Respiratory syncytial virus infections in the pediatric intensive

care unit: Clinical characteristics and risk factors for adverse

outcomes
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Steven C. Buckingham, MD; Michael W. Quasney, MD, PhD; Andrew J. Bush, PhD;
John P. DeVincenzo, MD
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Objectives: To describe the clinical characteristics of infants
admitted to a pediatric intensive care unit (PICU) with respiratory
syncytial virus (RSV) infection, including the prevalence of indi-
cations for RSV passive antibody prophylaxis (as currently rec-
ommended by the American Academy of Pediatrics), and to iden-
tify risk factors that predict adverse outcomes among this
population.
Design: Retrospective medical record review.
Setting: Tertiary care PICU.
Patients: Children <2 yrs of age admitted to PICU for the
management of RSV disease during the 1994 –95, 1995–96, and
1996 –97 RSV seasons.
Measurements and Main Results: The medical records of 89
infants were reviewed. Of these, 55% were born before 36-wks
gestation, 14% had chronic lung disease that required medical
therapy within the previous 6 months, and 30% met at least one
indication for RSV passive antibody prophylaxis. Seven infants
had congenital heart disease, five had upper airway abnormali-
ties, and six had various noncardiac congenital malformations.
Logistic regression was used to determine which characteristics
were associated with prolonged durations (>75th percentile) of
mechanical ventilation, PICU stay, and hospital stay. Prolonged
mechanical ventilation was associated with congenital heart dis-
ease (p ⴝ 0.014), chronic lung disease (p ⴝ 0.007), and noncar-
diac congenital malformations (p ⴝ 0.022). Only congenital heart
disease was associated with prolonged PICU stay (p ⴝ 0.004) or
prolonged hospital stay (p ⴝ 0.006). All of the infants with airway
abnormalities had prolonged ventilator days, PICU days, and
hospital days. Currently recommended indications for RSV pas-
sive antibody prophylaxis were not predictive of prolonged ven-
tilation, PICU stay, or hospital stay.
Conclusions: A minority of infants admitted to our PICU for
severe RSV disease meet currently recommended indications for
RSV passive antibody prophylaxis. Risk factors that predict pro-
longed durations of ventilation, PICU stay, or hospital stay among
this population include congenital heart disease, chronic lung
disease, upper airway abnormalities, and noncardiac congenital
malformations. (Pediatr Crit Care Med 2001; 2:318 –323)
KEY WORDS: respiratory syncytial virus; intensive care unit;
mechanical ventilation; antibodies; RSV immune globulin; chronic
lung disease; prematurity; congenital heart disease; congenital
malformations; airway abnormalities

R espiratory syncytial virus
(RSV) is the leading cause of
lower respiratory infection in
infants. In the United States,
RSV infection is estimated to cause be-
tween 73,400 and 126,300 hospitaliza-
tions annually among infants ⬍5 yrs of
age, and the occurrence rate of RSV-
associated hospitalizations is reportedly
increasing (1). RSV is known to cause
severe disease in certain infants, such as
From the Department of Pediatrics, Divisions of
Infectious Disease (Drs. Buckingham and DeVincenzo)
and Critical Care (Dr. Quasney), University of Tennes-
see Health Science Center and Le Bonheur Children’s
Medical Center; the Crippled Children’s Foundation
Research Center at Le Bonheur Children’s Medical
Center (Drs. Quasney and DeVincenzo); the Depart-
ment of Preventive Medicine, Division of Biostatistics
and Epidemiology, University of Tennessee Health Sci-
ence Center (Dr. Bush); and the Department of Infec-
tious Diseases (Dr. Buckingham), St. Jude Children’s
Research Hospital, Memphis, Tennessee.
those with chronic lung disease (CLD)
(previously termed bronchopulmonary
dysplasia), congenital heart disease
(CHD), and immunodeficiency (2–5).
Passive antibody prophylactic strategies
have been developed to protect infants at
high risk of severe RSV disease. A poly-
clonal immune globulin with high levels
of neutralizing activity against RSV (RSV-
IG) and a humanized murine monoclonal
antibody directed against the fusion pro-
Address requests for reprints to: Steven C.
Buckingham, MD, Room 301, West Patient Tower,
Crippled Children’s Foundation Research Center, Le
Bonheur Children’s Medical Center, 50 North Dunlap
Street, Memphis, Tennessee 38103. E-mail:
sbuckingham@utmem.edu
This article’s abstract appears in Japanese trans-
lation on page 357 of this issue.
Copyright © 2001 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
tein of RSV (palivizumab) have both been
demonstrated to be effective in reducing
the occurrence rate of RSV-associated
hospitalization among infants born pre-
maturely and among infants with CLD
(6 – 8). The American Academy of Pediat-
rics (AAP) currently recommends that
RSV passive antibody prophylaxis be con-
sidered up to 12 months of age for infants
born before 29 wks gestation, up to 6
months of age for infants born before 33
wks gestation, and for children younger
than 2 yrs of age who have required ther-
apy for CLD within 6 months before the
anticipated onset of the RSV season (9).
The AAP guidelines further state that,
given the large number of infants who are
born between 33 and 35 wks gestation,
prophylaxis in this group of infants
should be reserved for those infants with
additional risk factors (9).
Risk factors associated with increased
severity of RSV disease have been defined

318 Pediatr Crit Care Med 2001 Vol. 2, No. 4

 primarily among hospitalized infants.
Among RSV-infected infants who require
pediatric intensive care unit (PICU) ad-
mission, risk factors predictive of out-
comes are not as clearly defined. In a
multicenter trial, high-risk infants re-
ceiving monthly palivizumab prophylaxis
were less likely to require PICU admis-
sion than were those receiving placebo
(3.0% vs. 1.3%; p ⫽ 0.026) (8). Many
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infants who require ICU admission for
severe RSV disease, do not, however,
come from high-risk groups (10). Thus, it
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is presently unclear how the widespread
implementation of RSV passive antibody
prophylaxis in high-risk infants will affect
the PICU population.
This study was designed to ascertain
the prevalence of risk factors for severe
RSV disease and the prevalence of indica-
tions for RSV passive antibody prophy-
laxis among children admitted to a PICU
for the management of severe RSV dis-
ease. In addition, we wished to identify
risk factors that predict worse outcomes
among this population. To these ends, we
retrospectively reviewed the medical
records of all children admitted to our
tertiary care PICU for the management of
RSV disease over three consecutive win-
ters.
MATERIALS AND METHODS
Hospital. The study was conducted in a
200-bed free-standing pediatric tertiary care
facility. Approximately 200 children are admit-
ted to this hospital each year for the manage-
ment of diseases caused by RSV. The 20-bed
PICU at this children’s hospital admits approx-
imately 1200 patients each year and is the only
PICU in its geographic region.
Patients. The medical records of all pa-
tients ⬍2 yrs of age who were admitted to the
PICU for management of RSV disease during
the 1994 –95, 1995–96, and 1996 –97 RSV sea-
sons (October through April, inclusive) were
reviewed. Patients were identified by review-
ing the records of the clinical virology labora-
tory for specimens that tested positive for RSV
and by reviewing the billing records of the
PICU physicians for patients whose discharge
diagnoses included RSV, bronchiolitis, apnea,
or respiratory failure. In this PICU, it is stan-
dard practice to submit nasal secretions for
viral antigen detection and viral culture in
young infants admitted with respiratory symp-
toms during winter months. A single investi-
gator reviewed the charts of PICU patients
with laboratory-confirmed (antigen detection
or culture) RSV infection.
Each chart was reviewed for data regarding
patient characteristics, including age at ad-
mission, gestational age at birth, ethnicity,
gender, significant medical history, and pres-
Pediatr Crit Care Med 2001 Vol. 2, No. 4
ence of indications for passive antibody pro-
phylaxis for RSV. Infants were considered to
meet indications for RSV passive antibody pro-
phylaxis if they were: (1) born before 29 wks
gestation and ⬍12 months of age in October
(the anticipated onset of the RSV season in
this community); (2) born before 33 wks ges-
tation and younger than 6 months of age in
October; or (3) younger than 2 yrs of age in
October with a history of requiring supple-
mental oxygen, corticosteroid, or diuretic
therapy for CLD within 6 months before ad-
mission (9). Infants who had been born at or
beyond 33 wks gestation were not considered
candidates for prophylaxis because the pres-
ence of additional risk factors in these infants
could not be assessed by chart review. In keep-
ing with the 1998 AAP recommendations, pa-
tients with cyanotic CHD were not considered
candidates for prophylaxis (9).
The outcome measures evaluated were in-
hospital mortality and durations of mechani-
cal ventilation, PICU stay, and hospitalization.
For these determinations, a day was defined as
a calendar day or portion thereof spent on the
ventilator, in the PICU, or in the hospital. The
characteristics and outcomes to be reviewed
were selected before chart review began.
In this community, RSV-IG was not avail-
able before the 1996 –97 RSV season. During
the 1996 –97 winter, a defined cohort of 56
infants in this community received at least
one dose of RSV-IG. Information regarding
any prior receipt of RSV-IG among patients
admitted to the PICU during the 1996 –97
season was also recorded.
Statistical Analyses. Data were analyzed
using the SAS System for Windows, Release
6.12 (SAS Institute, Cary, NC). All hypothesis
tests were performed with two-tailed ␣ ⬍0.05
considered significant. Continuous variables
were compared using the Wilcoxon rank sum
test or Kruskal-Wallis test. Differences in cat-
egorical variables were assessed using the chi-
square test or Fisher’s exact test. Logistic re-
gression was used to determine which patient
characteristics predicted prolonged durations
of mechanical ventilation, PICU stay, and hos-
pital stay. For these analyses, prolonged ven-
tilator days, PICU days, and hospital days were
defined as those values falling in the upper
quartile of those of the entire cohort. We
chose to analyze these outcomes as categorical
variables using logistic regression, rather than
as continuous variables using linear regres-
sion because these outcome variables did not
follow normal distributions and because we
wished to define which independent variables
were specifically associated with adverse out-
comes (i.e., prolonged durations of mechani-
cal ventilation, PICU stay, or hospital stay).
The logistic regression analysis used a back-
ward elimination approach, and the signifi-
cance level for maintaining or removing inde-
pendent variables from the analysis was ␣ ⫽
0.05. Only patients who required mechanical
ventilation were included in the analyses of
ventilator days. The entire cohort was used for
the analyses of PICU days and hospital days.
RESULTS
A total of 92 infants younger than 2
yrs of age were admitted to the PICU with
RSV infection during the three RSV sea-
sons (October through April) from
1994 –95 to 1996 –97. Three patients were
excluded from the analysis; one without
severe disease was admitted to the PICU
solely because of staffing considerations,
one was in the PICU only briefly while
diagnostic bronchoscopy was performed,
and one was admitted to the PICU with
concurrent neurologic devastation re-
lated to trauma and RSV infection, mak-
ing it impossible to evaluate the contri-
bution of RSV infection to outcome.
Thus, 89 patients are included in the
analysis. One patient with CLD was
chronically ventilated before admission;
for this patient, the number of days until
the ventilator was returned to baseline
settings was recorded in place of the
number of days of mechanical ventila-
tion.
The baseline characteristics and un-
derlying medical conditions of the pa-
tients are listed in Table 1. Although 55%
of the patients were born before 36 wks
gestational age, only 14% had CLD that
required medical therapy within the 6
months before admission. Infants of Afri-
can American ethnicity were more likely
to have been born prematurely than were
those of white ethnicity (37 of 48 vs. 17 of
38; p ⫽ 0.003), but the difference in prev-
alence of CLD between African American
infants and white infants was not statis-
tically significant (9 of 48 vs. 2 of 38; p ⫽
0.06). Less than one third of the patients
had underlying conditions that would
have made them candidates for RSV pas-
sive antibody prophylaxis, according to
existing recommendations (9). Mean-
while, several infants suffered from med-
ical conditions for which prophylaxis is
not routinely recommended. Seven in-
fants had CHD, five had abnormalities of
the airway (proximal to the carina), and
six had various noncardiac congenital
malformations (Table 1). As might be ex-
pected, some infants had multiple under-
lying conditions. One infant had Cornelia
DeLange syndrome and a patent ductus
arteriosus. Another had tracheomalacia
and a patent foramen ovale. Of the three
children with Trisomy 21, one had sub-
glottic stenosis, one had a ventricular
319
 Table 1. Baseline characteristics and underlying medical conditions of patients admitted to the CLD, presence of indications for RSV pas-
pediatric intensive care unit for severe RSV disease sive antibody prophylaxis (9), presence of
CHD, and presence of noncardiac con-
Patients Receiving
genital malformations. Presence of air-
Ventilatory Support All Patients
(n ⫽ 72) (n ⫽ 89) way anomalies could not be included in
this analysis because all of the infants
Mean age, days 132 (150)a 140 (157) with this condition had durations of me-
Female gender 35 (49) 42 (47) chanical ventilation, PICU stay, and hos-
Ethnicity pital stay that fell in the upper quartile of
White 27 (38) 38 (43)
the cohort. The logistic regression anal-
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African American 42 (58) 48 (54)

Hispanic 2 (3) 2 (2) ysis revealed that prolonged mechanical
Arabic 1 (1) 1 (1) ventilation was significantly associated
Estimated gestational age at birth with CHD (p ⫽ 0.014), CLD (p ⫽ 0.007),
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⬎35 wks 31 (43) 40 (45) and noncardiac congenital malforma-

33–35 wks
29–32 wks
⬍29 wks
Indications for RSV passive antibody prophylaxis
Chronic lung disease,b ⬍24 mos of age
No CLD, EGA ⬍33 wks, ⬍6 mos of age
No CLD, EGA ⬍29 wks, ⬍12 mos of age
Congenital heart disease
Tetralogy of Fallot (with aorto-pulmonary shunt)
Atrial septal defect
Ventricular septal defect
Atrial and ventricular septal defects
Patent ductus arteriosus
Patent foramen ovale
Upper airway abnormalities
Laryngomalacia
Tracheomalacia
Pierre-Robin sequence
Subglottic stenosis
Noncardiac congenital malformations
Trisomy 21
Cornelia DeLange syndrome
Occipital encephalocele
Spina bifida with paraplegia
RSV, respiratory syncytial virus; CLD, chronic lung disease; EGA, estimated gestational age.
a
Numbers in parentheses, SD or %.
b
Requiring medical management (oxygen, corticosteroids, or diuretics) during the preceding 6
months.
septal defect, and one had a history of
duodenal atresia.
Infants were in the PICU for a mean
(SD) of 9.5 (8.0) days and in the hospital
for a mean (SD) of 15.3 (13.0) days. The 72
patients who required mechanical venti-
lation spent a mean (SD) of 10.1 (7.8) days
on the ventilator. Table 2 lists the results
of direct comparisons of ventilator days,
PICU days, and hospital days between pa-
tients with and without specified charac-
teristics. Infants with CHD and infants
with upper airway abnormalities had sig-
nificantly increased ventilator days, PICU
days, and hospital days compared with
other infants. Infants who were not white
had longer durations of PICU stay and
hospitalization than did white infants.
PICU days were also increased among in-
fants with noncardiac congenital malfor-
mations, and hospital days were in-
creased among infants born before 36
15 (21) 16 (18)
14 (19) 18 (20)
12 (17) 15 (17)
23 (32) 27 (30)
9 (13) 12 (14)
9 (13) 9 (10)
5 (7) 6 (7)
6 (8) 7 (8)
0 1
1 1
1 1
1 1
1 1
2 2
5 (7) 5 (6)
1 1
1 1
1 1
2 2
6 (8) 6 (7)
3 3
1 1
1 1
1 1
wks gestation. Infants who met indica-
tions for RSV passive antibody prophy-
laxis had longer hospital stays than did
those lacking these indications, but this
difference fell short of statistical signifi-
cance. Ventilator days and PICU days
were not significantly increased among
infants who met indications for prophy-
laxis.
Logistic regression was used to deter-
mine which patient characteristics were
associated with prolonged durations of
mechanical ventilation, PICU stay, and
hospital stay. The cutoff values defining
the upper quartiles (i.e., prolonged dura-
tions) of these outcome measures were
13 days for mechanical ventilation, 14
days for PICU stay, and 17 days for hos-
pital stay. The following independent
variables were entered into the regression
analysis: age, year of admission, gesta-
tional age, ethnicity, gender, presence of
tions (p ⫽ 0.022). Meanwhile, CHD was
the only independent variable associated
with prolonged PICU stay (p ⫽ 0.004) or
with prolonged hospital stay (p ⫽ 0.006).
Table 3 summarizes the characteris-
tics of the six patients with severe RSV
disease who died following admission to
the PICU. Of these infants, three were
born after term gestations and none had
CLD. Only one met any indications for
RSV passive antibody prophylaxis. A
higher proportion of white infants than of
nonwhite infants died, but this difference
was not statistically significant (5 of 38
vs. 1 of 51; p ⫽ 0.08). Both of the infants
with neural tube dysraphism disorders
died. Bacterial infections of normally
sterile body fluids were documented be-
fore death in both of these infants.
The year-to-year variations in baseline
characteristics and outcomes of PICU pa-
tients are displayed in Table 4. Over the
three RSV seasons that were studied,
baseline characteristics and indications
for passive antibody prophylaxis did not
vary significantly. Patients admitted in
1996 –97 had significant reductions in
ventilator days, PICU days, and hospital
days, compared with those admitted in
1994 –95 and 1995–96. To evaluate
whether these improved outcomes might
be related to the use of RSV-IG prophy-
laxis in the community, these analyses
were stratified by presence of indications
for prophylaxis. In fact, the reductions in
these outcome measures were limited to
patients who did not meet indications for
prophylaxis. Among the 27 infants who
met indications for prophylaxis, there
were no significant variations in ventila-
tor days (p ⫽ 0.75), PICU days (p ⫽ 0.70),
or hospital days (p ⫽ 0.41) over the three
RSV seasons, suggesting that the overall
improved outcomes seen during 1996 –97
were caused by factors other than the
limited use of RSV-IG in the community.
Three patients admitted in 1996 –97
had received at least one infusion of

320 Pediatr Crit Care Med 2001 Vol. 2, No. 4

 Table 2. Additional ventilator days, pediatric intensive care unit days, and hospital days in patients with specific characteristics

Ventilator Days PICU Days Hospital Days

Condition DMa pb DM p DM p

Female gender 1.4 0.83 1.3 0.59 3.5 0.71

Nonwhite ethnicity 0.1 0.72 2.2 0.049 4.8 0.006
Gestational age ⬍36 wks 1.2 0.62 2.1 0.20 2.6 0.04
Gestational age ⬍33 wks 1.4 0.57 1.0 0.55 2.1 0.13
Gestational age ⬍29 wks 0.1 0.67 0.6 0.44 1.2 0.32
Chronic lung diseasec
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5.0 0.07 3.9 0.11 5.3 0.19

Indications for RSV passive antibody prophylaxis 1.0 0.53 1.7 0.13 2.0 0.052
Congenital heart disease 11.3 0.004 11.4 0.009 18.4 0.01
Upper airway abnormalities 14.5 0.001 16.4 0.0008 31.4 0.0005
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Other noncardiac congenital malformations 4.9 0.07 6.0 0.04 13.8 0.07

PICU, pediatric intensive care unit; DM, difference in means; RSV, respiratory syncytial virus.
a
DM, difference in mean durations of mechanical ventilation, pediatric intensive care unit stay, and hospital stay between patients with specified
characteristic and those without this characteristic.
b
Wilcoxon rank sum test.
c
Requiring medical management (oxygen, corticosteroids, or diuretics) during the preceding 6 mos.

RSV-IG before hospitalization; two of
these infants required mechanical venti-
lation. These three infants spent a me-
dian (range) of 9.5 (4 –15) days on me-
chanical ventilation, 7 (5–17) days in the
PICU, and 13 (5–22) days in the hospital.
None of the 89 infants studied received
ribavirin during their hospital stays.
DISCUSSION
Over a 3-yr period, 30% of patients
admitted to our PICU for severe RSV dis-
ease would have fulfilled current indica-
tions for RSV passive antibody prophy-
laxis. Thus, the majority of critically ill
infants with RSV infection would not
have qualified to receive the protection of
passive immune prophylaxis. Moreover,
we did not find the presence of indica-
tions for RSV passive antibody prophy-
laxis to be significantly associated with
prolonged ventilator days, PICU days, or
hospital days. To our knowledge, the
prevalence of these characteristics among
PICU patients with RSV disease and their
relative contributions to outcomes in this
population have not been previously re-
ported. Our findings suggest that the
widespread use of existing passive anti-
body prophylactic strategies in premature
infants, according to current recommen-
dations, is not likely to dramatically affect
the burden of RSV disease in PICUs.
Our results underscore the impor-
tance of CHD as a risk factor for severe
RSV disease. As in previous studies (11–
13), we noted significant increases in
ventilator days, PICU days, and hospital
days among infants with CHD compared
with other infants. Although infants with
CHD constituted only 7% of this cohort,
they accounted for 16% of all RSV PICU
days and 17% of all RSV ventilator days
over three winter seasons. The safety and
efficacy of RSV-IG prophylaxis in infants
and children with CHD was previously
evaluated in a randomized, controlled
trial (14). Infants receiving prophylactic
RSV-IG were hospitalized for RSV infec-
tion significantly less frequently than
were infants receiving placebo (58% re-
duction; p ⫽ 0.01); however, unantici-
pated cyanotic episodes and poor out-
comes after cardiac surgery were more
common among infants with cyanotic
CHD in the RSV-IG group (28% vs. 8.5%;
p ⫽ 0.009). Although RSV-IG prophylaxis
is not recommended for infants with cy-
anotic CHD (9), palivizumab (with its in-
significant volume of administration)
may prove to be safe and effective for
such infants. A prospective trial is being
conducted to address this question.

Table 3. Characteristics of critically ill patients with severe RSV disease who died after admission

Age at Gestational Died on

Year of Admission Age Infections Other Than RSV Hospital
Admission (days) Sex Race (wks) Underlying Conditions (source) Cause of Death Day

1994–95 66 F W 27 none none progressive respiratory 7

failure
1994–95 311 M W term spina bifida, paraplegia Streptococcus pneumoniae progressive respiratory 4
(blood) failure
1994–95 45 F A 33 none none progressive respiratory 2
failure
1995–96 43 M W term none none progressive respiratory 12
failure
1995–96 49 F W 34 small patent foramen ovale none progressive respiratory 26
failure
1995–96 161 F W term occipital encephalocele Enterobacter cloacae not determined 20
(urine)

RSV, respiratory syncytial virus; M, male; F, female; W, white; A, African American.

Pediatr Crit Care Med 2001 Vol. 2, No. 4 321

 Table 4. Characteristics and outcomes of patients admitted to PICU for RSV infection: Breakdown by year

1994–95 1995–96 1996–97 pa

Patients 26 32 31
Mean age, days 117 (110)b 129 (122) 170 (213) 0.89
Female gender 12 (46) 15 (47) 15 (48) 0.99
Ethnicity 0.68
White 13 (50) 13 (41) 12 (39)
African American 12 (46) 17 (53) 19 (61)
Other 1 (4) 2 (6) 0 (0)
Gestational age 0.46
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⬎35 wks 14 (53) 14 (44) 12 (39)

33–35 wks 6 (23) 5 (16) 5 (16)
29–32 wks 4 (15) 5 (16) 9 (29)
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⬍29 wks 2 (8) 8 (25) 5 (16)

Indications for RSV passive antibody prophylaxis 5 (19) 12 (38) 10 (32) 0.31
Chronic lung disease,c ⬍24 mos of age 1 6 5
No CLD, EGA ⬍33 wks, ⬍6 mos of age 2 3 4
No CLD, EGA ⬍29 wks, ⬍12 mos of age 2 3 1
Congenital heart disease 2 (8) 4 (13) 1 (3) 0.39
Upper airway abnormalities 1 (4) 2 (6) 2 (6) 0.90
Noncardiac congenital malformations 2 (8) 3 (9) 1 (3) 0.61
Mean ventilator days 11.1 (10.0) 16.8 (9.9) 12.7 (10.6) 0.04
Mean PICU days 10.4 (9.9) 11.2 (6.9) 7.1 (6.7) 0.03
Mean hospital days 16.6 (18.0) 16.8 (9.9) 12.7 (10.6) 0.05
Deaths 3 (12) 3 (9) 0 (0) 0.17

RSV, respiratory syncytial virus; CLD, chronic lung disease; EGA, estimated gestational age.
a
Chi-square test for categorical variables; Kruskal-Wallis test for continuous variables.
b
Numbers in parentheses, SD or %.
c
Requiring medical management (oxygen, corticosteroids, or diuretics) during the preceding 6 mos.

Our results differ from those of previ-
ous studies of RSV infection in PICU pa-
tients in that we found that abnormalities
of the upper airway and noncardiac con-
genital malformations were significantly
predictive of a protracted disease course.
Infants with underlying abnormalities of
the upper airway had significantly longer
durations of mechanical ventilation,
PICU stay, and hospital stay compared
with infants with normal upper airways.
Infants with other noncardiac congenital
malformations had significantly longer
PICU stays than did infants without these
conditions, and logistic regression found
these other noncardiac congenital mal-
formations to be associated with pro-
longed mechanical ventilation. These re-
sults are intriguing, considering that
infants with Trisomy 21 have an in-
creased risk of severe disease and mortal-
ity from pneumonias of all types (15, 16),
possibly owing to immune defects, in-
cluding diminished delayed type hyper-
sensitivity (17–19), impaired neutrophil
chemotaxis and phagocytosis (20), and
deficient immunoglobulin G subclasses
(21). Prospective studies are needed to
clarify the risk of RSV disease among
infants with upper airway abnormalities
and infants with noncardiac congenital
malformations and to establish the safety
and efficacy of passive immune prophy-
laxis among these groups of infants.
In some previous studies of PICU pa-
tients with RSV disease, mortality was
observed only in patients with underlying
disease states (11, 12, 22). In contrast,
three of six deaths in our cohort occurred
in previously healthy infants, and only
one of the six infants that died met a
current indication for passive immune
prophylaxis. These findings suggest that
the effect of RSV passive antibody prophy-
laxis on mortality in the PICU may not be
profound. Furthermore, our observation
that both of the infants in our cohort
with neural tube dysraphism died under-
scores the potential severity of RSV dis-
ease in infants with risk factors other
than those defined by the current AAP
guidelines for RSV immune prophylaxis.
Although the role of dysraphism in the
deaths of these 2 infants is unclear, it is
known that infants with neural tube de-
fects may have compromised respiratory
function because of abnormal control of
breathing, laryngeal paralysis, recurrent
aspiration, or cor pulmonale (23).
It is important to recognize the limi-
tations of this study. We evaluated pa-
tients admitted to a single center. The
characteristics and outcomes of infants
admitted elsewhere may vary, as regional
variations in RSV disease severity have
been described (24). However, the char-
acteristics of patients in our cohort are
similar to those of infants admitted to a
PICU in Los Angeles from 1986 to 1990
(22). Another limitation of our study is
that we only reviewed the data available
in medical records. Because information
regarding environmental risk factors for
RSV disease such as exposure to tobacco
smoke, lack of breast-feeding, and pres-
ence of siblings in the home are often
incompletely recorded in medical
records, we were unable to assess the
prevalence of these characteristics in our
population. These data may be important,
as the current AAP recommendations for
RSV immune prophylaxis suggest that
these and other additional risk factors be
considered in deciding whether to admin-
ister prophylaxis to infants born between
33 and 35 wks gestation (9). Further
studies using prospective data collection
could establish the prevalence of these
environmental risk factors among RSV-
infected infants admitted to the PICU.
Finally, it should be noted that our re-
sults only apply to infants who require
PICU admission for severe RSV disease;
thus we cannot draw conclusions regard-
ing the effectiveness of RSV prophylactic
strategies in general.

322 Pediatr Crit Care Med 2001 Vol. 2, No. 4


O
ur results sug-
gest that cur-
rently recom-
mended passive antibody
prophylactic strategies may
Downloaded from http://journals.lww.com/pccmjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hC
not have a dramatic effect on
the burden of respiratory
ywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 11/22/2023
syncytial virus disease
among infants who require
pediatric intensive care unit
admission.
Our results suggest that currently rec-
ommended passive antibody prophylactic
strategies may not have a dramatic effect
on the burden of RSV disease among in-
fants who require PICU admission. More-
over, many RSV-infected PICU patients
suffer from underlying medical condi-
tions for which prophylaxis is not cur-
rently recommended. It is premature to
suggest broad changes in passive anti-
body prophylactic strategies on the basis
of these findings in a group of critically ill
infants. An ideal prophylactic strategy, of
course, would protect all infants, includ-
ing those born after term gestations who
lack any known risk factors for severe
RSV disease. Such a strategy (e.g., a vac-
cine that would be protective in young
infants) is not likely to be available in the
near future. Effective therapies are,
therefore, needed for children with severe
RSV disease.
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