniae
Kollef. NEJM 1999
VAP: a framework

(2)
Late-onset VAP
occurs after 72 hrs of mechanical ventilation
 multiple theories behind it’s actual development
 usually due to antibiotic-resistant bacteria

 Oxacillin-resistant
Staph aureus (“MRSA”)
 Pseudomonas aeruginosa
 Acinetobacter species
 Enterobacter species
Kollef. NEJM 1999
Why are we talking about VAP ?

Single most common ICU nosocomial infection

Incidence: 20 - 25% (though controversial !)

Mortality

Differing reports throughout the world…



range 20 - 80%
depends on type of ICU and organism
difficult to ascertain actual incidence



Varying definitions
Varying populations
Varying techniques & diagnostic methods
Epidemiology

Mechanically ventilated patients



Morbidity




9 – 24 % incidence
some authors report as high as 44%
increased ICU length of stay (5x longer)
increased total length of stay (2x longer)
increased ventilator days (7x longer)
Costs

Additional $8,800 for VAP
Papazian et al. Am J Res
CCM 1996.
Craven et al. Am Rev Res
Dis. 1996.
Kollef. JAMA 1993.
Torres et al. Am Rev Res
Dis 1990.
Pathogenesis of VAP
2 Key Steps
a. Bacterial colonization
of the aerodigestive
tract
b. Aspiration of
contaminated
secretions into the
lower airway
Kollef, NEJM 1999
Pathophysiology

Bacterial entry into the lower airway



(1)
Inhalation
Hematogeneous (“seeding”)
Contributing factors




impaired gastric and intestinal motility
altered LOC
diminished gag reflex
decreased mucociliary clearance
Pathophysiology
(2)
the endotracheal tube creates an abnormal continuum
between the upper airway and the trachea
as well as establishing a subglottic reservoir of
secretions rich in bacterial pathogens…
those secretions, over time,
become part of a biofilm that lines the ET tube – allowing
distal aerosolization of particulate matter via
the ventilatory cycle
Morehead et al. Arch Intern Med 2000
The Airway
Intubation

(1)
Greatest risk factor !!
increased incidence 7 - 21 fold
 reintubation
 47% compared to 10% in matched controls
 ICU stay and crude mortality higher


Etiology



Microaspiration
Oral and gastric bacteria colonize subglottic area
ET quickly invested with biofilm above and below cuff
Intubation

(2)
Mechanical factors

Glottis is eliminated


primary barrier to aspiration lost
Balloon cuff erodes tracheal epithelium
Allows direct bacterial invasion
 Role of low-pressure cuffs…?


Airway desiccation
loss of mucus/antibody production in oral cavity
 Role of humidified circuits…?

Role of the Gastric Tube

Intubated patients have gastric tubes


Decrease gastric distension
Access for enteral feedings

Provides a conduit for bacterial migration

Higher rate of reflux and sinusitis (NGT vs.
OGT)
H-2 Blockers

Gastric alkalinization


Promotes bacterial overgrowth
Presumably higher rates of significant aspiration


Gastric pH > 4 predisposition to GNR/S. aureus
Use of sulcrafate associated with lower rates of VAP
( Am J med 1987 and 1991, Ann Int Med, 1995 Infec Control Hosp
Epidemiol 1994)
 VAP: sulcrafate 5%, antacid 10%, ranitidine 21%

Benefit: lack of gastric alkalinization and lower bacterial
colonization
Stress Ulcer Prophylaxis and VAP

Controversial Topic !


A Meta-analysis of previous studies found no significant difference
Prospective randomized trials

Simms et al, J Trauma, 1991


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Thomason et al, J Trauma, 1996

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99 trauma patients on antacids, cimetidine, or sulcralfate
No difference in nosocomial pneumonia or gastric bacteria
242 intubated ICU patients on antacid, ranitidine, or sulcralfate
No difference in rates of VAP or GI bleeding
Markowicz et al, Am J Respir Crit Care Med, 2000



Multicenter, prospective trial
Found sulcrafate significantly associated with pneumonia in ARDS
? mechanism
Diagnosis: Nosocomial Pneumonia


Difficult in ventilated patient
Typical criteria



Clinical
Radiographic
Laboratory
Statistically, a specific combination of clinical
diagnostic criteria has not been identified to reliably
diagnose bacterial pneumonia
What is “VAP” ?
Reliability of Clinical Signs

Signs


Fever, pulmonary infiltrate, and purulent tracheal secretions
Fagon et al, Am J Med, 1993

23 patients with tracheobronchitis


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clinical “pneumonia” criteria, but negative protected brushings and
BAL
Matched with patients unsuspected to have pneumonia
Mortality rates were similar (26% vs. 27%)

Lower than patients with a “proven” pneumonia ( BAL)
Diagnosis: Nosocomial Pneumonia

Objective tests can be unreliable



After 48 hrs, endogenous flora of aerodigestive tract
replaced by hospital microflora
Antibiotic usage allows for selection and overgrowth of
resistant organisms
CXR has been notoriously inaccurate
No single radiographic sign has > 68% accuracy
 Due to high incidence of SIRS and ARDS in ICU, the
validity of a radiographic infiltrate becomes less reliable

Differential Diagnosis

Pulmonary Edema








Cardiogenic
Non-cardiogenic
Atelectasis
Infarction
Nosocomial pneumonia
Hemorrhage
Systemic Inflammatory Response Syndrome
Adult Respiratory Distress Syndrome (ARDS)
Diagnosis
Remember, VAP is a sub-type of
nosocomial pneumonia defined specifically in
relation to a bacterial etiology
? Role of Candida species…
Why an accurate diagnosis ?

Inappropriate treatment of pneumonia has been
shown to correlate directly with an increased mortality

Indiscriminate use of antibiotics leads to the
development of multi-resistant strains

Empiric antibiotic therapy predisposes to infection
with more virulent strains

Fagon et al, Am Rev Respir Dis, 1989


Increased proportion of pneumonias due to Pseudomonas and
Acinetobacter from 19% to 65% when antibiotics were administrated
before the development of an actual pneumonia
Increased mortality in previously-treated group (48% vs. 83%)
Diagnostic Tests


Tracheal aspirations
Selective airway sampling



Bronchoalveolar lavage (BAL)
Protected specimen brush
Direct airway visualization
Quantitative Cultures

Becoming a mainstay in the “academic
diagnosis” of VAP

However, regardless of technique, laboratory
standardization is essential



Cumbersome
Labor intensive
Associated Costs
Tracheal Aspirates (TA)

Gram stains plagued by low specificity



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Tracheal colonization
Correlate with cultures in only 46% (EAST Study)
GNR better predictive, whereas gram positive or no
bacteria was unreliable
Quantitative cultures and TA



Probably comparable to invasive procedures
Sensitivity (82% vs. 64%) and specificity (83% vs. 96%)
Overall more cost-effective than invasive procedures
Diagnostic Tests: TA

Presence of elastin fibers in TA



Specific indicator of pulmonary necrosis
Increased specificity to 73-100%
Shlaes et al, Chest, 1984
Sputum samples strongly correlated to radiographic
evidence of pulmonary necrosis
 Histologically proven positive in 9 cases without
radiographic findings
 Can be non-specific for noninfectious causes of
necrotizing lung diseases

Bronchoaveolar Lavage (BAL)


Performed by bronchoscopy
BAL samples larger portion of lung than TA

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Increased with protected catheter

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Sensitivity 72-100%, specificity 69-100%
Sens 92%, Spec 97%
Recommend threshold of 104 CFU/ ml
Blind mini-BAL



Can be done by respiratory technicians
Protected catheter-approach
Compares favorably to bronchoscopic BAL
Protected Specimen Brush


Performed via bronch or non-bronchoscopic
Sensitivity and specificity varies


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Sensitivity 70-100%
Specificity 60-92%
Sensitivity drops with antibiotic use (13%)
Threshold 103 CFU/ml
Combination of Test

Inherent drawback with BAL and PSB


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Delays in cultures of 24-48 hrs.
Lower than acceptable sens. and spec. when either
method used alone
Combined BAL and PSB



BAL recovered cells determine empiric antibiotic if
more than 5% of infected cells
Therapy is altered based on PSB with 103 CFU cutoff
Improves sensitivity 100% and specificity 96%
Prevention is Critical…

Intubation
 Intubate only if necessary
 Early extubation if criteria meet…though need to
minimize the risk of re-intubation !

? Semi-upright positioning
? Subglottic continuous aspiration
? Use of oral gastric tubes instead of NGT
? Limited use of gastric alkalinization
? Selective digestive decontamination

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Subglottic Continuous Aspiration

Valles et al, Ann Int Med, 1995

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Randomized blinded study
Reduction of VAP
Controls 39.6 episodes /1000 vent days
 Intervention 19.9 episodes / 1000 vent days

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Increased time to developing VAP

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(control) 5.9 days to (intervention) 12 days
Drawbacks

Expensive specialized ET tubes
Semi-Upright Positioning

Evidence For: (Torres et al, Ann Int Med, 1992)

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Used radioactive labeling of gastric contents
Significantly less aspiration with 45 degree elevation
Magnitude of supine aspiration time-dependent
Evidence Against: (Ibanez et al, JPEN, 1992)

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Similar study in 70 patients
No statistical difference in supine vs. upright
Significant difference of reflux in patients with NGT
Use of Oral Gastric Tubes

Use significantly reduces



Incidence of infectious sinusitis
Incidence of VAP
Recommendations


Convert NGT to OG
Consider gastrostomy if long term use necessary
Sample Current Practice ?
Empirical Antibiotics: VAP
Why such a concern: Abx-Resistance

MMWR – July 5, 2002
 VRSA

in Michigan
MMWR - October 11, 2002
 VRSA
in Pennsylvania
Wake-up Call….
Antibiotics & VAP
what is the “appropriate use”
of antibiotics in
either
suspected or “proven” VAP ?
Mortality related to Abx-Coverage
VAP:
Summary of Approach
Critical Care Medicine
Boston Medical Center
Boston University School of
Medicine
Nonpharm.
Prevention
Measures
Kollef, NEJM 1999.
Pharm.
Prevention
Measures
Kollef, NEJM 1999.
VAP: Conclusions

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Most common nosocomial infection in the ICU
Most significant risk is intubation/reintubation
? Preventable Disease
Treatment should be rationale


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Hospital-based patterns of infection (i.e. biograms)
Unit-specific protocols validated through time
Accurate & accepted diagnosis of VAP
Clinical, radiographic, and laboratory findings
 Such a diagnosis may be most accurate with quantitative
cultures via either TA, BAL, PSB

VAP: Questions
Critical Care Medicine
Boston Medical Center
Boston University School of Medicine
Ventilator-Associated
Pneumonia
Critical Care Medicine
Boston Medical Center
Boston University School of Medicine
Bradley J. Phillips, M.D.