0021-7557/02/78-05/403 Jornal de Pediatria - Vol.

78, Nº5, 2002 403

Jornal de Pediatria
Copyright © 2002 by Sociedade Brasileira de Pediatria

ORIGINAL ARTICLE

Assessment of pulmonary function

of preterm newborn infants with respiratory distress syndrome
at different positive end expiratory pressure levels
Luiz C.T. Consolo,1 Durval B. Palhares,2 Lourdes Z.Z. Consolo3

Abstract
Objective: to verify the alterations of pulmonary function in preterm newborn infants with respiratory
distress syndrome (RDS). The parameters analyzed were Dynamic Compliance (Cdyn), Inspiratory Tidal
Volume (TVinsp), partial arterial pressure of carbon dioxide (PaCO2).
Methods: eleven preterm newborn infants, with gestational age < 35 weeks, and birth weight < 2.500
g, were include in a control case study. All infants presented RDS and were treated with 120 mg/Kg of
porcine surfactant. The initial positive end expiratory pressure (PEEP) was 3 cm H2O. A pneumotachograph
with a graphical monitor was used to assess the pulmonary function. After each increase in the PEEP (4
and 6 cm H2O), there was an interval of 20 minutes before measuring the arterial data of pulmonary function
and arterial gases.
Results: there were three males and eight females (1:2,7) among the infants with RDS. The mean
gestational age was 30.78. 2.05 weeks, ranging from 26 to 34 weeks. The increase in the PEEP from 3 to
6 cm H2O caused significant decrease in the TVinsp (6.46 ±3.43 to 4.20 ±2.35, p=0.0262). With the
increase in the PEEP from 4 to 6 cm H2O, there was also a decrease in the TVinsp (5.98.± 3.33 to 4.20.±
2.35), (p=0.0044). Regarding the Cdyn, when there was an increase in the PEEP from 3 to 6 cm H2O, the
reduction was statistically significant (0.58.± 0.27 to 0.46± 0.25, p=0.0408) and from 4 to 6 cm H2O, the
reduction in the Cdyn was also important (0.77± 0.27 to 0.46± 0.25), (p=0.0164). Increases in the PEEP
from 4 to 6 cm H2O caused increases in the PaCO2 (52.81± 15.49 to 64.90± 12.69), (p= 0,0141). A more
significant increase was observed when the PEEP was elevated from 3 to 6 cm H2O (41.45± 7.87 to 64.90±
12.69, p=0.0033).
Conclusions: the study showed that the PEEP from 3 to 4 cm H2O produces better results in terms of
Cdyn and less collateral effects regarding respiratory acidosis and pulmonary hyperventilation with
impairment of the alveolar ventilation, evidenced by the increase in the PaCO2 and the decrease in the
TVinsp.

J Pediatr (Rio J) 2002; 78 (5): 403-8: peep, dynamic compliance, inspiratory tidal volume, PaCO2, RDS,
preterm newborn.

1. Assistant Professor, Department of Pediatrics, Universidade Federal de Mato Grosso do Sul. Master’s Degree in Medicine - Pediatrics.
2. Associate Professor, Ph.D., Department of Pediatrics, Universidade Federal do Mato Grosso do Sul.
3. Associate Professor, Department of Pediatrics, Universidade Federal do Mato Grosso do Sul. Master’s Degree in Medicine - Pediatrics.
Manuscript received Jan 31 2002. Accepted for publication Jun 19 2002.

403
404 Jornal de Pediatria - Vol. 78, Nº5, 2002 Assessment of pulmonary function of preterm newborn... - Consolo LCT et alii
Introduction
The respiratory distress syndrome (RDS), more than a
disease process, is a developmental disorder that is generally
associated with premature birth. Despite great advances in
understanding the pathophysiology of RDS and the role
surfactant plays as a cause, it remains the principal clinical
problem and one of the most common causes of morbidity
in preterm newborns (PTNs).1 Of all the respiratory problems
that affect newborns, hyaline membrane disease is one of
the most serious and frequent. Close to 50% of deaths that
occur in the neonatal period are related to respiratory
disorders. RDS is present in approximately 80 to 90% of the
cases, during the first week of life.2
Nearly 30% of PTNs with RDS generally require the use
of continuous distension pressure, whether as continuous
positive airway pressure (CPAP), or through tracheal
intubation with positive end expiratory pressure (PEEP). In
the treatment of PTNs with hyaline membrane disease,
principally those who are submitted to mechanical
ventilation, respiratory mechanics should be intensely
monitored. Flow and volume analysis, through
pneumotachograph, is widely used. Pressure-volume curves
are also determined by this equipment. Dynamic compliance,
inspiratory and expiratory tidal volume and system air loss
can be continuously and simultaneously evaluated.3,4
Therefore, it is possible to minimize the adverse effects of
mechanical ventilation, from the use of PEEP, and thus
prevent lung injury (barotrauma and volutrauma),
cardiocirculatory and systemic injuries.
The object of the present study is to evaluate alterations
to lung function: Dynamic compliance (CDyn), inspiratory
tidal volume (VTinsp), and alterations to arterial carbon
dioxide pressure (PaCO2), in preterm newborns with
respiratory distress syndrome with PEEP of 3.4 to 6 cm
H2O.
Patients and Methods
Eleven PTNs with gestational age less than 35 weeks
and with birthweight less than 2,500 grams were evaluated
by modified Ballard method.5 Both clinical and radiological
diagnosis of RDS was established in all PTNs. All patients
were admitted to the NICU of the Teaching Hospital of
Universidade Federal de Mato Grosso do Sul (HU - UFMS).
They were under mechanical ventilation and were submitted
to the study after presenting clinical data and stable blood
gases for at least two hours after surfactant administration.
Permission and a signed consent form was obtained from
the parents for the participation of their children in the
study. The research was approved by the Medical Ethics
Committee of UFMS.
All the newborns were sedated and curarized, if
necessary, so that spontaneous respiration and/or breathing
effort would not interfere with the assessment of lung
function. Children with cardiac, pulmonary, neuromuscular
or renal diseases, malformations, and hydroelectric,
metabolic or cardiocirculatory disorders were not included
in the study.
The clinical diagnosis was based on the criteria adopted
by Walter and Taeusch,6 which include clinical and
radiological data.
Soon after the diagnosis of RDS, the patients received
porcine surfactant (Curosurf®) in the dose of 120 mg/kg
(1.5 ml is equivalent to 120 mg) Depending on the clinical
development and on the results of the blood gas analysis, the
patients received a second dose.
The umbilical artery was properly catheterized. Blood
gases were measured from a sample of blood heparinized
(50 units) in an insulin syringe. The analyses were performed
with a Radiometer ABL 330 for different PEEP levels (3 cm
H2O, 4 cm H2O and 6 cm H2O) at an interval of twenty
minutes between them. Pulse oximetry was carried out
continuously, from the arrival of the patient up to the end of
the blood gas analysis, by means of a digital Ohmeda
oximeter. A pulse oximeter transducer was placed at the
level of the right thumb.
A time-cycled, pressure-limited ventilator - Sechrist IV
100B (Sechrist, Anaheim,California, USA) - was used. The
initial ventilatory parameters (PIP, RF, IT, ET, I/E ratio and
FiO2) were adjusted with the objective of maintaining
blood gases at predetermined levels: pH between 7.20 and
7.407; PaCO2 between 20 and 50 mmHg; PaO2 between 50
and 80 mmHg and Hb saturation >90%. The initial PEEP
was 3 cm H2O.
After the patient remained stable for at least two hours
after surfactant administration, PEEP levels were changed
from 4 to 6 cm H2O. Twenty minutes were allowed for a new
blood gas analysis between one PEEP increase and the
other.
To guarantee saturation above 90%, the remaining
ventilator parameters, except for FiO2, were not altered in
order to eliminate confounding variables. Each PEEP level
was maintained for 20 minutes and, at the end of this period,
blood gases (PaCO2 and PaO2) were analyzed.
A pneumotachograph with a graphic monitor, NewPort
Navigator GM - 250, (NMI Newport Medical Instruments,
INC, USA), coupled with a Varfley - Bicore flow transducer
was used to evaluate lung function. Air was not allowed to
escape through the lateral walls of the tube, as evaluated by
the same pneumotachograph (the pneumotachograph
detected whether the air escaped). The following parameters
were measured for each PEEP level after twenty minutes
with the aim of stabilizing the patient: dynamic compliance
(CDyn), in milliliters/centimeters of H2O; inspiratory tidal
volume (VTinsp), in liters.
The mean, standard deviation and percentage were
calculated for statistical analysis of the results. The Shapiro-
Wik test was used to verify the normality of the variables.
The Wilcoxon8 signed-rank test (Wilcoxon apud Daniel,
1995) was used to compare the differences between groups
Assessment of pulmonary function of preterm newborn... - Consolo LCT et alii Jornal de Pediatria - Vol. 78, Nº5, 2002 405

before and after PEEP increases. The p value was considered
significant if less than 0.05. All statistical tests were
performed using Microsoft® Excel 4.0, licensed by the
Center for Pediatric Improvement (CAPE), of the Pediatric
Department of UFMS, under the identification number
61616, and the program Stataquest 4.0 for Windows 95,
serial number: W-902103040, Stata Corporation TX, USA.
Results
Of the 11 patients with RDS, three were male and eight
were female (1:2,7). Gestational age was 30.78± 2.05
weeks, with a variation of 26 to 34 weeks. Birthweight
ranged from 860 to 2,270 grams, with a mean and standard
deviation of 1,489.10 ± 358.28 grams, respectively. The
average time for the administration of the first dose of
exogenous surfactant was 7.5± 6.54 hours, with a variation
of 1.5 to 24 hours.
For the PEEP levels of 3.4 and 6 cm H2O, the values
corresponding to dynamic compliance (CDyn), inspiratory
tidal volume (VTinsp); and arterial carbon dioxide pressure
(PaCO2) are shown in Table 1.
With a PEEP increase of 3 to 4 cm H2O, there was a
reduction in the VTinsp from 6.46± 3.43 to 5.98± 3.33,
respectively. However, this difference was not statistically
significant (p=0.4234). The PEEP increase from 3 to 6 cm
H2O immediately caused a statistically significant reduction
in VTinsp (from 6.46± 3.43 to 4.20±2.35, p=0.0262). With
the PEEP increase from 4 to 6 cm H2O, there was also a
statistically significant reduction in VTinsp (from 5.98±
3.33 to 4.20± 2.35, p=0.0044).
In terms of dynamic compliance, the effects of the PEEP
increase from 3 to 4 cm H2O, showed no statistically
significant alterations (p=0.5045). When the PEEP increase
was from 3 to 6 cm H2O, the CDyn decrease was statistically
significant (0.58± 0.27 to 0.46± 0.25, p=0.0408) and from
4 to 6 cm of H2O the CDyn decrease was also important
(0.77± 0.27 to 0.46± 0.25, p=0.0164).
Positive end expiratory pressure increases from 3 to 4
cm H2O did not alter PaCO2 (41.45± 7.87 to 52.81± 15.49,
p=0.0749). H2O increases of 4 to 6 cm caused statistically
significant increases in PaCO2 (52.81± 15.49 to 64.90
±12.69, p=0.0141). A more pronounced increase was
observed when PEEP was altered from 3 to 6 cm H2O
(41.45± 7.87 to 64.90± 12.69, p=0.0033).

Table 1 - Values of pulmonary function parameters and PaCO2, obtained with PEEP of 3, 4 and 6 cm H2O, from newborns with
RDS

Patients CDyn* VTinsp † PaCO2 ‡

PEEP3 PEEP4 PEEP6 PEEP3 PEEP4 PEEP6 PEEP3 PEEP4 PEEP6

1 0.31 0.28 0.18 1.6 2.2 1.9 50 56 56

2 0.87 0.78 0.55 7.6 7 3.7 45 45 64
3 0.24 0.34 0.39 3.4 2.4 2.6 34 79 64
4 1.1 1.27 0.80 12.1 10.1 5.5 40 43 60
5 0.92 1.02 1.04 7.5 5.3 5.0 32 70 85
6 0.56 0.62 0.45 6.5 6.4 4.7 41 43 58
7 0.39 2.39 0.25 3.3 3.5 1.6 36 37 54
8 0.63 0.63 0.42 7.0 6.6 4.8 44 30 51
9 0.44 0.30 0.33 6.2 6.7 5.7 59 56 67
10 0.58 0.56 0.4 12.7 12.9 9.4 40 50 63
11 0.41 0.33 0.28 3.7 2.7 1.3 35 72 92

Mean 0.58± 0.77± 0.46± 6.46± 5.98± 4.20± 41.45± 52.81± 64.90±
and SD 0.77 0.62 0.25 3.43 3.33 2.35 7.87 15.49 12.69

* dynamic compliance; † inspiratory tidal volume; ‡ arterial carbon dioxide pressure.

PEEP from 3 to 6 cm H2O, decrease in VTinsp (p=0.0262).
PEEP from 4 to 6 cm H2O, decrease in VTinsp (5.98 ± 3.33 to 4.20 ± 2.35. p=0.0044).
PEEP 3 to 6 cm H2O, decrease in CDyn (p=0.0408); PEEP 4 to 6 cm H2O, decrease in CDyn, (p=0.0164).
PEEP 4 to 6 cm H2O, increase in PaCO2 (p=0.0141); PEEP from 3 to 6 cm H2O (p=0.0033).
406 Jornal de Pediatria - Vol. 78, Nº5, 2002 Assessment of pulmonary function of preterm newborn... - Consolo LCT et alii
Discussion
In mechanical ventilation of preterm newborns with
RDS, even with surfactant administration, PEEP is largely
used to prevent alveolar collapse, maintain functional
residual capacity (FRC) and improve oxygenation. PEEP
refers to the maintenance of positive airway pressure during
expiration, combined with intermittent mechanical
ventilation with positive pressure.2 This results in a better
distribution of ventilation in regions with a low V/Q
(ventilation perfusion) of the lungs, and in a better V/Q
balance.9-11 Therefore, PEEP has a paramount importance
to the improvement of oxygenation, the decrease in the
necessity for high concentrations of inhaled O2, increase of
FRC and improvement of total respiratory compliance in
the cases of diseases associated with low residual volume
and compliance.
Falke et al.12 (1972) studied ten mechanically-ventilated
newborns with acute respiratory insufficiency and verified
the effect of PEEP of 0, 10 and 15 cm H2O applied every 30
minutes. CDyn progressively decreased as PEEP was
increased (p<0.01) and PaO2 increased when PEEP was
altered from 5 to 15 cm H2O (p<0.01). The reduction in
CDyn results in the enhanced stiffness of highly distended
alveoli. On the other hand, the rise in PaO2 could indicate
simultaneous recruitment of air spaces associated with the
hyperinflation of previously open alveoli. Philips III et al.8
(1980) evaluated CDyn in twenty-four preterm newborns
with RDS, associated with PEEP, and observed significant
reductions (p<0.05) for each PEEP increase. In the present
study, the effects of PEEP increase from 3 to 4 cm H2O did
not cause significant alteration to CDyn (p=0.5045). With
a PEEP increase from 3 to 6 cm H2O, there was a statistically
significant decrease in CDyn (p=0.0408), as occurred with
PEEP from 4 to 6 cm H2O (p=0.0164).
The reduction in CDyn could be explained by the fact
that the application of a PEEP greater than 3 or 4 cm H2O
could lead to alveolar expansion and to an increase in FRC.
Alveoli that are more expanded have a greater elastic recoil
pressure, and since they share a common airway, some air
tends to follow the pressure gradient and moves to other
alveoli. Presumably, this limit represents the point at which
the maximum recruitment of air space was reached.
Additional PEEP increases will merely overexpand the the
open air spaces. CDyn is reduced from this moment on.12,13
Dimitrou et al.2 (1999) studied eight premature newborns
and found average CDyn values for three PEEP values.
Field et al.15 (1985) evaluated 15 patients with RDS and
observed CDyn variations related to the PEEP variations.
When the results of this study are compared with literature
data, only the PEEP of 6 cm H2O are similar to the findings
of Dimitrou et al.2 (1999) In comparison with the data
obtained by Graff16 (1986), the values are very similar,
especially regarding PEEP levels of 3 and 4 cm H2O and the
levels obtained by Field et al.(1985).15
The data obtained in this study show that the best CDyn
average was that produced by a PEEP of 4 cm H2O (0.77±
0.62). According to Cheifetz et al.14 (1998), a reduction
greater than or equal to 20% in CDyn indicates the presence
of lung hyperinflation. The greatest CDyn reductions
occurred between a PEEP increase from 3 to 6 cm H2O
(21.42%) and a PEEP increase from 4 to 6 cm H2O
(40.25%), which explain the other alterations caused by
probable lung hyperinflation.
It is therefore clear that an adequate PEEP prevents
alveolar collapse and maintains the volume at the end of
expiration, thus improving the V/Q ratio, and increasing
PaO2. Since PEEP variations modify the pressure gradient
between inspiration and expiration, carbon dioxide (CO 2)
elimination can be affected. This way, an elevation in PEEP
can diminish tidal volume and CO2 elimination, leading to
a rise in partial arterial carbon dioxide pressure (PaCO 2).17
Therefore, alveolar hypoventilation should occur after PEEP
increase, followed by a corresponding increase in PaCO 2.
Thus, a PEEP reduction should be considered when CO2
retention occurs, especially if hypoxemia is not a problem.
In the present study, a PEEP increase from 3 to 4 cm H2O
did not lead to significant alterations in PaCO2 (41.45± 7.87
to 52.81± 15.49, p=0.0749). Increases from 4 to 6 cm H2O
caused a statistically significant increase in PaCO 2 (52.81
±15.49 to 68.90± 12.69, p=0.0141). A more pronounced
increase was observed when PEEP was increased from 3 to
6 cm H2O (41.45± 7.87 to 64.90± 12.69, p=0.0033).
Another consequence of tidal volume reduction and,
consequently of alveolar ventilation, is CO2 retention and
probable respiratory acidosis. It has been shown that after
PEEP increases from zero to 6 cm H2O, there was average
reduction in pH of 7.33 (7.3 - 7.43) with PEEP of 3 cm H2O
and an average of 7.29 (7.16 to 7.38) for PEEP of 6 cm
H2O.2
Likewise, Bartolomew et al.17 (1999) observed that a
reduction in tidal volume (Vt) diminished the minute volume
and also had implications on CO2 exchange. A reduction in
PEEP of 2 cm H2O increased the tidal volume by 30%. This
effect is determined by ventilation/minute in accordance
with the alveolar air equation: PaCO2 = VT / minute volume
+ K, where K is a constant. VCO2 is the volume of CO2
produced. This is especially applied to extremely premature
newborns in whom alveolar ventilation may already be
compromised by an anatomically disproportionately large
space. The ratio of dead space volume and VT is an
important determinant of alveolar ventilation and can be
significantly improved by a VT increase or diminished by
VT reduction.
Philips III et al. 4 (1980) also concluded that if the tidal
volume falls due to a PEEP increase, the minute volume also
falls; therefore, increased alveolar expansion and
intrathoracic pressure lead to CO2 retention, alveolar
collapse and/or a decrease in cardiac output.
Assessment of pulmonary function of preterm newborn... - Consolo LCT et alii
In this study, with a PEEP increase from 3 to 6 and from
4 to 6 cm H2O, VTinsp diminished significantly (p=0.0262
and p=0.0044, respectively).
The study thus evidenced that PEEP of 3 and 4 cm H2O
produces better results in terms of CDyn and fewer adverse
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Tel.: +55 67 351.8820 - E-mail: tesini@nin.ufms.br