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The effect of tidal volume on mortality and ventilator free days for children with acute lung injury (ALI)

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The effect of tidal volume on mortality and ventilator free days for children with acute lung injury (ALI)

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THE EFFECT OF TIDAL VOLUME ON MORTALITY AND VENTILATOR FREE
DAYS FOR CHILDREN WITH ACUTE LUNG INJURY (ALI)

by

Robinder G. Khemani

A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(CLINICAL AND BIOMEDICAL INVESTIGATIONS)

August 2008

Copyright 2008 Robinder G. Khemani

ii
Table of Contents

List of Tables iii
List of Figures iv
Abstract v
Introduction 1
Methods 4
Results 9
Discussion 19
References 27

iii
List of Tables

Table 1: Univariate Analysis by Survival 11
Table 2: Ventilator and Blood gas values by day of mechanical ventilation 13
Table 3: Lung Disease Severity Markers 16
Table 4: Tidal Volume, Mortality, and Ventilator Free Days 18

iv
List of Figures

Figure 1: Tidal Volume and Mortality by Day of Mechanical Ventilation 12
Figure 2: Tidal Volume by Lung Injury Score 15
Figure 3: Tidal Volume and Mortality by Peak Inspiratory Pressure 15
Figure 4: Lung Injury by Day and Mortality 17

v

Abstract

Objective: To determine whether Tidal Volume (Vt) between 6 and 10 ml/kg affects
outcome for children with ALI.
Methods: Review of PICU admissions from 2000-2007. Inclusion criteria were
intubation and ventilation with at least one PaO
2
/FiO
2
ratio < 300.
Results: 398 patients were included. Overall mortality was 20% with a median Vt of 7.4
ml/kg. Median Vt on the first day of mechanical ventilation was lower in the group that
died, although not statistically significant (p=0.06). After controlling for year, Delta P
(PIP-PEEP), PEEP, and severity of lung disease, Vt was not associated with mortality
(p>0.1), but higher Vt on day one of ventilation was associated with more ventilator free
days (p<0.05). This was particularly true in patients with better respiratory compliance
(OR=0.70, (0.52, 0.95)).

Conclusions: Between 6-10 ml/kg using pressure control ventilation, Vt early in
mechanical ventilation is not associated with mortality, and higher Vt is associated with
more ventilator free days.

1
Introduction

Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) result in
significant morbidity and mortality for patients admitted to Pediatric Intensive Care Units
(PICUs). It is estimated that 30-64% of all PICU patients require mechanical ventilation
[1], and of these patients up to 25% may have ALI [2] and 5-10% may meet criteria for
ARDS[1].

Data from the 1980s and early 1990s revealed mortality rates between 40 and 60% for
adults and children with ARDS, although survival has improved significantly over the
past 15 years with changes in ventilator strategies [3]. Recent randomized controlled
trials estimate mortality between 30-40% for adults [4], and 8-20% for children [5, 6].

In addition to higher mortality, children with ALI or ARDS have longer lengths of
mechanical ventilation and longer ICU lengths of stay than patients that require
mechanical ventilation for other reasons [1]. While the severity of lung disease can
explain much of this, Ventilator Induced Lung Injury (VILI) may contribute to longer
lengths of mechanical ventilation and mortality. The ARDS Network (ARDSNet) low
tidal volume study as well as a smaller study by Amato and coworkers demonstrated
significant reductions in mortality and more ventilator free days for adults managed with
tidal volumes of 6ml/kg compared to 12ml/kg [4, 7].

2
It is unclear, however, whether a low tidal volume strategy of 5-7 ml/kg should be
applied universally to all patients with ALI or ARDS, and if this is better than moderate
tidal volumes such as 8-10 ml/kg. Three randomized trials in adults have shown no
difference between groups ventilated with mean tidal volumes of 10.2-10.6 ml/kg
compared to 7.2-7.3 ml/kg [8-10]. Moreover, in the two beneficial trials mean tidal
volume of the control group actually increased by 17-18% after randomization, with
resultant increases in mean airway plateau pressures of 4-6 cmH20 [4, 7, 11]. As such,
the perceived mortality benefits of “lung protective ventilation” could have actually been
the result of increased mortality in the control group.

Designing similar randomized controlled trials for pediatric ALI and ARDS poses several
challenges. Smaller number of patients, lower mortality, heterogeneity of disease
conditions, lack of established uniform ventilator management strategies and protocols,
and unclear surrogate outcomes, all make multi-center randomized pediatric mechanical
ventilation trials difficult [12, 13]. As a result, many pediatric intensivists extrapolate
conclusions from adult studies regarding practices to minimize VILI. To this end, over
the last ten years most pediatric intensivists target lower tidal volumes for children with
ALI, and in a retrospective examination it appears that tidal volumes in the 11-12 ml/kg
range are harmful [14].

Moreover, there are several important differences between adult and pediatric critical
care regarding measurement and reporting of tidal volume. First, most pediatric

3
intensivists target tidal volume to actual body weight as opposed to ideal body weight
(IBW), utilized in most adult studies. In general this strategy is employed in adults to
account for obesity, as patients would receive potentially large tidal volumes if actual
body weight were used. While obesity is an issue in pediatric critical care as well,
pediatric intensivists are generally faced with the opposite scenario with chronic disease
or developmental abnormalities predisposing children to have lower than predicted body
weight. Second, despite advances in accuracy of tidal volume measurements with modern
mechanical ventilators, there are potentially large differences in measured exhaled tidal
volume at the mechanical ventilator compared to the proximal airway using a flow
sensor, particularly for small children. Therefore, while general trends regarding the
relationship between tidal volume and mortality may be comparable between adults and
children, the reported numbers may be calculated in different ways, and the absolute
values are not the same.

Finally, pediatric centers frequently use less volume control ventilation, with pressure
control or pressure limited modes being utilized close to 75% of the time [1]. These large
differences between adult and pediatric critical care bring into question the practice of
extrapolating adult evidence regarding tidal volume and outcome for acute lung injury to
children.

We seek to determine using historical data whether ventilator strategy and tidal volume
predict outcome for pediatric patients with ALI or ARDS, where tidal volume is

4
generally kept less than 10 ml/kg, employing mostly a pressure control mode of
ventilation. Additionally, we seek to examine the impact lung injury severity measures
such as PaO
2
/FiO
2
(PF) ratio, Oxygenation Index (OI), and a Modified Murray Pediatric
Lung Injury Score (LIS) [15] have on mortality at various time points during the initial
days of mechanical ventilation.

Methods
Patient Selection

A retrospective review of all admissions to a tertiary care Pediatric Intensive Care Unit
(PICU) between January 2000 and July 2007 was conducted. Patients were initially
screened for inclusion if they had at least two arterial blood gas values in which the PF
ratio was less than 300. Patients were eligible for inclusion in the study if they were
endotracheally intubated and mechanically ventilated, and persisted with at least one PF
ratio less than 300 within twenty-four hours of intubation and mechanical ventilation.
Patients were excluded from the study if they had evidence of left ventricular dysfunction
either by echocardiography or clinical exam, cyanotic congential heart disease,
cardiomyopathy, myocarditis, or primary pulmonary hypertension. Patients were also
excluded if they had incomplete data on ventilator management or intubation and
extubation times. All patients met three of the four diagnostic criteria for ALI (acute
onset of disease, PF ratio <300, and lack of left ventricular dysfunction). The presence
of bilateral infiltrates on chest radiograph (the fourth criteria for ALI) was handled as a

5
separate variable, and analysis was made comparing those who met all four criteria to the
entire cohort. Finally, to account for the effect a leak around the endotracheal tube may
have on volume and compliance measurements and calculations, all patients with an
endotracheal tube leak [(Inhaled Tidal Volume-Exhaled Tidal Volume)/(Inhaled Tidal
Volume)] greater than 20% were excluded from analysis [16].

Variable Selection

Two databases are routinely used for clinical and research purposes in our intensive care
unit. Information on demographics, vital signs, laboratory, blood gas results, and
ventilator settings were extracted from an electronic ICU flow sheet (Phillips CareVue®),
which captures data in real-time from several integrated parts of the patient medical
record. In addition, a separate database (Microsoft Access ©) with diagnosis information,
procedures, and standardized mortality scores is maintained in real-time by the ICU
attendings and fellows providing clinical care. From these two databases, information on
patient age, race, gender, weight, primary diagnosis, year of admission, chest x-rays, and
a 12-hour Pediatric Risk of Mortality (PRISM III) Score were extracted [17, 18]. Primary
diagnosis was grouped into general diagnostic categories, based on primary organ system
or disease process involved. All chest x-rays were read by an attending pediatric
radiologist, and reports were reviewed for the presence of diagnostic criteria for ALI, i.e.
bilateral infiltrates, consolidation. In addition, all arterial blood gas values and
respiratory therapy records were reviewed and ventilator variables extracted.

6

Ventilator and Arterial Blood Gas Variable Definition

The time of first PF ratio < 300 after intubation and mechanical ventilation was defined
as “baseline.” At this time, information for baseline blood gas measurements of pH,
PaCO
2
, PaO
2
, HCO
3
, and Base Deficit were extracted. In addition, the closest charted
ventilator settings at or prior to the ABG values were also extracted. This included
information on mode of ventilation, ventilator rate, Peak Inspiratory Pressure (PIP),
Positive End Expiratory Pressure (PEEP), Mean Airway Pressure (MAP), Fraction of
inspired Oxygen (FiO
2
), Inspiratory Time (Ti), Inspired Tidal Volume (Vti), and Exhaled
Tidal Volume (Vte). Tidal Volume (Vt ml/kg) was calculated using Vte measured at the
mechanical ventilator with appropriate compensation for tubing compliance and make of
the ventilator. This value was then divided by actual body weight to report tidal volume
in ml/kg.

Next, aggregate variables were created to express time-weighted averages of ventilator
settings and blood gas values over the first three days after “baseline.” For example,
PEEP1 was defined as the patient’s time-weighted average value for PEEP for the first 24
hours after baseline. Each charted PEEP in the first 24 hours was multiplied by the time
over which the patient remained at that PEEP, summed with the other time-weighted
PEEP values in that 24-hour period, and divided by 24 hours. If the patient was
extubated, died, or had no charted ventilator data during that time period, then the

7
aggregate variable was only averaged over the time when data was available (i.e. if a
patient was extubated at hour 22, then the values would be averaged over 22 hours
instead of 24). The same methodology was used for the second and third 24-hour
intervals, each representing independent 24-hour periods, not aggregate 48 or 72-hour
values.

Lung Injury Severity Markers

PaO
2
/FiO
2
(PF) ratio, Oxygenation Index [OI= (Mean Airway Pressure*FiO
2
)/(PaO
2
)
*100], Dynamic Compliance of the Respiratory System [Crs= Vt (ml/kg)/(PIP-PEEP)],
and a Modified Murray Lung Injury Score (LIS) for pediatric application [15] were
determined at “baseline” and then again aggregated over the first three days after
baseline, as discussed above. Of note, the Lung Injury Score is a composite of PF ratio,
PEEP, Crs, and involved quadrants on chest radiograph, with integer values from zero to
four assigned for each component. Specific data on number of quadrants of alveolar
consolidation on chest x-ray were not included in this analysis. As a result, the total
Lung Injury Score was the average of three, rather than four components.

Outcome Measures

The primary outcome measure of the study was ICU mortality. Secondary outcome was
28-day ventilator free days, defined as the total number of days in the 28 days after

8
intubation for which the patient was alive and free from mechanical ventilator support
[19]. Data on both outcome measures were complete for all patients; as such no censoring
was necessary.

Statistics

Descriptive statistics regarding distribution of variables and population characteristics
were first performed. Next, univariate analysis was performed examining the variables of
interest against the outcome of mortality. Continuous variables were analyzed with a
Wilcoxon Rank-Sum test, as assumptions of normality could not always be satisfied.
Dichotomous outcomes were analyzed using a Yates-Corrected Chi-squared test.
Kruskall-Wallis ANOVA was utilized to examine differences in median tidal volume
stratified by lung injury score. Next, logistic regression analysis was performed to
examine the impact of the variables of interest on the outcome of mortality, and control
for potential confounding variables, or effect modifiers. A multivariate logistic
regression model was built incorporating variables with univariate associations with
mortality (p<0.2), with care taken to avoid terms that were collinear. Terms were deemed
collinear if standard errors for point estimates in the regression model became large, or if
terms were thought to measure similar clinical parameters (i.e. Mean Airway Pressure
and Peak Inspiratory Pressure). Analysis was limited to subjects with complete data for
all the variables included in the multivariate model. Assumptions of linearity of the
dependent variables in the logistic model were examined and satisfied, and no

9
transformations were necessary. Overall goodness of fit was assessed using the Hosmer-
Lemeshow test, as well as graphical evaluation for influential points. ROC plots were
created and overall discrimination ability of the various predictive models was assessed
using empirical estimates of the overall Area Under the Curve (AUC).

The outcome of 28-day ventilator free days had an almost bimodal distribution, as has
been noted in previous studies. As such, for the purpose of regression analysis and
controlling for confounding variables, it was examined as a dichotomous outcome of <14
days, or ≥ 14 days, as previously described [20]. Logistic regression modeling was used
to examine the effect of tidal volume on ventilator free days, and again control for
potential confounding variables and effect modifiers. However, when appropriate,
comparisons of median number of ventilator free days between two groups were analyzed
using a Wilcoxon Rank-Sum test [19].

Results

8,246 patients less than 18 years of age were admitted to the PICU during this time
period. Of these patients, 773 had at least 2 arterial PF ratios <300. 700 were
mechanically ventilated and 507 had at least 1 PF ratio <300 after endotracheal intubation
and mechanical ventilation. 9 patients were excluded because of incomplete ventilator or
blood gas data, 49 patients had left ventricular dysfunction, cyanotic congenital heart

10
disease, myocarditis, cardiomyopathy, or primary pulmonary hypertension. Finally, 51
patients were excluded because they had an endotracheal tube leak percentage >20%.

398 patients were included in the final analysis, of which 227 were male (57%), 194 were
Latino (49%), with a median age of 4.3 years. 80 patients died, with an overall mortality
of 20%. 192 patients (48%) had bilateral pulmonary infiltrates on chest x-ray, and
therefore met formal criteria for either ALI or ARDS (Table 1).

Mortality

There was no difference in median weight, median age, race proportion, gender
proportion, or proportion of bilateral pulmonary infiltrates on chest x-ray between those
who survived and those that died. Patients that died had higher median 12-hour PRISM
III scores. Compared to the group of patients that had primary pulmonary parenchymal
disease (i.e. pneumonia, bronchiolitis, asthma), patients that had a primary diagnosis of
shock or sepsis were more likely to die, and those with primarily orthopedic diagnoses
were less likely to die (Table 1).

11

Table 1: Univariate Analysis by Survival.
All Survived Died P value
(n=398) (n=318) (n=80)
Demographics
Weight (kg) 16 (8,36) 15 (9,34) 17 (8,44) 0.728
Age (yrs)
4.29
(0.98,11.46)
3.84
(0.99,10.92)
5.92
(0.84,12.54) 0.734
Race
Latino 194 (48.74) 157 (49.37) 37 (46.25) 0.708
White 74 (18.59) 56 (17.61) 18 (22.5) 0.399
Black 45 (11.31) 35 (11) 10 (12.5) 0.857
Other 85 (21.36) 70 (22.01) 15 (18.75) 0.629
Male 227 (57.04) 180 (56.6) 47 (58.75) 0.826
CXR Bilateral Infiltrates 192 (48.24) 148 (46.54) 44 (55) 0.219
PRISM III Probability of Death
0.06
(0.02,0.20)
0.06
(0.02,0.17)
0.14
(0.04,0.42) <0.001
Admission Diagnosis OR (95% CI)
Parenchymal Lung Disease* 117 (29.40) 92 (28.93) 25 (31.25) Reference
Other Respiratory Disease 30 (7.54) 23 (7.23) 7 (8.75) 1.47 (0.57,3.81)
Shock or Sepsis 43 (10.80) 29 (9.12) 14 (17.50) 2.33 (1.08,5.04)
Trauma 16 (4.02) 12 (3.77) 4 (5) 1.61 (0.48,5.41)
Neurologic Compromise 50 (12.56) 37 (11.64) 13 (16.25) 1.70 (0.79,3.65)
Metabolic/Renal Compromise 24 (6.03) 22 (6.92) 2 (2.5) 0.44 (0.10,1.99)
Other Diagnosis 28 (7.04) 21 (6.61) 7 (8.75) 1.61 (0.62,4.20)
Gastrointestinal Diagnosis 61 (15.33) 53 (16.67) 8 (10) 0.73 (0.31,1.73)
Orthopedic Diagnosis 29 (7.29) 29 (9.12) 0 (0) 0 (0,0.27)
Continuous variables expressed as median and interquartile range. Categorical Variables expressed as
count and percentage. * Parenchymal Lung disease used as baseline group for computation of Odds Ratios
for diagnostic category for admission.

For the entire population, the median PF ratio at baseline was 138 with a median Lung
Injury Score of 2.33. Patients were managed almost exclusively with Pressure Control
ventilation (>90%), with a median PEEP of 6 cmH
2
0, Tidal Volume of 7.4 ml/kg, and
PIP of 26 cmH
2
0. When looking specifically at ventilator and blood gas data, at baseline
patients that died had higher median OI, lower median PF Ratio, and higher median Lung
Injury Score, as well as higher FiO
2
, PIP, PEEP, Mean Airway Pressure, lower pH, PaO
2
,

12
HCO
3
and base deficit. Median tidal volume was slightly lower in the group that died
(7.04 vs 7.60 ml/kg), although this was not statistically significant. These trends for
blood gas, ventilator, and lung severity markers remained consistent over the first 3 days
of ventilation (Table 2).

While tidal volume did not appear to be associated with mortality, 70% of patients were
managed with a tidal volume between 6 and 10 ml/kg, and this general target for tidal
volume was maintained throughout the first three days of mechanical ventilation (Figure
1). There was a non-significant trend for improved survival with higher tidal volumes.

Figure 1: Tidal Volume and Mortality by day of mechanical ventilation

There is a general trend for higher mortality with lower tidal volumes, which remains consistent both at the
beginning of mechanical ventilation, and throughout the first three days. Most patients are ventilated
between 6 and 10 ml/kg throughout the first three days of mechanical ventilation.

Initial Vt and Mortality
n=398
0
20
40
60
80
100
120
<6 6 to 8 8 to 10 >10
Vt (ml/kg)
C ount
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
Mortality
Surv iv ed Died Mortality
Day 1 Vt and Mortality
n=376
0
20
40
60
80
100
120
<6 6 to 8 8 to 10 >10
Vt (ml/kg)
C ount
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
Mortality
Surv iv ed Died Mortality
Day 2 Vt and Mortality
n=343
0
20
40
60
80
100
120
<6 6 to 8 8 to 10 >10
Vt (ml/kg)
C ount
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
Mortality
Surv iv ed Died Mortality
Day 3 Vt and Mortality
n=290
0
20
40
60
80
100
120
<6 6 to 8 8 to 10 >10
Vt (ml/kg)
Count
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
Mortality
Surv iv ed Died Mortality
Initial Vt and Mortality
n=398
0
20
40
60
80
100
120
<6 6 to 8 8 to 10 >10
Vt (ml/kg)
C ount
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
Mortality
Surv iv ed Died Mortality
Day 1 Vt and Mortality
n=376
0
20
40
60
80
100
120
<6 6 to 8 8 to 10 >10
Vt (ml/kg)
C ount
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
Mortality
Surv iv ed Died Mortality
Day 2 Vt and Mortality
n=343
0
20
40
60
80
100
120
<6 6 to 8 8 to 10 >10
Vt (ml/kg)
C ount
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
Mortality
Surv iv ed Died Mortality
Day 3 Vt and Mortality
n=290
0
20
40
60
80
100
120
<6 6 to 8 8 to 10 >10
Vt (ml/kg)
Count
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
Mortality
Surv iv ed Died Mortality

13
Table 2: Blood Gas, Ventilator, and Lung Severity Markers by day of mechanical ventilation, stratified by mortality.
Baseline Baseline Baseline Day 1 Day 1 Day 1
All Survived Died p value All Survived Died p value
n=398 n=318 n=80 n=376 n=298 n=78
Blood Gas
PaCO 2
45
(38,53)
44
(38,52)
46.5
(38,57) 0.135
42.6
(37.5,49)
42
(37.5,48.0)
45.5
(37.9,52.1) 0.07
PaO 2
75
(61,92)
77
(64,94)
63.5
(53.5,80) <0.001
100.1
(79.9,122.2)
100
(20.1,122.5)
101.1
(73.6,117) 0.764
pH
7.35
(7.27,7.40)
7.35
(7.29,7.41)
7.29
(7.20,7.36) <0.001
7.37
(7.32,7.42)
7.37
(7.33,7.42)
7.32
(7.26,7.38) <0.001
HCO 3
24
(21,28)
24
(21,28)
22
(19,27) 0.002
24
(21.2,27.2)
24.1
(21.8,27.3)
22.1
(19.3,25.8) 0.003
BE
-2.1
(-5.3,1.5)
-1.55
(-4.7,1.85)
-4.6
(-8.8,-0.3) <0.001
-1.43
(-4.16,1.73)
-0.89
(-3.51,1.96)
-3.22
(-6.18,-0.08) <0.001
Vent Support
FiO 2
0.6
(0.4,1)
0.5
(0.4,0.9)
0.8
(0.5,1) <0.001
0.46
(0.4,0.6)
0.45
(0.40,0.53)
0.58
(0.43,0.80) <0.001
MAP
11
(9,15)
11
(9,14)
14
(9,17) 0.001
13
(10.2,17)
12.3
(9.8,15.7)
17.1
(13.2,22) <0.001
PIP
26
(22,30.5)
26
(22,30)
30
(24,34) 0.003
26.5
(22.8,31.7)
25.5
(22.2,30.4)
30.1
(26,36) <0.001
PEEP
6
(4,8)
6
(4,8)
8
(4,10) <0.001
7.4
(5,10)
6.8
(4.8, 10)
9.5
(6.6,12.4) <0.001
VT (ml/kg)
7.45
(5.79,9.14)
7.6
(5.86,9.22)
7.04
(5.46,8.74) 0.129
7.46
(6.08,9.02)
7.49
(6.24,9.18)
7.30
(5.53,8.65) 0.06
Injury Markers
PF Ratio
138.1
(82.5,192.5)
149.4
(95,200)
79.5
(60.1,147.1) <0.001
196
(139.7,268)
209.4
(148.2,271.1)
167.9
(96.3,247.5) 0.008
OI
8.1
(5.1,15.3)
7.4
(4.8,13.1)
14.3
(7.9,24.4) <0.001
6.2
(3.8,10.6)
5.6
(3.7,9.2)
10.1
(4.5,18.2) <0.001
CRS
0.38
(0.27,0.50)
0.38
(0.28,0.51)
0.36
(0.23,0.47) 0.0857
0.40
(0.30,0.54)
0.42
(0.32,0.55)
0.35
(0.26,0.44) 0.001
LIS
2.33
(2,3)
2.33
(1.67,3)
3
(2.33,3.33) <0.001
2.33
(1.67,3)
2.33
(1.67,2.67)
3
(2, 3.33) <0.001

14

Day 2 Day 2 Day 2 Day 3 Day 3 Day 3
All Survived Died p value All Survived Died p value
n=343 n=276 n=67 n=290 n=238 n=52
Blood Gas
PaCO 2
42.8
(37.8,48.6)
42.5
(37.7,48.3)
43.4
(38.1,50.5) 0.307
44.3
(38.8,50.7)
43.5
(38.3,49.4)
48.3
(40,55.7) 0.01
PaO 2
97.2
(78.8,122.6)
98
(80.4,121.9)
95.5
(67.6,127.7) 0.257
96
(77.5,117)
96.4
(79.8,117.7)
80
(68.1,114.4) 0.04
pH
7.40
(7.35,7.44)
7.40
(7.36,7.44)
7.37
(7.30,7.43) 0.014
7.40
(7.36,7.45)
7.41
(7.36,7.45)
7.37
(7.30,7.44) 0.002
HCO 3
25.2
(22.6,29.2)
25.4
(22.9,29.2)
24.2
(21,29.2) 0.122
27.2
(23.6,31)
27.5
(24,30.8)
25.4
(23.1,33.5) 0.123
BE
0.40
(-2.45,4.42)
0.5
(-2.02,4.42)
-1.24
(-4.48,4.35) 0.031
1.65
(-1.1,5.8)
2.02
(-0.9,5.71)
0.02
(-2.90, 7.60) 0.135
Vent Support
FiO 2
0.41
(0.39,0.52)
0.4
(0.37,0.47)
0.50
(0.4,0.649) <0.001
0.4
(0.36,0.50)
0.4
(0.36,0.46)
0.5
(0.4,0.8) <0.001
MAP
12.8
(10.1,26.7)
12
(9.5,15.2)
16.6
(12.8,21.6) <0.001
13.6
(10,16.6)
12.5
(9.5,15.6)
16.8
(13.9,20.8) <0.001
PIP
26
(21.7,30.7)
25.1
(21.4,29.7)
30
(27.1,35) <0.001
26
(21.5,30.6)
24.9
(20.1,29.6)
30.1
(27,35.4) <0.001
PEEP
7.8
(5.7,10)
7
(5.1,9.5)
10
(6.8,12.4) <0.001
8
(5.8,10)
7.3
(5.6,9.9)
10
(7.8,13.5) <0.001
VT (ml/kg)
7.17
(5.76,8.73)
7.20
(5.79,8.79)
7.01
(5.52,8.52) 0.377
7.19
(5.88,8.45)
7.15
(5.88,8.45)
7.39
(5.98,8.44) 0.894
Injury Markers
PF Ratio
232.6
(163,311)
235
(171.7,314.4)
192.7
(107.7,292.5) 0.01
214.3
(151.8,300)
223.8
(167.9,303.9)
157.5
(102.6,283.8) 0.002
OI
5.2
(3.4,9.5)
4.8
(3.3,7.6)
8.6
(4.6,15) <0.001
5.5
(3.6,9.8)
5
(3.4,8)
11
(4.9,18.3) <0.001
CRS
0.40
(0.29,0.52)
0.42
(0.30, 0.55)
0.35
(0.27,0.48) 0.007
0.42
(0.30,0.54)
0.43
(0.32,0.55)
0.35
(0.28, 0.48) 0.017
LIS
2
(1.67,3)
2
(1.33,2.67)
2.7
(2, 3.33) <0.001
2.33
(1.67, 3)
2
(1.67,2.67)
3
(2, 3.33) <0.001
Variables expressed as median and interquartile range, and analyzed with a Wilcoxon Rank Sum test.

15
Patients with higher Lung Injury Scores were managed with lower median tidal volume
than those with lower lung injury scores (K-W ANOVA p<0.001, Figure 2). However,
patients who were ventilated on day one with Peak Inspiratory Pressures >30 that
achieved tidal volumes >10 ml/kg had higher mortality than those who received tidal
volumes between 6-10 ml/kg (30% vs 18.6%, (Figure 3)), although this occurred only in
ten patients and was not statistically significant (p=0.34).
Figure 2: Median Baseline Tidal Volume by Lung Injury Score

Patients with higher lung injury scores were managed with lower median Vt.

Figure 3: Tidal Volume and Mortality, stratified by Peak Inspiratory Pressure
For patients who received PIP >30, there is a trend for higher mortality
when Vt is >10 ml/kg, although this was not statistically significant.
Baseline Lung Injury Score
Vt (ml/kg)
Day 1 Vt and M ortality by PIP
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
<6 6-8 8-10 >10
V t (m l/kg)
Mortality
P IP >30 P IP <30

16

Markers of Lung Injury including PF Ratio, OI, and LIS were all significantly associated
with mortality at baseline (Table 2) with similar overall classification in a logistic
regression model (Table 3). Further, there was a trend for stronger degrees of association
with mortality for all measures with each additional day the patient remained on
mechanical ventilation (Figure 4). Compliance of the respiratory system, while not
statistically significantly associated with mortality at baseline, was when aggregated at
day 1, 2, and 3.

Table 3: Lung Disease Severity markers and mortality for all patients, and those that had
radiographic evidence of ALI or ARDS.
All Patients All Patients CXR Criteria
n=398 n=398 n=192
OR (95% CI) AUC (95% CI) OR (95%CI)
PF Ratio (per 20 pt decrease)
1.23
(1.13,1.34)
0.693
(0.626, 0.720)
1.19
(1.06,1.34)
PF Ratio <200
2.88
(1.33,6.24)
23% sensitivity
91% specificity
2.32
(0.85,6.37)
OI (per 1 pt increase)
1.04
(1.02,1.06)
0.691
(0.628, 0.754)
1.03
(1.00,1.05)
LIS (per 1 pt increase)
2.32
(1.65,3.27)
0.68
(0.609,0.751)
1.81
(1.13,2.91)

17

Figure 4: Lung Injury by day and Mortality.

OR for death per one unit increase in OI, one unit increase in LIS, 0.1 unit decrease in Crs, and 20 pt
decrease in PF Ratio. LIS and OI are associated with mortality at baseline and over the first three days.
Crs over the first three days and PF ratio at baseline, second and third day are associated with mortality.

Multivariate logistic regression modeling was performed to determine whether severity of
lung disease impacted the relationship between tidal volume and mortality. Of note,
initial median tidal volume tended to be lower over time (from 2001-2007), although this
was not true for aggregate values at 1, 2, and 3 days. Tidal volume was not associated
with mortality after controlling for year of admission, Delta P (PIP-PEEP), PEEP, and
severity of lung disease using LIS, PF Ratio, or OI (all tidal volume coefficients p>0.1,
Baseline Day 1 Day 2 Day 3
Odds Ratio (95% CI)
OI by Day
Baseline Day 1 Day 2 Day 3
Odds Ratio (95% CI)
LIS by Day
Baseline Day 1 Day 2 Day 3
Odds Ratio (95% CI)
Crs by Day
Baseline Day 1 Day 2 Day 3
Odds Ratio (95% CI)
PF Ratio by Day
95% CI
Odds Ratio
Baseline Day 1 Day 2 Day 3
Odds Ratio (95% CI)
OI by Day
Baseline Day 1 Day 2 Day 3
Odds Ratio (95% CI)
LIS by Day
Baseline Day 1 Day 2 Day 3
Odds Ratio (95% CI)
Crs by Day
Baseline Day 1 Day 2 Day 3
Odds Ratio (95% CI)
PF Ratio by Day
95% CI
Odds Ratio
95% CI
Odds Ratio

18
H-L test p>0.2). Moreover, there were no significant interaction effects between tidal
volume and presence of bilateral infiltrates on chest x-ray, diagnostic category of
admission, or severity of lung disease as measured by OI, PF Ratio, dynamic compliance
of the respiratory system (<0.5 or ≥ 0.5 ml/cmH
2
0/kg), or LIS and mortality (all
interaction term p-values >0.1).

Ventilator Free Days

Looking at the secondary outcome measure of 28 day ventilator free days, lower baseline
tidal volume and tidal volume on day 1 were both univariately associated with fewer
ventilator free days (Table 4). Moreover, all variables that had a univariate association
with mortality were also associated with fewer ventilator free days. In addition, except
for tidal volume at baseline and day 1, variables that were not associated with mortality
were also not associated with fewer ventilator free days (analysis not shown).

Table 4: Tidal Volume by day of mechanical ventilation
in relation to mortality and ventilator free days, OR (95% CI).

This relationship between lower tidal volume on day 1 of ventilator management and
fewer ventilator free days held after controlling for year of admission, Delta P, PEEP, and
measures of lung disease severity such as OI, PF ratio, or LIS (p<0.05). Further, when
Tidal Volume Mortality < 14 VFD
Baseline 0.94 (0.85,1.03) 0.91 (0.84,0.98)
Day 1 0.87 (0.76,0.99) 0.85 (0.77,0.94)
Day 2 0.93 (0.80,1.07) 0.91 (0.81, 1.02)
Day 3 0.97 (0.83,1.15) 0.97 (0.85, 1.10)

19
stratifying patients by dynamic compliance of the respiratory system <0.5 or ≥ 0.5
ml/cmH
2
0/kg, higher tidal volume on day one was associated with more ventilator free
days for patients with respiratory system compliance ≥ 0.5 (n=76, OR=0.73 (0.56,0.95))
than for patients with compliance <0.5 (n=254, OR=0.90 (0.80, 1.01)). This relationship
held even after controlling for year of admission, Delta P, PEEP, and LIS (n=76,
OR=0.70 (0.52, 0.95)).

Finally, when limiting the analysis to the 192 patients that had bilateral pulmonary
infiltrates, the association between lower tidal volume on day one and fewer ventilator
free days held true (OR=0.82 (0.70, 0.96)), however this did not reach statistical
significance when controlling for year of admission, Delta P, PEEP, and LIS (OR=0.87
(0.72, 1.06)).

Discussion

In the typical range of 6-10 ml/kg using pressure control ventilation, tidal volume in the
first three days of ventilator management for children with ALI does not appear to be
associated with mortality. However, higher tidal volume up to 10 ml/kg on day one of
ventilator management appears to be associated with more ventilator free days,
particularly for patients with less severe lung disease.

20
While large tidal volumes (>10 ml/kg) may be associated with worse outcome for
children with lung injury, this study shows that there may be no difference ventilating
children with 6ml/kg versus 10 ml/kg using a pressure control mode. In fact, there is
some evidence to suggest that children that are ventilated with slightly higher tidal
volumes in the first day of lung injury may actually have more ventilator free days than
those with lower tidal volumes. Given that patients in this study were managed almost
exclusively with pressure control ventilation, this finding held even after adjusting for the
PIP and PEEP used to attain the tidal volume.

Previous work in adults has shown that a universal approach to tidal volume selection for
patients with acute lung injury may not be best. In fact, higher tidal volume may be
associated with better outcome for patients with less severe lung disease, as it may help
with alveolar recruitment and prevent atelectasis, regardless of PEEP. In our study, the
association between higher tidal volume on day one and more ventilator free days was
more dramatically seen in patients with better dynamic respiratory system compliance
(Crs ≥ 0.5), controlling for the PIP and PEEP used to attain this tidal volume. As such,
perhaps patients with less severe lung disease would benefit from a higher tidal volume
strategy [11, 21]. Of course, this may be deleterious for patients with more severe lung
disease, seen in our analysis with the trend towards higher mortality in the small number
of patients with Peak Inspiratory Pressures >30 who received tidal volumes >10 ml/kg.

21
Inherently a pressure control ventilation strategy will facilitate changing tidal volume
based on compliance, as patients with poor respiratory system compliance will achieve a
lower tidal volume for a given pressure than patients with better compliance. This is seen
clearly in Figure 2, where patients with more severe disease, as measured by Lung Injury
Score, were managed with lower median tidal volume. Moreover, the decelerating flow
pattern of pressure control ventilation imparts additional benefit over the constant flow
pattern of volume modes of ventilation for patients with heterogeneous lung disease. The
distribution of ventilation may be more even as the initial flow opens the alveoli, and the
pressure maintained during inspiration allows gas to flow from more distended alveoli to
more collapsed areas [22].

Some critics of a pressure control strategy argue that if a patient’s compliance improves
significantly, they may be subject to harmful periods of high tidal volume if the
practitioners are not paying close attention to the tidal volume that is attained. While
time-weighted tidal volume was <10 ml/kg for close to 85% of patients in the first day,
99 (25%) patients had at least one 2 hour period during the first 24 hours where the tidal
volume was >10ml/kg. However, these patients in fact had a trend towards lower
mortality (13.5% vs. 22%, p=0.1) and more ventilator free days (21.7 vs. 16.4, p=0.03)
than patients with no 2 hour period with a tidal volume >10 ml/kg. This held regardless
of Peak Inspiratory Pressure used to attain that tidal volume.

22
Of course given the almost universal use of pressure control ventilation in this cohort, the
observed relationship between higher tidal volumes and more ventilator free days may
indeed all be explained by the severity of lung disease. Patients with poorer compliance
and more severe disease will inherently achieve a lower tidal volume than those with
better compliance, given the same pressure. It is therefore possible that in this setting
tidal volume and compliance are really measuring the same things: severity of lung
disease. We attempted to tease this relationship out by using other measures to control
for disease severity such as OI, PF ratio, Lung Injury Scores, as well as the pressure used
to attain that tidal volume, and still found the relationship to hold for higher first day tidal
volume and more ventilator free days. Short of a randomized controlled trial in which
different tidal volumes within the 6-10 ml/kg range are targeted using pressure control
ventilation, it is hard to answer definitively the question of whether higher tidal volumes
are in some way protective. Nonetheless, it does appear from our data that tidal volumes
of 6ml/kg do not appear to be more beneficial than 10ml/kg.

In this cohort of patients, a choice was made to analyze the presence of bilateral
pulmonary infiltrates on chest radiograph separately. All patients in our study met the rest
of the diagnostic criteria for ALI or ARDS: acute onset of disease, PF ratio <300, and
lack of left ventricular dysfunction. We chose this strategy because by including all
patients with non-cardiac acute hypoxemic respiratory failure, we hoped to find larger
variability in ventilator and tidal volume strategies. We reasoned that if this were true we
could separately model what, if any, influence bilateral infiltrates have on management

23
and outcome. Not surprisingly, initial median tidal volume for patients with bilateral
pulmonary infiltrates was lower than those without bilateral infiltrates (7.84 vs 7.13
ml/kg, p=0.02). However there was no difference for aggregate tidal volume values at
day 1, 2, or 3. Moreover, the presence of bilateral infiltrates on chest x-ray had a non-
significant trend towards higher mortality (17.5 vs 22.8%, p=0.2), and significantly fewer
ventilator free days (median 20.8 vs. 16.4 days, p=0.02), although this was not significant
if ventilator free days were dichotomized at 14 days. In the end, the presence of bilateral
infiltrates on chest x-ray in fact did not significantly confound or modify the relationship
between tidal volume and mortality or ventilator free days, and in fact the same trends
were seen if the analysis was restricted to the 192 patients who met all 4 criteria for ALI
or ARDS, although some power was lost.

In addition to the effects of tidal volume on mortality and ventilator free days, this study
shows the association between common lung injury severity markers and outcome.
Oxygenation Index, PF ratio, and a pediatric modification of the Murray Lung Injury
Score were all clearly associated with mortality. We found that each 20-point decrease
in initial PF ratio increased mortality by 23%, each one-point increase in initial OI
increased mortality by 4%, and each one-point increase in initial lung injury score
increased mortality by 133%.

Moreover, when limiting the analysis to the 192 patients with bilateral pulmonary
infiltrates, similar associations with mortality were seen for PF ratio, OI, and LIS.

24
Therefore, when designing future trials on ALI or ARDS in children, any of these three
markers could be utilized to accurately gauge disease severity and stratify risk.

Inherently, given the limitations of retrospective data there are several shortcomings to
this study. First, tidal volume measurements were not made at the airway using a
proximal flow sensor, but rather at the mechanical ventilator with appropriate
compensation for tubing compliance and make of the ventilator. This could potentially
result in less accurate tidal volume measurements, particularly for small children.
Unfortunately, proximal measurements were not available for a large cohort of these
patients, and therefore could not be used for analysis. Second, consistency in charting
may be variable depending on personnel, patient, or unit acuity. While this cannot be
controlled for retrospectively, we feel confident in the integrity of the data as most
information was captured electronically in real-time, and human transcription error
should be minimized. Third, the time period chosen for this analysis constituted a 7-year
period with potentially changing ventilator strategies. In fact, there was a tendency for
tidal volume to decrease over time, perhaps representing changes in pediatric practice as
adult data regarding the detrimental effects of large tidal volume on outcome became
more available. We attempted to control for this by including year in our multivariate
analysis, along with lung severity indices, and in fact year had a minimal impact on the
relationship. Finally, since this was not a randomized trial we could not control for all
potential confounding variables. While we attempted to spread the scope of our variables
to control for degree of lung injury, demographics, standardized mortality scores and

25
other ventilator settings, there certainly could still be unmeasured variables that affect the
relationship between tidal volume and mortality.

While many of these issues could be resolved with a randomized controlled trial, an
adequately powered prospective trial on tidal volume management for children with ALI
would be extremely challenging. For example, a hypothetical study comparing two tidal
volume strategies (6 ml/kg) versus (10 ml/kg) to detect a 5% reduction in mortality from
20% to 15% assuming a two-tailed hypothesis with an alpha level of 0.05 and a power of
0.8 would require 975 patients per group. Looking at our data, we screened over 8000
PICU admissions over a 7-year period, and found only 192 intubated and mechanically
ventilated patients that met all 4 diagnostic criteria for ALI. This represents only 2.25%
of all PICU admissions during this time period, in a relatively busy tertiary care PICU.
While there could have been several patients that met criteria for ALI for a short period
of time that were missed because of our requirement for PF criteria to persist after
intubation and mechanical ventilation, these are likely not the patients we would want to
target for future studies on ALI (i.e. those that resolve hypoxemia very shortly after
mechanical ventilation). Therefore, with an overall incidence of 2.25%, and a desired
enrollment of 1950 patients, a total of 86,667 ICU admissions would be necessary. This
of course also assumes complete patient enrollment, when in reality approximately half
of eligible patients are enrolled in most pediatric randomized trials on Acute Lung Injury
[13]. Therefore, an adequately powered randomized controlled trial on tidal volume
management and mortality in children with ALI may not be feasible.

26

In conclusion, we have shown using retrospective data that using a pressure control
ventilation strategy, tidal volume (between 6 and 10 ml/kg) in the first three days of
ventilator management for children with ALI does not appear to be associated with
mortality. Moreover, higher tidal volume up to 10 ml/kg on day one of ventilator
management is associated with more ventilator free days, particularly for patients with
less severe lung disease. Finally, Oxygenation Index, PF ratio, and a pediatric
modification of the Murray Lung Injury Score were all clearly associated with mortality
for children with ALI, both on initiation of mechanical ventilation and during the first
three days of ventilator support.

27

References
14. Albuali WH, Singh RN, Fraser DD, Seabrook JA, Kavanagh BP, Parshuram CS,
Kornecki A, Have changes in ventilation practice improved outcome in children
with acute lung injury? Pediatric Critical Care Medicine 8(4):324-30, 2007 Jul

7. Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho
G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho
CR, Effect of a protective-ventilation strategy on mortality in the acute respiratory
distress syndrome. New England Journal of Medicine 338(6):347-54, 1998 Feb 5

4. Anonymous, Ventilation with lower tidal volumes as compared with traditional
tidal volumes for acute lung injury and the acute respiratory distress syndrome.
The Acute Respiratory Distress Syndrome Network. New England Journal of
Medicine 342(18):1301-8, 2000 May 4

9. Brochard L, Roudot-Thoraval F, Roupie E, Delclaux C, Chastre J, Fernandez-
Mondejar E, Clementi E, Mancebo J, Factor P, Matamis D, Ranieri M, Blanch L,
Rodi G, Mentec H, Dreyfuss D, Ferrer M, Brun-Buisson C, Tobin M, Lemaire F,
Tidal volume reduction for prevention of ventilator-induced lung injury in acute
respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume
reduction in ARDS. American Journal of Respiratory & Critical Care Medicine
158(6):1831-8, 1998 Dec

10. Brower RG, Shanholtz CB, Fessler HE, Shade DM, White P, Jr., Wiener CM,
Teeter JG, Dodd-o JM, Almog Y, Piantadosi S, Prospective, randomized,
controlled clinical trial comparing traditional versus reduced tidal volume
ventilation in acute respiratory distress syndrome patients. Critical Care Medicine
27(8):1492-8, 1999 Aug

5. Curley MA, Hibberd PL, Fineman LD, Wypij D, Shih MC, Thompson JE, Grant
MJ, Barr FE, Cvijanovich NZ, Sorce L, Luckett PM, Matthay MA, Arnold JH,
Effect of prone positioning on clinical outcomes in children with acute lung
injury: a randomized controlled trial. JAMA 294(2):229-37, 2005 Jul 13

13. Curley MA, Arnold JH, Thompson JE, Fackler JC, Grant MJ, Fineman LD,
Cvijanovich N, Barr FE, Molitor-Kirsch S, Steinhorn DM, Matthay MA, Hibberd
PL, Pediatric Prone Positioning Study G, Clinical trial design--effect of prone
positioning on clinical outcomes in infants and children with acute respiratory
distress syndrome. Journal of Critical Care 21(1):23-32, 2006 Mar

28
21. Deans KJ, Minneci PC, Cui X, Banks SM, Natanson C, Eichacker PQ,
Mechanical ventilation in ARDS: One size does not fit all. Critical Care Medicine
33(5):1141-3, 2005 May

11. Eichacker PQ, Gerstenberger EP, Banks SM, Cui X, Natanson C, Meta-analysis
of acute lung injury and acute respiratory distress syndrome trials testing low tidal
volumes. American Journal of Respiratory & Critical Care Medicine
166(11):1510-4, 2002 Dec 1

1. Farias JA, Frutos F, Esteban A, Flores JC, Retta A, Baltodano A, Alia I, Hatzis T,
Olazarri F, Petros A, Johnson M, What is the daily practice of mechanical
ventilation in pediatric intensive care units? A multicenter study. Intensive Care
Medicine 30(5):918-25, 2004 May

20. Flori HR, Glidden DV, Rutherford GW, Matthay MA, Pediatric acute lung injury:
prospective evaluation of risk factors associated with mortality. American Journal
of Respiratory & Critical Care Medicine 171(9):995-1001, 2005 May 1

15. Hammer J, Numa A, Newth CJ, Acute respiratory distress syndrome caused by
respiratory syncytial virus. Pediatric Pulmonology 23(3):176-83, 1997 Mar

3. Hanson JH, Flori H, Application of the acute respiratory distress syndrome
network low-tidal volume strategy to pediatric acute lung injury. Respiratory Care
Clinics of North America 12(3):349-57, 2006 Sep

22. Heulitt MJW, Gerhard K. Arnold, John H. (2008) Mechanical Ventilation. In:
Nichols DG (ed) Rogers' Textbook of Pediatric Intensive Care. Lippincott
Williams and Wilkins, Philadelphia, PA, pp. 519-520

2. Khemani RG, Markovitz, Barry, Curley, Martha A.Q., (2007) Epidemiologic
Factors of Mechanically Ventilated PICU patients in the United States. Pediatric
Critical Care Medicine Suppl 8: A39

16. Main E, Castle R, Stocks J, James I, Hatch D, The influence of endotracheal tube
leak on the assessment of respiratory function in ventilated children. Intensive
Care Medicine 27(11):1788-97, 2001 Nov

17. Pollack MM, Patel KM, Ruttimann UE, PRISM III: an updated Pediatric Risk of
Mortality score. Critical Care Medicine 24(5):743-52, 1996 May

12. Randolph AG, Meert KL, O'Neil ME, Hanson JH, Luckett PM, Arnold JH, Gedeit
RG, Cox PN, Roberts JS, Venkataraman ST, Forbes PW, Cheifetz IM, Pediatric
Acute Lung Injury and Sepsis Investigators Network, The feasibility of
conducting clinical trials in infants and children with acute respiratory failure.

29
American Journal of Respiratory & Critical Care Medicine 167(10):1334-40,
2003 May 15

19. Schoenfeld DA, Bernard GR, Network A, Statistical evaluation of ventilator-free
days as an efficacy measure in clinical trials of treatments for acute respiratory
distress syndrome. Critical Care Medicine 30(8):1772-7, 2002 Aug

18. Slater A, Shann F, Pearson G, Paediatric Index of Mortality Study G, PIM2: a
revised version of the Paediatric Index of Mortality. Intensive Care Medicine
29(2):278-85, 2003 Feb

8. Stewart TE, Meade MO, Cook DJ, Granton JT, Hodder RV, Lapinsky SE, Mazer
CD, McLean RF, Rogovein TS, Schouten BD, Todd TR, Slutsky AS, Evaluation
of a ventilation strategy to prevent barotrauma in patients at high risk for acute
respiratory distress syndrome. Pressure- and Volume-Limited Ventilation Strategy
Group. New England Journal of Medicine 338(6):355-61, 1998 Feb 5

6. Willson DF, Thomas NJ, Markovitz BP, Bauman LA, DiCarlo JV, Pon S, Jacobs
BR, Jefferson LS, Conaway MR, Egan EA, Pediatric Acute Lung Injury and
Sepsis Investigators Network, Effect of exogenous surfactant (calfactant) in
pediatric acute lung injury: a randomized controlled trial. JAMA 293(4):470-6,
2005 Jan 26

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Asset Metadata

Creator Khemani, Robinder G. (author)

Core Title The effect of tidal volume on mortality and ventilator free days for children with acute lung injury (ALI)

School Keck School of Medicine

Degree Master of Science

Degree Program Clinical and Biomedical Investigations

Publication Date 07/24/2008

Defense Date 08/01/2008

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag lung volume measurements,OAI-PMH Harvest,Pediatrics,positive pressure respiration

Language English

Advisor Newth, Christopher J. L. (committee chair), Alonzo, Todd (committee member), Bart, Robert, III (committee member), Conti, David V. (committee member)

Creator Email rkhemani@chla.usc.edu

Permanent Link (DOI) https://doi.org/10.25549/usctheses-m1395

Unique identifier UC1280734

Identifier etd-Khemani-20080724 (filename),usctheses-m40 (legacy collection record id),usctheses-c127-193037 (legacy record id),usctheses-m1395 (legacy record id)

Legacy Identifier etd-Khemani-20080724.pdf

Dmrecord 193037

Document Type Thesis

Rights Khemani, Robinder G.

Type texts

Source University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

Repository Name Libraries, University of Southern California

Repository Location Los Angeles, California

Repository Email cisadmin@lib.usc.edu