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(1)

THE

RESPIRATORY

DISTRESS

SYNDROME

OF

PREMATURITY

I. Changes

in Potassium in

the

Serum

and

the

Electrocardiogram

and

Effects

of

Therapy

Robert Usher, M.D.

Departments of Obstetrics and Pediatrics, Royal Victoria Hospital, Montreal

(Accepted May 7, 1959; submitted October 22, 1958.)

These studies were carried out with the aid of a National Health Grant (Canada). ADDRESS: Montreal 2, Canada.

PnrATiucs, October 1959

562

T

HE MORTALITY rate for premature

in-fants during the first 5 days of life is

the same today1 as it was in Yllpo’s large

series2 40 years ago. Most premature infants

who die within this period show pathologic findings restricted to the lungs. The post-mortem picture has been called congestive

pulmonary failure (resorption atelectasis with hyaline-like membrane) by Potter.3 The

clinical course, usually 1 to 3 days in

dura-tion, is marked by respiratory distress and

is sufficiently constant to be termed the

respiratory distress syndrome.’

A detailed clinical and laboratory

inves-tigation of premature infants with

respira-tory distress syndrome has been in progress

at this hospital since July, 1957. Serial

ob-servations have been made over the 3-day

course with the main emphasis on the

respir-atory, cardiovascular and metabolic aspects

of the disease process.

The following is the first of a series of

reports on the findings obtained in this

study. This report presents data on the

concentrations of potassium in the serum

and

the

electrocardiograms

both

in infants

with respiratory distress syndrome and

con-trol infants. The effect of parenteral fluid

therapy in some of the affected subjects is

described.

There have been few previous clinical

studies of this syndrome. In the absence of

an adequate specffic clinical description in

the literature, the following definition of the respiratory distress syndrome of prematurity has been used in this study:

Infants weighing 500 to 2,500 gm who for

hours or days after birth have retraction of the

chest, expiratory grunting, and decreased entry of air on auscultation, without evidence of other

coexisting disease.

This working definition excludes other

causes of neonatal respiratory distress such

as pneumonia, meconium aspiration

syn-drome, or congenital heart disease. In fatal

cases of this syndrome, the postmortem

examination revealed only pulmonary

atel-ectasis with hyaline membrane formation, pulmonary congestion, and occasional sub-arachnoid hemorrhages.

SUBJECTS AND METHODS

Fifty-nine premature infants with respiratory

distress syndrome, 45 premature infants

with-out respiratory distress syndrome and 13

nor-mal full-term infants were studied (Table I).

The 59 infants with respiratory distress syn-drome included 47 available for study at this

hospital (of 57 premature infants who

devel-oped the syndrome during the past 18 months), and 12 seen at other hospitals. Of the total

69 patients with respiratory distress syndrome,

38 died, a mortality rate of 55%.

The premature infants without respiratory

distress syndrome were selected solely on the basis of absence of chest retraction and grunt-ing after birth. They followed a normal course for premature infants, all but three surviving. The three deaths occurred at 3 to 9 days of age

in infants weighing 1,100 to 1,300 gm. There

were no diagnostic postmortem findings on

two of these infants; the third showed severe bronchopneumonia.

All premature infants were given high

hu-midity without supersaturation, and

environ-mental temperatures of 29 to 32#{176}C.Feedings

were started at 12 to 24 hours of age in

(2)

TABLE I

.

Procedures Electrocardwgrams Concentration. of in Serum

Polassiurn

Num- Mean Num- Num- 1!ean

Num-ber Weight ber ber Weight ber

Case.s (gm) EKG’s Cases (gm) Tests

26

66

Is

105

ARTICLES 563

Premature infants without respiratory (listress syndrome

Premature infants with respiratory distress syndrome

Normal full-term infants

Total 117

45 1,750 143 11 1,810

59 1,50 195 40 1,660

13 3,190 13 13 3,19()

351 64

respiratory distress syndrome. The patients with

respiratory distress syndrome were given

sup-plemental oxygen for cyanosis.

Serial physical examinations were done by the author at 6- to 12-hour intervals during the first 4 days of life. Roentgenograms of the

chests of 15 of the patients with respiratory

dis-tress syndrome were made to help verify the

diagnosis; all showed the typical

reticulogranu-lar pattern.4’ Repeated electrocardiograms

were made and occasional blood samples taken.

There were 351 electrocardiograms and 105

determinations of the concentration of

potas-sium in the serum made in all, on 117 infants.

In 24 patients with respiratory distress

syn-drome during the latter half of the study, the

effect of parenteral fluid therapy on the electro-cardiogram and the concentration of

potas-sium in the serum was evaluated.

Determinations of the concentration of

potas-sium in the serum were done in duplicate on

a flame photometer. The blood was usually obtained from the umbilical or femoral vein

amid in sonic cases from heel prick. There was

ho significant difference (p greater than 0.500)

between the means of results obtained from venous (6.08 meq/1) and capillary blood (6.20

meq/l) in controls. In all samples the serum was separated from the cells within 2 hours

(usually within 1 hour) of blood drawing;

hemolyzed specimens were rejected.

The electrocardiograms were made with a Sanborn direct-writing Viso-Cardiette#{174}

ma-chine, using both standard and chest leads. The PR interval was measured in lead II and

the QRS interval in the chest lead with the largest QRS duration-usually V4.

In addition, serial electrocardiograms were

made on abnormal controls who had other

forms of neonatal respiratory insufficiency. Five

300- to 800-gm fetuses who died within 12

hours of birth were studied. They were cyanotic

and had recurrent apneic spells, but did not show the retraction and grunting seen with the respiratory distress syndrome. Serial electro-cardiograms were also made of three full-term

infants with meconium aspiration syndrome and two with pneumonia.

RESU LTS

Electrocardiograms

Early in the study it became apparent

that electrocardiographic abnormalities

ap-peared after 12 hours of age in infants with

respiratory distress syndrome, but not in

control infants.

EicmocuirnocnMs OF CONTROLS: In

premature infants without respiratory

dis-tress syndrome the duration of PR and

QRS showed no change with age (Figs. 1

and 2). In only 3 of 143 electrocardiograms

made of these infants were the PR and QRS prolonged beyond 0.11 and 0.04 seconds, respectively. There was characteristically a

flat or absent T wave at birth which

be-came larger after the second day, and right axis deviation with right ventricular

pre-ponderance in the chest leads. Thirteen

full-term controls had PR and QRS durations

which did not exceed values found in the

premature infants. A more complete

de-scription of

the

serial

electrocardiographic

changes with age in the normal will be

pre-sented

in a

later report.

(3)

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AGE (hr)

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yO 50 90 100 110

564 RESPIRATORY DISTRESS SYNDROME

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0 tO 20 30 40 50 60

. .

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FIG. 1. Duration of PR interval at different ages in the first 5 days of life

nicas-ured on 147 electrocardiograms made from 52 premature infants with respiratory

distress syndrome and 102 electrocardiograms made from 42 premature infants without respiratory distress syndrome. The mean PR duration between 12 and 60 hours of age was 0.086 seconds in control infants and 0. 1 12 seconds in infants with respiratory distress syndrome. This difference is statistically significant

(t :9.41;pless than 0.001).

vere respiratory distress from other causes) showed electrocardiographic conduction times similar to the normals. Hourly trac-ings on dying fetuses, in spite of marked

bradycardia, always showed normal

conduc-tion up to the moment of death (Fig. 3).

Serial tracings of all five full-term infants

with pneumonia or meconium aspiration

syndrome were also normal.

ELECTROCARDIOGRAM OF INFANTS WITH

RESPIRATORY DISTRESS SYNDROME : Although

similar to those in controls at birth, the

electrocardiograms in premature infants

with respiratory distress syndrome devel-oped the following abnormalities between

12 and 60 hours of age:

1. Prolongation of the PR interval over

0.11 seconds.

2. Prolongation of the QRS interval over

0.04 seconds.

3. Decreased QRS voltage in the

stand-ard leads.

4. Prolongation of the QT interval.

5. Broadening andi flattening of the P

wave.

6. Left axis deviation and left ventricular

preponderance.

7. Absence of P waves.

8. Peaked T waves.

9. Two-to-one atrioventricu lar heart

block.

The first six disturbances appeared in

most cases. Peaked T waves were less

fre-quent, and absence of P waves and

two-to-one atrioventricular block each appeared in

(4)

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70 SO 90. 100 110

AGE (hr)

lm(;. 2. Duration of QRS interval at different ages in the first 5 days of life measured on

147 electrocardiograms miade from 52 premature infants with respiratory distress

syn-(Ironic and 102 electrocardiogranis made from 42 premature infants without respiratory

(listress syn(lrOmiie. The mean QRS duration between 12 and 60 hours of age was 0.035

S(COflds in control infants and 0.052 seconds in infants with respiratory distress syndrome. This difference is statistically significant (t :4.84; p less than 0.001).

II

hrs.

45mm.

II

hrs.

55 mm.

1I(;. .3. Terminal

electrocardio-grams ( lead II) on a very

imma-tore fetus weighing 610 gm who

died at age 12 hours after a cya-notic course with repeated apneic spells. Electrocardiographic con-duction was normal on serial

frac-ings up to minutes before death.

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20 120

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peared after 12 hours of age. They increased until death in fatal cases and disappeared

with recovery in survivors. Examples of the

electrocardiographic changes in three cases

___________________________ are presented in Figures 4 to 6.

The most constant and easily recognized

changes were in the durations of the PR

and QRS intervals. These intervals are

com-_____________________ pared in Figures 1 and 2 with those found

_____

in premature infants without respiratory

dis-_________________________

tress syndrome. The mean durations of PR

and QRS intervals were both significantly

longer in patients with respiratory distress

syndrome than in the infants without

respir-atory distress syndrome between 12 and 60

hours of age (p less than 0.001

),

though not

before or after this period. These conduc-tion differences were unrelated to rate; the

(5)

566 RESPIRATORY DISTRESS SYNDROME

AGE

I’hrs

3lhrs

43hrs

69hrs

I

rtr

+*+

]I

__________

____

__

oVR

VL

aVF

__

_

v4R

_

- .

_

vi

v2

V

__

__

__

v6_

_

FIG. 4. Serial electrocardiograms made from a 1,200-gm infant with respiratory distress syndrome who survived. At 1 hours of age there was retraction of the

chest and grunting and electrocardiogram showed normal axis and conduction.

At 31 hours of age there was marked flaccidity and duskiness and

electro-cardiogram showed prolonged PR, QRS and QT with left axis deviation and

left ventricular preponderance. At 43 hours of age there was improved tone and color and electrocardiogram was returning to normal. At 69 hours of age there was continued clinical improvement and electrocardiogram had returned

to normal.

distress syndrome was 138/mm and for

controls was 144/mm.

The incidence of PR and QRS

prolonga-tion in respiratory distress syndrome is

pre-sented in Figure 7 for different time periods

during the first 4 days of life. While only

8% of the tracings made of infants with

(6)

____

33

hrs

132

hrs

LA& 14

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FIG. 5. Serial electrocardiograms made from a 1,100-gm infant with respiratory distress syndrome who survived. At 21 hours of age there was retraction of the chest, grunting and edema and the QRS interval was prolonged. At 223k hours of

age there was two-to-one atrioventricular block with shorter QRS, left axis

devia-tion and left ventricular preponderance. At 33 hours of age there was clinical

improvement and the electrocardiogram was returning to normal but left

yen-tricular preponderance remained. At 132 hours of age there was no respiratory distress but apneic spells were frequent. Electrocardiogram was normal.

ARTICLES 567

AGE

21

hrs

22

hrs

I

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first 6 hours of life showed prolonged

con-duction, 75% of those made between 12 and

48 hours were abnormal. Thirty-six of 37

infants with respiratory distress syndrome

who had more than one tracing between

12 and 60 hours of age showed these

abnor-malities in conduction at some time. All but four of the infants who died with

respira-tory distress syndrome showed

(7)

35

hrs

v4

568 RESPIRATORY DISTRESS SYN l)RONI E

AGE

13

hrs

18

hrs

I

j4

=

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rv

aVL

4-+*

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V

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tr

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V

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NjIJ

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ti:

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v6_

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Fic. 6. Serial electrocardiogramiis made from a 1,500-gin infant with

r-spiratory distress syndrome who died at agc 40 hours. At 1:3 hours of agc

there was retraction, grunting, and edenut with prolonged PR and QRS

intervals. At 18 hours of age electrocardiographic conduction was

worsen-ing with left axis deviation and left ventricular preponderance. At :35 hours of age there was flaccidity, sclerema, bradycardia and absence of P waves, peaked T wave, disruption of QES complex. The concentration of potassium

in the serum at this time was 10.7 meq/l.

last 12 hours of life; three of the four who Concentration of Potassium in Serum

did

not

develop abnormalities died before The resemblance of these

electrocardio-12 hours of age. The average duration of graphic changes to those reported in

hyper-the electrocardiographic disturbance in the kalemic states (see Discussion

)

prompted an

individual case was 36 hours in both dying investigation of the associated concentration

(8)

TABLE II

(oNcENTItATIoNs 01? PoTAssIuo IN SEuuM oF

MATURE INFANTS “,%!TIIOUT REsPIRATORY

1)msrmsF:ss SYNDROME

Birth (‘oncenira- Age

Jl7eight lratwrm

----(get) (rneq/l) (days) (ler)

0 6 2 6 24 36 48 96

13

ii

Si

G’)

‘24

13 16

4

1

a iz

6

5 1

7

54

1 1

was present when the concentration of

p0-tassiurn was below 7.0 meq/l and that

con-duction was prolonged with concentrations

of potassium over 7.0 meq/l.

The mean concentration of potassium in

the serum rose from 5.1 meq/1 in the first

6 hours of life to 9.0 meq/1 at 18 to 24

hours of age, and fell again after 48 hours

of age. A curve of the incidence of

“abnor-mal” electrocardiograms at different ages in

infants with respiratory distress syndrome is

superimilpose(l 011 the curve of niean

concen-FIG. 7. Incidence of prolonged conduction (solid

columns) at different ages during the first 4 days of life in 149 electrocardiograms niade from

prc-mature infants with respiratory distress syndrome.

Conduction was considered prolonged if PR

in-terval was more than 0.11 seconds or QRS interval

more than 0.04 seconds.

CONCENTRATION OF POTASSIUM IN

CON-TROLS : Thirty-nine determinations of the concentration of potassium in the serum

were performed on 11 premature infants

without respiratory distress syndrome

(Table II) and 13 normal full-term infants.

Twenty-four of these determinations were

made during the important 12- to 60-hour

age period, and were associated with

“nor-mal” electrocardiograms made

simultane-ously. The concentration of potassium

dur-ing this period ranged from 4.2 to 7.0 meq/l

(

mean 6.09) for the premature, and 5.1 to

6.8 meq/1 (mean 6.01) for the full-term

in-fants.

CONCENTRATION OF POTASSIUM IN INFANTS WITH RESPIRATORY DISTRESS SYNDROME : The

concentrations of potassium found in infants

with respiratory distress syndrome are

re-ported in Table III. The individual

concen-trations of potassium are plotted against age

in the scattergram (Fig. 8

)

. The

conduc-tion times on simultaneously made

electro-cardiograms are indicated as normal or

pro-longed by open and solid circles,

respec-tively. It is evident that normal conduction

10.

ARTICLES 569

1. 1,100 6.0 1

). 1,110 6.8 1

3. 1,300 7.4

6.9 1

4. 1,510 .5.3

6.4 10

o:i so

:5. 1,590 4.4

6.1

6.7 6

6. 1,690 6.1)

7.3 7.1

7. ‘2,044) 6.7

7.0 1

6. 8

8. 2,240 4.1

4.2 1

6.3 9

9. 2,410 5.7

6.6

2,470 6.2

5.’2 6.2

11. 6.1

(9)

Birth Concen- Age at

Weight tratwn Age (hr) Death

(gm) (meq/l) (hr)

Birth Concen- Age at

Weight tration Age (hr) Death

(gm) (meq/l) (hr)

1. 1,800 6.4 14 64

. 1,800 10.5 16 144

23. 1,860 7.5

9.7

W

29

Lived

24. 1,860 4.8 3 Lived

25. 1,860 8.9

11.7 9.1 12 25 43 52

26. 1,870 6.0 6 45

27. 1,880 7.4

6.4

36

312

Lived

28. 1,930 10.7 32 52

29. 1,950 5.6 34 Lived

30. 2,090 7.9 33 345

31. 2,090 8.5 38 Lived

32. 2,130 7.4

10.3

15

26

47

83. 2,140 4.4 96 Lived

34. 2,160 6.7 34 44

35. 2,240 5.2

7.7 6.5 3 20 .53 Lived 36. 2,250 87. 2,330

1. 740 5.3 13 30

8.2 20

2. 900 9.3 99 113

3. 1,000 8.2 17 23

4. 1,110 9.0 18 26

5. 1,180 7.1 26 27

6. 1,240 8.9 12 Lived

7. 1,250 5.3 4 Lived

3.3 216

8. 1

,

270 6.3 60 Lived

9. 1,300 5.4 2 28

7.0 8.9

25 26

10. 1,340 4.4 5 105

8.6 104

11. 1,370 5.9

10.6

34

14

18

12. 1,390 5.2 14 34

13. 1,400 6.2 4 144

6.2 15

14. 1,500 6.0 5

7.9

9.5

26

27

15. 1,500 10.7 36 40

16. 1,520 5.6 13 Lived

17. 1,600 12.7 18 80

18. 1,670 6.1 26 Lived

6.5 48

19. 1,690 4.0

6.6 6.2 4.6 7 26 120 Lived

20. 1,750 4.6 2 Lived

4.5 44 4.5 44 8.2 16 Lived 19 Lived 41

38. 2,350 7.7 25

7.9 33

8.2 49

39. 2,S9() 7.0 15

10.0 27

40. 2,430 9.9 120 120

570 RESPIRATORY DISTRESS SYNDROME

TABLE Ill

(10)

1 3 12

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8

ARTICLES 571

S

S

5,

P100 9O ‘80

70

‘60

50

40

‘30

‘20

‘IO

0

0 I’2 18 24 36 48 72 96

AGE (hr)

FIG. 8. The scattergram represents the distribution with age of 69 determinations of concentration of potassium in serum of 39 premature infants with respiratory distress syndrome (Table III). Open circles represent determinations associated

with normal electrocardiograms; solid circles are associated with

electrocardio-grams showing prolonged conduction; dots represent concentrations of potassium with no associated electrocardiogram made. The solid line represents the mean concentration of potassium in the serum and the interrupted line represents the percentage of electrocardiograms which were abnormal during each age interval

(Fig. 7).

S. #{149}55

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0

trations of potassium

(Fig.

8). These curves

closely parallel each other.

The mean concentration of potassium in

serum of infants with respiratory distress

syndrome was markedly elevated when

compared to that found in control

prema-ture infants between 12 and 60 hours of

age, though not before or after this period.

Although none of the control infants had

concentrations over 7.0 meq/l between 12

and 60 hours of age, 18 of 29 (62%) of the

infants with respiratory distress syndrome

tested during this period had concentrations

over 8.0 meq/l.

Of 23 infants who died who had

potas-sium determinations, 17 had concentrations

at some time over 8.0 meq/l, 3 had

concentrations from 6.7 to 8.0 meq/l, and

3 others had lower concentrations but

were not tested during the last 12 hours of life. There was a surprising degree of

cor-relation between concentration of potassium and the mortality rate considering the small numbers and the sporadic nature of the

de-terminations. It can be seen from Table III

that while none of the eight infants with

concentrations of potassium over 10.0 meq/l lived, one of four with concentrations

be-tween 9.0 and 10.0 meq/l, three of eight

with concentrations between 8.0 and 9.0

meq/l, and 6 of 11 who had concentrations

less than 8.0 meq/l survived.

Examples of electrocardiograms with

si-multaneously determined concentrations of

potassium in serum of two premature

(11)

concen-CASE

AGE

K

AGE

K

AGE

K

IH

4.1

24H

4.2

9D

6.2

I

__

IH

.

22H

5.3

100

6.4

2

_

IH

4.5

18H

8.2

3

4

5

4H

6.0

3H 6.1

24H

7.9

36H

8.3

2TH

9.5

6

9H5.3

18H

8.2

FIG. 9. in serum

Serial of six

electrocardiograms (lead II) awl concentration of potassium

infants:

Case

1.

. . Clmnmcal Condition

Normal

Birth Weight (gm)

Age at Death

(hr)

2,240 Lived

2. Normal 1,520 Lived

.3. R.D.S. 2,330 19

4. R.D.S. 1,500 29

5. R.D.S. 800 62

6. R.D.S. 740 30

572 RESPIRATORY DISTRESS SYNDROME

tration of potassium and a deterioration of

the electrocardiogram with age in the

in-fants with respiratory distress syndrome, which did not occur in the control infants.

Effects of Therapy

A

solution of glucose, insulin and

bicar-bonate was given intravenously to 24

in-fants with respiratory distress syndrome at

the stage when they appeared to be dying. In almost all of the cases there was

immedi-ate decrease in concentration of potassium

in the serum amid correction of the

abnor-mal electrocardiographic conduction .

Ex-amples are illustrated in Figure 10.

When the fluid was administered

inter-mittently, an electrocardiographic effect was

noted within 10 minutes, which persisted for 1 to 2 hours. There was usually an asso-ciated strengthening of the heart sounds,

improvement in the gray mottled skin color,

increased responsiveness, and sometimes a

rise in blood pressure.

Eighteen of the 24 infants went oil to

die although they seemed to live longer

(12)

1500 GM

AGE K

9.3 16TH 8.3

GLUCOSE

INSU

26

H

27 H

1900 GM

AGE K

35H

7.4

ITED AT

37 H

31 H

48H

5.8.

27H 1.3

ttt1r1T11TTTTn1r11mm1 h-rt

30

H

5.1

-

. #{149}U

DIED

101 H

DIED 115K DIED

SIH

LIVED

ARTICLES 573

terventli)n. Iiie Iiiean duration of life in

in-fants who died without therapy was 37

hours, and the mean age at death with

ther-apy was 58 hours. The average age at

initia-tion of therapy was 26 hours.

With the sustained administration of fluid to the dying infants, the electrocardiogram never again showed prolonged conduction

time. The usually (lied after a course

marked by progressively severe apneic

spells. Six infants lived, but in the absence of an alternate control group of infants, it

is not possible to say that their survival was

due to the treatment.

The intravenous solution used contained

15 gni glucose, 5 Ifl((l sodium l)icarhonate,

and 7.5 units of regular insulin per 100 ml

for the initial correction of the

electrocardi-ogram. Subsequent maintenance fluids to

prevent recurrence of the hyperkalemia

con-sisted of 10% solution of glucose with 40

meq/l sodium bicarbonate. The fluid was

administered at the rate of 60 mI/kg of body

weight per day. The intravenous therapy

was continued until adequate oral intake

had been established as it was found that

the infants did very poorly if all fluid and

caloric intake were suddenly stopped.

Al-though intravenous or even gastric

adminis-tration of glucose or glucose-saline was

sometimes effective in correcting the

hyper-kalemia, the above solution seemed to act

1090 GM

4ic

26H 8.6

UN

BICARBONATE

STA

99H

6TH

___________

#{149}7H

6.1

____

_______

7’

H

IOOH 69

101 H

so. H

FIG. 10. Four examples of the correction of hyperkalemic electrocardiographic

con-(luction defects in premature infants with respiratory distress syndrome after intra-venous infusion of fluid containing 15 gin of glucose, 5 meq of sodium bicarbonate, and 7.5 units of insulin per 100 ml. In the first two cases, as the two-to-one

(13)

574 RESPiRATORY DISTRESS SYNDROME

more rapidly and occasionally was found to

be effective after there had been no

re-sponse to glucose alone.

DISCUSSION

Previous clinical studies of this syndrome

have been mainly related to respiratory function. They have found a typical

retic-ulogranular pattern on roentgenograms of

the decreased lung compliance and

vital capacity,7 and anoxemia with

respira-toly and metabolic acidosis.

The importance of the disease as the

prime cause of neonatal death, the striking

pathologic picture, and the lack of clinical

knowledge pertaining to etiology and

path-ogenesis have resulted in a prolific

litera-ture full of conjecture.8 The many different

hypotheses agree on only one point: that

the cause of death is respiratory

insuffi-ciency. This is felt by some to be due to

primary disease of the lung, and by others

to be secondary to pulmonary congestion

from left heart failure or from patent ductus

arteriosus.

The results obtained in this study

indi-cate that premature infants with the

respir-atory distress syndrome develop hyperkal-emia with consequent electrocardiographic

disturbances

of conduction.

There is no previous evidence in the

literature associating hyperkalemia or

ab-normalities in the electrocardiogram with

the respiratory distress syndrome of

prema-turity. However, several workers have

de-scribed changes which probably represented

the same pathologic processes observed

here.

Two articles from Germany have reported

the finding of similar electrocardiograms in

premature infants who were sick with signs

which might here have been called respira-tory distress yndr91#{176} McCance and Widdowson11 mentioned several premature

infants with respiratory distress syndrome

who had elevated concentrations of potas-sium in the serum; they believed such levels were a normal concomitant of prematurity

and were innocuous;12 electrocardiograms

were not obtained. Lynch et al.’ has

de-scribed a metabolic disturbance with

hyper-kalemia in experimental animals dying with induced hyaline membrane syndrome.

Rose’4 found hyperkalemia in infants with

respiratory distress syndrome born to

dia-belie mothers. There have been no previous

reports of autointoxication with potassium

in a newborn infant with any disease,

al-though hyperkalemia in an infant from

ex-cessive

administration

of

potassium has

been described.15

Concentrations of potassium in serum of

premature and full-term infants without

respiratory distress syndrome have been

found by many workers’’9 to be within

the upper half of the normal adult range,

usually 4 to 7 meq/l. Asphyxiated

new-borns have been shown to have high

con-centrations of potassium in serum at birth2#{176}

and

premature infants recently were shown

to have normal adult levels unless fed a

high potassium intake.21 The findings of

the present study would indicate that

fu-ture

investigations of the concentration of potassium in the serum of premature

in-fants should carefully distinguish between

infants with, and those without respiratory distress syndrome.

The causative role of hyperkalemia in pro-ducing electrocardiographic disturbance was

borne out by the correlation with the con-centration of potassium in the serum, the re-versal with glucose and insulin, and the

sim-ilarity of the tracings to those seen in adults

with hyperkalemia.22 The absence of peaked

T waves might possibly be attributed to an

intracellular deficit of potassium instead of an extracellular excess as the primary cause of the abnormal electrocardiograms. It

would seem, however, more probable that the absence of peaked T waves in the

pres-ence of hyperkalemia is somehow related

to the phenomenon of low or absent T

waves during the first days of life in healthy premature infants.

Bjorklund,23 . the basis of slight T wave

changes, has suggested that infants born to

(14)

ARTICLES 575

The parenteral administration of potassium

which he advises would appear to be not

without danger.

There is some evidence from this study

that hyperkalemia might be a cause of

death in infants with respiratory distress

syndrome. There was a direct correlation between the concentration of potassium and mortality rate, and there was a longer life

span when hyperkalemia was treated.

How-ever, most of the treated infants died after

the concentration of potassium had been

lowered to normal, and it has yet to be

proved that treatment directed against hy-perkalemia can effectively lower the

mor-tality rate.

Parenteral fluid therapy might well be

more effective if given from birth as rou-tine prophylactic therapy to infants with

respiratory distress syndrome, as it has been shown here that almost all such infants will develop hyperkalemia after 12 hours of age. The lower mortality of infants born to

dia-betic mothers which Reardon et al.24 have reported after administration of a solution of glucose and saline from birth might be attributed to the prevention of

hyperkale-mia.

The cause of hyperkalemia during

respir-atory distress syndrome is uncertain.

Possi-ble factors which might increase the

re-lease of intracellular potassium are

respir-atory acidosis, dehydration, and starvation.

Alternative or additional factors which

might decrease excretion of potassium are

shock, adrenocortical exhaustion, and the

known inability of the neonatal kidney to

handle large solute loads.

Anoxia, immaturity, and terminal change

might be considered as causes of the

hy-perkalemia and/or the abnormal electro-cardiograms during respiratory distress syn-drome. The development of the

abnormali-ties in surviving infants, and long before

death in those who die, and the normal

tracings obtained from anoxic dying fetuses

would, however, all seem to indicate that

anoxia, immaturity and death itself are not the direct causative factors.

Sources of error in such a clinical study

of an indefinite disease entity will always

include the difficulty of diagnosis. The

sub-jective error was in this study at least made

uniform by having all cases evaluated by

one observer. The clinical signs,

roentgeno-graphic findings and postmortem findings in

these infants with respiratory distress syn-drome were typical of those reported else-where.

SUMMARY

A study of 59 premature infants with respiratory distress syndrome has revealed the presence of severe increase in

concentra-tion of potassium with electrocardiographc

changes. Thirty-six of 37 of these infants

examined

serially between 12 and 60 hours

of age developed electrocardiographic

ab-normalities. Concentrations of potassium in

serum of over 7.0 meq/l were associated

with these prolonged conduction times.

Concentrations of over 9.0 meq/l occurred

in 12 infants, 11 of whom died. Parenteral administration of glucose, insulin, and

bicar-bonate produced a fall in the concentration

of potassium in the serum and a correction

of the electrocardiogram.

Control premature and full-term infants

had concentrations of potassium between

4 and 7 meq/l and never showed

electro-cardiographic disturbances.

Evidence is produced that premature

in-fants with the respiratory distress syndrome

develop a toxic degree of hyperkalemia

which is reversible.

Acknowledgment

The aid received from Dr. George Maughan, Dr. Aubrey Geddes, Dr. Alan Ross, Miss

Fran-ces MacLean, R.N., Miss Arlene Maximchuk,

M.Sc., and from the nursing staff of the Pre-mature Nursery is gratefully acknowledged.

REFERENCES

1. Dunham, E. : Premature Infants, 2nd Ed. New York, Hoeber, 1955, p. 70.

2. Hess,

J. :

Premature and Congenitally Dis-eased Children. Philadelphia, Lea, 1922,

(15)

576 RESPIRATORY DISTRESS SYNDROME

3. Potter, E. L. : Pathology of the Fetus and

the Newborn. Chicago, Yr. Bk. Pub.,

1952, p. 249.

4. Bauman, W., and Nadelhaft,

J. :

Radiog-raphy of prematures : a practical tech-nique of correlation with respiratory distress. PEDIATRICS, 21:813, 1958. 5. Blystad, W. : Blood gas determinations of

premature infants. II. Investigations of

premature infants with early neonatal

dyspnoea (the hyaline membrane

syn-drome). Acta paediat., 45: 103, 1956. 6. Peterson, H., amid Pendleton, M. :

Con-trasting roentgenographic pulmonary

patterns of the hyaline membrane and the fetal aspiration syndromes. Am.

J.

Roentgenol., 74:800, 1955.

7. Drorbaugh, J., et a!.: “Vital capacity” and lung compliance in normal newborns, amid infants with “hyaline membrane

syndrome.” A.M.A. J. Dis. Child.,

94:434, 1957.

8. Brown, R. : Respiratory difficulties at birth.

Brit. M.

J.,

1:404, 1959.

9. Kottgen, H., and Feverabend, H. :

St#{246}run-germ der Reizbildung und

Erregungslei-tung im Herzen bei fruhgeborenen

Kindern. Monatsschr. Kinderh., 100:244, 1952.

10. Joppich, G., and Stoermer,

J. :

Das EKG

bei unterkuhlten Fruhgeborenen.

Mon-atsschr. Kinderh., 105:264, 1957.

1 1. McCance, R., and Widdowson, E. : Pro-tein catabolism and renal function in the first two days of life in premature in-fants and multiple births. Arch. Dis. Childhood, 30:405, 1955.

12. Widdowson, E., and McCance, R. : The

effect of development on the composition

of the serum and extracellular fluids.

Chin. Sc., 15:361, 1956.

13. Lynch, M., Mellor, L., and Badgery, A.: Hyaline membrane disease; its nature and etiology. The poisonous metabolic

effects of excess oxygen. Neural control

of electrolytes.

J.

Pediat., 48:602, 1956. 14. Rose, V. : Problems of the infants of

dia-betic mothers. Bull. Hosp. for Sick Chil-dren, Toronto, 7:110, 1958.

15. Govan, C., and Weiseth, W. : Potassium intoxication; report of an infant

surviv-ing a serum potassium level of 12.27 millimoles per liter.

J.

Pediat., 28:550,

1946.

16. Hansen,

J.,

and Smith, C. : Effects of

with-holding fluid in the immediate postnatal period. PEDIATRICS, 12:99, 1953. 17. Earle, D., Bakwin, H., and Hirsch, D.:

The plasma potassium level in the new-born. Proc. Soc. Exper. Biol. & Med., 76:756, 1951.

18. Spivek, M. : Microchemical blood

stand-ards for normal five-day-old newborn

in-fants.

J.

Pediat., 48:581, 1956.

19. Pincus,

J.,

et al.: A study of plasma values

of sodium, potassium, chloride, carbon

dioxide, carbon dioxide tension, sugar, urea, and the protein base-binding

power, pH and hematocrit in prematures

on the first day of life. PEDIATRICS,

18:39, 1956.

20. James, L. : Changes in acid-base balance

and blood electrolytes in vigorous and

depressed newborn infants (Abstract). A.M.A.

J.

Dis. Child., to be published. 21. Keitel, H. C. : The concentration of

potas-sium in the plasma (of premature

in-fants). A.M.A.

J.

Dis. Child., 97:583, 1959.

22. Levine, H. : Electrolyte imbalance and the

electrocardiogram. Mod. Concepts

Car-diovas. Dis., 23:246, 1954.

23. Bjorklund, S. : Children of diabetic

moth-ers : electrocardiographic studies in the newborn. Acta paediat., 42:526, 1953.

24. Reardon, H., et a!. : Treatment of acute

respiratory distress in newborn infants of diabetic and “prediabetic” mothers

(Abstract). A.M.A.

J.

Dis. Child., 94:558,

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1959;24;562

Pediatrics

Robert Usher

Potassium in the Serum and the Electrocardiogram and Effects of Therapy

THE RESPIRATORY DISTRESS SYNDROME OF PREMATURITY: I. Changes in

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1959;24;562

Pediatrics

Robert Usher

Potassium in the Serum and the Electrocardiogram and Effects of Therapy

THE RESPIRATORY DISTRESS SYNDROME OF PREMATURITY: I. Changes in

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References

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