ARTICLE

A Prospective Study of Ventilator-Associated

Pneumonia in Children
Ramya Srinivasan, MDa, Jeanette Asselin, MS, RTb, Ginny Gildengorin, PhDc, J. Wiener-Kronish, MDd, H. R. Flori, MDe

aUniversity of California, San Francisco, California; bNeonatal Pediatric Research Group and ePediatric Critical Care Department, Children’s Hospital and Research Center

Oakland, Oakland, California; cPediatric Clinical Research Center, Children’s Hospital Oakland Research Institute, Oakland, California; dDepartment of Anesthesia and
Critical Care, Massachusetts General Hospital, Boston, Massachusetts

The authors have indicated they have no financial relationships relevant to this article to disclose.

What’s Known on This Subject What This Study Adds

To our knowledge, only 5 studies exist in the pediatric literature (PubMed search, Janu- Our study is one of the few prospective studies in pediatrics that elucidates risk factors
ary 30, 2008) that describe the epidemiology and risk factors for VAP as a primary out- for VAP within a 72-hour period before diagnosis and the only pediatric study to state
come in a prospective fashion in neonates and children compared, with countless stud- the cost of VAP in pediatric patients.
ies in adults.

ABSTRACT
OBJECTIVE. We conducted a prospective, observational study in a tertiary care pediatric
center to determine risk factors for the development of and outcomes from ventila-
tor-associated pneumonia. www.pediatrics.org/cgi/doi/10.1542/
peds.2008-1211
METHODS. From November 2004 to June 2005, all NICU and PICU patients mechani- doi:10.1542/peds.2008-1211
cally ventilated for ⬎24 hours were eligible for enrollment after parental consent. Key Words
The primary outcome measure was the development of ventilator-associated pneu- intensive care, outcome, pneumonia,
monia, which was defined by both Centers for Disease Control and Prevention/ prospective study, ventilator-associated
National Nosocomial Infections Surveillance criteria and clinician diagnosis. Second- Abbreviations
ary outcome measures were length of mechanical ventilation, hospital and ICU ALI—acute lung injury
ARDS—acute respiratory distress
length of stay, hospital cost, and death. syndrome
CHRCO—Children’s Hospital and Research
RESULTS. Fifty-eight patients were enrolled. The median age was 6 months, and 57% Center Oakland
were boys. The most common ventilator-associated pneumonia organisms identified CDC—Centers for Disease Control and
were Gram-negative bacteria (42%), Staphylococcus aureus (22%), and Haemophilus Prevention
FIO2—fraction of inspired oxygen
influenzae (11%). On multivariate analysis, female gender, postsurgical admission NNIS—National Nosocomial Infections
diagnosis, presence of enteral feeds, and use of narcotic medications were associated Surveillance
with ventilator-associated pneumonia. Patients with ventilator-associated pneumo- PELOD—pediatric logistic organ
dysfunction
nia had greater need for mechanical ventilation (12 vs 22 median ventilator-free VAP—ventilator-associated pneumonia
days), longer ICU length of stay (6 vs 13 median ICU-free days), higher total median
Accepted for publication Aug 5, 2008
hospital costs ($308 534 vs $252 652), and increased absolute hospital mortality
Address correspondence to Ramya Srinivasan,
(10.5% vs 2.4%) than those without ventilator-associated pneumonia. MD, Pediatric Critical Care Department, 747
52nd Street, Oakland, CA 94609-1809. E-mail:
CONCLUSIONS. In mechanically ventilated, critically ill children, those with ventilator- rsrinivasan2004@yahoo.com.
associated pneumonia had a prolonged need for mechanical ventilation, a longer ICU PEDIATRICS (ISSN Numbers: Print, 0031-4005;
stay, and a higher mortality rate. Female gender, postsurgical diagnosis, the use of Online, 1098-4275). Copyright © 2009 by the
American Academy of Pediatrics
narcotics, and the use of enteral feeds were associated with an increased risk of
developing ventilator-associated pneumonia in these patients. Pediatrics 2009;123:
1108–1115

V ENTILATOR-ASSOCIATED PNEUMONIA (VAP) is the second most common nosocomial infection in PICU patients in
the United States.1 VAP is defined as nosocomial pneumonia diagnosed in patients mechanically ventilated for
ⱖ48 hours with signs of a new lower respiratory tract infection. Despite advances in supportive care, antimicrobial
therapies, and mechanical ventilation, VAP remains a major disease entity in ICU patients. In adults, the reported
incidence of VAP worldwide ranges from 8% to 28%,2 with an incremental risk of 1% for each day on the ventilator.3
In 2004, the National Nosocomial Infections Surveillance (NNIS) system of the Centers for Disease Control and
Prevention (CDC) reported a mean VAP rate of 2.9 per 1000 ventilator days for participating PICUs in the United
States.4 The European Multicenter Study Group found pneumonia, at 53% of all infections, to be the most common
PICU nosocomial infection.5
The epidemiology, associated risk factors, and outcomes of VAP are not as well documented in pediatric patients
as they are in adult patients. In adults, independent risk factors for development of VAP include duration of

1108 SRINIVASAN et al
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mechanical ventilation, severity of illness, patient age,
supine head position, previous antibiotic treatment, re-
intubation, transport out of the ICU, and use of hista-
mine-2 blockers.2 In addition, VAP in adults has been
associated with prolonged duration of mechanical ven-
tilation as well as increased length of ICU stay, hospital
stay, hospital cost, and absolute mortality.2
PICU patients not only encompass a wide range of ages
different from adult ICU patients but also differ in their
developmental physiology, underlying disorders, and treat-
ment needs. More studies are needed in the pediatric pop-
ulation given the changing epidemiology, microbiology,
and preventive and treatment strategies of VAP.
We conducted a prospective cohort study in an urban
children’s hospital to evaluate the risk factors, outcomes,
and cost of VAP in mechanically ventilated pediatric
patients.
MATERIALS AND METHODS
Setting
Children’s Hospital and Research Center Oakland
(CHRCO) is a tertiary-care, level 1 trauma center and
freestanding children’s hospital that receives referrals
from the greater Northern California region. The PICU
has 23 beds and admits ⬎1800 children annually. The
NICU has 38 beds and admits 600 outborn patients an-
nually.
Patients
This study was part of a parent Specialized Centers of
Clinically Oriented Research (SCCOR) grant, “Bacterial
Defense and Host Genetics in Acute Lung Injury” at the
University of California, San Francisco with participation
by CHRCO. All pediatric and neonatal patients admitted
to CHRCO ICUs from October 2004 through June 2005
were screened for study enrollment and eligible if ven-
tilated for ⬎24 hours. Patients were excluded based on
parent study requirements: if their physical condition
precluded suctioning beyond the endotracheal tube (ie,
tracheal reconstruction), respiratory status was unstable
(ie, need for fraction of inspired oxygen [FIO2] ⬎80% or
high frequency oscillatory ventilation), consent was un-
obtainable, or withdrawal of support or declaration of
death were imminent. Patients unstable from a respira-
tory standpoint were eligible for enrollment if their clin-
ical status improved. This study was approved by the
CHRCO institutional review board.
Data Acquisition
After consent, enrolled patients had demographic data,
risk factors, culture results, and outcome data prospec-
tively collected by a clinical research nurse and entered
into an Access (Microsoft, Redmond, WA) database sys-
tem. All data from time of intubation to time of study
enrollment, chest radiograph results, pediatric logistic
organ dysfunction (PELOD) scores, and hospital charges
were retrospectively entered from electronic patient
records. All patients were followed until the time of
hospital discharge, transfer, or death.
Data collected included: demographic data (age at
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time of intubation, gender, race, and admission diagno-
sis); potential risk factors: use of a device (tracheal tube,
urinary catheter, central line), use of medications (ste-
roids, continuous inotrope or vasoactive infusions, in-
haled bronchodilators, histamine type-2 receptor block-
ers, proton-pump inhibitors, sulcrafate, metoclopromide,
infusions or doses of narcotics, infusions or doses of
benzodiazepines, infusions or doses of neuromuscular
blocking agents, nutrition method [total parenteral nu-
trition, gastric feeds via nasogastric tube or gastric tube,
transpyloric feeds via nasojejeunal tube or jejeunal
tube]), route of mechanical ventilation (nasotracheal,
orotracheal, or tracheostomy), ventilation tube charac-
teristic (cuffed versus uncuffed tube or tracheostomy);
procedures (transport out of the ICU for surgery or ra-
diographic studies, transfusion of blood products, under-
going cardiac bypass, need for reintubation); patient-
specific data (presence of cyanotic heart disease defined
as presence of a right to left intracardiac shunt in the
setting of complex cyanotic heart disease, presence of
acute lung injury [ALI] or acute respiratory distress syn-
drome [ARDS] based on the 1994 American European
Consensus Conference on ARDS,6 maximum tempera-
ture, presence of purulent sputum defined as thick, non-
white in color, and copious, FIO2 at time of the lowest
PaO2); laboratory data: maximum white cell count, low-
est PaO2 from arterial source; chest radiograph data:
development of new infiltrate, bilateral versus unilateral
infiltrate; and culture data: results of endotracheal tube,
blood, urine, and other tissue cultures.
Data calculated included: admission PELOD scores for
all patients,7 admission pediatric risk of mortality scores
for only PICU patients based on published guidelines,8
and PaO2/FIO2 ratio for patients with an arterial PaO2
measurement at time of a positive endotracheal tube
culture result.
Definitions
The primary outcome was diagnosis of VAP based on
either of 2 criteria: (1) CDC/NNIS definition based on
age-specific criteria9 or (2) qualified intensivist diagnosis
based on clinical assessment of clinical, laboratory, ra-
diographic, and culture results. Any disagreements be-
tween the CDC/NNIS and intensivist diagnoses were
resolved at the time of analysis by the independent
opinion of a second intensivist. The secondary outcomes
included ventilator-free days, defined as the duration of
unassisted breathing in the first 28 days after onset of
mechanical ventilation10 and ICU-free days, defined as
days alive not needing ICU care in first 28 days after
hospitalization.11 These 2 measures were calculated by
using the National Heart, Lung, and Blood Institute
ARDS network convention to minimize any bias from
interhospital transfers, especially from outborn NICU
infants in our study cohort.
Data Analysis
Cohort Analysis
Statistical analyses were performed with SAS 9.1 (SAS
Institute, Inc, Cary, NC). Descriptive statistics for all
PEDIATRICS Volume 123, Number 4, April 2009 1109
 Eligible study patients, N = 60
Patients with endotracheal cultures, n = 53
No. of endotracheal cultures: 162
Patients with positive endotracheal cultures, n = 36
No. of endotracheal cultures: 96
Excluded: All endotracheal cultures during 7-d course of antibiotics for VAP
Eligible: No. of cultures remaining: 78
No. of patients with VAP, n =19 No. of patients without VAPb , n = 27
No. of endotracheal cultures: 26 No. of endotracheal cultures: 52
FIGURE 1
Patient endotracheal cultures analyzed for risk factors.
a All in this group did not develop VAP.
b i.e. ET colonized.
patients included demographics, admission and intuba-
tion characteristics, organisms cultured, and clinical out-
comes.
All potential risk factors were recorded for the time
period of interest (ie, 72 hours before a positive endo-
tracheal culture). Exceptions included race (dichoto-
mized to white and nonwhite) and admission diagnosis
(dichotomized to medical and surgical). The PaO2/FIO2
ratio at the time of positive endotracheal culture was
dichotomized for analysis based on the American Euro-
pean Consensus Conference (AECC) definition of ALI
and ARDS.6
Primary Outcome Analysis
Univariate analyses for demographic and admission
characteristics were performed by using the Mann-
Whitney rank-sum test for continuous data and ␹2 or
Fisher’s exact tests for categorical data.
We assumed the time at which an endotracheal cul-
ture was sent signified the time of highest suspicion for
VAP clinically. Therefore, to discover temporally related
risk factors immediately before a VAP episode, we ana-
lyzed risk factors present within 72 hours of all positive
endotracheal cultures. Patients with positive endotra-
cheal cultures who met the study definition for VAP
were considered to have VAP; those who had no clinical
signs and symptoms of pulmonary infection were con-
sidered to have endotracheal colonization. A logistic re-
gression model, along with the method of generalized
estimating equations to handle repeated measures data,
was used to assess the association of risk factors to the
development of VAP versus simple endotracheal coloni-
zation (Fig 1). Based on the results of univariate models
of risk factors for VAP, variables significant at the P ⬍ .10
level were considered for development of the multivar-
iate model. Correlations and collinearity diagnostics
were used to detect any collinearity among the signifi-
1110 SRINIVASAN et al
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Patients with no endotracheal cultures, n = 7
Patients with negative endotracheal culturesa , n = 27
No. of endotracheal cultures: 66
cant variables. We used the deviance and log-likelihood
statistics to compare models. The final multivariate
model was chosen for clinical and biological plausibility
and included age, gender, race, PELOD score, and ad-
mission diagnosis.
Secondary Outcome Analysis
Multivariate regression models were developed to deter-
mine if VAP was an independent risk factor for the need
for prolonged mechanical ventilation (ventilator-free
days), ICU stay (ICU-free days), hospital length of stay,
increased total hospital charges, or increased risk of
death after adjusting for age, gender, race, PELOD score,
presence of ALI/ARDS, and admission diagnosis. Specif-
ically, Poisson regression was used to analyze ventilator-
free days and ICU-free days and log-transformation of
data was performed before regression analysis of hospital
length of stay and total hospital charges.
RESULTS
Patient Cohort Characteristics
During the study period, 174 total patients met study
criteria and a total of 58 (34%) patients were consented
and enrolled. Of the 84 patients who met study criteria
in the PICU, 46 (55%) were enrolled. Major reasons for
nonenrollment in the PICU were intubation ⬍72 hours
(16%), unable to find a parent or legal guardian for
consent (13%), unstable cardiorespiratory status (11%),
and near death or do-not-resuscitate status (11%). Of
the 90 patients who met study criteria in the NICU, 14
(16%) were enrolled. Major reasons for nonenrollment
in the NICU were unstable cardiorespiratory status
(25%), missed consent or transfer out of NICU (21%),
parental emotional/psychologic burden (13%), intuba-
tion ⬍72 hours (11%), and near death or do-not-resus-
citate status (8%). In both ICUs, there were no statisti-
 TABLE 1 Study Population Characteristics (N ⴝ 60) VAP episodes (ⱕ5 days of intubation), and 8 (42%)
Characteristics Median (Range) or n (%) were late VAP episodes. Four patients developed mul-
tiple episodes of VAP recurring between 9 and 65 days
Demographics
from their first episode.
Gender, male 34 (56.7)
Age, mo 6 (0–234)
Premature (⬍37 wk EGA) 14 (23.3) Univariate Analysis of Baseline Patient Characteristics and the
⬍ 1 y, not premature 25 (41.7) Development of VAP
1–12 y 16 (26.7)
Univariate analysis of age, gender, admission pediatric
ⱖ13 y 5 (8.4)
Race
risk of mortality score, PELOD score, and diagnosis were
Black 11 (18.3) not significantly different between those who developed
Asian 6 (10.0) VAP and those who did not. However, a positive asso-
Hispanic 14 (23.3) ciation between patients’ race and development of VAP
White 26 (43.3) was observed (P ⫽ .05). Of note, no patient admitted
Other 3 (5.0) with a diagnosis of community-acquired pneumonia/
Prism3a 7 (0–32) bronchiolitis developed VAP (Table 2).
PELOD score 12 (0–31)
Admission diagnosis
Pneumonia/bronchiolitis 15 (25.0) Endotracheal Cultures and Bacteria Identified
Infection not pneumonia 13 (21.7) A total of 162 lower respiratory tract samples were sent
After cardiovascular surgery 8 (13.3) for culture and 96 (59%) were positive. The majority of
After general surgery 6 (10.0) samples were endotracheal tube cultures with 26 (16%)
Trauma 3 (5.0) sent from bronchoalveolar lavage. Table 3 describes the
Other medical 15 (25.0)
microbiology of VAP and endotracheal colonization in
Intubation characteristics
these patients. Staphylococcus aureus (9 [23%]) and
Route
Nasotracheal 4 (6.7) Gram-negative bacteria (22 [57%]) were the most com-
Orotracheal 53 (88.3) mon etiologic agents associated with VAP. Many of the
Tracheostomy 3 (5.0) endotracheal cultures positive for VAP, 10 (38%) of 26,
Endotracheal tube type were polymicrobial in nature. In patients without lower
Cuffed 25 (41.7) respiratory tract infection, major endotracheal colonizers
Uncuffed 35 (58.3) were found to be coagulase-negative staphylococci (17
Reintubation 21 (35.0) [25%]), S aureus (14 [21%]), and fungal (12 [18%])
Hospital outcomes organisms. Of interest, of all S aureus organisms cultured,
Ventilator-associated pneumonia 19 (31.7)
3 (13%) were methicillin resistant.
1 episode only 15 (79.0)
⬎1 episode 4 (21.0)
Ventilator days 8 (2–96) Univariate Analysis of Risk Factors Associated With
Ventilator-free days 20 (0–26) Development of VAP
ICU length of stay 16 (2–197) The cohort of 36 patients who had positive endotracheal
Hospital length of stay 25 (2–197)
cultures was used for analysis of risk factors for VAP
Total hospital charges 274 824 (30 443–1 731 237)
Hospital disposition
versus endotracheal colonization. Results are shown in
Death 3 (5.0) Table 4. Of the 3 main components of the CDC criteria
Home 45 (75.0) for a diagnosis of VAP, we found the presence of a new
Other 12 (20.0) chest radiographic finding and fever were associated
EGA indicates estimated gestational age. with VAP, but total white cell count was not. Oxygen-
a Calculated only for PICU patients (n ⫽ 45). ation deficit (measured by PaO2/FIO2 ratio), use of met-
oclopramide, reintubation, receipt of blood products,
and presence of enteral feeds were all significantly asso-
cally significant differences in age in the NICU (P ⫽ ciated with the development of VAP (P ⬍ .05) (Table 4).
.390), age in the PICU (P ⫽ 1.00), gender (P ⫽ .75), or
race (P ⫽ .50) between those enrolled and not enrolled. Multivariate Analysis of Risk Factors Associated With
Over the 9-month study period, 2 of the 58 patients Development of VAP
were readmitted, resulting in a total of 60 admissions (45 The following risk factors present within 72 hours of a
PICU and 14 NICU) analyzed. Demographic, severity of positive culture were entered into our multivariate
illness scores, admission diagnoses, and intubation char- model for development of VAP: age, gender, race, ad-
acteristics of the study cohort are presented in Table 1. mission diagnosis, PELOD score, PaO2/FIO2 ratio of ⬎200
or ⬍200, reintubation, presence of enteral feeds, use of
Development of VAP narcotics, use of metoclopramide, and receipt of any
Nineteen (32%) admissions resulted in the develop- blood products (red blood cells, platelets, or fresh frozen
ment of VAP. Median time to diagnosis of the first plasma). On multivariate analysis of risk factors for VAP,
episode of VAP was 4 days from the time of intuba- female gender, postsurgical diagnosis, narcotics, and en-
tion. Eleven (58%) of the VAP episodes were early teral feeds were found to be independently associated

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 TABLE 2 Characteristics and Outcomes of Patients With and Without VAP (N ⴝ 60)
Patients With VAP (N ⴝ 19) Patients Without VAP P
(N ⴝ 41)
Gender, male 9 (47.4) 25 (61) .32a
Age, mo 8.7 (0–159) 5.6 (0–234) .56b
Race .05a
Black 4 (21.1) 7 (17.1)
Asian 5 (26.3) 1 (2.4)
Hispanic 4 (21.1) 10 (24.4)
White 5 (26.3) 21 (51.2)
Other 1 (5.3) 2 (4.9)
Admission diagnosis .71a
Medical 14 (73.7) 32 (78.1)
Surgical 5 (26.3) 9 (22)
Prism3c 5 (0–32) 8 (0–24) .29b
PELOD score 12 (0–30) 12 (1–31) .52b
Ventilator-free days 12 (0–21) 22 (0–26) ⬍.001d
ICU-free days 6 (0–19) 13 (0–25) ⬍.0001d
Hospital length of stay 27 (12–125) 23 (2–197) .46d
Total hospital charges $308 534 (107 350–1 731 237) $252 652 (30 443–1 114 317) ⬍.01d
Hospital mortality 2 (10.5) 1 (2.4) .56d
Data shown are either n (%), for categorical data, or median (range), for continuous data.
a ␹2 test used.

b Mann-Whitney rank-sum test used.

c Calculated only for PICU patients (n ⫽ 45).

d Result of regression model controlled for age, gender, race, admission PELOD score, presence of ALI/ARDS, and admission diagnosis.

with VAP. Administration of blood products was in- PICU and NICU in an urban pediatric hospital. There is
versely related to the development of VAP (Table 5). no gold standard for the diagnosis of VAP in pediatric
patients; therefore, we used a clinical definition of VAP
Clinical Outcomes Associated With VAP based on NNIS age-specific guidelines and clinical inten-
After adjustment for age, gender, race, PELOD score, sivist diagnosis.
presence of ALI/ARDS, and admission diagnosis, we Our multivariate analysis of risk factors revealed fe-
found that patients with VAP exhibited a greater need male gender, postsurgical admission diagnosis, use of
for mechanical ventilation (P ⬍ .001), greater length of narcotics, and presence of enteral feeds to be positively
ICU stay (P ⬍ .0001), and increased total hospital associated with the development of VAP versus having
charges (P ⬍ .01) (Table 2). simple endotracheal colonization. Several risk factors for
the development of VAP identified by other studies such
DISCUSSION as reintubation, transport out of the ICU, and use of
We conducted a prospective, observational study to gastric stress ulcer prophylaxis were not found to be
characterize risk factors and outcomes from VAP in me- independently associated with VAP in our study. This
chanically ventilated pediatric patients. Our study pop- may be due to the fact that we analyzed risk factors
ulation included patients from the multidisciplinary temporally related, in the 72-hour period, before a pos-
itive endotracheal tube culture result and not simply at
any time during intubation to find the closest association
TABLE 3 Organisms Cultured From Patients With Positive of risk factors to an incident of VAP.
Endotracheal Cultures: VAP Versus Endotracheal The most common etiologic agents cultured in VAP
Colonization are bacterial. Both the NNIS in the United States and
Endotracheal Organism Types VAP, n Endotracheal the European Multicenter Study Group found pneu-
(%) Colonization, monia in their pediatric populations was most often
n (%) associated with Pseudomonas aeruginosa and S aureus.4,5
Staphylococcus aureus 9 (23.1) 14 (20.6) In our study, the 3 most common organisms cultured
Haemophilus influenzae 4 (10.3) 2 (2.9) in VAP were S aureus, Haemophilus influenzae, and
Streptococcus pneumoniae 1 (2.6) 0 (0.0)
other Gram-negative organisms with the first 2 pre-
Pseudomonas spp 1 (2.6) 3 (4.4)
Escherichia coli 4 (10.3) 3 (4.4)
dominating in early VAP and the latter more common
Enterobacter spp 3 (7.7) 3 (4.4) in late VAP. Of interest, we report for the first time an
Serratia spp 2 (5.1) 6 (8.8) incidence for polymicrobial VAP in pediatrics, which
Coagulase-negative staphlococci 2 (5.1) 17 (25.0) was 38% in our study. Combes et al,12 reported a
Fungal 1 (2.6) 12 (17.6) polymicrobial incidence of 48% in a cohort of adult
Other Gram-negative organisms 8 (20.5) 4 (5.9) ICU patients and found no difference in baseline de-
Other Gram-positive organisms 4 (10.3) 4 (5.9) mographics or outcomes between polymicrobial and

1112 SRINIVASAN et al
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 TABLE 4 Univariate Analysis of Risk Factors for VAP in Positive TABLE 5 Multivariate Analysis of Independent Risk Factors for
Endotracheal Culture Patients (n ⴝ 36) VAP in Positive Endotracheal Culture Patients (n ⴝ 36)
Factors Present 72 h Before OR 95% CLs P Adjusted ORa 95% CLs P
Positive Endotracheal Culturea Gender, female 10.32 2.87, 37.16 ⬍.001
Gender, male ⫺0.79 ⫺1.74, 0.16 .10 Admission diagnosis, postsurgical 9.98 2.16, 46.13 .003
Age, mo ⫺0.002 ⫺0.01, 0.01 .78 Any narcotic use 77.5 7.11, 844.63 ⬍.001
Race (white vs nonwhite) ⫺0.58 ⫺1.66, 0.49 .29 Enteral feeds 8.78 2.13, 36.20 .003
Admission diagnosis (medical vs ⫺0.64 0.48, ⫺1.57 .18 Any blood product administration 0.1 0.02, 0.56 .009
surgical) CLs indicate confidence limits.
PELOD score ⫺0.04 ⫺0.08, 0.01 .12 a Adjusted for age, gender, race, PELOD score, admission diagnosis, ventilator days, and

Cyanotic heart disease 1.89 ⫺0.43, 4.21 .11 presence of ALI/ARDS.

ALI/ARDS ⫺0.16 ⫺1.4, 1.09 .80
PaO2/FIO2 ratio ⫺0.01 ⫺0.01, ⫺0.002 .01
⬍300 ⫺0.37 ⫺1.34, 0.59 .44 Many studies have described mixed associations be-
⬍200 0.89 ⫺0.06, 1.84 .07
tween the development of VAP and enteral feeds
New chest radiographic finding 1.96 0.51, 3.4 .008
thought to be secondary to microaspiration of stomach
White blood cell count 0.02 ⫺0.03, 0.07 .46
Purulent sputum 0.57 ⫺0.31, 1.45 .20 contents and flora into the lower airways. Of 3 published
Maximum temperature 0.66 ⫺0.01, 1.33 .05 prospective pediatric studies of VAP,13–15 only Almuneef
Nasotracheal, orotracheal, or 0.53 ⫺0.77, 1.82 .42 et al13 found enteral feeds strongly associated with VAP.
tracheostomy intubation Additional studies are needed to evaluate for differences
Cuffed endotracheal tube 0.74 ⫺0.22, 1.69 .13 in risk for VAP based on different feeding methods such
Inhaled bronchodilators 0.41 ⫺0.50, 1.32 .37 as intermittent enteral feedings or postpyloric feeds. An
Systemic steroids ⫺0.84 ⫺1.93, 0.26 .14 evidence-based review of methods for VAP prevention
Inotropes/pressors ⫺0.16 ⫺1.14, 0.81 .74 found inconclusive results and was unable to make a
Any antacid medication 0.26 ⫺1.27, 1.80 .74
strong recommendation for a particular feeding method
Histamine-2 receptor blockers 0.15 ⫺0.82, 1.11 .77
associated with lower VAP risk.16
Proton-pump inhibitors ⫺0.81 ⫺2.39, 0.76 .31
Metoclopromide 1.30 0.22, 2.38 .02
We identified use of narcotics to be associated with
Sulcrafate 0.73 ⫺1.99, 3.45 .60 VAP. Many studies have identified use of sedation, and
Antibiotics ⫺0.28 ⫺1.20, 0.64 .55 more importantly, neuromuscular blockade, to be inde-
Paralytics used ⫺0.06 ⫺0.93, 0.80 .89 pendently associated with VAP.2,15 We found no differ-
Sedatives used 0.73 ⫺0.34, 1.80 .18 ence in use of sedative or neuromuscular blockade
Narcotics used 0.59 ⫺0.06, 1.24 .07 agents between patients who developed VAP versus
Cardiac bypass ⫺0.01 ⫺2.46, 2.44 .99 those who had endotracheal colonization. The particular
Reintubation 1.30 0.37, 2.25 .006 association of narcotics with VAP may indicate that gas-
Transport out of ICU 0.42 ⫺0.49, 1.33 .37
trointestinal hypomotility secondary to narcotics may be
Any blood product ⫺0.92 ⫺1.82, ⫺0.01 .05
a mechanism for increased risk of VAP via microaspira-
Packed red blood cells ⫺0.30 ⫺1.32, 0.71 .56
Platelets ⫺0.75 ⫺1.87, 0.36 .19 tion of gastric contents.
Fresh frozen plasma 1.05 ⫺0.55, 2.64 .20 We found that the administration of blood products did
Parenteral feeds ⫺0.65 ⫺1.55, 0.26 .16 not increase the risk factor for VAP. Both a pediatric VAP
Enteral feeds 1.27 0.34, 2.20 .01 study14 and a recent randomized-controlled trial of blood
Transpyloric feeds ⫺0.03 ⫺0.96, 0.90 .95 transfusion strategies in pediatric patients17 did not find the
Blood culture positive ⫺0.91 ⫺2.26, 0.43 .18 receipt of blood products to be an independent predictor of
Central venous line ⫺0.77 ⫺1.61, 0.07 .07 VAP, despite many other studies showing a statistical asso-
Results are of a logistic regression model using generalized estimating equations to han- ciation between risk for VAP and blood transfusions.18,19
dle repeated measures data. OR indicates odds ratio; CLs, confidence limits. The association of female gender with increased risk of
a Presence of characteristic or administration of drug or product.
VAP is interesting and to our knowledge has not been
reported in other pediatric studies. Rello et al20 performed a
matched cohort study of a large US database and found
monomicrobial VAP. Additional studies are needed to male gender significantly associated with VAP in adults
characterize any differences between monomicrobial (P ⬍ .001). Additional studies to clarify the significance of
versus polymicrobial pediatric VAP. gender association with pediatric VAP are needed.
Risk factor analysis in our study implies that post- Our study’s intent was not to analyze the impact of
surgical patients are at higher risk for VAP than med- treatment or prevention strategies on the development
ical patients in the ICU. Higher VAP rates for surgical of VAP. However, these are important factors to consider
and trauma ICUs versus pediatric and medical ICUs but are complicated by the lack of consensus for appro-
were reported in the 2004 NNIS Survey and docu- priate antibiotic regimens for VAP treatment in pediatric
mented in several adult studies.2 One prospective pe- patients. We did not find previous antibiotic use to be
diatric study in a tertiary-care hospital in Saudi Arabia associated with VAP, although 70% of patients with VAP
also found surgical patients at significantly higher risk received antibiotics in the immediate 72-hour period
for VAP versus medical or trauma patients on univar- before a positive endotracheal tube culture. Nursing pro-
iate analysis.13 tocols for keeping the head of the bed up at 45 degrees

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and use of oral care kits for mechanically ventilated
PICU patients were in place for 6 months before enroll-
ment of study patients; their impact is unclear.
VAP did have serious impact on clinically relevant
outcomes. After controlling for baseline demographic,
organ failure, and presence of lung injury, we found
patients with VAP had significantly prolonged mechan-
ical ventilation and length of ICU stay, confirming data
from other pediatric studies by Almuneef et al and El-
ward et al.13,14 Although we found an absolute difference
in hospital mortality rate of 8.1% between patients with
and without VAP, the result was not statistically signif-
icant. These data are similar to results published by both
Almuneef et al and Elward et al. This is likely due to the
low baseline incidence of mortality in critically ill pedi-
atric patients and lack of statistical power in our studies
to discern a significant difference. A matched cohort in
adult ICU patients estimated each episode of VAP re-
sulted in more than $40 000 in excess hospital charges.20
We found the total hospital costs for VAP patients was
greater than those without VAP after controlling for
baseline demographics, organ failure, and presence of
lung injury. Despite the small size of our study, to our
knowledge this is the only study to date to report the
cost of VAP in the pediatric population. Future large,
multicenter trials relating to pediatric VAP are needed
and should report costs related to care of the pediatric
patient, because this is a relevant outcome in our present
health care system.
The main limitation of this study is the small sample
size despite being a good representation demographically
of a large, multidisciplinary PICU and NICU. A priori, we
enrolled and analyzed patient data from both NICU and
PICU populations together as representing the pediatric
arm of the parent study. Our subpopulation size is inad-
equate to elucidate relevant differences in risk factors
and outcomes for VAP in NICU versus PICU patients;
however, larger studies may reveal differences between
these groups. In addition, per our parent study enroll-
ment criteria, we did not enroll extremely high-risk
patients who had high ventilatory and cardiovascular
support until they were more stable. Another limitation,
as in most other studies of VAP, is the lack of gold
standard for the definition of VAP and the use of a
clinical definition with high sensitivity but not specificity
in this study, which limits the accuracy of correlation
with risk factors and outcomes.
CONCLUSIONS
Our study is one of few prospective observational studies
in mechanically ventilated children describing the risk
factors and outcomes from development of VAP. We
found, in the setting of a multidisciplinary PICU and
NICU, that there is a differential risk for VAP among
patients based on their admission diagnosis, gender, en-
teral feeds, and receipt of narcotics. These findings need
to be confirmed in larger, multicenter studies to clarify
risk factors and the impact of prevention strategies, such
as spontaneous breathing trials and daily sedation wean-
ing protocols, on the development of VAP. Our study
shows that VAP negatively impacts clinical and eco-
1114 SRINIVASAN et al
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nomic outcomes in critically ill pediatric patients by pro-
longing the length of mechanical ventilation and ICU
stay and may increase total hospital charges and absolute
hospital mortality rate.
ACKNOWLEDGMENTS
This study was supported by SCCOR grants PH50HL
074005 and RR01271 and the CHRCO Neonatal Pediatric
Research Group.
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A PINCH OF SCIENCE

“The New York City Department of Health and Mental Hygiene, a leader in
promoting public health, has embarked on a campaign to persuade the
makers of processed food to reduce its salt content by more than 40% over
the next 10 years. The goal is commendable: to prevent strokes and heart
attacks. And the premise is logical: if people eat less salt, they’ll have lower
blood pressure, and this could translate into better cardiovascular health. If
such a large reduction were actually to be achieved, however, New Yorkers
would consume less sodium than people in most other developed countries
do. And there is a possibility that such a big change in one element of their
diet might have unintended harmful consequences. Prudence requires that
logic and good intentions also be supported by strong evidence that such an
action would be safe. The best available evidence on how salt consumption
affects our health comes from observational studies, in which groups of
subjects are investigated to identify any correlations between usual sodium
intake and subsequent heart attacks and strokes. Nine such studies, looking at
a total of more than 100 000 participants who consume as much sodium as
New Yorkers do, have had mixed results. In 4 of them, reduced dietary salt
was associated with an increased incidence of death and disability from heart
attacks and strokes. In one that focused on obese people, more salt was
associated with increased cardiovascular mortality. And in the remaining 4,
no association between salt and health was seen. Nevertheless, the research
on salt intake can help identify questions to address in randomized clinical
trials, the most rigorous kind of medical research. In such a study, people who
share relevant characteristics like age, weight, blood pressure and cholesterol
levels are divided into 2 groups, which follow the same diet in every way
except that those in one group would reduce their salt intake. This way any
differences in outcomes (heart attacks and strokes) can be reliably attributed
to sodium consumption. Only one such rigorous clinical trial on salt intake
has been reported so far, and it focused on patients with fairly advanced heart
problems. As if turned out, the group that adhered to a lower sodium diet
actually suffered significantly more cardiovascular deaths and hospitalizations
than did the one assigned to the higher sodium diet. Absent convincing
scientific evidence of a benefit to eating less salt, much less an assurance of
safety, it might be wiser for the New York City Health Department to press for
the research that could provide a solid scientific basis for action.”
Alderman M. New York Times. February 6, 2009
Noted by JFL, MD

PEDIATRICS Volume 123, Number 4, April 2009 1115

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 A Prospective Study of Ventilator-Associated Pneumonia in Children
Ramya Srinivasan, Jeanette Asselin, Ginny Gildengorin, J. Wiener-Kronish and H.R.
Flori
Pediatrics 2009;123;1108
DOI: 10.1542/peds.2008-1211

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 A Prospective Study of Ventilator-Associated Pneumonia in Children
Ramya Srinivasan, Jeanette Asselin, Ginny Gildengorin, J. Wiener-Kronish and H.R.
Flori
Pediatrics 2009;123;1108
DOI: 10.1542/peds.2008-1211

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/123/4/1108

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