An infant incubator

AN INFANT EMPLOYING

CONTROLLED

INCUBATOR

MIXTURES

OB

HELIU~~

RESPIRATORY FRANCIS

G.

BENEDICT,

ROBERT

(From

the Nutrition

PH.D.,

C.

LEE,

AND

OXYGEN

TO

COMBAT

FAII~URE PRISCILLA

B.CH.E.,

Laboratory of the Carnegie New lCn,ylanfZ Deaconess

M.D.,

WHITE,

BOSTON,

AND

MASS.

Institution Hospital)

of Washington

and

the

U

P TO the year 1938 many infants of diabetic mothers had experienced respiratory failure immediately after birth, the exact cause of which at that time seemed obscure but now appears to be related to a disturbed hormone balance. Prior to this knowledge it was suggested by one of us (P. W.) that heliumoxygen therapy might be of aid to such infants. For this purpose the incubator here described was constructed. The objectives of this incubator are to maintain the infant at the proper temperature and in an atmosphere containing only oxygen and helium. According to Alvan L. Barach,i to whom we are indebted for helpful sugge,stions and advice, a mixture of 20 per cent oxygen and 80 per cent helium has a measurably lighter density than room air and hence should require less effort in breathing on the part of the infant. Thus the aid to respiration is a mechanical one. Other investigators2 have also reported beneficial effects of breathing helium-oxygen mixtures when respiration is embarrassed. Since the use of this chamber was started, the respiratory failure of newborn infants of diabetic mothers has been successfully prevented by prenatal hormone therapy. However, during the three years that this apparatus has been in use, a number of infants have been aided by being placed in the incubator, and the use of the equipment with other gaseous mixtures than the one originally proposed has proved helpful in some cases. In addition to its special feature of making it passible to determine and maintain the composition of the gaseous mixture in the chamber, this apparatus incorporates the four basic requirements of an incumaintenance of proper temperature, maintenance of proper ven bator, namely, tilation or oxygenation, maintenance of adequate humidity, and easy aeress to the infant without harmful exposure. CONSTRUCTIOX

OF

APPARATUS”

The chamber (Figs. 1 and 2) is made of galvanized sheet iron, its inside measurements being 56 by 30.5 by 23 cm. and its volume, 39.3 liters. The cover, which has a large plate glass window, fits into a water seal, making the chamber air-tight. A pipe at the top, D (Fig. 2) and another, d, at the diagonally opposite, lower corner facilitate thorough ventilation of the chamber and complete evacuation of the air in the chamber when it is to be filled with a gaseous mixture other than room air. The lower pipe has a metal screen in front of it, which prevents any obstruntion of this pipe by bed clothing or pillows. The cover is held in place by two stout across the cover, and attached to rubber bands, fastened securely on one ride, drawn snap hooks on the other side. The cover can be removed in two or three seconds by snapping up the hooks, throwing a lever operating a quick-throw release valve, S, which opens the chamber to the room, and lifting the cover by the two handles on its The chamber itself serves as a bassinet. The mattress is formed by inflating t,op. air pillows, which are placed in the bottom. By suitable combination these may work

*The

construction

of V.

Coropatchinsky

of

the

of

chamber an13 the Nutrition 63

the assembly Labolatorl.

of

thr

:lppa1’atus

were

the

be arranged as desired, to product the J,roper Tilt of lh: infant. ‘J’he cJmmb~r is insulated on all sides by asbestos board, to prevent rapid ~ltangcs 01’ ttmperaiurr. Heat is obtained from four N-watt bulbs of the bung-JWIP type ( IV-I to Fc’-IJ’:), .\ piece of sheet metal situated about 50 mm. Jtelow tire bottom of the chamber. aii1.r in uniform ~listrilrution of the heat. halfway between them and the ~,h:~mber lamps are cou The arrangement of the lamps is indicated in Kg. 2. Tlw middle trolled by the thermostat, C, whit,h nnlintains the temperature constant wit,hin 3” F. The two additional lamps permit rapi(l Imating at the start or ~hcnever, for any reason, it is desired to increase the tempcrat~ure rapidly. l‘nder ordinary conditions the thermostat adequately maintains the desired temperature. To indicat,e what the tcrnpnatuw (entlitionh a~$. a t t~c~rrntrmcter. T, is locatr4 inside the chamber,

To insurc~ that the heat transmitted through the the cover. does not become excessive, a brass tube closed at the end has side of the chamber. This tube fits int,o a fold in the rubber in the way. A\ thrrmomcter, TT’, whirli can easily he with to be rea(l, is insert& in this tube. The reatilntion sylstmn, wllirll is on flm (~Josetl-Arcuit principle, consists of 3 (entrifugal type, nonpositive J>lowt~r.C 8. :I sodalime rsontainer, C, a flow meter, R, ant1 necessary pipe connecting with the chamber. E’lrxible metal pipe was used for making the connections to the various instruments, as it. was thought that rubber tubing might permit helium to escape by dift’usion. Tests of one hour’s duration, made since the construction of the apparatus, have indicated that rubber tubing will apparently hold helium satisfactorily. Provision for contraction and expansion of the air in the chamber is made through either the aut,omatic filling device, E, 01’ the calibrated, l-liter spirometer, K, which is also used for testing the composition of the gaseous mixture. The carbon dioxide produced by the infant is absorbed from being suspended from bottom of the chamber been soldered into the pillow and thus is not drawn a sufficient length

*Manufacturecl

by

Warrm

E.

Cdins.

Inr..

Boston,

Massnchusctts.

BENEDICT

ET

AL.

:

AN

INFAKT

INClTBATOR

65

the ventilat,ing air current by JWson soda-lime, which also serves to maintain 5 high moisture content of the air. The capacity of the soda-lime container is approximately 3 liters, which is sufficient to remove the carbon dioxide produced by a new-born infant during 72 hours. The flow meter or “ rotamesser ” gives visual Indication of the rate at which the air is being circulated through the chamber and is also uPet1 when the system is being filled with a gaseous mixture. The ventilation is usually maintained at 10 liters per minute.

Fig. 3.--Schematic outline of incubator and respiration apparatus for continuous administration of a helium-oxygen mixture to infants. A, pipe for outcoming chamber air; B, rotary blower; C, container for soda-lime; D. pipe for ingoing chamber air; W-I to W-17’, electrical heating units; CT’. thermostat; T and TT, thermometers; Y’, rheostat controlling speed of blower: 8. release valve; 7. valve for introduction of helium-oxygen mixture: R, flow meter indicating rate of flow of gas thl ough ventilation circuit : IS, automatic gas reguiator acting also as expansion chamber ; o, o, cork to compensate for weight of regulator bell : F, pressure-regulating bottle; G, valve through which oxygen enters regulator: H, valve used to disconnect gas regulator from oxygen supply ; Ii, densimometer (l-liter spirometer) to determine composition of gaseous mixture in chamber: L, valve connecting densimometer with main ventilating air current or with orifice in disk N; P, enlargement of disk N; ,W, valve

to

connect

densimometer

cylinder of gas with the densimometer gas regulator E to main circuit.

with

main

ventilating

or the chamber,

air

current

as desired;

or

to

Q, valve

connect

a

to close

Hethotl of Pilling With. Ozygrr~-ErEil*m Nli.rtzlre.-lt is desirable to replace the room air present at the start in the system and chamber as completely as possible with the helium-oxygen mixture, because any nitrogen in the chamber air will increase the density of the gaseous mixture and this in turn will necessitate more effort by the infant’s lungs in breathing. This is effected by introducing at the inlet to valve V (which has been closed to pipe d and opened toward blower B) a mixture of 75 per cent helium and 25 per cent oxygen from a cylinder.* With the *As mixtures of 75 per cent helium and 25 per cent oxygen cu. ft. cylinders from the Ohio Chemical and Manufacturing Ohio, this mixture is now used instead of the mixture of 80 per cent oxygen employed in the preliminary studies.

can be obtained in 200 Company Cleveland. cent heiium and 20

per

Fig.

;I.-Densimometer

and ministration

gas of

regulator of hriium-oxygen

respiratiOn

mixture

aPParatus to infants.

for

continuoue

all-

the chamber will be completel? 7 rwvrpt out and the sykenr will he filled with the desired mixture. By shutting valve H during the early part of the filling and by opening valve Q to connect with regulator E ant1 valves .?I and L to connect with spirometer K, the reservoirs of thrl units Z? and K can by manual manipulation be washed out with the oxygen-hrlium mixture and then partially filled with this mixture. This is done to prevent the introduction into the system of gases other than the desired mixture. This extra gas replaces gas used in testing the eompoxi. tion of the mixture.

BENEDI(:T

ET

AI,. :

AN

INFANT

INCUBATOR

67

Method of Analysis of Gaseous Content of Chamber.-It is important to know that the gaseous mixture inside the chamber is composed of the desired percentages of helium and oxygen and that this composition remains constant during the use of the equipment. It is also necessary to know that the infant has sufficient oxygen at all times. Therefore a simple method for determining the composition of the gaseous mixture was needed. For this purpose a densimometer (Fig. 3 and h; Fig. 2) was designed, based upon the principle that, because of the difference in density of helium and oxygen, the rate of effusion of a mixture of these gases will vary according to the composition of the mixture. The densimometer consists of a l-liter spirometer, the bell of which (originally exactly counterpoised) is overweighted by a 100 gm. brass ring. The spirometer is sealed with mineral oil.* Provision is made for passage of the gas from the spirometer through an orifice in the disk N. This disk (enlargement P, Fig. 2) is of brass, 0.8 mm. thick, in which an orifice 0.23 mm. in diameter has been made with a No. 80 drill, Even with great care the size of the orifice produced by the No. 80 drill will not be uniform in all cases. A number of disks with these orifices were made and tested. After a standard time for passage of a given quantity of gas had been established, the orifices of the disks that required longer than the standard time for the passage of Disks with orifices permitting too gas were enlarged by reaming with a needle.

Fig. I.-Calibration curve obtained with densimometer. The curve shows the time in minutes required for a deflnite volume of a gaseous mixture, having the composition indicated by the abscissae in the chart, to escape from the closed system through the standard orifice. rapid flow of gas were discarded. After the air originally in the densimometer has been swept out, the instrument is filled with the gaseous mixture, the composition of which is to be determined. This is accomplished by connecting the densimometer with the ventilation system, closing valve H, and manually raising the bell of the densimometer. The gas thus withdrawn from the system into t,he densimometer is replaced by gas from regulator E. The gas in the spirometer bell is washed back into the system, and the bell is then filled again, to secure as representative a sample as possible. The test of the gas is then performed by turning valve L to the position shown in Fig. 2 and noting the time required for a portion of the gas in the spirometer E, under the pressure caused by the 100 gm. excess weight of the bell, to pass t.hrough the orifice at N. Two marks 50 mm. apart on the counterpoise cord (Fig. 3) designate the volume to be measured. The time required for these two marks to pass a fixed point is a measure of the rate of effusion of the gaseous mixture. From the results of calibration tests of the densimometer with ordinary air, pure oxygen, pure helium, and various helium-oxygen mixtures, the calibration curve in Fig. 4 has been derived. This curve indicates the percentages of oxygen and helium in the gaseous mixture in the system, according to the established rxtr of effusion from the densimomrter. The practicability of this instrument is demonstrated by the fact that :I second densimometrr was constructed am1 adjusted to *Squibb’s

heavy

California

mineral

oil.

have the same calibration curvf! fur. standard u&ices. I I’ ilust, or other foreign material clogs the orifice, it is best to replace tlir tlisk by another tested disk rather than to attempt to clean the orit&,. For (:onreniencr, aevcrul Ilisks are kept at hand in a sealed container. To control I he ac~uru~y of functioning of the instrnmfnt anal to make sure that- the orifice is ~,lean, thr tinl(J l’or tlitfnsion of room air (.3.X? _C 0.M minutes) is used as a standarrl.

3,utonutic Replacrnwnt of G.UJU~ ,L.- To uutintxin constanvg in the composition of the gaseous mixture when the infant is in the chxmbcr. tile oxygen consumed by the infant is constantly repl:u~c:~l hy an automatic: arrangement connected at 0 (Fig. 21. This consists of a Murrill reguIator,:i whiczh has its be11 floated by a cork ring attached at o, o. As the volumr~ of thv g:rseous mixture in the ~Iosed system is decreased by the infant’s c*oneurnption of oxygen (the carbon dioxide produced by the infant is removed by the soda-lime). the tendency for reduced pressure in t,he system causes replacement of the oxygen from container E. *%s the bell of this instrument falls, it causes valve C to he opened, admitting oxygen from the supply line. By a tee dipping into the bottle F. containing water, oxygen from a cylinder is constantly supplied undfar :tpprosin~:~trly 2.5 mm. of water pressure to the valve C. at a rate of 30 to 50 C.C. per minute. .\i the hell is raised by the udmittance of oxygen, the valve G closes and tin ex~ss oxygen escapes through bottle 27. Rut it valve G is open, oxygen will be suI,plierl to the r?ontninrr K without contamination, any excess oxygen escaping into the room. LZs tlie chamber, with its blower am1 it vvoultl contain IO liters of oxyconnecting pipes, has a iota1 cnp:u~ity of Ill liters, mixture is us~V1, If for any reason oxygen failed gen when a 05 per cent oxygen to be supplied, the chamber woul11 rontinue to hare sufficient oxygen for the infant’s needs for at least two hours (the rate of oxygen consumption of these infants 11as without tllc oxpgen per0mt:lge be been found to be xpproximatelp 20 P.P. per minute) ing reduced to an unphysioloeic~ level.. l7’se of Other Pcrcmtnge Jli.rturc,s of Helium rind Oxygen or af 3fizture.s of Other. Gases.-Some infants have benefited by the gas mixtures of low density, but others have required higher oxygen c~oncentration to improve their condition. The oxygen content of the chamber air can be reallily increased by admitting oxygen through the valve P (Fig. 2) until a calculated quantity of gas in the chamber has been displaced. This is done by stopping tlm bloxvcr, turning valve r so that it does not communicate with blower 11 but (lees communi~ntr with the pipe .I and the oxygen This insures that the oxygen introduced will go into the chamber. The supply. volume of gas introduced is tleterrninecl by mrterin, cv the gas ~lisplncetl, h,v connerting to the valve $1 an or~linary wet gas rnc~ter or spirometer. If, for example. a mixture of 40 per cent oxygen is tlesircd and the gas nlreadv present in the r:hanrhel contains 25 per cent oxygen, by ~disl~lnccn~cnt of 7 liters o’f the contents with mire oxygen the oxygen percentage will be in~~reasr~l to xpprorirr~ately -il1 per Pent. TIP composition of the new mixture V:UI 1~ re:uIily tested, to insure that the desired percentage of oxygen has been attuinctl. ‘l’his new perrentage will then be automatically maintained, as the oxygen used by the infant will he replaced by the automatic arrangement. 111 some (ases it is rlesirablr to IISC u mixture of carbon . . This mixture can be admitted in dioxide and oxygen as a respiratory stimulant. the same manner as described above for enrichment of the oxygen content of thcl chamber air. When the carbon-dioxide and oxygen mixture is used in the ~hnmber, as the sodalime would remove t,he ventilation system must not 1)~ in operation, the carbon dioxide. When it is desiretl to resume the use of the chamber with some other gaseous mixture, the mixture of carbon dioxide and oxygen should be swept out into the room and not through the ventilation system, as otherwise the carbonwill he exhausted unnecessarily soon dioxide absorption capacity of the soda-lime and the technical problem will be emounterrd of compensntin,g rapidly for the dt>crease in volume of the gas in tile s~5tcm. Test for Tight,less.-The al~I~ar:~tus is rcutlil, testr(1 for tightness 1jy closing valve Q to the system, having valves Jf and L open to the spirometer, and valves S and P in the position shown in Fig. 2. The bell of spirometer K (whirh has been overweighted b,y 100 gm. for use as a densimometer, see page 65) is exactly counter

CENE,ElCT

ET

AL.

:

AN

INFANT

ISClJBATOR

69

balanpetl by attaching a 100 gm. weight t,o the c*ounterpoisr cord ; the level of the bell is then noted, and the weight is removed. This places slight pressure on the system, because of the original overweighting of the bell. After fifteen or twenty minutes the weight is replaced, and if the system is tight, the bell should return to its original level. Slight changes in temperature and slight changes in pressure OE the chamber, caused, for example, by placing something on the cover, will alter the apparent volume of the system. ACTUAL

USE

OF INCUBATOR

ln acztual use this incubator has proved excellent in providing the essential conditions for infants needing special care. The temperature is adequately maintained and, even when the chamber is open, the chamber walls prevent marked exposure of the infant to cold. The humidity is maintained in the vicinity of 90 per cent by the use of Wilson soda-lime. Our experience with this incubator has been confined to infants of diabetic mothers. These infants have required attention usually every four hours, to obtain blood samples for sugar determination and for other care. Over a period of four hours, with the chamber sealed, the cornposition of the gas has been held essentially constant in all cases. The infant is visible through the large window (which could be even larger, if desired) and is readily accessible in the event that immediate attention is needed. It is frequently helpful to have little or no covering on the infant, to facilitate observation and to avoid any possible hindrance to respiration. In this case, the temperature can be held at such a level that the infant will require little or no covering. Between May, 1936, and May, 19.39, ten infants of diabetic mothers were placed in the oxygen-helium incubator in an attempt to combat neonatal asphyxia. The clinical picture associated with fatal asphyxia neonatorum in our experience had been slight respiratory excursion, rising temperature, long periods of apnea and cyanosis, and the development of terminal r$les. For many years this picture had been attributed to hypoglycemia due to maternal insulin or hyperplastic islet tissue. The latter is an almost universal finding at autopsy. Our own belief, however, was that hypoglycemia could not be the responsible factor, as it occurs in normal infants without abnormal behavior, is remedied easily by glucose, and the seizures observed in our children were found to occur with blood sugar values above normal and at normal levels as well as below normal. Eventually, through the work on hormones by Smith and Smith+ and later the prolan determinations by White and Hunt,5 it became apparent that the fatalities could be predicted by a knowledge of the prolanestrin balance and prevented by substitutional estrin and progesterone therapy. Thus, among the infants of 14 mothers whose values for prolan were maintained at a normal level by treatment with massive doses of estrin and progesterone three to six weeks prior to delivery, there were 3 deaths, 1 neonatal associated with asphyxia In the latter instance, the mother’s pallida in a premature infant and 1 stillbirth. Among the infants of twelve mothers with supernormal therapy had been omitted. values for prolan, there were 6 fatalities, 4 associated with prematurity and asphyxia and 2 stillbirths. Ten infants were placed in the incubator. all of whom had respiratory difficulties or were cyanaCe. The mothers of 0 of these had supernormal values for prolan and their infants were, tberefore, in the group in which the mortality rate was high. Despite the oxygen-helium t,reatment, 3 of these infants died. Hence this treatment does not always result in a successful outcome in this particular complication. Of the 4 infants whose mothers had normal values for prolan, all survived, but we know now that this was to be expected in nearly 100 per cent of these cases. One infant, we believe, was distinct,ly helped. This infant, who had aspirated amniotic content and for whom the pediatrician had given a fatal prognosis, had long periods of The cyanosis was relieved when the infant wax cyanosis witbout periods of apnea. placed in an atmosphere of almost pure oxygen. She remained in the incubator for forty-eight hours, and then behavior became entirely normal. Two other infants also survived, being apparently aided to some extent by the oxygen-helium treatment. Although this treatment was not successful in all instances in preventing respiratory

An incubator is described in which an infant can be kept at the proper temperature and humidity, with proper ventilation and, to facilitate respiration, in an atmosphere containing a known :tngl controlled mixture of oxygen and helium. A densimomot.er serves to determine the c,oulposititrn of the ganroul: mixture within the chamber and to make rsertain that this composition remains constant (luring its a mixture of csarhon dioxide and oxygen can he used as a use. When necessary, respiratory stimulant. Originally the incaubator was designed for newborn infants of diabetic mothers, in an attempt to combat neonatal asphyxia, and the equipment ]ms proved helpful in several instances. Rullsequentlv it ~8s found that the respiratory failure of such infants car1 lie successfully prevented 1,~ prenatal hormone therapy. The clinical experience with the inmhator is discussed. RFFFRFVCIW 1 , ,.

(I) Barach, 8. L.: J. Clin. Investigation 1936. (2) Eversole, U. H.: J. h. M. Lawrence, R. C.: Brit. M. J. 2: 448, 1938. 501, 1898. (4) Bmith, 0. W., and Smith, 1937. (5) White, P., Titus, R. S., .Tosli,f, 198: -182, 1939.

1.

15: 47, 1936; J. &I. 110: 878, 1938. (3 ) 3izlrrilZ, P.: J. G. V.: AM. J. OBST. S. P., rind Hunt, H.

A. M. A. 107: 127Z, Rykes, W. S.. nncl ilm. Chem. Sot. 20: 65 GYNEC.

M.:

Am.

33:

365,

J. M.

SP.

LEUCEMIC INFILTRATION OF THE FEMALE INTER’NAL GENITALIA A8 A (‘ATBE OF VAGINAL BLEEDING HARRY (From

HAUPTMAK, thr

Gynecologic

M.D.?

AND

Ber&tI

of

FR,ED J. TAUSSIG, M.D., ST. Lours, the ZWnnrrl

Free

Skin

and

Cnncer

Hospit

310. i

T

HE leucemias have always constituted a sphere of medicine into which the gynecologist. rarely, if ever. entered. The patient suffering with leucemia would come to the surgeon becanse of enlarged lymph nodes, to the internist, because of an enlarged spleen, or to the dermatologist because of infiltrations of the skill. In the case reported in this paper, the leuwmic patient came to the gynecologist because of vaginal bleeding, and the constitutional disease was discorered by investigation of the ca.nse of the bleeding. Since women are being educated to the importance of ascertaining the cause of any abnormal vaginal bleeding, some (‘ases of lencemia may be discovered and diagnosed by the gynecologist. Leucemic infiltration of the female genitalia has always, been a rare entity, although it may have been present in some cases where it was either undiscovered or not diagnosed.

The textbooks and handbooks in gynecology (with one exception) make no mention of a relationship between leucemia and pelvic pathology. MacCallum refers to a case of a lymphoid nodule in the cervix uteri extending to the vagina, with Xt autopsy there was found ulceration and bleeding. I ‘an infitration of lymphoid cells in many of the organs in association with a leucemic condition of the blood.” Leucemic infiltration may occur in any part of the body, although, as noted by