THORACIC
GAS
VOLUME
CHANGES
IN PREMATURE
INFANTS
D. W. Thibeault, M.D., M. M. Wong, M.D., and P. A. M. Auld, M.D.
1ront the Department of Pediatrics, Cornell University Medical College, New York City
(Submitted February 7; accepted for publication April 21, 1967.)
Supported by’ the New York Health Research Council (under contract U-1264) and the Educational
Foundation of America, New York, New York.
P.A.M.A. holds an Investigatorship of the Health Research Council of the city’ of New York (under
contract 1-236). ADDRESS: 525 East 68th Street, New York, New York 10021.
PEDIATIuc5, Vol. 40, No. 3, Part I, September 1967
403
P
ULMONAHY INSUFFICIENCY in smallpre-mature infants for long periods
postna-tally has been reported in recent studies.’2
Burnard, et a!.,’ using a battery of
pulmo-nary function studies, demonstrated
physi-ologic abnormalities of lung function in
clinically normal infants. Low arterial
oxy-gen tensions for days or weeks after birth
have been shown to be present in a similar group of infants.2 The possibility that these above-mentioned findings could be related to atelectasis is suggested by pathologic studies. Grtienwald’ has fou.nd extensive diffusc atelectasis in the lungs of premature infants who lived up to 48 hours after birth.
Ogawa has noted atelectasis at autopsy in premature infants who lived for 24 diys.1 These observations led to the present study, which was an attempt to determine if an atelectatic state is present in vivo by
mak-ing serial measurements of thoracic gas vol-ume. An attempt was made to determine if the low arterial oxygen tension of these small infants was related to a low thoracic
gas volume. The effect of changes in
func-tional residual capacity on breathing pat-terns of infants was also studied in a few infants.
MATERIALS AND METHODS
The subjects were 24 premature infants with birth weights ranging between 880 and 2,140 gm and from 5 hours to 68 days of age. Eighty-four determinations of tho-racic gas volume were performed on this group, with an additional 13 measurements on full-term infants. This report includes only those infants who were without clini-cal and radiologic evidence of lung disease,
although some of the smaller infants
quired an increased ambient oxygen con-centration for several days after birth.
The thoracic gas volume (TGV ) was de-termined by the plethysmograph method of DuBois, et a!. as modified for
The 43 liter plethysmograph was filled with
aluminum foil and calibrated with the
in-fant removed and an equivalent volume
substituted. The calibration was performed
at the observed frequency of breathing of the infant to compensate for possible adia-batic effects. The method used differed
slightly from that of others in that the mask
was removed from the infant’s face after each run through a port in the end of the box. This port was sealed with a pressure-tight cork during the procedure. A check was made for leaks before and after each run by opening the box to a weighted
spi-rometer and noting any decrease in spirome-ter volume. A minimum of five separate runs were performed for each TGV reported, one breath at random being analyzed in each run. The pressure changes obtained during the test were recorded on a paper trace and on an X-Y oscilloscope. Only
breaths that resulted in a straight line on
the oscilloscope were analyzed.
This method of measurement of thoracic gas volume is based on the compression and decompression of gas occurring
isother-mally, thus the size of the face mask
1.
#{149}<l200gmbirth weight
0 1200 1500gm birth weight
1.
1.
.c
C
a, E ‘a
E
> Ui
0.
0.
I 1 I
I
I
I I m 1 I m I m I 1 u0 3 6 9 12 18 24 30 36 42 48 54 60 66
Days
Fic. 1. Serial measurenients of thoracic gas volume in small and large premature infants. Note the high
initial TGV, followed by a decrease, and a subsequent slow increase.
of the dead space varied between 11 and 18 cc, depending on the size of the infants. Abdominal gas has minimal effect on tho-racic gas volume u7
lOOr-90
80
70
60
0
50
#{149}#{149} S. #{149}
.. .
S #{149}
.1:
#{149}Arterial blood obtained from the tem-poral artery was measured for oxygen ten-sion, using a platinum cathode, and carbon
dioxide tension, using a Severinghaus
dcc-trode.#{176} Pa02 and Pao2 measurements were corrected to the rectal temperature of the infant. The oxygen electrode was calibrated with gases of known Po,, and the discrep-ancy between blood and gas measure-ments when the instrument is calibrated with gases was determined by prior tonom-etry with blood; the appropriate correc-tion factors were applied to all blood oxygen values.’ Calibration of the Pco2 electrode with blood and gas was found to be iden-tical so that gas calibration was used. The alveolar arterial oxygen gradient breathing
air (AaDO2 ) was calculated using the al-veolar air equation.1#{176} A respiratory exchange
I ratio of 0.8 was assumed and the arterial
1.4 1.6 1.8 alveolar carbon dioxide difference (aAD1.o) was assumed to be negligible. Body length
0 Ultra-micro, Instrumentation Laboratories,
Boston, Massachusetts.
404
41
30
2O ‘ 0.4 0.6 ‘ 0.8 ‘ 1.0 ‘ 1.2 TGV, mt/cm length
FIG. 2. Relationship of thoracic gas volume and
arterial oxygen tension using values after initial
0
10
-(A-a)0o2 mmHg
S
S S
S
S $S
S
S S
S
30
40
S
S S
S
S S
1.4
was measured on each infant at the time of study in a specially constructed
measur-ing box. Breathing patterns were obtained with a mercury-in-rubber strain gauge
pneumograph applied to the lower anterior chest. Increase in functional residual
capac-ity was obtained by placing the infant in
a negative pressure chamber with the head
projecting through an air-tight collar. This
maneuver was performed on five infants.
Negative pressure ranged between - 2 to
- 10 cm water.
RESULTS
The data of all studies are shown in Table I. TGV ml/cm length at the time of the
study is related to age for infants below
1,500 gm birth weight in Figure 1. This
group may take as long as 2 to 8 weeks to reach a TGV mi/cm length of 1.0. Two
dysmature infants (data in Table I) reached
a TGV mi/cm of 1.0 in the first week. Fig-ure 1 also demonstrates that all infants
studied serially from birth showed a de-crease in TGV in the first week after birth.
405
Infants of birth weight greater than 1,500 gm are like full-term infants in that the fall of TGV is small and a TGV mi/cm length of 1.0 or greater is rapidly regained or main-tamed. An occasional infant in this higher weight group maintained a low TGV mi/cm for weeks (see Table I). TGV mi/cm length
in the full-term infants is similar to values
reported by others.”
Figure 2 relates Pa00 and TGV mi/cm
in the same infants. The Pa02 approached
adult levels when the TGV mi/cm reached 1.0. Only values obtained after the
mi-tial fall in TGV are shown. Figure 3 issimilar to Figure 2 except the AaDO2 is
substituted for Po2 on the ordinate. The
same trend as shown in Figure 2 is evident.
Representative examples of TG\’ mi/cm plotted with respect to age for various sze infants is presented in the lower part of Figure 4, and Pa09 is plotted against age in the upper part of Figure 4 for the same infants. In premature infants the Pa02 rises slowly, reaching adult levels in weeks, and the TGV shows the same trend; however,
20-I #{149}
. S
m I I
0.4 0.6 0.8 1.0 1.2
TGV. mi/cm length
FIG. 3. Relationship between thoracic gas volunie and alveolar-arterial oxygen
T(;J’/ Pa,t,
(?flh/(’liI) (titus JIg)
59
flirt/i Present
Patient JI’eight Weight
(gin) (gin)
BA 11 880 850
13 880 19 980 7?1 1,010 8 1,110 35 1,30 46 1,500 67? 1,975 68 2,090
WA* 17?hr 940 935
TO* 17?hr 980 970
3 900
JO Shr 1,106 1,070
7?6hr 1,040
7? 1,000
4 980
10 950
14 1,000
17 1,060
1I. 17 1,106 1,160
7? 1,’260 36 1,500 40 1,660 44 1,935 54 2,100 61
FE 53 1,130
TI l8hr 1,160 1,100
L() 46 1,7?30
WE 1,280 1,0
3 1,190
7 1,30
17 1,660
‘29 1,960
34 ,140
Lit 11 1,350 1,70
F2 1,760
33 ,540
44
* Died, witl, aI)neic episodes.
Present weight-weight when studied.
TGV-thoracic gas volume.
Pat) -arterial oxygen tension.
Paco-arterial carbon dioxide tension.
TGI’ (iii!) 15±1.7? 17 2.() )4 4.7 4 2.5 2 1.7 37? 5.1 33 3.9 34 1.1 44 3.4
3 ±4.3
36 ± 5.4
18 1.8
53 ±5.7?
43 4.3 46 3. 38 7?.1 33 .6 34 4.9 36 4.9
4 ±1 .1
7 5.5 31 3.6 )9 7?.3 41 5.1 39 5.1 48 5.9
45 ±5 .3
3 ± 7?.6
46 ±3 .
43 ± I .6
37 3.8
34 3.1
43 ?.7
46 7.1 44 3.2
46 ± 6 .7 46 7?.5 54 8.2 65 5.4 0.4 0.5 0.6 0.7 0.6 0.8 0.8 0.8 I .0 0.7 1.0 0.5 I .4 I .7? I .7? I .0 0.9 0.9 I .0 0.6 0.7 0.8 0.8 0.9 0.9 1.1 1.0 0.9 1.0 I .1 I .0 0.9 I.! I.! I .1 1.1 1.1 1. 1.4 Pa-o,
(nun Jig)
43 40 44 40 40 60 34 41 57? 45 41 38 41 39 38 41 37 38 40 40 33 34 40 35 70 66 65 81 7?3 53 54 57? 70 74 57 65 84 84 78 53 66 66 75 93 83 81 83 84 100 406 TABLE I
t l)ysmature infant, inappropriate weight for gestation. TABLE I-(Continued)
Birth Present
Patient .lge JJ’eight JJ’eight (do)
(gin) (gin)
La 7?8 hr I ,410 I,380
6 1 ,7?60
7 1 1,7?90
17? 1,37?0
34 1,840
58 ‘2,800
lIe 3 1,418 1,7?30
Co 7 1,418 1,341)
11 1,435
11 1,435
14 1,560
20 I ,860
‘27 ‘2,140
33
Fot 14 hr 1,440 1,430
7? 1,4(1(1
4 1,400
8 1,56(1
(; 3 1,551) 1,540
5 1,5’20
Sn ‘26 1,560 1,99()
li:e ; 1 ,670 1 ,580
10
.
1 ,65()17 I ,90()
‘29 ‘2,30(1
/29 ‘2,300
. ‘29 ‘2,300
Br ‘29 1,7’2I) ‘2,1’2()
Al 47 1,7’29 ‘2,840
48 ‘2,860
51 ‘2,990
6! 3,575
67? 3,575
Mit 37 1 ,800
Wi 19 1,860 1,94()
‘21 1,980
1,e 10 1,881) l,7’20
ii 1,740
17? 1,760
13 1,780
17 ‘2,000
19 ‘2,080
TGL’ TGJ’/cm Pao Pacts
(iii!) (mucus) (‘iii,, Jig) (tutu iJ’g)
40±4.1 1.0
31 5.1) ! 0.8
31 3.9 0.8
37 6.4 0.9 53 49
41 ‘2.9 1.1) 78
53 3.3 1.1 89 48
‘26±3.5 0.7 60 45
‘20±1.7 0.5 (;(; 43
‘28 4.3 0.7
37? 4.7 0.8 77? 47?
37 ‘2.7? 0.9
47? 9.6 1.0 77? 44
43 3.7 1.0
47 3.4 1.1 73 45
47±3.4 1.7? 65 36
34 4.8 0.9 68 35
37 6.1 0.9
47? 7.1 1.0
66±9.3 1.7
49 7.4 1.7?
46±0.8 1.1
44±1.4 1.1 68 40
41 4.8 0.9 68 45
36 4.5 0.8 68 48
41 ‘2.9 0.9 81 40
40 4.0 0.9
40 1.9 0.9 80 38
67?±4.4 1.4
34±’2.9 0.8 44 47
36 3.8 0.8
39 1 .2 0.9 70 41
51 ‘2.7? 1.1
54 4.1 1.1 80 37
46±3.9 . 1.0 74 33
50±0.8 1.1 84 47?
45 4.0 1.0 79 47?
47±3.9 1.1
43 ‘2.3 1.0
47 4.5 1.1
43 ‘2.5 1.0
49 5.1 1.1 91 40
Patient .4ge (do) Birth Weight (gin) Present Weight (gin) TGV (iii!)
I
,
985TGI’/cin (ui//cut) Fi Cu Ne Ko (;r Be Lo ‘24 7? 3 4 ()r 5 ‘29 ‘2,470
‘29hr ‘2,140 ‘2,070
H ‘2,060
18 hr ‘2,760 ‘2,760
x? ‘2,760 7?,77?0
4 . 7?,77?0
.5 ‘2,770
4hr 3,130 3,130
7? 3,180
3 3,180
3 3,7?60 3,s27?0
3,470 3,390
3,’240 3,7?40
3,’260
3,50)0 3,’260
57 ±‘2.3
60±5.0
68 5.7?
68 ± ‘2.4
77 ± 6.9 63 ‘2.7
63 9.5
73 ±4.0
70 8.8
54 4.5
67? ± 3.5
71±5.3 63 ‘2.9 50 1.8 53 4.8 71±7?.’2 Pa/I. Pa(’o. (miii Jig) (uuiuuz Jig)
89 34 80 40 94 37 69 37 80 38 85 3/3 100 38 57 37 78 39 84 39 1.’? IS I .5 1.4 I .6 1.3 I .3 1.5 I .4 1.1 I .4 I .4 1 .3 I .0 I .1 ‘.4 I,r newborn variation TABLE I-(Continued)
in full-term infants the falling TGV is asso-ciated with a Pa02, rising to adult levels
by the fourth day.
Figures 5 and 6 are examples of breath-ing patterns in an infant with regular respi-ration and in another with periodic breath-ing, showing the frequent appearance of deep inspiration or sighs. Figure 7 demon-strates that the frequency of sighs decreases as the functional residual capacity is in-creased. Of note as well is the disappear-ance of periodic breathing when the func-tional residual capacity is increased. This
result was obtained many times in the same
infant.
COMMENT
The evidence presented indicates that small premature infants have a much small-er TGV than full-term infants when this lung volume is related to length. Birth weight and length have been used as a basis for correlation with lung volume in
infants, but because of the erratic in body weight in the first month of life in premature infants, the latter cor-relation was used. A higher correlation be-tween TG\ and body length has been re-ported by others.u Jjg addition, the data were related to arterial oxygen tension which is another general index of lung function. It is clear that as the arterial ox)’-gen tension of the premature infants at-tamed values noted in full-term infants, the TGV mi/cm approached or exceeded a value of 1.0 mi/cm. Thus on the basis of
this evidence, a decreased lung volume in the premature infant is an accompaniment of the immature state and suggests atelec-tasis or partially expanded alveoli for a long period after birth.
neces-100
D90
E80
E 70
cm
Q- 60
50
BB,880gm birth wt
BH, 1106gm birth wt
a Bi. 1106gm birth wt
0 BW,l280gmbirthwt
BL, 1410gm birth wt
. Full term
1.
1.
1.
1.
0.
30 40
Days
60 70
C
a,
E‘a
E
>
I-Fit. 4. Serial determinations of Pafl. and TGV in infants of various birth weights.
sary and technical problems. Almost any procedure performed on a premature infant causes a degree of hyperventilation, tend-ing to produce a respiratory exchange ratio approaching 1.0 which may take consider-able time to return to the resting state and,
furthermore, periodic breathing results in
large fluctuations of Pa.” In this study, blood was sampled over a 1-minute period. The aAD09 was assumed to be negligible; however, this may not be warranted because of the effects of carbonic anhydrase
deficien-cy known to exist in premature infants’2 and
the technical problem of accurately
mea-r
Sigh
lnsplratlonl
FIG. 5. Piseumogr.tph tracing of a premature infant with regular breathing. Note frequent large
THORACIC GAS VOLUME
..:1:..:1::::1..I... #{149}:)....):...) I
Fic. 6. Pneumograph tracing of a premature infant with periodic breathing. The infant was 16 (lays old,
had weighe(l 1,276 gm at birth, and the present weight was 1,340. Note frequerst sighs and the (kcrease
in functional residual capacity (luring the apneic pauses. Paper sp(’ed, 1 mm per scc(tIm(l.
suring end tidal Pco2 at rapid respiration or
with periodic breathing.’
In all subjects on whom serial TGV’s were measured from birth, the values were
always higher in the first few days of life
and decreased to a low value in the first
week. In the case of most infants, at the initial period when TGV was falling, the
FIG. 7. Pneumograph tracing with infant in negative pressure chamber. A and B are continuous. A,
negative I)r’ssure applied with a return to atmospheric pressure. When negative pressure is applied the
baseline is shifted upward indicating an increase in FRC. Breathing is regular, tidal Volume is smaller,
and no sighs are apparent. \Vhen the pressure is released sighs and periodic breathing return. B, note
ARTICLES
oxygen tension was either stable or
increas-ing, indicating that there was no progres-sive deterioration of lung function at this time; however, in some small infants the
onset of apneic spells makes this difficult
to assess and further study is needed. The few full-term infants studied, and the iarg-er prematures, demonstrated a rising Pao at the time of the initial fall in TGV. This latter observation suggests an improvement in lung function in the first few days in larger infants and is consistent with the
ob-servation of Ledbetter, Homma, and
Far-hi,’4 who noted abnormalities of
ventila-tion-perfusion which were generally
cor-rected by the third day of life. The cx-planation for the fall in TGV noted in this
study is not readily apparent, although an
initial period of gas trapping with
subse-quent correction is a probability.
The physiologic role of frequent periodic sighs in inflating atelectatic areas has been suggested by Bendixen, et a!.,’ Mead, and Ferris.’7 Our data suggests these small infants may be sighing to compensate for, or as a result of, their small thoracic gas volume. Attempts to increase functional re-sidual capacity by negative pressure result-ed in the disappearance of the sighs.
SUMMARY
Serial measurements of thoracic gas vol-time and arterial oxygen tension in a group of small premature infants are reported. The study demonstrated that when thoracic gas volume reached levels for normal,
full-term infants arterial oxygen tension
ap-proached full-term values. The study
mdi-cates extensive pulmonary abnormality in
clinically non-distressed premature infants,
most likely iue to persistent atelectasis or partially aerated alveoli. Observations sug-gest that the infant attempts to correct this abnormality by frequent periodic hyper-inflations or sighs.
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