(Received December 19, 1969; revision accepted for publication June 25, 1970.)
Supported by a grant from the Association for the Aid of Crippled Children, New York, N.Y., and in
part by U.S. Public Health Service Research Grant HE-04010 of the National Heart Institute, Bethesda, \larvland.
J.S.H. isrecipient of Career Research Program Award K3-HE-07248 of the National Heart Institute.
ADDRESS FOR REPRINTS: (J.S.H.) Cardiopulmonary Laboratory, Mary Fletcher Unit, Medical Center
hospital of Vermont, Burlington, \‘ermont 05401.
PEDIATRICS, Vol. 46, No. 6, December 1970 900
DISTRIBUTION
AND
LUNG
VOLUME
I. Normal
Newborn
Infants
John S. Hanson, M.D., and Tamotsu Shinozaki, M.D.
From the Cardiopulmonary Laboratory, Department of Medicine, and the Division of Anesthesia, Department of Surgery, University of Vermont College of Medicine, Burlington, Vermont
ABSTRACT. The applicability of a computerized, on-line, breath-by-breath nitrogen washout tech-nique to respiratory studies in newborn infants is described. Reproducibility and accuracy of the sys-tem are entirely comparable to standards previ-ously established in adult studies.
Methodology allows simple, rapid, and direct as-sessment of a newborn infant’s functional residual capacity, the uniformity of inspired gas distribu-tion, and longitudinal time changes in these param-eters.
Studies in 40 normal infants < 2 to 128 hours of age have confirmed some previously published
findings, but do not support the concept of very
early establishment of optimal ventilatory distribu-tion.
Coupled with hemodynamic and blood gas
stud-ies, results obtained by this technique can provide a thorough evaluation of an infant’s cardiopulmo-nary status. It is anticipated that such studies will provide valuable help in guiding and assessing re-sults of ventilatory assistance and pharmacologic interventions in the respiratory distress syndrome. Pediatrics, 46:900, 1970, LUNG VOLUME,
VENTILA-TORY DISTRIBUTION, COMPUTER STUDIES, NORMAL
NEWBORN PHYSIOLOGY.
T
HE relatively recent emergence ofneo-natology as a pediatric subspecialty
has been coincident with intense
investiga-tive efforts to characterize all aspects of the
“most hazardous period of one’s life.”
Be-cause initiation and subsequent
mainte-nance of respiration represent such an
inte-gral portion of extra-uterine adaptation,
postpartum pulmonary physiology has
been a major area for this research. The
in-cidence and consequences of neonatal
re-spiratory distress have further intensified
such studies.
Application of “modern” investigative
technology to this field might properly be
considered to have been initiated 15 to 20
years ago with the work of Smith and his
group.”3 Establishment of normal values
for newborn ventilatory variables, lung
vol-umes,36 pulmonary mechanics,’” and other
respiratory parameters’2’4 has been
ac-complished. The important aspects of
venti-latory efficiency and ventilation/perfusion
relationships15’9 have of necessity usually
been examined indirectly.
The present communication describes
methods for and results of direct,
breath-by-breath assessment of the newborn infant’s
alveolar ventilatory efficiency with
simulta-neous measurement of functional residual
capacity. Longitudinal time course changes
in these parameters during the first 128
hours of life are described.
MATERIALS AND METHODS
The basic concepts and techniques of
pulmonary nitrogen washout2#{176} were
em-ployed. These consist basically of
replac-ing, through breathing of 100% oxygen, the
classi-%s ..
N
“i
If’#{233}
#{149}f
3
:i
i
#{149}-j
1&:
ci’ll
4ll1t
-LU
- I.
1111
1ll1
o.s
IHIIIIJIIIJIIIIIIIJ I UI
0.SIlHIIlI1tIlEt till.----I1IIItIlIIt 11111-till11III
1iltIIIIIllht11ti11
11
III
utiiiiiiiiiiiiil 111111 III
!.lff1il3.lt..IIJ 111
0
250
TOTAL
“ALVEOLAR”
ARTICLES
NITROGEN WASHOUT
UWIVIRIOY OFVUN :i i__I .: #{149}.::.:: i:
.!r
:! : !:diiii!ET
: : #{149}
rn-I
rJI
!t5#{243}0
71125O
VENTILATION, ml
i
tI
FIG. 1. On-line, breath-by-breath nitrogen washouts in a newborn to empha-size reproducibility. FRC = functional residual capacity; V = cumulative
alveolar ventilatory volume; T mean tidal volume; I.D.I. = inspired air
distribution index.
cal nitrogen washout curve, hand-plotted
from individual measurements and analyses
of each variable concerned, shows for each
breath the relationship between expired
ni-trogen concentration as a function of the
ventilatory volume, time, or the number of
breaths to reach a certain nitrogen
con-centration. During oxygen breathing the
rate of decline in expired nitrogen
concen-tration with time depends on the volume of
the space being washed out
(
functionalresidual capacity-FRC
)
, the alveolaryen-tilation (VA ), and the degree of ventilatory
uniformity. In the present experiments, by
expressing decrease in nitrogen
concentra-tion as a function of cumulative alveolar
ventilation
(
Fig. 1)
, a curve was obtainedwhich is dependent only on the size of FRC
and uniformity of ventilation. The
concen-Fic. 2. Diagrammatic representation of components for nitrogen washout studied in newborn infants. A: glass inspiratory-expiratory valve; B: milled nylon adapter; C: nosepiece with soft rubber tips; D: nitrogen sampling needle; E: three-way stopcock for switching from room air to oxygen source; F:
pneumotachograph; G: pneumotachograph transducer.
tration (FN,), expired volume (VE), and
from the relationship of Fic, to VE
calcu-lates anatomical dead space and thence
alveolar ventilation (VA). The output is
displayed as a plot of FN, against VA.
More detailed theoretical and
mathemati-cal considerations are given in the
Appen-dix.
Although this technique is a
time-hon-ored procedure for evaluation of adult
pul-monary function, it has only rarely been
ap-plied to the study of infants.13’16”7 The
present investigation was conducted with a
special-purpose, hybrid computer devised
and constructed to produce
breath-by-breath, on-line analysis of nitrogen
wash-out. This instrument has been described in
great detail elsewhere,’1” and an
evalua-tion has been made of its clinical
applica-tion.’3 Despite the fact that the original
computer was designed for adult function
testing, relatively simple logic modifications
have allowed its application to infant
stud-ies. The net effect of these changes has
been the capability of sensing and
calculat-ing extremely small ventilatory flows and
volumes with maintenance of the original
instrument’s overall accuracy.
The following description applies to the
original hardware as modified for use in
in-fant studies. Components consist of: Fleisch
#00 pneumotachograph,#{176} Statham PM97
pressure tranducer,f Vertek 3000 nitrogen
#{176}Instrumentation Associates, Inc., 17 West 60th Street, New York, N.Y.
ARTICLES
FIG. 3. Relationship between birth weight and FRC in 30 newborn infants comprising Groups II (solid circles) and III (open circles). The
correla-tion is expressed by a second degree polynomial equation.
analyzer, heaters, computer logic,
appro-priate inspiratory-expiratory valve and
pa-tient airway adapter, and Hewlett-Packard
Model 7004A X-Y plotter. The
pneumo-tachograph, respiratory valve and nitrogen
sampling needle are heated to obviate
mois-hire condensation. The block diagram of
Figure 2 shows the equipment
configura-tion. The glass inspiratory-expiratory valve
(A, Fig. 2) is connected to the patient via
a milled nylon adapter with neoprene
0-ring seal (B, Fig. 2). This adapter contains
the nitrogen sampling needle (D, Fig. 2).
These valves are available in several sizes
and have found application in other
neo-natal respiratory studies.2425 Patient
at-tachment is made with a soft plastic Y-tube
fitted with tapered rubber tips (C, Fig. 2)
which are applied to the infant’s nose
seal-ing off the nares from external atmosphere.
Total dead space of the airway valve
sys-tem is 0.76 ml. Inspiratory side of the valve
Vermont Technical Group, Inc., 346 Dorset St., South Burlington, Vermont 05401.
Hewlett-Packard Company, San Diego
Divi-sion, 16399 W. Bemardo Drive, San Diego,
Cali-fornia 92127.
is connected to a 3-way stopcock
(
E, Fig.2) allowing switching between atmosphere
and the 100% oxygen source.
During performance of a washout the
ta-pered rubber tips are positioned carefully
but firmly in the infant’s nares. Following
confirmation of a good volume signal, the
infant is switched from room air to oxygen
breathing. An atmospheric leak due to
im-proper nasal valve positioning or an oral
leak is immediately detectable by nitrogen
concentration spikes at each breath’s peak.
Expiratory flow is measured by the
pneu-motachograph
(
F, Fig. 2) and itstrans-ducer (G, Fig. 2), output of the latter
be-ing integrated by the computer to volume
information. Nitrogen concentration is
con-tinuously monitored and relayed to the
computer. Logic systems in the latter
calcu-late from this information average
anatomi-cal or airway dead space on the basis of the
first four breaths (Appendix). This is
subse-quently subtracted from each breath’s total
volume giving nominal alveolar ventilatory
volume which is plotted as the X-axis of
output. The varying expired nitrogen
20
1800 2000 2200
2400
r:O.75
y :3642X -17 49
.18
.21
24
27
FIG. 5. Relationship of body surface area at birth and FRC in 30 newborn
infants of Group II (solid circles) and Group III (open circles). 50
40
30
2600
FIG. 4. Correlation of birth weight with FRC in five normal newborn infants
weighing less than 2,500 gm.
and continuously plotted as the Y-axis.
Characteristic on-line nitrogen washout
plots are shown in Figure 1.
Functional residual capacity is
continu-ously calculated on the basis of expired
ni-trogen volume, an appropriate correction
being made for tissue nitrogen excretion.’3
The washout may be terminated at any
ar-bitrarily set point, usually an
end-expira-tory nitrogen concentration of 1% or 2%.
80
60
50
40
E
2.5’
2.0-1.5
1.0
AGE-
hrs
0
4
8
12
16
20
24
FIG. 7. Group I time course changes in inspired gas distribution index during the first24 hours of life.
Fic. 6. Sequential newborn nitrogen washouts during the first 24 hours of life. Note increase in FRC following crying at age 1% hours and improvement
in ventilatory efficiency between 12 and 24 hours.
The FRC value is then read directly from will complete a washout in 20 to 35 breaths,
Nixie tubes which register this progres- a matter of 1 to 1% minutes. Maintaining a
sively incremental value, conservative approach and allowing five
TABLE I
EXAMINATION OF SEQUENTIAL FRC MEASUREMENTS
Group I
Subject
(gm) BSA
(m’)
Age
(hr)
FRC
(ml) I.D.l.
1 3,175 .2024 4 55 1.93
24 56 2.16
2 3,232 .2040 6 48 2.’29
25 63 1.67
S 2,722 .1862 4 51 2.48
12 24
48 51
1.92 1.53
4 3,260 .2045 2 36 2.17
3
12
24
52
53
55
2.02
2.08
1.70
5 2,438 .1711 3 46 1.47
13
26 26
49 49 52
1.30 1.30 1.16
2.4-
2.2-I I
2.0-1.8
AGE
-hrs.
1.6’
1.4’
25
75
,,125
Fic. 8. Longitudinal time changes in I.D.I. between the first and sixth days
of life in 10 newborns comprising Group II.
procedure may then be repeated in 10
mm-utes or less. Because of the recognized
effect of oxygen on the FRC,1#{176}particularly
where “trapped gas” is a pertinent factor, as
many as six washouts in a 2-hour period
were performed in the same infant to assess
effects on the lung volume being measured.
Within
these limits, an individual FRCmeasurement did not vary more than ±5%
from the mean of all six washouts. Thus,
de-pendable and rapid repeatability is a
desir-able feature of the method.
In order to express the uniformity of
al-veolar ventilation in terms of the variables
measured during washout, the Inspired Gas
Distribution Index (I.D.I.) was devised.
This consists essentially of the ratio
be-tween the theoretical and actual cumulative
alveolar ventilations required to reduce
al-veolar nitrogen concentration of the FRC to
a given level during 100% oxygen
breath-ing. A single, uniformly ventilated space
will have an I.D.I. of 1.0, a value both
TABLE II
EXAMINATION OF SEQUENTIAL FRC MEASUREMENTS
1 3,204 .2033 14 67 1.71
19 64 1.72
43 71 1.59
62 71 1.59
2 3,629 .2144 6 71 2.29
30 68 1.97
3 3,374 .2115 20 61 2.31
32 61 2.31
128 58 1.94
4 3,629 .2220 15 58 2.02
43 69 1.85
5 3,260 .2010 21 61 2.06
45 69 2.19
6 3,175 .1951 21 68 2.14
45 63 2.16
68 69 2.19
7 2,438 .1677 17 49 1.77
36 44 1.75
8 8,874 .2078 22 53 2.02
51 63 1.63
75 63 1.49
9 3,175 .2024 4 55 1.93
24 51 2.16
76 46 2.02
10 3,232 .2040 6 48 2.29
25 63 1.67
ARTICLES
human lung. Normal values for adult
hu-mans are 1.8 ± 0.1. Theory and
computa-lion of the I.D.I. are in the Appendix.
SUBJECTS
A total of 40 newborn infants was
stud-ied. Ages ranged from 1% to 128 hours and
birth weights from 1,899 to 4,338 gm. Four
subject groups were established according
to age, weight, and number of
examina-tions. Group I consisted of five babies
stud-ied 2 to 4 times during the first 24 hours of
life. In Group II, 10 infants were examined
at least twice during their nursery stay, the
first study having taken place within 24
hours postpartum. Group III contained 20
subjects who were studied on only one
oc-casion at various ages. Five infants with
birth weights less than 2,500 gm comprised
Group IV.
With the exception of Group I subjects in
whom the first feeding was given at age 12
hours, and three members of Group II
whose studies were made prior to 12 hours
age, washouts were always performed
within 2 to 3 hours following feeding. No
sedation was employed. Subjects were
wrapped in their usual nursery blankets
and placed in the study bassinette on their
sides or backs. No infants were studied in
whom persistent problems of temperature
regulation existed. Pre- and poststudy
checks of rectal temperature confirmed that
this variable was maintained practically
constant during the procedures. Four
ba-bies with initially low temperatures (35.2#{176}
to 36.0#{176})at the time of the first study
be-came normothermic during the procedure.
Determinations were not initiated until the
infant was obviously deeply asleep with a
regular respiratory pattern and was
undis-turbed by positioning of the nasal adapters.
RESULTS
It has become obvious that the
establish-ment of normal values for newborn FRC
and I.D.I. require that the measured
vari-ables be related to infants’ size and age.
Despite such intra-group correlation, it is
also apparent that the initial FRC size, its
subsequent alterations, and the state of
al-Group II Birth Subject Weight (gm) BSA (m2) Age (hr) FRC I.D.I. (ml)
veolar ventilatory uniformity are highly
in-dividualized and frequently modulating
characteristics for any given infant. In the
discussion below it should thus be kept in
mind that grouping of results into mean
values for categories of weight, surface
area, and age represents a somewhat
artifi-cial classification which ignores individual
variability and unpredictable time factors. Functional Residual Capacity
In all subject groups FRC exhibited a
TABLE III
EXAMINATION OF SINGLE FRC MEASUREMENTS
Subject Birth Weight (gm) Group BSA (m ) Ill Age (hr) FRC (ml) iD.!.
1 3,544 .2122 44 60 1.93
2 2,722 .1757 96 46 1.90
3 4,338 .2477 70 74 2.31
4 3,742 .2326 120 76 1.86
5 4,224 .2410 67 67 2.18
6 2,523 .1736 54 50 1.94
7 2,778 .1843 48 39 2.13
8 2,863 .1867 60 55 1.64
9 2,977 .1898 96 43 1.73
10 2,948 .1962 57 43 1.64
11 8,515 .2153
42
56 1.5112 2,835 .1895 51 46 1.81
13 2,665 .1776 85 50 2.22
14 3,090 .2002 24 57 2.38
15 2,722 .1897 24 49 2.05
16 3,856 .2278 23 72 1.89
17 4,338 .2395 42 59 1.69
18 3,175 .1989 46 49 2.28
19 3,940 .2299 56 54 v.27
20 3,997 .2233 25 75 2.14
and body surface area
(
Fig. 3, 4, and 5).For Groups II and III the relationship of
FRC and birth weight was better expressed
by
a second degree polynomial correlation(
Fig. 3) rather than the linear associationseen for Group IV
(
Fig. 4)
or for BSA(
Fig. 5)
. When mean FRC values wereob-tamed through a classification of Group II
and III infants according to weights alone,
the following distribution pertained: 2,500
to 3,000 gm: 46.8 ml; 3,000 to 3,500 gm:
58.2 ml; 3,500 to 4,000 gm: 65.9 ml; 4,000 to
4,500 gm: 66.7 ml. Statistically significant
differences were established by t-test
be-tween the first and second weight
catego-ries
(
P < .001)
as well as the second andthird groups
(
P < .05) . Thus for birthweights greater than 4,000 gm, the subjects
of Groups II and III did not evidence
larger FRC’s than those measured in the
3,500 to 4,000 gm range.
Examination of sequential FRC
measure-ments in Groups I and II revealed
progres-sive expansion of this volume with time in
approximately 50% of babies. This
phe-nomenon was therefore evident not only
during the first 24 hours of life, but also
during the course of the day following
(Ta-bles I and II) . Changes in the first day,
comparing the initial FRC value with that
at 24 hours, were significant at the 0.05
probability level by paired t-test analysis.
Statistical significance could not be
estab-lished for FRC increases in Group II, but
many of the initial determinations were
made between the twelfth and eighteenth
hours postpartum. The point at which FRC
expansion occurred could be closely
ap-proximated for one baby
(
Subject 4, TableI) in whom a period of lusty crying during
bathing was followed by a 44% increase in
FRC (Fig. 6).
Uniformity of Ventilation and l.D.l.
The I.D.I. bore no correlation to birth
weight. Time course changes in this
van-able were, however, impressive during the
first day
(
Group I, Fig. 7) and up to thesixth day of life
(
Group II, Fig. 8)
. Figure6 indicates the improvement in ventilatory
uniformity seen in a Group I baby between
the twelfth and twenty-fourth hours, I.D.I.
decreasing from greater than 2.0 to 1.72
de-spite a large expansion of FRC occurring
during the first 12 hours. This trend toward
a lower I.D.I. 24 hours following birth was
also noted in the 20 subjects of Group III
who were studied on only one occasion
(Table III) . The observed improvement in
ventilatory efficiency with increasing age
was independent of initial body weight.
Mean values for I.D.I. derived from
age-grouping of Groups II and III also indicate
a temporal reduction of this variable < 24
hours: 2.09; 24 to 48 hours: 1.97; 48 to 72
hours: 1.94; > 72 hours: 1.90. However,
none of the changes between consecutive
age rankings was statistically significant at
the 0.05 probability level.
DISCUSSION
Considerable dialogue in the past 10
years’ pediatric literature has centered
new-TABLE IV
EXAMINATION OF SINGLE FRC MEASUREMENTS
909
born infant’s functional pulmonary
devel-opment. This had included discussion of
(
1) the rapidity of lung volume expansion;(2) temporal course for establishment of
uniform ventilatory distribution; and (3)
time required to effect proper matching of
ventilation and perfusion. As is often the
case, divergent results and opinions appear
to be at least partially explained by
differ-ences in experimental methods. This is
typi-fled by current reports on ventilation!
perfusion uniformity employing
arterial-al-veolar N, pressure differencesl9 and others
using N, pressure in urine and a calculated
alveolar PN,.
Absolute values for FRC related to body
weight in our infants are considerably
lower than earlier reported by 7-minute
washout with expired gas collectionls,17 or
various adaptations of closed circuit
sys-tems5’10”6 and plethysmography.#{176}’
How-ever, with regard to the former method, it
can be shown by calculation that use of a
mean N, concentration in a given expired
gas volume will result in a larger calculated
N2 volume
(
FRC)
than one calculatedpoint-by-point cumulatively as with the
present method. Also, a 7-minute washout
involves a relatively large total collected
volume in relation to the FRC to be
mea-sured, and since a negative N, concentration
factor cannot be introduced, error in
esti-mates of FRC must therefore be of a positive
nature. Compared to closed circuit helium
dilution,5,b0 the present method does not
de-pend on maintenance of constant spirometer
volume via oxygen addition to the system,
nor attainment of a constant helium
concen-tration during several minutes of necessarily
quiet breathing.
Absolute magnitude of “exchangeable”
FRC does not appear to be entirely fixed
within the first few minutes or hours of life,
but it has also been seen that the majority
of infants experience FRC variations of
only 1 to 4 ml after
age
12 hours. Mostpre-vious observers have also noted little
signifi-cant change after the first few hours.’6
However, considerable expansions of this
space (20%) were occasionally observed
Subject Birth Weight (gm) Group BSA (m2) IV Age (hr) FRC (ml) l.D.i.
1 1,899 .1477 113 26 1.51
2 2,041 .2041 65 33 1.95
3 2,098 .1604 10 39 2.39
4 2,211 .1672 43 47 1.61
5 2,438 .1677 17 49 1.77
after the initial 12-hour postpartum period.
These findings are consistent with those of
Nelson,
et
al.13 who found relatively poorlyventilated portions of thoracic gas volume
in almost 50% of normal newborn infants
and as late as 23 days of age. It is also
rea-sonable to assume that the 33% of normal,
unselected newborn infants less than 24
hours old reported by Hilding’T to have
ra-diographic evidence of atalectasis should at
least partially expand their lung volumes.
Although “perfect distribution of
ventila-tion” has been described in normal
new-born infants,16 we did not observe this in a
single subject of the present series. In other
words, no infant exhibited a single-space
washout with a straight peak-expiratory N,
concentration slope and a calculated I.D.I.
of 1.0. Rather, a “slow space” usually made
its appearance in the 4 to 7% N2 range, and
washout to 2% N, therefore consisted of a
large, fast space and the final slow space
which usually represented 10 to 20% of
to-tal alveolar ventilation. This two-space
pat-tern has been reported earlier.’8 Several of
the present infants, however, manifested a
slow space of considerably greater
magni-tude as reflected in I.D.I. values of 2.1 to
2.5. These would be considered definitely
abnormal in adult washout studies and in
the range seen with moderate chronic
ob-structive lung disease.
Evaluation of directly recorded,
breath-by-breath N, washout employing alveolar
ventilatory volume indicates that
con-N2%
C
(
I
FIG. 9. Calculation of anatomical dead space Fowler’s method.
tinues for several days following birth. Also,
improvement in ventilatory distribution
of-ten continues for several days following
birth. This distribution is seldom “as even in
the first hour of life as on the 3rd or 4th
day.”6 Striking and significant changes in
Xp ‘-(X2--XI): VCONDUCTING AIRWAY
Fic. 10. Computer calculation of dead space from
the relationship between expired nitrogen volume
and total expired gas volume.
0 A B
distribution can and do occur quite
sud-denly during both the first 24 hours and
subsequently as reflected in the contour of
the washout curve. On more than one
occa-sion this has been observed in close time
re-lationship to lung volume alterations. One
must thus assume that poorly ventilated
spaces, perhaps partially atalectatic,1
per-haps intermittently ventilated, can exist for
variable periods postpartum although they
may well be unrecognized clinically and
have no major clinical significance. This
concept correlates well with previous
stud-ies of “trapped gas.”13
Obviously, no direct conclusion can be
V
EXPIR. drawn from present results with regard tothe newborn infant’s ventilation/perfusion
by relationships per se or the longitudinal time
course of such relationships postpartum.
However, it is difficult to reconcile patently
poor uniformity of inspired gas distribution
seen in several of our subjects with the
prevalent concepV5 that “excellent
uni-formity of pulmonary distribution of gas
and blood” is achieved soon
(
4 hours)
afterbirth.”
This
latter situation would bydefi-nition require that a reduction of
pulmo-nary blood flow had occurred to exactly
those functional areas with inadequate
yen-tilation producing high I.D.I.’s in these
in-fants.
Although this might initially appear a
highly unlikely circumstance, the extreme
degree of pulmonary vascular reactivity
re-tained by neonates might effect perfusion
reduction to match local ventilation
inade-quacies. Such a mechanism could maintain
well matched ventilation and blood flow
despite gross local abnormalities in each
variable. The present means of estimating
ventilatory distribution and “efficiency”
should be well suited to simultaneous
wash-outs, blood gas,29 and hemodynamic30’31
studies for better evaluation of the
neonate’s ventilatory and pulmonary blood
flow relationships. It is these very factors,
and aberrations in them, which form one of
the central points of interest in study and
treatment of the respiratory distress
911
REFERENCES
1. Moss, A.
J.,
and Monset-Couchard, M.: Placen-tal transfusion : Early versus late clamping ofthe umbilical cord. Pm.&iiucs, 40:109,
1967.
2. Boutourline-Young, H. J., and Smith, C. A.:
Respiration of full term and of premature
infants. Amer J. Dis. Child., 80:753, 1950. 3. Cook, C. D., Cherry, R. B., O’Brien, D., Karl..
berg, P., and Smith, C. A. : Studies of
respi-ratory physiology in the newborn infant. I. Observations on normal premature and
full-term infants.
J.
Clin. Invest., 34:975, 1955. 4. Berglund, C., and Karlberg, P.: Determinationof the functional residual capacity in
new-born infants; preliminary report. Acta Paed-iat., 45:541, 1956.
5. Geubelle, F., Karlberg, P., Koch, G., Lind, J.,
Waligren, C., and Wegelius, C. : L’aeration du poumon chez le nouveau-ne. Biol. Neo-nat., 1:169, 1959.
6. Klaus, M., Tooley, W. H., Weaver, K. H., and Clements, J. A. : Lung volume in the
new-born infant. PEDIATRICS, 30: 111, 1962.
7. Cook, C. D., Sutherland, J. M., Segal, S.,
Cherry, R. B., Mead,
J.,
Mcllroy, M. B., andSmith, C. A. : Studies of respiratory
physiol-ogy in the newborn infant. III. Measurement
of mechanics of respiration. J. Clin. Invest., 36:440, 1957.
8. Drorbaugh,
J.
E., Segal, S., Sutherland,J.
M., Oppe, T. E., Cherry, R. B., and Smith, C. A. : Compliance of lung during first week oflife. Amer. J. Dis. Child., 105:63, 1963.
9. Chu, J. S., Dawson, P., Klaus, M., and Sweet, A. Y. : Lung compliance and lung volume measured concurrently in normal full-term and premature infants. PEDIATRICS, 34:525, 1964.
10. Oh, W., Waflgren, C., Hanson, J. S., and Lind,
J.: The effects of placental transfusion on
re-spiratory mechanics of normal term newborn
infants. PEDIATRICS, 40:6, 1967.
11. Fomon, S. J., ed.: Normal and abnormal respi-ration in children. Report of the
thirty-sev-enth Ross Conference on Pediatric Research.
Columbus, Ohio: Ross Laboratories, 1961.
12. Auld, P. A., Nelson, N. M., Cherry, R. B.,
Ru-dolph, A. J., and Smith, C. A.: Measurement of thoracic gas volume in the newborn
in-fant.
J.
Clin. Invest., 42:476, 1963.13. Nelson, N. M., Prod’hom, L. S., Cherry, R. B.,
Lipsitz, P. J., and Smith, C. A.: Pulmonary
function in the newborn infant. V. Trapped
gas in the normal infant’s lung.
J.
Clin.In-vest., 42:1850, 1963.
14. Thibeault, D. W., Wong, M. M., and Auld, P. A. M.: Thoracic gas volume changes in pre-mature infants. PEDIATRICS, 40:403, 1967.
15. Nelson, N. M., Prod’hom, L. S., Cherry, R. B.,
Lipsitz, P. J., and Smith, C. A. : Pulmonary
function in the newborn infant. II. Perfusion -estimation by analysis of the arterial-alveo-lar carbon dioxide difference. PEDIATRICS,
30:975, 1962.
16. Nelson, N. M., Prod’hom, L. S., Cherry, R. B.,
Lipsitz, P. J., and Smith, C. A.: Pulmonary
function in the newborn infant: The
alveo-lar-arterial oxygen gradient. J. Appl.
Phys-iol., 18:534, 1963.
17. Prod’hom, L. S., Levison, H., Cherry, R. B.,
Drorbaugh,
J.
E., Hubbell,J.
P., Jr., andSmith, C. A.: Adjustment of ventilation,
in-trapulmonary gas exchange and acid-base
balance during the first day of life.
PEDIAT-RICS, 33:682, 1964.
18. Ledbetter, M. K., Homma, T., and Farhi, L.
E. : Readjustment in distribution of alveolar
ventilation and lung perfusion in the
new-born. PEDIATRICS, 40:940, 1967.
19. Nourse, C. H., and Nelson, N. M.: Uniformity
of ventilation in the newborn infant: Direct
assessment of the arterial-alveolar N2
differ-ence. PEDIATRICS, 43:226, 1969.
20. Darling, R. C., Command, A., and Richards, D.
W., Jr.: Studies on the intrapulmonary
mix-ture of gases. III. An open circuit method
for measuring residual air.
J.
Clin. Invest., 19:609, 1940.21. Shinozaki, T., Abajian,
J.
C., Jr., Tabakin, B.S., and Hanson, J. S. : Nitrogen washout
computer. Amer.
J.
Med. Electron, 4:23,1965.
22. Abajian,
J.
C., Jr., Shinozaki, T., Hanson, J. S., and Tabakin, B. S. : A computerizedmethod for instantaneous and continuous
measurements of expired nitrogen.
Aero-space Medical Research Laboratories
Tech-nical Report AMRL-TR-67-77,
Wright-Patterson Air Force Base, Ohio, 1967. 23. Shinozaki, T., Abajian,
J.
C., Jr., Tabakin, B.S., and Hanson, J. S. : Theory and clinical application of a digital nitrogen washout
computer. J. Appl. Physiol., 21 :202, 1966. 24. Lees, M. H., Way, R. C., and Ross, B. B.:
Ventilation and respiratory gas transfer of
infants with increased pulmonary blood
flow. PEDIATRICS, 40:259, 1967.
25. Lees, M. H., Burnell, R. H., Morgan, C. L., and Ross, B. B.: Ventilation-perfusion
rela-tionships in children with heart disease and
diminished pulmonary blood flow.
PEDIAT-RICS, 42:778, 1968.
26. Chu, J., Clements, J. A., Cotton, E. K., Klaus, M. H., Sweet, A. Y., and Tooley, W. H.:
Neonatal pulmonary ischemia. Part I: Clini-cal and physiological studies. PEDIATRICS,
If:
Then:
Vc =
n
This is identical with:
Since, in a power series:
log(1+x)=x-x+x’+
and if x<1, then:
loge(1 + x) x with an error less than 5%.
27. Hilding, A. C.: A study of the inflation of the lungs of the newborn-a preliminary report.
Calif. Med., 71 :332, 1949.
28. Tooley, W. H., Klaus, M., Weaver, K. H., and
Clements, J. A.: The distribution of
ventila-tion in normal newborn infants (Abst.).
Amer. J. Dis. Child., 100:731, 1960.
29. Engstrbm, L., Karlberg, P., Booth, C., and
Tunell, R.: The onset of respiration. A study of respiration and changes in blood gases and acid-base balance. New York City: As-sociation for the Aid of Crippled Children, 1966.
30. Arcilla, R. A., Oh, W., Wallgren, C., Hanson,
J. S., Gessner, I.H., and Lind,
J.:
Quantita-tive studies of the human neonatal circula-tion. II. Hemodynamic findings in early and
Nitrogen Washout
late clamping of the umbilical cord. Acta
Paediat. Scand., (Suppi.) 179:23, 1967.
31. Wallgren, C., Hanson,
J.
S., Tabakin, B. S.,R#{228}ih#{228},N., and Vapaavuori, E.: Quantitative
studies of the human neonatal circulation.
V. Hemodynamic findings in premature in-fants with and without respiratory distress.
Acta Paediat. Scand. (Suppl.) 179:69, 1967.
32. Fowler, W. S., Cornish, E. R., and Kety, S. S.: Lung function studies: Analysis of alveolar ventilation by pulmonary N2 clearance curves.
J.
Clin. Invest., 31:40, 1952.Acknowledgment
The extensive technical assistance of Miss
Bev-erly Koilmar, R.N. and Mrs. Eleanor Benson, R.N. is gratefully acknowledged.
APPENDIX
The analysis of nitrogen washout from the
lungs is affected by the size of the lung space
and the alVeOlar ventilation during the
wash-out period. When expiratory nitrogen
con-centration is related to time alone,
breath-to-breath variation in ventilation will markedly
influence the slope of the nitrogen washout
curve. however, when nitrogen
concentra-tion is plotted against alveolar ventilation,
slope of the washout curve will be
exponen-tilLl if inspired air distribution is uniform. In
addition, this slope will then be related
solely to tile size of the space being washed
out. This can be substantiated by the
follow-ing basic considerations. If VA = nominal
alveolar ventilation; FRC = functional
re-sidual capacity; FN = alveolar nitrogen
con-centration; FN, = initial alveolar nitrogen
concentration breathing room air (80%);
cuiiiulative nominal alveolar
ventila-tion at any given time, then the
concentra-tion of nitrogen remaining in the lungs after
the nth breath will be expressed by:
FRC IN = FN#{149} ()
If 80% nitrogen concentration is taken= 1,
this becomes
/ FRC \ri
FN=
FRc+vA)
Taking the natural logarithm of both sides:
FRC
log0F = n log (FRC + VA)
V / FRC
logeFN = -.loge( )
VA \FRC + VA
Vc / VA\
logeFN = - . loge (1 +
