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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.

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.
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
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-
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:

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

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mechanical ventilation, severity of illness, patient age, time of intubation, gender, race, and admission diagno-
supine head position, previous antibiotic treatment, re- sis); potential risk factors: use of a device (tracheal tube,
intubation, transport out of the ICU, and use of hista- urinary catheter, central line), use of medications (ste-
mine-2 blockers.2 In addition, VAP in adults has been roids, continuous inotrope or vasoactive infusions, in-
associated with prolonged duration of mechanical ven- haled bronchodilators, histamine type-2 receptor block-
tilation as well as increased length of ICU stay, hospital ers, proton-pump inhibitors, sulcrafate, metoclopromide,
stay, hospital cost, and absolute mortality.2 infusions or doses of narcotics, infusions or doses of
PICU patients not only encompass a wide range of ages benzodiazepines, infusions or doses of neuromuscular
different from adult ICU patients but also differ in their blocking agents, nutrition method [total parenteral nu-
developmental physiology, underlying disorders, and treat- trition, gastric feeds via nasogastric tube or gastric tube,
ment needs. More studies are needed in the pediatric pop- transpyloric feeds via nasojejeunal tube or jejeunal
ulation given the changing epidemiology, microbiology, tube]), route of mechanical ventilation (nasotracheal,
and preventive and treatment strategies of VAP. orotracheal, or tracheostomy), ventilation tube charac-
We conducted a prospective cohort study in an urban teristic (cuffed versus uncuffed tube or tracheostomy);
children’s hospital to evaluate the risk factors, outcomes, procedures (transport out of the ICU for surgery or ra-
and cost of VAP in mechanically ventilated pediatric diographic studies, transfusion of blood products, under-
patients. going cardiac bypass, need for reintubation); patient-
specific data (presence of cyanotic heart disease defined
MATERIALS AND METHODS as presence of a right to left intracardiac shunt in the
setting of complex cyanotic heart disease, presence of
Setting acute lung injury [ALI] or acute respiratory distress syn-
Children’s Hospital and Research Center Oakland drome [ARDS] based on the 1994 American European
(CHRCO) is a tertiary-care, level 1 trauma center and Consensus Conference on ARDS,6 maximum tempera-
freestanding children’s hospital that receives referrals ture, presence of purulent sputum defined as thick, non-
from the greater Northern California region. The PICU white in color, and copious, FIO2 at time of the lowest
has 23 beds and admits ⬎1800 children annually. The PaO2); laboratory data: maximum white cell count, low-
NICU has 38 beds and admits 600 outborn patients an- est PaO2 from arterial source; chest radiograph data:
nually. development of new infiltrate, bilateral versus unilateral
infiltrate; and culture data: results of endotracheal tube,
Patients blood, urine, and other tissue cultures.
This study was part of a parent Specialized Centers of Data calculated included: admission PELOD scores for
Clinically Oriented Research (SCCOR) grant, “Bacterial all patients,7 admission pediatric risk of mortality scores
Defense and Host Genetics in Acute Lung Injury” at the for only PICU patients based on published guidelines,8
University of California, San Francisco with participation and PaO2/FIO2 ratio for patients with an arterial PaO2
by CHRCO. All pediatric and neonatal patients admitted measurement at time of a positive endotracheal tube
to CHRCO ICUs from October 2004 through June 2005 culture result.
were screened for study enrollment and eligible if ven-
tilated for ⬎24 hours. Patients were excluded based on Definitions
parent study requirements: if their physical condition The primary outcome was diagnosis of VAP based on
precluded suctioning beyond the endotracheal tube (ie, either of 2 criteria: (1) CDC/NNIS definition based on
tracheal reconstruction), respiratory status was unstable age-specific criteria9 or (2) qualified intensivist diagnosis
(ie, need for fraction of inspired oxygen [FIO2] ⬎80% or based on clinical assessment of clinical, laboratory, ra-
high frequency oscillatory ventilation), consent was un- diographic, and culture results. Any disagreements be-
obtainable, or withdrawal of support or declaration of tween the CDC/NNIS and intensivist diagnoses were
death were imminent. Patients unstable from a respira- resolved at the time of analysis by the independent
tory standpoint were eligible for enrollment if their clin- opinion of a second intensivist. The secondary outcomes
ical status improved. This study was approved by the included ventilator-free days, defined as the duration of
CHRCO institutional review board. unassisted breathing in the first 28 days after onset of
mechanical ventilation10 and ICU-free days, defined as
Data Acquisition days alive not needing ICU care in first 28 days after
After consent, enrolled patients had demographic data, hospitalization.11 These 2 measures were calculated by
risk factors, culture results, and outcome data prospec- using the National Heart, Lung, and Blood Institute
tively collected by a clinical research nurse and entered ARDS network convention to minimize any bias from
into an Access (Microsoft, Redmond, WA) database sys- interhospital transfers, especially from outborn NICU
tem. All data from time of intubation to time of study infants in our study cohort.
enrollment, chest radiograph results, pediatric logistic
organ dysfunction (PELOD) scores, and hospital charges
Data Analysis
were retrospectively entered from electronic patient
records. All patients were followed until the time of Cohort Analysis
hospital discharge, transfer, or death. Statistical analyses were performed with SAS 9.1 (SAS
Data collected included: demographic data (age at Institute, Inc, Cary, NC). Descriptive statistics for all

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Eligible study patients, N = 60

Patients with endotracheal cultures, n = 53 Patients with no endotracheal cultures, n = 7

No. of endotracheal cultures: 162

Patients with positive endotracheal cultures, n = 36 Patients with negative endotracheal culturesa , n = 27
No. of endotracheal cultures: 96 No. of endotracheal cultures: 66

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

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- cant variables. We used the deviance and log-likelihood
tion characteristics, organisms cultured, and clinical out- statistics to compare models. The final multivariate
comes. model was chosen for clinical and biological plausibility
All potential risk factors were recorded for the time and included age, gender, race, PELOD score, and ad-
period of interest (ie, 72 hours before a positive endo- mission diagnosis.
tracheal culture). Exceptions included race (dichoto-
mized to white and nonwhite) and admission diagnosis Secondary Outcome Analysis
(dichotomized to medical and surgical). The PaO2/FIO2 Multivariate regression models were developed to deter-
ratio at the time of positive endotracheal culture was mine if VAP was an independent risk factor for the need
dichotomized for analysis based on the American Euro- for prolonged mechanical ventilation (ventilator-free
pean Consensus Conference (AECC) definition of ALI days), ICU stay (ICU-free days), hospital length of stay,
and ARDS.6 increased total hospital charges, or increased risk of
death after adjusting for age, gender, race, PELOD score,
Primary Outcome Analysis presence of ALI/ARDS, and admission diagnosis. Specif-
Univariate analyses for demographic and admission ically, Poisson regression was used to analyze ventilator-
characteristics were performed by using the Mann- free days and ICU-free days and log-transformation of
Whitney rank-sum test for continuous data and ␹2 or data was performed before regression analysis of hospital
Fisher’s exact tests for categorical data. length of stay and total hospital charges.
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- Patient Cohort Characteristics
lyzed risk factors present within 72 hours of all positive During the study period, 174 total patients met study
endotracheal cultures. Patients with positive endotra- criteria and a total of 58 (34%) patients were consented
cheal cultures who met the study definition for VAP and enrolled. Of the 84 patients who met study criteria
were considered to have VAP; those who had no clinical in the PICU, 46 (55%) were enrolled. Major reasons for
signs and symptoms of pulmonary infection were con- nonenrollment in the PICU were intubation ⬍72 hours
sidered to have endotracheal colonization. A logistic re- (16%), unable to find a parent or legal guardian for
gression model, along with the method of generalized consent (13%), unstable cardiorespiratory status (11%),
estimating equations to handle repeated measures data, and near death or do-not-resuscitate status (11%). Of
was used to assess the association of risk factors to the the 90 patients who met study criteria in the NICU, 14
development of VAP versus simple endotracheal coloni- (16%) were enrolled. Major reasons for nonenrollment
zation (Fig 1). Based on the results of univariate models in the NICU were unstable cardiorespiratory status
of risk factors for VAP, variables significant at the P ⬍ .10 (25%), missed consent or transfer out of NICU (21%),
level were considered for development of the multivar- parental emotional/psychologic burden (13%), intuba-
iate model. Correlations and collinearity diagnostics tion ⬍72 hours (11%), and near death or do-not-resus-
were used to detect any collinearity among the signifi- citate status (8%). In both ICUs, there were no statisti-

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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
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)
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
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

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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 nomic outcomes in critically ill pediatric patients by pro-
PICU patients were in place for 6 months before enroll- longing the length of mechanical ventilation and ICU
ment of study patients; their impact is unclear. stay and may increase total hospital charges and absolute
VAP did have serious impact on clinically relevant hospital mortality rate.
outcomes. After controlling for baseline demographic,
organ failure, and presence of lung injury, we found
patients with VAP had significantly prolonged mechan- ACKNOWLEDGMENTS
ical ventilation and length of ICU stay, confirming data This study was supported by SCCOR grants PH50HL
from other pediatric studies by Almuneef et al and El- 074005 and RR01271 and the CHRCO Neonatal Pediatric
ward et al.13,14 Although we found an absolute difference Research Group.
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 REFERENCES
Almuneef et al and Elward et al. This is likely due to the 1. Richards MJ, Edwards JR, Culver DH, Gaynes RP; National
Nosocomial Infections Surveillance System. Nosocomial infec-
low baseline incidence of mortality in critically ill pedi-
tions in pediatric intensive care units in the United States.
atric patients and lack of statistical power in our studies
Pediatrics. 1999;103(4). Available at:
to discern a significant difference. A matched cohort in content/full/103/4/e39
adult ICU patients estimated each episode of VAP re- 2. Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J
sulted in more than $40 000 in excess hospital charges.20 Respir Crit Care Med. 2002;165(7):867–903
We found the total hospital costs for VAP patients was 3. Fagon JY, Chastre J, Domart Y, et al. Nosocomial pneumonia in
greater than those without VAP after controlling for patients receiving continuous mechanical ventilation—
baseline demographics, organ failure, and presence of prospective analysis of 52 episodes with use of a protected
lung injury. Despite the small size of our study, to our specimen brush and quantitative culture techniques. Am Rev
knowledge this is the only study to date to report the Respir Dis. 1989;139(4):877– 884
4. National Nosocomial Infections Surveillance System. National
cost of VAP in the pediatric population. Future large,
Nosocomial Infections Surveillance System Report, data sum-
multicenter trials relating to pediatric VAP are needed
mary from January 1992 through June 2004, issued October
and should report costs related to care of the pediatric 2004. Am J Infect Control. 2004;32(8):470 – 485
patient, because this is a relevant outcome in our present 5. Raymond J, Aujard Y; European Study Group. Nosocomial
health care system. infections in pediatric patients: a European, multicenter pro-
The main limitation of this study is the small sample spective study. Infect Control Hosp Epidemiol. 2000;21(4):
size despite being a good representation demographically 260 –263
of a large, multidisciplinary PICU and NICU. A priori, we 6. Bernard G, Artigas A, Brigham K, et al. The North American-
enrolled and analyzed patient data from both NICU and European consensus conference on ARDS. Am J Respir Crit Care
PICU populations together as representing the pediatric Med. 1994;149(3 pt 1):818 – 824
7. Leteurtre S, Martinot A, Duhamel A, et al. Validation of the
arm of the parent study. Our subpopulation size is inad-
paediatric logistic organ dysfunction (PELOD) score: prospec-
equate to elucidate relevant differences in risk factors
tive, observational, multicentre study [published correction ap-
and outcomes for VAP in NICU versus PICU patients; pears in Lancet. 2006;367(9514):897]. Lancet. 2003;362(9379):
however, larger studies may reveal differences between 192–197
these groups. In addition, per our parent study enroll- 8. Pollack MM, Patel KM, Ruttimann UE. PRISM III: an updated
ment criteria, we did not enroll extremely high-risk pediatric risk of mortality score. Crit Care Med. 1996;24(5):
patients who had high ventilatory and cardiovascular 743–752
support until they were more stable. Another limitation, 9. Centers for Disease Control and Prevention. Criteria for defining
as in most other studies of VAP, is the lack of gold nosocomial pneumonia. Available at:
standard for the definition of VAP and the use of a NNIS/members/pneumonia/Final/PneuCriteriaFinal.pdf. Ac-
cessed July 2, 2007
clinical definition with high sensitivity but not specificity
10. Acute Respiratory Distress Syndrome Network. Ventilation
in this study, which limits the accuracy of correlation
with lower tidal volumes as compared with traditional tidal
with risk factors and outcomes. volumes for acute lung injury and the acute respiratory distress
syndrome. N Engl J Med. 2000;342(18):1301–1308
CONCLUSIONS 11. Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of
Our study is one of few prospective observational studies two fluid-management strategies in acute lung injury. N Engl
in mechanically ventilated children describing the risk J Med. 2006;354(24):2564 –2575
factors and outcomes from development of VAP. We 12. Combes A, Figliolini C, Trouillet JL, et al. Incidence and out-
found, in the setting of a multidisciplinary PICU and come of polymicrobial ventilator-associated pneumonia.
NICU, that there is a differential risk for VAP among CHEST. 2002;121(5):1618 –1623
13. Almuneef M, Memish ZA, Balkhy HH, Alalem H, Abataleb Al.
patients based on their admission diagnosis, gender, en-
Ventilator-associated pneumonia in a pediatric intensive care
teral feeds, and receipt of narcotics. These findings need
unit in Saudi Arabia: a 30-month prospective surveillance.
to be confirmed in larger, multicenter studies to clarify Infect Control Hosp Epidemiol. 2004;25(9):753–758
risk factors and the impact of prevention strategies, such 14. Elward AM, Warren DK, Fraser VJ. Ventilator-associated
as spontaneous breathing trials and daily sedation wean- pneumonia in pediatric intensive care unit patients: risk factors
ing protocols, on the development of VAP. Our study and outcomes. Pediatrics. 2002;109(5):758 –764
shows that VAP negatively impacts clinical and eco- 15. Fayon MJ, Tucci M, Lacroix J, et al. Nosocomial pneumonia

1114 SRINIVASAN et al
Downloaded from by guest on July 9, 2019
and tracheitis in a pediatric intensive care unit: a prospective fusions and nosocomial infections in critically ill patients. Crit
study. Am J Respir Crit Care Med. 1997;155(1):162–169 Care Med. 2006;34(9):2302–2308
16. Collard H, Saint S, Matthay MA. Prevention of ventilator- 19. Shorr AF, Duh MS, Kelly KM, Kollef MH; CRIT Study Group.
associated pneumonia: an evidence-based systematic review. Red blood cell transfusion and ventilator-associated
Ann Intern Med. 2003;138(6):494 –501 pneumonia: a potential link? Crit Care Med. 2004;32(3):
17. Lacroix J, Hebert PC, Hutchison JS, et al. Transfusion strategies 666 – 674
for patients in pediatric intensive care units. N Engl J Med. 20. Rello J, Ollendorf DA, Oster G, et al. Epidemiology and out-
2007;356(16):1609 –1619 comes of ventilator-associated pneumonia in a large US Data-
18. Taylor RW, O’Brien J, Trottier SJ, et al. Red blood cell trans- base. CHEST. 2002;122(6):2115–2121


“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.
Pediatrics 2009;123;1108
DOI: 10.1542/peds.2008-1211

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References This article cites 18 articles, 1 of which you can access for free at:
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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.
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:

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since 1948. Pediatrics is owned, published, and trademarked by
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