By James E. Drorbaugh,* and Wallace 0. Fenn
P
LETHYSMOGRAPHIC techniques have beenused by several workers8 to measure
ventilation in newborn infants. The
maxi-mal error has been reported to be ±10
per cent; it is probable that the great
major-ity of measurements have an accuracy of
less than ±5 per cent. However, the
methods used depend upon attaching a
cobbar either around the infant’s face’ or
around his neck.’8 .It was felt that this
limited the usefulness of the techniques
employed by previous workers. Therefore
we have attempted to develop a system for
measuring tidal and minute volumes which
could be operated while the infant was
al-bowed to remain unrestrained in a closed
chamber similar to an incubator.
In this paper animal experiments are
re-ported which compare minute volumes and
tidal volumes by standard methods with
the same quantities measured by the
baro-metric method to be described. In addition,
simultaneous records of pressure changes
within the chamber and respiratory air flow
are shown. Tidal and minute volume
rec-ords of 5 premature infants are presented
as a preliminary evaluation of the method’s applicability to the study of ventilation in newborn infants.
THEORETICAL CONSIDERATIONS
The theoretical basis for the method may be
presented by considering the conditions
in-fluencing air temperature and vapor pressure
within a closed chamber, the temperature and
vapor pressure of air contained within the
From the Departments of Physiology and
Pedi-atrics, University of Rochester, School of Medicine and Dentistry.
This work was supported in part by the Air
Research and Development Command, Wright
Field, Ohio, and in part by the John Bunn Corpo-ration, Buffalo, N.Y.
(Submitted for publication February 7, 1955.) * PRESENT ADDRESS: Boston Lying-in Hospital, 221 Longwood Avenue, Boston 15, Massachusetts.
lungs of an animal within the chamber, and
the effect on the pressure within the chamber of transferring a tidal volume of air from the chamber to the lungs of the animal on
inspira-tion. If an animal is placed in a closed
cham-ber at room temperature, the flow of heat from
the animal will warm the interior of the cham-her and initiate a flow of heat from the chamber
to the room. When these rates of heat
cx-change are equal, equilibrium will be estab-lished. The air temperature within the
cham-her, represented by the symbol T, will be less
than the body temperature of the animal,
rep-resented by TA, and greater than room
tem-perature. Any water within the chamber will
result in a vapor content which will approach saturation pressure. The final vapor pressure
reached will depend, in part, on T and i1i
part on the relative humidity within the cham-her. If we let pc be the final vapor pressure,
PS be the saturation vapor pressure for
tem-perature T, and RH be relative humidity in
per cent then:
(1) RH
PC X Ps
100
The above considerations would determine the
temperature and vapor pressure of inspired air
for an animal in a closed chamber. The rate at which values of T and pc are reached depends on size of the chamber, heat conductivity of its wall, temperature differential between ani-mal and room air, circulation of air within the chamber, and the availability of water for satu-ration of air within the chamber.
Air within the animal’s lungs is present at body temperature TA, and saturated with water
vapor which may be represented by
A.
As theanimal breathes, air is inspired at temperature
T and vapor pressure P1. At the end of
in-spiration a volume of air which we have as-sumed to be approximately equal to the volume of the inspired air is now present at
tempera-ture TA and pressure ‘A. That volume of air
which is now at PA and TA will thus be present
at a higher pressure because of added heat
repre-CALIBRATING CHAMBER
FIG. 1. An anesthetized cat with tracheotomy tube in place resting on a tray within the calibrating chamber. P and B are removable clips. If P is in place and B removed the animal is breathing from the chamber. If B is in place but P removed the animal is breathing from outside the chamber. The drawing
is schematic and not meant to show the relative size of the parts involved. TR., tracheotomy tube. T, tray. W, water. F, fan. H, humidity sensing element. SC, strain gage. Amp, Hathaway amplifier. Rec, Hathaway oscillograph recorder. 5, calibrating syringe.
sented by P. P will be directly proportional to
the volume of air warmed and wetted within
the animal and inversely proportional to the
size o the chamber in which the animal rests.
Therefore, P is a measure of the tidal volume
which may be designated V. On expiration the
reverse process will occur and pressure in the
chamber will be reduced by P.
If the animal has a respiratory quotient, or
exchange ratio which is constant, the total
number of dry gas molecules within the
cham-her will change at a constant rate, and the
total number of molecules present before and
after inspiration of a tidal volume VT may be
expressed as follows:
(2)
VO(PB
_
P) V1(P - PA)+ =
T( TA
(V0 - VT) (PB + “ - P)
+
(V5 + VT) (PB + ‘ - PA)
TA
In the above equation V0 equals the volume
of the chamber outside the animal, V1 equals
the volume of air inside the animal to which
the tidal volume is added, and PB equals
baro-metric pressure.
V0 and V1 are not known. However, their
sum may be obtained by changing V0 by a
known amount which may be designated VE,
and observing the change in pressure which
may be designated ‘K
(3)
(V0 + VK) (PB
_
P) VI(PB_
PA)T TA
VO(PB + PK P) VI(PB + K PA)
T TA
Equations (2) and (3) may be combined
eliminating V0 and V5. Solving for the tidab
volume then gives: (4)
P
VT j X VK X
K
TA (PB _ P)
TA (PB ‘c + P) -T (PB A + P)
The tidal and minute volumes obtained by
the barometric method are calculated by
equa-tion (4). When making the calculation P is omit-ted from terms where it is added to P since P is very small compared to PB. The ratio of P/Pa is obtained from the experimental record in units of millimeters of galvanometer deflection rather than in absolute pressure units. Volumes
are expressed in cubic centimeters,
tempera-ture as absolute temperature in degrees
METHODS
Chamber for animal experiments. A
modi-fled Castle sterilizer was used (Fig. 1). The
chamber was equipped with a tray to
sup-port animals and equipment beneath which
water was placed so that the final air volume of the sterilizer was approximately 44.0 liters.
A fan was placed on the tray to stir the air.
A pipe was put through the side of the
cham-her, with the inside end connected to a
trache-otomy tube in the experimental animal and
the outside end attached to a T-tube. One arm
of the T-tube was bed into the chamber again
and the other to the outside air. The arms of
the T-tube were equal in volume so that the
animal would have the same dead-space
whether breathing from the air or from the
chamber. In this way without opening the box
the animal could be made to breathe from
either the chamber or the outside air. When
breathing from the chamber a record of
venti-lation could be made by the barometric method
and when breathing from the outside
measure-ments could be made by plethysmographic or
spirometric methods.
Humidity inside the chamber was measured
by an electric hygrometer manufactured by
American Instrument Co., and accurate to
±:1 per cent relative humidity.
Temperature of the experimental animal
was measured by rectal thermometer. This
and the chamber temperature were read to
the nearest degree centigrade.
Pressure inside the chamber was measured by means of a Statham differential strain gage made for ranges of ±0.05 PSI (approximately
±30.O mm. H20). The gage was connected
to a Hathaway strain gage amplifier and
oscil-lograph. The oscilbograph galvanometer gave
a direct current sensitivity of 980 mm./ma/M.
This pressure recording system was used for
both the plethysmographic and barometric
methods. When used in the barometric method
pressures in the range of 0.1 to 1.0 mm. of water were measured, and a linear response was
oh-tamed when the volume of the system was
changed by known amounts ranging from 1.0
to 10.0 ml. A glass syringe was attached to the
side of the chamber for this purpose.
Comparison of Methods
The barometric method was compared with
3 standard methods: (1) Spirometric
measure-ments were made by attaching the tracheotomy
tube to water valves so that expired air could
be collected in a rubber balloon to minimize
resistance and transferred to a small Tissot
spirometer. The number of expirations so
col-lected and the frequency of breathing was
re-corded in order to calculate tidal and minute
volumes. (2) Plethysmographic measurements
were obtained by allowing the animal to
breathe through the pipe in the chamber wall
while the pressure changes within the
cham-her were recorded. (3) A pneumotachometer
made by Dr. Benjamin Ross was used to record
respiratory airflow while the barometric method was in operation.
Chamber Used for Studies on Premature Infants
A Bboxsom airlock of approximately 65 liters
volume equipped with carbon dioxide
ab-sorber and hygrometer was used. The humidity
measurement was necessary since the chamber
was not saturated with water vapor. After an infant had been maintained in the airlock for
30 minutes, oxygen and carbon dioxide
concen-trations were measured by means of a
Scho-lander gas analyzer and found to vary less than 1.0 per cent from their initial concentrations.
Animals used in the calibrating experiments were cats weighing from 1.7 to 4.8 kg.
anes-thetized with approximately 25 mg./kg. of
sodium pentobarbital injected intraperitoneally prior to tracheotomy. Initially the animal was
allowed to breathe from the chamber until
temperature and vapor pressure equilibrium
was established. This required from 10 to 15
minutes. A record of pressure changes within
the chamber was made and calibrated after
which the animal was switched immediately
to the standard method used for comparison.
The pneumotachometer, however, could be
operated simultaneously with the barometric method.
The procedure followed with infants was
exactly the same as that for cats except that only barometric records of ventilation were
made. The values obtained were compared
with those from plethysmographic methods re-ported in the literature. The infants varied in age from 4 to 39 days and in weight from 1.8
to 2.3 kg. The records were made from 30
PRESS.
NM. H20 VOL. CC.
0.2-
20
0_I
-
lOr0- I I
5
10
TIME,
SECONDS
‘5
Expt. f
Standard Barometric Skindard Barometric
Method Met/wd Method Method
VT JT V V
Per Cent
Error
1 18 19 18 340 320 -6
1 H 32 35 260 280 +8
1 ii 28 31 310 340 +1()
4 12 37 35 440 420 - 5
5 7 36 38 250 270 +8
6 10 38 33 380 330 -13
7 18 31 29 560 520 -7
Average tidal and initiute volumes measured by a standard method and the barometric method under the same conditions. The standard method used in experiments 1, 2, and 3 vas spirometric, in 4 and 5 plethysmographic, and
in 6and 7 pneumotachoiiietric. All volumes are at BTPS.f=frequency of breathing per minute. Vr=tidal volume in ml. V=minute volume in ml. Minute volumes have been rounded off to the nearest 10.0 ml. and tidal volumes to the nearest 1.0 ml. The per cent error is the algebraic difference between standard niethod and barometric method
expressed as per cent of the standard method value and rounded to the nearest per cent.
-PRESSUNE
1.0 FLOW
1(L/MIN) ,cxp.
:‘
I SEC. I
.
‘
-FIc. 2 (Upper). Simultaneous record of air flow in the airway of the cat and pressure changes within the calibrating chamber. Note that the onset of inspiration and end of expiration is at the same instant in each record. The values of 13 cc. and 14 cc. for the tidals in the pressure record were obtained by averaging the inspiration and expiration volumes obtained by planimetry from the airflow record.
Fic. 3 (Lower). Pressure changes produced by infant C within a closed chamber. The pressure scale
was calculated by assuming an approximate volume of 66 liters for the chamber. The volume scale represents the volume of air which must be inspired or expired by the infant in order to produce the observed pressure changes. The high frequency oscillations are artefacts.
TABLE IL
Baby V Range f Range V2 Range
N 80 240-360 1 18-3 13 4-3
It 400 360-440 45 44-46 9 4-3
A 590 450-7’20 37 31-43 16 6-71
G 400 300-500 57 51-69 7 3-45
K 410 30-470 75 57-85 5 2- 8
Ventilation data obtained from .5 premature infants. Tolumes are at BTPS. V=average minute volume in ml.
f=average frequency of breathing per minute. VT=average tidal volume in ml.
to allow a record within the pressure range of
the recording instrument.
RESULTS
Tidal and minute volumes obtained in
animal experiments by standard methods
are compared to the same measurements
ob-tamed by the barometric method in Table
I. The variation of the barometric minute
volume from the standard minute volume is
- 13.0 per cent to + 10 per cent. The
aver-age error for all 7 experiments is only 1
per cent. Figure 2 shows a simultaneous
barometric and pneumotachometric record
and demonstrates that changes in flow at
the onset of inspiration and at the end of
expiration are recorded by the barometric
method within 0.1 second.
The results of the measurements on
pre-mature infants are presented in Table II. A
sample record is reproduced without
re-duction in size of the observed deflections
in Figure 3.
DISCUSSION
The barometric method for recording
ventilation was first used by Dr. John
Chapin9 in the Department of Physiology
of this University. Calibration by means of
a set of syringes which warmed and wetted
a known volume of air without changing the
volume of the chamber produced calculated
and observed results agreeing within 8 per
cent. Our series of animal experiments
comparing tidal and minute volume
meas-urements by standard methods with those
obtained barometrically indicate about the
same degree of accuracy. Chapin found the
method sufficiently sensitive to record tidal
volumes of unanesthetized hamsters in the
range of 1.0 to 3.0 ml. at frequencies of 20
to 120 per minute. It was therefore utilized
in investigating the effects of autonomic
drugs on ventilation of small animals.’#{176}
Since simultaneous pneumotachometric and
barometric records show close
correspond-ance between chamber pressures and
changes in respiratory air flow, expired air
must come into temperature and vapor
pressure equilibrium with chamber air very
rapidly. Another indication of the rapid
transfer of heat and water from expired air
is the fact that the baseline remains
ap-proximately steady except for slow rhythmic
fluctuations in both directions. Therefore
relatively high frequencies of breathing
need not interfere with application of the
method.
The results for minute volume and
fre-quency of breathing of premature infants
listed in Table II are in the same range as
those recorded by Cross11 and by
Boutour-line-Young and Smith2 using
plethysmo-graphic methods. Cross gives values of
396.3 ± 96.2 ml. for minute volume and
34.39 ± 8.63 for frequency per minute.
Smith gives 430 ml. and 32.8 breaths per
minute for average values of the same
func-tions. We have not averaged our values
since only 5 experiments are presented and
no attempt was made to exclude babies not
in a “basal” state of ventilation.
At the present stage of development 3
factors limit the usefulness of the
baro-metric technique. (1) When the baby is
not possible to measure individual tidals
ac-curateby. During activity such baseline
changes might be explained by muscular
activity of the baby resulting in
compres-sion of air within the lungs or
gastroin-testinal tract thus producing a change in
pressure within the chamber. This was
sug-gested by Chapin who noted the same
phenomenon during his study of hamsters.
Such changes could also result from large
changes in the infant’s functional residual
capacity. (2) It is necessary to wait at least
10 minutes before records can be made
since time is required for vapor pressure
and temperature equilibrium in a relatively
large chamber. (3) The chamber must be
opened every 20 to 30 minutes in order to
prevent oxygen concentration in the
in-spired air from falling more than 1 per cent.
These disadvantages must be weighed
against the advantage of being able to
study ventilation of a seriously ill newborn
infant without the necessity of interfering
with his medical care. Further experiments
will be necessary before the usefulness of
the method can be definitely established.
CONCLUSIONS
A barometric method for measurement
of ventilation of newborn infants is
de-scribed.
Experiments with cats are reported to
show the degree of accuracy obtainable at
present. The variation from standard
meth-ods was found to average ± 1 per cent.
Minute volume, frequency, and tidal
volume of premature infants measured by
the barometric method are within the range
of such measurements made by
pbethysmo-graphic methods.
The barometric principle deserves further
study since it offers the possibility of
secur-ing ventilation data with a minimum of
dis-turbance to the infant.
REFERENCES
1. Cross, K. W. : The respiratory rate and
ventilation in the newborn baby.
J.
Ph>’-siol., 109:459, 1949.
2. Boutourline-Young, H.
J.,
and Smith, C.A.: Respiration of full term and
pre-mature infants. Am.
J.
Dis. Child.,80:753, 1950.
3. Howard, P.
J.,
and Bauer, A. R. :Irregu-larities in breathing in the newborn
period. Am.
J.
Dis. Child., 77:592,1949.
4. Wilson,
J.
L., Long, S. B., and Howard,P. : Respiration of premature infants;
response to variations of oxygen and to increased carbon dioxide in inspired air. Am.
J.
Dis. Child., 63:1080, 1942. 5. Murphy, P. P., and Thorpe, E. S. :Breath-ing measurements on normal newborn
infants.
J.
Clin. Investigation 10:545,1931.
6. Deming,
J.,
and Washburn, A. H. :Res-piration in infancy: Method of study
of rates, volume, and character of
res-pirations. Am.
J.
Dis. Child., 49:108,1935.
7. Deming,
J.,
and HannerJ.
P. : Respirationin infancy : Study of rate, volume and
character of respiration in healthy
in-fants during neonatal period. Am.
J.
Dis. Child., 51 :823, 1936.
8. Shaw, L. A. K., and Hopkins, F. R. :
Res-piration of premature infants. Am.
J.
Dis. Child., 42:335, 1931.
9. Chapin,
J.
: The ventilatory response ofthe unrestrained hamster to carbon
di-oxide. Am.
J.
Physiol., to be published.10. Tawab, S. A. A. : The influence of drugs
on the respiratory center. Thesis for B.S.
Degree, University of Rochester,
Roch-ester, New York, 1950.
1 1. Cross, K. W., and Opp#{233},T. H. : The re-spiratory rate and volume in the prema-ture infant.
J.
Physiob., 1 16: 168, 1952.SPANISH ABSTRACT
M#{233}todo Barom#{233}trico para Medir la
Ventilaci#{243}n Puhnonar
en los
Reci#{233}nNacidos
Los autores presentan un m#{233}todopara medir
ci aire cornente y vobumen-minuto en raci#{233}n
nacidos y lactantes y describen sus bases te#{243}ri-cas y el manejo deb equipo. Despu#{233}sde haberlo
experimentado en gatos, bo observaron en 5
espirom#{233}trico y neumotacom#{233}trico (ve#{225}setabla 2). Aun cuando este m#{233}todobarom#{233}trico parece ser muy satisfactorio pues favorece el estudio de la ventilaci#{243}n pulmonar en ni#{241}osinclusive
gravemente enfermos sin tener que interferir
con los cuidados medicos a que est#{233}sujeto, y
proporciona datos semejantes a los de los
m#{233}todosstandard, los autores se#{241}alantres
fac-tores que limitan su utilidad: Ia presencia de
actividad exagerada en los ni#{241}osque impide medir con exactitud el aire corriente individual; necesidad de esperar con ci ni#{241}oen Ia c#{225}mara
diez minutos por bo menos con el objeto de
equibibrar el vapor y ba temperatura, antes
de iniciar Ia anotaci#{243}n de los datos; y por iIltimo necesidad de abril la c#{225}maracada 20
0 30 minutos a fin de evitar que el oxIgeno
del aire inspirado baje a m#{225}sdel 1%.
INTERLINGUA ABSTRACT
Un Methodo Barometric pro Mesurar
Ventilation in Neonatos
Technicas plethysmographic ha essite usate
per plure baborantes pro mesurar ventilation in
neonatos. Ii es probabile que be majoritate de
iste methodos ha un exactitude de infra 5
pro cento. Tamen, illos omnes require un collar attachate circa le facie o le cob del subjecto, lo que limita br utilitate.
Per consequente nos ha interprendite
dis-veboppar un systema pro mesurar Ic
volumine-minuta e be volumine respiratori be quab esserea executabibe con be neonato jacente sin
restringi-mento intra un camera claudite simile a un
in-cubator.
In be presente reporto nos publica be
re-subtatos de experimentos con cattos in que
volumines-minuta e volumines respiratori
mesurate secundo be methodos standard esseva
comparate con mesurationes del mesme
quanti-tates per be methodo barometric. Le exactitude
del methodo barometric nunc obtenibile es
indicate per Ic facto que su vabores mOnstrava
Un deviation median de ±1 pro cento ab be
valores del methodo standard.
Nos etiam presenta registrationes barometric
del volumine-minuta, del frequentia, e del
volumine respiratori ab 5 infantes prematur.
Iste registrationes permitte un evalutation pre-biminari del applicabilitate del methodo baro-metric al studio ventilatori in neonatos. Le re-subtatos obtenite cade intra be limites de
cor-respondente mesurationes executate per
metho-dos plethysmographic.
Le principio barometric merita attention e
studios additional proque illo offere le
possi-bilitate de obtener datos ventilatori con un
