*Prone positioning alone was stopped on day 2 in a patient with sickle
cell disease because of splenic sequestration.
No significant differences were found between the 2 groups (2-sample t test P = .91).
Baseline reflects supine values in both groups before the implementation
of ventilator protocols. Each calculation includes data from all patients,
regardless of how many measurements were available from each patient on that
day. The number of patients who contributed at least 1 measurement to the
calculation are included. The morning supine PaO2:FIO2 ratio and oxygenation index were not significantly
different between the 2 groups for any of the acute phase days (2-sample t test P≥.15). Error bars indicate
Curley MAQ, Hibberd PL, Fineman LD, Wypij D, Shih M, Thompson JE, Grant MJC, Barr FE, Cvijanovich NZ, Sorce L, Luckett PM, Matthay MA, Arnold JH. Effect of Prone Positioning on Clinical Outcomes in Children With Acute
Lung InjuryA Randomized Controlled Trial. JAMA. 2005;294(2):229-237. doi:10.1001/jama.294.2.229
Caring for the Critically Ill Patient Section Editor: Deborah J. Cook, MD, Consulting Editor, JAMA.
Author Affiliations: Children’s Hospital
Boston, Boston, Mass (Drs Curley, Wypij, Shih, and Arnold, and Mr Thompson);
Tufts-New England Medical Center, Boston, Mass (Dr Hibberd); University of
California, San Francisco (Dr Matthay and Ms Fineman); Primary Children’s
Medical Center, Salt Lake City, Utah (Dr Grant); Vanderbilt Children’s
Hospital, Nashville, Tenn (Dr Barr); Children’s Hospital Oakland, Oakland,
Calif (Dr Cvijanovich); Children’s Memorial Hospital, Chicago, Ill (Ms
Sorce); and Children’s Medical Center of Dallas, Dallas, Tex (Dr Luckett).
Context In uncontrolled clinical studies, prone positioning appeared to be safe
and to improve oxygenation in pediatric patients with acute lung injury. However,
the effect of prone positioning on clinical outcomes in children is not known.
Objective To test the hypothesis that at the end of 28 days infants and children
with acute lung injury treated with prone positioning would have more ventilator-free
days than those treated with supine positioning.
Design, Setting, and Patients Multicenter, randomized, controlled clinical trial conducted from August
28, 2001, to April 23, 2004, of 102 pediatric patients from 7 US pediatric
intensive care units aged 2 weeks to 18 years who were treated with supine
vs prone positioning. Randomization was concealed and group assignment was
Intervention Patients were randomized to either supine or prone positioning within
48 hours of meeting acute lung injury criteria, with those patients in the
prone group being positioned within 4 hours of randomization and remaining
prone for 20 hours each day during the acute phase of their illness for a
maximum of 7 days, after which they were positioned supine. Both groups were
treated using lung protective ventilator and sedation protocols, extubation
readiness testing, and hemodynamic, nutrition, and skin care guidelines.
Main Outcome Measure Ventilator-free days to day 28.
Results The trial was stopped at the planned interim analysis on the basis of
the prespecified futility stopping rule. There were no differences in the
number of ventilator-free days between the 2 groups (mean [SD], 15.8 [8.5]
supine vs 15.6 [8.6] prone; mean difference, −0.2 days; 95% CI, −3.6
to 3.2; P = .91). After controlling for
age, Pediatric Risk of Mortality III score, direct vs indirect acute lung
injury, and mode of mechanical ventilation at enrollment, the adjusted difference
in ventilator-free days was 0.3 days (95% CI, −3.0 to 3.5; P = .87). There were no differences in the secondary end
points, including proportion alive and ventilator-free on day 28 (P = .45), mortality from all causes (P>.99), the time to recovery of lung injury (P = .78),
organ-failure−free days (P = .88),
and cognitive impairment (P = .16) or overall
functional health (P = .12) at hospital
discharge or on day 28.
Conclusion Prone positioning does not significantly reduce ventilator-free days
or improve other clinical outcomes in pediatric patients with acute lung injury.
Acute lung injury is a major cause of acute respiratory failure in patients
who are critically ill and is associated with several clinical disorders,
including sepsis, pneumonia, and aspiration.1 Although
lifesaving, traditional ventilation strategies with higher tidal volumes and
airway pressures can exacerbate lung inflammation and injury.2 Acute
lung injury produces parenchymal lung damage that is heterogeneous and may
place the patient at risk for ventilator-associated lung injury. When patients
are supine, the reduced volume of the nondependent-aerated lung is at risk
for alveolar overdistention,3 and the cyclical
ventilation of the dependent lung at low volumes can cause recruitment-derecruitment
with subsequent mechanical strain.4 Prone positioning,
as first suggested by Bryan,5 is a maneuver
that can improve ventilation-to-perfusion matching6 and
lung mechanics7 in both adult and pediatric
patients with severe impairment of gas exchange.8- 13 The
improved oxygenation and regional changes in ventilation may result in decreased
ventilator-associated lung injury14 and facilitate
Although prone positioning is frequently used in the management of pediatric
patients with acute lung injury,15 there are
no data that suggest improved clinical outcomes. Gattinoni et al16 showed
no effect of 7 hours per day of prone positioning with survival in adult patients
with acute lung injury. Prone positioning improved oxygenation and a post
hoc analysis suggested improved outcomes in those patients with severe acute
lung injury. Using a similar study design, Guerin et al17 extended
the study population to include all adult patients with acute hypoxemic respiratory
failure and found improved oxygenation but no difference in survival or ventilator
days between the prone and supine groups. Both trials used prone positioning
for relatively short periods each day, did not require a lower tidal volume
approach, and did not include children. Therefore, we examined prolonged periods
of prone ventilation combined with a lower tidal volume approach in children
aged 2 weeks to 18 years with acute lung injury. We tested the hypothesis
that children with acute lung injury treated with prone positioning would
have more ventilator-free days than those treated with supine positioning.
Patients were enrolled from August 28, 2001, to April 23, 2004, at 7
US pediatric intensive care units that participate in the Pediatric Acute
Lung Injury and Sepsis Investigators network. The study design was approved
by the institutional review board of each hospital. Written informed consent
was obtained from the parent or legal guardian of each patient.
Inclusion criteria were pediatric patients aged 2 weeks to 18 years
who were intubated and mechanically ventilated with a ratio of partial pressure
of arterial oxygen (PaO2) to the fraction of inspired
oxygen (FIO2) of 300 or less (adjusted to 253 in
Salt Lake City, Utah, because of altitude), bilateral pulmonary infiltrates,
and no clinical evidence of left atrial hypertension.18 Patients
were excluded if they were younger than 2 weeks of age (newborn physiology),
less than 42 weeks postconceptual age (considered preterm), unable to tolerate
a position change (persistent hypotension, cerebral hypertension), had respiratory
failure from cardiac disease, had hypoxemia without bilateral infiltrates,
had received a bone marrow or lung transplant, were supported with extracorporeal
membrane oxygenation, had a nonpulmonary condition that could be exacerbated
by the prone position, had participated in other clinical trials within the
preceding 30 days, or if there was a decision to limit life support. Randomization
was performed by using a permuted blocks design, stratified by center, with
random block sizes. Allocation was concealed; each center received serially
numbered, opaque, sealed envelopes containing study assignments.
Eligible patients were randomized within 48 hours of meeting study criteria
to either supine or prone positioning. The clinical and research teams were
not blinded to treatment assignment. Patients randomized to the supine group
remained supine. Patients randomized to the prone group were positioned prone
within 4 hours of randomization and remained prone for 20 hours each day during
the acute phase of their illness for a maximum of 7 days of treatment, after
which they were positioned supine. When prone, individually sized cushions
were used to splint the most compliant aspect of the chest wall over the sternum
and unrestrain the diaphragmatic-abdomen component of the chest wall.7
The acute phase of illness was defined as the time interval between
randomization and the time at which extubation readiness criteria were met;
specifically, spontaneous breathing, oxygenation index (mean airway pressure/[PaO2:FIO2 ratio] × 100)
of less than 6, and a decrease in ventilator support over the previous 12
hours.19 Patients in both groups were assessed
each morning while in the supine position. Thus, the length of prone positioning
could be less than 20 hours on day 1. Other than positioning, both groups
were treated with specific care algorithms, which included ventilator and
sedation protocols, extubation readiness testing, as well as hemodynamic,
nutrition, and skin care guidelines during the 28-day period.
At enrollment, admission functional health20 and
Pediatric Risk of Mortality III (PRISM III)21 data
were recorded. Race and ethnic group were categorized by the investigators.
Circulatory, pulmonary, coagulation, hepatic, renal, and neurological system
function was also monitored daily for 28 days.
Patients randomized to prone positioning had their physiological values
and arterial blood gases assessed before and 1 hour after each supine-to-prone
and prone-to-supine turn. Days in which a patient exhibited an increase in
the PaO2:FIO2 ratio of
at least 20 or a decrease in oxygenation index of at least 10% after a supine-to-prone
turn were classified a priori as responder days.22 Patients
who experienced more responder days than nonresponder days over the entire
study period were considered overall responders; when equal, the patient’s
overall response was categorized by the day 1 response.9
The primary outcome measure was ventilator-free days, which were defined
as the number of days a patient breathed without assistance for at least 48
consecutive hours from day 1 to day 28 after randomization.23 Secondary
end points included alive and ventilator-free on day 28, mortality from all
causes, the time to recovery of lung injury, organ-failure−free days,
and functional health. Time to recovery of lung injury was defined as the
number of days from randomization to meeting extubation readiness testing
criteria for 24 consecutive hours through day 28. Organ-failure−free
days were defined as the number of days from day 1 to day 28 in which a patient
was without clinically significant nonpulmonary organ dysfunction. The Paediatric
Logistic Organ Dysfunction score parameters24 were
used to define pediatric organ dysfunction. Functional health was defined
as differences in cognitive impairment and overall functional health from
intensive care admission to hospital discharge or day 28, whichever occurred
first, using the Pediatric Cerebral Performance Category score and Pediatric
Overall Performance Category score.20
To ensure adequate power for the interim and final analyses, we conservatively
based our sample estimate on a dichotomous outcome—the proportion of
patients who were alive and ventilator-free at the end of 28 days. We used
data from our phase 1 study9 in which 25 consecutive
prone-positioned patients were matched (on acute lung injury trigger, age,
and closest PRISM III score on admission and oxygenation index at enrollment)
1:2 to a historical control group derived from the pediatric acute respiratory
distress syndrome data set.19 After we excluded
bone marrow transplant recipients from the analysis, 18 (90%) of 20 prone-positioned
patients were alive and ventilator-free on day 28 compared with 26 (65%) of
40 matched supine-positioned patients. Prone-positioned patients also experienced
more ventilator-free days (mean [SD], 15  days) than supine-positioned
patients (mean [SD], 8  days). Assuming 10% noncompliance in each group,
we calculated that a sample size of 90 patients per group was required to
yield 90% power to detect the noncompliance-adjusted difference of 87.5% [(90% × 90%) + (65% × 10%)]
vs 67.5% [(65% × 90%) + (90% × 10%)]
in the proportion of patients alive and ventilator-free on day 28, using a
fixed sample size χ2 test (nQuery Advisor 3.0, Statistical
Solutions, Boston, Mass).
A single interim analysis was planned after 50% of patients had completed
their participation in the study using the O’Brien-Fleming stopping
rule,25 with a priori boundaries of P<.006 (|Z|>2.74) to reject the null hypothesis (efficacy boundary,
if large treatment differences appear before the end of the study) and P>.52 (|Z|<0.70) to accept the null hypothesis (futility
boundary, if there is little chance of finding a significant difference between
groups). Allowing for this interim analysis with possible early stopping,
a sample size of 90 patients per group provided 88% power to detect the difference
of 87.5% vs 67.5% in proportion of patients alive and ventilator-free on day
28 between treatment groups using a χ2 test, and 82% power
to detect a difference of at least 4 ventilator-free days between treatment
groups via a t test, assuming a common SD of 9 days
for each group (East 3.1, Cytel Software Corporation, Cambridge, Mass). Thus,
this study was adequately powered to detect the hypothesized difference of
at least 4 ventilator-free days or a 20% or more difference in the proportion
of patients who were ventilator-free and alive on day 28.
The primary analyses were performed on an intention-to-treat basis.
We used the 2-sample t test, χ2 test,
or Fisher exact test to compare baseline characteristics. The t test was used to compare the number of ventilator-free days between
the 2 groups. Multiple linear regression analysis was then used to control
for age, PRISM III score, mode of mechanical ventilation at enrollment, and
direct vs indirect cause of lung injury. Center was not included in regression
models because it did not appreciably affect treatment group comparisons and
center effects were not statistically significant. No lack of fit, deviation
from the homoscedasticity assumption, or outliers were indicated in the residual
plots against variables in the model or against selected variables not in
the model. A quantile normal plot of the residuals revealed no clear deviation
from normality. The secondary outcomes and adverse events were compared using
the 2-sample t test for continuous variables and
χ2 test or Fisher exact test for categorical variables, except
that the time to recovery of lung injury was analyzed using the log-rank test.
Although 2-sample t tests are known to be robust
for deviation from normality for the sample sizes in the current study, Wilcoxon
rank sum tests were also performed because they may be more powerful than t tests for nonnormal data. The P values
for Wilcoxon rank sum tests were not reported unless the significance result
differed from t tests. All analyses were performed
with SAS software version 9.0 (SAS Institute, Cary, NC). A 2-sided P<.05 indicated statistical significance.
The data and safety monitoring board stopped the trial at the interim
analysis, after 102 patients had been enrolled, on the basis of the prespecified
futility stopping rule. At this time, based on the 94 patients who had completed
the 28-day study period (47 in the prone group and 47 in the supine group),
comparison of the primary outcome variable (ventilator-free days) either via t test (P = .87) or
multiple linear regression (P = .55) crossed
the a priori futility boundary for early stopping with acceptance of the null
hypothesis of no difference between groups. An identical conclusion was reached
using the comparison between proportions of patients alive and ventilator-free
on day 28 (χ2 test P = .60).
At the interim analysis, it was calculated that if the study had continued
to the planned enrollment of 180 patients, the probability of demonstrating
a difference in ventilator-free days between treatment groups was less than
1% under the alternative hypothesis based on the observed unadjusted ventilator-free
day treatment group differences. Analyses report on data from all 102 patients
Of the 8017 pediatric patients who were intubated, ventilated, and screened
for the study, 184 met acute lung injury criteria and 102 were enrolled and
randomized, 51 patients to each group (Figure
1). The baseline characteristics and respiratory variables at enrollment
were similar between the 2 groups (Table 1 and Table 2). More patients in the prone-positioned
group were initially supported on high-frequency oscillatory ventilation (12%
supine and 29% prone; χ2 test P = .03).
This difference was no longer significant after the implementation of study
protocols when patients in both groups with an oxygenation index of more than
20 were transitioned to high-frequency oscillatory ventilation.
The primary outcome, number of ventilator-free days, was not significantly
different between the 2 groups (mean [SD], 15.8 [8.5] for supine and 15.6
[8.6] for prone; 2-sample t test P = .91; prone-to-supine mean difference, −0.2 days;
95% confidence interval [CI], –3.6 to 3.2) (Table 3 and Figure 2). After
controlling for age, PRISM III score, direct vs indirect cause of acute lung
injury, and mode of mechanical ventilation at enrollment in a multiple linear
regression analysis, the adjusted prone-to-supine mean difference was 0.3
days (95% CI, –3.0 to 3.5; Wald test P = .87).
In addition, we found no evidence that age was a confounder (when excluding
age from model, prone-to-supine mean difference was 0.4 days, similar to that
when age was included in the model; 95% CI, −2.9 to 3.7) or effect modifier
of the association between prone vs supine positioning and ventilator-free
days (F test for position by age interaction P = .53).
In particular, the mean (SD) ventilator-free days for patients in the supine
and prone position for the 3 age groups were for less than 2 years, 18.7 (7.1)
vs 18.6 (7.6) days (mean difference, −0.1 days; 95% CI, −4.4 to
4.1); for 2 to 8 years, 14.6 (8.3) vs 11.5 (8.3) days (mean difference, −3.1
days; 95% CI, −10.4 to 4.1); for more than 8 years, 12.2 (9.4) vs 14.0
(9.2) days (mean difference, 1.8 days; 95% CI, −5.3 to 9.0).
The proportion of patients alive and ventilator-free on day 28 was 86%
in the supine and 80% in the prone group (risk ratio [RR], 0.93; 95% CI, 0.78-1.11;
χ2 test P = .45). The mortality
rate was 8% in both groups (RR, 0.98; 95% CI, 0.26-3.71; Fisher exact P>.99). There were no significant differences in the other
secondary end points of time to recovery of lung injury, organ-failure−free
days, and functional outcomes (Table 3)
or sedative use (Table 4) between the
2 groups. There were also no significant differences in the number of survivors
who were oxygen dependent on day 28 (20% supine and 26% prone, χ2 test P = .49).
Patients who were randomized to the prone-positioned group were positioned
within a median 28 hours of meeting study criteria (interquartile range, 18-39
hours) and within a median 2.3 hours of randomization (interquartile range,
1.6-3.5 hours). Patients remained prone for a mean 18 (SD, 4) hours per day
for 4 days (range, 1-7 days), which accounted for a mean 79% (SD, 9%) of the
acute phase of illness. The PaO2:FIO2 ratio and oxygenation index response to positioning are shown in Figure 3.
Sixty-four percent of 202 daily pronation procedures resulted in a PaO2:FIO2 ratio increase of at
least 20 mm Hg, or an oxygenation index decrease of at least 10%. Based on
the patient’s multiple day oxygenation response, 90% of patients in
the prone group were categorized as overall responders to prone positioning.
The number of ventilator-free days was not significantly different between
overall responders and nonresponders to prone positioning (2-sample t test P = .85).
All positioning and adjunctive therapy protocols were stopped during
the acute phase in 4 patients (3 in the prone group and 1 in the supine group)
(Figure 1). In the prone group, 1 patient
became hemodynamically unstable after consent had been obtained (day 1), 1
patient did not respond to conventional therapies and was cannulated for extracorporeal
membrane oxygenation (day 2), and 1 patient demonstrated persistent hypercarbia
in the prone position (day 3). One parent in the supine group withdrew consent
on day 1. Prone positioning alone was stopped on day 2 in a patient with sickle
cell disease because of splenic sequestration. Except for 1 patient in the
supine group for whom parental consent was withdrawn, all patients were included
in the intention-to-treat analysis.
All position-related adverse events are listed in Table 5. Five patients experienced serious study-related events,
4 in the prone group and 1 in the supine group (Fisher exact P = .36). In the prone group, 3 patients experienced hypercarbia
and 1 patient’s endotracheal tube was twisted and partially obstructed
during a head turn while prone. All 4 of these patients were on high-frequency
oscillatory ventilation at the time of the event and all 4 survived. The single
study-related serious adverse event in the supine group was a stage IV pressure
ulcer28,29; the patient did survive.
In this randomized trial of 102 pediatric patients with acute lung injury,
there were no significant differences in the number of ventilator-free days,
mortality, time to recovery of lung injury, organ-failure−free days,
or functional outcome between the prone and supine groups. Although we examined
prolonged periods of prone ventilation combined with a lower tidal volume
approach in children with acute lung injury, our results are similar to previously
reported studies in the adult population.16,17
As described in several nonrandomized studies,9,10,12 most
of our patients who were positioned prone did exhibit an improvement in oxygenation;
however, these improvements were not associated with a decrease in the duration
of ventilator support. Our 20-hour per day protocol was much longer than the
7- and 8-hour protocols that were previously tested in adult patients.16,17 This study was designed so that patients
could be afforded the potential lung-protective effects of prone ventilation
early and throughout the acute phase of illness. This goal was achieved as
patients were positioned prone on average 28 hours after meeting eligibility
criteria and were treated in the prone position for 79% of the acute phase
of illness. Although patients in this trial received early and prolonged use
of the prone position, we were unable to demonstrate beneficial effects on
Ninety percent of prone-positioned patients were categorized as responders
by some improvement in oxygenation efficiency. The mechanism by which prone
positioning leads to an improvement in oxygenation is not fully understood,
especially in a patient who is developmentally immature. In infancy, chest
wall compliance is nearly 3 times that of the lung.30 By
the second year of life, the increase in chest wall stiffness is such that
the chest wall and lung have similar compliance as in adults. By 8 years,
the height of the chest wall is similar to that of an adult. Pelosi et al7 reported that thoracoabdominal compliance decreases
in the prone position and the magnitude of this change is associated with
the observed change in oxygenation; that is, the greater the decrease in thoracoabdominal
compliance, the greater the improvement in oxygenation with prone positioning.
Given the demonstration that improved oxygenation with prone positioning is
associated with the magnitude of supine-prone difference in chest wall compliance
in adults,7 we predicted that prone positioning
would be more effective for improving oxygenation and clinical outcomes in
the younger patients enrolled in our clinical trial. Our results did not support
The primary outcome for this study was ventilator-free days, a composite
outcome that reflects both survival and duration of mechanical ventilation.23 We selected this outcome variable because we hypothesized
that prone positioning would simultaneously reduce mortality and shorten the
duration of ventilation. Compared with previous studies investigating acute
lung injury in adult patients,2,16,17,31- 33 we
report lower mortality and more ventilator-free days. Aside from age and excluding
patients after bone marrow transplant, our patient population was similar
to previous studies investigating prone positioning in adult patients.16,17
To evaluate the nonpulmonary effects of the prone position, a number
of secondary outcomes were analyzed. Nonpulmonary organ-failure−free
days, an outcome that provides insight into the lethal multiple organ dysfunction
related to acute lung injury,34 were not significantly
different between the 2 groups. This may be related to the small number of
patients who were septic in our study, a population that consistently manifests
the largest number of organ failures in clinical trials.1 Furthermore,
the use of a lung-protective ventilator protocol limited the potential for
differences in treatment outside of the positioning protocols.
Our study design also included assessment of functional health, which
provided additional insights. Not all pediatric patients who survived acute
lung injury returned to their previous level of function. Specifically, 11%
of survivors experienced worsening cerebral function and 16% of survivors
had worsening overall functional ability. To our knowledge, this is the first
study of acute lung injury describing the impact of acute lung injury on functional
outcomes in the pediatric population.
Little is known about the relationship between acute phase management
(specifically, optimal levels of oxygenation in the acute phase) and functional
outcomes in patients with acute lung injury. In pediatrics, several functional
outcome and quality of life measures are now available. Future interventional
studies should concentrate on looking past the immediate outcome of the episode
of illness and focus on the patient’s functional capacity and quality
There are limitations to this clinical trial. First, it was not possible
to blind clinicians to group assignment, so observer bias may have been introduced.
However, several aspects of the trial design should have limited this potential
bias, including the use of algorithms for most aspects of clinical care as
well as the use of objective outcome measures (available from the authors
upon request). Second, this study was not designed to show equivalence between
prone and supine positioning. Our trial design included a futility stopping
boundary because we thought it would be inappropriate to continue to randomize
patients into a study in which there was little chance of finding statistically
significant differences in the main clinical outcomes. Stopping the study
for futility at the planned interim analysis could have caused a type II error
(false-negative result); that is, failing to detect a prone positioning possible
benefit of 3.5 ventilator-free days or possible harm of 3.0 ventilator-free
days as indicated from the 95% CI. Third, given the smaller total sample size
induced by stopping early, we might not have observed a rare position-related
complication in the study.
Shortcomings of previous clinical studies of prone positioning have
included the lack of treatment algorithms for adjunctive care of study patients
that might impact primary or secondary study outcomes. In this trial, carefully
designed protocols to define ventilator management, extubation readiness,
and the use of sedative agents were implemented to minimize variation in the
daily management of both groups. Despite careful control of these cointerventions,
pediatric patients positioned prone did not demonstrate improved clinical
outcomes. Although we can rule out a large beneficial treatment effect, we
cannot exclude a small treatment effect, including a small negative effect.
However, based on the interim analysis performed at the study midpoint, the
results of this trial do not support the continued use of prone positioning
as a therapeutic intervention to improve the outcomes in pediatric patients
with acute lung injury.
Corresponding Author: Martha A. Q. Curley,
RN, PhD, Children’s Hospital Boston, Medical-Surgical Intensive Care
Unit, 300 Longwood Ave, Boston, MA 02115 (firstname.lastname@example.org).
Advisory Board: David Bihari, MD; Christian
Brun-Buisson, MD; Timothy Evans, MD; John Heffner, MD; Norman Paradis, MD;
Adrienne Randolph, MD.
Author Contributions: Dr Curley had full access
to all of the data in the study and takes responsibility for the integrity
of the data and the accuracy of the data analysis.
Study concept and design: Curley, Hibberd,
Wypij, Thompson, Matthay, Arnold.
Acquisition of data: Curley, Fineman, Grant,
Barr, Cvijanovich, Sorce, Luckett.
Analysis and interpretation of data: Curley,
Hibberd, Wypij, Shih, Thompson, Arnold.
Drafting of the manuscript: Curley, Hibberd,
Wypij, Shih, Matthay, Arnold.
Critical revision of the manuscript for important
intellectual content: Curley, Hibberd, Fineman, Wypij, Shih, Thompson,
Grant, Barr, Cvijanovich, Sorce, Luckett, Matthay, Arnold.
Statistical analysis: Curley, Hibberd, Wypij,
Obtained funding: Curley, Thompson, Hibberd,
Administrative, technical, or material support:
Curley, Fineman, Wypij, Grant, Barr, Cvijanovich, Sorce.
Study supervision: Curley.
Financial Disclosures: None reported.
Funding/Support: This study was supported by
grants RO1NR05336 from the National Institutes of Health/National Institute
of Nursing Research (NIH/NINR) and RR00064 and RR00054 from the NIH/National
Center for Research Resources (NCRR). Novametrix Medical Systems, Medical
Ventures, and i-STAT Corporation contributed equipment for this study.
Role of the Sponsor: The NIH/NINR, NIH/NCRR,
Novametrix Medical Systems, Medical Ventures, and i-STAT Corporation were
not involved in the design and conduct of the study; in the collection, management,
analysis, and interpretation of the data; or in the preparation, review, or
approval of the manuscript.
Participants in the Pediatric Prone Study Group:Children's Hospital Boston, Boston, Mass: J. H. Arnold,
R. Johnson, M. LaBrecque, J. E. Thompson; Children's Memorial
Hospital, Chicago, Ill: L. Sorce, D. Steinhorn; Primary Children's Medical Center, Salt Lake City, Utah: M. J. Chellis
Grant, C. Maloney; University of California, San Francisco: L. D. Fineman, J. Gutierrez, M. A. Matthay; Vanderbilt
Children's Hospital, Nashville, Tenn: F. E. Barr, J. Forlidas, A. Johnson; Children's Medical Center of Dallas, Dallas, Tex: P. M.
Luckett, S. Molitor-Kirsch; Children's Hospital Oakland,
Oakland, Calif: N. Cvijanovich, L. Wertz. Data Coordination
Center: P. L. Hibberd, P. Hopkins, M. McCarthy, A. Netson, M. C. Shih,
S. Wong, D. Wypij. Project Director: M. LaBrecque. External Quality Monitor: R. Lebet. Data and Safety Monitoring Board: K. Stone (chair), R. Clark, R. M.
Kacmarek, D. A. Schoenfeld.
Acknowledgment: We thank the pediatric critical
care nurses, respiratory therapists, physicians, and our patients and their
families who supported this clinical trial, and our colleagues in the Pediatric
Acute Lung Injury and Sepsis Investigators network who helped sustain this